Will vitamin D reduce insulin resistance? Still a long way to go

We read with interest the article by Alvarez et al, which aimed to investigate the relations of circulating 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) concentrations with direct measurements of insulin sensitivity, after robust measures of body composition and fat distribution were accounted for. We would like to express our opinion and a different interpretation of the data provided by authors, with the hope that other points for discussion are brought up. In a very recent publication, Alvarez et al provided novel findings suggesting that dietary vitamin D is independently associated with insulin sensitivity in African Americans (AAs) but not in European Americans (EAs). Interestingly, the 2 groups were identical for hepatic insulin sensitivity [homeostatic model assessment (HOMA)], whereas Si, a method for measuring insulin sensitivity that encompasses both hepatic and peripheral tissues, was lower in AAs, therefore suggesting a pivotal role for insulin resistance in skeletal muscle [especially in the presence of identical body mass index (BMI)] in correlation with 25(OH)D. In the present article, the authors suggest that 25(OH)D and PTH concentrations are independently associated with whole-body insulin sensitivity and suggest that these variables may influence insulin sensitivity through independent mechanisms. In fact, multiple linear regression analysis indicated that 25(OH)D and PTH concentrations were independently related to Si after adjustment for age, race, and intraabdominal adipose tissue. It is well known, however, that adipose tissue is the natural reservoir for lipo-soluble 25(OH)D. The higher BMI and the higher subcutaneous fat content found in AAs (although the latter difference was not statistically significant) could therefore explain the differences in 25(OH)D concentration, as well as in HOMA index, found by the authors. We examined the effect of 25(OH)D on insulin sensitivity in obese subjects and found a linear correlation between them, which is apparently in agreement with Alvarez et al. Obesity, however, is not invariably associated with insulin resistance, because normal insulin sensitivity can be present in some obese subjects. If 25(OH)D concentration influences insulin sensitivity independently of obesity, it should be found to be low in insulin-resistant obese subjects and high in insulin-sensitive obesity. We divided our obese population into 2 subgroups, according to their insulin sensitivity (low and high). The 2 groups were similar in BMI, age, and sex but did not show any difference in 25(OH)D concentration, thus confirming the hypothesis that 25(OH)D concentrations are not influenced by the degree of insulin resistance but mainly by the adipose tissue’s reservoir, at least in our EA participants. Unfortunately, in the presentstudied population but not in the previous one, AAs had higher BMI (and HOMA) and the actual role of these variables in determining hypovitaminosis D was not ruled out. In conclusion, we are certain that 25(OH)D concentration mainly reflects body fatmass, either subcutaneous or visceral; the reduction of fat mass, rather than vitamin D supplementation, is the best route for the prevention and treatment of insulin resistance and diabetes.