Glucose Metabolism Effects of Vitamin D Supplementation in Prediabetes

Study Overview
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Brief Summary
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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.

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

Conditions
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Prediabetic State, Overweight, Obese

Intervention / Treatment
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* Dietary Supplement: Vitamin D3
* Dietary Supplement: Placebo
* Dietary Supplement: Vitamin D 80


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D 40<br>Vitamin D3 40 micrograms (1600 IU) per day | Dietary Supplement: Vitamin D3<br>* Vitamin D3 40 micrograms (1600 IU) per day<br>|
| Experimental: Vitamin D 80<br>Vitamin D3 80 micrograms (3200 IU) per day | Dietary Supplement: Vitamin D 80<br>* Vitamin D3 80 micrograms (3200 IU) per day<br>|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Inactive placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, cholecalciferol, supplementation, prediabetic state, obesity, glucose metabolism, gene expression, transcriptomics, epigenomics, immunological function, insulin sensitivity, peripheral mononuclear cells