青年起病2型糖尿病缓解的机制、干预策略及预测因素研究进展
Remission in Young-Onset Type 2 Diabetes: Mechanisms, Intervention Strategies, and Predictive Factors
摘要: 随着2型糖尿病(Type 2 Diabetes Mellitus, T2DM)发病年龄逐渐年轻化，青年起病2型糖尿病(Young-Onset T2DM, Y-T2DM)的患病负担不断加重，已成为全球公共卫生领域的重要问题。相较于晚发病T2DM，Y-T2DM患者通常表现出更明显的胰岛素抵抗、更迅速的β细胞功能衰退及更高的慢性并发症风险。近年来，“糖尿病缓解”作为一种新的治疗目标逐渐受到关注，并形成相对统一的国际共识。研究表明，Y-T2DM患者在疾病早期仍具有一定的代谢可逆性，通过积极干预有望实现血糖长期达标，甚至在停用降糖药物后维持正常血糖水平。本文为叙述性综述，通过查阅国内外相关文献，围绕Y-T2DM的流行病学特点及病理生理基础，系统综述糖尿病缓解的概念演变及其临床意义，并重点归纳当前主要干预策略，包括强化生活方式管理、优化降糖治疗方案及代谢手术等，同时探讨其潜在作用机制。现有证据提示，以减重为核心的综合干预在促进糖尿病缓解过程中具有关键作用，且缓解效果与体重下降幅度密切相关。未来仍需开展大样本、长期随访研究，以进一步明确缓解状态的维持情况及其影响因素，从而为Y-T2DM的早期干预及个体化治疗提供更为可靠的循证依据。
Abstract: With the onset age of type 2 diabetes mellitus (T2DM) progressively decreasing, the burden of young-onset T2DM (Y-T2DM) has been steadily increasing, becoming a significant global public health concern. Compared with late-onset T2DM, Y-T2DM patients typically exhibit more pronounced insulin resistance, faster decline in β-cell function, and a higher risk of chronic complications. In recent years, “diabetes remission” has emerged as a novel therapeutic goal and has been increasingly recognized in international consensus statements. Evidence indicates that Y-T2DM patients retain a certain degree of metabolic reversibility in the early stages of the disease, and active interventions may help achieve long-term glycemic control, with some patients maintaining normal blood glucose levels even after discontinuing glucose-lowering medications. This narrative review summarizes the epidemiological characteristics and pathophysiological basis of Y-T2DM based on relevant literature from China and abroad. It reviews the evolution and clinical significance of diabetes remission, and highlights current major intervention strategies, including intensive lifestyle modification, optimized glucose-lowering therapy, and metabolic surgery, as well as their potential mechanisms. Current evidence indicates that weight-loss-centered interventions play a key role in promoting diabetes remission, with outcomes closely related to the degree of weight reduction. Further large-scale, long-term follow-up studies are needed to clarify the durability of remission and its influencing factors, providing stronger evidence for early intervention and individualized management of Y-T2DM.
文章引用：邹易宏, 刘东方. 青年起病2型糖尿病缓解的机制、干预策略及预测因素研究进展[J]. 临床医学进展, 2026, 16(5): 301-311. https://doi.org/10.12677/acm.2026.1651819

参考文献

[1] Xie, J., Wang, M., Long, Z., Ning, H., Li, J., Cao, Y., et al. (2022) Global Burden of Type 2 Diabetes in Adolescents and Young Adults, 1990-2019: Systematic Analysis of the Global Burden of Disease Study 2019. BMJ, 379, e072385. [Google Scholar] [CrossRef] [PubMed]
[2] Zhou, Y., Chen, Y., Tang, Y., Zhang, S., Zhuang, Z. and Ni, Q. (2025) Rising Tide: The Growing Global Burden and Inequalities of Early-Onset Type 2 Diabetes among Youths Aged 15-34 Years (1990-2021). Diabetology & Metabolic Syndrome, 17, Article No. 103. [Google Scholar] [CrossRef] [PubMed]
[3] Kim, J.Y., Lee, J., Moon, J.H., Park, S.E., Ko, S., Choi, S.H., et al. (2025) Prevalence, Incidence, and Metabolic Characteristics of Young Adults with Type 2 Diabetes Mellitus in South Korea (2010-2020). Diabetes & Metabolism Journal, 49, 172-182. [Google Scholar] [CrossRef] [PubMed]
[4] Gerencser, A.A. (2024) 1749-P: Deficient Mitochondrial Activation in Type 2 Diabetic Human ß-Cells during Insulin Secretion. Diabetes, 73, 1749-P. [Google Scholar] [CrossRef] 
[5] Yeow, T.P., Pacini, G., Tura, A., Hor, C.P., Lim, S.L., Tan, F.H.S., et al. (2017) Preserved Glucagon-Like Peptide-1 Responses to Oral Glucose, but Reduced Incretin Effect, Insulin Secretion and Sensitivity in Young Asians with Type 2 Diabetes Mellitus. BMJ Open Diabetes Research & Care, 5, e000352. [Google Scholar] [CrossRef] [PubMed]
[6] Deng, H., et al. (2020) 962-P: Impacts of Different Hypoglycemic Agents on Adipokines and Inflammatory Markers in Newly Diagnosed T2D Patients. Diabetes, 69, 962-P.
