Dissertations / Theses: 'Bone Diabetes'

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Retzepi, Maria. "The effect of experimental diabetes on guided bone regeneration." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/18575/.

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The aim of the present PhD thesis was to investigate the impact of uncontrolled and controlled experimental diabetes on the neo-osteogenesis and bone regeneration potential following Guided Bone Regeneration (GBR). Wistar strain rats (n=128) were allocated in three experimental groups: a) streptozotocin-induced, uncontrolled diabetes; b) systemic insulin controlled diabetes; c) systemic health. The impact of the diabetic status on the neo-osteogenesis and on the bone regeneration potential were evaluated histometrically in GBR treated models of de novo mandibular bone formation and regeneration of critical size calvarial defects respectively. Genome-wide microarray analysis was conducted in tissue samples obtained from GBR treated calvarial defects during the early healing stages. Following application of the GBR therapeutic principle, significant neo-osteogenesis and regeneration of critical size osseous defects were observed histologically and morphometrically, even in the presence of uncontrolled diabetes. Nonetheless, the diabetic status was associated with lower outcome predictability, which was improved via systemic insulin mediated glycaemic control. Uncontrolled diabetes compromised the initial stages of intramembranous bone regeneration following GBR, as evidenced by aberrations in fibrin mesh organisation, inflammatory and mesenchymal cells influx and woven bone formation. In parallel, the uncontrolled diabetic condition featured downregulation of genes encoding chemoattractants and inflammatory mediators during the inflammatory phase of the GBR healing process. Further, pathways related to cell division, energy production and osteogenesis were underexpressed during the proliferative phase, while the NF-kB and Wnt signalling pathways were misregulated. The insulin controlled diabetic state enhanced granulation tissue formation and osteogenesis and upregulated genes encoded growth factors and for extracellular matrix proteins during the early healing phases. It is suggested that, although experimental diabetes may compromise the initial stages of osteogenesis, GBR treatment can provide an environment permissive for significant, even though delayed, bone formation. Insulin mediated glycaemic control may enhance the bone regeneration potential in the diabetic status. Genome-wide expression profiling revealed perturbed pathways in GBR healing depending on the metabolic status, which may be applied in the design of novel therapeutic strategies for the reconstruction of osseous defects in diabetic patients.

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Rees, S. M. "Bone density and neuropathy in type 2 diabetes mellitus." Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419549.

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Mansur, Sity Aishah. "Extrapancreatic actions of incretin-based therapies on bone in diabetes mellitus." Thesis, Ulster University, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.694218.

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Diabetes mellitus is correlated with modifications in bone micro architectural and mechanical strength, leading to increased bone fragility. The in cretin hormones, with a classical effect to increase insulin secretion following food ingestion, are now postulated to have important direct effects on bone. As such, glucose-dependent insulinotropic polypeptide (GIP) has dual actions on bone cells; enhancing boneforming activity of osteoblasts and suppressing bone resorption by osteoclasts. The sister incretin of GIP, glucagon-like peptide-l (GLP-I), is also suspected to directly influence bone health in a beneficial manner, although mechanism are less clear at present. The physiological actions of incretins are attenuated by dipeptidyl peptidase (DPP-4) activity and it is speculated that introduction of DPP-4 inhibitor may also positively affect quality of the skeleton. As such, this thesis evaluates the potential beneficial effects of a DPP-4 resistant GIP analogue, namely [D-Ala2]GIP, on osteoblastic-derived, SaOS-2 cells, and also preliminary in vivo studies on the impact of genetic deficiencies of GIPRs and GLP-IRs on bone mineral density and content. Further studies characterised the beneficial effects of incretin-based therapies on metabolic control, bone microstructure and bone mechanical integrity in animal models of pharmacologically-, genetically- and environmentally-induced diabetes. GIP and related stable analogue increased bone-forming biomarkers in SaOS-2 cells and importantly, [D-Ala2]GIP was shown to be more potent than native GIP. Knockout mouse studies revealed that both GIPR and GLP-IR signaling are important for optimum bone mass. All diabetic mouse models displayed reduced bone mass, altered bone micromorphology and impairment of bone mechanical strength, similar to the human situation, confirming their appropriateness. The incretin-based therapeutics, [D-Ala2]GIP and Liraglutide, in streptozotocin-diabetic significantly increased bone matrix properties, indicating recovery of bone strength at the tissue level. The beneficial effects of administration of [D-Ala2]GIPoxyntomodulin on bone health in db/db mice were more prominent as the Oxm analogue did not only improve bone strength at tissue level, but also at whole-bone level. These modifications were independent of metabolic status. Twice-daily Exendin-4 therapy improved glycaemic control and increased work required to resist bone fracture in high-fat fed mice. It was also established that Sitagliptin had neutral effects on bone microstructure and mechanical strength in high-fat mice.

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Urbina, Princess. "Bone Morphogenetic Protein-7 Attenuates Inflammation and Apoptosis and Improves Cardiac Function in Diabetes." Master's thesis, University of Central Florida, 2013. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5716.

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Bone Morphogenetic Protein-7 (BMP-7) belongs to the transforming growth factor-β (TGFβ) family of cytokines has is known to have potent anti-inflammatory properties. It has been used in patients to treat osteoporosis clinically and has been reported to treat diabetic nephropathy in murine models. Moreover, studies show that inflammation is up-regulated in patients with pre-diabetes (PD). We, therefore, hypothesize that the administration of BMP-7 will attenuate inflammation in the heart of Streptozotocin (STZ)-induced PD mice. In this study, we divided C57Bl/6 mice into three groups: CONTROL, PD, and PD+BMP-7. CONTROL mice received intraperitoneal (i.p.) injections of Sodium Citrate Buffer while PD and PD+BMP-7 groups received i.p. injections of Streptozotocin (STZ) for two days. In addition, PD+BMP-7 mice received intravenous injections (i.v.) of BMP-7 (200µg/kg) on the last day of STZ injection and for the following two days. Animals were sacrificed 21 days post last injection and examined for levels of oxidative stress, inflammatory immune response, apoptosis, fibrosis and cardiac function. Our results indicate significant glucose intolerance in PD mice (p<0.05), which was attenuated in the PD+BMP-7 group (p<0.05). We also observed increased oxidative stress (p<0.001) and secretion of pro-inflammatory cytokines (p<0.05), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), in PD mice as compared with the controls. PD+BMP-7 mice revealed significant up-regulation of M2 macrophages (p<0.05) and secretion of anti-inflammatory cytokines (p<0.05), interleukin-10 (IL-10) and interleukin-1RA (IL-1RA), as compared to PD mice. This was observed with a concomitant down-regulation of pro-inflammatory cytokines, IL-6 and TNF-α, as compared to the PD group. Moreover, we observed significantly increased cardiac apoptosis and fibrosis in PD mice (p<0.001) as compared to the control group. These observations, however, were down-regulated upon treatment with BMP-7. Lastly, analysis of echocardiograms revealed significantly depressed cardiac function in PD mice as compared with controls, while the PD+BMP-7 group presented improved cardiac function compared to PD mice. In conclusion, our data suggest that treatment with BMP-7 is effective in alleviating cardiac inflammation, inhibiting apoptosis, blunting cardiac remodeling and improving cardiac function in the hearts of STZ-induced PD mice. This reveals the potential of BMP-7 as a therapy in PD patients who present an increased inflammatory immune response.
M.S.
Masters
Molecular Biology and Microbiology
Medicine
Molecular and Microbiology

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Singh, Dhruvaraj Kailashnath. "Clinical studies in diabetic vasculopathy to assess interactions between blood, bone and kidney." Thesis, University of Hertfordshire, 2010. http://hdl.handle.net/2299/4186.

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Diabetic vasculopathy (DV) is the most important consequence of chronic hyperglycemia in patients with diabetes mellitus (DM). This thesis explores the interaction of blood, bone and kidney in the pathogenesis of DV by i) reviewing the current understanding of pathogenesis of macrovascular and microvascular diseases in DM to identify gaps in literature and generate hypotheses relating to various facets of DV ii) undertaking a series of prospective studies to examine these hypotheses iii) analysing the findings and integrating any new information obtained from the clinical studies into the current knowledge base and iv) generating hypotheses upon which future work might be based. The literature search was carried out with the aim of understanding current concepts of pathogenesis of DV and its potential modulators. The original reviews resulting from this process are presented in chapters 2 to 4. A series of pilot studies reported in chapters 7 to 11, were then carried out to interrogate hypotheses originating from this process. The first study was carried out in healthy individuals to define the biological variation of potential modulators of DV, namely erythropoietin (EPO), parathyroid hormone, 25 hydroxyvitamin D and 1, 25-dihydroxyvitamin D to facilitate the design and interpretation of subsequent studies. It revealed a wide biological variation of these modulators in the healthy population thus,emphasizing the need to have a control group in the subsequent study population. To examine whether tubulointerstitial dysfunction occurs before the onset of microalbuminuria, a measurement of the above mentioned parameters was carried out along with markers of tubulointerstitial injury in patients with type 1 and type 2 DM without microalbuminuria and in non-diabetic controls. It was found that tubulointerstitial dysfunction with low levels of EPO and 1, 25-dihydroxyvitamin D and higher excretion of tubular injury markers, occurs before the onset of microalbuminuria. Subsequently, diabetic and nondiabetic chronic kidney disease (CKD) patients with EPO deficiency anaemia were examined to study the effects of EPO therapy on the excretion of tubular injury markers. However, in these patient groups, we were unable to demonstrate an effect of EPO therapy on the markers of tubular injury in spite of a beneficial haematological response. To examine whether vascular calcification (VC) and bone mineral density (BMD) were linked in patients with diabetes mellitus and to explore their relationship to modulators of DV, an assessment of VC and BMD was undertaken in patients with type 2 DM with different degrees of proteinuria and normoalbuminuria. VC was assessed by CT scan and BMD by a DEXA scan. Modulators of DV were measured including serum Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-b-ligand (RANKL). The findings were i) a high prevalence of VC and osteopenia in normoalbuminuric type 2 DM patients with normal serum creatinine ii) a weak inverse relationship between VC and osteopenia iii) proteinuric patients had worse VC but not osteopenia iv) weak relationships between OPG levels and both VC and osteopenia, masked by age in multivariate analysis. The final study examined the relationship between modulators of DV, including OPG and RANKL, and the degree of CKD. It was found that abnormalities of OPG and RANKL occur before the onset of microalbuminuria and progress with deterioration of renal function. Compared to nondiabetics, DM patients have higher OPG levels in the predialysis phase and lower levels in haemodialysis phase, a phenomenon that might indicate endothelial exhaustion in dialysis patients with DM. The derangements associated with DV seem to occur earlier than previously thought. Further work is required to untangle these complexities and to define the contribution of factors such as the adverse blood milieu, the vasculature, abnormal bone and mineral metabolism, and early tubulointerstitial damage. The findings from the studies reported here may help in the formulation of new hypotheses, which might contribute to future work in this area.

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Stabley, John Nathan. "Relationship between autonomic nervous system function and bone mineral density in type 1 diabetic individuals." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 65 p, 2006. http://proquest.umi.com/pqdweb?did=1203584531&sid=6&Fmt=2&clientId=8331&RQT=309&VName=PQD.

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Al-Qarakhli, Ahmed. "Altered bone cell biology associated with Type Two Diabetes Mellitus : consequences for periodontal disease." Thesis, Cardiff University, 2018. http://orca.cf.ac.uk/112980/.

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Periodontitis is a widely spread disease, affecting about 80% of the worldwide population, resulting in teeth loss, a heavy impact on patients in terms of function and aesthetic. Type 2 Diabetes Mellitus (T2DM) is described to be linked to the exacerbation of periodontitis and delayed healing. This link between these two diseases, however, is not fully evaluated and the mechanisms are yet to be fully elucidated. Osteopontin (OPN) is described to inhibit mineral crystal formation. Herein, it has been hypothesized that increased OPN in diabetic healing bone may be the causative factor of delayed healing in periodontitis and subsequent deterioration, leading to teeth loss. This project aims to gain a greater understanding of the effect of high glucose (HG) levels on mesenchymal stem cells (MSCs) and macrophages, their ability to synthesise OPN and hence, its effects on MSCs to synthesise new bone tissue. Further, the influence of Porphyromonas gingivalis lipopolysaccharides (Pg-LPS) on these cells was analyzed, in an attempt to create a model to study the healing in the presence of periodontitis and T2DM. Investigating the MSCs isolated from the rat compact bone (CB-MSCs) during the growth in culture, revealed two main populations; a heterogenous population appeared with predominantly mature characteristics at PD15. This population then demonstrated a change in its heterogeneity and became more immature in nature at PD50. These two main populations differed in their growth rate and capability of osteodifferentiation. HG environments exerted significant decreases in osteogenic differentiation on PD15, but not PD50. Addition of pg-LPS showed inhibitory effects on osteodifferentiation on PD15 cells more than PD50. Conversely, in the combined presence of HG and pg-LPS, PD50 showed a significant decrease in osteodifferentiation. OPN levels demonstrated a gradual decrease in CB-MSCs in both normal and HG conditions. Investigating OPN levels secreted by macrophages, however, revealed interesting results. Synergistic effects of both HG and pg-LPS exhibited a significant increase in OPN levels in both pro-inflammatory M1 macrophages and in repair related M2 macrophages. In conclusion, HG was mainly reported to inhibit osteogenic differentiation of the mature cell population, whereas the immature population was found to be affected by combined pg-LPS and HG. OPN levels in HG conditions were shown to decrease along the osteodifferentiation period. However, macrophages showed increase secretion of OPN by the synergistic effects of both pg-LPS and HG in both M1 and M2 and by pg-LPS effects in M2 macrophages. These outcomes as far as we are aware, are novel and disclose a new mechanism of bone resorption in the case of T2DM patients concurrently with periodontal disease.

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Berchieri, Carolina Bragiola [UNESP]. "Avaliação da densidade mineral óssea e os fatores a ela associados em indivíduos adultos com Diabetes Mellitus." Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/92167.

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Made available in DSpace on 2014-06-11T19:25:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-16Bitstream added on 2014-06-13T19:32:58Z : No. of bitstreams: 1 berchieri_cb_me_botfm.pdf: 270323 bytes, checksum: d429f18f90912ef77b56c68d82ce635d (MD5)
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O esqueleto é um dos maiores sistemas do corpo humano e é responsável pela manutenção da estrutura corporal e pelo armazenamento de minerais e proteínas, sendo a massa óssea determinada pela formação e reabsorção óssea. A osteoporose é um distúrbio osteometabólico crônico, multifatorial, relacionado à perda progressiva de massa óssea, geralmente de progressão assintomática até a ocorrência de fraturas. Caracteriza-se pela diminuição da densidade mineral óssea (DMO), com deterioração da microarquitetura óssea, que leva a um aumento da fragilidade esquelética e do risco de fraturas. As principais manifestações clínicas são as fraturas, sendo mais freqüentes as de vértebras, fêmur e antebraço. Desde 1949, quando Albright e Reifeinstein relataram a ocorrência de osteoporose em pacientes com diabetes (DM) de longa duração e mal-controlados, vários outros trabalhos foram publicados sobre o assunto, permanecendo não estabelecido o papel do DM como um fator de risco para osteoporose e fraturas ósseas. Avaliar a DMO e os possíveis fatores envolvidos em sua manutenção e formação, em adultos jovens com DM 1 e DM 2, comparando-os a um grupo controle homogêneo quanto à idade, gênero e índice de massa corpórea (IMC). Constituíram-se 2 grupos, sendo o primeiro de indivíduos com diabetes, subdividido em 25 indivíduos DM 1 e 25 indivíduos DM 2. O segundo grupo foi determinado como controle, composto por 18 indivíduos, os quais não apresentavam DM ou outras doenças que pudessem interferir no metabolismo ósseo e cuja faixa etária, gênero e IMC foram semelhantes aos diabéticos, compondo assim um grupo homogêneo. Os critérios de inclusão para os DM foram: idade entre 20 e 50 anos, tempo de diagnóstico do DM ≥5 anos, estar em acompanhamento ambulatorial, sem...
The skeleton is one of the largest systems in the human body and it is responsible for the maintenance of the body structure and also the storage of minerals and proteins. The bone mass is determined by the bone formation and reabsorption. Osteoporosis is a osteometabolic chronic multifactor disturb, related to progressive loss of bone mass, usually of asymptomatic progression until the occurrence of fractures. It is characterized by the decrease of the bone mineral density (BMD), with deterioration of the bone microarchitecture, which leads to a raise of the bone fragility and the risk of fractures. The main clinical manifestations are the fractures, more commonly on lumbar spine, femoral neck and forearm. Since 1949 when Albright & Reifeinstein described the occurrence of osteoporosis on long-term diabetic patients with poor metabolic control, many other studies were developed in this issue, remaining not well established the role of diabetes (DM) as a risk factor for osteoporosis and bone fractures. Assess the BMD and the possible factors involved in its maintenance and formation, in young type 1 and 2 diabetic adults, comparing them to a control group, alike on age, gender and body mass index (BMI). Two groups were established, the first one with type 1 (DM 1) and type 2 (DM 2) diabetic patients (25 individuals each) and the second one the control group, with 18 individuals without DM or any other disease which could affect bone metabolism. Age, gender and BMI were in parallel with the diabetic group characteristics, establishing a homogeneous group. Inclusion criteria for diabetic patients were: age between 20 and 50 years, diagnosis time ≥5 years, in actual clinical follow up, without further complications due to diabetes, not in use of drugs or having any disease which could interfere on bone metabolism, and non-pregnant or menopause women. A protocol was ...(Complete abstract click electronic access below)

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Abdalrahaman, Naiemh. "The assessment of bone health in young women with childhood-onset type one diabetes mellitus." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/8413/.

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The risk of hip fracture in people with type one diabetes mellitus (T1DM) is reported to be 7 to 12 times greater than in those without T1DM, and this increased risk is evident in both children and young adults. This fracture risk is higher than expected bone mineral density (BMD) measurements, which indicates the likelihood that other skeletal factors, not captured by DXA, may contribute toward increased fracture risk. There is increasing evidence that alteration in trabecular bone microarchitecture and increased bone marrow adiposity (BMA) are causes for excess skeletal fragility, yet these data are lacking in people with T1DM. Recent technological advances in magnetic resonance imaging (MRI) have allowed the quantification of trabecular bone architecture. In addition, MRI can quantify the amount of intra-abdominal fat, and magnetic resonance spectroscopy (MRS) can also be used to assess BMA. These advances may enhance our understanding of the underlying causes of diabetic osteopathy which may lead to improved fracture risk predictors and preventive measures in patients with T1DM beyond that provided by dual energy x-ray absorptiometry (DXA). The overall objective of this thesis was to improve the understanding of the bone pathology of young adult women with childhood-onset T1DM by using high resolution MRI. A cross-sectional study was first carried out to assess trabecular bone microarchitecture of the tibia, vertebral BMA and abdominal adiposity in patients with childhood onset T1DM (n=30) compared with healthy controls (n=28). Additionally, the biochemical markers of bone turnover, adiposity and GH/IGF-1 axis (IGF-1, IGFBP3, and ALS) were examined to evaluate the underlying mechanism that might result in bone deficit in this group of people. We found that young women with childhood onset T1DM had reduced apparent trabecular bone volume (appBV/TV) and apparent trabecular number (appTbN) and greater apparent trabecular separation (appTbSp) than women without T1DM. Interestingly, these differences remained significant after adjustment for multiple confounders. Furthermore, these abnormalities were markedly obvious in those with microvascular complication compared with those without microvascular complication. Although women with T1DM had greater abdominal adiposity compared with healthy controls, there was no significant difference in BMA between the groups. However, BMA showed positive significant association with current glycaemic control (r= 0.45, p=0.02). Women with T1DM had lower bone turnover and decreased GH/IGF axis compared with healthy controls. Osteocalcin and ALS were negatively correlated with trabecular separation in women with T1DM. III Next, a one-year prospective study was conducted in a subset (n=28) of the participants involved in the cross-sectional study. The aim of this study was to compare one year changes in trabecular bone microarchitecture and BMA in women with and without T1DM. Additionally, the study aimed to evaluate the effect of glycaemic control on these changes over this period. After adjustment for relevant confounders, the cases (n=17) had a lower median appTbN and a higher median appTbSp at baseline and 12 months compared with healthy controls (n=11). Although the sample size was small at follow-up, the trabecular bone deficits were clearly noticeable in those with retinopathy compared with those without retinopathy. Similarly, there was no difference in median BMA which was 26.2% (12.1, 62.1) and 22.4% (9.6, 41.9) in cases and controls, respectively (p=0.57). Additionally, over the 12 month period, there was no significant change in MRI-measured parameters in cases or in controls, and no differences in the change of these variables between the two groups. Mixed model effect analysis showed that age was a negative predictor of percent changes of appBV/TV, appTbN and appTbSp in both cases and controls (p=0.02, p=0.02, p=0.002, respectively). Interestingly, there was a strong correlation between change in HbA1c and change in BMA (r=0.8; p=0.002). In the third study, we aimed to assess adiposity-based determinants of bone mineral density and bone microarchitecture in healthy young women and women with T1DM. Additionally, we aimed to compare the feasibility of using DXA and MRI-measured bone parameters to differentiate women with and without T1DM. In addition to high resolution MRI we used DXA scans to measure BMD and body composition from the same participants (n=26) involved in the longitudinal study. Vertebral BMA was positively correlated with VAT. Additionally, we demonstrated evidence of an inverse association of vertebral BMA and DXA-measured bone parameters of femoral neck, lumbar spine and total body independent of demographics and body composition in healthy young women and women with T1DM. These finding support the hypothesis that BMA is linked with low bone density, and may contribute to excess bone fragility. Moreover, this study suggested that MRI-measured trabecular bone measurements were able to differentiate between T1DM with and without microvascular complication compared with DXA-measured BMD. In summary, differences in MRI-measured trabecular microarchitecture parameters identified in this body of work provide preliminary explanations for elevated fracture risk in young women with childhood onset T1DM. Additionally, these findings provide potential insight into a number of possible underlying mechanisms of diabetic osteopathy.

