Chromium, Cellular Energy Status and Whole Body Energy Balance

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DESCRIPTION (provided by applicant): Insulin resistance is a key pathophysiologic feature of the "metabolic syndrome" and is strongly associated with co-existing cardiovascular risk factors and accelerated atherosclerosis. Strategies to improve insulin resistance by pharmacological means have represented the traditional approach for clinical medicine. However, because of the widespread use of dietary supplements by the general public, nutritional supplementation with the use of biologically based therapies that effectively increase insulin sensitivity represent a very attractive and novel approach for future studies designed to intervene in the development of metabolic syndrome. Chromium has been proposed as one such therapy. Unfortunately, considerable controversy exists regarding the effect of chromium in human metabolism as there is a paucity of data in humans in regard to proposed mechanism of action, and as such, chromium remains as one of the only trace minerals where the mechanism of action is not known. Our recent findings have suggested that chromium supplementation over a long-term period of observation may significantly attenuate weight gain and percent body fat in human subjects. The observed change in body weight and fat stores would suggest a novel new mechanism for chromium to improve whole body energy balance by enhancing energy expenditure and/or altering dietary intake. In addition, we provide experimental evidence to suggest that a primary event contributing to cellular energy status, i.e. activation of AMP kinase, appears to be a cellular target for chromium. Activation of AMP kinase is known to enhance glucose uptake, reduce hepatic glucose production, increase oxidation of fatty acids and enhance cellular signaling. Thus, this project's overall objective is to perform exploratory studies on the effect of chromium on whole body energy balance, lipid metabolism, and cellular energy status in subjects with Type 2 diabetes as part of an ongoing chromium supplementation trial. We hypothesize that, in subjects with type 2 diabetes, chromium will enhance cellular AMP kinase activation resulting in an increase in skeletal muscle lipid metabolism and adipose tissue function These findings will be associated with an improved whole body energy balance and will provide the preliminary data in order to plan larger more definitive clinical research studies.