th9507 and Insulin-Resistance

Subcutaneous atrophy and central fat accumulation are common among HIV-infected patients receiving highly active antiretroviral therapy, and may be accompanied by dyslipidemia and insulin resistance. These fat changes, although commonly referred to together as lipodystrophy, are best considered as separate disorders, with distinct pathogeneses and treatment approaches. These morphological and metabolic abnormalities first appeared after introduction of protease inhibitors more than 10 yr ago, but research has demonstrated that their pathogenesis is multifactorial, with contributions from other antiretroviral medications, patient-related factors, and HIV itself. Switching to a less toxic highly active antiretroviral therapy regimen has shown partial effectiveness for the management of fat atrophy and lipid abnormalities. Lifestyle modification or surgical approaches are the treatment of choice for lipohypertrophy, although novel therapies targeting the GH axis show promise. HIV-related dyslipidemia may be difficult to treat, and can be complicated by drug-drug interactions between some lipid-lowering medications and antiretroviral medications. Treatment of diabetes in HIV-infected patients should generally follow established guidelines, but thiazolidinediones, rather than metformin, may be considered first-line treatment in a patient with lipoatrophy, given their potential to increase sc fat. The contribution of body fat changes and metabolic abnormalities to cardiovascular risk and the changing risk profiles of newer antiretroviral regimens are under intense investigation.

Topics: Antiretroviral Therapy, Highly Active; Cardiovascular Diseases; Diabetes Mellitus; Dyslipidemias; Growth Hormone-Releasing Hormone; HIV Infections; Humans; Insulin Resistance; Lipodystrophy; Male; Middle Aged; Risk Factors

Use of growth hormone is associated with side effects, including insulin resistance. The objective of this study was to determine whether tesamorelin, a stabilized growth hormone-releasing hormone analogue, would alter insulin sensitivity or control of diabetes.. A 12-week randomized, placebo-controlled study of 53 patients with type 2 diabetes. Three treatment groups: placebo, 1 and 2 mg tesamorelin.. Fasting glucose, glucose and insulin from oral glucose tolerance test, glycosylated hemoglobin (HbA1c), home blood glucose, insulin-like growth factor-1, and lipids.. Relative insulin response following oral ingestion of glucose.. No significant differences were observed between groups in relative insulin response over the 12-week treatment period. At Week 12, fasting glucose, HbA1c and overall diabetes control were not significantly different between groups. In addition, relevant modifications in diabetes medications were similar between groups. Total cholesterol (-0.3±0.6 mmol/L) and non-HDL cholesterol (-0.3±0.5 mmol/L) significantly decreased from baseline to Week 12 in the tesamorelin 2 mg group (p<0.05 vs. placebo). No patient discontinued the study due to loss of diabetes control.. Treatment of type 2 diabetic patients with tesamorelin for 12 weeks did not alter insulin response or glycemic control.. ClinicalTrials.gov NCT01264497.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Growth Hormone-Releasing Hormone; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Lipids; Male; Middle Aged