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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulation of dorsocervical fat, or a "buffalo hump" (BH), is commonly reported in adults with HIV-associated lipodystrophy (HIVLD). The pathogenesis underlying this aspect of a syndrome characterized by loss of subcutaneous fat from other body sites is poorly understood. We aimed to identify risk factors for a BH in HIV-infected adults in cross-sectional analyses of 2 HIV-infected ambulatory populations. The first group (Australian Lipodystrophy Prevalence Survey [APS]) consisted of 1348 Australian HIV-infected adults (95% male) irrespective of changes in body composition. The second group (Lipodystrophy Case Definition [LDCD] study) comprised 417 subjects (83% male) with at least 1 reported moderate or severe feature of HIVLD. A BH was reported in 24 (2%) APS subjects and 79 (19%) LDCD study subjects. A BH was not an isolated finding. Patients with a BH had a high prevalence of other features of HIVLD, similar to lipodystrophic patients without a BH, such as facial lipoatrophy reported in 100% and 61% BH-positive subjects from the APS and LDCD study, respectively. In both groups, those with a BH had higher fasting insulin (P<or=0.007), a higher body mass index (P<or=0.003), a higher waist/hip ratio (P<or=0.001), higher limb fat (P<or=0.003), and higher systolic blood pressure (P<0.05). On multivariate analysis, higher serum insulin, systolic blood pressure, age, and duration of exposure to ritonavir were independently associated with a BH in the APS group. In the LDCD group, higher insulin, diastolic blood pressure, and duration of exposure to zidovudine were independently associated with a BH. There was no association between a BH and hyperlipidemia. These data show that a BH is associated with other physical features of the lipodystrophy phenotype and suggest that hyperinsulinemia, a feature common to HIVLD, obesity, and hypercortisolism, is an important component of this phenotype, thus warranting closer monitoring of BH-positive patients for glucose intolerance and diabetes.
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PMID:Buffalo hump seen in HIV-associated lipodystrophy is associated with hyperinsulinemia but not dyslipidemia. 1567

Obesity is defined as increased mass of adipose tissue, conferring a higher risk of cardiovascular and metabolic disorders such as diabetes, hyperlipidemia, and coronary heart disease. To investigate the role of transcriptional factors, which are involved in adipocytes differentiation and adiposity, we have generated peroxisome proliferator-activated receptor (PPAR) gamma or CREB-binding protein (CBP)-deficient mice by gene targeting. Heterozygous PPARgamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. Heterozygous CBP-deficient mice showed increased insulin sensitivity and were completely protected from body weight gain induced by a high-fat diet. PPARgamma or CBP deficiency results in increased effects of hormones such as adiponectin and leptin. Adiponectin was decreased in obesity and lipoatrophy, and replenishment of adiponectin ameliorated insulin resistance. Moreover, adiponectin-deficient mice showed insulin resistance and atherogenic phenotype. Finally, cDNA encoding adiponectin receptors (AdipoR1/R2) have been identified by expression cloning. The expression of AdipoR1/R2 appears to be inversely regulated by insulin in physiological and pathophysiological states such as fasting/refeeding, insulin deficiency, and hyperinsulinemia models, and it is correlated with adiponectin sensitivity. These results facilitate the understanding of molecular mechanisms of adiponectin actions and obesity-linked diseases such as diabetes and atherosclerosis and propose the molecular targets for anti-diabetic and anti-atherogenic drugs.
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PMID:Nuclear receptors as targets for drug development: molecular mechanisms for regulation of obesity and insulin resistance by peroxisome proliferator-activated receptor gamma, CREB-binding protein, and adiponectin. 1572 3

Lipodystrophies represent a group of diseases characterized by altered body fat repartition and major metabolic alterations with insulin resistance. Genetic forms of partial lipodystrophy are currently recognized as two syndromes with subcutaneous lipoatrophy but preserved or increased fat at the level of face and neck (Dunnigan syndrome or FPLD due to LMNA mutations) and/or abdomen (PPARgamma-linked forms) and are both transmitted as dominant diseases. FPLD is further characterized by muscular hypertrophy, hyperandrogenism, acanthosis nigricans, hepatomegaly with steatosis and at the biological level, marked hypertriglyceridaemia, low HDL cholesterol, insulin resistance and altered glucose tolerance or diabetes. These signs occur after puberty and their prevalence and severity are more marked in female than in male patients. At the genetic level, LMNA mutations concern in most cases the type-A lamin C-terminal domain and more than 80% are heterozygous substitutions located at position 482 (R482W/Q/L). The other locations are G465D, K486N, R582H and R584H. The presence of signs evocative of limb-girdle muscular dystrophy has been reported in patients with typical forms of FPLD. In addition, forms presenting with lipodystrophy and myopathy have been reported for patients with mutations at position R28W, R60G, R62G or R527P. In addition, lipodystrophy, either partial or generalized, can be associated with syndromes of premature ageing like Hutchinson-Gilford progeria or acromandibular dysplasia, but also with other phenotypes, as we described in a patient bearing the LMNA R133L heterozygous substitution.
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PMID:A-type lamin-linked lipodystrophies. 1577 53

