Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000

Abstract

Objective: Accumulating epidemiological evidence suggests that hypovitaminosis D may be associated with type 2 diabetes and related metabolic risks. However, prospective data using the biomarker serum 25-hydroxyvitamin D [25(OH)D] are limited and therefore examined in the present study.

Research design and methods: A total of 524 randomly selected nondiabetic men and women, aged 40-69 years at baseline, with measurements for serum 25(OH)D and IGF-1 in the population-based Ely Study, had glycemic status (oral glucose tolerance), lipids, insulin, anthropometry, and blood pressure measured and metabolic syndrome risk (metabolic syndrome z score) derived at baseline and at 10 years of follow-up.

Results: Age-adjusted baseline mean serum 25(OH)D was greater in men (64.5 nmol/l [95% CI 61.2-67.9]) than women (57.2 nmol/l [54.4,60.0]) and varied with season (highest late summer). Baseline 25(OH)D was associated inversely with 10-year risk of hyperglycemia (fasting glucose: beta = -0.0023, P = 0.019; 2-h glucose: beta = -0.0097, P = 0.006), insulin resistance (fasting insulin beta = -0.1467, P = 0.010; homeostasis model assessment of insulin resistance [HOMA-IR]: beta = -0.0059, P = 0.005), and metabolic syndrome z score (beta = -0.0016, P = 0.048) after adjustment for age, sex, smoking, BMI, season, and baseline value of each metabolic outcome variable. Associations with 2-h glucose, insulin, and HOMA-IR remained significant after further adjustment for IGF-1, parathyroid hormone, calcium, physical activity, and social class.

Conclusions: This prospective study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance. These associations are potentially important in understanding the etiology of abnormal glucose metabolism and warrant investigation in larger, specifically designed prospective studies and randomized controlled trials of supplementation.

FIG. 1.

The distribution of serum 25(OH)D by month in men (solid line) and women (broken line) in the Ely study. Vertical lines are the 95% CIs around the mean values at each month point. Month 1 represents January, while month 12 represents December.

FIG. 2.

Association between baseline serum 25(OH)D and 10-year follow-up fasting glucose (A and B) and 2-h glucose (C and D). A and C: The association in the entire cohort. B and D: The association was modified in participants with below and above median values of IGFBP-1. B: □, lower IGFBP-1, P = 0.0028; ▪, higher IGFBP-1, P = 0.6802; IGFBP-1–vitamin D interaction, P = 0.00047. C: □, lower IGFBP-1, P = 0.0031; ▪, higher IGFBP-1, P = 0.4935; IGFBP-1–vitamin D interaction, P = 0.0286. The MRC Ely Study 1990–2000.