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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of human immunodeficiency virus (HIV) disease, with longer survival and improved quality of life of HIV-infected subjects. However, HAART regimens, especially those including protease inhibitors, have been shown to cause in a high proportion of HIV-infected patients a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (coronary artery disease and stroke). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART is needed according to the most recent clinical guidelines.
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PMID:Highly active antiretroviral therapy-associated metabolic syndrome and cardiovascular risk. 1667

The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV disease, with longer survival and improved quality of life of HIV-infected subjects. However, HAART regimens, especially those including protease inhibitors (PIs) have been shown to cause in a high proportion of HIV-infected patients a metabolic syndrome that may be associated with an increased risk of cardiovascular disease (about 1.4 cardiac events per 1,000 years of therapy according to the Framingham score). Metabolic features associated with somatic changes (lipodystrophy/lipoatrophy) include dyslipidemia (about 70% of patients), insulin resistance (elevated C-peptide and insulin), type 2 diabetes mellitus (8%-10% of the patients), hypertension (up to 75% of patients), coagulation abnormalities (25% of patients), lactic acidemia, and elevated hepatic transaminases (nonalcoholic steatohepatitis). HAART-associated metabolic syndrome is an increasingly recognized clinical entity. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the cardiovascular risk in patients under HAART. A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART is needed according to the most recent clinical guidelines.
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PMID:Highly active antiretroviral therapy-associated metabolic syndrome: pathogenesis and cardiovascular risk. 1677 67

Lipodystrophies represent a heterogeneous group of diseases characterized by an abnormal subcutaneous fat distribution, the extent of which can vary from localized, to partial, to generalized lipoatrophy. Whereas partial and generalized lipodystrophies are each associated with metabolic abnormalities, the localized form is not. These metabolic changes include insulin resistance with type 2 diabetes, acanthosis nigricans, dyslipidaemia predominantly consisting of hypertriglyceridaemia (associated with the onset of pancreatitis) and depressed HDL cholesterol, liver steatosis and hypertension. Affected women are often hirsute and this can be associated with the presence of polycystic ovarian syndrome (PCOS). Most of these clinical features are present to some extent in patients with the common metabolic syndrome. As the prevalence of metabolic syndrome far outweighs that of lipodystrophy, the diagnosis of this rare disorder may often be overlooked with the affected patient diagnosed as merely being 'yet' another case of metabolic syndrome. In this article, we draw attention to the importance of recognizing patients with lipodystrophy who present with metabolic abnormalities, as both the diagnostic as well as the therapeutic approach of these patients differ profoundly from patients with the metabolic syndrome.
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PMID:Inherited lipodystrophies and the metabolic syndrome. 1756 81

The use of highly active antiretroviral therapy (HAART) in HIV-1 infection confers immunological and survival advantages, at the cost of induction of significant metabolic disturbances. These include insulin resistance, disturbances in lipid metabolism, glucose homeostasis, adipocyte physiology and body fat partitioning with peripheral lipoatrophy and visceral obesity. These metabolic disturbances produce clinical manifestations which impact on the future health of the HIV-infected patient, including hyperlipidaemia, lipodystrophy, metabolic syndrome, cardiovascular disease and type 2 diabetes. These conditions are evident in the relative short term as HAART (and possibly HIV infection) appears to accelerate their pathogenesis. The current understanding of the mechanisms and time courses for developing metabolic complications on HAART is reviewed in this paper. The efficacy of therapeutic interventions for insulin resistance, hyperlipidaemia, body fat partitioning disorders and metabolic syndrome is summarized.
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PMID:Metabolic consequences and therapeutic options in highly active antiretroviral therapy in human immunodeficiency virus-1 infection. 1807 Aug 30

The overall mortality of diabetic patients after myocardial infarction is 3-4 times higher than non-diabetics. The cellular mechanisms underlying such a poor clinical prognosis remain incompletely understood. Recent reports suggest that lipotoxicity associated with impaired liporegulation is among the leading factors in the pathogenesis of type 2 diabetes. The goal of this study was to investigate whether excess lipid accumulation specifically in heart muscle cells contributes to the expansion of myocardial infarction in type 2 diabetic patients. Comparative structural analysis of cardiac tissue was performed on autopsy samples from the infracted hearts of diabetic and non-diabetic individuals with special reference to the expansion of the infarction, degenerative changes, lipoatrophy, cell death, and replacement fibrosis. We found that progressive accumulation of lipids in cardiac myocytes was accompanied by considerable loss of myofibrils and was frequently observed in the heart tissue of type 2 diabetic patients. This indicates that disassembly of the contractile apparatus in the cells infiltrated with lipids weakens their capability for functional activity. Analysis of degenerative changes in the diabetic tissue has shown that lipid-laden cardiac myocytes were more susceptible to necrotic and apoptotic cells death leading to expansion of the infarction and the development of progressive focal replacement fibrosis both in the perinecrotic zone and in the areas located far from the site of injury. Our data show that lipoatrophy and loss of muscle cells during the post-infarction period aggravate the functional impairment in the diabetic heart and limits its adaptive capacity for compensatory remodeling. This suggests that lipotoxic myocardial injury associated with defects of lipid metabolism in type 2 diabetes predisposes its evolution toward congestive heart failure and is an important factor contributing to a high mortality following infarction.
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PMID:Intracardiac lipid accumulation, lipoatrophy of muscle cells and expansion of myocardial infarction in type 2 diabetic patients. 1809 36