Octreotide is the first somatostatin analogue to become available for clinical use in the treatment of acromegaly. To our knowledge, there are no reports describing lipoatrophy in patients treated with octreotide. Here, we report three patients who developed lipoatrophy after treatment with subcutaneous octreotide. Three patients (all women; 36, 43, and 50 years of age) with diagnosis of acromegaly due to pituitary macroadenoma who had undergone transsphenoidal surgery and radiotherapy received subcutaneos octreotide because of uncontrolled disease. The dose of octreotide was increased gradually in all patients. Lipoatrophy was noticed around the injection sites after about 6 years, 30 months, and 4 years of subcutaneous octreotide treatment in all patients. Thereafter, subcutaneous octreotide treatment was changed to intramuscular octreotide-LAR injection in all patients. In two of them, lipoatrophy around all injection sites did not regress after about 8 and 12 months of octreotide-LAR treatment, respectively. In the third patient, lipoatrophy around the injection sites regressed after 12 months of octreotide-LAR treatment. These cases highlight a potential for subcutaneous octreotide to induce lipoatrophy. The underlying mechanism is unknown but an immunological mechanism which is seen in lipoatrophy induced by insulin may be involved in the pathogenesis. Besides; simple trauma, personal susceptibility, mistakes in the administration of the drug, a problem in drug pH, or an idiosyncratic reaction of adipocytes to octreotide or additives in the drug may have caused lipoatrophy in our patients. Lipoatrophy in these cases was observed on long-term subcutaneous octreotide administration. Although intramuscular octreotide-LAR has largely replaced subcutaneous octreotide, we suggest close clinical follow-up for lipoatrophy in patients who are still on subcutaneous octreotide.
Exp Clin Endocrinol Diabetes 2005 Jun
PMID:Lipoatrophy induced by subcutaneous administration of octreotide in the treatment of acromegaly. 1597 2

Recent studies identifying obesity as a significant and increasingly more common cause of morbidity and mortality have intensified research efforts aimed at increasing our understanding of adipose tissue biology. These efforts have culminated in the discovery of several adipokines, or adipose tissue-derived hormones, that have been implicated in the regulation of multiple physiological functions, as well as the realization that adipose tissue dysfunction plays an important role in the pathogenesis of diseases such as obesity and diabetes. To better understand the role of adipose tissue in these physiological/pathological events, several studies have employed transgenic strategies to eliminate adipose tissue. However, these mouse models of congenital lipoatrophy/lipodystrophy exhibit severe metabolic and somatic cell dysfunction. To circumvent this limitation, we have designed and characterized the first inducible fatless mouse. The FAT-ATTAC mouse is a transgenic model whereby expression of a myristoylated caspase 8-FKBP fusion protein enables selective ablation of adipocytes via induction of apoptosis that occurs upon treatment with a chemical dimerizer. The FAT-ATTAC mouse model not only has the advantage that adipocyte ablation be induced at any time during development, but it is also fully reversible, as adipose tissue regenerates after cessation of dimerizer treatment. The inducibility of this fatless mouse model holds potential for revealing novel physiological roles for adipose tissue as well as its contribution to the etiology and pathogenesis of various disease states. Here we describe several ongoing areas of research employing the FAT-ATTAC mouse; in addition we describe potential uses of the targeted transgenic apoptotic approach to study other cell types of interest.
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PMID:Apoptosis through targeted activation of caspase 8 ("ATTAC-mice"): novel mouse models of inducible and reversible tissue ablation. 1609 75

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20

Obesity and lipoatrophy are major risks for insulin resistance, non-insulin-dependent diabetes and cardiovascular disease. In the past three decades, significant advances have been made in delineating the key transcription factors of adipogenesis, as well as extracellular effectors and intracellular signalling pathways that regulate fat cell formation. This review focuses on in vitro models of adipocyte differentiation, and on the balance between pro- and anti-adipogenic factors that drive the adipocyte differentiation process. Full understanding of the mechanisms of adipose tissue differentiation represents a major issue to develop a comprehensive strategy to prevent and treat obesity.
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PMID:Adipogenesis: cellular and molecular aspects. 1631 Dec 13