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Yusop, Norhayati. "Altered biological responsiveness of cells regulating intramembraneous bone repair associated with Type 2 Diabetes Mellitus." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/75468/.

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The successful outcome from implant procedure relies heavily on the integration between the implant and the surrounding bone tissues. Besides, Type 2 Diabetes Mellitus (T2DM), which is linked with delay of osseointegration and reduction of bone-implant interface, further compromises the success rate of implant in diabetic patients. Apart from hyperglycaemia, the precise mechanism of diabetes influence on bone repair associated with dental implants is not completely understood. Nevertheless, the transforming growth factor-β1 (TGF-β1) has been indicated to increase healing processes, by exerting the stimulatory role on mesenchymal stem cells (MSCs) and macrophage populations during the inflammatory stage of bone repair. Moreover, the bioavailability of growth factors has been associated with the functional role of SLRPs, particularly biglycan and decorin. However, the responsiveness of each relevant bone-repair cell and biomolecule during bone repair in a diabetic environment has not been fully evaluated. On the other hand, the in vivo osseointegration of implant in T2DM animal models,investigated in respect to the expression of TGF-β1 by MSCs, demonstrated statistically significant differences in TGF-β1 labelled between the young diabetic and the control groups. Besides, the in vitro assessment demonstrated alterations for TGF-β1 expression and synthesis by osteoprogenitor cells, macrophages populations,between cells with different proliferative states, and prior hyperglycaemic-induction. Moreover, hyperglycaemia altered osteogenic and adipogenic differentiation capacities in MSCs. The data also suggested that hyperglycaemia induced lower proliferative capacity in MSCs, which led to significant changes in growth factor and proteoglycans bioactivity in bone repair. Hence, the data gathered from both in vivo and in vitro experiments suggested the potential association of MSCs proliferative stage with bioavailability of TGF-β1 and proteoglycans sequestration in the extracellular matrix compartment. Apart from that, the inter-dependent relationship observed between the osseointegration biomolecules directly exerted a synergical impact on the capability of MSCs to form osteoblast and further stimulate bone formation in order to induce bone-healing processes. Thus, the original contribution of this study to the field of reparative medicine is the novel identification and the characterisation of key biological components in both cellular and molecular bone repairs; the osteoprogenitor cell populations, as well as the macrophages, in relation to hyperglycaemia that directly influences growth factors, signalling the role of proteoglycans during the bone repair processes in T2DM. Collectively, the evidence gathered within this study is highly valuable to assist in elucidating the relevant therapeutic target to accelerate bone repair processes in T2DM patients. Keywords: diabetes, osseointegration, hyperglycaemia, bone, growth factors.

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Böhler, Nina. "Auswirkungen von Gewichtsreduktion und einem kontrollierten Trainingsprogramm auf die Serumkonzentration der Bone morphogenetic proteins (BMPs) -2 und -4 bei Patienten mit Typ 2 Diabetes." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-149795.

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Adipositas und Typ-2-Diabetes sind häufige Erkrankungen des Stoffwechsels. Zur Basistherapie der Adipositas und des Typ-2-Diabetes gehören eine gesunde Ernährungs- weise und die Erhöhung der körperlichen Aktivität unter anderem mit dem Ziel der Gewichtsreduktion. Vermehrte Bewegung führt neben der Verbesserung der körperlichen Leistungsfähigkeit zur Fettmassenreduktion, Verbesserungen der Hyperglykämie, Lipo- proteinstoffwechsels und des Adipokinprofils. Bone morphogenetic proteins (BMPs) werden im Fettgewebe produziert und spielen eine wichtige Rolle in der Adipogenese und Transdifferenzierung von Adipozyten. Während ein Zusammenhang zwischen der BMP-7-Serumkonzentration und Adipositas vor kurzem belegt wurde, ist bisher nicht bekannt, ob weitere BMPs wie BMP-2 und -4 mit Adipositas und Typ-2-Diabetes assoziiert sind. Ziel dieser Arbeit war es deshalb zu untersuchen, ob die BMP-2 und -4 Serumkonzentrationen im Zusammenhang mit Körpergewicht, Fett- verteilung und Parametern des Glukosestoffwechsels bei Patienten mit Adipositas und Typ-2-Diabetes (n=213) stehen. Im Rahmen von drei Interventionsstudien wurde der Einfluss einer hypokalorischen Ernährungsweise über sechs Monate (n=19), eines 45,3 ± 7,4 kg Gewichtsverlustes ein Jahr nach bariatrischer Chirurgie (n=32) sowie eines zwölf- wöchigen Trainingsprogramms (n=60) auf die BMP-2- und -4-Serumkonzentrationen untersucht. Zusätzlich wurde die BMP-2-und -4-mRNA-Expression in humanen omentalen und subkutanen Fettgewebsproben von 161 Patienten charakterisiert. Die BMP-2- und -4-Serumkonzentrationen und die BMP-2- und -4-mRNA-Expression im viszeralen Fettgewebe korrelieren signifikant mit dem BMI und dem Körperfettgehalt. Zirkulierende BMP-4-Spiegel sind geschlechtsabhängig und bei Patienten mit T2D signifikant niedriger als bei gesunden Kontrollpatienten. Sowohl eine moderate Gewichts- reduktion durch kalorienreduzierte Ernährung als auch ein Gewichtsverlust von 45,3 ± 7,4 kg nach bariatrischer Chirurgie führen zu einer signifikanten Reduktion der zirkulierenden BMP-2- und -4-Spiegel. Das zwölfwöchige Trainingsprogramm führte lediglich zu einer signifikanten Reduktion der BMP-2-Serumkonzentration und zu signifikanten Ver- besserung der Leistungsfähigkeit, von Parametern des Glukosestoffwechsels und der Serumkonzentrationen von Adiponektin und Interleukin-6. Zusammengefasst zeigen die Daten, dass erhöhte Serumkonzentrationen von BMP-2 und 4 mit Adipositas assoziiert sind und durch Gewichtsreduktion und Erhöhung der körperlichen Aktivität verringert werden können. Die BMP-2- und -4-mRNA-Expression im viszeralen Fettgewebe kann zu erhöhten Serumkonzentrationen dieser Adipokine bei viszeraler Fettverteilung beitragen.

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Nunes, Nara Lhays Teixeira. "Effects of Local Administration of Tiludronic Acid on Experimental Periodontitis in Diabetic Rats." Universidade Federal do CearÃ, 2015. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=15097.

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The bisphosphonate tiludronic acid (TIL) presents anti-resorptive and anti-inflammatory properties and it has not been evaluated in the association periodontitis-diabetes mellitus (DM) to date. The purpose of this study was to evaluate the effects of local administration of TIL on experimental periodontitis (EP) in rats with streptozotocin (STZ)-induced DM. On day 1, thirty two rats received STZ injection. The animals were divided into groups (n=8): DM/C (Control), DM/EP, DM/EP/TIL1 and DM/EP/TIL3. In groups EP, a ligature was placed around the cervical area of mandibular first molars at day 8. In groups DM/EP/TIL1 and DM/EP/TIL3, TIL solutions of 1 and 3 mg/kg body weight, respectively, were injected into the buccal gingival margin of mandibular first molars every other day. Animals were euthanized at day 18. Histomorphometric analyses were performed. Data were statistically analyzed (p<0.05). Group DM/EP/TIL3 presented reduced alveolar bone loss and attachment loss when compared with group DM/EP (p<0.05). Within the limits of this study, it can be concluded that i) the local administration of TIL solutions presented a protective effect on tissue destruction in EP in diabetic rats and ii) the dosage of TIL may influence its effects.
O bisfosfonato Ãcido tiludrÃnico (TIL) apresenta propriedades antirreabsortivas e anti-inflamatÃrias e ainda nÃo foi estudado na associaÃÃo periodontite-diabetes mellitus (DM). O objetivo deste estudo foi avaliar os efeitos da administraÃÃo local do TIL na periodontite experimental (PE) em ratos com DM induzido por streptozotocina (STZ). No 1Â dia, trinta e dois ratos receberam injeÃÃo de STZ. Os animais foram divididos nos grupos (n = 8): DM/C (Controle), DM/PE, DM/PE/TIL1 e DM/PE/TIL3. Nos grupos PE, uma ligadura foi colocada na Ãrea cervical dos primeiros molares inferiores no 8Â dia. Nos grupos DM/PE/TIL1 e DM/PE/TIL3, soluÃÃes de TIL (1 e 3 mg/kg de peso corporal, respectivamente) foram injetadas na margem gengival vestibular dos primeiros molares inferiores em dias alternados. Os animais foram submetidos Ã eutanÃsia no 18Â dia. AnÃlises histomorfomÃtricas foram realizadas. Os dados foram estatisticamente analisados (p<0,05). O grupo DM/PE/TIL3 apresentou perda Ãssea alveolar e perda de inserÃÃo reduzidas quando comparado com o grupo DM/PE (p<0,05). Dentro dos limites deste estudo, pode-se concluir que i) a administraÃÃo local de soluÃÃes de TIL apresentou um efeito protetor na destruiÃÃo tecidual na PE em ratos diabÃticos e ii) a dosagem de TIL pode influenciar seus efeitos.

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13

Ahmad, Tashfeen. "Diabetic osteopathy : a study in the rat /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-615-4/.

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14

Manaia, Cristiane Nalin [UNESP]. "Estudo da fragilidade em fêmures de ratos diabéticos pela análise densitométrica e biomecânica." Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/94738.

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Diabetes é uma desordem metabólica que interfere no tecido ósseo. Objetivou-se avaliar a fragilidade de fêmures de ratos diabéticos tipo 1 (DM1), pela densitometria e ensaio biomecânico. Foram utilizados 22 animais (Rattus novegicus, albinus, Wistar), com aproximadamente 250 gramas, divididos em grupo: Controle e Diabetes aleatoriamente. A DM1 foi inoculada pela estreptozotocina dissolvida em tampão citrato a 0,01M, pH 4,5, na concentração de 35mg/Kg na via peniana. Após 4 semanas da indução, foram sacrificados e os fêmures desarticulados. Para análise densitométrica utilizouse densitômetro DPX Lunar ™, para densidade radiográfica o sistema digital Digora®. No ensaio mecânico usou a máquina universal de ensaio EMIC® na região diafisária do fêmur. Os resultados passaram por análise estatística, teste t de Student, paramétrico e não pareado, onde o Conteúdo Mineral Ósseo (g), Densidade Mineral Óssea (g/cm²), Densidade Óssea (mmAl), Força Máxima (N) observadas nos fêmures de portadores de diabetes foi inferior ao grupo controle comprovado estatisticamente. Na Rigidez (x103N/m) e na Área (cm²) não houve diferença estatística. Conclui-se que o diabetes tipo 1 causou fragilidade nos fêmures dos ratos, reduzindo sua densidade mineral e consequentemente sua resistência mecânica.
Diabetes is a metabolic disorder that interferes with bone mass reducing the minerals density and consequently its mechanical strength. Our objective was to evaluate the femurs fragility in rats with type 1 diabetes (DM1)by densitometry and biomechanical tests. A total of 22 animals (Rattus novegicus, Albinus, Wistar), with approximately 250 grams were divided into group: Control and Diabetes. In-group Diabetes animals received streptozotocin dissolved in citrate buffer 0.01 M, pH 4.5, at a concentration of 35 mg/kg single dose in the penile vein. After 4 weeks of induction, the animals were sacrificed and the femurs were disarticulated for biomechanical analysis (Maximum Strength and stiffness) and densitometric analysis (Bone Mineral Density, Bone Mineral Content and Area). For densitometric analysis was used densitometer Lunar DPX ™ for the radiographic density digital Digora®. The biomechanical analysis used the universal testing machine EMIC ® in the femoral shaft. The results passed through statistical analysis, Student t test, parametric and nonpaired where of bone mineral content (g), bone mineral density (g/cm²), Bone Density (mmAl) Maximum Force (N) observed in the femurs of diabetic patients was lower than the control group accused significative differences. In Stiffness (x103N/m) and Area (cm²) there was no statistical difference.. Concluded that type 1 diabetes has caused weaknessin the femurs of mice, reducing its mineral density and consequently its mechanical strength.

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15

Bezerra, Beatriz de Brito. "Tratamento de defeitos ósseos com gel de ácido hialurônico a 1% em animais normais e diabéticos." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290388.

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Orientador: Antonio Wilson Sallum
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: O ácido hialurônico (HA) é um importante componente da matriz extracelular e desempenha importante papel na cicatrização. Além de sua função durante o processo cicatricial ele também atua na homeostasia dos tecidos e no reparo ósseo. Devido as suas características propomos este estudo com o objetivo de avaliar o efeito do tratamento de defeitos ósseos com ácido hialurônico em ratos normais e diabéticos. Para este trabalho foram utilizados 64 ratos Wistar machos, sendo que 32 destes animais tiveram um quadro de diabetes induzida por meio de injeção única intraperitoneal de estreptozotocina (STZ) (60mg/Kg). Os animais somente foram considerados diabéticos quando o nível de glicose no sangue ultrapassasse 250mg/dL. Dois defeitos de tamanho crítico, de 5mm de diâmetro, foram confeccionados na calota dos animais e os tratamentos 1) gel de HA a 1%; 2) gel de HA a 1% associado a esponja de colágeno absorvível (ACS); 3) ACS; 4) controle (coágulo sanguíneo) foram aleatoreamente distribuídos entre os defeitos. Após 60 dias do procedimento cirúrgico os animais foram sacrificados e os especimes passaram por processamento histológico para posterior avaliação histométrica. Análise histométrica foi realizada tomando duas medidas lineares nos defeitos: tamanho inicial e tamanho final do defeito. A quantidade de preenchimento do defeito foi obtida pela diferença entre os tamanhos inicial e final do defeito e os dados obtidos analisados estatisticamente. Para análise dos dados foram utilizados o teste t de Student para comparação entres os pesos inicial e final dos animais. O teste ANOVA comparou os níveis glicêmicos dos animais diabéticos antes e após a administração de STZ e no sacrifício, e o teste de Tukey foi utilizado para detectar as diferenças significativas. Para comparação dos tratamentos o teste ANOVA one-way foi usado com o teste de Bonferroni post hoc. O nível de significânica foi estabelecido a 5%. Os animais apresentaram ganho de peso significativo (p<0.05) ao longo do estudo. A indução da diabetes foi bem sucedida, com os níveis glicêmicos ultrapassando 250mg/dL e permanecendo altos até o final dos experimentos (p<0.05). A avaliação histométrica demostrou que o HA associado a ACS acelerou o reparo dos defeitos nos animais normais quando comparado aos demais tratamentos (p<0.05). Nos animais diabéticos o tratamento com HA favoreceu o reparo ósseo dos defeitos quando comparado aos defeitos não tratados e aqueles tratados com HA+ACS (p<0.05), sendo no entanto semelhante ao tratamento com ACS (p>0.05). Dentro dos limites deste estudos pode-se concluir que o HA pode ser utilizado como adjunto no tratamento de defeitos ósseos.
Abstract: Hyaluronic acid (HA) is an important component of extracellular matrix and has an important role in wound healing. Besides its role in wound healing it also participates in tissue hemostasis e bone repair. Due to these characteristics this study was suggested with the aim of evaluating the effects of HA treatment of bone defects in normal and diabetic animals. Sixty-four male Wistar rats were used in this study, and 32 of these animals underwent diabetes induction by a single intraperitoneal injection of streptozotocin (STZ) (60mg/Kg). The animals were considered diabetic only if their glucose levels were higher that 250mg/dL. Two 5mm round defects were created in the calvaria of the animals and four treatments were randomly distributed: 1) 1% HA gel, 2) 1% HA gel soaked absorbable collagen sponge (ACS), 3) ACS and 4) control (blood clot). Sixty days post-surgery the animals were sacrificed and the specimens processed for histometric analysis. Histometric analyses were performed and 2 measurements were taken: initial and final sizes of the defect. The amount of bone fill was calculated as the difference between the initial and final sizes of the defects and the data statistically analyzed. For statistical analysis Student t test was used to compare initial and final body weights. One-way ANOVA test compared glucose levels between diabetic animals before and after STZ injections and at sacrifice, Tukey test was used to identify significant differences. Comparisons between treatments were performed by one-way ANOVA and Bonferroni post hoc. Significance level was set at 5%. The animals had a significant increase in body weight (p<0.05) throughout the study. Diabetes induction was successful with glucose levels exceeding 250mg/dL and remaining high until the end of the study (p<0.05). Histometric analysis showed that HA associated with ACS improved bone healing in normal animals compared to other treatments (p<0.05). In diabetic animals HA treatment showed significantly greater repair than control and HA+ACS treated defects (p<0.05), this treatment was similar to ACS alone (p>0.05), though. Within the limits of this study it can be concluded that HA can be used as an adjunct in the treatment of bone defects.
Doutorado
Periodontia
Doutor em Clínica Odontológica

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Bighetti, Bruna Barros. "Avaliação do reparo de defeito ósseo em calvária de ratos diabéticos tratados com Matriz Óssea Desmineralizada." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/25/25149/tde-09122011-094237/.