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

Genetic screening for HIV-related complications is emerging as a clinically relevant prediction tool. A number of single nucleotide polymorphisms associated with conditions such as dyslipidemia and type 2 diabetes have been identified in both the general population and in HIV-infected individuals. Additionally, genome-wide association studies have looked at hepatitis C susceptibility in HIV-infected people, and genetic studies are ongoing for coronary artery disease, osteoporosis, and neurocognitive dysfunction. To date, understanding the contribution of genetic variation to the pathogenesis of lipoatrophy and kidney disease in HIV-infection is limited.
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PMID:Genetic screening for metabolic and age-related complications in HIV-infected persons. 2117 Mar 75

A 54-year-old Italian female patient was admitted to our Department with the diagnosis of type 2 diabetes poorly controlled with insulin therapy. The patient was born by consanguineous parents (first degree cousins); she had acromegaloid features, diffuse lipoatrophy and muscular pseudo-hypertrophy since childhood. To confirm the clinical hypothesis of congenital generalized lipodystrophy (CGL) or Berardinelli-Seip syndrome, the sequences of AGPAT2 (encoding for 1-acyl-sn-glycerol-3-phosphate acyltransferase beta) and BSCL2 (encoding for seipin) candidate genes were analyzed. DNA analysis showed the presence of a homozygous mutation in exon 3 of the AGPAT2 gene (P112L). This is the first description of a Caucasian subject with CGL who carries the pathologic allelic variant P112L of the AGPAT2 gene.
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PMID:Description of an AGPAT2 pathologic allelic variant in a 54-year-old Caucasian woman with Berardinelli-Seip syndrome. 2174 63

The highly active antiretroviral therapy (HAART) can cause a metabolic syndrome consisting of lipodystropy/lipoatrophy, dyslipidemia, and type 2 diabetes mellitus with an increased cardiovascular risk. The pathogenetic bases of HAART-associated lipodystrophy are poorly known. A genetic screen was used to evaluate proteins that are modulated in HIV-1-infected patients with or without lipodystrophy syndrome, that are routinely treated with HAART regimens. The most significant modulation was represented by FAP48 expression. Stable over-expression of FAP48 was able to alter, in vitro, adipogenesis, acting both on calcineurin and glucocorticoid pathways. Finally, we demonstrated that FAP48 over-expression was able to influence the capacity of some HIV drugs, Saquinavir and Efavirenz, but not Stavudine, Amprenavir, and Indinavir to inhibit adipocyte formation. In conclusion, this molecule could be a potential target for novel therapeutic approaches to the HAART related lipodystrophy in HIV patients.
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PMID:Role of FAP48 in HIV-associated lipodystrophy. 2267 19

Berardinelli-Seip congenital lipodystrophy (BSCL) syndrome is a rare autosomal-recessive disease characterised by lipoatrophy and associated with deregulations of glycidic and lipid metabolism. We report three BSCL cases with its typical clinical picture and complications. Clinically, they all show marked atrophy of adipose tissue, acromegaly, acanthosis nigricans and tall stature. Two cases present attention deficit hyperactivity and developmental learning disorders; another patient has hypertrophic myocardiopathy and polycystic ovary syndrome. In all the cases AGPAT2 was the identified mutation. All the cases present hypertriglyceridemia. One case has developed hyperinsulinism controlled with metformin and another case already has type 2 diabetes with a difficult clinical control. There is no curative treatment and the current treatment options are based only on symptomatic control of the complications. Recently, published studies showed that leptin-replacement therapy appears a promising tool in the metabolic correction of BSCL complications, highlighting the importance of further investigations in BSCL treatment.
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PMID:Berardinelli-Seip syndrome: highlight of treatment challenge. 2336 58


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