Elsevier

Metabolism

Volume 56, Issue 12, December 2007, Pages 1652-1655
Metabolism

Phenotype of subjects with type 2 diabetes mellitus may determine clinical response to chromium supplementation

https://doi.org/10.1016/j.metabol.2007.07.007Get rights and content

Abstract

Considerable controversy exists regarding the use of chromium (Cr) supplementation to modulate carbohydrate metabolism in subjects with diabetes. Recently, we reported that Cr supplementation, provided as 1000 μg/d as Cr picolinate, enhanced insulin sensitivity in subjects with type 2 diabetes mellitus. Our data agreed with some, but not all, studies that evaluated a similar dose and formulation in type 2 diabetes mellitus and suggested that subject selection and characteristics may be important considerations when assessing the clinical response. Thus, the goal of this study was to assess which metabolic or clinical characteristics, when obtained at baseline, best determine a clinical response to Cr when assessing changes in insulin sensitivity. Seventy-three subjects with type 2 diabetes mellitus were assessed in a double-blinded, randomized, placebo-controlled study. Subjects were assessed at baseline for glycemic control with glycated hemoglobin measures, oral glucose tolerance tests, and body weight and body fat measures (dual-energy x-ray absorptiometry). After baseline, insulin sensitivity in vivo was assessed with the use of hyperinsulinemic-euglycemic clamps. After the baseline clamp, subjects were randomized to receive Cr supplementation (1000 μg Cr/d provided as Cr picolinate) or placebo daily for 6 months. All study parameters were repeated after 6 months. The relationship of the baseline characteristics of the study subjects to the change in insulin sensitivity was determined. Sixty-three percent of the subjects with type 2 diabetes mellitus responded to the Cr treatment as compared with 30% with placebo. The only subject variable significantly associated with the clinical response to Cr was the baseline insulin sensitivity, as assessed with the hyperinsulinemic-euglycemic clamp (partial R2 = .4038) (P = .0004). Subject phenotype appears to be very important when assessing the clinical response to Cr because baseline insulin sensitivity was found to account for nearly 40% of the variance in the clinical response to Cr.

Introduction

It is well observed in clinical trials that the measured response to an identical pharmacologic or lifestyle intervention will vary greatly among individuals. The reasons that explain a minimal as opposed to a very robust effect for subjects provided the same clinical intervention are not precisely known, but may be secondary to differences in genetic or physiologic makeup, in addition to differences in other subject characteristics. Such an observation may partially explain the considerable controversy that exists regarding the use of chromium (Cr) supplementation to modulate carbohydrate metabolism in subjects with diabetes. In part, the controversy regarding the differences reported for Cr's effect in humans stems from the lack of definitive randomized trials, the lack of “gold standard” techniques to assess glucose metabolism, the use of differing doses and formulations, and the study of heterogeneous study populations [1]. We recently reported that Cr supplementation, provided as 1000 μg/d as Cr picolinate, enhanced insulin sensitivity in subjects with type 2 diabetes mellitus [2]. However, our data agreed with some, but not all, studies that evaluated a similar dose and formulation in subjects with type 2 diabetes mellitus [3], [4]. We concluded that patient selection may be an important consideration when assessing the clinical response to this nutritional supplement [2]. If a specific patient phenotype is shown to be more responsive to Cr or, alternatively, if a particular characteristic suggests that a patient is not likely to respond, such information would prove clinically invaluable. Therefore, the goal of this study was to assess which metabolic or clinical patient factors, when obtained at baseline, appear to best determine the clinical response to Cr. To accomplish our goal, we assessed insulin sensitivity with the use of hyperinsulinemic-euglycemic clamps before and after a specified period of Cr supplementation in subjects with type 2 diabetes mellitus. We then determined which subject characteristic accounted for the greatest contribution to the change in insulin sensitivity.

Section snippets

Research design and methods

Subjects were required to have type 2 diabetes mellitus for more than 6 months, an age range of 25 to 70 years, and a fasting glucose ≥125 mg/dL at the time of screening. All procedures were approved and conducted in strict compliance with institutional human research guidelines.

The evaluations were double blinded, randomized, and placebo controlled. After entry criteria had been met, each subject met with the study nutritionist, who provided instructions for a weight maintenance diet. During

Results

A total of 73 subjects (38 male, 35 female) completed the protocol, in which 38 were randomized to Cr. The subjects had an average (±SD) age of 57.8 ± 8.7 years, GHb of 7.4% ± 2.4%, fasting glucose of 145.7 + 46.5 mg/dL, body mass index (BMI) of 30.4 ± 4.2, body weight of 87.4 + 12.7 kg, and whole-body glucose disposal (by clamp) of 287 ± 144 mg/min.

The response rate (defined by an increase in insulin sensitivity from baseline clamp to the end of study clamp) was 63% for the subjects randomized

Conclusions

This preliminary report suggests that a major determinant for assessing clinical response to Cr in subjects with type 2 diabetes mellitus is the presence of insulin resistance before intervention. As described, variables assessed in this report included demographic parameters such as age, race, and sex; metabolic parameters that included assessment of GHb, glucose disposal obtained during clamp, insulin, and glucose response to OGTT; and phenotype parameters, as assessed by BMI, percentage of

Acknowledgments

Authors and contribution to the study:

Zhong Q Wang: study design, manuscript preparation

Jianhua Qin: data analysis, manuscript review

Julie Martin: study coordination, subject recruitment, manuscript review

Xian H Zhang: study conduct, manuscript review

Olga Sereda: study conduct, performance of clamp procedures, manuscript review

Richard Anderson: study design, data review and analysis, manuscript review

Patricia Pinsonat: study coordination, subject recruitment, manuscript review

William T Cefalu:

References (11)

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