Academic literature on the topic 'Lipoatrophie'

Abstract Total congenital lipoatrophic diabetes is characterized by absence of subcutaneous adipose tissue, hypertriglyceridemia, and insulin resistance. We hypothesized that mutations in the β-3-adrenergic receptor (β3AR) gene might result in the lipoatrophic phenotype by preventing triglyceride storage in adipocytes; thereby, resulting in secondary insulin resistance. We screened the β3AR gene in 7 subjects with total congenital lipoatropic diabetes. We found a heterozygous substitution of a guanine to cytosine at position −153 (G-153C) in the 5′-untranslated region of 3 African-American lipoatrophic siblings and 1 sibling without lipoatrophy but with insulin resistance. To determine whether the base change was related to the lipoatrophic phenotype, we genotyped 69 African-Americans without lipoatrophy and found the G-153C substitution in 2 control subjects (allele frequency = 0.01). No other single-stranded polymorphism variants were found in any of the 7 lipoatrophic subjects. Direct sequencing of both alleles of 1 lipoatrophic subject demonstrated a thymidine insertion at position− 300 in both alleles. All lipoatrophic subjects along with 20 African-American control subjects were homozygous for the base insertion, suggesting an error in the published sequence. In conclusion, mutations in the β3AR gene do not appear to be involved in the development of congenital total lipoatrophy.

Insulin-induced lipoatrophy is a rare skin complication in patients with diabetes mellitus. It is characterized primarily by localized subcutaneous atrophy of the fatty tissue at the site of frequent insulin injection. We report a clinical case of a 38-year-old woman with lipoatrophy, developed during treatment with insulin analogues. Lipoatrophic zone formation began 3 months after the treatment was initiated. A lipoatrophic defect developed on the thighs and the upper outer arms, resulting from repeated insulin injections at the same site. Regarding lipoatrophic areas, treatment with topical administration of corticosteroids was attempted but without a significant clinical effect. The best prevention from lipoatrophy development is education of patients regarding rotation of insulin injection sites and more frequent needle change.

Les inhibiteurs nucléosidiques de la transcriptase inverse (INTIs) sont des médicaments anti-VIH pouvant induire des lipodystrophies. Le but de cette thèse a été d'évaluer les effets mitochondriaux et métaboliques des INTIs (AZT, d4T, ddC,ddI, 3TC chez la souris. Après deux semaines de traitement, seuls les analogues de la thymide (AZT et d4T) augmentaient l'oxydation hépatique des acides gras et les corps cétoniques plasmatiques, sans induire un dysfonctionnement mitochondrial profond. Ces effets étaient reproduits par l'acide β-aminoisobutyrique (BAIBA), un catabolite de la thymine. Après six semaines, seuls le d4T, l'AZT et le BAIBA augmentaient les corps cétoniques et diminuaient la masse grasse corporelle des souris Swiss,sans dépléter l' ADNmt dans le tissu.
Nucleoside reverse-transcriptase inhibitors (NRTIs), used in the treatment of HIV infection can induce lipodystrophy. The aim of this work was to better characterize the mitochondrial and metabolic effects induced by NRTIs (AZT, d4T, ddC, ddI, 3TC) in mice. The thymidine analogs AZT and d4T increased fatty acids oxidation in liver and plasma ketone bodies after 2 weeks of treatment, without a profund mitochondrial dysfunction. These effects were reproduced by β-aminoisobutyric acid (BAIBA), a thymine catabolite. The derivatives d4T, AZT and BAIBA still increased ketone bodies and decreased body fat mass after 6 weeks of treatment in Swiss mice. However, mitochondrial DNA was not decreased in epididymal white adipose tissue and glucido-lipidic metabolism was unchanged

