Rationale: Chromium supplementation has been postulated to have a beneficial effect in the management of diabetes, but routine use is not currently recommended due to the conflicting evidence regarding efficacy. Further, the cellular mechanisms by which chromium affects glucose homeostasis are currently unknown. Several lines of evidence, however, suggest that chromium may modulate intracellular pathways of glucose metabolism. Hypothesis: Our hypothesis is that, in subjects with Type 2 diabetes, chromium supplementation will improve whole-body, insulin-mediated glucose uptake by increasing non-oxidative glucose disposal (Aim 1). This increase will be due to changes in glucose transport and glycogen synthase activity at the myocellular level (Aim 2) and in cellular signaling through the insulin receptor regulating glucose uptake and glycogen synthase activity (Aim 3). Experimental Approach: We will conduct a double-blinded, placebo-controlled intervention study in subjects with Type 2 diabetes. After assessment of baseline measures, subjects will be randomized to chromium or placebo for 12 weeks. We will then assess whole-body physiologic measures in addition to obtaining skeletal muscle biopsies for myocellular studies in situ. Significance: Chromium supplementation by the general public, and in people with diabetes in particular, has surpassed our ability as a scientific community to provide evidence regarding the safety and efficacy of its use; As such, randomized controlled trials with mechanistic aims are warranted and provide the rationale for this project. Therefore, the experiments proposed will provide new information regarding the effects of chromium on glucose homeostasis, and will provide the data necessary to generate recommendations for or against routine clinical use.