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O objetivo deste trabalho foi avaliar as atividades osteoindutoras e osteocondutoras da matriz alogênica óssea desmineralizada (MAOD) frente à diabetes no reparo de defeito de tamanho crítico em calvárias de ratos diabéticos. Para isso, 100 ratos machos Wistar foram divididos em 2 grupos: no grupo diabético (DIAB, n=50) foi injetado 47 mg/Kg de massa corporal de estreptozotocina, enquanto que no grupo controle (CTL, n=50) foi injetado solução fisiológica a 0,9%. A MAOD foi obtida de 50 ratos, cujo fêmur e tíbia foram retirados, desmineralizados com HCl a 0,6M por 24 horas, particulados em 1-2mm³, neutralizados com soro fisiológico e armazenados em álcool. Após a anestesia, foram realizados defeitos ósseos de 8 mm nas calvárias dos animais, sendo os grupos CTL COAG (n=25) e DIAB COAG (n=25) preenchidos com coágulo e os grupos CTL MAOD (n=25) e DIAB MAOD (n=25) preenchidos com MAOD. Após os períodos de 0, 7, 14, 21 e 42 dias, as calvárias foram coletadas. A análise radiográfica mostrou que houve formação de ilhas radiodensas no interior dos defeitos nos grupos CTL e DIAB tratados com MAOD, enquanto que nos grupos tratados com coágulo houve formação de áreas mais radiodensas somente nas bordas do defeito, corroborando com os resultados morfológicos, que mostraram nos grupos tratados com coágulo que o reparo ósseo teve início nas bordas do defeito, enquanto que nos grupos tratados com MAOD, a neoformação óssea ocorreu também nas áreas de reabsorção nas partículas de MAOD. De acordo com os resultados morfométricos, o volume de tecido ósseo aumentou gradativamente em todos os grupos, porém, esse aumento foi maior nos grupos CTL em relação aos seus respectivos tratamentos nos grupos DIAB (CTL COAG > DIAB COAG e CTL MAOD > DIAB MAOD) e maior quando comparados os grupos tratados com MAOD versus os respectivos grupos tratados com COAG (CTL MAOD > CTL COAG e DIAB MAOD > DIAB COAG). Assim, ao término de 42 dias, o volume de tecido ósseo no grupo CTL MAOD foi em média 3,24 vezes maior em relação aos demais grupos, os grupos CTL COAG e DIAB MAOD não apresentaram diferenças significativas e o grupo DIAB MAOD foi 1,81 vezes maior em relação ao DIAB COAG. Com esses resultados, conclui-se que embora o quadro de diabetes tenha influenciado no atraso do reparo, ainda assim, pode-se afirmar que a MAOD contribuiu com a neoformação óssea e com o reparo do defeito na calvária de animais saudáveis e diabéticos, por terem sido preservadas as suas características osteoindutoras e osteocondutoras.
The aim of this work was to evaluate the osteoinductive and osteoconductive activities of demineralized allogeneic bone matrix (DABM) against diabetes in repairing critical size defects in diabetic rats skulls. Therefore, 100 male Wistar rats were shered into two groups: in the diabetic group (DIAB, n=50) was 47 mg/Kg of body weight streptozotocin, while in the control group (CTL, n=50) was injected saline 0.9%. The DABM was obteined using 50 rats which were removed their femur and tibia bones, demineralized in 0.6 N HCl during 24 hours, cut into 1-2mm³ pieces, neutralized in saline and stored in alcohol. After anesthesia, were made 8 mm bone defects on skulls of rats, being the CTL CLOT group (n=25) and DIAB CLOT group (n=25) filled with blood clot and the CTL DABM group (n=25) and DIAB DABM group (n=25) filled with DABM. After 0, 7, 14, 21 and 42 days, the skulls were collected. The radiographic analysis showed radiodense islets inside the defects filled with DABM in CTL and DIAB groups, while groups filled with blood clot showed radiodense areas near the defect border, which is in agreement to the morphologic results, that had showed the begining of bone healing was near the defects border in groups filled with blood clot, while groups filled with DABM showed new bone formation also in resorption DABM areas. According to morphometric results, the volume of bone tissue had increased in all groups, however, this increase was more accentuated in CTL groups when compared to DIAB groups with respected treatments (CTL CLOT > DIAB CLOT and CTL DABM > DIAB DABM) and bigger when groups treated with DABM are compared to respestive groups treated with CLOT (CTL DABM > CTL CLOT e DIAB DABM > DIAB CLOT). Thereby, at the end of 42 days, the CTL DABM bone tissue volume was 3.24 greater than the other groups, the CTL CLOT and DIAB DABM groups didnt show any significant differenceand the DIAB DABM was 1,81 greater than DIAB CLOT. From these results, the conclusion is that although diabetes had delayed the repair, nevertheless, DABM contributed to bone neoformation and to the defect repair in skulls of healthy and diabetic animals, due to the osteoinductive and osteoconductive qualities had been preserved.

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Frascino, Alexandre Viana Monteiro. "Efeitos do ozônio diluído em água no reparo de feridas monocorticais em fêmures de ratos induzidos ou não ao diabetes: estudo histomorfológico e histomorfométrico." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/23/23149/tde-18062011-104529/.

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Alguns relatos encontrados na literatura sobre as propriedades da molécula de ozônio de interferir de maneira favorável na reparação de tecidos e da sua ação antimicrobiana têm fundamentado emprego do ozônio com fins terapêuticos no tratamento de diversas doenças. Nenhuma pesquisa ainda conseguiu comprovar, por meio de estudos padronizados, os efeitos terapêuticos sobre os processos de reparação óssea desta molécula triatômica de oxigênio quando diluído em água. Nesta investigação foram avaliados os aspectos histomorfológicos e histomorfométricos do processo de reparo tecidual ósseo após a irrigação com 100mL de 4ppm de ozônio diluído em água Milli-Q® durante a perfuração de feridas monocorticais padronizadas, realizadas por meio de broca trefina (2mm), após 7, 14 e 21 dias, em fêmures de ratos Wistar induzidos e não induzidos ao diabetes por injeção intraperitoneal de Estreptozotocina (STZ- Sigma®). Nos grupos controles as feridas foram irrigadas com de 100mL de água Milli-Q® pura. Os resultados histomorfológicos revelaram que os animais diabéticos que receberam o ozônio apresentaram intensa hemorragia, maior proliferação de vasos sanguíneos e trabeculado ósseo imaturo quando comparados aos animais diabéticos não submetidos à aplicação de ozônio em todos os períodos avaliados. Os animais não diabéticos que receberam ozônio apresentaram intenso infiltrado inflamatório e maior proliferação de vasos sanguíneos quando comparados aos animais do grupo controle. Comparativamente as feridas nos animais que receberam a irrigação por meio de água ozonizada mostraram maior proliferação de vasos sanguíneos e trabéculas ósseas mais imaturas quando comparados aos animais dos grupos que não receberam ozônio. A avaliação histomorfométrica mostrou as médias percentuais de trabéculas ósseas neoformadas. O estudo estatístico, entre os grupos de animais diabéticos e não diabéticos, não apresentou resultados estatisticamente significantes (7 dias, P=0,362; 14 dias, P=0,54; 21 dias, P=0,351) nos períodos de 7, 14 e 21 dias pós-operatórios. A comparação entre o grupo de animais não diabéticos que receberam e não receberam o ozônio, 21 dias pós-operatórios mostrou resultados estatisticamente significantes (P=0,034) confirmando um retardo no processo de maturação das trabéculas. Os resultados desta pesquisa sugerem que a irrigação de feridas ósseas de animais induzidos e não induzidos ao diabetes empregando solução de 4ppm de ozônio diluídos em água Milli-Q® foram capazes de estimular a proliferação de vasos sanguíneos durante a fase inflamatória da reparação tecidual, sem produzir efeitos tóxicos ou prejudiciais, mas não mostrou benefícios na neoformação de trabéculas ósseas em animais diabéticos.
Some accounts in the medical literature about ozones molecule properties to favorably interfere with tissue repair and its antimicrobial action have based the therapeutic usage of ozone to treat several diseases. No standardized investigation yet succeeded to establish the therapeutic effects over bone repair process of this triatomic molecule of the oxygen when diluted in pure water. In this investigation we evaluated the histomorphological aspects of bone tissue repair process after irrigation with 100 ml of the 4 ppm of the ozone dissolved in Milli-Q ® during drilling of the standardized monocortical wounds performed through trephine drill (2mm), after 7, 14 and 21 days in femurs of rats induced and not induced to diabetes by intraperitoneal injection of streptozotocin (STZ, Sigma®). The wounds of the control groups were irrigated with 100ml of Milli-Q®. The histomorphological evaluation revealed that the diabetic animals that received ozone showed intense hemorrhage, increased proliferation of blood vessels and immature bone trabeculae when compared with diabetic animals not submitted to the application of ozone in all evaluated periods. The non-diabetic animals that received ozone presented intense inflammatory infiltrate and increased proliferation of blood vessels compared to the control group. Comparatively wounds of the animals that received irrigation through ozonized water showed higher proliferation of blood vessels and bone trabeculae more immature when compared to groups that did not receive ozone. Histomorphometric of bone trabeculae development, comparatively in wounds of diabetic and non diabetic animals showed no statistically significant results (7 days, P=0,362; 14 days, P=0,54; 21 days, P=0,351) . The comparison of bone trabeculae development between wounds in the group of non-diabetic animals that received and did not receive ozone, 21 days postoperatively showed statistically significant (P = 0.034). These results suggests that the irrigation of bone wounds of animals induced and not induced to diabetes with 4 ppm of ozone diluted in Milli-Q® were capable to stimulate the proliferation of blood vessels during the inflammatory phase of tissue repair without producing toxic or detrimental effects but did not improve bone trabeculae development when a diabetes state is present.

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18

Manaia, Cristiane Nalin. "Estudo da fragilidade em fêmures de ratos diabéticos pela análise densitométrica e biomecânica /." Araçatuba : [s.n.], 2009. http://hdl.handle.net/11449/94738.

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Orientador: Mário Jefferson Quirino Louzada
Banca: Alessandra Aranega
Banca: Stela Márcia Mattiello Gonçalves Rosa
Resumo: Diabetes é uma desordem metabólica que interfere no tecido ósseo. Objetivou-se avaliar a fragilidade de fêmures de ratos diabéticos tipo 1 (DM1), pela densitometria e ensaio biomecânico. Foram utilizados 22 animais (Rattus novegicus, albinus, Wistar), com aproximadamente 250 gramas, divididos em grupo: Controle e Diabetes aleatoriamente. A DM1 foi inoculada pela estreptozotocina dissolvida em tampão citrato a 0,01M, pH 4,5, na concentração de 35mg/Kg na via peniana. Após 4 semanas da indução, foram sacrificados e os fêmures desarticulados. Para análise densitométrica utilizouse densitômetro DPX Lunar ™, para densidade radiográfica o sistema digital Digora®. No ensaio mecânico usou a máquina universal de ensaio EMIC® na região diafisária do fêmur. Os resultados passaram por análise estatística, teste t de Student, paramétrico e não pareado, onde o Conteúdo Mineral Ósseo (g), Densidade Mineral Óssea (g/cm²), Densidade Óssea (mmAl), Força Máxima (N) observadas nos fêmures de portadores de diabetes foi inferior ao grupo controle comprovado estatisticamente. Na Rigidez (x103N/m) e na Área (cm²) não houve diferença estatística. Conclui-se que o diabetes tipo 1 causou fragilidade nos fêmures dos ratos, reduzindo sua densidade mineral e consequentemente sua resistência mecânica.
Abstract: Diabetes is a metabolic disorder that interferes with bone mass reducing the minerals density and consequently its mechanical strength. Our objective was to evaluate the femurs fragility in rats with type 1 diabetes (DM1)by densitometry and biomechanical tests. A total of 22 animals (Rattus novegicus, Albinus, Wistar), with approximately 250 grams were divided into group: Control and Diabetes. In-group Diabetes animals received streptozotocin dissolved in citrate buffer 0.01 M, pH 4.5, at a concentration of 35 mg/kg single dose in the penile vein. After 4 weeks of induction, the animals were sacrificed and the femurs were disarticulated for biomechanical analysis (Maximum Strength and stiffness) and densitometric analysis (Bone Mineral Density, Bone Mineral Content and Area). For densitometric analysis was used densitometer Lunar DPX ™ for the radiographic density digital Digora®. The biomechanical analysis used the universal testing machine EMIC ® in the femoral shaft. The results passed through statistical analysis, Student t test, parametric and nonpaired where of bone mineral content (g), bone mineral density (g/cm²), Bone Density (mmAl) Maximum Force (N) observed in the femurs of diabetic patients was lower than the control group accused significative differences. In Stiffness (x103N/m) and Area (cm²) there was no statistical difference.. Concluded that type 1 diabetes has caused weaknessin the femurs of mice, reducing its mineral density and consequently its mechanical strength.
Mestre

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19

Berchieri, Carolina Bragiola. "Avaliação da densidade mineral óssea e os fatores a ela associados em indivíduos adultos com Diabetes Mellitus /." Botucatu : [s.n.], 2009. http://hdl.handle.net/11449/92167.

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Orientador: Walkyria de Paula Pimenta
Banca: Glaucia Mazeto
Banca: Rosa dos Santos
Resumo: O esqueleto é um dos maiores sistemas do corpo humano e é responsável pela manutenção da estrutura corporal e pelo armazenamento de minerais e proteínas, sendo a massa óssea determinada pela formação e reabsorção óssea. A osteoporose é um distúrbio osteometabólico crônico, multifatorial, relacionado à perda progressiva de massa óssea, geralmente de progressão assintomática até a ocorrência de fraturas. Caracteriza-se pela diminuição da densidade mineral óssea (DMO), com deterioração da microarquitetura óssea, que leva a um aumento da fragilidade esquelética e do risco de fraturas. As principais manifestações clínicas são as fraturas, sendo mais freqüentes as de vértebras, fêmur e antebraço. Desde 1949, quando Albright e Reifeinstein relataram a ocorrência de osteoporose em pacientes com diabetes (DM) de longa duração e mal-controlados, vários outros trabalhos foram publicados sobre o assunto, permanecendo não estabelecido o papel do DM como um fator de risco para osteoporose e fraturas ósseas. Avaliar a DMO e os possíveis fatores envolvidos em sua manutenção e formação, em adultos jovens com DM 1 e DM 2, comparando-os a um grupo controle homogêneo quanto à idade, gênero e índice de massa corpórea (IMC). Constituíram-se 2 grupos, sendo o primeiro de indivíduos com diabetes, subdividido em 25 indivíduos DM 1 e 25 indivíduos DM 2. O segundo grupo foi determinado como controle, composto por 18 indivíduos, os quais não apresentavam DM ou outras doenças que pudessem interferir no metabolismo ósseo e cuja faixa etária, gênero e IMC foram semelhantes aos diabéticos, compondo assim um grupo homogêneo. Os critérios de inclusão para os DM foram: idade entre 20 e 50 anos, tempo de diagnóstico do DM ≥5 anos, estar em acompanhamento ambulatorial, sem ...(Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The skeleton is one of the largest systems in the human body and it is responsible for the maintenance of the body structure and also the storage of minerals and proteins. The bone mass is determined by the bone formation and reabsorption. Osteoporosis is a osteometabolic chronic multifactor disturb, related to progressive loss of bone mass, usually of asymptomatic progression until the occurrence of fractures. It is characterized by the decrease of the bone mineral density (BMD), with deterioration of the bone microarchitecture, which leads to a raise of the bone fragility and the risk of fractures. The main clinical manifestations are the fractures, more commonly on lumbar spine, femoral neck and forearm. Since 1949 when Albright & Reifeinstein described the occurrence of osteoporosis on long-term diabetic patients with poor metabolic control, many other studies were developed in this issue, remaining not well established the role of diabetes (DM) as a risk factor for osteoporosis and bone fractures. Assess the BMD and the possible factors involved in its maintenance and formation, in young type 1 and 2 diabetic adults, comparing them to a control group, alike on age, gender and body mass index (BMI). Two groups were established, the first one with type 1 (DM 1) and type 2 (DM 2) diabetic patients (25 individuals each) and the second one the control group, with 18 individuals without DM or any other disease which could affect bone metabolism. Age, gender and BMI were in parallel with the diabetic group characteristics, establishing a homogeneous group. Inclusion criteria for diabetic patients were: age between 20 and 50 years, diagnosis time ≥5 years, in actual clinical follow up, without further complications due to diabetes, not in use of drugs or having any disease which could interfere on bone metabolism, and non-pregnant or menopause women. A protocol was ...(Complete abstract click electronic access below)
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20

Feinglass, Erica A. "DESCRIPTIVE STUDY OF VITAMIN D STATUS AND CYSTIC FIBROSIS RELATED DIABETES." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429758063.

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Ma, Liangyu [Verfasser]. "Ex situ analysis of bone mineral density and cellular activity in type 1 diabetes mellitus / Liangyu Ma." Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/1221084941/34.

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Pires, Juliana Rico [UNESP]. "Influência do estado diabético na doença periodontal induzida em ratos: análise metabólica, genética e radiográfica." Universidade Estadual Paulista (UNESP), 2008. http://hdl.handle.net/11449/104733.

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Evidências sugerem existir correlação positiva entre diabetes mellitus e destruição periodontal. Com intuito de estudar a influência do Diabetes Mellitus sobre a evolução da doença periodontal induzida, o presente estudo apresenta como objetivos, avaliar alterações metabólicas como, peso corporal, níveis séricos de cálcio, fósforo e fosfatase alcalina, alterações macroscópicas e óssea, e a expressão tecidual de mieloperoxidase e das citocinas IL-1β, IL-6, TNF-α, IFN-γ. Foram utilizados ratos machos Wistar divididos em 4 grupos de 24 ratos, sendo: Grupo I controle; Grupo II diabético; Grupo III controle com doença periodontal induzida e Grupo IV diabético com doença periodontal induzida. Após dois dias da confirmação do estado diabético induzido por estreptozotocina, foi realizada a colocação da ligadura. Oito animais de cada grupo foram sacrificados nos períodos experimentais de 3, 7, 15 e 30 dias após colocação da ligadura. Foi utilizado testes bioquímicos para avaliação das enzimas séricas, lupa esteroscópica para análise macroscópica, programa analisador de imagens digital para mensuração da perda óssea, leito de ELISA para determinar a concentração de MPO e Real-time PCR para expressão das citocinas. Os resultados demonstraram que o estado diabético perdurou até o final do experimento nos grupos II e IV, com níveis glicêmicos elevados. Dentre os marcadores bioquímicos, somente a ALP apresentou-se estatisticamente maior nos grupos diabéticos (II e IV). Macroscopicamente, houve diferença somente entre os grupos com e sem doença periodontal, independente da presença do diabetes, com maior alteração tecidual, caracterizada por migração apical da gengiva marginal, perda de contorno marginal e de tecido interdental, nos períodos tardios de periodontite (15 e 30 dias).
Evidences suggest the existence of a positive correlation between diabetes mellitus and periodontal collapse. In order to evaluate the influence of Diabetes Mellitus on the progression of periodontal disease induced in rats, the objective of the present study was to verify glycemic, calcium, phosphorus and alkaline phosphatase serum levels, to evaluate tissue and alveolar bone loss, myeloperoxidase (MPO) gingival levels, as IL-1β, IL-6, TNF-α, IFN-γ tissue expression. Wistar male rats were used in this study. They were divided into 4 groups of 24 rats each, as follows: Group I – control; Group II – diabetic; Group III – control with periodontal disease induced; and Group IV – diabetic with periodontal disease induced. After streptozotocin diabetic state was confirmed, a ligature was placed on the mandibular first molar teeth of Groups III and IV rats. Eight animals of each group were killed at the experimental periods of 3, 7, 15 and 30 days after the ligature placement. Was used biochemical tests for evaluation of serum enzymes, magnifying glass to macroscopic analysis, digital image analyzer program for measurement of bone loss, ELISA to determine the concentration of MPO and Real-time PCR for expression of cytokines. Results demonstrated that the diabetic state lasted up to the end of the experiment at groups II and IV. Significant increases in serum alkaline phosphatase were observed at diabetic groups (II and IV). Macroscopically, in the groups where periodontal disease was induced, it was possible to observe more tissue alterations and it was higher in the 30-day experimental period. The MPO levels were significantly higher in induced periodontitis groups (III and IV) (p<0.05). The Group IV showed higher bone loss significantly when compared to the other groups (p < 0.05). The cytokines IL-6 and IFN-γ were elevated in groups III and IV at 30 ° day. The cytokine IL-1β was reduced at group II.

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Bighetti, Bruna Barros. "Avaliação das citocinas TNF-α, RANKL e OPG e do número de osteoclastos no reparo de defeito ósseo em calvária de ratos diabéticos tratados com matriz óssea desmineralizada." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/25/25149/tde-25112016-114638/.