https://diabetesjournals.org/diabetes/article/69/Supplement_1/962-P/56634/962-P-Impacts-of-Different-Hypoglycemic-Agents-on
[7] Salama, O.E., Hizon, N., Del Vecchio, M., Kolsun, K., Fonseca, M.A., Lin, D.T.S., et al. (2024) DNA Methylation Signatures of Youth-Onset Type 2 Diabetes and Exposure to Maternal Diabetes. Clinical Epigenetics, 16, Article No. 65. [Google Scholar] [CrossRef] [PubMed]
[8] Son, J. and Accili, D. (2023) Reversing Pancreatic β-Cell Dedifferentiation in the Treatment of Type 2 Diabetes. Experimental & Molecular Medicine, 55, 1652-1658.
https://www.nature.com/articles/s12276-023-01043-8
[9] Cree-Green, M., Gupta, A., Coe, G.V., Baumgartner, A.D., Pyle, L., Reusch, J.E.B., et al. (2017) Insulin Resistance in Type 2 Diabetes Youth Relates to Serum Free Fatty Acids and Muscle Mitochondrial Dysfunction. Journal of Diabetes and Its Complications, 31, 141-148. [Google Scholar] [CrossRef] [PubMed]
[10] Patel, S. and Remedi, M.S. (2024) Loss of β-Cell Identity and Dedifferentiation, Not an Irreversible Process? Frontiers in Endocrinology, 15, Article 1414447. [Google Scholar] [CrossRef] [PubMed]
[11] Serbis, A., Giapros, V., Tsamis, K., Balomenou, F., Galli-Tsinopoulou, A. and Siomou, E. (2023) β Cell Dysfunction in Youth-and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients. Nutrients, 15, Article 2217. [Google Scholar] [CrossRef] [PubMed]
[12] Kim, J.Y., Lee, J., Kim, S.G. and Kim, N.H. (2025) β-Cell Function, Insulin Sensitivity, and Metabolic Characteristics in Young-Onset Type 2 Diabetes Mellitus: Findings from Anam Diabetes Observational Study. Diabetes & Metabolism Journal, 49, 1287-1297. [Google Scholar] [CrossRef] [PubMed]
[13] Vienberg, S., Geiger, J., Madsen, S. and Dalgaard, L.T. (2017) MicroRNAs in Metabolism. Acta Physiologica, 219, 346-361. [Google Scholar] [CrossRef] [PubMed]
[14] Prosperi, S. and Chiarelli, F. (2025) Insulin Resistance, Metabolic Syndrome and Polycystic Ovaries: An Intriguing Conundrum. Frontiers in Endocrinology, 16, Article 1669716. [Google Scholar] [CrossRef] 
[15] Wang, Q., Kangas, A.J., Soininen, P., Tiainen, M., Tynkkynen, T., Puukka, K., et al. (2015) Sex Hormone-Binding Globulin Associations with Circulating Lipids and Metabolites and the Risk for Type 2 Diabetes: Observational and Causal Effect Estimates. International Journal of Epidemiology, 44, 623-637. [Google Scholar] [CrossRef] [PubMed]
[16] Krewson, C. (2026) Experts Urge More Research into Youth-Onset Diabetes. Contemporary Pediatrics.