HIV infection requires the continuous administration of antiretroviral molecules. Individual molecules belonging to the two main classes, protease inhibitors (PIs) and nucleoside analogues inhibitors of the viral reverse transcriptase (NRTIs) have been shown to be involved in deleterious side effects collectively called the lipodystrophy syndrome. This syndrome associates altered body fat repartition (peripheral lipoatrophy and visceral fat hypertrophy) and metabolic alterations (dyslipidemia, insulin resistance and diabetes). The pathophysiology of these alterations is complex but different studies argue for adipose tissue being a target of some PIs and NRTIs acting through different mechanisms. NRTIs are able to induce mitochondrial dysfonction and to modify adipocyte phenotype and adipose tissue pattern of secretion of cytokines (TNFalpha, IL-6) and other adipokines (adiponectin, leptin) probably through the production of reactive oxygen species. Some PIs also act on adipocyte, alter its differentiation and insulin sensitivity and also the pattern of secretion of adipokines by adipose tissue. These hypotheses could explain the loss of adipose tissue, while the mechanisms of visceral fat hypertrophy remain speculative. Since some adipokines and the free fatty acids released by adipocytes play a major role in the control of liver and muscles insulin sensitivity, these alterations are probably involved in the metabolic alterations seen in the patients. In addition, lipodystrophic adipose tissue could be involved in the increased lesions of atherogenesis and steatohepatitis presented by these patients. The treatment of lipodystrophy remains difficult and, at present, privileges the switch of the more deleterious drugs towards new molecules less aggressive for adipose tissue.
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PMID:[Lipodystrophies related to antiretroviral treatment of HIV infection]. 1668 23

Insulin treatment in Type 1 and Type 2 diabetes has come a long way since its discovery by Banting and Best in 1922. Early insulin therapy was life-saving, but was associated with practical problems and had side effects such as lipoatrophy. Initial modifications of insulin structure produced several classes of insulins with varying pharmacokinetics, but did not sufficiently mimic physiological insulin release. Novel long- and short-acting insulin analogues, the so-called 'designer insulins', developed through genetic engineering in the 1990s, paved the way for more physiological insulin therapy, which was theoretically less problematic in terms of hypoglycaemia and patient satisfaction. Insulin glargine (glargine) was the first DNA-recombinant long-acting insulin analogue. The replacement of asparagine with glycine and the addition of two arginine molecules in the molecular structure results in modified pharmacokinetics. Consequently, glargine has a longer, often 24-h profile, which is described as 'peakless' compared with other insulins such as neutral protamine Hagedorn insulin (NPH) and insulin ultralente. Since its launch, the use of glargine in Type 1 and Type 2 diabetes has been extensively reviewed to determine its place in the current insulin market. A potential advantage of glargine seems to be a lower risk of hypoglycaemia, particularly at night. The UK National Institute of Clinical Excellence has recommended that glargine is a treatment option for people with Type 1 diabetes. In Type 2 diabetes, it has been advised that glargine only be considered for: those who require assistance to administer insulin injections; those whose lifestyle is restricted significantly by recurrent symptomatic hypoglycaemic episodes; or those who would otherwise need twice-daily basal insulin injections in combination with oral glucose-lowering drugs.
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PMID:Insulin glargine and its place in the treatment of Types 1 and 2 diabetes mellitus. 1680 21

Dermatologic problems are common in diabetes, with approximately 30% of patients experiencing some cutaneous involvement during the course of their illness. Skin manifestations generally appear during the course of the disease in patients known to have diabetes, but they may also be the first presenting sign of diabetes or even precede the diagnosis by many years. The skin involvement can be autoimmune in nature, such as acanthosis nigricans, necrobiosis lipoidica, diabetic dermopathy, scleredema, and granuloma annulare, or infectious in the form of erythrasma, necrotizing fasciitis, and mucormycosis. Pharmacologic management of diabetes, in addition, can also result in skin changes, such as lipoatrophy and lipohypertrophy, at the site of injection of insulin, and oral antidiabetic agents can cause multiple skin reactions as adverse effects. The management of these cutaneous manifestations is tailored according to the underlying pathophysiology, but a tight control of blood glucose is a prerequisite in all management strategies.
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PMID:Diabetes mellitus. 1682 3


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