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Neste trabalho, foi avaliado a participação dos osteoclastos bem como a ação das citocinas RANKL, OPG e TNF-α durante a formação e remodelação óssea em defeitos ósseos de tamanho crítico em ratos normoglicêmicos e diabéticos tratados ou não com a MAOD. Para isso, foram utilizados 250 ratos machos Wistar. Trinta ratos foram utilizados para coleta dos fêmures e tíbias, os quais foram processados para obtenção da MAOD. Os demais 220 ratos foram divididos em Grupo Não Diabétido (CTL, n=110) e Grupo Diabético (DIAB, n= 110) induzido pela aplicação de uma dose única de 47 mg/Kg de massa corporal de estreptozotocina. Um defeito transósseo de 8 mm de diâmetro foi realizado nos ossos parietais dos ratos, sendo que, nos subgrupos CTL MAOD e DIAB MAOD, os defeitos foram preenchidos com MAOD e nos grupos CTL COAG e DIAB COAG apenas com coágulo sanguíneo. Após 0, 7, 14, 21 e 42 dias, as calotas cranianas foram coletadas para determinação da densidade de volume, número de osteoclastos/mm2 na área do defeito, quantificação por imunoistoquimica e expressão do RNAm para as proteínas RANKL, OPG e TNF-α. Os resultados para volume do tecido ósseo neoformado foi maior nos grupos CTL COAG e CTL MAOD, bem como no grupo DIAB MAOD quando comparado com DIAB COAG (CTL MAOD > CTL COAG e DIAB MAOD > DIAB COAG). O número de osteoclastos nos grupos CTL aumentaram significantemente (3,69 osteoclasto/mm2), enquanto que nos grupos MAOD aumentaram gradualmente até os 42 dias (2,8 osteoclasto/mm2). Os resultados para imunomarcação mostraram que a MAOD promove 1,28 vezes maior expressão de OPG, bem como de TNF-α tanto no grupo CTL (1,59 vezes) como no DIAB (1,76 vezes). Os resultados para expressão do RNAm para OPG mostrou que a média dos valores do grupo COAG comparado com a do grupo MAOD foi 1,91 vezes maior no grupo COAG. Já os valores para expressão de RANKL permaneceram constantes no grupo DIAB MAOD, com aumento significativo de 2,57 vezes aos 42 dias, sendo 4,3 vezes maior, quando comparado com a média dos outros grupos no mesmo período. Conclui-se que nos animais normoglicemicos, o tratamento com a MAOD aumenta a expressão de OPG, RANKL e TNF-α, assim como a atividade osteoclástica, promovendo reabsorção da MAOD e formação de tecido ósseo, enquanto que nos animais diabéticos, a atividade osteoclástica foi reduzida, sem alteração nos níveis de OPG e RANKL, reduzindo a reabsorção da MAOD e consequentemente da formação óssea.
Participation of osteoclasts was evaluated in reabsorption process of demineralized allogenic bone matrix (DABM) as well as the activity of cytokines RANKL, OPG and TNF- α during formation and bone remodeling in critial size defect of normoglycemic and diabetic rats treated or not with DABM. Therefore, 250 male Wistar rats were used. Thirty rats had femurs and tibias collected and processed to obtain DABM. 220 rats were divided into control group (CTL, n=110) and diabetic group (DIAB, n= 110) injected by a single dose of 47 mg/Kg of body weight streptozotocin. Were made 8mm bone defect on skulls of rats, in subgroups CTL DABM and DIAB DABM, defects were filled with DABM and subgroups CTL CLOT and DIAB CLOT were filled with blood clot. After 0, 7, 14, 21 and 42 days, the skulls were collected to determine the volume density, number of osteoclasts/mm2 into defects area, quantification by immunohistochemistry and RNAm expression of RANKL, OPG and TNF-α cytokines. The results of volume density of newly formed bone was higher in CTL CLOT and CTL DABM, as well as in DIAB DABM compared to DIAB CLOT (CTL DABM > CTL CLOT and DIAB DABM > DIAB CLOT). The number of osteoclasts in CTL groups increased to 3,69 osteoclasts/mm2, while in subgroups treated with DABM gradually increased up until 42 days (2,8 osteoclasts/mm2). Immunohistochemistry showed that DABM promotes an increase of 1.28-fold of OPG expression, as well as TNF-a expression in CTL group (1.59-fold) and DIAB group (1.76-fold). The results of RNAm expression of OPG showed that the average values of the CLOT subgroup compared to the average values of DABM subgroup was 1.91- fold higher in CLOT subgroup. The values of RANKL RNAm expression increase 2.57-fold at 42 days, being 4.3-fold higher than the average os the other groups in the same period. In conclusion, in the normoglicemic animals (CTL group), the treatment with DABM increase the expression of OPG, RANKL and TNF-α as the activity of osteoclasts, leading to DABM resorption and bone tissue formation, while in diabetic animals, the osteoclast activity was reduced, without changes in the leves of OPG and RANKL, decreasing DABM resorption and bone formation.

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Bozkurt, Ozlem. "Study Of Bone Characteristics And Muscle Quality In Metabolic Disorders." Phd thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614561/index.pdf.

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Although the effects of diabetes on bone mineral content has been studied, little is known about the structural alterations in collagen, maturation of apatite crystals and carbonate content in diabetic bone. The first part of this study aimed to investigate the mineral and organic properties of cortical, trabecular and growth plate regions of rat femur tissues in type I diabetes using FTIR microspectroscopy and Vickers microhardness test. A decrease in mineral content (degree of mineralization), decrease in microhardness, increase in carbonate content, increase in size and maturation of hydroxyapetite crystals, which are the implications of increased osteoporosis, were observed in diabetic bone. In addition, a decreased carbonate substitution into bone apatite and an increase in labile type carbonate was observed in diabetic bone. There was a decrease in the level of crosslinking of collagen in cortical and trabecular regions of diabetic femurs, implying a decrease in bone collagen quality that may contribute to bone fragility. Recent evidence implies that intramyocellular lipid accumulation is directly correlated with insulin resistance, a key parameter in the generation of obesity. The second part of this study is mainly focused on the determination of the structural and compositional characterization of macromolecules of longissimus dorsi and quadriceps muscles of Berlin fat mouse inbred (BFMI) lines using ATR-FTIR spectroscopy and FTIR microspectroscopic imaging, together with the quantification of fiber specific distribution of lipids in these muscles by the use of confocal microscopy. The study groups included 10 weeks old standard breeding diet fed (juvenile) and 20 weeks old high fat diet fed control and BFMI lines. The results revealed the loss of unsaturation in lipids, increased triglyceride content, increased amount of lipids having shorter chain length, increased lipid peroxidation and fiber specific accumulation of lipids in type IIa and intermediate fibers in skeletal muscles of both 10 weeks old and 20 weeks old BFMI lines, emphasizing their obese phenotype. However, the alterations were more prominent in skeletal muscles of 20 weeks old high fat diet fed BFMI lines, displaying a more severe obesity phenotype. The results of the characterization revealed that BFMI860 and BFMI861 lines are convenient models for the study of spontaneous obesity and studies to enlighten the genetic basis of obesity.

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Räkel, Agnès. "Importance of diabetes as a risk factor for fractures after solid organ transplantation." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112348.

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Background. Diabetes seems to be associated with an increased risk of fractures in the general population. We aimed to determine whether pre-transplant diabetes increases the risk of fractures among patients receiving solid organ transplantation.
Methods. We conducted a nested case-control study in a cohort of subjects 18 years and older who received a first solid organ transplantation in Quebec between January 1st 1986 and July 31st 2005, and who were covered by the RAMQ drug plan at least 1 year before the transplantation and 3 months after the date of discharge from the transplantation hospitalization. Cases were subjects from the cohort who had sustained a fracture between the date of discharge from the hospitalization for transplantation and the end of the study period or the patient's death. The fracture date was the case index date. All incidental fractures were included except fractures of the skull, phalanges of the hand and foot, multiple fractures and pathological fractures, and were identified by medical service claims. Controls were matched to cases on the type of organ transplanted and on the date of the transplantation (+/- 3 months). Crude and adjusted odds ratios (OR) were obtained with univariate and multivariate conditional logistic regression models.
Results. The study included 238 cases and 873 controls. Pre-transplant diabetes was present in 30% of the cases and 22% of the controls (crude OR: 2.16, 95% CI: 1.7--2.8). After adjusting for potential confounders, pre-transplantation diabetes remained a significant risk factor for fractures (adjusted OR: 1.94, 95% CI: 1.5--2.6).
Conclusion. Pre-transplant diabetes appeared to significantly increase post-transplant fractures among adults receiving solid organ transplantation.

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Arnez, Maya Fernanda Manfrin. "Diabetes mellitus altera a sinalização osteogênica e atrasa o processo de reparo ósseo após expansão rápida da maxila." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/58/58135/tde-03022015-094136/.

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Introdução: O diabetes mellitus (DM) é uma doença crônica caracterizada pela hiperglicemia associada a diversas alterações sistêmicas e uma das suas complicações é o processo de reparo ósseo comprometido. Entretanto, ainda não há estudos utilizando análises celulares e biomoleculares que avaliem o processo de reparo ósseo desta desordem metabólica quando associada à expansão rápida da maxila (ERM). Objetivo: O objetivo deste estudo foi avaliar a remodelação óssea e sinalização osteogênica durante a aplicação de mecânica ortodôntica para ERM em ratos diabéticos tipo1- induzidos. Material e Métodos: Cento e cinquenta ratos Wistar, machos, foram divididos aleatoriamente em seis grupos de estudo. Grupos: controle (C, n=30), veículo (V, n=15), diabetes mellitus tipo 1 induzido com estreptozotocina (D, n=30), controle submetido à ERM (Cd, n=30), veículo submetido à ERM (Vd, n=15) e diabetes mellitus tipo 1 induzido com estreptozotocina submetido à ERM (Dd, n=30). Os animais foram eutanasiados aos 3, 7 e 10 dias após ERM . Análises histológicas, mudanças no padrão de expressão gênica e proteica de osteoprotegerina, (OPG), RANK, RANKL, osteonectina (ONC), osteocalcina (OCC), sialoproteína óssea (BSP), osteopontina (OPN) e proteína morfogenética óssea 2 (BMP2), assim como as mudanças no peso corporal, na ingestão de água na glicemia foram avaliadas. A análise da expressão gênica e proteica foram realizadas por qRT-PCR e Western Blotting, respectivamente. Os dados foram submetidos ao teste estatístico ANOVA de duas vias e pós-teste de Tukey (α= 0,05). Resultados: Histologicamente no grupo Dd foi notado maior reabsorção óssea, com diversas áreas em degradação com ausência de osteoblastos, intensa atividade de reabsorção óssea solapante, presença de osteoclastos, células inflamatórias associada ao comprometimento da formação óssea quando comparado aos grupos D e Cd. Estes resultados foram confirmados também nos achados moleculares, uma vez que algumas sinalização gênicas e proteicas relacionadas a osteogênese foram reduzidas, ao passo que a sinalização osteoclastogênica foi estimulada, principalmente no período inicial de reparo ósseo. No grupo D, o processo de formação ósseo estava atrasado comparado ao grupo C, devido a alteração da expressão dos genes e proteínas que regulam o catabolismo e anabolismo ósseo, haja vista que havia maior presença de tecido ósseo imaturo e maior quantidade de áreas de remodelação ativa até o período mais tardio de estudo. No grupo Cd foi observado remodelação óssea, caracterizada por um tecido desorganizado na região da sutura palatina mediana, com intensas áreas inflamatórias, hemorrágicas e reabsortivas comparado ao grupo C. Contudo, até o período de 10 dias pós abertura da sutura, não foi possível observar o completo preenchimento do gap sutural por tecido ósseo. Estes resultados histológicos foram observados na sinalização de genes e proteínas no grupo Cd, uma vez que estes biomarcadores de formação e reabsorção óssea estavam alterados quando comparados aos grupos C e Dd. Conclusões: O DM alterou a sinalização para o metabolismo ósseo e atrasou o processo de reparo após ERM. Estes resultados reforçam a necessidade de avaliar o status do metabolismo ósseo dos pacientes durante tratamento ortopédico e/ ou ortodôntico, visto que a aplicação destas forças na presença do DM podem promover efeitos indesejáveis.
Background: Diabetes mellitus (DM) is a disease associated with several disorders of health in humans and one of the most important is the jeopardizing of bone formation. However, to the best of our knowledge there is no information about the influence of diabetes on orthodontic and orthopedic treatment at cellular and molecular levels. Objective: The aim of this study was to evaluate bone remodeling process in palatal suture during orthopedic mecanotherapy in rats with type 1-induced diabetes mellitus. Material and Methods: One hundred and fifty Wistar male rats were randomly assigned to six groups. Groups: control (C, n=30), vehicle (B, n=15), type 1-induced diabetes mellitus using streptozotocin (D, n=30), control with RME (C+RME, n=30), vehicle with RME (C+RME, n=15) and type 1-induced diabetes mellitus using streptozotocin with RME (D+RME, n=30). The animals were euthanized at 3, 7 and 10 days after RME. Histologic evaluations, changes in genes and proteins expression of osteoprotegerin (OPG), RANK, RANKL, osteonectin (ONC), osteocalcin (OCC), bone sialoprotein (BSP), osteopontin (OPN) and bone morphognetic protein 2 (BMP2) were evaluated along with the changes in body weight, water intake and glycemic profile. Real-Time RT-PCR and Western Blotting were used to evaluate gene and the protein expression. Data were submitted to statistical analysis using two-way ANOVA followed by Tukey test ( α= 0,05). Results: On group D+RME it was observed an increased bone resorption, serveral undermining and tissue degradation areas. On the suture gap there were mainly inflammatory and osteoclasts cells associated with compromised bone formation compared to groups D and Cd. These results were observed also in molecular levels, since there were a reduced osteogenesis and an upregulation of osteoclastogenesis, mainly in early period of healing. On group D, bone formation was compromised compared to group C, due to changes on genes and proteins expression which regulates bone metabolism, considering that there was more immature bone and incresead active remodeling areas until late periods. On group Cd it was observed bone remodeling, characterized by desorganized tissue on the gap of midpalatal suture, with intense inflammatory hemorhagic and resorptive areas compared to group C. However until 10 days after RME, on group D the gap was not completely filled with bone tissue. These results were observed on the signaling of molecular biomarkers on group Cd, since they were changed compared to groups C and Dd. Conclusions: DM modify the signaling for bone metabolism and compromise bone repair after RME. During orthopedic and orthodontic treatment is necessary to evaluate metabolism status of subjects, since the application of these forces have been shown to promote undesirable effects mostly when associated with DM.

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Bezerra, Juciléia Barbosa. "Estudo dos efeitos do ultra-som de baixa intensidade e do exercício físico sobre consolidação de fraturas em ratos diabéticos." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/82/82131/tde-28062005-103643/.

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O diabetes Mellitus é uma doença na qual o organismo perde a habilidade de regular adequadamente o metabolismo dos carboidratos e é caracterizada entre outros sintomas, por hiperglicemia permanente. Especificamente, o diabetes Tipo I, está associado com a diminuição da integridade do tecido ósseo e, por isso, mais propenso à fraturas. Esta pesquisa refere-se ao estudo aplicação do ultra-som e do exercício físico (natação) como formas de consolidação de fraturas em fíbulas de ratos diabéticos e apresenta resultados das avaliações glicêmicas, radiológicas, histológica e de microscopia de luz polarizada. A avaliação do grau de birrefringência nos permitiu observar que os animais diabéticos, tanto os exercitados quanto os tratados apresentaram melhores resultados que os controles. O tratamento com ultra-som de baixa intensidade e o exercício físico foram eficazes na consolidação de osteotomias experimentais
Diabetes Mellitus is a desease characterized by lost of ability in the regulating the carbohydrate metabolism and it is represented by constant hiperglycaemia and others sintoms. Among the types of diabetes, the type I, is associated with the decrease of the bone tissue integrity and therefore more susceptible to fractures. This research is related to the aplication of ultrasound and physical exercise(swimming) to help healing of osteotomized fibulae in diabetics rats. The results were evaluated by glycaemics, radiological, hystological and polarized light microscopy analysis. Birefringence analysis showed that diabetic animals, exercited and treated with ultrasound presented better results as compared to the controls. The treatment with low intensity ultrasound and physical exercise demonstrated efficacy in experimental healing fractures

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Boyar, Handan. "Biophysical Investigation Of The Effects Of Antioxidants On Normal And Diabetic Rat Bone Tissues At Molecular Level." Phd thesis, METU, 2004. http://etd.lib.metu.edu.tr/upload/12605038/index.pdf.

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In the first part of this study, the effect of diabetes mellitus on the long bones (femur and tibia) of the streptozocin induced diabetic rats and the effect of selenium (Se) treatment on these bones are investigated at molecular level by Fourier transform infrared (FTIR) spectroscopy, light and electron microscopy. In the second part of this study, the effect of selenium and vitamin E deficiency or selenium toxicity on rat bones have been studied by FTIR spectroscopy. The results of the first part of the present study revealed that the changes observed in the mineral and matrix phases of diabetic bones, briefly, the increase in the mineral crystal size, the decrease in the acid phosphate and carbonate content, the increase in the ratio of pyridinoline [Pyr] cross-links to dihydroxylysinonorleucine [DHLNL] cross-links present in collagen I of the bone tissue as well as the increase in the lipid to protein ratio of the matrix are quite similar to those seen in osteoporotic patients and animal models and confirms the evidence of diabetic osteoporosis. Histologic studies carried out with light and electron microscopy supported these findings. FTIR spectroscopic analysis revealed that sodium selenite treatment had some restoring effects on the deviated properties of the microstructure of diabetic bones. The results of the second part of this study revealed that the deficiency of selenium led to increase in the crystal size of the bone minerals, decreases in acid phosphate and labile carbonate content and increase in the Pyr to DHLNL ratio as in the case of diabetic bones. These results can be indicative of the importance of selenium in glucose metabolism.The results of Se excess group are similar to those of Se deficient group except that toxic amount of selenium led to increase in the relative amount of acid phosphate. This can affect the pH of the mineral environment and lead to deformation of the bone tissue. It can be concluded from FTIR spectroscopic and light microscopic findings that both antioxidant deficient and excess diets cause almost similar defects in the mineral matrix phases of rat long bones. Overall results may reflect the importance of antioxidants for human life and if they are used in proper amounts they can be preventive for the complications of diabetes seen in bones as well as other organs. However, further investigations are necessary for the therapeutic usage of selenium, since the treatment of control group rat femurs with sodium selenite led to some structural defects.

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Laura, Ever Elias Mena. "Efeito das drogas antidiabéticas na movimentação dentária em ratos diabéticos tipo 1. Avaliação microtomográfica e histológica." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/25/25149/tde-26022016-140028/.

