Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation

Phase 2

Completed

Conditions: Insulin Resistance

Interventions: Drug: Placebo
Drug: Vitamin D

Registration Number: NCT01354964

Lead Sponsor: Albert Einstein College of Medicine

Brief Summary: The purpose of this research is to study the effects of Vitamin D supplementation on the body's response to insulin (a hormone that controls blood sugar), on inflammation, and on specific cells and processes in fat tissue.

Detailed Description: Over the last several years, studies have shown that low vitamin D levels may increase risk of developing Type 2 Diabetes. The investigators will administer vitamin D3 (cholecalciferol) to non-diabetic, insulin resistant subjects with vitamin D deficiency (total vitamin D levels \<20 ng/ml) to increase the level of vitamin D3. The investigators will study the effects of increased Vitamin D on insulin action, adipose tissue inflammation, and on certain cells and processes in fat tissue.

Investigators will study participants with a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Adipose tissue inflammation will be measured using the following inflammatory markers: IL-6, PAI-1, TNF-alpha, and iNOS.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Serum 25(OH)D<20ng/ml
Insulin Resistant based on HOMA-IR score of >3
Able and willing to provide informed consent
BMI 20-35

Exclusion Criteria

HIV/AIDS
History of any cancer
Sarcoidosis
Alcohol or substance abuse
Cushing's syndrome
Primary hyperparathyroidism
Nephrolithiasis
Pregnancy or breastfeeding
Regular visits to a tanning salon
Hypercalcemia or hypocalcemia
Untreated or uncontrolled hypertension
Any chronic illness requiring medication, other than arthritis, hypertension and hyperlipidemia

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D) for up to six months.
Vitamin D	Vitamin D	Participants received weekly oral vitamin D drops using a weight-based calculated dosage for up to six months.

Primary Outcome Measures

Name	Time	Method
Percent Change in Hepatic Insulin Sensitivity	2nd clamp visit (after up to 3 months) and 3rd clamp visit (after up to 6 months)	Endogenous glucose production (EGP) was assessed at each study visit to evaluate hepatic insulin sensitivity. Percent change between the EGP at baseline and second visit (after treatment for up to 3 months with Vitamin D to reach a target level of ≥30 ng/ml), and baseline and third visits (after treatment for up to 6 months with Vitamin D in order to reach a target level of ≥50 ng/ml) will be calculated.

Secondary Outcome Measures

Name	Time	Method
Percent Change in Peripheral Glucose Uptake	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)	The rate of glucose uptake to determine peripheral insulin sensitivity was measured using the rate of disappearance (Rd) of glucose at each study visit. Percent change between the Rd at baseline and second visit (after treatment with Vitamin D for up to 3 months to target level of ≥30 ng/ml), and baseline and third visits (after treatment with Vitamin D for up to 6 months to target level of ≥50 ng/ml) will be calculated.
Evaluated Expression of Pro-inflammatory Gene IL-6	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)	Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. IL-6 gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes \[HKGs\]) as a ratio, which is a measure of relative gene expression.
Evaluated Expression of Pro-inflammatory Gene iNOS	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)	Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. iNOS gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes \[HKGs\]) as a ratio, which is a measure of relative gene expression.
Evaluated Expression of Pro-inflammatory Gene TNF-α	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)	Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. TNF-α gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes \[HKGs\]) as a ratio, which is a measure of relative gene expression.
Evaluated Expression of Pro-inflammatory Gene PAI-1	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)	Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. PAI-1 gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes \[HKGs\]) as a ratio, which is a measure of relative gene expression.