Comment on ‘Prediabetes is an independent risk factor for sarcopenia in older men, but not in older women: the Bunkyo Health Study’ by Kaga et al.

We read, with great interest, the recent article by Kaga et al., in which prediabetes was reported to be associated with sarcopenia in older men but not in older women based on the cross-sectional analysis using the baseline data from the Bunkyo Health Study.¹ This finding indicates that sarcopenia could have occurred prior to the onset of diabetes, particularly in older men, and highlights the need of conducting screening-oriented strategy for sarcopenia prevention in the aging population. However, in this article, several issues are worthy of discussion.

First, as indicated in the Methods part, the authors performed separate analyses by sex for the association of glycaemic status with sarcopenia. They found that after multivariate adjustment, prediabetes was associated with higher odds for sarcopenia compared with normoglycaemia (odds ratio [OR] 2.08, 95% confidence interval [CI]: 1.03 to 4.20) in men but not in women (OR 1.04, 95% CI: 0.61 to 1.76). However, when combining older men and women together, results from the fixed meta-analytical approach showed that prediabetes might not be significantly associated with higher odds of sarcopenia (OR 1.33, 95% CI: 0.87 to 2.03, P for heterogeneity = 0.12). Moreover, the interaction effect between men and women was not significant (P = 0.12), based on the test for interaction,² suggesting that sex may not mediate the association of prediabetes with sarcopenia. A possible explanation for this inconsistent outcome between men and women, as shown by Kaga et al.,¹ might be attributable to the difference in the sample sizes of male and female participants and hence the statistical power. However, as already noted by the authors in their Methods part that there existed considerable differences in body composition, muscle strength, or physical function in the aging population, it is therefore appropriate and reasonable to perform sex-stratified analyses. As a result, future studies with larger sample sizes are required to confirm the present findings regarding the association of prediabetes with sarcopenia between sex in the aging population.

Second, employing oral glucose tolerance test and haemoglobin A1c (HbA1c) to ascertain prediabetes diagnostic criteria by the Japan Diabetes Society is a strength of this article. However, there exists controversies regarding the cut-off points of fasting blood glucose and HbA1c for defining prediabetes. For example, the American Diabetes Association recommends a fasting blood glucose at 5.6–6.9 mmol/L to diagnose prediabetes, while the World Health Organization suggests 6.1–6.9 mmol/L; the American Diabetes Association recommends a HbA1c at 5.7–6.4% (39–47 mmol/mol) to diagnose prediabetes, while the International Expert Committee advocates 6.0–6.4% (42–47 mmol/mol).³ It is therefore of interest to know whether the study outcomes are influenced by the different diagnostic criteria for prediabetes employed.

Third, prediabetes could be stratified as different phenotypes including isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), or both, based on fasting blood glucose and 2-h blood glucose. While it is commonly accepted that both IFG and IGT manifest insulin resistance and β-cell dysfunction, they differ substantially in the underlying pathophysiology, along with distinctly different metabolic abnormalities.⁴ For example, IFG is considered being characterized by severe hepatic insulin resistance but with no clear evidence of impairment in skeletal muscle (peripheral) insulin sensitivity, whereas IGT is featured by marked skeletal muscle insulin resistance but with only moderate hepatic insulin resistance. Given these and considering that the benefit of lifestyle-based type 2 diabetes prevention is suggested to be influenced by prediabetes phenotypes,⁴ it is intriguing to further examine the association of prediabetes phenotypes with sarcopenia.

Finally, prediabetes is an intermediate glycaemic condition, which may progress to diabetes, maintain as prediabetes, or regress to normoglycaemia, during the natural history. Prior studies have shown that prediabetes progression may increase risk of cardiovascular disease and all-cause mortality, while prediabetes regression may bring health benefits including lowered risk of diabetes or cardiovascular disease.⁴ Although the present study might not be able to address whether prediabetes status alteration would affect the development of sarcopenia because of its cross-sectional design, future studies using prospective cohort design might benefit from focusing on this issue, as it may provide some clues for implementing effective approaches for sarcopenia prevention in the aging population with prediabetes.

The authors declare that they have no conflict of interest.