Effect of Vitamin D3 Supplementation on Insulin Resistance- The DIR Study

Not Applicable

Completed

Conditions: Insulin Resistance
Pre-diabetes
Sub-optimal Vitamin D Status

Interventions: Dietary Supplement: Vitamin D3 supplementation

Registration Number: NCT01889810

Lead Sponsor: Queen's University, Belfast

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 81

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vitamin D3 supplementation	Vitamin D3 supplementation	Patients will take 3000IU (75 µg) Vitamin D3 supplementation per day for a period of 26 weeks.
Placebo	Vitamin D3 supplementation	Placebo group

Primary Outcome Measures

Name	Time	Method
Change in Insulin Resistance	Measured at baseline and after 6 months	Insulin resistance will be measured using the gold standard euglycaemic-hyperinsulinaemic clamp method (note - it is anticipated that a total of 60 volunteers will complete the primary endpoint assessment).

Secondary Outcome Measures

Name	Time	Method
Change in Vitamin D Status	Measured at baseline and after 6 months	Change in vitamin D status will be measured using the gold standard Ultra performance liquid chromatography followed by tandem mass spectrometry
Change in Markers of Cardiovascular Risk	Measured at baseline and after 6 months	Measurements of seated and 24-hour ambulatory blood pressure, lipids, homeostasis model assessment (HOMA), HbA1c, and inflammatory and immune function markers including tumour necrosis factor-alpha and high sensitivity c-reactive protein
Change in Carotid-femoral Pulse Wave Velocity (PWV)	Measured at baseline and after 6 months	Assessed by sequential tonometry with ECG gating using the SphygmoCor PWV System
Change in Hand Grip Strength	Measured at baseline and after 6 months	Assessed using hand held dynamometer
Health Status	Measured at baseline and after 6 months	SF-36 Questionnaire