Glucose Metabolism Effects of Vitamin D Supplementation in Prediabetes (VitDmet)

Randomized Controlled Trial of Vitamin D Supplementation on Glucose Metabolism in Subjects With Components of the Metabolic Syndrome

Vitamin D deficiency is widespread throughout the world, and the deficiency has been associated with several chronic diseases, such as cardiovascular diseases and diabetes. In Nordic countries, like in Finland, there is a particular variation in vitamin D status, and during wintertime, when there is no exposure to ultraviolet-B light from the sun, serum concentrations of vitamin D decrease substantially. In Finland, some 40% of middle-aged men and one third of women also have some degree of impairment of glucose metabolism.

The purpose of this trial is to investigate the effects of two different daily doses of vitamin D on glucose metabolism in men 60 years of age or older and who are vitamin D deficient, have a high body mass index and at least two characteristics of cardio-metabolic syndrome.

Altogether 102 subjects with low serum calcidiol (<60 nmol/L) will be recruited and randomized to one of the three groups: 1) 40 µg/d vitamin D3, 2) 80 µg/d vitamin D3 or 3) placebo. The supplementation period will last for 6 months from September 2011 to March 2012.

The main hypotheses of the trial are: (1.) Vitamin D supplementation will improve glucose and insulin metabolism in people with a low baseline vitamin D status, in a dose-dependent manner. (2.) Vitamin D supplementation will have an effect on the expression of genes involved in glucose and insulin metabolism and inflammation. (3.) Vitamin D supplementation will have an effect on epigenetic changes in key genes participating in vitamin D metabolism.

Study Overview

• Status: Completed
• Conditions: Overweight; Prediabetic State; Obese
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Vitamin D3; Dietary supplement: Vitamin D 80

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Kuopio, Finland, 70211
    • University of Eastern Finland, Kuopio campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 60 years or older
• Serum calcidiol <75 nmol/L
• Body mass index 25-35 kg/m2
• Impaired fasting glucose or impaired glucose tolerance (fasting glucose 5.6-7.0 mmol/L or 2h oral glucose tolerance test glucose 7.8-11.0 mmol/L)

Exclusion Criteria:

• Any chronic disease and condition, which may hamper to follow the intervention protocol (such as alcohol abuse)
• Any chronic disease or therapy which may mask or interact with the investigated effects (such as diabetes or systemic corticosteroid therapy)
• Any disease or state that raises a vitamin D related safety concern (such as chronic liver, thyroid or kidney disease, hypercalcemia, sarcoidosis or other granulomatous diseases such as active chronic tuberculosis or Wegener's granulomatosis)
• Use of supplements yielding vitamin D over 20 µg/d and unwillingness to discontinue the use.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Dietary supplement: Placebo; Inactive placebo
EXPERIMENTAL: Vitamin D 40; Vitamin D3 40 micrograms (1600 IU) per day	Dietary supplement: Vitamin D3; Vitamin D3 40 micrograms (1600 IU) per day
EXPERIMENTAL: Vitamin D 80; Vitamin D3 80 micrograms (3200 IU) per day	Dietary supplement: Vitamin D 80; Vitamin D3 80 micrograms (3200 IU) per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Change in insulin sensitivity measured by oral glucose tolerance test at baseline and after 6 months	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral blood mononuclear cell gene expression		Six months
Inflammation	Change in inflammation measured as serum cytokines and adipose tissue inflammation at baseline and after 6 months	Baseline to six months
Adipose tissue gene expression		Six months

Collaborators and Investigators

• Sponsor: University of Eastern Finland
• Collaborators: Academy of Finland; Juho Vainio Foundation; Finnish Foundation for Cardiovascular Research; Diabetes Research Foundation, Finland

Publications and helpful links

General Publications

• Ryynanen J, Neme A, Tuomainen TP, Virtanen JK, Voutilainen S, Nurmi T, de Mello VD, Uusitupa M, Carlberg C. Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals. Mol Nutr Food Res. 2014 Oct;58(10):2036-45. doi: 10.1002/mnfr.201400291. Epub 2014 Jul 28.

Helpful Links

• University of Eastern Finland

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): May 1, 2012

Study Registration Dates

• First Submitted: August 29, 2011
• First Submitted That Met QC Criteria: November 22, 2011
• First Posted (ESTIMATE): November 28, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 5, 2013
• Last Update Submitted That Met QC Criteria: March 3, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: insulin sensitivity; obesity; supplementation; vitamin D; cholecalciferol; prediabetic state; gene expression; glucose metabolism; transcriptomics; epigenomics; immunological function; peripheral mononuclear cells
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Body Weight; Prediabetic State; Overweight; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: VitDmet