https://www.contemporarypediatrics.com/view/experts-urge-for-more-research-into-youth-onset-diabetes
[17] Devaraj, S., Hemarajata, P. and Versalovic, J. (2013) The Human Gut Microbiome and Body Metabolism: Implications for Obesity and Diabetes. Clinical Chemistry, 59, 617-628. [Google Scholar] [CrossRef] [PubMed]
[18] Kim, H. and Fang, S. (2018) Crosstalk between FXR and TGR5 Controls Glucagon-Like Peptide 1 Secretion to Maintain Glycemic Homeostasis. Laboratory Animal Research, 34, 140-146. [Google Scholar] [CrossRef] [PubMed]
[19] Buse, J.B., Caprio, S., Cefalu, W.T., Ceriello, A., Del Prato, S., Inzucchi, S.E., et al. (2009) How Do We Define Cure of Diabetes? Diabetes Care, 32, 2133-2135. [Google Scholar] [CrossRef] [PubMed]
[20] 中华医学会糖尿病学分会中华医学会代谢与减重外科学分会. 2型糖尿病代谢手术术后管理中国专家共识(2018版) [J]. 中华消化外科杂志, 2018, 17(10): 977-986.
[21] Nagi, D., Hambling, C. and Taylor, R. (2019) Remission of Type 2 Diabetes: A Position Statement from the Association of British Clinical Diabetologists (ABCD) and the Primary Care Diabetes Society (pcds). British Journal of Diabetes, 19, 73-76. [Google Scholar] [CrossRef] 
[22] Carrasco, I., Ferrer, L. and Puigdemont, A. (2022) Efficacy of Oclacitinib for the Control of Feline Atopic Skin Syndrome: Correlating Plasma Concentrations with Clinical Response. Journal of Feline Medicine and Surgery, 24, 787-793. [Google Scholar] [CrossRef] [PubMed]
[23] Lean, M.E., Leslie, W.S., Barnes, A.C., Brosnahan, N., Thom, G., McCombie, L., et al. (2018) Primary Care-Led Weight Management for Remission of Type 2 Diabetes (DiRECT): An Open-Label, Cluster-Randomised Trial. The Lancet, 391, 541-551. [Google Scholar] [CrossRef] [PubMed]
[24] Taheri, S., Zaghloul, H., Chagoury, O., Elhadad, S., Ahmed, S.H., El Khatib, N., et al. (2020) Effect of Intensive Lifestyle Intervention on Bodyweight and Glycaemia in Early Type 2 Diabetes (DIADEM-I): An Open-Label, Parallel-Group, Randomised Controlled Trial. The Lancet Diabetes & Endocrinology, 8, 477-489. [Google Scholar] [CrossRef] [PubMed]
[25] Weng, J., Li, Y., Xu, W., Shi, L., Zhang, Q., Zhu, D., et al. (2008) Effect of Intensive Insulin Therapy on Β-Cell Function and Glycaemic Control in Patients with Newly Diagnosed Type 2 Diabetes: A Multicentre Randomised Parallel-Group Trial. The Lancet, 371, 1753-1760. [Google Scholar] [CrossRef] [PubMed]
[26] Matthews, D.R., Paldánius, P.M., Proot, P., Chiang, Y., Stumvoll, M. and Del Prato, S. (2019) Glycaemic Durability of an Early Combination Therapy with Vildagliptin and Metformin versus Sequential Metformin Monotherapy in Newly Diagnosed Type 2 Diabetes (VERIFY): A 5-Year, Multicentre, Randomised, Double-Blind Trial. The Lancet, 394, 1519-1529. [Google Scholar] [CrossRef] [PubMed]
[27] Liu, Y., Chen, Y., Ma, J., Lin, J., Liu, C., Li, X., et al. (2025) Dapagliflozin Plus Calorie Restriction for Remission of Type 2 Diabetes: Multicentre, Double Blind, Randomised, Placebo Controlled Trial. BMJ, 388, e081820. [Google Scholar] [CrossRef] [PubMed]
[28] Tsapas, A., Avgerinos, I., Karagiannis, T., Malandris, K., Manolopoulos, A., Andreadis, P., et al. (2020) Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-Analysis. Annals of Internal Medicine, 173, 278-286. [Google Scholar] [CrossRef] [PubMed]
[29] Inge, T.H., Courcoulas, A.P., Jenkins, T.M., Michalsky, M.P., Helmrath, M.A., Brandt, M.L., et al. (2016) Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents. New England Journal of Medicine, 374, 113-123. [Google Scholar] [CrossRef] [PubMed]
