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05-30-2022 | Prediabetes | News

Vitamin D fails to prevent type 2 diabetes among adults with impaired glucose tolerance

Author: Lynda Williams


medwireNews: Daily treatment with the vitamin D analog eldecalcitol has not prevented the development of type 2 diabetes or promoted a return to normoglycemia in a study of Japanese adults with impaired glucose tolerance.

But the investigators say that, as the trial was designed to detect a 36% lower risk of type 2 diabetes rather than the smaller 13% effect size found after consideration of confounding risk factors, it was likely “underpowered to detect the beneficial effect of eldecalcitol” without adjustment.

As reported in The BMJ, the trial included 1256 individuals (45.5% women; average age 61.3 years) who had impaired glucose tolerance based on an oral glucose tolerance test plus glycated hemoglobin and random glucose levels.

Among these participants, the average serum 25-hydroxyvitamin D level was 20.9 ng/mL, a concentration denoting vitamin D insufficiency, and 43.6% of participants had vitamin D deficiency (<20 ng/mL).

After a median of 2.9 years of follow-up, 12.5% of 630 participants who were randomly assigned to receive eldecalcitol 0.75 µg/day developed type 2 diabetes, as did a comparable 14.2% of the 626 participants instead given placebo.

The rate of regression to normoglycemia among the eldecalcitol-treated individuals and their placebo-treated counterparts was also similar (23.0 vs 20.1%).

However, Tetsuya Kawahara (University of Occupational and Environmental Health, Kitakyushu, Japan) and co-workers found that the risk for type 2 diabetes was significantly lower among participants given eldecalcitol than controls (hazard ratio [HR]=0.69) after adjusting for 11 prespecified covariables including age, sex, comorbidity, family history of diabetes, and insulinogenic index.

In addition, eldecalcitol may have “a beneficial effect on insufficient basal insulin secretion,” the researchers say. Post-hoc analysis using multivariable analysis adjusting for glycated hemoglobin and 2-hour plasma glucose and nine continuous covariables gave a significant HR for type 2 diabetes of 0.41 with eldecalcitol versus placebo among individuals with the lowest levels of fasting immunoreactive insulin.

Writing in a linked comment, Tatiana Christides (Queen Mary University of London, UK) observes that the “clinical relevance of this finding remains unclear,” and emphasizes that post-hoc analyses “should be considered hypothesis generating only.”

While praising the current trial for its “rigorously defined and tested diagnostic criteria,” Christides notes that “it may have been underpowered to detect a small effect” of eldecalcitol on type 2 diabetes risk.

“Several questions remain, including whether vitamin D supplementation may be more effective for particular populations, such as people of colour or people with severe vitamin D deficiency (≤25 mmol/L 25-hydroxyvitamin D), and whether longer duration of treatment or younger age at initiation might be more beneficial,” she continues.

“Until further data are available from high quality randomised trials, healthcare professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

BMJ 2022; 33: e066222
BMJ 2022; 377: o1166


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