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Lipoatrophy as a cutaneous complication of insulin therapy has been practically forgotten since the introduction of recombinant human insulin. Here we present two cases of marked lipoatrophy associated with rapid-acting insulin analogues (aspart and lispro) administered with continuous subcutaneous insulin infusion or multiple daily injections in a toddler and a young woman with type 1 diabetes mellitus. The exact mechanisms related to the development of localized lipoatrophy in the insulin injection area are unknown. In cases of lipoatrophy the beneficial therapeutic approach is to change the insulin molecule. With switching from one insulin analogue to another administered in insulin pump and changing the sites of insulin injections no progression of the lipoatrophic lesions was observed. Unfortunately, only decrease but no total regression of the formed lesions was achieved and future studies are needed to establish the method of treatment of localized lipoatrophy in children treated with continuous subcutaneous insulin infusion.
Pediatr Endocrinol Diabetes Metab 2008
PMID:[Lipoatrophy associated with rapid-acting insulin analogues in young patients with type 1 diabetes mellitus]. 1872 99

Lipodystrophy syndromes comprise a group of rare, heterogeneous disorders characterized by progressive loss of fat tissue, mainly from subcutaneous compartment and occasionally affecting visceral fat. Lipoatrophy may be partial, localized, or generalized. The latter cases are usually accompanied by metabolic-related disorders, including insulin resistance, diabetes mellitus, hyperlipemia, progressive hepatic disease and anabolic state. Treatment for lipodystrophy has increased interest in recent years because a new lipoatrophic population-patients who have HIV-associated lipodystrophy--is much more numerous than the whole number of patients affected by classic lipodystrophy entities.
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PMID:Lipodystrophy syndromes. 1879 91

Treated HIV infection and HIV-lipoatrophy increases risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Circulating inflammatory molecules may, in part, explain this increased risk. This study examined circulating inflammatory molecules in treated HIV infection in relation to insulin sensitivity, lipids total body, and intramyocellular fat, compared to insulin-resistant obesity (an index group at high risk of diabetes). Detailed metabolic phenotypes were measured in 20 treated HIV-infected men (with and without subcutaneous lipoatrophy) vs. 26 insulin-resistant obese men (IR-O, n = 26), including inflammatory molecules, insulin sensitivity, total body fat (TBF), visceral fat (visceral adipose tissue (VAT)), and intramyocellular lipid (IMCL). C-reactive protein (CRP) levels in treated HIV were similar to those in IR-O, despite lower TBF and greater insulin sensitivity in treated HIV. In HIV-lipoatrophy, CRP was higher than that found in IR-O. Adiponectin was similar between treated HIV and IR-O, but significantly lower in those with HIV-lipoatrophy. In treated HIV, subjects with higher CRP had significantly higher total cholesterol, VAT, and IMCL. In treated HIV, subjects with lower adiponectin had significantly lower HDL and higher triglycerides, glucose, VAT, and IMCL. In conclusion, a proinflammatory milieu equivalent to that of insulin-resistant obesity characterizes lean men with treated HIV infection, worse in those with subcutaneous lipoatrophy. These factors may contribute to the accelerated diabetogenesis and cardiac risk observed in treated HIV infection.
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PMID:Proinflammatory markers, insulin sensitivity, and cardiometabolic risk factors in treated HIV infection. 1900 69

The introduction of highly active antiretroviral therapy (HAART) for the treatment of acquired immunodeficiency syndrome (AIDS) has resulted in greater survival of patients infected with the human immunodeficiency virus (HIV). However, the use of these drugs has been associated with lipodystrophic syndrome (LS), which is characterized by metabolic alterations (dyslipidemia, insulin resistance, diabetes, and lactic acidosis) and abnormal corporal fat distribution. Clinically, LS may manifest as three different forms: lipohipertrophy (accumulation of fat in the central part of the body), lipoatrophy (loss of fat in the extremities, face and buttocks) and mixed (lipohipertrophy + lipoatrophy). Although its physiopathology has not been elucidated, some mechanisms have been described, including leptin and adiponectin deficiency, mitochondrial dysfunction and use of antiretroviral drugs. The type, dose and duration of the antiretroviral treatment, as well as age and puberty are the main risk factors. LS is also associated with increased incidence of cardiovascular illnesses, atherosclerosis and diabetes mellitus. Treatment includes physical activity, cautious restriction of caloric intake, changes in antiretroviral therapy, and use of insulin-sensitizing and lipid-lowering agents. Follow up must be periodic, consisting of measurement of body fat distribution, evaluation of the lipid profile and insulin resistance.
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PMID:Lipodystrophic syndrome in children and adolescents infected with the human immunodeficiency virus. 1903 Jul 39

Highly active antiretroviral therapy (HAART)-associated metabolic complications include lipoatrophy (loss of subcutaneous adipose tissue (SAT)) and insulin resistance. Thiazolidinediones are insulin-sensitizing antidiabetic agents which-as an untoward side effect in obese diabetic patients-increase SAT. Furthermore, troglitazone has improved lipoatrophy and glycemic control in non-HIV patients with various forms of lipodystrophy. These data have led to 14 clinical trials to examine whether thiazolidinediones could be useful in the treatment of HAART-associated metabolic complications. The results of these studies indicate very modest, if any, effect on lipoatrophic SAT, probably due to ongoing HAART negating the beneficial effect. The benefit might be more prominent in patients not taking thymidine analoges. Despite the poor effect on lipoatrophy, thiazolidin-ediones improved insulin sensitivity. However, especially rosiglitazone induced harmful effects on blood lipids. Current data do not provide evidence for the use of thiazolidinediones in the treatment of HAART-associated lipoatrophy, but treatment of lipoatrophy-associated diabetes may be warranted. The role of thiazolidinediones for novel indications, such as hepatosteatosis, should be studied in these patients.
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PMID:The effects of Thiazolidinediones on metabolic complications and Lipodystrophy in HIV-infected patients. 1909 12