[30] Aung, L., Lee, W., Chen, S.C., Ser, K., Wu, C., Chong, K., et al. (2016) Bariatric Surgery for Patients with Early-Onset vs Late-Onset Type 2 Diabetes. JAMA Surgery, 151, 798-805. [Google Scholar] [CrossRef] [PubMed]
[31] Inge, T.H., Jenkins, T.M., Xanthakos, S.A., Dixon, J.B., Daniels, S.R., Zeller, M.H., et al. (2017) Long-Term Outcomes of Bariatric Surgery in Adolescents with Severe Obesity (FABS-5+): A Prospective Follow-Up Analysis. The Lancet Diabetes & Endocrinology, 5, 165-173. [Google Scholar] [CrossRef] [PubMed]
[32] DeFronzo, R.A. (2009) From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus. Diabetes, 58, 773-795. [Google Scholar] [CrossRef] [PubMed]
[33] Taylor, R. (2016) Calorie Restriction and Reversal of Type 2 Diabetes. Expert Review of Endocrinology & Metabolism, 11, 521-528. [Google Scholar] [CrossRef] [PubMed]
[34] Lim, E.L., Hollingsworth, K.G., Aribisala, B.S., Chen, M.J., Mathers, J.C. and Taylor, R. (2011) Reversal of Type 2 Diabetes: Normalisation of β Cell Function in Association with Decreased Pancreas and Liver Triacylglycerol. Diabetologia, 54, 2506-2514. [Google Scholar] [CrossRef] [PubMed]
[35] Lean, M.E.J., Leslie, W.S., Barnes, A.C., et al. (2019) Durability of a Primary Care-Led Weight-Management Intervention for Remission of Type 2 Diabetes: 2-Year Results of the DiRECT Open-Label, Cluster-Randomised Trial. The Lancet Diabetes & Endocrinology, 7, 344-355.
[36] Li, C., Zhao, Z., Zhou, Z. and Liu, R. (2016) PKM2 Promotes Cell Survival and Invasion under Metabolic Stress by Enhancing Warburg Effect in Pancreatic Ductal Adenocarcinoma. Digestive Diseases and Sciences, 61, 767-773. [Google Scholar] [CrossRef] [PubMed]
[37] Tremaroli, V. and Bäckhed, F. (2012) Functional Interactions between the Gut Microbiota and Host Metabolism. Nature, 489, 242-249. [Google Scholar] [CrossRef] [PubMed]
[38] Hackett, R.A. and Steptoe, A. (2017) Type 2 Diabetes Mellitus and Psychological Stress—A Modifiable Risk Factor. Nature Reviews Endocrinology, 13, 547-560. [Google Scholar] [CrossRef] [PubMed]
[39] Mansori, K., Shiravand, N., Shadmani, F.K., Moradi, Y., Allahmoradi, M., Ranjbaran, M., et al. (2019) Association between Depression with Glycemic Control and Its Complications in Type 2 Diabetes. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 13, 1555-1560. [Google Scholar] [CrossRef] [PubMed]
[40] TODAY Study Group (2012) A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes. New England Journal of Medicine, 366, 2247-2256. [Google Scholar] [CrossRef] [PubMed]
[41] Aikens, J.E. and Piette, J.D. (2013) Longitudinal Association between Medication Adherence and Glycaemic Control in Type 2 Diabetes. Diabetic Medicine, 30, 338-344. [Google Scholar] [CrossRef] [PubMed]
[42] Marcus, M.D., Gandica, R., El ghormli, L., Higgins, J., Tesfaldet, B., Koren, D., et al. (2022) Longitudinal Association of Depressive Symptoms, Binge Eating, and Quality of Life with Cardiovascular Risk Factors in Young Adults with Youth-Onset Type 2 Diabetes: The TODAY2 Study. Diabetes Care, 45, 1073-1081. [Google Scholar] [CrossRef] [PubMed]
[43] Rivera, J., McPherson, A., Hamilton, J., Birken, C., Coons, M., Iyer, S., et al. (2016) Mobile Apps for Weight Management: A Scoping Review. JMIR mHealth and uHealth, 4, e87. [Google Scholar] [CrossRef] [PubMed]
[44] Fisher, E.B., Coufal, M.M., Parada, H., Robinette, J.B., Tang, P.Y., Urlaub, D.M., et al. (2014) Peer Support in Health Care and Prevention: Cultural, Organizational, and Dissemination Issues. Annual Review of Public Health, 35, 363-383. [Google Scholar] [CrossRef] [PubMed]

为你推荐