Prospective Associations of Vitamin D With β-Cell Function and Glycemia : The PROspective Metabolism and ISlet cell Evaluation (PROMISE) Cohort Study

Abstract

OBJECTIVE

To examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), β-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes.

RESEARCH DESIGN AND METHODS

We followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index (IS _OGTT) and the homeostasis model assessment of IR (HOMA-IR), β-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve (AUC _glucose). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI.

RESULTS

Multivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up IS _OGTT or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (β = 0.005, P = 0.015) and ISSI-2 (β = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up AUC _glucose (β = −0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53–0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59–1.02]).

CONCLUSIONS

Higher baseline 25(OH)D independently predicted better β-cell function and lower AUC _glucose at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology.