There is an association between elevated Type II Diabetes Mellitus (T2DM) risk and low serum levels of vitamin D. It is important to examine whether Vitamin D can enhance oral glucose tolerance in individuals at risk for developing T2DM. As such, the hypothesis suggested is that Vitamin D supplementation (4,000 IU/day) for 24 weeks in pre-diabetic individuals will decrease insulin resistance and the associated metabolic indices linked to the later development of T2DM.

Epidemiologically, there is an association between elevated T2DM risk and low serum levels of vitamin D and suggest that it may protect against the diseases through the improvement of insulin sensitivity as well as secretion and reducing chronic inflammation. Although some of these effects were shown in clinical studies, no study permitted the inference that vitamin D can reduce blood glucose and attenuate inflammation. Post-prandial glucose is the most sensitive to alterations in insulin sensitivity. Therefore, it is rational to examine whether vitamin D can enhance oral glucose tolerance in individuals at risk for developing T2DM and to elucidate the mechanism by which this occurs, i.e. via improved insulin sensitivity or improved insulin secretion, or both. Furthermore, identifying a distinct proteomics-based signature that can be used to distinguish responders to supplementation from non-responders is critical to define the bases for inter-individual variation in response and the effect of vitamin D on the prevention of T2DM. Identification of this proteomics-based signature will enable us to tailor alternative preventive measures to adjust the vitamin D dose to non-responders, leading to more effective and precise intervention protocols.

Inclusion Criteria:

• male or non-pregnant, non-lactating females, aged 18-75

• volunteered to participate by signing the consent form

• BMI ˂ 40kg/ m2

• serum 25(OH) vitamin D3 (25(OH)D) concentration ˂75nmol/L

• fasting serum glucose <7.0 mmol/L

• HOMA insulin resistance index ≥1.3

• presence of any ONE OR MORE of the following risk factors for type 2 diabetes:

  • high BMI (>23)
  • high waist circumference according to IDF ethnic specific values for non- Caucasian (females >80cm; males >90cm)
  • family history of diabetes in first-degree relative (parent or sibling)
  • previous history of gestational diabetes
  • history of high blood glucose, high triglycerides and/or low HDL cholesterol

Exclusion Criteria:

• fasting serum glucose ≥7.0mmol/L
• history of renal failure or liver disease
• serum urea or creatinine >1.8 times upper limit of normal (ULN)
• serum aspartate or alanine transaminase (AST,ALT) >1.5 times ULN
• current use of drug or drugs to treat diabetes or which influence glucose metabolism
• medical or surgical event requiring hospitalization within 3 months of randomization
• presence of any condition affecting nutrient absorption