Vitamin D supplementation and prevention of type 2 diabetes

Authors: PITTAS, ANASTASSIOS - Tufts Medical Center; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SHEEHAN, PATRICIA - Spaulding Rehabilitation Hospital; WARE, JAMES - Harvard University; KNOWLER, WILLIAM - National Institute Of Diabetes And Digestive And Kidney Diseases; ARODA, VANITA - Brigham & Women'S Hospital; BRODSKY, IRWIN - Maine Medical Center; CEGLIA, LISA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CHADHA, CHHAVI - Health Partners Research Foundation; CHATTERJEE, RANEE - Duke University; DESOUZA, CYRUS - University Of Nebraska; DOLOR, ROWENA - Duke University; FOREYT, JOHN - Baylor University; FUSS, PAUL - Tufts Medical Center; GHAZI, ADLINE - Medstar Good Samaritan Hospital; HSIA, DANIEL - Pennington Biomedical Research Center; JOHNSON, KAREN - University Of Tennessee; KASHYAP, SANGEETA - Cleveland Clinic; KIM, SUN - Stanford University; LEBLANC, ERIN S - Kaiser Permanente Center For Health Research; LEWIS, MICHAEL - University Of Vermont; LIAO, EMILIA - Northwell Health Lenox Hill Hospital; NEFF, LISA - Northwestern University; NELSON, JASON - Tufts Medical Center; O'NEIL, PATRICK - Medical University Of South Carolina; PARK, JEAN - Medstar Research Institute; PETERS, ANNE - University Of Southern California; PHILLIPS, LAWRENCE - Emory University; PRATLEY, RICHARD - Adventhealth Translational Research Institute For Metabolism And Diabetes; RASKIN, PHILIP - University Of Texas; RASOULI, NEDA - University Of Colorado; ROBBINS, DAVID - University Of Kansas; ROSEN, CLIFFORD - Maine Medical Center Research Institute (MMCRI); VICKERY, ELLEN - Tufts Medical Center; STATEN, MYRLENE - National Institute Of Diabetes And Digestive And Kidney Diseases

Submitted to: New England Journal of Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/10/2019
Publication Date: 6/7/2019
Citation: Pittas, A.G., Dawson-Hughes, B., Sheehan, P., Ware, J.H., Knowler, W.C., Aroda, V.R., Brodsky, I., Ceglia, L., Chadha, C., Chatterjee, R., Desouza, C., Dolor, R., Foreyt, J., Fuss, P., Ghazi, A., Hsia, D., Johnson, K.C., Kashyap, S.R., Kim, S., Leblanc, E., Lewis, M.R., Liao, E., Neff, L.M., Nelson, J., O'Neil, P., Park, J., Peters, A., Phillips, L.S., Pratley, R., Raskin, P., Rasouli, N., Robbins, D., Rosen, C., Vickery, E.M., Staten, M. 2019. Vitamin D supplementation and prevention of type 2 diabetes. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa1900906.
DOI: https://doi.org/10.1056/NEJMoa1900906

Interpretive Summary: Vitamin D sufficiency is crucial for skeletal health but the relation between vitamin D and other health outcomes is less clear. Several observational studies have shown that low vitamin D levels were associated with increased risk of progression to type 2 diabetes. This large long-term clinical trial was done to determine whether supplemental vitamin D would alter the progression to type 2 diabetes in adults at high risk for developing type 2 diabetes. In the trial, 2,423 adults with prediabetes were treated for approximately 2.5 years with either 4000 IU of vitamin D or placebo. There was no difference in the rate of conversion to type 2 diabetes in the two groups. However, in an exploratory analysis in the 4.3% of subjects who met criteria for vitamin D deficiency, supplementation was associated with a reduced rate of conversion. Although the proportion of D deficient subjects in D2d was small, it is about the same as the proportion who are deficient in the general adult population. In conclusion, among adults at high risk for type 2 diabetes and not selected for vitamin D insufficiency, vitamin D supplementation did not result in a significant reduction in risk of developing diabetes.

Technical Abstract: BACKGROUND: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS: We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS: A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (0.95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo.