C肽在2型糖尿病管理中的最新应用进展: 从生物标志物到临床决策工具
Recent Advances in the Application of C-Peptide in Type 2 Diabetes Management: From Biomarker to Clinical Decision Tool
DOI: 10.12677/acm.2026.1641593, PDF,   
作者: 许 茜, 周厚地*:重庆医科大学附属大学城医院内分泌与代谢科,重庆
关键词: 2型糖尿病C肽胰岛素抵抗Type 2 Diabetes Mellitus C‑Peptide Insulin Resistance
摘要: 2型糖尿病(T2DM)作为一类慢性代谢性疾病,其核心病理特征为胰岛素抵抗以及胰岛β细胞功能的渐进性衰退。以往临床主要借助C肽完成糖尿病的分型与诊断工作,而越来越多的研究证实,该指标的临床价值远不止于此。本文通过系统梳理相关研究,总结了C肽在辅助分型诊断、评估并发症风险以及优化治疗方案等方面的重要价值,旨在推动糖尿病管理模式由传统经验型向精准化、个体化方向发展。
Abstract: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and progressive impairment of pancreatic β-cell function. Clinically, C-peptide has long been used for the classification and diagnosis of diabetes, yet a growing body of evidence indicates that its clinical value extends far beyond these applications. This article systematically reviews the relevant literature and summarizes the important roles of C-peptide in assisting disease classification and diagnosis, stratifying the risk of complications, and optimizing therapeutic strategies, aiming to promote the transformation of diabetes management from a traditional empirical model to precision and personalized care.
文章引用:许茜, 周厚地. C肽在2型糖尿病管理中的最新应用进展: 从生物标志物到临床决策工具[J]. 临床医学进展, 2026, 16(4): 3314-3323. https://doi.org/10.12677/acm.2026.1641593

参考文献

[1] Ong, K.L., Stafford, L.K., McLaughlin, S.A., Boyko, E.J., Vollset, S.E., Smith, A.E., et al. (2023) Global, Regional, and National Burden of Diabetes from 1990 to 2021, with Projections of Prevalence to 2050: A Systematic Analysis for the Global Burden of Disease Study 2021. The Lancet, 402, 203-234. [Google Scholar] [CrossRef] [PubMed]
[2] Saisho, Y. (2016) Postprandial C-Peptide to Glucose Ratio as a Marker of Β Cell Function: Implication for the Management of Type 2 Diabetes. International Journal of Molecular Sciences, 17, Article 744. [Google Scholar] [CrossRef] [PubMed]
[3] Leighton, E., Sainsbury, C.A. and Jones, G.C. (2017) A Practical Review of C-Peptide Testing in Diabetes. Diabetes Therapy, 8, 475-487. [Google Scholar] [CrossRef] [PubMed]
[4] Alemán-Contreras, R., Gómez-Díaz, R.A., Noyola-García, M.E., Mondragón-González, R., Wacher, N. and Ferreira-Hermosillo, A. (2024) Utility of Fasting C-Peptide for the Diagnostic Differentiation of Patients with Type 1, Type 2 Diabetes, MODY, and LADA. Life, 14, Article 550. [Google Scholar] [CrossRef] [PubMed]
[5] Kumar, N., Khan, A.A., Yadav, A., et al. (2025) Correlation of C-Peptide Levels with Complications of Type 2 Diabetes Mellitus. Cureus, 17, e93754.
