Residual Confounding and Gender Heterogeneity in the Association Between 30‐s Arm Curl Performance and Incident Type 2 Diabetes in Older Adults

Dear Editor,

1.

We read with great interest the prospective cohort study investigating the association between 30‐s arm curl test performance and new‐onset type 2 diabetes mellitus (T2DM) in community‐dwelling older adults. This simple, feasible functional assessment provides valuable insights for geriatric diabetes risk stratification and population‐based prevention [1]. However, several methodological considerations regarding residual confounding and subgroup heterogeneity warrant further discussion.

First, the observed protective association between upper‐limb muscular endurance and lower T2DM risk may be overestimated due to insufficient adjustment for body composition. The study only controlled for BMI and waist circumference, which cannot precisely distinguish lean mass from adipose tissue and fail to account for sarcopenic obesity, a highly prevalent condition in aging populations [2]. Participants with better arm curl performance typically have greater skeletal muscle mass and less visceral fat accumulation, both of which independently improve insulin sensitivity. Therefore, the beneficial metabolic outcome observed in this study may not be solely driven by upper‐limb muscular function but could be partially explained by inherently healthier body composition profiles. Incorporating detailed body composition measurements in future analyses is essential to validate the independent predictive value of the 30‐s arm curl test.

Second, inadequate control of habitual physical activity may introduce notable residual confounding. Older adults with superior functional fitness often maintain more active lifestyles and engage in more regular exercise. Habitual physical activity independently ameliorates glucose homeostasis and insulin resistance, which substantially reduces T2DM risk. Accordingly, the reduced diabetes incidence in participants with better arm curl performance may reflect overall lifestyle advantages rather than isolated upper‐limb muscular benefits. Future studies should quantitatively adjust for daily activity intensity, volume, and exercise patterns to eliminate such confounding and consolidate the study's conclusions.

Third, the study identified evident gender heterogeneity, with the protective association significant only in males but absent in females. The authors attributed this discrepancy to estrogen‐related physiological alterations and age‐related muscle loss in older women, which is biologically reasonable. Nevertheless, the study did not account for female‐specific effect modifiers, including menopausal status and hormone replacement therapy, which may substantially modulate glucose metabolism and muscle metabolic responses. Mechanistically, such gender‐based divergence can be further explained by inherent differences in tissue‐specific glucose disposal capacity. A positron emission tomography study has confirmed that insulin‐stimulated glucose uptake varies substantially across key metabolic organs, including skeletal muscle, adipose tissue, and the liver, and is strongly modulated by age and gender [3]. Older women tend to exhibit weaker muscle glucose uptake efficiency and distinct adipose and hepatic metabolic responses to insulin compared with age‐matched men, which largely blunts the metabolic benefits of improved upper‐limb muscular function. These tissue‐level metabolic differences further weaken the predictive and protective value of upper‐limb muscular function in older female populations. Given that women constituted over half of the study population, the non‐significant findings in the female subgroup carry important clinical implications. It suggests that upper‐limb strength‐based screening and intervention strategies established for men cannot be indiscriminately applied to older women. Gender‐adaptive functional indicators and targeted prevention protocols are required to achieve precise T2DM prevention in elderly female populations.

In conclusion, the present study demonstrates the potential of the 30‐s arm curl test as a practical tool for identifying older adults at high risk of T2DM. Further refinement in body composition adjustment, rigorous control of lifestyle confounding factors, and in‐depth exploration of gender‐specific mechanisms will strengthen the robustness and generalizability of this functional screening approach, facilitating its broader application in geriatric metabolic disease prevention.

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Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.