Obesity
Conditions
Keywords
vitamin D, Obesity, Insulin sensitivity, Adolescent Obesity
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTVitamin 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.
Sponsors
National Center for Research Resources (NCRR)
Thrasher Research Fund
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insulin Resistance After 12 Weeks of Vitamin D3 Supplementation | Baseline, 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Cholesterol After 12 Weeks of Vitamin D Supplementation | baseline, 12 weeks | Less than 200 mg/dL is desirable, \>200 mg/dL is borderline high, \>240 mg/dL is High |
| Change in Low Density Lipoprotein (LDL) Cholesterol After 12 Weeks of Vitamin D Supplementation | baseline, 12 weeks | 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. |
| Change in High Density Lipoprotein (HDL) Cholesterol After 12 Weeks of Vitamin D Supplementation | baseline, 12 weeks | 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. |
| Change in Triglycerides After 12 Weeks of Vitamin D Supplementation | baseline, 12 weeks | 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. |
| Change in High-Sensitivity C-Reactive Protein After 12 Weeks of Vitamin D Supplementation | baseline, 12 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at the Mayo Clinic in Rochester, Minnesota.
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D3-low Dose Vitamin D3 400 IU capsule, one capsule daily | 23 |
| Vitamin D3-high Dose Vitamin D3 2000 IU capsule, one capsule daily | 24 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Baseline Assessment | Poor IV access | 1 | 0 |
| Baseline Assessment | Protocol Violation | 0 | 1 |
| Baseline Assessment | Withdrawal by Subject | 1 | 1 |
| Week 12 Follow-up | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Vitamin D3-low Dose | Total | Vitamin D3-high Dose |
|---|---|---|---|
| Age, Continuous | 14.5 years | 14.5 years | 14.7 years |
| Region of Enrollment United States | 23 participants | 47 participants | 24 participants |
| Sex: Female, Male Female | 9 Participants | 27 Participants | 18 Participants |
| Sex: Female, Male Male | 14 Participants | 20 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 23 | 0 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 |
Outcome results
Primary
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.
Time frame: Baseline, 12 weeks
Population: All subjects had blood drawn but some tests such as insulin could not be done in some cases due to sample issues. This lab test was calculated from other parameters and not drawn per se. If the values obtained did not allow a calculation of the lab test, then the results could not be reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3-low Dose | Change in Insulin Resistance After 12 Weeks of Vitamin D3 Supplementation | 0.01 HOMA score | Standard Deviation 1.34 |
| Vitamin D3-high Dose | Change in Insulin Resistance After 12 Weeks of Vitamin D3 Supplementation | -0.27 HOMA score | Standard Deviation 4.95 |
p-value: 0.95ANCOVA
Secondary
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.
Time frame: baseline, 12 weeks
Population: One subject in the high-dose arm dropped out before the week 12 assessment, so the reporting population on the high dose arm was 23, not 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3-low Dose | Change in High Density Lipoprotein (HDL) Cholesterol After 12 Weeks of Vitamin D Supplementation | 1.3 mg/dL | Standard Deviation 6.8 |
| Vitamin D3-high Dose | Change in High Density Lipoprotein (HDL) Cholesterol After 12 Weeks of Vitamin D Supplementation | 1.9 mg/dL | Standard Deviation 5.7 |
p-value: 0.68ANCOVA
Secondary
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.
Time frame: baseline, 12 weeks
Population: One subject in the high-dose arm dropped out before the week 12 assessment, so the reporting population on the high dose arm was 23, not 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3-low Dose | Change in High-Sensitivity C-Reactive Protein After 12 Weeks of Vitamin D Supplementation | -0.2 mg/L | Standard Deviation 1.2 |
| Vitamin D3-high Dose | Change in High-Sensitivity C-Reactive Protein After 12 Weeks of Vitamin D Supplementation | -0.5 mg/L | Standard Deviation 1.7 |
p-value: 0.47ANCOVA
Secondary
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.
Time frame: baseline, 12 weeks
Population: One subject in the high-dose arm dropped out before the week 12 assessment, so the reporting population on the high dose arm was 23, not 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3-low Dose | Change in Low Density Lipoprotein (LDL) Cholesterol After 12 Weeks of Vitamin D Supplementation | 4.6 mg/dL | Standard Deviation 22 |
| Vitamin D3-high Dose | Change in Low Density Lipoprotein (LDL) Cholesterol After 12 Weeks of Vitamin D Supplementation | 1.3 mg/dL | Standard Deviation 15.6 |
p-value: 0.65ANCOVA
Secondary
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
Time frame: baseline, 12 weeks
Population: One subject in the high-dose arm dropped out before the week 12 assessment, so the reporting population on the high dose arm was 23, not 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3-low Dose | Change in Total Cholesterol After 12 Weeks of Vitamin D Supplementation | 4.7 mg/dL | Standard Deviation 24.3 |
| Vitamin D3-high Dose | Change in Total Cholesterol After 12 Weeks of Vitamin D Supplementation | 3.5 mg/dL | Standard Deviation 16.8 |
p-value: 0.8ANCOVA
Secondary
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.
Time frame: baseline, 12 weeks
Population: One subject in the high-dose arm dropped out before the week 12 assessment, so the reporting population on the high dose arm was 23, not 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3-low Dose | Change in Triglycerides After 12 Weeks of Vitamin D Supplementation | -4.7 mg/dL | Standard Deviation 56.7 |
| Vitamin D3-high Dose | Change in Triglycerides After 12 Weeks of Vitamin D Supplementation | 1.7 mg/dL | Standard Deviation 43.5 |
p-value: 0.4ANCOVA