[6] Iqbal, S., Jayyab, A.A., Alrashdi, A.M. and Reverté-Villarroya, S. (2023) The Predictive Ability of C-Peptide in Distinguishing Type 1 Diabetes from Type 2 Diabetes: A Systematic Review and Meta-Analysis. Endocrine Practice, 29, 379-387. [Google Scholar] [CrossRef] [PubMed]
[7] Jones, A.G. and Hattersley, A.T. (2013) The Clinical Utility of C-Peptide Measurement in the Care of Patients with Diabetes. Diabetic Medicine, 30, 803-817. [Google Scholar] [CrossRef] [PubMed]
[8] Lin, Y.Y., McCrimmon, R.J. and Pearson, E.R. (2025) Exploring the Potential Role of C‐peptide in Type 2 Diabetes Management. Diabetic Medicine, 42, e15469. [Google Scholar] [CrossRef] [PubMed]
[9] Vinay, E.S., Laxmi Narsimha Rao, B., Saf, N. and Gautam, D. (2026) C-Peptide in Precision Diabetes Care and beyond: A Comprehensive Review. Clinical Medicine Insights: Endocrinology and Diabetes, 19, Article 11795514251397811. [Google Scholar] [CrossRef
[10] Souto, S.B., Campos, J.R., Fangueiro, J.F., Silva, A.M., Cicero, N., Lucarini, M., et al. (2020) Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection. International Journal of Molecular Sciences, 21, Article 645. [Google Scholar] [CrossRef] [PubMed]
[11] Dakroub, A., Dbouk, A., Asfour, A., Nasser, S.A., El-Yazbi, A.F., Sahebkar, A., et al. (2024) C-Peptide in Diabetes: A Player in a Dual Hormone Disorder? Journal of Cellular Physiology, 239, e31212. [Google Scholar] [CrossRef] [PubMed]
[12] Alves, M.T., Ortiz, M.M.O., dos Reis, G.V.O.P., Dusse, L.M.S., Carvalho, M.D.G., Fernandes, A.P., et al. (2019) The Dual Effect of C-Peptide on Cellular Activation and Atherosclerosis: Protective or Not? Diabetes/Metabolism Research and Reviews, 35, e3071. [Google Scholar] [CrossRef] [PubMed]
[13] Nagaratnam, S., Rojo, S., Long Bidin, M.B., Rahim, N.S.C., Tharmathurai, S., Arip, M., et al. (2023) A Cross-Sectional Study to Assess Beta-Cell Function in Individuals with Recently Diagnosed Young-Onset Type 2 Diabetes Mellitus and Its’ Complications. Journal of the ASEAN Federation of Endocrine Societies, 38, 20-27. [Google Scholar] [CrossRef] [PubMed]
[14] Cui, D., Feng, X., Lei, S., Zhang, H., Hu, W., Yang, S., et al. (2024) Pancreatic β-Cell Failure, Clinical Implications, and Therapeutic Strategies in Type 2 Diabetes. Chinese Medical Journal, 137, 791-805. [Google Scholar] [CrossRef] [PubMed]
[15] Li, H.F. and Zhu, Z.M. (2025) Involvement of C-Peptide in the Progression of Type 2 Diabetes Mellitus through Triglyceride-Centered Lipid Metabolism. Hormones, 25, 129-137.
[16] Xu, S., Jiang, Y., Wang, H., Wang, Z., Liu, H., Peng, L., et al. (2015) C-Peptide Ameliorates Renal Injury in Type 2 Diabetic Rats through Protein Kinase A-Mediated Inhibition of Fibronectin Synthesis. Biochemical and Biophysical Research Communications, 458, 674-680. [Google Scholar] [CrossRef] [PubMed]
[17] Funakoshi, S., Fujimoto, S., Hamasaki, A., Fujiwara, H., Fujita, Y., Ikeda, K., et al. (2011) Analysis of Factors Influencing Postprandial C-Peptide Levels in Japanese Patients with Type 2 Diabetes: Comparison with C-Peptide Levels after Glucagon Load. Journal of Diabetes Investigation, 2, 429-434. [Google Scholar] [CrossRef] [PubMed]
[18] Richards, J.P., Bowles, E.A., Gordon, W.R., Ellsworth, M.L., Stephenson, A.H. and Sprague, R.S. (2015) Mechanisms of C-Peptide-Mediated Rescue of Low O2-Induced ATP Release from Erythrocytes of Humans with Type 2 Diabetes. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 308, R411-R418. [Google Scholar] [CrossRef] [PubMed]
[19] Morita, S., Shimajiri, Y., Matsuoka, Y., Kadoya, Y., Yamada, S., Matsuoka, T., et al. (2025) Exploring Genetic Risk Factors for β-Cell Deterioration in Type 2 Diabetes Mellitus: Insights from Longitudinal C-Peptide Analysis. Diabetes Research and Clinical Practice, 222, Article 112049. [Google Scholar] [CrossRef] [PubMed]