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A diabetes mellitus (DM) é um grupo de doenças metabólicas caracterizadas por hiperglicemia resultante do déficit na secreção e/ou ações de insulina. Dentre as muitas complicações da diabetes incluem a osteopenia diabética, que causa osteoporose e aumento do risco de fraturas ósseas. A patofisiologia da baixa resistência óssea associada a DM é considerada multifatorial, podendo ser decorrente da deficiência de insulina, resistência à insulina, insuficiência de osteoblastos, deficiência de vitamina D, formação e acúmulo dos produtos finais da glicação avançada e complicações microvasculares. Por isso, existe um interesse crescente no estudo da diabetes associada a outras alterações metabólicas e o efeito das drogas antidiabéticas, de forma a reverter os efeitos maléficos. O objetivo desse estudo foi avaliar a influência das drogas antidiabéticas na movimentação dentária ortodôntica e na densidade/microarquitetura óssea alveolar em ratos diabéticos. Assim, ratos Normoglicêmicos (NG,n=20) e Diabéticos induzidos pela estreptozotocina (DM1,n=60) foram divididos em: TinDM1(n=20) tratados com Insulina, TinmetDM1(n=20) tratados com Insulina+Metformina, e os STDM1(n=20) e STNG(n=20) que não receberam tratamento. Após 14 dias da indução, o 1o molar superior direito recebeu força ortodôntica (50g) em sentido mesial. Nos periodos experimentais de 0, 3, 7 e 14 dias, as maxilas foram coletadas e submetidas às análises microtomográficas para quantificar a movimentação dentária e a densidade óssea e histológica, para avaliar as alterações periodontais ocorridas durante a movimentação. Os dados microtomográficos foram submetidos à ANOVA a dois critérios e teste de Tukey (p<0,05). A indução com estreptozotocina induziu ao quadro de diabetes grave (glicemia de jejum de 325mg/dL) os quais foram acentuados com o tempo no grupo STDM1 (404mg/dL). A utilização de insulina e da associação insulina e metformina reduziram consideravelmente os níveis glicêmicos (127mg/dL). A força de 50g aplicadas no 1o molar promoveu movimentação dentária linear, sendo menor no grupo STNG (116μm) e maior nos diabéticos (173μm). Durante a movimentação a densidade óssea no grupo STNG foi mantida (BV/TV=83%), enquanto nos TinDM1 e TinmetDM1 ocorreu pequena redução (BV/TV=76%). Já nos STDM1 a força produziu grande perda óssea (BV/TV=62%). No grupo STDM1 O quadro histopatológico confirma os efeitos deletérios nas estruturas dentarias e periodontais durante a movimentação dentária, com acentuada perda óssea e processo inflamatório. A redução dos índices glicêmicos com utilização das drogas hipoglicemiantes nos grupos TinDM1 e TinmetDM1 equilibrou o processo de formação e reabsorção óssea no STNG, após os 3 dias da movimentação. Concluímos que, a utilização contínua de insulina ou insulina e metformina nos animais diabéticos diminuem significativamente o quadro de perda óssea alveolar decorrente das forças ortodônticas no estado diabético.
Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting in deficits in the secretion and/or insulin action. Among the many complications of diabetes, it includes diabetic osteopenia that causes osteoporosis and increased risk of bone fractures. The pathophysiology associated with low bone strength in DM is considered multifactorial and may be due to insulin deficiency, insulin resistance, osteoblast deficiency, vitamin D deficiency, formation and accumulation of advanced glycation end products and microvascular complications. Therefore, there is a growing interest in the study of diabetes associated with other metabolic abnormalities and the effect of antidiabetic drugs, in order to reverse the deleterious effects. The objective of this study was to evaluate the influence of antidiabetic drugs in orthodontic tooth movement and alveolar bone density/microarchitecture in diabetic rats. Thus, normoglycemic rats (NG, n=20) and streptozotocin-induced diabetic (DM1, n=60) were divided into TinDM1 (n=20) treated by insulin, TinmetDM1 (n=20) treated by Insulin + Metformin and STDM1 (n = 20) and STNG (n = 20) that received no treatment. After 14 days of induction, the M1 received orthodontic force (50g) to move mesially. After 0, 3, 7 and 14 days jaws were collected and subjected to microtomographic images analysis to quantify, tooth movement and bone density and histological analysis to evaluate periodontal changes occurred during the movement. Microtomographic data were submitted to two-way ANOVA and Tukey test (p <0.05). The induction with streptozotocin induced severe diabetes frame (fasting blood glucose 325 mg/dL) which accentuated over the time of the disease in STDM1 group (404mg/dL). The use of insulin and insulin and metformin reduced blood glucose levels to satisfactory values (127mg/dL). The strength of 50g applied on M1 promoted linear tooth movement, being lower in STNG group (116μm) and higher in diabetics (173μm). When handling bone density was maintained at STNG group (BV/TV = 83%), in TinDM1 and TinmetDM1 small reduction occurred (BV/TV = 76%). Already in STDM1 the force produced large bone loss (BV/TV = 62%). Histopathological analysis confirmed the deleterious effects on periodontal and dental structures during tooth movement in STDM1 group, with marked bone loss and inflammatory process. Reducing the glycemic index by using insulin in TinDM1 group and insulin + metformin in TinmetDM1 balanced process of bone formation and resorption after 3 days of mechanical loading. We conclude that the continuous use of insulin or insulin and metformin in diabetic animals diminishesalveolar bone loss resulting from orthodontic forces in the diabetic condition.

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Butner, Katrina Lindauer. "An Evaluation of 1) Bone Changes Following Bariatric Surgery and 2) Fat and Muscle Indices Assessed by pQCT: Implications for Osteoporosis and Type-2 Diabetes Risk." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/73000.

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STUDY 1 Aim: To compare the effects of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) on changes in bone mineral density (BMD), weight loss and blood biomarkers related to bone turnover, hormonal, and nutrient status. Subjects: Nine bariatric surgery patients. Methods: Patients had a DXA bone scan and fasting blood draw at baseline, three, and six months following surgery. Results: RYGB patients had greater weight loss vs. LAGB at both three (mean loss: 19 vs. 9%) and six months (26 vs. 11%), p<0.01. RYGB patients lost an average of 7% hip BMD at six months. Hip BMD loss at six months was correlated to decreased leptin (r=0.88) and increased adiponectin (r=-0.82), p<0.05. Bone turnover was indicated by elevated serum bone biomarkers after surgery. Conclusions: Research with larger sample sizes is warranted to better evaluate potential implications for late-life osteoporosis risk following bariatric surgery. STUDY 2 Aim: To determine repeatability for IMAT and muscle density, to evaluate the distribution of foreleg muscle and fat indices measured by pQCT and to determine predictors of muscle density and type-2 diabetes risk. Subjects: 82 women with varying BMI and physical activity levels. Methods: Subjects had DXA and pQCT bone scans, a fasting blood draw, and completed a 4-day physical activity record. Results: Fat and muscle distribution in the foreleg was highly correlated to total and central body adiposity. The pQCT device reliably measured muscle density (CV=0.8%), thus justifying use as surrogates for IMAT. Muscle density was positively related to physical activity (r=0.29; p<0.05) and negatively associated with markers of fat distribution and risk for type-2 diabetes [HOMA-IR (r=-0.44, p<0.01)]. Conclusions: Further research is necessary to determine whether specific fat or muscle depots can be targeted through exercise training to help with the prevention and treatment of obesity or type-2 diabetes.
Ph. D.

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Yamamoto, Aline Pedro de Melo [UNESP]. "Efeito do treinamento resistido na densidade mineral óssea e no conteúdo de GLUT4 em ratos diabéticos (tipo 2) osteopênicos." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/116015.

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Made available in DSpace on 2015-03-03T11:52:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-06-05Bitstream added on 2015-03-03T12:06:56Z : No. of bitstreams: 1 000795119.pdf: 2453841 bytes, checksum: e19b07c8eebd62f3e8420a38c9ef487c (MD5)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Fundação para o Desenvolvimento da UNESP (FUNDUNESP)
O diabetes melittus (DM) é considerado um importante problema na saúde pública em vários países do mundo, pois além de estar em ascendente prevalência, compromete tanto a produtividade quanto a qualidade de vida e sobrevida dos seus portadores. Sua principal característica é a presença de hiperglicemia crônica decorrente de defeitos na secreção e/ou ação da insulina. A literatura tem mostrado uma associação de DM com redução da massa óssea. Contudo, os mecanismos de mudanças da densidade mineral óssea (DMO) nesses pacientes diabéticos ainda não estão claros. Portanto, o objetivo deste estudo foi investigar o efeito do treinamento resistido (TR) sobre a DMO, as propriedades biomecânicas do osso, glicemia, calcemia, fosfatemia, a sensibilidade à insulina e a expressão de GLUT4 em ratos osteopênicos com diabetes tipo 2 (DM2). Para tanto, foram utilizados 64 ratos machos (5 dias de idade) divididos em dois grandes grupos: grupo controle (CN), que recebeu injeção de veículo (tampão citrato 10 mmol/L, pH 4.5 i.p.) e grupo diabético (DM), que recebeu injeção de estreptozotocina (150 mg/kg i.p.). Após 55 dias, foi mensurada a glicose de cada animal utilizando o monitor (Accu-Chek Advantage, Roche Diagnostics, Indianapolis, IN) para verificar se os animais do grupo DM estavam diabéticos. Apenas os ratos do grupo DM com glicose acima de 200mg/dl foram utilizados no experimento. Logo em seguida, todos os animais foram anestesiados com cloridrato de quetamina (80 mg/kg de peso corporal, i.m) e xilazina (10 mg/kg de peso corporal, i.m) para realizar a primeira análise densitométrica (AD) (pré-suspensão) da tíbia direita por emissões de absorciometria de raios-X (DXA), do aparelho DPX (Lunar DPX Alpha, WI, USA). Em seguida, esses grupos foram subdivididos em quatro grupos: CN, controle osteopênicos (CO), DM e diabéticos...
Diabetes mellitus (DM) is considered an important public health problem in many countries of the world, because, besides being in ascending prevalence, it commits the productivity, the quality of life and survival of their bearers. Its main characteristic is the presence of chronic hyperglycemia due to defects in secretion and/or insulin action. The literature has shown an association between DM and reduced bone mass. However, the mechanisms of change in bone mineral density (BMD) in these diabetic patients are still unclear. Therefore, the aim of this study was to investigate the effect of resistance training (RT) on BMD, bone biomechanical properties, glycemia, calcemia and phosphatemia, insulin sensitivity and GLUT4 expression in osteopenic rats with type 2 diabetes (DM2). Thus, we used 64 male rats (5 days old) divided into two groups: control (CN), which received an injection of vehicle (citrate buffer 10 mmol/L, pH 4.5 i.p.) and diabetic (DM), which received an injection of streptozotocin (150 mg/kg i.p). After 55 days, glucose was measured in each animal using the monitor (Accu-Chek Advantage, Roche Diagnostics, Indianapolis, IN) to verify if animals of DM group were diabetic. Only diabetic group rats with glucose above 200mg/dl were used in the experiment. After that all animals were anesthetized with ketamine (80 mg/kg body weight, i.m) and xylazine (10 mg/kg bodyweight i.m) so that the first densitometric analysis (DA) (pre-suspension) of the right tibia by dual X-ray absorptiometry emissions (DXA), from apparatus DPX (Lunar DPX Alpha, WI, USA) was performed. Then, these groups were subdivided into four groups: CN, osteopenic control (OC), DM and osteopenic diabetic (OD). Animals in groups OC and OD were suspended by their tails for a period of 21 days to promote osteopenia in hindlimb. Thereafter, the second DA (post-suspension)...
FAPESP: 10/14755-5

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32

Green, Kathy H. "Type 1 diabetes and bone mass, interrelationships with nutrient intake and physical activity in children and with dietary fish oil in weanling rats." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ57543.pdf.

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Pacios, Pujadó Sandra. "Cellular Mechanisms that affect Periodontal Destruction induced by Bacteria Infection in Diabetic and Non Diabetic Rats." Doctoral thesis, Universitat Internacional de Catalunya, 2014. http://hdl.handle.net/10803/275965.

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The aim of this study was to evaluate the histologic and cellular response to A.actinomycetemcomitans (A.a) infection, and how diabetes-enhanced TNF-α production and diabetes-enhanced apoptosis contribute to the periodontal disease progression and bone coupling. Conclusion. The results link A. a infection with important characteristics of periodontal destruction and provide new insight into how diabetes aggravates A. a induced periodontal destruction in rats by significantly increasing the inflammatory response, leading to increased bone loss and enhancing apoptosis of gingival epithelial and connective tissue cells through a caspase-3-dependent mechanism. Antibiotics had a more pronounced effect on many of these parameters in diabetic than in normoglycemic rats, suggesting a deficiency in the capacity of diabetic animals to resist infection. In addition, diabetes prolongs inflammation and osteoclastogenesis in periodontitis and through TNF limits the normal reparative process by negatively modulating factors that regulate bone.
El objetivo de este estudio fue evaluar la respuesta histológica y celular a la infección por A.actinomycetemcomitans (A.a) y como la diabetes exacerba la producción de TNF- α y la apoptosis que contribuye a la progresión de la enfermedad periodontal y al acoplamiento del hueso. Los resultados enlazan la infección de A. a con características importantes de destrucción periodontal y ofrece una nueva visión de cómo la diabetes agrava la destrucción periodontal con A. a mediante un aumento significativo de la respuesta inflamatoria, lo que lleva al aumento de pérdida ósea y produce un aumento de apoptosis en el epitelio gingival y en las células del tejido conectivo a través de un mecanismo de caspasa-3 dependiente. Los antibióticos tuvieron un efecto más pronunciado en mucho de los parámetros evaluados en las ratas diabéticas que en las normoglucémicas, sugiriendo una deficiencia en la capacidad de los animales diabéticos en combatir la infección. Además la diabetes prolonga la inflamación y la osteoclastogénesis en la periodontitis y a través de TNF limita el proceso normal de reparación modulando negativamente factores que regulan el hueso.

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Tabatabaei, Negar. "Is there a threshold at which vitamin D status during pregnancy optimizes maternal and neonatal health outcomes? A focus on bone and gestational diabetes." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119564.

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Low vitamin D status, defined by circulating 25-hydroxy vitamin D (25(OH)D) <50 or <75 nmol/L is prevalent among pregnant women and has been associated with neonatal rickets and gestational diabetes mellitus (GDM). Osteocalcin (OC), a bone formation biomarker, linking the bone to glucose metabolism is stimulated by 1,25-dihydroxyvitamin D (1,25(OH)2D), the active form of vitamin D. In the first study, maternal serum 25(OH)D and OC were explored at early and mid-gestation in GDM (case, n=48) vs healthy (control, n=48) Caucasian pregnant women. Maternal serum 25(OH)D was not different (p=0.80) while OC was higher (p=0.006) in those with GDM vs controls across all trimesters. There are no vitamin D dose-response studies on glucose tolerance and bone outcomes in human and animals. Animal studies commonly use isoflurane, an anaesthetic, which may affect OC and glucose concentrations. Therefore, in the second study, the effect of isoflurane exposure was studied on bone biomarkers in guinea pigs (n=10) at 5, 9 wk of age and glucose at postpartum (26 wk). Isoflurane increased OC during rapid growth (p<0.001) and increased glucose at postpartum (p<0.0001). In the third study, the dose-response effect of maternal dietary vitamin D was investigated on maternal glucose tolerance. Female 4 mo old guinea pigs (n=45) were randomized to isocaloric diets containing different dosages of vitamin D3 (0, 0.25, 0.5, 1 and 2 IU/g diet) from mating to delivery. The results revealed no differences in AUC (area under the curve) for maternal glucose from the OGTT (oral glucose tolerance test) across groups during pregnancy. However, an inverse association was observed between pre-mating 25(OH)D and AUC for glucose. In the fourth study, the dose-response effect of dietary vitamin D was studied on maternal and neonatal bone outcomes. In the sows, a positive dose-response (p<0.0001) was observed in plasma 25(OH)D but 1,25(OH)2D reached a plateau once dietary vitamin D was >0.5 IU/g diet. No differences in areal (aBMD) or volumetric bone mineral density (vBMD) or biomarkers were observed among maternal groups. In the 2 d guinea pig neonate: both 25(OH)D and 1,25(OH)2D followed a dose-response (p<0.0001) to maternal diet, femoral aBMD was 10 % higher in the 2 IU vs all groups except the 0 IU (p=0.04). At the neonatal distal femur and proximal tibia, response to maternal diet was U-shaped for trabeculae (Tb.) vBMD. Expansion of the femur growth plate was observed in the 0 IU vs all other groups. In conclusion, vitamin D status may be more important at pre-mating than mid-gestation in protecting against pregnancy induced glucose intolerance. To reflect normal metabolism, measurements of OC and glucose prior to isoflurane anaesthesia are recommended. Maternal vitamin D status below recommendations may result in features similar to rickets in the offspring but status above recommendations may not be advantageous to the bone in the guinea pig.
Un taux faible en vitamine D, soit une concentration inférieure à 50-75 nmol/L de 25-hydroxy vitamine D (25(OH)D) dans le sang, est fréquent chez les femmes enceintes et est associée au rachitisme néonatal et au diabète gestationnel (GDM). L'ostéocalcine (OC), un biomarqueur qui relie le métabolisme du glucose à la formation osseuse, est stimulée par la forme active de la vitamine D (1,25-dihydroxyvitamine D (1,25(OH)2D)). La première étude de cette thèse a identifié les taux sérique de 25(OH)D et d'OC chez les femmes enceintes blanches du Québec, en santé (n=48), ou atteintes de GDM (n=48), au début et au milieu de leur gestation. Les résultats ont révélé que chez les personnes atteintes de GDM vs en santé, les taux sériques maternels de 25(OH)D ne sont pas différents (p=0.80) mais les taux d'OC sont plus élevés (p=0.006) durant tous les trimestres. Aucune étude n'a examiné simultanément les doses en vitamine D et ses effets sur la tolérance au glucose et la formation osseuse. De plus, les études précédentes sur modèles animaux ont utilisé de l'isoflurane comme anesthésique, un produit qui peut affecter les concentrations d'OC et de glucose dans le sang. Afin d'étudier ces critères, une examination chez les cochons d'indes (n=10) à 5 et 9 semaines de gestations, l'effet de l'isoflurane (20-25 min) sur les biomarqueurs osseux (OC, désoxypyridinoline totale (tDPD)) ainsi que les niveaux de glucoses après l'accouchement (26 semaines) a été exécutée. Les résultats démontrent que l'isoflurane augmente les taux d'OC pendant la croissance rapide (p<0.001), et accrois les niveaux de glucose après l'accouchement (p<0.0001). Le troisième projet consiste d'étudier les effets des doses alimentaires en vitamine D et la tolérance au glucose des femelles cochon d'indes enceintes. Des femelles âgées de quatre mois (n=45) ont été soumises à une diète de différentes doses de vitamine D3 (0, 0,25, 0,5, 1 et 2 IU/g d'aliments) pendant leur grossesse. Les résultats révèlent aucune différence de l'ASC (l'aire sous la courbe) pour le glucose ainsi que les concentrations d'OC. Cependant, une association inverse a été observée entre les niveaux de 25(OH)D et l'ASC du glucose avant accouplement. La dernière étude examine chez les mères enceintes et nouveaux-nés, l'effet des doses en vitamine D provenant de l'apport alimentaire sur les densités des os. Chez les femelles cochon d'indes, une réponse positive (p<0.0001) aux doses de vitamine D alimentaire a été observée sur les niveaux de 25(OH)D dans le plasma, tandis que les taux en 1,25(OH)2D ont atteint un plateau lorsque les doses alimentaires en vitamine D était plus grande que 0.5 IU/g d'aliments. Aucune différences de superficie ou volume de la densité minérale osseuse (sDMO – vDMO), ou des niveaux de biomarqueurs, ont été observées entre les groupes maternels. Chez les nouveaux-nés de 2 jours, bien que les taux de 25(OH)D et 1,25(OH)2D ont suivie une réponse par rapport à l'alimentation de la mère (p<0.0001), le sDMO fémorale était 10% plus élevé dans le groupe 2 IU/g par rapport à tous les autres groupes sauf le groupe 0 IU/g d'aliments (p=0.04). De plus, au niveau du fémur distal et du tibia proximal des nouveaux-nés, la réponse au régime alimentaire de la mère était en forme de trabécule. Les résultats d'histologie suggèrent une expansion de croissance du fémur dans le groupe 0 IU/g d'aliments vs tous les autres groupes. Dans l'ensemble, cette thèse suggère que les niveaux en vitamine D sont plus importants avant la grossesse que pendant car ils génèrent une protection à l'intolérance au glucose. Elle recommande aussi de mesurer les niveaux d'OC et de glucose avant l'utilisation d'isoflurane dans les modèles animaux de GDM. De plus, les études démontrent que les taux de vitamine D en dessous des recommandations peuvent entraîner chez la progéniture des caractéristiques ressemblant au rachitisme. Par contre, un apport en dessus des doses recommandées n'est pas avantageux pour les os.

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Yamamoto, Aline Pedro de Melo. "Efeito do treinamento resistido na densidade mineral óssea e no conteúdo de GLUT4 em ratos diabéticos (tipo 2) osteopênicos /." Araçatuba, 2013. http://hdl.handle.net/11449/116015.

