Sarcopenia

Abstract

Skeletal muscle is the primary endocrine and metabolic organ responsible for approximately 80% of insulin-mediated postprandial glucose clearance¹. Consequently, the loss of muscle mass and function (sarcopenia), exacerbated by central obesity, acts as an early, bidirectional pathogenic driver in the transition from prediabetes to type 2 diabetes mellitus (T2DM). Visceral adipose tissue dysfunction promotes ectopic intramuscular lipid accumulation (myosteatosis) and the subsequent build-up of diacylglycerols and ceramides. These lipotoxic mediators disrupt the insulin receptor substrate-1 (IRS-1/PI3K/Akt) signaling cascade, preventing GLUT4 transporter translocation to the cell membrane. This process drives metabolic inflexibility, impairing mitochondrial capacity to efficiently switch between glucose and fatty acid oxidation¹.

Concurrently, subclinical hyperglycemia exerts a direct glucotoxic effect on muscle tissue. A critical HbA1c inflection point at 5.2% has recently been identified in non-diabetic individuals; above this threshold, appendicular muscle mass loss accelerates significantly through the activation of proteolytic pathways, such as the ubiquitin-proteasome system via the WWP1/KLF15 axis².

In clinical practice, diagnosing sarcopenic obesity requires a systematic, sequential approach based on the ESPEN/EASO international consensus, prioritizing muscle strength assessment (handgrip strength) followed by body composition confirmation (appendicular skeletal muscle mass normalized by weight using DXA or BIA)^3,4.

Finally, in the current era of incretin-based therapies (GLP-1 receptor agonists and GIP/GLP-1 co-agonists), clinical management of obesity faces a crucial challenge: mitigating lean mass loss, which can account for 25% to over 40% of total weight loss. To ensure "high-quality weight loss," preserve resting energy expenditure, and restore insulin sensitivity, it is mandatory to prescribe progressive resistance training and guarantee an optimized protein intake of 1.2 to 1.6 g/kg/day.