OBJECTIVE To provide a comprehensive evaluation of chromium (Cr) supplementation on metabolic parameters in a cohort of Type 2 DM subjects representing a wide phenotype range and to evaluate changes in “responders” and “non-responders”. DESIGN After pre-intervention testing to assess glycemia, insulin sensitivity (assessed by euglycemic clamps), Cr status, body composition, subjects were randomized in a double-blind fashion to placebo or 1,000 μg Cr. A sub-study was performed to evaluate 24 hour energy balance/substrate oxidation and myocellular/intra-hepatic lipid content. RESULTS There was not a consistent effect of chromium supplementation to improve insulin action across all phenotypes. Insulin sensitivity was negatively correlated to soleus and tibialis muscle intramyocellular lipids and intra-hepatic lipid content. Myocellular lipids were significantly lower in subjects randomized to Cr. At pre-intervention, “responders”, defined as insulin sensitivity change from baseline > 10%, had significantly lower insulin sensitivity and higher fasting glucose and A1c when compared to placebo and “non-responders”, i.e. insulin sensitivity change from baseline < 10%. Clinical response was significantly correlated (p < 0.001) to the baseline insulin sensitivity, fasting glucose and A1c. There was no difference in Cr status between “responders”, and “non-responders”. CONCLUSIONS Clinical response to chromium is more likely in insulin resistant subjects who have more elevated fasting glucose and A1c levels. Cr may reduce myocellular lipids and enhance insulin sensitivity in subjects with type 2 DM independent of effects on weight or hepatic glucose production. Thus, modulation of lipid metabolism by Cr in peripheral tissues may represent a novel mechanism of action.

Background and Aims-Considerable controversy exists regarding use of chromium (Cr) supplementation to modulate carbohydrate metabolism in subjects with diabetes. Recently, we reported that Cr supplementation, provided as 1000 ug/day as Cr picolinate, enhanced insulin