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Orientador: Doris Hissako Sumida
Banca: Sérgio Eduardo de Andrade Perez
Banca: Maria Aparecida Visconti
Resumo: O diabetes melittus (DM) é considerado um importante problema na saúde pública em vários países do mundo, pois além de estar em ascendente prevalência, compromete tanto a produtividade quanto a qualidade de vida e sobrevida dos seus portadores. Sua principal característica é a presença de hiperglicemia crônica decorrente de defeitos na secreção e/ou ação da insulina. A literatura tem mostrado uma associação de DM com redução da massa óssea. Contudo, os mecanismos de mudanças da densidade mineral óssea (DMO) nesses pacientes diabéticos ainda não estão claros. Portanto, o objetivo deste estudo foi investigar o efeito do treinamento resistido (TR) sobre a DMO, as propriedades biomecânicas do osso, glicemia, calcemia, fosfatemia, a sensibilidade à insulina e a expressão de GLUT4 em ratos osteopênicos com diabetes tipo 2 (DM2). Para tanto, foram utilizados 64 ratos machos (5 dias de idade) divididos em dois grandes grupos: grupo controle (CN), que recebeu injeção de veículo (tampão citrato 10 mmol/L, pH 4.5 i.p.) e grupo diabético (DM), que recebeu injeção de estreptozotocina (150 mg/kg i.p.). Após 55 dias, foi mensurada a glicose de cada animal utilizando o monitor (Accu-Chek Advantage, Roche Diagnostics, Indianapolis, IN) para verificar se os animais do grupo DM estavam diabéticos. Apenas os ratos do grupo DM com glicose acima de 200mg/dl foram utilizados no experimento. Logo em seguida, todos os animais foram anestesiados com cloridrato de quetamina (80 mg/kg de peso corporal, i.m) e xilazina (10 mg/kg de peso corporal, i.m) para realizar a primeira análise densitométrica (AD) (pré-suspensão) da tíbia direita por emissões de absorciometria de raios-X (DXA), do aparelho DPX (Lunar DPX Alpha, WI, USA). Em seguida, esses grupos foram subdivididos em quatro grupos: CN, controle osteopênicos (CO), DM e diabéticos...
Abstract: Diabetes mellitus (DM) is considered an important public health problem in many countries of the world, because, besides being in ascending prevalence, it commits the productivity, the quality of life and survival of their bearers. Its main characteristic is the presence of chronic hyperglycemia due to defects in secretion and/or insulin action. The literature has shown an association between DM and reduced bone mass. However, the mechanisms of change in bone mineral density (BMD) in these diabetic patients are still unclear. Therefore, the aim of this study was to investigate the effect of resistance training (RT) on BMD, bone biomechanical properties, glycemia, calcemia and phosphatemia, insulin sensitivity and GLUT4 expression in osteopenic rats with type 2 diabetes (DM2). Thus, we used 64 male rats (5 days old) divided into two groups: control (CN), which received an injection of vehicle (citrate buffer 10 mmol/L, pH 4.5 i.p.) and diabetic (DM), which received an injection of streptozotocin (150 mg/kg i.p). After 55 days, glucose was measured in each animal using the monitor (Accu-Chek Advantage, Roche Diagnostics, Indianapolis, IN) to verify if animals of DM group were diabetic. Only diabetic group rats with glucose above 200mg/dl were used in the experiment. After that all animals were anesthetized with ketamine (80 mg/kg body weight, i.m) and xylazine (10 mg/kg bodyweight i.m) so that the first densitometric analysis (DA) (pre-suspension) of the right tibia by dual X-ray absorptiometry emissions (DXA), from apparatus DPX (Lunar DPX Alpha, WI, USA) was performed. Then, these groups were subdivided into four groups: CN, osteopenic control (OC), DM and osteopenic diabetic (OD). Animals in groups OC and OD were suspended by their tails for a period of 21 days to promote osteopenia in hindlimb. Thereafter, the second DA (post-suspension)...
Mestre

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36

Davidson, Melissa Anne. "A Pharmacovigilance Approach for Assessing Cardiovascular, Osteological, and Carcinogenic Risk Associated with Thiazolidinedione Drugs Used in the Treatment of Type 2 Diabetes Mellitus." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/38062.

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Diabetes is a chronic and debilitating disease that affects nearly half a billion people worldwide with the vast majority of diabetics suffering from Type 2 diabetes mellitus (T2DM), a disease characterized by insulin insensitivity that often requires pharmacotherapy to effectively maintain target blood sugar levels. The thiazolidinedione (TZD) class of drugs consists of oral hypoglycaemic agents used alone or in combination with other antidiabetic drugs to treat T2DM. The drugs within this class, which include rosiglitazone and pioglitazone, were originally heralded as providing novel first and second-line treatment of T2DM with glycaemic control and physiological effects comparable to, and in some cases, better than, first-line treatments such as metformin. However, over time they have also been associated with adverse cardiovascular, osteological, and carcinogenic effects in some, but not all clinical trials, observational studies, and meta-analyses. Given the conflicting evidence to date on the safety of TZD drugs, their role in the treatment of T2DM continues to be debated and epidemiological gaps remain. The objectives of this doctoral research are fourfold: 1) to conduct an in-depth review of the epidemiology of TZD pharmacotherapy including pharmacokinetics and modes of action, the results of previous studies investigating health risks and benefits associated with TZD treatment, and new and future uses for this class of drugs; 2) to determine whether diabetic patients treated with TZDs are at increased risk of adverse cardiovascular outcomes; 3) to assess whether TZD pharmacotherapy is associated with an increased risk of bone fractures and whether risks differ depending on fracture site and patient sex; and, 4) to investigate associations between TZD use and risk of bladder cancer. Specific research questions were investigated using nested case-control analyses designed to capture incident users of antidiabetic drugs and electronic health data from Cerner Health Facts®, an electronic medical record database that stores time-stamped patient records from more than 480 contributing hospitals throughout the United States. Findings from this work are reported in a series of manuscripts, including a published review paper. Key findings include: 1) TZD use was associated with an increased risk of incident myocardial infarction and congestive heart failure compared to never use of TZD drugs with a trend towards a potential early treatment effect within the first year of exposure to pioglitazone; 2) TZD use was associated with an increased risk of closed bone fractures among Type 2 diabetics with use of pioglitazone or rosiglitazone associated with an increased risk across multiple fracture sites in women, but only rosiglitazone use in men and only at peripheral fracture sites; 3) use of either pioglitazone or rosiglitazone were associated with an increased risk of incident bladder cancer compared to never users, however, a low number of bladder cancer cases resulted in underpowered analyses; and, 4) insulin use in a hospital setting may replace a patient's normal course of antidiabetic therapy which, when combined with other potential sources of bias in traditional nested case-control studies using hospital-based data, may lead to overestimation or underestimation of adverse health risks associated with non-insulin antidiabetic therapies. Although these findings warrant replication, the results of the research contained within this dissertation suggest that caution should be exercised when prescribing diabetic patients TZD drugs if they have cardiovascular, osteological, or carcinogenic risk factors. Additional pharmacovigilance studies should also continue to strive to better understand the health risks related to TZD therapy, especially as new therapeutic roles for TZDs in the prevention and treatment of some cancers, inflammatory diseases, and other conditions in non-diabetic populations are being explored.

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Ingberg, Claes-Mårten. "Type 1 diabetes mellitus: Aspects of long-term complications and body composition." Doctoral thesis, Uppsala University, Department of Medical Sciences, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3287.

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Studies concerning social consequences, gastrointestinal and urinary tract symptoms were conducted in a population-based cohort comprising patients with long-standing type 1 diabetes and matched control persons. Three different questionnaires were sent by mail to diabetic patients and control persons. After a mean duration of 28.7±2.6 years, compared to the controls the diabetic patients showed an almost 10 times higher mortality, a lower employment rate and greater need for welfare benefits. These differences were mainly due to diabetic late complications. Education, housing conditions, life-style, civil state, alcohol and smoking habits were similar in the two groups. The prevalence of gastrointestinal symptoms was significantly higher in the diabetic patients than in the controls, and this was found to be attributable to the female diabetic patients. Female diabetic patients had been treated with antibiotics for urinary tract infections more often than controls, they experienced more social problems than controls in daily life because of urinary tract problems and used clamps to prevent wetting more often than did controls.

Body composition and bone mineral density were evaluated in parts of the cohort with long-standing type 1 diabetes and control persons in another population-based cohort comprising diabetic females aged 16-19 years with type 1 diabetes since childhood and matched controls. Besides a tendency to reduced abdominal fat mass in diabetic males, no difference was observed in fat mass, muscle mass or bone mineral density between the patients with long-standing type 1 diabetes and controls. Significant correlations were found between insulin dosage and whole body fat mass in diabetic females and between serum cholesterol levels and abdominal fat mass in diabetic males. The female adolescents had a higher body mass index than the controls, and their overweight was shown to consist almost entirely of an increased fat mass. The distribution of fat, expressed as abdominal-to-leg ratio, correlated significantly to HbA1c and daily dosage of insulin. Bone mineral density did not differ between the groups. IGF I was significantly lower both in patients with long-standing type 1 diabetes and in the adolescent diabetic females compared with their matched controls.

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Pires, Juliana Rico. "Influência do estado diabético na doença periodontal induzida em ratos : análise metabólica, genética e radiográfica /." Araraquara : [s.n.], 2008. http://hdl.handle.net/11449/104733.

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Resumo: Evidências sugerem existir correlação positiva entre diabetes mellitus e destruição periodontal. Com intuito de estudar a influência do Diabetes Mellitus sobre a evolução da doença periodontal induzida, o presente estudo apresenta como objetivos, avaliar alterações metabólicas como, peso corporal, níveis séricos de cálcio, fósforo e fosfatase alcalina, alterações macroscópicas e óssea, e a expressão tecidual de mieloperoxidase e das citocinas IL-1β, IL-6, TNF-α, IFN-γ. Foram utilizados ratos machos Wistar divididos em 4 grupos de 24 ratos, sendo: Grupo I controle; Grupo II diabético; Grupo III controle com doença periodontal induzida e Grupo IV diabético com doença periodontal induzida. Após dois dias da confirmação do estado diabético induzido por estreptozotocina, foi realizada a colocação da ligadura. Oito animais de cada grupo foram sacrificados nos períodos experimentais de 3, 7, 15 e 30 dias após colocação da ligadura. Foi utilizado testes bioquímicos para avaliação das enzimas séricas, lupa esteroscópica para análise macroscópica, programa analisador de imagens digital para mensuração da perda óssea, leito de ELISA para determinar a concentração de MPO e Real-time PCR para expressão das citocinas. Os resultados demonstraram que o estado diabético perdurou até o final do experimento nos grupos II e IV, com níveis glicêmicos elevados. Dentre os marcadores bioquímicos, somente a ALP apresentou-se estatisticamente maior nos grupos diabéticos (II e IV). Macroscopicamente, houve diferença somente entre os grupos com e sem doença periodontal, independente da presença do diabetes, com maior alteração tecidual, caracterizada por migração apical da gengiva marginal, perda de contorno marginal e de tecido interdental, nos períodos tardios de periodontite (15 e 30 dias).
Abstract: Evidences suggest the existence of a positive correlation between diabetes mellitus and periodontal collapse. In order to evaluate the influence of Diabetes Mellitus on the progression of periodontal disease induced in rats, the objective of the present study was to verify glycemic, calcium, phosphorus and alkaline phosphatase serum levels, to evaluate tissue and alveolar bone loss, myeloperoxidase (MPO) gingival levels, as IL-1β, IL-6, TNF-α, IFN-γ tissue expression. Wistar male rats were used in this study. They were divided into 4 groups of 24 rats each, as follows: Group I - control; Group II - diabetic; Group III - control with periodontal disease induced; and Group IV - diabetic with periodontal disease induced. After streptozotocin diabetic state was confirmed, a ligature was placed on the mandibular first molar teeth of Groups III and IV rats. Eight animals of each group were killed at the experimental periods of 3, 7, 15 and 30 days after the ligature placement. Was used biochemical tests for evaluation of serum enzymes, magnifying glass to macroscopic analysis, digital image analyzer program for measurement of bone loss, ELISA to determine the concentration of MPO and Real-time PCR for expression of cytokines. Results demonstrated that the diabetic state lasted up to the end of the experiment at groups II and IV. Significant increases in serum alkaline phosphatase were observed at diabetic groups (II and IV). Macroscopically, in the groups where periodontal disease was induced, it was possible to observe more tissue alterations and it was higher in the 30-day experimental period. The MPO levels were significantly higher in induced periodontitis groups (III and IV) (p<0.05). The Group IV showed higher bone loss significantly when compared to the other groups (p < 0.05). The cytokines IL-6 and IFN-γ were elevated in groups III and IV at 30 ° day. The cytokine IL-1β was reduced at group II.
Orientador: Denise Madalena Palomari Spolidorio
Coorientador: Carlos Rossa Junior
Banca: Marinella Holzhausen
Banca: Solange Alonso Vergani
Banca: Joni Augusto Cirelli
Banca: Benedicto Egbert Corrêa de Toledo
Doutor

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Cignachi, Nat?lia Pradella. "Regenera??o ?ssea em camundongos : correla??o entre diabetes tipo 1 e menopausa experimental." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2018. http://tede2.pucrs.br/tede2/handle/tede/8172.

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
This thesis encompasses two parts: firstly, we compared the bone healing in female and male mice, after induction of type 1 diabetes (T1D); secondly, the bone regeneration was evaluated in a menopause model induced by bilateral ovariectomy (OVX), with or without T1D induction. For the part I, the animals (female and male) were initially assigned into two groups, namely control or T1D (elicited by streptozotocin; STZ). In the part II, the females were divided into four experimental groups: sham-operated or OVX, with or without STZ T1D induction. After T1D induction, a monocortical femoral defect was created. In either parts of the present study, we evaluated the effects of supplementation with vitamin D3 and/or insulin. In the second part, the effects of estrogen replacement were also analyzed. Following 21 days of bone defect creation, the animals were euthanized; the femurs and blood were collected for posterior analysis. Both T1D females and males presented a reduction in body weight gain, associated with hyperglycemia. There were no changes in the serum levels of the pro-inflammatory cytokines [interleukin-1? (IL-1?), tumor necrosis factor (TNF) and interferon-? (IFN-?)] in all the evaluated groups. T1D mice of both sexes presented a delayed bone regeneration, according to the histological and micro-CT assessment. The supplementation with vitamin D3 restored the bone healing in female and male T1D mice, reaching values close to controls. The insulin therapy improved the bone remodeling in T1D mice of both sexes, but the effects of this hormone were superior in males. The evaluation of osteoclast activity did not reveal significant differences among the experimental groups. Real time PCR revealed slight differences in the mRNA expression of two transcription factors related to osteoblast differentiation, namely runx2 and osterix, as measured in the area into the bone defect. A higher upregulation of both factors was seen in T1D males treated with vitamin D3. Conversely, vitamin D3-treated T1D females displayed an upregulation of insulin-like growth factor 1 (IGF-1), further indication sex-related differences for the treatments. Besides the experimental protocols described for the 12 part I of this thesis, in the part II, we also evaluated some behavioral locomotor parameters and serum levels of calcium and alkaline phosphatase. OVX animals presented increased body weight gain, accompanied by uterus atrophy. Otherwise, T1D induction elicited a reduction of body weight gain, which was more pronounced in OVX-T1D animals. Serum levels of alkaline phosphatase were divergent in the non-diabetic and T1D OVX animals. Calcium or cytokine levels were similar in all the experimental groups. The sham-operated T1D, the non-diabetic OVX and the OVX-T1D groups presented a delayed bone regeneration, as indicated by histological and micro-CT analysis. Estrogen replacement improved the bone healing in all OVX groups. There was a trend toward an upregulation of IGF-1 mRNA in non-diabetic OVX animals, which was not mirrored in OVX-T1D mice. Locomotor parameters remained unaltered, except by a general reduction of rearing numbers in T1D animals.
A presente tese est? dividida em duas partes: na parte I, comparou-se a regenera??o ?ssea em camundongos f?meas e machos, com diabetes do tipo 1 (T1D). Na parte II, foi avaliada a regenera??o ?ssea no modelo de menopausa experimental induzido por ovariectomia (OVX), com ou sem T1D. Na parte I, os animais (machos e f?meas) foram divididos em dois grandes grupos: controle e T1D (induzido por estreptozotocina; STZ). Na parte II, os animais foram divididos em quatro grandes grupos: f?meas falso-operadas e OVX, com ou sem T1D. Ap?s a indu??o do T1D, foi criado um defeito ?sseo monocortical no f?mur. Nas duas partes do trabalho, foram avaliados os efeitos da suplementa??o com vitamina D3 e/ou insulina. Na segunda parte, tamb?m se avaliou o efeito da reposi??o hormonal com estradiol. Decorridos 21 dias do procedimento da cria??o do defeito, os animais foram eutanasiados; o f?mur e o sangue foram coletados para an?lises posteriores. Tanto as f?meas, quanto os machos T1D, apresentaram uma redu??o do ganho de peso corporal, associado ? hiperglicemia. N?o houve altera??es nos n?veis s?ricos das citocinas pr?-inflamat?rias interleucina-1? (IL-1?), fator de necrose tumoral (TNF) ou interferon-? (IFN?). Os animais T1D, de ambos os sexos, apresentaram um comprometimento na regenera??o ?ssea, como demonstrado pelas an?lises histol?gicas e de micro-CT. A suplementa??o com vitamina D3 reestabeleceu a regenera??o ?ssea em f?meas e machos T1D, apresentando valores pr?ximos aos encontrados nos animais do grupo controle. A terapia com insulina melhorou a remodela??o ?ssea nas f?meas e machos T1D; por?m, os efeitos foram mais pronunciados nos machos. A avalia??o da atividade osteocl?stica n?o revelou diferen?as significativas entre os grupos experimentais, ap?s a indu??o de T1D, em machos ou f?meas. Os resultados do PCR em tempo real para runx2 e osterix (dois fatores de transcri??o relacionados aos osteoblastos), no tecido ?sseo, n?o demonstraram nenhuma diferen?a significativa, exceto por um aumento nos n?veis de RNAm dos dois fatores nos camundongos machos T1D, que receberam suplementa??o com vitamina 10 D3. Por outro lado, f?meas T1D que receberam vitamina D3 apresentaram um aumento na express?o dos n?veis de RNAm para o fator de crescimento semelhante ? insulina do tipo 1 (IGF-1), quando comparado com os machos que tiveram o mesmo tratamento, sugerindo assim, diferen?as relacionadas ao sexo. Al?m das an?lises j? mencionadas anteriormente, na parte II da tese, par?metros comportamentais e n?veis s?ricos de c?lcio e fosfatase alcalina tamb?m foram analisados. Os resultados da segunda parte do trabalho demonstraram que os animais submetidos a OVX tiveram um aumento do peso corporal, com atrofia uterina. Em contrapartida, quando foi induzido T1D, houve uma diminui??o do peso corporal mais acentuada no grupo OVX que no grupo falso-operado. Os animais falso-operados e OVX T1D apresentaram hiperglicemia, confirmando o desenvolvimento do diabetes. Os n?veis s?ricos de fosfatase alcalina foram divergentes entre os grupos n?o-diab?ticos OVX e OVX T1D. N?o houve varia??es dos n?veis de c?lcio. Os animais falso-operados T1D, n?o diab?ticos OVX e OVX T1D apresentaram preju?zos similares na regenera??o ?ssea, como observado pelas an?lises histol?gicas e imagens de micro-CT. A reposi??o com estradiol melhorou a cicatriza??o ?ssea nos animais n?o-diab?ticos OVX e OVX T1D. Houve uma tend?ncia ao aumento nos n?veis de RNAm de IGF-1 no grupo OVX, o que n?o foi observado quando da associa??o de T1D e menopausa. N?o foram observadas diferen?as na atividade locomotora dos animais com T1D e/ou OVX, a n?o ser por uma diminui??o no n?mero de rearings no grupo falso-operado T1D, independente do tratamento com vitamina D3, insulina e estradiol, de forma isolada ou em associa??o.

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Wispel, Juliana. "AVALIAÇÃO DAS CONCENTRAÇÕES PLASMÁTICAS DE STWEAK NO DIABETES MELLITUS E FRATURAS ÓSSEAS EM MULHERES NA PÓS MENOPAUSA." Universidade Federal de Santa Maria, 2015. http://repositorio.ufsm.br/handle/1/5864.

