Corrao Salvatore, Falcone Fabio, Mirarchi Luigi, Amodeo Simona, Calvo Luigi
Department of Clinical Medicine, UOC Medicina Interna iGR, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Piazza Nicola Leotta, 2, 90127, Palermo, Italy.
Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties [PROMISE], University of Palermo, Palermo, Italy.
Diabetes Ther. 2025 Jun 13. doi: 10.1007/s13300-025-01761-4.
Type 2 diabetes mellitus (T2DM) is a global health priority, with an estimated 629 million people projected to be affected by the year 2045. T2DM significantly increases the risk of atherosclerotic cardiovascular disease and other complications. Hyperglycaemia imprints early molecular and cellular changes, often termed "metabolic memory", predisposing individuals to long-term microvascular and macrovascular complications, even after glycaemic normalisation. T2DM remission is increasingly recognised as an achievable target, offering substantial benefits such as reduced morbidity, improved quality of life, and preservation of beta-cell function. Among therapeutic options, metabolic surgery (MS) demonstrates the most significant impact, particularly for long-term outcomes. MS induces profound hormonal changes, including increased glucagon-like peptide 1 (GLP-1) levels and improved bile acid metabolism, alongside reductions in ectopic fat in the liver and pancreas, which improve insulin sensitivity and secretion. However, intensive lifestyle and pharmacological interventions, such as GLP-1 receptor agonists and glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 dual agonists like tirzepatide, also show promise, particularly when implemented early in the disease course. Predictors of sustained remission include younger age, shorter diabetes duration, lower baseline HbA1c, absence of insulin use, fewer medications and greater total weight loss percentage. Emerging tools such as the DiaRem score, machine learning models, and biomarkers like FGF-21 enhance patient stratification and predict remission likelihood. This narrative review explores the mechanisms and therapeutic options for T2DM remission, evaluates their impact on long-term outcomes and highlights the importance of early, multidisciplinary, and personalised interventions to optimize remission and improve metabolic health.
2型糖尿病（T2DM）是全球卫生重点问题，预计到2045年将有6.29亿人受其影响。T2DM显著增加动脉粥样硬化性心血管疾病和其他并发症的风险。高血糖会引发早期分子和细胞变化，通常称为“代谢记忆”，使个体易患长期微血管和大血管并发症，即使血糖恢复正常后也是如此。T2DM缓解越来越被认为是一个可实现的目标，能带来诸多益处，如降低发病率、改善生活质量以及保护β细胞功能。在治疗选择中，代谢手术（MS）显示出最显著的影响，尤其是对长期预后。MS会引发深刻的激素变化，包括胰高血糖素样肽1（GLP-1）水平升高和胆汁酸代谢改善，同时肝脏和胰腺中的异位脂肪减少，从而提高胰岛素敏感性和分泌。然而，强化生活方式和药物干预，如GLP-1受体激动剂以及像替尔泊肽这样的葡萄糖依赖性促胰岛素多肽/胰高血糖素样肽1双重激动剂，也显示出前景，特别是在疾病病程早期实施时。持续缓解的预测因素包括年龄较小、糖尿病病程较短、基线糖化血红蛋白较低、未使用胰岛素、用药较少以及总体重减轻百分比更高。诸如DiaRem评分、机器学习模型以及成纤维细胞生长因子21（FGF-21）等生物标志物等新兴工具可加强患者分层并预测缓解可能性。这篇叙述性综述探讨了T2DM缓解的机制和治疗选择，评估了它们对长期预后的影响，并强调了早期、多学科和个性化干预对于优化缓解及改善代谢健康的重要性。
