Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation

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.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance
• Intervention / Treatment: Drug: Placebo; Drug: Vitamin D

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D; Participants received weekly oral vitamin D drops using a weight-based calculated dosage for up to six months.	Drug: Vitamin D; Other Names: Vitamin D3 (cholecalciferol)
Placebo Comparator: Placebo; Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D) for up to six months.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Hepatic Insulin Sensitivity	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.	2nd clamp visit (after up to 3 months) and 3rd clamp visit (after up to 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Peripheral Glucose Uptake	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.	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Evaluated Expression of Pro-inflammatory Gene TNF-α	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.	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Evaluated Expression of Pro-inflammatory Gene IL-6	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.	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Evaluated Expression of Pro-inflammatory Gene iNOS	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.	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Evaluated Expression of Pro-inflammatory Gene PAI-1	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.	2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Meredith A Hawkins, M.D., M.S., Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2009
• Primary Completion (Actual): June 3, 2015
• Study Completion (Actual): September 3, 2015

Study Registration Dates

• First Submitted: May 12, 2011
• First Submitted That Met QC Criteria: May 16, 2011
• First Posted (Estimate): May 17, 2011

Study Record Updates

• Last Update Posted (Actual): November 2, 2020
• Last Update Submitted That Met QC Criteria: October 9, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Vitamin D; Insulin Resistance; Glucose Metabolism Disorders; Endocrine System
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Inflammation; Insulin Resistance; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 2008-225; 5K23RR023335-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No