The results of what we believe is the first randomized placebo controlled trial of chromium in metabolic syndrome did not demonstrate an effect of pharmacologic dosing of CrPic on insulin sensitivity or other features of metabolic syndrome. CrPic did, however, increase the early phase of insulin secretion in response to glucose as measured by AIRg.
Multiple prior studies have examined the effects of chromium supplementation on glucose metabolism with inconsistent results. This is most likely due to significant variability among these studies with respect to the dose and preparation of chromium given, the duration of use, the measurement techniques, and the study population. Whereas most of the studies have been in patients with T2DM, few studies have been performed in patients at high risk for developing the disease, such as those with IGT, obesity, or a family history of T2DM.17,18
An improvement in insulin sensitivity as assessed by the minimal model was reported in patients with obesity and a family history of T2DM after receiving CrPic (1000 μgrams/day) for 32 weeks.18
However neither the exact magnitude of this effect nor the effect on AIRg data were reported. Similar findings were made using a hyperglycemic clamp to assess SI after administering CrCl3
for 12 weeks to patients IGT in an open-label study.17
Others have not shown any change in insulin sensitivity after Cr+3
supplementation in a nondiabetic elderly population and in patients with IGT.19,20
Specifically, a recent smaller study targeted patients with IGT and reported no improvement in insulin sensitivity after treatment with CrPic (800 μg/day) using the homeostasis model assessment (homeostasis model assessment [HOMA] index).20
Studies have demonstrated lower plasma insulin levels in both the fasting and glucose stimulated state in response to chromium treatment.18,21,22
However, none of these studies used AIRg as a measure of insulin secretion. Joseph et al. demonstrated a decrease in insulin AUC without an increase in insulin secretion in patients treated with chromium and resistance training for 12 weeks.23
Our study also describes the effect of chromium supplementation on insulin secretion as measured by AIRg. AIRg is a measure of the acute β-cell response to rising glucose through insulin secretion24
and has been shown to be an independent predictor of the development of T2DM, even after adjusting for SI.25
Although accumulating evidence from randomized trials support the role of targeting IR as a means of preventing T2DM, data on insulin secretagogues are lacking, although the short-acting sulfonylurea nateglidine is being prospectively evaluated alone and with the angiotensin receptor blocker valsartan in the NAVIGATOR trial to study whether these drugs can delay or prevent T2DM in patients with IGT.26
Although our finding is intriguing, it should be interpreted with caution because the relative effect was small and could have been a chance finding, and the clinical relevance of the observed increase AIRg may be limited.
This study also explored the effects of chromium on other metabolic syndrome features. Despite previous literature suggesting a weight loss effect of CrPic,27
we found no changes in body weight or waist circumference over 16 weeks. Additionally, CrPic did not affect fasting serum TG or HDL-C as previously suggested.18,19,28
Our results did not demonstrate any changes in markers of vascular inflammation or oxidative stress after chromium supplementation. Whereas we were admittedly underpowered to detect changes in hs-CRP, we are reassured by the fact that CrPic did not increase oxidative stress as has previously been suggested by others.29
Additionally, we did not find that CrPic supplementation led to adverse events or to a worsening of renal function or a reduction in iron stores as has been previously been reported,30,31
suggesting that up to 16 weeks of a supraphysiologic dose of CrPic is safe.
Our study has several limitations. First, our study was single center and short term and included a heterogeneous patient population. Patients with metabolic syndrome, while easy to identify clinically, are quite heterogeneous with regard to their level of insulin sensitivity as demonstrated by our baseline FSIGT data. This is documented by the fact that only 52% of our metabolic syndrome subjects had impaired glucose metabolism (IFG or IGT) at baseline, a variable commonly used in diabetes prevention intervention trials. Recent data in patients with T2DM suggests baseline insulin resistance as assessed by the hyperinsulinemic eyglycemic clamp may predict response of CrPic on insulin sensitivity.32
Our study was not designed to answer this question; however, our data do not support this finding in obese patients with IGT as assessed by FIGTT. Another possibility is that we initially overestimated the effect size for chromium on SI, resulting in an underpowered analysis for this variable. Our intervention was for 16 weeks and it is possible (though unlikely) that a longer duration of chromium use is needed to observe any clinically beneficial effects. Finally, it is possible that CrPic supplementation is more effective in chromium-deficient patients and that our population had normal baseline chromium balance based on urinary chromium, thus limiting an effect, although we do not have any data available on the prevalence of chromium deficiency in adults with metabolic syndrome.20
In conclusion, the study does not support the use of chromium as a treatment for patients with metabolic syndrome. Despite its widespread use, we were unable to demonstrate any beneficial effect of CrPic supplementation on detailed measures of insulin sensitivity, body weight, lipids, and inflammatory markers in obese nondiabetic patients with metabolic syndrome. Currently, there are clinically proven alternatives (diet and exercise) for the prevention of diabetes in this patient population that are highly effective and should remain the mainstay of treatment. The unanticipated effect of CrPic on insulin secretion may warrant further study in larger samples of pre-diabetic patients to reproduce this finding and further elucidate its mechanism.