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Osteoporosis is defined as an osteometabolic disease characterized by the reduction of bone mineral density (BMD) and micro-architectural deterioration, leading to enhanced bone fragility and increased susceptibility to fractures. Chronic inflammation affecting bone resorption and/or bone formation is an important mechanism in the hystopathology of osteoporosis. In this regard, several inflammatory markers are associated in special, tumor necrosis factor alpha (TNFα). Recent evidence from the literature pointed out that other members of the TNF superfamily, the tumor necrosis factor TNF-like weak inducer of apoptosis (TWEAK), in its soluble bioactive form (sTWEAK), has been related with diverse endocrine metabolic disarrangements such as diabetes mellitus or metabolic syndrome. Thus, we hypothesized a possible association between sTWEAK plasma levels and bone fractures and diabetes mellitus in post menopausal women. This was a cross sectional study nested in a cohort of 1057 post menopausal women outpatients attending the UBS, Unidades Básicas de Saúde, of Santa Maria. We used data from 52 individuals recruited who reported major bone fractures. For the control group, we aleatory recruited 110 individuals without the history of major bone fractures. All subjects in this study proceeded to a standard questionnaire about clinical data and were submitted to anthropometry evaluation. Blood samples were obtained for the biochemical profile consisting in fast glucose, total cholesterol, TG, HDL, LDL, creatinine, albumin, calcium and phosphorus in serum. sTWEAK concentration was established by ELISA. Assimetric variables were logN transformed. Student T test or Mann-Whitney test were used to comparison of data between two groups. For statistical analysis that form more than two groups were employed ANOVA or Chi quadrate and Fisher s test. An statistical significant reduction (p=0.002) of sTWEAK (log transformed) was observed in diabetes mellitus (DM) subjects in comparison to non-diabetics. There was no differences in the plasma levels of sTWEAK when the history of major bone fractures was analysed. Even when stratified for DM and fractures, Ln sTWEAK remained consistently reduced in the group of individuals with DM without fractures against non-diabetics no-fractures women (p <0.01). Findings from this study indicated that plasma levels of sTWEAK was not related with bone fragility in post menopausal women population. Nevertheless, low plasma levels of this biomarker were associated with diabetes mellitus, as previously described in the literature.
A osteoporose é um transtorno osteometabólico caracterizado pela diminuição da densidade mineral óssea (DMO) e deterioração de sua microarquitetura com o consequente aumento da fragilidade do osso e suscetibilidade à fraturas. A fisiopatologia dessa doença tem a inflamação crônica como importante mecanismo no aumento da reabsorção e redução da formação óssea. Entre os marcadores inflamatórios associados à osteoporose destacam-se aqueles do grupo dos fatores de necrose tumoral, em particular, o fator de necrose tumoral alfa (TNFα). Evidências recentes da literatura observaram que um outro membro da mesma família, o TNFlike weak inducer of apoptosis (TWEAK), em sua forma solúvel (sTWEAK), foi relacionado com a presença de outros distúrbios endócrino metabólicos, tais como diabetes mellitus (DM) e síndrome metabólica. Com base nisso, testamos a hipótese de associação entre sTWEAK e fraturas ósseas maiores, e também DM, em mulheres na pós menopausa. Este é um estudo transversal que partiu de uma coorte de 1057 pacientes na pós menopausa que consultam nas Unidades Básicas de Saúde da cidade de Santa Maria-RS. Foram recrutadas 52 pacientes com histórico de fraturas ósseas maiores e, para o grupo controle, escolhidas aleatoriamente 110 pacientes sem história de fraturas ósseas. Todos os indivíduos do estudo responderam a um questionário padronizado sobre a sua história clínica além de serem submetidos a avaliação antropométrica e exames bioquímicos (glicose de jejum, colesterol total, triglicerídeos, HDL, LDL, creatinina, albumina, cálcio e fósforo). Os níveis plasmáticos de sTWEAK foram avaliados pelo método de ELISA. As variáveis com distribuição assimétrica foram submetidas à transformação para o seu logaritmo natural e então comparadas. Para a análise estatística entre dois grupos foi feita a utilização dos testes T de Student ou Mann-Whitney. Para mais de dois grupos foram empregados ANOVA ou os testes de Chi Quadrado ou Fisher. Foi observada redução significativa (p=0.002) dos valores do sTWEAK (transformado para logN) nos indivíduos com DM em comparação com os sem DM. Não houveram diferenças quando analisado somente o histórico de fraturas. Estratificando a população em subgrupos de acordo com o critério de existência de fratura reportada ou de diagnóstico de DM, permaneceu somente a diferença entre os grupos com DM sem fratura e sem DM sem fratura (p<0.01). Os achados indicam que na população de mulheres na pós menopausa com e sem história de fraturas ósseas maiores, os níveis plasmáticos de sTWEAK não tem associação com a fragilidade óssea. Entretanto, níveis baixos deste biomarcador estão associados com o diagnóstico de DM, como reportado na literatura.

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Sherman, Shermel B. "Tibia Morphology & Bone Marrow Adipose Tissue Phenotype is Controlled by Sex Steroids in C57BL/6 Mice." University of Toledo Health Science Campus / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=mco1461972446.

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Silva, Tatiane Lopes Patrocinio da. "Efeitos do laser terapêutico de baixa intensidade e do treinamento resistido no metabolismo ósseo em ratos com Diabetes Mellitus tipo I." Universidade Federal de São Carlos, 2013. https://repositorio.ufscar.br/handle/ufscar/262.

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Universidade Federal de Sao Carlos
The DM is a chronic metabolic disorder characterized by a deficiency in the secretion or action of insulin, leading to a series of physiological changes that determine changes in normal operation of various organs and tissues, among which bone tissue is affected, leading to bone fragility. In this context, several treatments have been shown to accelerate bone metabolism. The Resistance Exercise (ER) is highly recommended for diabetics and among its beneficial effects promotes increased bone mineral density. The low-level laser therapy (LLLT) is able to stimulate the activity of osteoblasts, as well as increase the biomechanical properties of bone. However, its effects on bone metabolism in diabetic animals are not completely understood, and its action associated with the ER. Therefore, this study aimed to investigate the action of a protocol and resistance exercises LLLT applied individually or in combination on bone metabolism in diabetic rats. Fifty male Wistar rats were randomly divided into 5 experimental groups (N = 10): non-diabetic control group (CG), diabetic control (GD), diabetic group irradiated with laser (GL), trained diabetic group (TG) and trained group laser and diabetic (GTL). In the first study we evaluated the effects of LLLT on bone diabetic in three groups: GC, GD and GL. The GL was subjected to laser irradiation Ga-Al-As, 808 nm, 100 mW, 3.57 W/cm2, 0.028 cm2, 120J/cm2, 33s, for 18 sessions, on alternate days for 6 weeks. As the GL results showed increased cortical area and RUNX-2 immunoreactivity increased compared to GD. Furthermore, LLLT produced a significant increase in the strength of fracture, and bone mineral density (BMD and BMC), compared with DG. Therefore LLLT stimulated bone formation, reducing osteopenia animals. The second study evaluated the effects associated with ER LLLT in diabetic animals from group 4: GC, GD, GT and GTL. The ER consisted of climbing, load tied to the tail of the animal, and these loads were increased weekly throughout the training sessions, the GTL at the end of each session ER animals were irradiated with laser Ga-Al-As. Performed 6 weeks, 3 times per week, totaling 18 sessions. The GT and GTL showed increased cortical area, BMD and biomechanical properties. The BMC, fracture strength and stiffness were higher in GTL over the GT. Furthermore, immunohistochemical analysis showed that GT and GTL immunoassayed for RUNX-2 increased relative to GD. Already RANK-L immunoreactivity was moderated at GD and week on the others experimental groups. In conclusion, resistance exercise promoted osteoblast activation, with the increase in the biomechanical properties and BMD. The combination of exercise and LLLT, promoted the osteogenic potential additional effect of ER performed alone. Consequently, these data highlight the potential of exercise in the treatment of bone loss due to DM. Further studies should be conducted to provide additional information on the effects of LLLT as adjuvant therapy resistance exercise.
A Diabetes Mellitus (DM) é uma doença metabólica crônica, caracterizada pela deficiência na secreção ou ação da insulina, levando a uma série de modificações fisiológicas, que determinam alterações do funcionamento normal de diversos órgãos e tecidos, dentre os quais, o tecido ósseo é afetado, levando à fragilidade óssea. Neste contexto, alguns tratamentos têm demonstrado melhorar o metabolismo ósseo. O Exercício Resistido (ER) é recomendado para indivíduos diabéticos e dentre seus efeitos benéficos promove o aumento da densidade mineral óssea. A terapia laser de baixa intensidade (LLLT) é capaz de estimular a atividade dos osteoblastos, e aumentar as propriedades biomecânicas ósseas. No entanto, seus efeitos sobre o metabolismo ósseo de animais diabéticos não estão completamente esclarecidos, bem como sua ação associado ao ER. Diante disso, este estudo teve o objetivo de investigar os efeitos de um protocolo de exercicios resistidos e da LLLT, aplicados individualmente ou em associação no metabolismo ósseo de ratos diabéticos. Cinquenta ratos Wistar machos foram distribuídos aleatoriamente em 5 grupos experimentais (N=10 cada grupo): Grupo Controle não diabético (GC), grupo controle diabético (GD), grupo Irradiado com Laser diabético (GL), grupo treinado diabético (GT) e grupo treinado e laser diabético (GTL). No primeiro estudo foram avaliados os efeitos da LLLT no osso diabético em 3 grupos: GC, GD e GL. O GL foi submetido à irradiação laser Ga-Al-As, 808 nm, 100 mW, 3,57W/cm2, 0,028cm2, 120J/cm2, 33s, durante 18 sessões, em dias alternados, por 6 semanas. Como resultados o GL mostrou aumento da área cortical e imunoexpressão de RUNX-2 aumentada em comparação o GD. Além disso, a LLLT produziu um aumento significativo na força de fratura, densidade e conteúdo mineral ósseo (DMO e CMO), em comparação com GD. Portanto a LLLT estimulou a formação óssea, reduzindo a osteopenia dos animais. O segundo estudo avaliou os efeitos da LLLT associado ao ER em animais diabéticos, a partir de 4 grupos: GC, GD, GT e GTL. O ER consistiu em escaladas, com carga atrelada à cauda dos animais, e estas cargas foram aumentadas semanalmente ao longo das sessões de treinamento, no GTL ao final de cada sessão de ER os animais foram irradiados com laser Ga-Al-As. Realizados durante 6 semanas, 3 vezes por semana, totalizando 18 sessões. O GT e GTL mostraram aumento da área cortical, DMO e propriedades biomecânicas. O CMO, a força de fratura e rigidez foram maiores no grupo GTL em relação ao GT. Ainda, a análise imunohistoquímica revelou que GT e GTL apresentaram imunoexpressão de RUNX-2, aumentada em relação à GD. Já a imunoexpressão de RANK-L foi moderada no GD e fraca nos demais grupos experimentais. Como conclusão, o exercício resistido promoveu ativação osteoblástica, com o aumento nas propriedades biomecânicas e na densidade mineral óssea. A associação de exercícios físicos e LLLT, promoveu efeito adicional ao potencial osteogênico do ER realizado isoladamente. Consequentemente, estes dados evidenciam o potencial do exercício físico no tratamento da perda óssea devido à DM. Outros estudos devem ser realizados para fornecer informações adicionais sobre os efeitos da LLLT como terapia coadjuvante ao exercício resistido.

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Silva, Amanda Ferraz Salomé. "Estudo pioneiro do impacto da qualidade de vida em pacientes diabéticos submetidos ao transplante de medula óssea." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/59/59137/tde-21082008-182638/.

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O diabetes mellitus (DM) é uma síndrome de etiologia múltipla decorrente da falta de insulina e/ou incapacidade da insulina exercer adequadamente seus efeitos. Existem dois tipos de diabetes: diabetes mellitus tipo 1 e diabetes mellitus tipo 2. As conseqüências do DM, a longo prazo, incluem disfunção e falência de vários órgãos, especialmente rins, olhos, nervos, coração e vasos sanguíneos. O Transplante de Medula Óssea (TMO), na sua modalidade autóloga, é um procedimento utilizado no tratamento de doenças auto-imunes como o diabetes mellitus tipo 1, alternativa experimental ao tratamento convencional (insulinoterapia). Este procedimento, porém, é constituído por fases potencialmente estressoras para o paciente. O objetivo do presente estudo foi avaliar a qualidade de vida e ajustamento psicológico de pacientes com diabetes tipo 1 que se submeteram ao TMO. As avaliações ocorreram em dois momentos distintos: admissão do paciente (pré-TMO) e retorno ambulatorial de cem dias após o transplante (pós-TMO). A população foi composta por 14 pacientes, sendo 10 homens e quatro mulheres, com idades entre 14 e 31 anos. Todos ficaram internados na enfermaria da Unidade de Transplante de Medula Óssea do Hospital das Clínicas de Ribeirão Preto da Universidade de São Paulo (UTMO-HCRP-USP) entre os meses de outubro de 2005 e dezembro de 2006. Os instrumentos aplicados para a coleta de dados consistiram em entrevista semi-estruturada, questionário específico pós-TMO, ISSL, HAD, SF-36 e Escala Específica de Funcionalidade do TMO - FACT-BMT. Os instrumentos foram aplicados individualmente na Enfermaria (pré-TMO) e no Ambulatório da UTMO (pós-TMO). A aplicação foi dividida em duas ou mais sessões, conforme a necessidade. As entrevistas foram gravadas e transcritas na íntegra e literalmente. Os instrumentos aplicados foram analisados de acordo com as recomendações específicas de cada técnica e a entrevista foi analisada qualitativamente, por meio da análise de conteúdo. Os resultados obtidos demonstraram que a qualidade de vida no pós-TMO apresentou valores superiores ao pré, principalmente no que diz respeito aos aspectos físicos, vitalidade e saúde mental, que se mostraram comprometidos nas avaliações pré-transplante e preservados na avaliação posterior. Acompanhando a tendência de melhora na condição clínica dos pacientes, o ajustamento psicológico também se mostrou mais preservado, com destaque para diminuição de quadros instalados de estresse. Observou-se melhora significativa dos pacientes submetidos ao transplante 100 dias após o procedimento, tanto nos domínios da qualidade de vida, como no padrão adaptativo. Os resultados obtidos são relevantes para a confirmação do TMO como proposta promissora em relação à terapêutica tradicional no panorama do tratamento do diabetes mellitus tipo 1, contribuindo para a melhora de indicadores psicossociais.
The diabetes mellitus (DM) is a multiple etiology\'s syndrome caused by lack of insulin and/or inability of insulin perform adequately its effects. There are two diabetes types: type 1 and type 2 diabetes mellitus. The consequences of DM in long term include dysfunction and failure of various organs, especially kidneys, eyes, nerves, heart and blood vessels. Bone Marrow Transplantation (BMT), in autologous modality, is a procedure used to treat autoimmune diseases such as type 1 diabetes mellitus, experimental alternative to conventional treatment (insulin therapy). This procedure, however, consists in potential stressful phases for patient. This study aimed to assess the quality of life and Psychological adjustment of diabetes patients who decided to undergo BMT. The assessments were made at two distinct times: patient\'s admission and outpatient return one hundred days after the transplantation. The sample consisted of 14 patients, 10 men and four women, aged betweem 14 and 31 years. All of them were hospitalized at the nursing ward of the Bone Marrow Transplantation Unit (UTMO) at the University of São Paulo at Ribeirão Preto Hospital das Clínicas between October 2005 and December 2006. The instrument used for data collection was semi-structured interview, Post-BMT Recovery Interview, ISSL, HAD, SF-36 and Functional Assessment Cancer Therapy - Bone Marrow Transplantation (FACT-BMT). The instruments were applied individually in the nursing ward (pre-BMT) and ambulatory of UTMO (post-BMT). The application was divided into two or more sessions, as needed. The interviews were audio recorded and transcribed completely and literally. The instruments were scored according to the recommendations established by the specific literature for each technique and a qualitative approach was used for analysis of interviews, i.e. content analysis. The obtained results demonstrated that the quality of life escores post-TMO were higher than before, with significant differences for Physical Aspects, Vitality and Mental Health,which were committed in the pre-transplant evaluations and preserved in subsequent evaluation. Following the trend of improvement in clinical condition of patients, the psychological adjustment was preserved, with emphasis on reduction of clinical conditions installed of stress. There was significant improvement of patients undergoing transplant one hundred days after the transplantation, in quality of life domains and adaptation model. These results are relevant to confirm BMT as a promising proposal in relation to traditional therapy for treating type 1 diabetes, contributing to the improvement of psychosocial indicators.

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Lopes, Laura da Silva Girão. "O papel dos hormônios entéricos GLP-2 e serotonina no metabolismo ósseo de mulheres pós-menopausadas portadoras de Diabetes Mellitus tipo 2." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-23102014-143949/.

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O diabetes mellitus (DM) é uma doença metabólica associada a danos, disfunção e insuficiência de diversos órgãos, sendo a fragilidade óssea apontada por estudos recentes como também associada ao DM. Os mecanismos que justificam o maior risco de fraturas em diabéticos tipo 2 não são bem compreendidos. A influência do trato gastrointestinal e seus hormônios no remodelamento ósseo tem sido comprovada em animais e em indivíduos sadios, sendo o Glucagon-like peptide-2 (GLP-2) e a serotonina hormônios com produção intestinal estimulada pela ingestão de nutrientes, existindo algumas evidências de que os mesmos têm efeitos no metabolismo ósseo. O presente estudo comparou a dinâmica dos marcadores ósseos, da serotonina e do GLP-2 em resposta à refeição mista em mulheres pósmenopausadas diabéticas em relação a controles não diabéticas. Foram incluídas 43 mulheres pós-menopausadas com densidade mineral óssea (DMO) reduzida, 23 com diabetes (grupo DM) e 20 controles (grupo CO). Depois do jejum de 12 horas, essas mulheres foram submetidas ao teste de refeição padrão, e as amostras de sangue foram coletadas nos tempos 0, 30, 60, 120 e 180 minutos para a dosagem de telopeptídeo C-terminal do colágeno tipo I sérico (CTX), osteocalcina (OC), GLP-2 e serotonina. O grupo DM apresentou maior índice de massa corporal, bem como maior densidade mineral óssea (DMO) de colo de fêmur e quadril. Nos tempos basais as mulheres diabéticas apresentaram concentrações plasmáticas de LH e FSH, bem como dos marcadores ósseos osteocalcina e CTX menores que no grupo CO. Em resposta a refeição padrão houve, em ambos os grupos, diminuição na concentração do CTX e da osteocalcina, e aumento na de GLP-2, sem alteração significativa da serotonina. A resposta do CTX à refeição foi menor no grupo DM, e a da serotonina maior no grupo CO em um único tempo do teste. Em relação a OC e ao GLP-2, não houve diferença entre os grupos avaliados ao longo do teste de refeição. As mulheres diabéticas tipo 2 tiveram maior DMO de fêmur. Além disso, os resultados sugerem que o remodelamento ósseo das mulheres diabéticas está alterado, com os marcadores ósseos reduzidos. A influência da ingestão de nutrientes na reabsorção óssea também foi alterada pela DM, não se reconhecendo nesse estudo qualquer papel do GLP-2 ou da serotonina na alteração do metabolismo ósseo em mulheres diabéticas tipo 2
Type 2 diabetes mellitus is metabolic disease associated with long-term damage, dysfunction, and failure of various organs; recent studies indicate that diabetes itself is associated with bone fragility. The mechanisms underlying the increased fracture risk in type 2 diabetes are not well understood. The influence of the gastrointestinal tract and its hormones in bone remodeling has been demonstrated in animals and in healthy subjects. Glucagon-like peptide-2 (GLP-2) and serotonin are enteric hormones stimulated by nutrient intake, and there is some evidence that these hormones could have some effects on bone metabolism. We studied the dynamics of bone markers, serotonin and GLP- 2 in response to a mixed meal in diabetic postmenopausal women, in comparison with nondiabetic controls. 43 post-menopausal women with reduced bone mineral density (BMD) were enrolled, 23 with diabetes (DM group) and 20 normal control (CO group). After an overnight fast (12h), subjects were submitted to a standard meal test. Blood samples were drawn for C-terminal crosslinked telopeptide (CTX), osteocalcin (OC), GLP-2 and serotonin at 0, 30, 60, 120 and 180 minutes. The DM group had higher body mass index, and higher BMD of the femoral neck and hip. The basal values of of LH and FSH as well as the bone markers osteocalcin and CTX were lower in the DM group than in the CO group. After the standard meal test, there was a decrease in the concentration of CTX and osteocalcin, and an increase in GLP-2 in both groups. No changes in concentrations of serotonin were observed over the test meal. The response of the CTX meal was lower in the DM group, and the serotonin concentration was greater in the CO group in a single test time. In relation to e OC and GLP-2, there were no differences among the groups throughout the test meal. Type 2 diabetic women had higher bone mineral density (BMD) in the femur. Furthermore, the results suggest that the bone remodeling of diabetic women is altered, with their biochemical bone markers reduced. The influence of nutrient intake on bone resorption was also altered by DM, but in this study we could not recognize the role of GLP- 2 and serotonin in influencing the bone metabolism in type 2 diabetic

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Marques, Letícia Aparecida da Silva. "Qualidade de vida e ajustamento psicossocial de pacientes com diabetes mellitus tipo 1 submetidos ao transplante de células-tronco hematopoéticas: um estudo de acompanhamento." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/59/59137/tde-11072012-185027/.

