• glucose tolerance (fasting, after OGTT), systemic inflammation, lipoprotein profile, blood pressure, body weight and body composition [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
• Genetic studies on Vitamin D related genes and risk of type 2 diabetes and cardiometabolic outcomes [ Time Frame: 4 months ] [ Designated as safety issue: No ]
• To collect and archive biological specimens (serum, plasma, DNA) so that they can be used for testing of new hypotheses either within the parent stud or through future ancillary studies. [ Time Frame: 0 and 4 months ] [ Designated as safety issue: No ]

The purpose of the randomized trial is to quantify the effect of vitamin D and calcium supplementation on beta-cell function, insulin sensitivity, glucose tolerance and systemic inflammation and other cardiometabolic outcomes in ambulatory adults at high risk for type 2 diabetes.

There is animal and human observational evidence to suggest that vitamin D and calcium are important in modifying t2DM risk but there are critical gaps in our knowledge about the clinical magnitude of the association with t2DM and potential mechanisms in humans. We are conducting a randomized trial to quantify the effect of vitamin D and calcium supplementation on beta-cell function, insulin sensitivity, glucose tolerance and systemic inflammation and other cardiometabolic outcomes in ambulatory adults at high risk for t2DM. We anticipate that the research proposed in this application is significant because it will provide the basis for defining feasible nutritional interventions that promotes prevention of t2DM. Based on the results of the proposed studies and future work in this area, vitamin D and calcium supplementation can assume an important role in the treatment of t2DM and in the prevention of the disease in the 41 million Americans who are at risk of developing t2DM.

• Glucose Intolerance
• Type 2 Diabetes Mellitus
• Metabolic Syndrome

• Drug: Vitamin D3 2,000 IU orally once daily
• Drug: Calcium Carbonate 400 mg orally twice daily
• Drug: Vitamin D3-Placebo
• Drug: Calcium-Placebo

• Other: Vitamin D3 2,000 IU daily plus Calcium Carbonate 400 mg twice daily
• Other: Vitamin D3 2,000 IU daily plus Calcium-Placebo twice daily
• Other: Vitamin D3-Placebo plus Calcium Carbonate 400 mg twice daily
• Other: Vitamin D3-Placebo plus Calcium-Placebo

• Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29. Epub 2007 Mar 27. Review.
• Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007 Apr;30(4):980-6. Epub 2007 Feb 2.
• Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, Hu FB. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care. 2006 Mar;29(3):650-6.

Inclusion Criteria:

• Ethnicity: all ethnic groups
• Gender: men and women

• Age

  1. Lower age limit: 40 years inclusive
  2. Upper age limit: NONE

• BMI

  1. Lower BMI limit: 25 inclusive
  2. Upper BMI limit: 40 inclusive

• Glucose Intolerance / Mild Diabetes defined as

  1. Fasting glucose ≥100 mg/dl OR
  2. 2-hr glucose after OGTT ≥140 mg/dl OR
  3. 5.8 ≤ Hemoglobin A1c ≤ 7

Major Exclusion Criteria:

• Diabetes requiring pharmacotherapy
• Smoking
• Hyperparathyroidism
• Hypercalcemia (Calcium > 10.5 mg/dl)
• Kidney stone
• Pregnancy