Sinclair Alan, Siqueira Izel, Abdelhafiz Ahmed
King's College, London WC2R 2LS, UK.
Foundation for Diabetes Research in Older People (fDROP), Droitwich Spa WR9 0QH, UK.
Metabolites. 2025 Jun 9;15(6):381. doi: 10.3390/metabo15060381.
The association of frailty with body composition is complex. Frailty can be associated with significant anorexia and weight loss or overweight and obesity. In addition, the development of frailty leads to changes in muscle mass, muscle fibre type, and visceral fat. In older people with diabetes, frailty-induced body composition changes are clinically relevant as they may affect the metabolic profile of the frail person. The determinants of insulin resistance in frail older persons with diabetes include factors such as total body weight and the ratio of lean muscle mass to visceral fat mass. The predominant loss of insulin-resistant skeletal muscle fibres type II, in comparison to insulin-sensitive type I fibres, is another factor that modifies the overall insulin resistance of the individual. As a result, frailty appears to be a heterogeneous condition with variable insulin resistance across a metabolic spectrum. The spectrum spans from a sarcopenic obese frail phenotype at one end to an anorexic malnourished frail phenotype at the other end. The introduction of SGLT-2 inhibitors and GLP-1RA with novel anti-metabolic syndrome properties, not just glucose-lowering effect, should influence clinicians' choice in frail older persons with diabetes. These agents are likely to be beneficial in patients at the sarcopenic obese end of the frailty spectrum, who should benefit most due to their high baseline risk of progression of metabolic syndrome, high insulin resistance, and the increased prevalence of cardiovascular risk factors. On the other hand, patients at the anorexic malnourished end of the frailty spectrum are likely not suitable for such therapy due to the regression of metabolic syndrome in this group of patients and the increased risk of further weight loss, dehydration, and hypotension.
衰弱与身体成分之间的关联很复杂。衰弱可能与严重厌食、体重减轻或超重及肥胖有关。此外，衰弱的发展会导致肌肉量、肌纤维类型和内脏脂肪发生变化。在老年糖尿病患者中，衰弱引起的身体成分变化具有临床相关性，因为它们可能会影响衰弱者的代谢状况。老年衰弱糖尿病患者胰岛素抵抗的决定因素包括总体重以及瘦肌肉量与内脏脂肪量的比值等因素。与胰岛素敏感的I型纤维相比，胰岛素抵抗的II型骨骼肌纤维的显著减少是另一个改变个体整体胰岛素抵抗的因素。因此，衰弱似乎是一种异质性状况，在代谢谱中具有可变的胰岛素抵抗。这个谱一端是肌少症肥胖型衰弱表型，另一端是厌食营养不良型衰弱表型。具有新型抗代谢综合征特性（不仅仅是降糖作用）的钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2抑制剂）和胰高血糖素样肽-1受体激动剂（GLP-1RA）的引入，应该会影响临床医生对老年衰弱糖尿病患者的选择。这些药物可能对衰弱谱中肌少症肥胖端的患者有益，由于他们代谢综合征进展的基线风险高、胰岛素抵抗高以及心血管危险因素的患病率增加，他们应该受益最大。另一方面，衰弱谱中厌食营养不良端的患者可能不适合这种治疗，因为这组患者的代谢综合征会消退，且进一步体重减轻、脱水和低血压的风险增加。
