Obese, Overweight, Prediabetic State
Conditions
Keywords
vitamin D, cholecalciferol, supplementation, prediabetic state, obesity, glucose metabolism, gene expression, transcriptomics, epigenomics, immunological function, insulin sensitivity, peripheral mononuclear cells
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTVitamin D3
Vitamin D3 40 micrograms (1600 IU) per day
DIETARY_SUPPLEMENTPlacebo
Inactive placebo
DIETARY_SUPPLEMENTVitamin D 80
Vitamin D3 80 micrograms (3200 IU) per day
Sponsors
Academy of Finland
Juho Vainio Foundation
Finnish Foundation for Cardiovascular Research
Diabetes Research Foundation, Finland
University of Eastern Finland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity | Six months | Change in insulin sensitivity measured by oral glucose tolerance test at baseline and after 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral blood mononuclear cell gene expression | Six months | — |
| Inflammation | Baseline to six months | Change in inflammation measured as serum cytokines and adipose tissue inflammation at baseline and after 6 months |
| Adipose tissue gene expression | Six months | — |
Countries
Finland
Outcome results
None listed