Correction of Vitamin D Levels and Its Effect on Insulin Resistance and Weight Gain in Obese Youth

Insulin Resistance, Obesity, Vitamin D Deficiency

Obesity, Insulin Resistance, Vitamin D Deficiency, Children, Adolescents

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.

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