Insulin resistance is a state where the body does not respond as it should to the insulin it produces. Individuals who are insulin resistant are at increased risk of both heart disease and type 2 diabetes; importantly, diabetes more than doubles the risk of heart disease, independent of other recognised risk factors. Interventions that prevent or reverse insulin resistance may help to attenuate risk of heart disease and diabetes. A number of randomised controlled trials provide proof of concept evidence regarding a beneficial effect of vitamin D on insulin resistance and other cardiovascular risk markers but experts have stated that further studies are required. Importantly, these studies should use appropriate endpoints, provide a high enough dose of vitamin D to optimise vitamin D status, and they should be conducted in clearly defined populations, The vitamin D trial we propose addresses these issues and aims to evaluate a potentially straightforward and low cost health care intervention for populations at highrisk of heart disease and diabetes. Specifically, this study would provide clinically relevant information on the metabolic effects of optimising vitamin D status in these high risk patients. This has clear economic and social implications given the current, and projected, burden of heart disease and diabetes.

This study will investigate the effect of vitamin D3 supplementation on insulin resistance and cardiovascular risk factors in people at high risk of type 2 diabetes and cardiovascular disease using the gold standard euglycaemic hyperinsulinaemic clamp method.

Inclusion Criteria:

• Impaired glucose tolerance (Fasting glucose <7.0 mmol/L (126mg/dl) and 2hr post-glucose load 7.8-11.0 mmol/L (140-199 mg/dl) or Impaired fasting glucose 5.6-6.9 mmol/L (100-125mg/dL) defined according to American Diabetes Association
• Sub-optimal vitamin D status (<50nmol/L)

Exclusion Criteria:

• Diabetes mellitus
• Established cardiovascular disease
• Psychiatric problems
• Pregnant or lactating
• Medical conditions or dietary restrictions that would substantially limit ability to complete the study requirements
• Excessive alcohol consumption (>28 Units/week men or >21 Units/week women)
• Already taking vitamin D supplements > 10 µg/d
• Medical conditions or medications that could influence vitamin D metabolism
• History of kidney stones
• Hypercalcaemia
• Hyperparathyroidism
• Significant liver and renal disease (liver function tests >3x upper limit of normal and glomerular filtration rate <30ml/min)