Muscle Quality in Relation to Prediabetes Phenotypes: A Population-Based Study With Mediation Analysis

Abstract Context Prediabetes is associated with an increased risk of physical disability, yet no studies have assessed the extent to which muscle quality, a measure reflecting muscle functionality, was altered in prediabetes and its specific phenotype. Objective We evaluated their associations in a general US population with mediation analysis. Methods This was a cross-sectional study based on the National Health and Nutrition Examination Survey 2011-2014. Participants with prediabetes were stratified as having an isolated defect (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired hemoglobin A1c [IA1c]), 2 defects (IFG + IGT, IFG + IA1c, or IGT + IA1c), or all defects (IFG + IGT + IA1c). Muscle quality was calculated as dominant grip strength divided by dominant arm muscle mass measured by dual-energy X-ray absorptiometry. Results We included 2351 participants (938 with prediabetes and 1413 with normoglycemia). Despite higher grip strength and larger arm muscle mass, arm muscle quality was lower in prediabetes and all prediabetes phenotypes (except for IGT) than normoglycemia (all P < .04), and was unrelated to prediabetes awareness. Arm muscle quality was decreased and the odds of low arm muscle quality was increased in prediabetes with increasing numbers of glucometabolic defects (both P < .001), with insulin resistance being the predominant mediator. HbA1c-defined prediabetes (IA1c) had lower arm muscle quality and higher odds of low arm muscle quality than blood glucose–defined prediabetes (IFG, IGT, or IFG + IGT). Conclusion Muscle quality was impaired in prediabetes and its specific phenotype. Relative to blood glucose, elevated HbA1c might be a better predictor of reduced muscle quality.