title: Rationale and design of the Vitamin D and Type 2 Diabetes (D2d) study: a diabetes prevention trial.
abstract: OBJECTIVE
  Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type 2 diabetes.
  
  
  METHODS
  D2d was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The final protocol was approved by the D2d Research Group, the data and safety monitoring board, and NIDDK. Key eligibility criteria are age ≥30 years, BMI of 24 (22.5 for Asian Americans) to 42 kg/m(2), increased risk for diabetes (defined as meeting two of three glycemic criteria for prediabetes established by the American Diabetes Association [fasting glucose 100-125 mg/dL (5.5-6.9 mmol/L), 2-h postload glucose after 75-g glucose load 140-199 mg/dL (7.7-11.0 mmol/L), hemoglobin A₁c 5.7-6.4% (39-46 mmol/mol)]), and no hyperparathyroidism, nephrolithiasis, or hypercalcemia. D2d participants are randomized to once-daily vitamin D₃ (cholecalciferol 4,000 IU) or placebo and followed for an average of 3 years. The primary end point is time to incident diabetes as assessed by laboratory criteria during the study or by adjudication if diagnosed outside of D2d. Recruitment was initiated at the end of 2013.
  
  
  CONCLUSIONS
  D2d will test whether vitamin D supplementation is safe and effective at lowering the risk of progression to diabetes in people at high risk for type 2 diabetes.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, MA.
authors.forename: Anastassios G
authors.initials: AG
authors.lastname: Pittas
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, MA Bone Metabolism Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA.
authors.forename: Bess
authors.initials: B
authors.lastname: Dawson-Hughes
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, MA d2d@tuftsmedicalcenter.org.
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Sheehan
authors.affiliation: Maine Medical Center Research Institute, Scarborough, ME.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA.
authors.forename: James H
authors.initials: JH
authors.lastname: Ware
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
authors.forename: Myrlene A
authors.initials: MA
authors.lastname: Staten
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D002762:Cholecalciferol / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011236:Prediabetic State / Q000188:drug therapy*; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002762:Cholecalciferol; D006442:Glycated Hemoglobin; D010919:Placebos