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

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)

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.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Pre-diabetes; Sub-optimal Vitamin D Status
• Intervention / Treatment: Dietary supplement: Vitamin D3 supplementation

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • N. Ireland
    • Belfast, N. Ireland, United Kingdom, BT12 6BJ
      • Queen's University, Belfast

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo group	Dietary supplement: Vitamin D3 supplementation; 3000IU (75µg) vitamin D3 will be given daily for a period of 26 weeks to the group who receive the active comparator. The efficacy of vitamin D3 supplementation on insulin resistance will be compared to the placebo group.
Active Comparator: Vitamin D3 supplementation; Patients will take 3000IU (75 µg) Vitamin D3 supplementation per day for a period of 26 weeks.	Dietary supplement: Vitamin D3 supplementation; 3000IU (75µg) vitamin D3 will be given daily for a period of 26 weeks to the group who receive the active comparator. The efficacy of vitamin D3 supplementation on insulin resistance will be compared to the placebo group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Insulin Resistance	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).	Measured at baseline and after 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Vitamin D Status	Change in vitamin D status will be measured using the gold standard Ultra performance liquid chromatography followed by tandem mass spectrometry	Measured at baseline and after 6 months
Change in Markers of Cardiovascular Risk	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	Measured at baseline and after 6 months
Change in Carotid-femoral Pulse Wave Velocity (PWV)	Assessed by sequential tonometry with ECG gating using the SphygmoCor PWV System	Measured at baseline and after 6 months
Change in Hand Grip Strength	Assessed using hand held dynamometer	Measured at baseline and after 6 months
Health Status	SF-36 Questionnaire	Measured at baseline and after 6 months

Collaborators and Investigators

• Sponsor: Queen's University, Belfast
• Collaborators: Northern Ireland Chest Heart and Stroke; HSC Research & Development Division, Public Health Agency, Northern Ireland; The Metabolic Unit Research Fund, The Royal Hospitals, Belfast, Northern Ireland

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: June 26, 2013
• First Posted (Estimate): June 28, 2013

Study Record Updates

• Last Update Posted (Estimate): May 8, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Vitamin D, Pre-diabetes, Insulin Resistance
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Hyperglycemia; Prediabetic State; Glucose Intolerance; Insulin Resistance; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: QUB: B12/35; HSC: 12117MMcK-AS