Plasma 25-Hydroxyvitamin D and Progression to Diabetes in Patients at Risk for Diabetes

An ancillary analysis in the Diabetes Prevention Program

  1. the Diabetes Prevention Program Research Group
  1. 1Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Boston, Massachusetts
  2. 2Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts
  3. 3Tufts University School of Medicine, Boston, Massachusetts
  4. 4Clinical Genetics, Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts
  5. 5Diabetes Center, Massachusetts General Hospital, Boston, Massachusetts
  6. 6Harvard Medical School, Boston, Massachusetts
  7. 7Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  8. 8Channing Laboratory, Brigham and Women’s Hospital, Boston, Massachusetts
  9. 9Bone Metabolism Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
  1. Corresponding author: Anastassios G. Pittas, apittas{at}


OBJECTIVE To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes.

RESEARCH DESIGN AND METHODS Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes. We assessed the association between plasma 25-hydroxyvitamin D, measured repeatedly during follow-up, and incident diabetes in the combined placebo (n = 1,022) and intensive lifestyle (n = 1,017) randomized arms of the DPP. Variables measured at multiple study time points (25-hydroxyvitamin D, BMI, and physical activity) entered the analyses as time-varying “lagged” covariates, as the mean of the previous and current visits at which diabetes status was assessed.

RESULTS After multivariate adjustment, including for the DPP intervention, participants in the highest tertile of 25-hydroxyvitamin D (median concentration, 30.1 ng/mL) had a hazard ratio of 0.72 (95% CI 0.56–0.90) for developing diabetes compared with participants in the lowest tertile (median concentration, 12.8 ng/mL). The association was in the same direction in placebo (0.70; 0.52–0.94) versus lifestyle arm (0.80; 0.54–1.17).

CONCLUSIONS Higher plasma 25-hydroxyvitamin D, assessed repeatedly, was associated with lower risk of incident diabetes in high-risk patients, after adjusting for lifestyle interventions (dietary changes, increased physical activity, and weight loss) known to decrease diabetes risk. Because of the observational nature of the study, the potential association between vitamin D and diabetes needs to be confirmed in intervention studies.

  • Received September 14, 2011.
  • Accepted November 22, 2011.

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  1. Diabetes Care vol. 35 no. 3 565-573
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