Vitamin D Linked to Reduced Diabetes Risk in Adults With Prediabetes

Vitamin D has been shown to decrease the risk of diabetes in adults with prediabetes, according to a review published in Annals of Internal Medicine.

The systematic review and meta-analysis included 3 randomized, double-blinded, placebo-controlled trials designed to test oral vitamin D for diabetes prevention, with individual participant data available.

Compared with placebo, the trials assessed:

• Cholecalciferol 500 mcg (20,000 IU) weekly
• Cholecalciferol 100 mcg (4000 IU) daily
• Eldecalcitol 0.75 mcg daily

The 3 trials collectively included 4190 participants, with 2097 receiving vitamin D and 2093 receiving placebo. The mean (SD) age was 60.6 (9.5) years, and 44.2% were women.

According to the authors, these trials had low risk of bias. They found that vitamin D was beneficial in decreasing risk for diabetes and increasing the likelihood of regression to normal glucose regulation in individuals with prediabetes, with no offsetting safety signals.

Specifically, adjusted analyses showed vitamin D reduced diabetes risk by 15% (HR, 0.85; 95% CI, 0.75-0.96), with a 3-year absolute risk reduction of 3.3% (95% CI, 0.6%-6.0%). New-onset diabetes occurred in 22.7% of participants in the vitamin D group and 25% in the placebo group, with 8.42 and 9.5 events per 100 person-years, respectively. The authors found no differing effects of vitamin D in prespecified subgroups.

The trials also measured serum 25-hydroxyvitamin D via liquid chromatography-tandem mass spectrometry. Among participants who received cholecalciferol, achieving and sustaining higher serum 25-hydroxyvitamin D levels was linked to progressively lower risk of diabetes.

Cholecalciferol reduced diabetes risk by 76% (HR, 0.24; 95% CI, 0.16-0.36) in participants who maintained a higher mean serum 25-hydroxyvitamin D level of at least 125 nmol/L during follow-up compared with those maintaining a level between 50 and 74 nmol/L, with a 3-year absolute risk reduction of 18.1% (95% CI, 11.7%-24.6%).

Vitamin D also increased the likelihood of regression to normal glucose regulation by 30% (rate ratio [RR], 1.30; 95% CI, 1.16-1.46). There was no evidence of different rate ratios between the vitamin D and placebo groups for kidney stones (RR, 1.17; 95% CI, 0.69-1.99), hypercalcemia (RR, 2.34; 95% CI, 0.83-6.66), hypercalciuria (RR, 1.65; 95% CI, 0.83-3.28), and death (RR, 0.85; 95% CI, 0.31-2.36).

“Beyond delaying progression to diabetes, regression to normal glucose regulation is also important because euglycemia is associated with a lower prevalence of microvascular disease, nephropathy, and retinopathy compared with prediabetes, primarily due to lower glycemic exposure over time,” the authors added.

These findings are limited in their generalizability, however. First, the initial search excluded trials with vitamin D that targeted children, pregnant or lactating women, patients who were hospitalized, and patients with end-stage renal disease or HIV at enrollment. Additionally, the study population included individuals at high risk of type 2 diabetes, meaning these findings do not currently apply to the general healthy population or individuals at average risk for type 2, type 1, or other types of diabetes.

Reference

Pittas AG, Kawahara T, Jorde R, et al.Vitamin D and risk for type 2 diabetes in people with prediabetes: a systematic review and meta-analysis of individual participant data from 3 randomized clinical trials. Ann Intern Med. Published online February 6, 2023. doi:10.7326/M22-3018