Clinical trial NCT01889810: Effect of Vitamin D3 Supplementation on Insulin Resistance- The DIR Study
Official title: Effect of Vitamin D3 Supplementation on Insulin Resistance and Cardiovascular Risk Factors in People at High Risk of Type 2 Diabetes and Cardiovascular Disease (The DIR Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sub-optimal Vitamin D Status
Pre-diabetes
Insulin Resistance
Keywords: Vitamin D, Pre-diabetes, Insulin Resistance
Lead sponsor: Queen's University, Belfast
Sponsor class: OTHER
Collaborators: name: Health and Social Care Research and Development , Northern Ireland
name: Royal Victoria Hospital, Belfast
name: Northern Ireland Chest Heart and Stroke
First posted: 2013-06-28
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Change in Insulin Resistance
timeFrame: Measured at baseline and after 6 months
Secondary outcomes:
measure: Change in Vitamin D Status
timeFrame: Measured at baseline and after 6 months
measure: Change in Markers of Cardiovascular Risk
timeFrame: Measured at baseline and after 6 months
measure: Change in Carotid-femoral Pulse Wave Velocity (PWV)
timeFrame: Measured at baseline and after 6 months
measure: Change in Hand Grip Strength
timeFrame: Measured at baseline and after 6 months
measure: Health Status
timeFrame: Measured at baseline and after 6 months
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Queen's University, Belfast
state: N. Ireland
Study officials:
affiliation: Queen's University, Belfast
name: Michelle McKinley, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wallace HJ, Holmes L, Ennis CN, Cardwell CR, Woodside JV, Young IS, Bell PM, Hunter SJ, McKinley MC. Effect of vitamin D3 supplementation on insulin resistance and beta-cell function in prediabetes: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2019 Nov 1;110(5):1138-1147. doi: 10.1093/ajcn/nqz171.