Lipoatrophy syndromes are characterized by an absence of adipose tissue and low leptin levels. Metabolic derangements associated with these syndromes can include diabetes mellitus, insulin resistance, and hyperlipidemia.
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PMID:Lipoatrophic diabetes: a case report with a brief review of the literature. 1910 66

The nuclear hormone receptor, peroxisome proliferator-activated receptor (PPAR)-gamma, originally identified as a key mediator of adipogenesis, is expressed widely and implicated in diverse biological responses. Both natural and synthetic agonists of PPAR-gamma abrogated the stimulation of collagen synthesis and myofibroblast differentiation induced by transforming growth factor (TGF)-beta in vitro. To characterize the role of PPAR-gamma in the fibrotic process in vivo, the synthetic agonist rosiglitazone was used in a mouse model of scleroderma. Rosiglitazone attenuated bleomycin-induced skin inflammation and dermal fibrosis as well as subcutaneous lipoatrophy and counteracted the up-regulation of collagen gene expression and myofibroblast accumulation in the lesioned skin. Rosiglitazone treatment reduced the induction of the early-immediate transcription factor Egr-1 in situ without also blocking the activation of Smad2/3. In both explanted fibroblasts and skin organ cultures, rosiglitazone prevented the stimulation of collagen gene transcription and cell migration elicited by TGF-beta. Rosiglitazone-driven adipogenic differentiation of both fibroblasts and preadipocytes was abrogated in the presence of TGF-beta; this effect was accompanied by the concomitant down-regulation of cellular PPAR-gamma mRNA expression. Collectively, these results indicate that rosiglitazone treatment attenuates inflammation, dermal fibrosis, and subcutaneous lipoatrophy via PPAR-gamma in a mouse model of scleroderma and suggest that pharmacological PPAR-gamma ligands, widely used as insulin sensitizers in the treatment of type-2 diabetes mellitus, may be potential therapies for scleroderma.
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PMID:Rosiglitazone abrogates bleomycin-induced scleroderma and blocks profibrotic responses through peroxisome proliferator-activated receptor-gamma. 1914 27

Lipoatrophy is the long-term adverse effects developed in human immunodeficiency virus (HIV)-1-infected subjects receiving highly active antiretroviral therapy (HAART). This cross-sectional study aimed to evaluate the prevalence of and clinical factors associated with lipoatrophy in HIV-infected Koreans receiving HAART for more than 6 months. Lipoatrophy was diagnosed by concordance between physical examination and history taking performed by a single physician. Various covariates were examined, including diabetes mellitus (DM), lipid profiles after HAART, and HAART regimen and duration. Among total 144 patients (6 females and 138 males), 35 patients (24.3%) were diagnosed with lipoatrophy. The prevalence of lipoatrophy was significantly higher in females than that in males [83.3% (5/6) vs. 21.7% (30/138), p = 0.010] and higher in patients with DM than patients without DM [66.7% (4/6 DM) vs. 22.5% (31/138 non-DM), p = 0.030], or in patients with high total cholesterol levels than patients with low total cholesterol levels [31.9% (23/72 patients with high cholesterol) vs. 16.7% (12/72 patients with low cholesterol), p = 0.035]. Moreover, patients with stavudine treatment history (> 12 months) had a higher prevalence of lipoatrophy than patients who never received stavudine [50.0% (15/30) vs. 16.5% (17/103), p < 0.001]. In the multivariate logistic analysis, stavudine treatment for > 12 months (OR, 3.67; p = 0.011) and being female (OR, 24.93; p = 0.009) are independently associated with lipoatrophy. In conclusion, the prevalence of lipoatrophy in HIV-infected Koreans receiving HAART is not uncommon. Limited use of stavudine and regular monitoring are warranted to reduce lipoatrophy.
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PMID:Prevalence of and clinical factors associated with lipoatrophy in HIV-infected Koreans receiving highly active antiretroviral therapy. 1977 32

Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2(AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARgamma. Importantly, lamin A/Cmutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their etiology is generally unknown, they could be associated with signs of autoimmunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first-generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardiovascular and hepatic complications.
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PMID:Human lipodystrophies: genetic and acquired diseases of adipose tissue. 2055 64

Lipoatrophy is a rare complication of treatment with insulin analogues. It has been reported with insulin Lispro (Eli Lilly, Indianapolis, Indiana, USA) and insulin Glargine (Sanofi-Aventis, Paris, France). To our knowledge, this is one of the first reports of lipoatrophy with Aspart, biphasic Aspart and Detemir insulin analogues (Novo Nordisk, Bagsvaerd, Denmark). We report the cases of four children with type I diabetes who were commenced on NovoMix 30 or NovoRapid/Levemir insulin injections. They developed lipoatrophy at the injection sites after 2-3 years of treatment. In two of our patients, lipoatrophy resolved when the injection sites were changed, suggesting that local factors could be the cause of lipoatrophy. However, lipoatrophy developed at the new sites in the other two patients, requiring a change of insulin preparation. Regular examination of the injection sites facilitated early detection of lipoatrophy in our patients. Lipoatrophy completely resolved over 1-2 years in all patients with no recurrence after 3-4 years of follow-up.
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PMID:Lipoatrophy with insulin analogues in type I diabetes. 2057 Aug 43


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