Decreased Serum Concentrations of 25-Hydroxycholecalciferol Are Associated With Increased Risk of Progression to Impaired Fasting Glucose and Diabetes

  1. Ran D. Balicer, MD, PHD, MPH2,5
  1. 1Diabetes and Endocrinology Clinic, Clalit Health Services, Jerusalem, Israel
  2. 2Clalit Research Institute and Chief Physician Office, Clalit Health Services, Tel Aviv, Israel
  3. 3Department of Research and Information, Chief Physician Office, Clalit Health Services, Tel Aviv, Israel
  4. 4Endocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  5. 5Epidemiology Department, Ben-Gurion University of the Negev, Beer-Sheva, Israel
  1. Corresponding authors: Anat Tsur, tsuranat{at}, and Gil Leibowitz, gleib{at}
  1. A.T. and B.S.F. contributed equally to this study.


OBJECTIVE To study the association between vitamin D status and the risk of incident impaired fasting glucose (IFG) and diabetes in a population-based cohort of diabetes-free subjects.

RESEARCH DESIGN AND METHODS In a historical prospective cohort study of subjects from the Clalit Health Services database, which includes information on nearly 4 million people, diabetes-free subjects aged 40–70 years with serum 25-hydroxyvitamin D (25-OHD) measurements available were followed up for 2 years to assess the development of IFG and diabetes in five 25-OHD subgroups: ≥25, 25.1–37.5, 37.6–50, 50.1–75, and >75 nmol/L.

RESULTS The baseline cohort included 117,960 adults: 83,526 normoglycemic subjects and 34,434 subjects with IFG. During follow-up, 8,629 subjects (10.3% of the normoglycemic group) developed IFG, and 2,162 subjects (1.8% of the total cohort) progressed to diabetes. A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes. The odds of transitioning from normoglycemia to IFG, from normoglycemia to diabetes, and from IFG to diabetes in subjects with a 25-OHD level ≤25 nmol/L were greater than those of subjects with a 25-OHD level >75 nmol/L [odds ratio 1.13 (95% CI 1.03–1.24), 1.77 (1.11–2.83), and 1.43 (1.16–1.76), respectively].

CONCLUSIONS Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes.


  • G.L. and R.D.B. share senior authorship.

  • Received June 4, 2012.
  • Accepted November 1, 2012.

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  1. Diabetes Care
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