2007 Annual Report 1a.Objectives (from AD-416) To determine the role of chromium in glucose and insulin metabolism of human subjects and to determine methods to assess chromium status. 1b.Approach (from AD-416) We propose to use a double-linked placebo controlled randomized study design with well characterized subjects with type 2 diabetes on diet therapy only. Subjects will be divided into 2 groups and given daily 1000 micrograms of chromium or placebo and the effects on glucose and insulin metabolism and body composition will be determined. Chromium concentrations in urine, plasma, and red blood cells, before, during, and after glucose clamp studies will be evaluated as methods to assess status. 3.Progress Report This report documents research conducted under a reimbursable agreement between ARS and Pennington Biomedical Research Center, Baton Rouge, LA. Additional details of research can be found in the report for the in-house associated project 1235-51520-037-00D, "Chromium and Polyphenols from Cinnamon in the Prevention and Alleviation of Glucose Intolerance". This project entails a double-blind placebo controlled randomized study to determine the mode of action of chromium in people with type 2 diabetes. The form of Cr given was Cr picolinate at 1000 µg of Cr per day for 24 weeks with 56 subjects in the chromium group and an equal number in the placebo group. A sensitive measure of glucose metabolism, the hyperinsulinemic euglycemic clamp with stable isotope infusions, was used to monitor changes in glucose uptake and utilization. Blood, urine, and muscle biopsy samples were analyzed to evaluate the role of chromium in human nutrition. The measurement of insulin signaling proteins, protein phosphorylation, and kinase activity provides a cellular basis for evaluating the effects of Cr on insulin function. Chromium status was assessed by determining Cr levels in the urine, plasma, and red blood cells before and after supplementation during the hyperinsulinemic euglycemic clamps and oral glucose tolerance tests. This represents the most comprehensive chromium study performed to date, and should greatly aid in understanding of the role of chromium in human nutrition. All 56 people have enrolled in the study, and all the clinical tests have been completed for 10 subjects. Samples are currently being analyzed. All urine samples and serum samples from 20 subjects during the glucose tolerance tests, and also during the hyper insulinemic euglycemic clamps, have been completed. A manuscript demonstrating that response to chromium is dependent upon insulin sensitivity has been submitted. Conference calls are conducted on a bi-monthly basis and the ARS scientist has made a site visit to the partner’s laboratory to discuss the analysis and consult on publication material.