Correction of Vitamin D Levels and Its Effect on Insulin Resistance and Weight Gain in Obese Youth
Correction of Vitamin D Levels and Its Effect on Insulin Resistance and Weight Gain in Obese Youth
Vitamin D deficiency is extremely common in obese youth. In our obese population followed in
 the Endocrinology clinic at Children's Medical Center Dallas, vitamin D levels were inversely
 correlated with a measure of insulin resistance. We propose to show that correction of
 vitamin D levels in obese children and adolescents improves their insulin sensitivity. Obese
 youth presenting to the Center for Obesity and its Consequences on Health (COACH) clinic will
 be randomized to receive either the most recent Institute of Medicine (IOM) recommendations
 of minimum D3 dose of 600 IU/day (1), or receive higher doses of D3 such that the blood
 levels of vitamin D will be brought to a target level in either the low part or high part of
 the normal range. The goal is to determine if correction of vitamin D deficiency will improve
 insulin sensitivity in this group. Secondary goals include determining whether correction of
 vitamin D deficiency in obese adolescents and children results in less weight gain, and
 determining the amount of D3 required to correct vitamin D levels in this population.

 Our specific hypotheses are as follows:

 Hypothesis #1 Obese youth treated with Vitamin D3 who achieve low-normal 25-hydroxyvitamin D3
 (OHD) levels (30-50 ng/mL) or high-normal 25-OHD levels (60-80 ng/mL) will have improved
 insulin resistance, as measured by Homeostatic Model Assessment of Insulin Resistance
 (HOMA-IR), compared to those individuals with deficient 25-OHD levels (< 30 ng/mL).

 Hypothesis #2 Subjects with a higher BMI will have higher Vitamin D dose requirements than
 current IOM recommendations of 600 IU/day and will take a longer period of time to reach
 target 25-OHD levels.

 Hypothesis #3 Subjects with normal 25-OHD levels will demonstrate less weight gain compared
 to subjects on the control arm.
Concise Summary of Project: The proposed study is a prospective, unblinded dose-ranging trial
 to examine in obese youth 1) the effect of correcting Vitamin D (Vit D) deficiency on insulin
 resistance, 2) the effect of correcting Vit D deficiency on weight gain, and 3) the amount of
 Vit D3 required to achieve Vit D sufficiency in obese adolescents. Subjects will be recruited
 from obese children and adolescents aged 6 to 17 years presenting to the COACH clinic, a
 referral clinic for obese children at Children's Medical Center of Dallas. Approximately 1300
 new patients are seen in the COACH clinic each year. Ethnicity will be self-assigned as
 African-American, Caucasian, Hispanic, or Other. The ethnic makeup of the COACH clinic over
 the last 20 months was as follows: African-American 25%, Caucasian 19.5%, Hispanic 52%, and
 Other 3.5%.

 As per standard practice in the COACH clinic, a height (cm), weight (kg), and blood pressure
 will be obtained, and body mass index (kg/m2) calculated for each patient. Fasting total
 cholesterol, LDL, HDL, triglyceride, 25-OHD, Hemoglobin A1c (A1c), and fasting insulin will
 be obtained, and an Oral Glucose Tolerance Test (OGTT) performed. The baseline estimate of
 insulin sensitivity is calculated from the fasting insulin and glucose values, and reported
 as the HOMA-IR. After Informed Consent has been obtained, participants will be randomized to
 either the Control group (5000 IU/wk), the Low-normal 25-OHD group (target 25-OHD 30-50
 ng/mL), or the High-normal 25-OHD group (target 25-OHD 60-80 ng/mL). A 25-OHD < 25 ng/mL will
 be confirmed. These groups will be matched for age (6-12 years versus 13-17 years) and
 ethnicity (Caucasian versus African-American verus Hispanic). Approximately 60 patients will
 be recruited for each group. Subject participation will continue until Vit D sufficiency has
 been documented for 4 consecutive months, at which point the fasting insulin and glucose
 values will be repeated for calculation of HOMA-IR and assessment of insulin sensitivity, and
 amount of weight gain will be measured.
Inclusion Criteria:

 -  age 6-17 years

 -  BMI > 95% for age

 -  serum 25-OH D level < or + to 25 ng/mL

 Exclusion Criteria:

 -  BMI < 95% for age

 -  serum 25-OH D level > 25 ng/mL

 -  current Vitamin D supplementation > 400 IU/day

 -  anti-convulsant therapy, anti-hypertensive therapy, lipid lowering medication

 -  any medications that affect glucose metabolism (e.g., metformin, insulin)

 -  daily glucocorticoid therapy

 -  diabetes

 -  any disorders of bone or calcium metabolism

 -  hepatic or renal disease

 -  any malabsorptive disorder

 -  baseline serum Calcium > 11 ng/dL (> 2 SD above the mean)

 -  any genetic disorder that predisposes to obesity (e.g., Prader Willi

 -  hypothalamic obesity