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Abstract
Grant Number: 5R01AT002499-04 Project Title: Novel Therapy for Glucose Intolerance in HIV Disease
PI Information: Name Title GELATO, MARIE C. marie.gelato@sunysb.edu PROFESSOR OF MEDICINE Abstract: DESCRIPTION (provided by applicant): Multi-drug regimens in HIV disease are associated with an incidence of insulin resistance of at least 50%. Insulin resistance is associated with the development of dyslipidemia, type 2 diabetes, and hypertension. This constellation of metabolic abnormalities is known to cause accelerated atherosclerosis in patients with type 2 diabetes. The current guidelines from the American Diabetes Association and the American College of Endocrinologists recommends screening for glucose intolerance and treatment for patients at high risk of diabetes. This proposal seeks to establish a treatment option for insulin resistance / glucose intolerance in HIV/AIDS prior to the transition to overt diabetes. Chromium picolinate is a dietary supplement that has been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus and, in a preliminary study, in HIV+ patients. This dietary supplement has a wide margin of safety and may provide substantial therapeutic benefit without serious side-effects. This proposal will test the hypothesis that chromium picolinate improves insulin-stimulated glucose uptake by increasing the insulin receptor-mediated tyrosine phosphorylation of insulin receptor substrate-1, resulting in increased activity of phosphatidylinositol 3-kinase. The hypothesis will be addressed in two specific aims. Specific Aim 1 will assess quantitative improvements in insulin-mediated glucose disposal in a double-blind, placebo-controlled study of chromium supplementation with 1000 microgram (19.2 mu/mol) of chromium as chromium picolinate, over a two month course of therapy of subjects with glucose intolerance (defined with an oral glucose tolerance test, OGTT). Both safety and efficacy (improved glucose disposal with a hyperinsulineminc, euglycemic clamp and insulin secretion, OGTT) will be evaluated. The cellular mechanism for improved insulin sensitivity with chromium supplementation will be determined in Specific Aim 2 by assessing the effect of chromium supplementation on the insulin-stimulated activity of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase in biopsies of adipose tissue. Thus, this research will document the therapeutic benefit of chromium supplementation for insulin resistance / glucose intolerance in HIV disease and will provide a mechanistic framework to explain how chromium supplementation enhances insulin action.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
HIV infection, chelation therapy, chromium, diabetes mellitus therapy, diet therapy, dietary supplement, human therapy evaluation, insulin sensitivity /resistance, prediabetic state
antiAIDS agent, clinical trial, combination chemotherapy, drug adverse effect, enzyme activity, glucose metabolism, glucose tolerance, insulin receptor, medical complication, phosphatidylinositol 3 kinase, phosphorylation
alternative medicine, biopsy, clinical research, human subject, nutrition related tag, patient oriented research
Institution: STATE UNIVERSITY NEW YORK STONY BROOK STONY BROOK, NY 11794 Fiscal Year: 2008 Department: MEDICINE Project Start: 01-JUN-2005 Project End: 31-MAY-2009 ICD: NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE IRG: ACE