Keegan Grace L, Bhardwaj Namita, Abdelhafiz Ahmed H
Department of Geriatric Medicine, Rotherham General Hospital, Rotherham, UK.
Expert Rev Endocrinol Metab. 2023 Sep-Nov;18(5):361-375. doi: 10.1080/17446651.2023.2239907. Epub 2023 Jul 25.
Frailty is an emerging and newly recognized complication of diabetes in older people. However, frailty is not thoroughly investigated in diabetes outcome studies.
This manuscript reviews the effect of glycemic control and hypoglycemic therapy on the incidence of frailty in older people with diabetes.
Current studies show that both low glycemia and high glycemia are associated with frailty. However, most of the studies, especially low glycemia studies, are cross-sectional or retrospective, suggesting association, rather than causation, of frailty. In addition, frail patients in the low glycemia studies are characterized by lower body weight or lower body mass index (BMI), contrary to those in the high glycemia studies, who are either overweight or obese. This may suggest that frailty has a heterogeneous metabolic spectrum, starting with an anorexic malnourished (AM) phenotype at one end, which is associated with low glycemia and a sarcopenic obese (SO) phenotype on the other end, which is associated with high glycemia. The current little evidence suggests that poor glycemic control increases the risk of frailty, but there is a paucity of evidence to suggest that tight glycemic control would reduce the risk of incident frailty. Metformin is the only well-studied hypoglycemic agent, so far, to have a protective effect against frailty independent of glycemic control in the non-frail older people with diabetes. However, once frailty is developed, the choice of the best hypoglycemic agent for these patients will be affected by the metabolic phenotype of frailty. For example, sodium glucose transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are appropriate in the SO phenotype due to their weight losing properties, while insulin therapy may be considered early in the AM phenotype due to its anabolic and weight gaining benefits. Future studies are still required to further investigate the metabolic effects of frailty on older people with diabetes, determine the most appropriate HbA1c target, and explore the most suitable hypoglycemic agent in each metabolic phenotype of frailty.
衰弱是老年人糖尿病中一种新出现且新被认识的并发症。然而，在糖尿病结局研究中，衰弱并未得到充分研究。
本手稿综述了血糖控制和降糖治疗对老年糖尿病患者衰弱发生率的影响。
目前的研究表明，低血糖和高血糖均与衰弱有关。然而，大多数研究，尤其是低血糖研究，是横断面研究或回顾性研究，提示的是衰弱的相关性而非因果关系。此外，低血糖研究中的衰弱患者特征为体重较低或体重指数（BMI）较低，这与高血糖研究中的患者相反，后者要么超重要么肥胖。这可能表明衰弱具有异质性的代谢谱，一端是以厌食性营养不良（AM）为表型，与低血糖相关，另一端是以肌肉减少性肥胖（SO）为表型，与高血糖相关。目前证据很少表明血糖控制不佳会增加衰弱风险，但也缺乏证据表明严格的血糖控制会降低新发衰弱的风险。二甲双胍是目前唯一经过充分研究的降糖药物，在非衰弱的老年糖尿病患者中，它具有独立于血糖控制之外的抗衰弱保护作用。然而，一旦发生衰弱，这些患者最佳降糖药物的选择将受衰弱代谢表型的影响。例如，钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂和胰高血糖素样肽-1受体激动剂（GLP-1RA）因其减重特性适用于SO表型，而胰岛素治疗由于其合成代谢和体重增加的益处，可在AM表型中早期考虑使用。未来仍需要进一步研究衰弱对老年糖尿病患者的代谢影响，确定最合适的糖化血红蛋白（HbA1c）目标，并探索在每种衰弱代谢表型中最合适的降糖药物。