Thesis (PhD)--Stellenbosch University, 2013.
Bibliography
ENGLISH ABSTRACT: Introduction: Lipoatrophy is a common adverse effect of stavudine and this effect is strongly dose-dependent. Stavudine remains the most commonly used paediatric antiretroviral drug in sub-Saharan Africa, yet when the current study began in 2009, the prevalence and severity of lipoatrophy in children on antiretroviral therapy in sub-Saharan Africa had never been studied. The development of lipoatrophy may have serious and far-reaching consequences for patients and their families. The off-label stavudine dosing method, prescribed to children whose caregivers do not have access to a refrigerator, in which the contents of an adult capsule is mixed into tap water, has potential for over-dosing or under-dosing. In addition, children on stavudine continue to be exposed to a disproportionately high dose out of line with the reduced adult dose. Aims: 1. a) To investigate the prevalence and risk factors for lipoatrophy in HIV-infected children in Southern Africa b) To identify a simple anthropometric screening tool to detect early lipoatrophy in children 2. To validate the off-label stavudine dosing method prescribed to children whose caregivers do not have access to a refrigerator, with a view to reducing the recommended dose and thereby the side-effects. Methods: 1. a) We recruited pre-pubertal children on antiretroviral therapy from a family HIV clinic in our facility. Lipoatrophy was identified by two experienced paediatric HIV clinicians using a standardized grading scale. A dietician performed dietary assessment and anthropometric measurements. Previous antiretroviral exposures were recorded. A subset of recruits received Dual-Energy X-ray Absorbtiometry scanning. b) Anthropometric measurements in children with and without lipoatrophy were compared using multivariate linear regression adjusting for age and gender. The most discerning anthropometric variables underwent Receiver Operating Characteristic curve analysis to identify the most appropriate diagnostic cut-off. 2. a) Accuracy of the standard off-label stavudine dosing method was investigated using high-performance liquid chromatography to recover active drug from solutions made up using the prescribed method. This was compared to the stated drug content of the capsules. b) Bioavailability was investigated by performing a randomized crossover pharmacokinetic study wherein healthy HIV-seronegative adult volunteers received one of two generic stavudine capsule formulations, either intact or mixed in water using the prescribed method. Plasma stavudine concentrations were assayed by liquid chromatography tandem mass spectrometry. Results: 1. a) Prevalence of lipoatrophy was 36%, and incidence was 12% per person-year. Adjusted odds ratio for developing lipoatrophy was 1.9 (CI: 1.3–2.9) for each additional year of accumulated exposure to standard-dose stavudine. b) Baseline biceps skin-fold thickness correlated well with maximum lipoatrophy grading score at any site, giving a partial correlation coefficient of 0.33 (p=0.0006), and a receiver operating characteristic area-under-curve value of 0.75 (CI: 0.64 – 0.84). Biceps skin-fold thickness <5mm at baseline had a sensitivity of 89% (CI: 67–100%) and a negative predictive value of 97% (CI: 91–100%) for predicting which children would go on to develop lipoatrophy by 15 month follow-up. Specificity was 60% (CI: 46–75%) and positive predictive value was 32% (CI: 14–50%). 2. a) Recovery of active drug from solution was 97.1%, 97.4% and 93.8% for the proprietary and two generic formulations respectively. b) Pharmacokinetic parameters of the off-label dosing method were well within the target range of intact capsule dosing for both generics. Conclusions: 1. a) The prevalence and incidence of lipoatrophy in pre-pubertal children on antiretroviral therapy in South Africa is high. Cumulative exposure to standard-dose stavudine was the greatest risk factor for lipoatrophy. b) Biceps skin-fold thickness provided reasonable sensitivity and specificity to detect and predict lipoatrophy in pre-pubertal children on antiretroviral therapy. 2. The off-label dosing method for stavudine prescribed to children whose caregivers do not have access to a refrigerator is reasonably accurate and is bioequivalent to intact capsule administration.
AFRIKAANSE OPSOMMING: Inleiding: Lipoatrofie is 'n algemene nadelige uitwerking van stavudien en hierdie effek is sterk dosis-afhanklike. Stavudien bly die mees algemeen gebruikte paediatriese antiretrovirale medikasie in sub-Sahara Afrika, maar toe ons studie begin het, was lipoatrofie in kinders op antiretrovirale terapie in sub-Sahara Afrika nog nooit voorheen bestudeer nie. Die ontwikkeling van lipoatrofie kan ernstige en verreikende gevolge vir die pasiënt en hul familie hê. Die af-etiket stavudien dosering metode voorgeskryf aan kinders wie se versorgers nie toegang tot 'n yskas het nie het 'n aansienlike potensiäal vir oor-dosering of onder-dosering. Daarbenewens, is kinders op stavudien blootgestel aan 'n disproporsionele hoë dosis uit-pas met die verminderde volwasse dosis. Doelwitte: 1. a) Om ondersoek in te stel na die voorkoms en risiko faktore vir lipoatrofie in MIV-geïnfekteerde kinders in Suid Afrika b) Om 'n eenvoudige antropometriese instrument te identifiseer om vroeë lipoatrofie op te spoor in kinders op antiretrovirale medikasie 2. Om die af-etiket stavudien dosering metode wat voorgeskryf is aan kinders wie se versorgers nie toegang tot 'n yskas het nie te valideer, met 'n oog op die vermindering van die aanbevole dosis Metodes: 1. a) Ons het 'n groep van onder-puberteitsjarige kinders op antiretrovirale terapie gewerf uit 'n familie MIV kliniek in ons fasiliteit. Lipoatrofie is geïdentifiseer deur twee ervare MIV pediaters deur gebruik van 'n gestandaardiseerde gradering skaal. 'n Diëetkundige het diëet assessering en antropometriese metings uitgevoer. Vorige antiretrovirale blootstellings is aangeteken. In 'n subset was Dual-energie X-straal Absorbtiometry (DXA) skandering uitgevoer. b) Antropometriese metings in kinders met en sonder lipoatrofie is vergelyk met behulp van meerveranderlike lineêre regressie aangepas vir ouderdom en geslag. Die mees kieskeurige antropometriese veranderlikes het Receiver Operating Curve analise ondergaan om die mees geskikte diagnostiese afgesnypunt te identifiseer. 2. a) Akkuraatheid is ondersoek deur gebruik te maak van hoë werkverrigting vloeistofchromatografie om aktiewe medikasie vanuit oplossings te herstel, wat gemeng is soos aangedui deur die voorgeskrewe af-etiket dosering metode. b) Biobeskikbaarheid is ondersoek deur die uitvoering van 'n ewekansige oorgesteekde farmakokinetiese studie waarin gesonde MIV- negatiewe volwasse vrywilligers een van twee generiese stavudien kapsule formulerings ontvang het, óf heel of in water gemeng soos aangedui deur die voorgeskrewe af-etiket dosering metode. Plasma stavudien konsentrasies is gemeet deur vloeistofchromatografie tandem massaspektrometrie. Uitslae: 1. a) Voorkoms van lipoatrofie was 36%, en insidensie was 12% per persoon-jaar. Aangepaste Odds ratio vir die ontwikkeling van lipoatrofie was 1,9 (CI: 1,3-2,9) vir elke addisionele jaar van opgehoopte blootstelling aan standaard dosis stavudien. b) Biceps vel-vou dikte <5mm het 'n sensitiwiteit van 89% (CI: 83-96%) en 'n negatiewe voorspellende waarde van 90% (CI: 84-96%) vir die opsporing en voorspelling van lipoatrofie. 2. a) Herwinning van aktiewe medikasie uit oplossings was 97,1%, 97,4% en 93,8% vir die oorspronklike en twee generiese formulerings onderskeidelik. b) Farmakokinetiese parameters van die af-etiket dosering metode was wel binne die teikenband van ongeskonde kapsule dosering vir beide generiese formulerings. Gevolgtrekkings: 1. a) Die voorkoms van lipoatrofie in onder-puberteitsjarige kinders op antiretrovirale terapie in Suid-Afrika is hoog. Die bedrag stavudien waaraan kinders blootgestel is moet hersien word. Die standaard stavudien dosis vir kinders moet herge-evalueer word. b) Biceps vel-vou dikte het redelike goeie sensitiwiteit en spesifisiteit om lipoatrofie op te spoor en te voorspel. 2. Die af-etiket dosering metode vir stavudien voorgeskryf aan kinders wie se versorgers nie toegang tot 'n yskas het nie is redelik akkuraat en is bio-ekwivalent aan ongeskonde kapsule administrasie.

