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BackgroundThe use of chromium supplements is widespread for the prevention and treatment of diabetes mellitus but there are conflicting reports on efficacy, possibly reflecting discrepant effects across different populations. In the present studies, we test the hypothesis that chromium supplementation raises serum chromium levels and correspondingly improves insulin sensitivity.MethodsA double blind placebo-controlled randomized trial was conducted on 31 non-obese, normoglycemic subjects. After baseline studies, the subjects were randomized to placebo or chromium picolinate 500 μg twice a day. The primary endpoint was change in insulin sensitivity as measured by euglycemic hyperinsulinemic clamp. Pre-specified secondary endpoints included fasting lipids, blood pressure, weight, body composition measured by DXA scan.ResultsAfter 16 weeks of chromium picolinate therapy there was no significant change in insulin sensitivity between groups (p=0.83). There was, however, a strong association between serum chromium and change in insulin resistance (β = -0.83, p=0.01), where subjects with the highest serum chromium had a worsening of insulin sensitivity. This effect could not be explained by changes in physiological parameters such as body weight, truncal fat and serum lipids with chromium therapy.ConclusionsChromium therapy did not improve insulin sensitivity in non-obese normoglycemic individuals. Further, subjects who have high serum chromium levels paradoxically had a decline in insulin sensitivity. Caution therefore should be exercised in recommending the use of this supplement.Trial registrationThe study was registered on the NIH registry (clinicaltrials.gov) and the identifier is NCT00846248

rectification. A genetically encoded Eag domain fragment (amino acids 1-135) was shown to restore slow deactivation to N-truncated channels. Our present study sought to further investigate Eag domain contributions to hERG gating kinetics. We coexpressed the genetically encoded Eag domain fragment (N1-135) with hERG channels bearing a deletion of the N-terminus in Xenopus oocytes and measured current with two-electrode voltage-clamp recordings. Here we report that coexpression with the N1-135 peptide led to a reduction in relative outward current and slowed recovery from inactivation resulting in channels with properties similar to those measured in wild-type hERG. Through regulation of deactivation and inactivation gating, the Eag domain determines the physiologically critical resurgent component of hERG current via a non-covalent interaction with the channel.