Here’s another federally-funded study of chromium supplementation to counter insulin resistance and potentially help prevent the development of Type 2 Diabetes and Coronary Artery Disease.
Investigator: Dr. UMESH MASHARANI, Univ. of California at San Francisco
Sponsor: NCCAM/National Institutes of Health
Abstract: DESCRIPTION (provided by applicant): Background: Chromium is an essential nutrient for the maintenance of normal glucose tolerance. While studies of chromium supplementation in patients with type 2 diabetes (T2D) have indicated that this agent lowers glucose and insulin levels, its cellular mechanism of action is not welt understood. Studies both in humans and in cell culture suggest that chromium enhances the insulin signaling pathway. We propose, therefore, to study chromium’s effects on insulin-stimulated glucose uptake in a well characterized population of non-obese, non-diabetic subjects with insulin resistantance. This population is ideal for an analysis of the effects of chromium on insulin action, because they are as insulin resistant as T2D patients but do not have the important confounder of hyperglycemia. Because these insulin resistant subjects are at risk for the development of T2D, the Metabolic Syndrome, and coronary artery disease (CAD), a demonstration of the beneficial effects of chromium on insulin action could ultimately have important public health consequences. Hypotheses: (1) Chromium will improve insulin sensitivity in a general population of non-obese, insulin-resistant, non-diabetic subjects; and (2) The improvement of insulin action by chromium is due to its effects on the major components of the insulin signling pathway (insulin receptor, IRS proteins, PI 3-kinase, PKB/AKT and GLUT4); and/ or regulators of the insulin signaling pathway (PTP 1B, PC-1, IKK, NF-KappaB and PKC) Methods: The insulin sensitivity of 180 subjects will be initially estimated by homeostasis model assessment. The most insulin resistant subjects will then be randomized to 16 weeks of therapy with either chromium or placebo. To quantitate chromium-induced improvements in both in insulin sensitivity and the insulin signaling pathway, euglycemic hyperinsulinemic clamps with muscle biopsies will be performed before and after treament. Anticipated Results and Significance: We believe these studies will (1) confirm the beneficial effect of chromium on insulin sensitvity; (2) further our understanding of the molecular mechanisms of chromium action; and (3) form a basis for a larger project examining the long term efficacy of chromium in preventing the developement of T2D and CAD.
October 31, 2007
This research is being funded by NCCAM, the federal government’s chief dietary supplement research agency. It builds on past knowledge about the role of an inexpensive dietary supplement, chromium, for management of diabetes (insulin resistance/glucose intolerance). This research study is directed especially to the case of people with HIV on multi-drug regimens, who experience insulin resistance/glucose intolerance at a high rate.
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Investigator: Dr. Marie C Gelato, State University of New York at Stony Brook
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.
October 30, 2007