Pour eclaircir la physiopathogenie de l'insulino-resistance majeure presente dans le diabete lipoatrophique, cette etude examine les proprietes fonctionnelles du recepteur a l'insuline: (liaison, activite kinase tyrosine specifique) et du recepteur a l'igf-i, ainsi que les effets metaboliques de l'insuline, in vivo chez 3 patients

Patients with HIV have been seen to manifest unusual changes in body habitus that constitute variable combinations of peripheral fat loss ( lipoatrophy), central fat accumulation (lipohypertrophy), and the condition known as HIV-associated lipodystrophy (HAL). Although the origins of HAL are unclear, several factors have been linked to it. Because better antiretroviral therapy (ART) drug regimens have led to increased longevity, it is possible that the natural evolution of metabolic complications of HIV is the lipodystrophic phenotype. The specific effects of antiretroviral medications have also been implicated, and the initial usage of ART in the 1990s was accompanied by multiple reports of abnormalities in body fat distribution variously termed the “protease paunch,” “crixivan belly,” among others. Other factors include immune phenomenon and effects mediated directly by the HIV virus. Despite intensive research to understand the mechanistic underpinnings of HIV lipodystrophy and lipoatrophy, the answers remain elusive.

Panniculitis is an inflammation that originates primarily in the subcutaneous fatty tissue (panniculus adiposus). It is associated with rheumatological diseases and with adverse events to rheumatological therapies (e.g. poststeroid panniculitis, erythema nodosum, infective panniculitis). The panniculitides are classified histopathologically into mostly septal panniculitis and mostly lobular panniculitis, according to the major or denser localization of the infiltrate, and also into those with or without vasculitis. Additional criteria involve the composition of the inflammatory infiltrate, the cause, and an underlying or associated disease. The clinical hallmarks of panniculitis are subcutaneous nodules or plaques, often located on the lower limb. A deep excisional biopsy is often required for a more precise diagnosis, given the often sparse and monotonous clinical symptoms. Erythema nodosum is the most common form and a typical example of septal panniculitis. It occurs in response to many different provoking factors, the most common trigger in children being a 'strep throat', in adults sarcoidosis. Clinically, it presents with a sudden symmetrical appearance of painful, tender, warm, erythematous nodes or plaques, usually on the shins, which resemble bruises. Classical and cutaneous polyarteriitis nodosa present a mostly septal panniculitis associated with vasculitis. Here subcutaneous, partially ulcerating nodules are surrounded by livedo racemosa. The mostly lobular panniculitides not associated with vasculitis include lupus panniculitis (lupus erythematosus profundus, typically with ensuing lipoatrophy and predilection for the upper part of the body), panniculitis in dermatomyositis (often calcifiying), cold panniculitis, pancreatic panniculitis, panniculitis due toα‎-antitrypsin deficiency, poststeroid panniculitis (in children after rapid withdrawal of corticosteroids), calciphylaxis (with and without renal failure), and factitious panniculitis (after mechanical, physical, or chemical injuries to the subcutaneous tissue, often self-inflicted). Nodular vasculitis (formerly erythema induratum Bazin) is a lobular panniculitis with vasculitis involving mostly the small blood vessels of the fat lobule. It appears to present a (hyper)reactive response to certain infections (tuberculosis, streptococci, candida) or to cold exposure or chronic venous insufficiency in susceptible females. In conclusion, the panniculitides are a heterogenous group of diseases requiring a systematic work-up and knowledge of certain histological or clinical criteria.