Clinical trial NCT01779908: Role of Vitamin D in the Prevention and Treatment of Diseases Associated With Insulin Resistance
Official title: Role of Vitamin D in the Prevention and Treatment of Diseases Associated With Insulin Resistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin D-deficient
Insulin-resistant
Keywords: Vitamin D supplementation
Insulin resistance
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
Collaborators: name: Canadian Diabetes Association
name: Laval University
name: Fonds de la Recherche en Santé du Québec
First posted: 2013-01-30
Enrollment: 96
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Prospective, randomized and placebo-controlled 6-month trial of vitamin D supplementation in 130 Caucasian and vitamin D-deficient men and women aged 25 years and over. Participants will have abdominal obesity and at least one factor associated with insulin resistance. Participants will be randomized by sex, BMI and age. The primary aim is to compare the effect of daily vitamin D3 (cholecalciferol, 5000 IU) vs. placebo for 6 mo on insulin sensitivity (M-value by the gold standard method, the euglycemic hyperinsulinemic clamp). Secondary aims are to evaluate the effects of vitamin D3 vs. placebo on other indices of glucose metabolism, the lipid profile, blood pressure and anthropometric measurements. Questionnaires on physical activity and sunlight exposure, and a food frequency questionnaire will be administered at 0 and 6 mo to adjust for confounding factors. At 0 and 6 mo, changes in serum 25(OH)D will be correlated with changes in blood markers associated with insulin sensitivity \[hs-CRP, inflammatory cytokines (IL-6 and TNF-alpha), adiponectin, leptin, total and undercarboxylated osteocalcin\].

This research project intends to test 2 major hypotheses: (1) that vitamin D deficiency plays a causal role in the pathogenesis of insulin resistance in humans; and (2) that vitamin D increases insulin sensitivity.

Detailed description: Part 1: Prospective, randomized and placebo-controlled 6-month trial of vitamin D supplementation in 130 Caucasian and vitamin D-deficient \[serum 25(OH)D ≤55 nM\] men and women aged 25 years and over with a BMI ≤40 kg/m2. Participants will have abdominal obesity (increased waist circumference of at least 102 cm for men and 88 cm for women) and at least one factor associated with insulin resistance, namely: (1) serum triglyceride levels of at least 1.7 mmol/L or treated dyslipidemia; (2) prediabetes or untreated type 2 diabetes (HbA1c \>=5.6% or fasting glucose \>=5.6 mmol/L or glucose 2h post OGTT \>=7.8 mmol/L); (3) first degree relative with type 2 diabetes; (4) history of gestational diabetes. Participants will be randomized according to sex, BMI (\<30 kg/m2 vs. 30 kg/m2 and over) and age (\< or \>=50 years old). The primary aim is to compare the effect of daily vitamin D3 (cholecalciferol, 5000 IU) vs. placebo for 6 mo on insulin sensitivity (M-value by the gold standard method, the euglycemic hyperinsulinemic clamp). Secondary aims are to evaluate the effects of vitamin D3 vs. placebo on other indices of glucose metabolism (fasting glucose, 2-h plasma glucose post OGTT, HbA1c, insulin sensitivity index (HOMA-IS using fasting glucose and insulin), insulin secretion index (HOMA-B using fasting glucose and C-peptide), insulinogenic index \[(C-peptide at 30 min post OGTT - C-peptide at 0 min)/(glucose at 30 min post OGTT - glucose at 0 min)\] and disposition index (insulinogenic index x M-value)), the lipid profile, blood pressure and anthropometric measurements (weight, waist and hip circumference, bioimpedance analysis). Questionnaires on physical activity and sunlight exposure, and a food frequency questionnaire will be administered at 0 and 6 mo to adjust for confounding factors. At 0 and 6 mo, biochemical markers associated with insulin sensitivity will be measured (point 2).

Part 2: Mechanistic studies comparing, before and after vitamin D3 supplementation, changes in serum 25(OH)D with changes in blood markers associated with insulin sensitivity \[hs-CRP, inflammatory cytokines (IL-6 and TNF-alpha), adiponectin, leptin, total and undercarboxylated osteocalcin\].

Eligibility criteria: Inclusion Criteria:

* Caucasian men and women
* ≥25 yrs
* vitamin D deficiency \[serum 25(OH)D concentration ≤55 nM\]
* Abdominal obesity (waist circumference \>=102 cm for men and \>=88 cm for women) AND at least one factor associated with insulin resistance: (1) fasting serum triglycerides \>=1.7 mmol/L or treated dyslipidemia; (2) prediabetes or untreated type 2 diabetes (HbA1c \>=5.6% or fasting glucose \>=5.6 mmol/L or 2h glucose post OGTT \>=7.8 mmol/L); (3) first degree relative with type 2 diabetes; (4) history of gestational diabetes.

Exclusion Criteria:

* Type 2 diabetes under drug therapy
* HbA1c \>7%
* BMI \>40 kg/m2
* pregnancy or breast-feeding;
* medication influencing vitamin D or glucose metabolism in the last 3 mo
* regular consumption of supplements containing \>400 IU/d of vitamin D3 over the last 2 mo;
* renal insufficiency (creatinine clearance \<60 ml/min);
* cirrhosis,
* intestinal malabsorption (bypass surgery, celiac disease, etc);
* osteoporosis;
* history of nephrolithiasis;
* hypercalcemia (\>2.6 mM);
* hypercalciuria (\>0.6 fasting urine Ca/creatinine ratio);
* \>5% change in weight in the last 3 mo;
* diseases affecting glucose metabolism (e.g. hyperthyroidism);
* pacemaker (for bioimpedance only);
* inability to provide informed consent and complete questionnaires due to physical or mental problems.

Primary outcomes:
measure: Change in peripheral insulin sensitivity assessed by the euglycemic-hyperinsulinemic clamp between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in peripheral insulin sensitivity assessed by the euglycemic-hyperinsulinemic clamp between placebo and vitamin D groups
timeFrame: 0 and 6 months
Secondary outcomes:
measure: Change in insulin sensitivity indice assessed by fasting- and oral glucose tolerance test between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in insulin sensitivity indice assessed by fasting- and oral glucose tolerance test between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in insulin secretion indice between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in insulin secretion indice between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in insulin secretion indice between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in B-cell function between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in metabolic markers between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in metabolic markers between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in metabolic markers between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in anthropometry between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in anthropometry between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in anthropometry between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in anthropometry between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in anthropometry between placebo and vitamin D groups
timeFrame: 0 and 6 months
measure: Change in blood pressure between placebo and vitamin D groups
timeFrame: 0 and 6 months
Other outcomes:
Locations:
city: Quebec city
country: Canada
facility: CHU de Québec, Laval University Research Center
state: Quebec
Study officials:
affiliation: CHU de Québec Research Center
name: Claudia Gagnon, Dr.
role: PRINCIPAL_INVESTIGATOR
References: