Effect of Vitamin D Supplementation on Glucose Tolerance in Subjects at Risk for Diabetes With Low Vitamin D. (EVIDENCE)

• Change in plasma glucose concentration 2 hours after consuming 75g oral glucose (2 hour PC glucose, or 2hrPC glucose) [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
  Change from baseline in plasma glucose concentration 2 hours after consuming 75g oral glucose.
  
  

• Change in insulin resistance assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR) which is G*I/22.5 where G is fasting plasma glucose (mmol/L) and I is fasting plasma insulin (uU/mL).
  
  
• Change in Matsuda insulin sensitivity index [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in Matsuda insulin sensitivity index which is (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]).
  
  
• Change in insulin secretion assessed using the homeostasis model assessment of beta-cell function (HOMA-B) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in homeostasis model assessment of beta-cell function (HOMA-B) which is 20*I/(G-3.5) where I is fasting plasma insulin (uU/mL) and G is fasting plasma glucose (mmol/L).
  
  
• Change in insulinogenic index [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in insulinogenic index which is dI0-30/dG0-30, where dI0-30 is the change in plasma insulin between fasting and 30min and dG0-30 is the change in plasma glucose between fasting and 30min after 75g oral glucose.
  
  
• Change in disposition index derived from HOMA-IR and HOMA-B [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in disposition index which is HOMA-B/HOMA-IR, which have been defined above.
  
  
• Change in disposition index based on oral glucose tolerance test (OGTT) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in ISSI-2 index which is AUCi/AUCg x Matsuda insulin sensitivity index, where AUCi and AUCg, respectively, are the total areas under the plasma insulin and glucose response curves after 75g oral glucose and Matsuda insulin sensitivity index has been defined above.
  
  
• Change in fasting plasma glucose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting plasma glucose
  
  
• Change in glucose area under the curve [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in incremental area under the glucose response curve after 75g oral glucose
  
  
• Change in glycated hemoglobin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in glycated hemoglobin (HbA1c)
  
  
• Correlation between changes in serum 25-hydroxy-vitamin D concentration (25(OH)D) and changes in 2 hour PC glucose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Correlation between change from baseline in serum 25-hydroxy-vitamin D concentration and change from baseline in plasma glucose 2 hours after 75g oral glucose.
  
  

• Fasting serum 25(OH)D [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Absolute concentration of serum 25-hydroxy-vitamin D3
  
  
• Change in serum 25(OH)D [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in serum 25-hydroxy-vitamin D3
  
  
• Change in serum total cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting serum total cholesterol
  
  
• Change in serum low-density lipoprotein (LDL) cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting serum calculated LDL cholesterol
  
  
• Change in serum high-density lipoprotein (HDL) cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting serum HDL cholesterol
  
  
• Change in serum triglycerides [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting serum triglycerides
  
  
• Change in serum apolipoprotein B (apoB) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting serum apolipoprotein B
  
  
• Change in serum c-reactive protein (CRP) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting serum c-reactive protein
  
  
• Change in serum orosomucoid [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting serum orosomucoid
  
  
• Change in serum haptoglobin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting serum haptoglobin
  
  
• Change in serum alpha-1-antitrypsin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change from baseline in fasting serum alpha-1-antitrypsin
  
  
• Change in serum aspartate aminotransferase (AST) [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  Change from baseline in fasting serum aspartate aminotransferase
  
  
• Change in serum alanine aminotransferase (ALT) [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  Change from baseline in fasting serum alanine aminotransferase
  
  
• Serum calcium [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  Absolute concentration of serum calcium
  
  
• Urinary calcium:creatinine ratio [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  Urinary calcium:creatinine ratio
  
  

Type 2 diabetes (T2D) is an increasingly prevalent and serious condition whose risk appears to be increased by low serum vitamin D concentrations. Epidemiological studies show an association between increased diabetes risk and low serum vitamin D and studies suggest that vitamin D may protect against diabetes by reducing chronic inflammation and improving insulin sensitivity and insulin secretion. Although clinical studies show some of these effects, no studies have been able to show that vitamin D supplementation reduces post-prandial blood glucose, the most clinically relevant marker of diabetes and dysglycemia. Previously, the investigators showed that cheddar cheese and low-fat cheese can be fortified with high levels of vitamin D3 (28,000IU/ 30g portion) and that, in this form, it is at least as a effective as vitamin D3 supplements in raising serum vitamin D concentrations. Since post-prandial glucose is most sensitive to changes in insulin sensitivity the main purpose of this study is to determine the effect of vitamin D supplementation on oral glucose tolerance (ie. serum glucose 2h after 75g oral glucose) in individuals who are at risk for developing T2D. Secondary objective are to determine the effect of vitamin D supplementation on insulin sensitivity, insulin secretion, inflammatory markers, blood lipids and markers of safety including serum parathyroid hormone levels and urinary calcium excretion.