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)

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01889810

Enrollment

Registered

2013-06-28

Start date

2013-08-31

Completion date

2016-06-30

Last updated

2023-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sub-optimal Vitamin D Status, Pre-diabetes, Insulin Resistance

Keywords

Vitamin D, Pre-diabetes, Insulin Resistance

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.

Interventions

DIETARY_SUPPLEMENTVitamin 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

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)

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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

Countries

United Kingdom

Participant flow

Participants by arm

Arm	Count
Vitamin D3 Supplementation Patients will take 3000IU (75 µg) Vitamin D3 supplementation per day for a period of 26 weeks. 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.	35
Placebo Placebo group 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.	31
Total	66

Baseline characteristics

Characteristic	Vitamin D3 Supplementation	Placebo	Total
Age, Continuous	52.4 years STANDARD_DEVIATION 2	54.0 years STANDARD_DEVIATION 1.7	53.3 years STANDARD_DEVIATION 2.02
Race and Ethnicity Not Collected	—	—	0 Participants
Sex: Female, Male Female	16 Participants	11 Participants	27 Participants
Sex: Female, Male Male	19 Participants	20 Participants	39 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 35	0 / 31
serious Total, serious adverse events	0 / 35	0 / 31

Outcome results

Primary

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).