Eldecalcitol for sarcopenia prevention in adults with prediabetes

We read with great interest the recent study by Tetsuya Kawahara and colleagues,1Kawahara T Suzuki G Mizuno S et al.Active vitamin D treatment in the prevention of sarcopenia in adults with prediabetes (DPVD ancillary study): a randomised controlled trial.Lancet Healthy Longev. 2024; 5: e255-e263Summary Full Text Full Text PDF Scopus (0) Google Scholar which assessed the potential of eldecalcitol in the prevention of sarcopenia among adults with prediabetes. However, several issues are worthy of discussion. First, prediabetes encapsulates three phenotypes, including isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), and the combined phenotype (iIFG+iIGT), each with diverse pathophysiological and metabolic characteristics.2Campbell MD Sathish T Zimmet PZ et al.Benefit of lifestyle-based T2DM prevention is influenced by prediabetes phenotype.Nat Rev Endocrinol. 2020; 16: 395-400Crossref PubMed Scopus (60) Google Scholar Based on the definition of prediabetes described in the Article, individuals with iIGT and the combined phenotype were included in this trial, however, the authors did not clarify the proportions of each phenotype in the baseline characteristics table, nor did they use this as a stratification factor for subgroup analyses. Moreover, despite its high incidence, the iIFG phenotype was notably excluded. Could it be possible that the reported therapeutic effects of eldecalcitol might only be present in the specific phenotypes of the prediabetes population? We suggest that future research encompasses iIFG individuals and that analysis is conducted based on phenotypes, which enhances our comprehension of the therapeutic potential of active vitamin D in the broader prediabetes population. Second, prediabetes, as characterised by elevated blood glucose concentrations that do not meet the threshold for diabetes, presents with three potential outcomes: progression to diabetes, maintaining the status of prediabetes, and regression to normoglycaemia.3Echouffo-Tcheugui JB Perreault L Ji L Dagogo-Jack S Diagnosis and management of prediabetes: a review.JAMA. 2023; 329: 1206-1216Crossref PubMed Scopus (53) Google Scholar Even if the researchers excluded participants who progressed to diabetes at any point during the follow-up, there still existed different trajectories for prediabetes. Another investigation has identified prediabetes as an independent risk factor for sarcopenia among older men, which is potentially mediated by insulin resistance and diabetic neuropathy.4Kaga H Tamura Y Someya Y et al.Prediabetes is an independent risk factor for sarcopenia in older men, but not in older women: the Bunkyo Health Study.J Cachexia Sarcopenia Muscle. 2022; 13: 2835-2842Crossref PubMed Scopus (9) Google Scholar Despite the absence of large cohort studies to further confirm the correlation, it is still necessary to consider the impact of the prediabetic trajectories on research outcomes. An advisable approach is to conduct subgroup analyses based on different prediabetes trajectories, which examine the impact of active vitamin D across different glycaemic status trajectories, potentially providing a more nuanced understanding of its effectiveness. Lastly, incorporating the incidence of falls as a second endpoint to evaluate the therapeutic effect of eldecalcitol undoubtedly enhanced the credibility of the study's conclusions. However, as readers, we are keenly interested in more detailed information regarding the falls, such as the causes and frequency of these incidents. Moreover, the use of advanced statistical models, such as competing risk frameworks, could elucidate the specific pathways, in which eldecalcitol exerts its protective effect, thereby guiding targeted interventions. We declare no competing interests. Active vitamin D treatment in the prevention of sarcopenia in adults with prediabetes (DPVD ancillary study): a randomised controlled trialWe found that treatment with eldecalcitol has the potential to prevent the onset of sarcopenia among people with prediabetes via increasing skeletal muscle volume and strength, which might lead to a substantial risk reduction of falls. Full-Text PDF Open AccessEldecalcitol for sarcopenia prevention in adults with prediabetes – Authors' replyWe thank Honglian Luo for the comments on our Article.1 Full-Text PDF Open Access