D2d participating clinical sites To D or not to D? Design and Rational of the Vitamin D and Type 2 Diabetes (D2d) study Patricia Sheehan, Bess Dawson-Hughes, Clifford Rosen, James Ware, David Robbins, Myrlene Staten and Anastassios Pittas Background Study Conduct Results There is evidence to suggest that optimal vitamin D status may be important for a variety of non-skeletal outcomes, including type 2 diabetes (T2DM). Mechanistic studies indicate that vitamin D supplementation may alter the pathophysiology of T2DM. Additionally, in most longitudinal observational studies, higher 25OHD concentration is associated with lower risk of developing T2DM. However, because vitamin D status is an excellent marker of general health status, the positive results reported in the observational studies and post-hoc analyses of trials might reflect confounding. Therefore, the hypothesis that vitamin D may modify diabetes risk needs to be confirmed in trials specifically designed for that purpose. Inclusion criteria Pre-diabetes defined by meeting at least 2-out of the 3 criteria Fasting plasma glucose 100 -125 mg/dL 2-hour plasma glucose 140 -199 mg/dL Hemoglobin A1c 5.7 - 6.4% BMI ≥ 24.0 (22.5 for Asians) and ≤ 42 Age ≥ 30 years Key exclusion criteria Diabetes Recent history of nephrolithiasis, hypercalcemia or hypercalciuria Use of supplements containing Vitamin D > 1000 IU/day Use of supplements containing calcium > 600 mg/day D2d participating clinical sites Recruitment occurs year round and will conclude in 2016. Baseline participant characteristics are shown below. Design Women, % 46 BMI, kg/m2 32 Fasting glucose, mg/dL 108 2h-glucose,mg/dL 137 Hemoglobin a1c, % 5.9 The Vitamin D and Type 2 Diabetes (D2d) study is an NIH-supported randomized clinical trial designed to examine whether vitamin D3 supplementation (4000 units/day over 3 years) reduces risk of diabetes in a racially and ethnically diverse cohort of 2,382 people at high risk for T2DM, as defined by the American Diabetes Association criteria. The primary endpoint is incident diabetes, assessed by central laboratory criteria or by adjudication if diagnosed outside of D2d. Conclusion D2d addresses an important and timely question and results could have extensive public health implications, especially given that the cost of supplementation is low compared with treating the chronic disease and its complications. Size of bubble is proportional to the number of enrolled participants D2d Coordinating Center | Division of Endocrinology | Tufts Medical Center | d2dstudy.org | d2d@tuftsmedicalcenter.org