Phenotype of subjects with type 2 diabetes mellitus may determine clinical response to chromium supplementation
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:
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Unifying mechanisms of trivalent chromium in health and disease
2020, Essential and Toxic Trace Elements and Vitamins in Human HealthIsoproterenol exacerbates hyperglycemia and modulates chromium distribution in mice fed with a high fat diet
2017, Journal of Trace Elements in Medicine and BiologyDietary chromium supplementation for targeted treatment of diabetes patients with comorbid depression and binge eating
2015, Medical HypothesesCitation Excerpt :Studies in diabetes have nearly exclusively focused on patients with T2DM but there are case report data suggesting benefit in type 1 diabetes, as well [65]. Recent meta-analyses indicated that chromium supplementation lowers blood glucose in T2DM patients [66–68] but not all patients derive this benefit [60,69–71] or show improvements in glycated hemoglobin [72]; pre-treatment insulin sensitivity explains ∼40% of the clinical response to chromium [71,73], with individuals who are more insulin resistant trending toward greater improvements in glucose regulation post-treatment. In contrast, most, but not all, studies focused on dietary chromium supplementation in samples of non-diabetic overweight or obese individuals have failed to find a significant impact of chromium picolinate on glucose regulation [74]; the reasons for this lack of an effect in obesity, per se, are not precisely known.
A double-blind, randomized pilot trial of chromium picolinate for binge eating disorder: Results of the Binge Eating and Chromium (BEACh) Study
2013, Journal of Psychosomatic ResearchCitation Excerpt :Based on its known insulin sensitizing actions, chromium has been investigated as an alternative treatment in type-2 diabetes and other insulin-resistant conditions, but results have been mixed [20,22,50–54] and routine prescription of chromium for individuals with diabetes remains highly controversial [55]. Insulin sensitivity is thought to account for ~ 40% of the variance in the clinical response to chromium [56], but factors that account for the remaining variance are largely unknown. Neuroimaging studies demonstrate abnormalities in brain reward, emotion/attention, and sympathetic nervous system pathways [for review, 57] and, more specifically, in 5HT and DA activity [58–60] in individuals who binge eat.
Molecular mechanisms of chromium in alleviating insulin resistance
2012, Journal of Nutritional BiochemistryCitation Excerpt :In contrast, Kleefstra and coworkers [24] refute the claims of beneficial effects of chromium, citing their randomized, placebo-controlled, double-blind study that failed to show a difference in hemoglobin A1C in subjects from a Western population with moderate glycemic control when placed on chromium [25]. Wang and coworkers, who have extensively performed both human and animal studies on chromium, argue that the discrepancies associated with the benefits of chromium supplementation may be explained by “subject phenotype” that includes several factors such as baseline insulin resistance, alteration in chromium metabolism and genetic makeup of individuals receiving the supplement [26]. Other factors complicate the analysis of chromium studies.
Chromium
2012, Encyclopedia of Human Nutrition