Cancer Prevention Program
PI: Mario Kratz, PhD
Low-grade, chronic adipose tissue inflammation is a major cause of insulin resistance, and a risk factor for type 2 diabetes mellitus. The cause of adipose tissue inflammation has remained largely unclear. We hypothesize that vitamin D deficiency predisposes individuals to the development of adipose tissue inflammation, and that treatment of vitamin D deficient subjects with high dose vitamin D reduces adipose tissue inflammation. Vitamin D is an interesting candidate for an anti-inflammatory nutrient, as vitamin D deficiency is common and, like type 2 diabetes mellitus, associated with increased body mass. Further, vitamin D plays major roles in regulating immune function. In our preliminary studies, low plasma concentrations of vitamin D were strongly associated with several measures of adipose tissue inflammation in our study subjects, independent of body mass index. We propose to complete a randomized double-blind pilot clinical trial treating vitamin D deficient, obese subjects with either 2,000 IU or 4,000 IU vitamin D3 daily for six months to test whether treatment of vitamin D deficient subjects with vitamin D3 reduces subcutaneous adipose tissue inflammation. Subjects will be admitted for a clinic visit at baseline and after 3 and 6 months of treatment. Clinic procedures performed at all visits will include assessment of height and weight, an oral glucose tolerance test (OGTT), a fasting blood draw, and two subcutaneous abdominal adipose tissue biopsies. This pilot study will allow us to collect the preliminary data to design a larger, placebo-controlled clinical trial on the effect of vitamin D on adipose tissue inflammation. As adipose tissue inflammation is now known to be a major cause of insulin resistance and type 2 diabetes mellitus, our work may identify new strategies for preventing or treating this common disease.