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O transplante de células-tronco hematopoéticas tem surgido como alternativa ao tratamento de doenças autoimunes como artrite reumatóide, lúpus eritematoso sistêmico, esclerose múltipla e diabetes mellitus tipo 1. No diabetes mellitus tipo 1, uma síndrome de etiologia múltipla, o transplante de células-tronco hematopoéticas, na sua modalidade autóloga, tem sido utilizado como alternativa ao tratamento convencional (insulinoterapia), já que este retarda, mas não elimina as consequências da doença como disfunção e falência de vários órgãos, especialmente rins, olhos, nervos, coração e vasos sanguíneos. Apesar disso, o transplante é um procedimento altamente invasivo que acarreta repercussões intensas na qualidade de vida desses pacientes exigindo dos mesmos uma readaptação à essas repercussões. O presente estudo teve por objetivo avaliar a qualidade de vida e o ajustamento psicossocial de participantes com diabetes mellitus tipo 1. Participaram do estudo 22 pacientes que foram submetidos consecutivamente ao transplante de células-tronco hematopoéticas na Unidade de Transplante de Medula Óssea do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, no período de 2006 a 2008. Os instrumentos aplicados para a coleta de dados: Questionário Genérico de Avaliação de Qualidade de Vida Medical Outcomes Study 36 Item Short-Form Health Survey (SF-36), Escala de Ansiedade e Depressão Hospitalar - Hospital Anxiety and Depression Scale (HAD) e Inventário de Sintomas de Stress para Adultos de Lipp (ISSL). As avaliações ocorreram em três momentos distintos: na admissão do paciente, um ano após a realização do procedimento e dois anos após o transplante no retorno ambulatorial. A análise dos instrumentos aconteceu de acordo com as recomendações específicas preconizadas pela literatura. Os resultados obtidos mostraram, que para a maioria dos participantes deste estudo, após um ano do procedimento, os índices de qualidade de vida melhoraram significativamente principalmente os domínios Aspectos Físicos (p=0,0003), Estado Geral de Saúde (p=0,0142), Aspectos Sociais (p=0,0018) e Aspectos Emocionais (p=0,0316). Decorrido dois anos, o transplante teve um impacto também positivo sobre a qualidade de vida principalmente nos domínios Aspectos Físicos (p<0,0001), Aspectos Sociais (p=0,0235) e Aspectos Emocionais (p=0,0270). Em relação ao ajustamento psicossocial os resultados mostraram redução dos sintomas de ansiedade após o primeiro ano de transplante (p<0,01) e depressão nos dois momentos após o transplante (p<0,01). Observou-se ainda a diminuição dos sintomas de estresse nos momentos avaliados (p<0,01). Tais resultados podem representar uma possibilidade de retomada da vida e dos planos futuros que foram interrompidos por uma doença crônica que impunha inevitáveis dificuldades e limitações para esses participantes. Os resultados deste estudo oferecem subsídios para a equipe multidisciplinar de saúde refletir sobre as implicações dessa terapêutica inovadora em aspectos essenciais da vida do participante que vão além da dimensão biomédica, considerando as repercussões sobre sua qualidade de vida e ajustamento psicossocial.
Transplantation of hematopoietic stem cells has emerged as an alternative to the treatment of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and type 1 diabetes mellitus. In the latter, a syndrome of multiple etiology, the hematopoietic stem cell transplantation, in its autologous method, has been used as an alternative to conventional treatment (therapy with insulin), once it slows, but does not eliminate the consequences of the disease such as dysfunction and failure of various organs, especially kidneys, eyes, nerves, heart and blood vessels. Nevertheless, transplantation is a highly invasive procedure that carries severe repercussions on the quality of life of these patients, requiring from them a readjustment to these repercussions. The present study aimed to evaluate the quality of life and psychosocial adjustment of participants with type 1 diabetes mellitus. The study included 22 patients who underwent consecutive hematopoietic stem cell transplantation in the Bone Marrow Transplantation Ward of the Hospital das Clinicas of the University of Sao Paulo at Ribeirao Preto Medical School, between 2006 and 2008. The following instruments were used for data collection: Medical Outcomes Study 36 Item Short-Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HAD) and Lipp Stress Symptoms Inventory for Adults (LSSI). Assessments were performed at three different moments: at patient admission, one year after the performance of the procedure and two years after transplantation at the post-transplant outpatient clinic. Analysis of the instruments was done according to specific recommendations proposed in the literature. Results showed that, for most participants of the study, one year after the procedure, the indices of quality of life improved significantly, mainly the domains Physical Functioning (p=0.0003), General Health (p=0.0142), Social Functioning (p=0.0018) and Role-Emotional (p=0.0316). After two years, the transplant also had a positive impact on the quality of life, especially in the domains Physical Functioning (p<0.0001), Social Functioning (p=0.0235) and Role-Emotional (p=0.0270). In relation to psychosocial adjustment, results showed a reduction in symptoms of anxiety after the first year of transplantation (p<0.01) and depression at the two moments after transplantation (p<0.01). A decrease in symptoms of stress at the studied moments (p <0.01) was also observed. These results may represent a possibility of renewed life and future plans that were interrupted by a chronic illness that imposed inevitable difficulties and limitations to these participants. Results of this study provide support to the multidisciplinary health team reflect on the implications of this innovative therapy in essential aspects of participants life that go beyond the biomedical dimension, considering the repercussions on their quality of life and psychosocial adjustment.

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Böhler, Nina [Verfasser], Matthias [Akademischer Betreuer] Blüher, and Christoph [Gutachter] Baerwald. "Auswirkungen von Gewichtsreduktion und einem kontrollierten Trainingsprogramm auf die Serumkonzentration der Bone morphogenetic proteins (BMPs) -2 und -4 bei Patienten mit Typ 2 Diabetes / Nina Böhler ; Gutachter: Christoph Baerwald ; Betreuer: Matthias Blüher." Leipzig : Universitätsbibliothek Leipzig, 2014. http://d-nb.info/1238788483/34.

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Loureiro, Melina Bezerra. "Avalia??o da presen?a de osteopatia decorrente do diabetes tipo 1 em crian?as e adolescentes do Rio Grande do Norte." Universidade Federal do Rio Grande do Norte, 2008. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13487.

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Diabetes Mellitus (DM) and osteoposes are chronic diseases with great socioeconomic consequences, mainly due to the late complications and consequent disabilities. The potential effects of DM on bone metabolism remain a very conroversial issue, and disagreement exists with regard to the clinical implications of diabetic osteopenia and the mechanism of its ocurrence. The issue is further complicated by the contribuicion of the especific factors, such as duration of disease an dthe degree of metabolic control. The objective of this study is to identify the osteopathy in children and adolescents with DM 1 assisted in the hospital of pediatrics, UFRN, through biochemical markers of bone and mineral metabolism and the extent of bone mineral density. The study was composed by 74 diabetics type 1 patients (DM1) of both gender and aged 6 to 20 yars. Normoglic?mic group was composed by 97 healthy subjects of both genders, which showed the same age range of DM1, in addition to same socioeconomic class. These individuals qere students from the networks of public education in the city of Natal-RN, randomly invited to paticipate in our study. Both groups DM1 and NG were divided intofour subgroups, according to the classification of tanner , T1, T2, T3, T4 for achieving a benchmark. Diabetic individuals showed up with a poor glycemic control. the group DN1 T4 showed an incresead value for total protein, albumin, urea and microalbumiuria are predictors of grumelura injury in DM1 patients . The total alkaline phosphatase activitywas kept on high levels for both groups because they are in a stature development age. For osteocalcin there were decreased levels for groups Dm1 T1, T2, and T3 when compared to their NG (s), suggesting that this decrease could be associated with reduction in the number and/or differentiation os osteoblasts thereby contributing to reducing bone formation. There were no changes in the activity of TRAP. The serum concentrations of total and ionized calcium, phosphorus and magnesium were included within the RV. It was observed that the BMD (Z- SCORE ) has always been within the RV for both groups, despite to DM1 T4. Taking all together, our results support the hypothesis that children and adolescents with type 1 DM present the risk in the long run to suffer a reduction in the bone mass, associated to poor glicemic control and disease duration. It could limit the bone growth and increase the probality of development of osteopenia, as well as other complications surch as retinopathy and renal failure
Diabetes mellitus (DM) a osteoporose s?o doen?as cr?nicas com grandes consequ?ncias socioecon?micas, sobretudo devido ? complica??es tardias e consequente desabilidades. Os efeitos potenciais do DM no metabolismo ?sseo continua a ser uma quest?o controversa, e ainda n?o existe um consenso no que diz respeito ?s implica??es cl?nicas da osteopenia diab?tica e os mecanismos da sua ocorr?ncia. Entretanto, a contribui??o de fatores espec?ficos, tais como a dura??o da doen?a e o grau de controle metab?lico tem sido muito discutidos. O objetivo do presente estudo foi identificar precocemente a osteopatia diab?tica em crian?as e adolescentes com DM 1 atendidos no Hospital de Pediatria da UFRN atrav?s de marcadores bioqu?micos do metabolismo mineral e ?sseo, marcadores da fun??o renal e da medida da densidade mineral ?ssea (DXA; Z-score L1-L4) . O estudo foi constitu?do por uma amostra de 74 pacientes diab?ticos tipo 1 (DM1) de ambos os sexos, com faixa et?ria entre 6 a 20 anos. O grupo normoglic?mico (NG) foi constitu?do por 97 indiv?duos saud?veis, de ambos os sexos, os quais apresentaram a mesma faixa et?ria do DM1, al?m de compreenderem a mesma classe socioecon?mica. Estes indiv?duos eram alunos de escolas da rede p?blica de ensino da cidade de Natal-RN, convidados aleatoriamente a participar do nosso estudo. Tanto o grupo DM1 quanto o NG foram divididos em quatro subgrupos, de acordo com a Classifica??o de Tanner, T1, T2, T3, T4, para viabilizar uma avalia??o comparativa. Os indiv?duos diab?ticos apresentaram um controle glic?mico insatisfat?rio, com valores de glicemia e HbA1C significativamente superiores aos obtidos para os NG. O grupo DM1 T4 apresentou valores aumentados de prote?nas totais, albumina, ur?ia e microalbumin?ria, sugerindo assim um in?cio de comprometimento renal, visto que os valores elevados de microalbumin?ria s?o preditores de les?o glomerular em pacientes DM1. A atividade da fosfatase alcalina total mostrou-se acima dos VR nos grupos DM1 e NG por estes estarem numa faixa et?ria de desenvolvimento estatural. Observa-se uma diminui??o da concentra??o de osteocalcina para os grupos DM1 T1, T2 e T3 quando comparados aos respectivos NG (s), sugerindo que esta diminui??o estaria associada a diminui??o do n?mero e/ou da diferencia??o dos osteoblastos no seu est?gio final de matura??o, contribuindo consequentemente para a redu??o da forma??o ?ssea. N?o foram observadas altera??es na atividade da TRAP. As concentra??es s?ricas de c?lcio total e ionizado, f?sforo e magn?sio estavam compreendidos dentro dos VR, mas os grupos diab?ticos apresentaram hipozincemia e hiperzinc?ria. A DMO (Z-score L1-L4; DXA) esteve sempre dentro dos VR para os grupos estudados, entretanto os grupos DM1 apresentaram sempre valores abaixo do seu respectivo NG, alca?ando uma diferen?a significativa para DM1 T4. O conjunto de resultados obtidos indicam que o baixo controle glic?mico e o tempo de doen?a representaram fatores de risco importantes para o desenvolvimento precoce da osteopenia diab?tica, bem como para o comprometimento renal e sinais de retinopatia.

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Silva, Joyce Gouveia Nunes da. "Diabetes mellitus tipo 1, doença celíaca e sua associação: estudo comparativo do estado nutricional, consumo alimentar e qualidade de vida em indivíduos com duas doenças crônicas." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-23092015-153746/.

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INTRODUÇÃO: O diabetes mellitus tipo 1 (DM1) e a doença celíaca (DC) são doenças de origem autoimune, com padrão genético similar e terapias embasadas em alterações dietéticas distintas; ou seja, monitorização da ingestão de carboidratos nas refeições no DM1 e dieta livre de glúten na DC.OBJETIVO: O objetivo deste estudo foi comparar o estado nutricional, o consumo alimentar, a saúde óssea e a qualidade de vida em indivíduos com associação com duas doenças crônicas. PACIENTES E MÉTODOS: Os voluntários portadores de DM1, DC e indivíduos hígidos foram recrutados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e divididos conforme os grupos: DMDC (portadores de DM1 e DC), DM (portadores de DM1), DC (portadores de DC) e GC (indivíduos hígidos). Utilizamos a bioimpedância octopolar para aferir a área de gordura visceral e a densitometria de corpo inteiro para estimar o total de gordura corporal e a densidade mineral óssea; o índice de massa corporal (IMC) e a circunferência da cintura também foram empregados para avaliação nutricional, além de exames laboratoriais. Verificou-se o consumo alimentar pelo registro alimentar de três dias e a qualidade de vida pelo questionário SF-36. RESULTADOS: Foram incluídos no estudo sessenta indivíduos controlados segundo sexo, idade, índice de massa corporal (IMC) distribuídos em quatro grupos conforme diagnóstico prévio. Houve predomínio do sexo feminino (80%) e o tempo de diagnóstico de DM foi semelhante entre os grupos DMDC e DM; no entanto, a duração da DC foi significativamente maior no grupo DC comparado ao DMDC (p = 0,0015). Em relação ao IMC, os participantes foram classificados como dentro da normalidade ou pré-obesidade e em 53,3% deles observamos aumento da circunferência da cintura. A porcentagem média de massa gorda e a área de gordura corporal foi semelhante entre os grupos e não representou aumento de risco de doenças associadas à obesidade. O consumo diário de macronutrientes foi semelhante ao padrão de referência para a população adulta; mas a ingestão de fibras, cálcio e vitamina D foi menor que a recomendada. Os parâmetros descritos para saúde óssea e as medidas laboratoriais de vitaminas e minerais foram homogêneas entre os grupos, com exceção da concentração sérica de ácido fólico e de magnésio naqueles com DC e DM1, respectivamente. A análise do SF-36 evidenciou diferença significativa entre os grupos DM e GC no domínio estado geral de saúde e vitalidade. A presença de complicações relacionadas ao diabetes foi associada a menor escore no domínio limitação emocional. CONCLUSÃO: A ingestão dietética habitual de macronutrientes e micronutrientes dos portadores de diabetes mellitus tipo 1 e doença celíaca foi semelhante aos demais grupos e não houve associação com indicadores laboratoriais de deficiências nutricionais. Além disso, a presença das duas doenças não acarretou prejuízo adicional ao metabolismo ósseo e não impactou na qualidade de vida
BACKGROUND: Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are autoimmune diseases, they have similar genetic patterns and their therapies are based upon different dietary changes. Monitoring of carbohydrate intake per meal is recommended to patients with DM1, whereas a gluten-free diet, for those with CD.OBJECTIVE: The aim of the study was to compare the nutritional status, food intake, bone health and quality of life of individuals with the association of the two chronic diseases. PATIENTS AND METHODS: Volunteers with T1DM, CD and healthy subjects were recruited at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo divided into four different groups: patients with type 1 diabetes and celiac disease (DMDC group), only T1DM (DM group), only CD (DC group) and healthy controls (GC group). We used the octopolar bioimpedance to measure the area of visceral fat and whole-body densitometry to assess total body fat and bone mineral density; while nutritional status was determined by body mass index (BMI), waist circumference and general laboratory tests. We assessed food intake by a three-day food record and quality of life using the SF-36 questionnaire. RESULTS: The study included sixty individuals controlled by sex, age, BMI and distributed in four groups according to previous diagnosis and there were sex female predominance (80%). The time of diagnosis of T1DM was similar between DMDC and DM groups; however the duration of CD was significantly higher in DC group compared to DMDC (p = 0.0015). The participants were classified as normal or overweight through BMI and 53.3% of them had increased waist circumference. The average percentage of fat mass and body fat area was similar in both groups and did not represent an increased risk of diseases associated with obesity. The macronutrients consumed were usually distributed according to the reference standard for the adult population; while fiber, calcium and vitamin D intake did not reach the daily recommendations. The parameters described for bone health and laboratory measures of vitamins and minerals were similar in all groups, except for serum concentration of folic acid that was lower in individuals with CD and magnesium in those with diabetes. The SF-36 analysis revealed significant differences between the DM and the control groups regarding general health and vitality. The presence of diabetes-related complications was associated with lower scores on the emotional limitation domain among patients with T1DM. CONCLUSION: The nutritional status, food intake, bone health and quality of life of individuals of DMDC group were similar to the others groups. This allowed us to conclude that the combination of the two chronic diseases with therapies based upon different dietary changes did not deteriorate the general state of health

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49

Poidvin, Amélie. "La morbidité à long terme des enfants traités par hormone de croissance synthétique." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB011/document.

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Les données de la littérature concernant la tolérance à long terme du traitement par hormone de croissance (GH) recombinante sont très réduites. L’objectif du travail rapporté dans cette thèse porte sur l’analyse de la morbidité chez 6874 patients de l’étude SAGhE traités en France dans le cadre d’un déficit idiopathique en GH ou d’une petite taille constitutionnelle, avec les 3 axes de travail suivants : Risque neurovasculaire : Utilisant des données de référence issues de 2 registres de population, nous avons montré une augmentation du risque d’accident vasculaire cérébral (SIR à 3.5 ou 4.4 selon le registre considéré), et plus particulièrement d’hémorragies sous-arachnoïdiennes (SIR 5.7 ou 6.3). Risque de diabète : Utilisant les prescriptions d’antidiabétiques fournies par le SNIIRAM au sein de notre cohorte, nous n’avons pas mis en évidence d’augmentation de la prévalence du diabète traité (SPR 1.0). Risque de cancer : En comparaison au registre de référence du réseau FRANCIM, il n’y a pas de différence significative dans le risque de survenue d’un cancer (SIR 0.7). En revanche, le risque de développer une tumeur osseuse est 3.5 fois plus élevé chez les sujets exposés à l’hormone de croissance dans l’enfance. Les évènements ont été identifiés à partir de trois sources : a) RNIPP et CépiDC pour la connaissance du statut vital et les causes de décès si le sujet est décédé, b) Questionnaire de santé envoyé aux sujets non décédés, c) Données SNIIRAM à partir d’une extraction spécifique basée sur les identifiants des sujets de notre cohorte, permettant d’obtenir les codes CIM-10 des déclarations d’Affection Longue Durée, les codages PMSI entre 2008 et 2010 correspondant aux hospitalisations, et les prescriptions d’antidiabétiques
The literature is scarce regarding the long term effect of synthetic growth hormone (GH) treatment. The objective of this thesis was to analyse the morbidity of 6874 patients from the French SAGhE study treated by GH for short stature, focusing on three themes: Neurovascular risk: Using two population-based registries, we showed an increase in the risk of stroke (SIR 3.5 to 4.4 according the registry used), more specifically for the subarachnoid hemorrhage (SIR 5.7 or 6.3). Risk of diabetes : Using the antidiabetic drugs deliveries obtained from the French national health insurance database, no difference in the risk of treated diabetes was found (SPR 1.0). Risk of cancer : Compared with the French population-based registries of cancer, no significant difference in the risk of cancer was found (SIR 0.7), but the excess risk for bone tumor is 3.5 . Events were identified from three sources : a) Information on vital status collected from the Répertoire National d’Identification des Personnes Physiques and cause of death as indicated on death certificate, b) Health questionnaire sent to all living patients, c) Data extracted from the French national health insurance information, including the French hospital discharge database, also called Programme de Médicalisation des Systèmes d’Information from 2008 to December 2010, long-lasting affection statements, and antidiabetics drugs deliveries

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50

Guo, Qidong. "Healing of bone fracture in type 1 diabetic rat models : a potential gene therapy using bone morphogenetic protein." Thesis, University of Dundee, 2015. https://discovery.dundee.ac.uk/en/studentTheses/8946b0c7-d4b0-4d59-bbcb-ca914643673d.

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Dissertations / Theses on the topic 'Bone Diabetes'

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