Vitamin D does not reduce diabetes incidence

Treatment with eldecalcitol, an active vitamin D analogue, does not result in a significant reduction in diabetes incidence and has failed to improve the rate of regression to normoglycaemia relative to placebo among patients with impaired glucose tolerance at high risk for type 2 diabetes (T2D), results of a study have shown.

“Although treatment with eldecalcitol did not significantly reduce the incidence of diabetes among people with prediabetes, the results suggested the potential for a beneficial effect of eldecalcitol on people with insufficient insulin secretion,” the researchers said.

A double-blinded, multicentre, randomized, placebo-controlled trial was conducted in three hospitals in Japan between June 2013 and August 2019. A total of 1,256 individuals with impaired glucose tolerance (mean age 61.3 years, 45.5 percent women, 59.1 percent had a family history of T2D) were randomized to receive active vitamin D (eldecalcitol 0.75 μg per day; n=630) or matching placebo (n=626) for 3 years.

At baseline, participants had a mean serum 25-hydroxyvitamin D concentration of 20.9 ng/mL (52.2 nmol/L), and 548 (43.6 percent) had concentrations <20 ng/mL (50 nmol/L). During a median follow-up of 2.9 years, T2D developed in 79 participants (12.5 percent) in the eldecalcitol group and 89 (14.2 percent) in the placebo group (hazard ratio [HR], 0.87, 95 percent confidence interval [CI], 0.67‒1.17; p=0.39). [BMJ 2022;377:e066222]

Only 145 participants (23.0 percent) in the eldecalcitol group and 126 (20.1 percent) in the placebo group achieved regression to normoglycaemia (HR, 1.15, 95 percent CI, 0.93‒1.41; p=0.21). After adjusting for confounders, eldecalcitol led to a significant decrease in the development of diabetes (HR, 0.69, 95 percent CI, 0.51‒0.95; p=0.020). Eldecalcitol also provided benefits among participants with a lower level of basal insulin secretion (HR, 0.41, 95 percent CI, 0.23‒0.71; p=0.001).

In addition, treatment with eldecalcitol significantly increased bone mineral densities of the lumbar spine and femoral neck and serum osteocalcin concentrations relative to placebo during follow-up (p<0.001 for all). No significant difference was noted in serious adverse events.

“Eldecalcitol, an active vitamin D analogue, does not affect the serum 25-hydroxyvitamin D concentration, but it suppresses the expression of the CYP27B1 gene in the kidney, which promotes conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D intracellularly,” the researchers said. [J Steroid Biochem Mol Biol 2014;139:88-97]

“However, eldecalcitol has a similar physiological effect to 1,25-dihydroxyvitamin D. Hence, it increased the bone mineral densities of the lumbar spine and femoral neck in this study,” they added.

Glucose intolerance correlates with insufficient insulin secretion, insulin resistance, or both. [J Diabetes Investig 2010;1:212-228]

“Homoeostasis model assessment (HOMA)-β is a biomarker of insulin secretion, with a value of <40 percent indicating decreased β cell function,” the researchers said. [Cell Transplant 2012;21:1341-1347; Diabetes Care 2004;27:1487-1495]

“HOMA-insulin resistance is a biomarker of insulin resistance, and a value of ≥1.6 indicates that insulin is secreted from the pancreas but the target organ’s sensitivity to insulin is reduced and its action is slowed down—that is, insulin resistance,” they added. [BMC Endocr Disord 2013;13:47]