[20] Marx, N., Walcher, D., Raichle, C., Aleksic, M., Bach, H., Grüb, M., et al. (2004) C-Peptide Colocalizes with Macrophages in Early Arteriosclerotic Lesions of Diabetic Subjects and Induces Monocyte Chemotaxis in Vitro. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 540-545. [Google Scholar] [CrossRef] [PubMed]
[21] Vasic, D., Spyrantis, A., Durst, R., Bach, H., Vogt, S., Rottbauer, W., et al. (2012) C-Peptide Induces Human Renal Mesangial Cell Proliferation in Vitro, Activating Src-Kinase, PI-3 Kinase and ERK1/2. Molecular and Cellular Endocrinology, 351, 337-341. [Google Scholar] [CrossRef] [PubMed]
[22] Walcher, D. and Marx, N. (2009) C-Peptide in the Vessel Wall. The Review of Diabetic Studies, 6, 180-186. [Google Scholar] [CrossRef] [PubMed]
[23] de Boer, I.H., Zelnick, L., Afkarian, M., Ayers, E., Curtin, L., Himmelfarb, J., et al. (2016) Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD. Journal of the American Society of Nephrology, 27, 2861-2871. [Google Scholar] [CrossRef] [PubMed]
[24] Rahhal, M., Gharaibeh, N.E., Rahimi, L. and Ismail-Beigi, F. (2019) Disturbances in Insulin-Glucose Metabolism in Patients with Advanced Renal Disease with and without Diabetes. The Journal of Clinical Endocrinology & Metabolism, 104, 4949-4966. [Google Scholar] [CrossRef] [PubMed]
[25] Kwon, S.Y., Park, J., Park, S.H., Lee, Y., Kim, G., Hur, K.Y., et al. (2025) Plasma C-Peptide Levels and the Continuous Glucose Monitoring-Defined Coefficient of Variation in Risk Prediction for Hypoglycemia in Korean People with Diabetes Having Normal and Impaired Kidney Function. Endocrinology and Metabolism, 40, 268-277. [Google Scholar] [CrossRef] [PubMed]
[26] Vasic, D., Marx, N., Sukhova, G., Bach, H., Durst, R., Grüb, M., et al. (2012) C‐Peptide Promotes Lesion Development in a Mouse Model of Arteriosclerosis. Journal of Cellular and Molecular Medicine, 16, 927-935. [Google Scholar] [CrossRef] [PubMed]
[27] Yan, S.T., Sun, J., Gu, Z.Y., et al. (2022) The Bidirectional Association of C-Peptide with Cardiovascular Risk in Nondiabetic Adults and Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Retrospective Cohort Study. Cardiovascular Diabetology, 21, Article No. 201. [Google Scholar] [CrossRef] [PubMed]
[28] Lebherz, C. and Marx, N. (2013) C-Peptide and Its Career from Innocent Bystander to Active Player in Diabetic Atherogenesis. Current Atherosclerosis Reports, 15, Article No. 339. [Google Scholar] [CrossRef] [PubMed]
[29] Hernanz-Rodriguez, G., Pedrianes-Martin, P., de Pablos-Velasco, P. and Rodriguez-Perez, A. (2018) Pancreatic Beta Cell Function Is Preserved in the Short Term in Patients with Type 2 Diabetes Undergoing Non-Urgent Surgery. Minerva Endocrinology, 43, 109-116. [Google Scholar] [CrossRef] [PubMed]
[30] Berger, B., Stenström, G. and Sundkvist, G. (2000) Random C-Peptide in the Classification of Diabetes. Scandinavian Journal of Clinical and Laboratory Investigation, 60, 687-693. [Google Scholar] [CrossRef] [PubMed]
[31] Zhou, W., Li, J., Yuan, X., Wang, W., Zhou, H., Zhang, H., et al. (2022) Application of Urine C-Peptide Creatinine Ratio in Type 2 Diabetic Patients with Different Levels of Renal Function. Frontiers in Endocrinology, 13, Article 1052794. [Google Scholar] [CrossRef] [PubMed]
[32] Pappachan, J.M., Sunil, B., Fernandez, C.J., Lahart, I.M. and Ashraf, A.P. (2022) Diagnostic Test Accuracy of Urine C-Peptide Creatinine Ratio for the Correct Identification of the Type of Diabetes: A Systematic Review. Endocrinology, 18, Article 2. [Google Scholar] [CrossRef] [PubMed]
[33] Hope, S.V., Jones, A.G., Goodchild, E., Shepherd, M., Besser, R.E.J., Shields, B., et al. (2013) Urinary C-Peptide Creatinine Ratio Detects Absolute Insulin Deficiency in Type 2 Diabetes. Diabetic Medicine, 30, 1342-1348. [Google Scholar] [CrossRef] [PubMed]
[34] Freese, J., Al-Rawi, R., Choat, H., Martin, A., Lunsford, A., Tse, H., et al. (2021) Proinsulin to C-Peptide Ratio in the First Year after Diagnosis of Type 1 Diabetes. The Journal of Clinical Endocrinology & Metabolism, 106, e4318-e4326. [Google Scholar] [CrossRef] [PubMed]
