Effect of Vitamin D3 Supplementation on Insulin Resistance and Cardiovascular Risk Factors in Obese Adolescents

Significance of Vitamin D Status in Obese Adolescents- A Pilot Study to Examine the Effect of Vitamin D3 Supplementation on Insulin Resistance and Cardiovascular Risk Factors

The prevalence of obesity has reached epidemic proportions nationally as well as internationally. Currently, 16 % of American adolescents are obese. In adults, obesity is a risk factor for vitamin D insufficiency and up to 80% of obese adults have been noted to vitamin D insufficient. In adults, low vitamin D status appears to be associated with the development of type 2 diabetes and metabolic syndrome. There is little information on the prevalence of vitamin D insufficiency and its implications in obese adolescents. Additionally, it is unknown whether treatment of vitamin D insufficiency in adolescents might result in improvement in insulin resistance, lipids and cardiovascular risk markers.

We hypothesize that vitamin D insufficiency correlates positively with insulin resistance and cardiovascular risk in obese adolescents and that vitamin D3 supplementation improves insulin resistance and cardiovascular risk factors in this population. The purpose of the study is to determine the impact of vitamin D3 supplementation on various parameters of insulin secretion, insulin action, lipids and C-reactive protein in obese adolescents.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Dietary supplement: Vitamin D3

Detailed Description

The problem of childhood obesity has reached epidemic proportions both nationally and internationally. The prevalence of obesity has tripled in the last three decades and currently 16 % of American adolescents are obese. Nearly 30% of obese adolescents demonstrate a metabolic syndrome characterized by insulin resistance and dyslipidemia. These abnormalities lead to the development of type 2 diabetes mellitus and to increased cardiovascular morbidity and mortality. Obesity is a well-known risk factor for vitamin D insufficiency and up to 80% of obese adults have been found to be insufficient in vitamin D. Observational studies in adults have shown consistent associations between low vitamin D status and prevalence of type 2 diabetes mellitus and metabolic syndrome. There is paucity of data on the prevalence of vitamin D insufficiency and its implications in obese adolescents. It is also not known whether treatment of vitamin D insufficiency in children or adults might result in improvement in insulin resistance and cardiovascular risk factors.

Hypotheses: We hypothesize that vitamin D insufficiency correlates positively with insulin resistance and cardiovascular risk in obese adolescents and that vitamin D3 supplementation decreases insulin resistance and cardiovascular risk factors in this population.

Objectives:

1. Determine if there is any correlation between serum 25(OH)D levels and homeostasis model assessment of insulin resistance (HOMA-IR), HDL cholesterol and C-reactive protein, in obese adolescents.
2. Study the impact of vitamin D3 supplementation on various parameters reflecting insulin action, secretion, lipids and C-reactive protein in obese adolescents.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 12-18 years
2. BMI is at or greater than the 95th percentile for age and gender

Exclusion Criteria:

1. Subjects with 25 (OH)- D levels >100 ng/mL
2. Serum calcium >10.8 mg/dL
3. Current cancer
4. Those taking a multivitamin supplementation
5. Hepatic or renal disorders
6. Type 1 or type 2 diabetes mellitus.

7. Those receiving insulin, metformin or oral hypoglycemic medications

   • Use of glucocorticoids and anti-seizure medications in the previous 6 months
   • Malabsorption syndromes such as celiac disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D3-low dose; Vitamin D3 400 IU capsule, one capsule daily for 12 weeks.	Dietary supplement: Vitamin D3; One arm would receive vitamin D3 at a dose of 400 IU by mouth once daily for 12 weeks and the other arm would receive vitamin D3 as a single oral daily dose of 2000 IU for 12 weeks.
Experimental: Vitamin D3-high dose; Vitamin D3 2000 IU capsule, one capsule daily for 12 weeks.	Dietary supplement: Vitamin D3; One arm would receive vitamin D3 at a dose of 400 IU by mouth once daily for 12 weeks and the other arm would receive vitamin D3 as a single oral daily dose of 2000 IU for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Insulin Resistance After 12 Weeks of Vitamin D3 Supplementation	Insulin resistance (IR) is a physiological condition in which cells fail to respond to the normal actions of the hormone insulin. The body produces insulin, but the cells in the body become resistant to insulin and are unable to use it as effectively, leading to hyperglycemia. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to hyperinsulinemia. From the fasting glucose and insulin measurements, insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA -IR) as: HOMA -IR = fasting insulin concentration (µU/mL) x fasting glucose concentration (mmol/L)/22.5. High HOMA-IR scores denote increased insulin resistance.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Cholesterol After 12 Weeks of Vitamin D Supplementation	Less than 200 mg/dL is desirable, >200 mg/dL is borderline high, >240 mg/dL is High	baseline, 12 weeks
Change in Low Density Lipoprotein (LDL) Cholesterol After 12 Weeks of Vitamin D Supplementation	LDL cholesterol is considered to be the main source of cholesterol buildup and blockage in the arteries. Less than 100 mg/dL is optimal, >130 mg/dL is borderline high, >160 mg/dL is high, >190 mg/dL is very high.	baseline, 12 weeks
Change in High Density Lipoprotein (HDL) Cholesterol After 12 Weeks of Vitamin D Supplementation	HDL (good) cholesterol protects against heart disease, so for HDL, higher numbers are better. A level less than 40 mg/dL is low and is considered a major risk factor because it increases your risk for developing heart disease. HDL levels of 60 mg/dL or more help to lower your risk for heart disease.	baseline, 12 weeks
Change in Triglycerides After 12 Weeks of Vitamin D Supplementation	The current recommendation on fasting blood triglyceride levels: < 150 mg/dL is normal, >150 mg/dL is borderline high, and >200 mg/dL is high.	baseline, 12 weeks
Change in High-Sensitivity C-Reactive Protein After 12 Weeks of Vitamin D Supplementation	The high-sensitivity C-reactive protein test measures your risk for heart problems. <1.0 mg/L is lowest risk, 1.0-3.0 mg/L is average risk, and >3.0 mg/L is highest risk.	baseline, 12 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Center for Research Resources (NCRR); Thrasher Research Fund
• Investigators: Principal Investigator: Seema Kumar, M.D., Mayo Clinic

Publications and helpful links

General Publications

• Javed A, Vella A, Balagopal PB, Fischer PR, Weaver AL, Piccinini F, Dalla Man C, Cobelli C, Giesler PD, Laugen JM, Kumar S. Cholecalciferol supplementation does not influence beta-cell function and insulin action in obese adolescents: a prospective double-blind randomized trial. J Nutr. 2015 Feb;145(2):284-90. doi: 10.3945/jn.114.202010. Epub 2014 Dec 17.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: March 5, 2009
• First Submitted That Met QC Criteria: March 6, 2009
• First Posted (Estimate): March 9, 2009

Study Record Updates

• Last Update Posted (Estimate): May 20, 2014
• Last Update Submitted That Met QC Criteria: May 13, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Obesity; Adolescent Obesity; Insulin sensitivity; vitamin D
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Obesity; Insulin Resistance; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 08-008743; UL1RR024150 (U.S. NIH Grant/Contract)