Pathophysiological mechanisms and risk factors linking type 2 diabetes mellitus and sarcopenia: A narrative review

Abstract

Type 2 diabetes mellitus (T2DM) and sarcopenia often coexist in the elderly. This is a growing clinical challenge. T2DM accelerates the decline of skeletal muscle through metabolic disorders, and sarcopenia further aggravates insulin resistance and functional impairment. Yet the underlying mechanisms and optimal management strategies of T2DM-related sarcopenia are still not fully understood. This narrative review aims to systematically summarize the epidemiological characteristics, pathogenic mechanisms, risk factors, and current treatment strategies related to T2DM and sarcopenia. The words “T2DM“, “sarcopenia“, “skeletal muscle loss“, “insulin resistance“, “inflammatory“, “oxidative stress“ and “mitochondrial dysfunction“ and “therapeutic interventions“ were used as keywords to search the PubMed/MEDLINE and Web of Science databases for articles published from January 2000 to May 2026. Relevant clinical, experimental and review studies were screened and synthesized. The prevalence of sarcopenia varies according to diagnostic criteria and population characteristics. The prevalence in the elderly is about 10%-29%. In contrast, patients with T2DM are at significantly increased risk, and their prevalence is estimated to be about two to three times as high as those without diabetes. The prevalence of sarcopenia in Asian patients with T2DM is estimated to be 20%-37%. T2DM leads to muscle degeneration through impaired insulin signaling, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, accumulation of advanced glycation end products, fatty infiltration, alteration of gut microbiota, and genetic regulation at the mechanism level. The advanced age, poor glycemic control (especially glycosylated hemoglobin ≥ 8.0%), malnutrition, physical inactivity, diabetic peripheral neuropathy, chronic kidney disease, and drug-related changes in body composition are the main risk factors. Comprehensive management requires early screening, individualized glycemic control goals, adequate protein intake, and resistance exercise. The hypoglycemic drugs should be selected reasonably according to the effect of hypoglycemic drugs on muscle health. T2DM related sarcopenia is a complex metabolic-musculoskeletal disorder that requires comprehensive management beyond conventional glycemic control. Early identification of high-risk individuals and implementation of multidisciplinary interventions targeting glucose metabolism, nutrition, physical activity, and optimal medication may improve muscle function and clinical outcomes. Further longitudinal studies and clinical trials are needed to elucidate the long-term effects of glucose lowering therapy on skeletal muscle protection.

Keywords: Type 2 diabetes mellitus; Muscle loss; Sarcopenia; Risk factors; Resistance training

Core Tip: Type 2 diabetes mellitus significantly accelerates skeletal muscle decline and is an independent risk factor for sarcopenia, particularly in older adults. This review highlights key interconnected mechanisms – including insulin resistance, chronic inflammation, mitochondrial dysfunction, and altered protein metabolism – that drive muscle loss in type 2 diabetes mellitus. Given the high and often underrecognized prevalence of sarcopenia in diabetic populations, early screening and integrated management are essential. Multimodal strategies combining glycaemic control, resistance exercise, adequate nutrition, and muscle-protective pharmacotherapy may effectively mitigate functional decline and improve patient outcomes.