The risk of progressing to type 2 diabetes is reduced by vitamin D therapy in people with prediabetes, according to a systematic review and meta-analysis. “These results suggest that the blood 25-hydroxyvitamin D level needed to optimally reduce diabetes risk may be near and possibly above the range of 125 to 150 nmol/L (50 to 60 ng/mL) that the 2011 Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D provided as the range corresponding to the tolerable upper intake level (UL) of 4000 IU/d for vitamin D,” the authors write.
The literature search sought trials designed to compare the effects of oral vitamin D versus placebo on new-onset diabetes in participants with prediabetes. Based on a primary outcome of time to event for new-onset diabetes, the meta-analysis showed the following: “Three randomized trials were included, which tested cholecalciferol, 20,000 IU (500 mcg) weekly; cholecalciferol, 4000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, versus matching placebos. Trials were at low risk of bias. Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 [95% CI, 0.75 to 0.96]) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of vitamin D did not differ in prespecified subgroups. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 [CI, 0.16 to 0.36]), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46]). There was no evidence of difference in the rate ratios for adverse events (kidney stones: 1.17 [CI, 0.69 to 1.99]; hypercalcemia: 2.34 [CI, 0.83 to 6.66]; hypercalciuria: 1.65 [CI, 0.83 to 3.28]; death: 0.85 [CI, 0.31 to 2.36]).”
The authors make this point in discussing their findings: “Although the degree of relative reduction in risk for diabetes with vitamin D is small (15%) compared with other diabetes prevention strategies (58% with intensive lifestyle modification and 31% with metformin in the Diabetes Prevention Program study), the 3-year absolute risk reduction was 3.3%, translating to a number of persons with prediabetes needed to treat of 30 (compared with 7 with intensive lifestyle modification and 14 with metformin in the Diabetes Prevention Program study). Extrapolating to the more than 374 million adults worldwide who have prediabetes suggests that inexpensive vitamin D supplementation could delay the development of diabetes in more than 10 million people.”
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Editorial: “Professional societies, which advise physicians about benefits and harms of vitamin D therapy, have a duty of care to understand advice from government agencies,” editorialists write. “They should promote population health recommendations about vitamin D intake requirements, 25-(OH)D thresholds, and safe limits. There are important differences between supplementation and therapy. Vitamin D supplementation of 10 to 20 mcg (400 to 800 IU) daily can be applied safely at the population level to prevent skeletal, and possibly nonskeletal, disease. Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm.”