This study demonstrated independent associations of 25(OH)D with both insulin sensitivity and β-cell function in subjects without known diabetes, the majority of whom were free of diabetes based on OGTTs. The major contribution of this study is the finding of an association between vitamin D and β-cell function. Previous studies assessing the association between 25(OH)D and β-cell function have yielded inconsistent results (2
), possibly resulting from small sample sizes, the use of indirect measures of β-cell function (i.e., primarily fasting based measures), and/or the lack of adjustment for background IR. In contrast, our study found a significant positive association between vitamin D and β-cell function, using validated measures of β-cell function which account for the hyperbolic relationship between insulin secretion and insulin sensitivity (12
Although an inverse association between 25(OH)D and IR has been observed in previous studies (3
), the majority of these studies relied primarily on simple fasting-based measures and most did not adjust for physical activity or PTH. In addition, negative findings have been reported, even when more direct measures of insulin sensitivity were used (2
). Possible reasons for this discrepancy in findings may be due to small sample sizes or differences in study populations. The negative findings of Gulseth et al. (2
) among those with the metabolic syndrome may be attributable to the sequestering of 25(OH)D in adipose tissue (15
), resulting in reduced bioavailability of 25(OH)D. Similarly, we found a weaker association of vitamin D with IR and β-cell function in those with a BMI ≥30 kg/m2
Strengths of the current study include the measurement of serum 25(OH)D concentration, as well as the use of validated measures of both IR and β-cell dysfunction. In addition, the current study included a large, well-characterized multi-ethnic sample. Limitations include the cross-sectional design, and the lack of “gold standard” measures of IR and β-cell function, which are invasive and costly to use in large studies. Lastly, 25(OH)D was measured in blood samples obtained across different seasons, although we controlled for a seasonal effect and assessed potential interactions.
In conclusion, vitamin D was significantly related to IR and β-cell function in a multi-ethnic sample at risk for type 2 diabetes. Further research is needed on the prospective association between vitamin D and the underlying disorders of type 2 diabetes in large population-based studies.