the effect of vitamin d repletion on insulin resistance

Conditions: Obesity

Summary: the reason for doing this study is to learn whether raising a person's vitamin d level from below normal to normal levels will improve his or her body's ability to use sugar. vitamin d is well known to be an important vitamin for the development and maintenance of bones. recently, scientists have learned that vitamin d may have a role in the prevention of cancer, diabetes, and autoimmune diseases. the investigators are specifically interested in studying this question in the overweight/obese population as they are at greater risk for both vitamin d deficiency and impaired ability to metabolize sugar (glucose intolerance). primary hypotheses: vitamin d repletion (increasing the serum 25(oh)d level from ≤ 20 ng/ml to ≥ 30 ng/ml) will improve insulin sensitivity in individuals who are overweight/obese and insulin resistant. secondary hypotheses: 1.vitamin d repletion will improve biomarkers of cardiovascular risk and inflammation (directly altering macrophage cytokine production and/or indirectly as a result of improvement in insulin sensitivity.) 2.30,000 iu (0.25 mg) weekly of cholecalciferol (vitamin d3) will raise serum 25(oh)d levels from ≤ 20 ng/ml to ≥ 30 ng/ml overweight/obese population.


Eligibility criteria:
inclusion criteria: * nonsmoking men and women, ages 18-65 * body mass index (bmi) ≥ 28 kg/m² and within 10% of maximum weight * serum 25(oh)d level ≤ 20 ng/ml * serum insulin level ≥ 7.2 mu/l * willingness to maintain current body weight for the duration of the study * willingness to maintain baseline lifestyle activities and routines for the duration of the study * willingness to avoid the use of non-steroidal anti-inflammatory drugs (nsaids), including low-dose daily aspirin, for at least ten days prior to each admission (due to the potential effects of these agents on inflammatory markers.) * willingness to avoid the use of all over-the-counter or prescription vitamins, dietary supplements, and herbal products during the study, with the exception of a basic multivitamin supplement. * if of childbearing potential, willingness to use highly effective contraception for the duration of the study. exclusion criteria: * current tobacco smoking * history of bleeding or coagulation disorders * gastrointestinal disease resulting in significant gastrointestinal dysfunction or malabsorption * history of diabetes, or diagnosed during screening ogtt * current treatment with hypertensive medications * history of cardiovascular disease * renal disease, as evidenced by a serum creatinine above the upper limit of normal on more than one screening visit * history of kidney stones * history of chronic hepatitis, or liver enzymes (ast or alt) more than 2.5 times the upper limit of normal * primary hyperparathyroidism or baseline hypercalcemia from any cause * current treatment with over-the-counter or prescription weight loss medications, such as orlistat or sibutramine * history of bariatric surgery * current treatment with any cholesterol-lowering medications, such as statins, niacin, fibrates, or ezetimibe * blood pressure ≥ 145/90 after ten minutes of rest on more than one screen visit * hyperthyroidism or untreated hypothyroidism. subjects with chronic, treated, stable hypothyroidism may be included in the study at the discretion of the principal investigator. * pregnancy, desired pregnancy, or lactation within the study period. * hiv, hepatitis b and c * medical conditions requiring daily calcium supplementation or antacid use * use of medications known to interact with calcium or vitamin d metabolism (bisphosphonates, corticosteroids, thiazide diuretics, cholestyramine, colestipol, mineral oil, phenytoin, barbituates, dititalis glycosides, antacids) * subjects with known hypersensitivity to cholecalciferol * participation in an investigational drug study within one month of screening * history, physical, or laboratory findings suggestive of any other medical or psychological condition that would, in the opinion of the principal investigator, make the candidate ineligible for the study

Keywords: obesity metabolism