Clinical trial NCT01479933: Glucose Metabolism Effects of Vitamin D Supplementation in Prediabetes
Official title: Randomized Controlled Trial of Vitamin D Supplementation on Glucose Metabolism in Subjects With Components of the Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prediabetic State
Overweight
Obese
Keywords: vitamin D
cholecalciferol
supplementation
prediabetic state
obesity
glucose metabolism
gene expression
transcriptomics
epigenomics
immunological function
insulin sensitivity
peripheral mononuclear cells
Lead sponsor: University of Eastern Finland
Sponsor class: OTHER
Collaborators: name: Academy of Finland
name: Juho Vainio Foundation
name: Finnish Foundation for Cardiovascular Research
name: Diabetes Research Foundation, Finland
First posted: 2011-11-28
Enrollment: 73
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Insulin sensitivity
timeFrame: Six months
Secondary outcomes:
measure: Peripheral blood mononuclear cell gene expression
timeFrame: Six months
measure: Inflammation
timeFrame: Baseline to six months
measure: Adipose tissue gene expression
timeFrame: Six months
Other outcomes:
Locations:
city: Kuopio
country: Finland
facility: University of Eastern Finland, Kuopio Campus
Study officials:
affiliation: University of Eastern Finland
name: Tomi-Pekka Tuomainen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.