[35] Zheng, Z., Liu, N., Zhang, Y., Gu, X., Li, H. and Yu, X. (2025) Postprandial C-Peptide to Glucose Ratio as a Promising Systemic Marker of Diabetic Retinopathy in Type 2 Diabetes. Translational Vision Science & Technology, 14, 27. [Google Scholar] [CrossRef] [PubMed]
[36] Zhang, H., Bian, B., Hu, F. and Su, Q. (2017) OGTT 1h Serum C-Peptide to Plasma Glucose Concentration Ratio Is More Related to Beta Cell Function and Diabetes Mellitus. Oncotarget, 8, 51786-51791. [Google Scholar] [CrossRef] [PubMed]
[37] Okura, T., Nakamura, R., Fujioka, Y., Kawamoto-Kitao, S., Ito, Y., Matsumoto, K., et al. (2018) CPR-IR Is an Insulin Resistance Index That Is Minimally Affected by Hepatic Insulin Clearance—A Preliminary Research. PLOS ONE, 13, e0197663. [Google Scholar] [CrossRef] [PubMed]
[38] Briggs, L., Read, A., Darch, S., Williams, E.L., Loh, W.J. and Kenkre, J.S. (2026) The Evolution of C-Peptide’s Role in Diabetes Care. Current Opinion in Endocrinology, Diabetes & Obesity, 33, 16-24. [Google Scholar] [CrossRef
[39] Christensen, M.B., Gæde, P., Hommel, E., Gotfredsen, A. and Nørgaard, K. (2020) Glycaemic Variability and Hypoglycaemia Are Associated with C-Peptide Levels in Insulin-Treated Type 2 Diabetes. Diabetes & Metabolism, 46, 61-65. [Google Scholar] [CrossRef] [PubMed]
[40] Makina, J., S, M. and S.R., R. (2025) Correlation between Serum C-Peptide Level and Diabetic Retinopathy According to Estimated Glomerular Filtration Rate in Patients with Type 2 Diabetes. Irish Journal of Medical Science, 194, 873-877. [Google Scholar] [CrossRef] [PubMed]
[41] Dekker, P., de Vries, M., Aanstoot, H. and Groen, J. (2022) Which C-Peptide Assay Do You Use? Increasing Need for Describing C-Peptide Assay Performance. Pediatric Endocrinology Diabetes and Metabolism, 28, 101-103. [Google Scholar] [CrossRef] [PubMed]
[42] Li, Y., Liu, B., Xue, M., Zhang, Y., Jia, X., Guo, K., et al. (2025) Correlation between C-Peptide and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study. Scientific Reports, 15, Article No. 35896. [Google Scholar] [CrossRef
[43] Ma, J., Han, C., Lv, Y. and Cai, H. (2025) Non-Linear Relationship between Fasting C-Peptide and Retinopathy in Patients with Type 2 Diabetes Mellitus—A Retrospective Study. Diabetes, Metabolic Syndrome and Obesity, 18, 1035-1045. [Google Scholar] [CrossRef] [PubMed]
[44] Pan, T., Gao, J., Cai, X., Zhang, H., Lu, J. and Lei, T. (2023) The Average 30-Minute Post-Prandial C-Peptide Predicted Diabetic Retinopathy Progress: A Retro-Prospective Study. BMC Endocrine Disorders, 23, Article No. 63. [Google Scholar] [CrossRef] [PubMed]
[45] Kim, B.Y., Jung, C.H., Mok, J.O., et al. (2012) Association between Serum C-Peptide Levels and Chronic Microvascular Complications in Korean Type 2 Diabetic Patients. Acta Diabetologica, 49, 9-15. [Google Scholar] [CrossRef] [PubMed]
[46] Chen, L., Hu, Y., Ma, Y. and Wang, H. (2023) Non-Linear Association of Fasting C-Peptide and Uric Acid Levels with Renal Dysfunction Based on Restricted Cubic Spline in Patients with Type 2 Diabetes: A Real-World Study. Frontiers in Endocrinology, 14, Article 1157123. [Google Scholar] [CrossRef] [PubMed]
[47] Yang, Q., Liu, Y., Peng, J., Pan, J., Chen, L., Cui, J., et al. (2023) High Levels of Serum C-Peptide Are Associated with a Decreased Risk for Incident Renal Progression in Patients with Type 2 Diabetes: A Retrospective Cohort Study. BMJ Open Diabetes Research & Care, 11, e003201. [Google Scholar] [CrossRef] [PubMed]
[48] Potaliya, U., Tak, S. and Goyal, M. (2023) Association of C-Peptide Level with Peripheral Neuropathy in Type 2 Diabetes: An Observational Cross-Sectional Preliminary Study. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 17, Article 102725. [Google Scholar] [CrossRef] [PubMed]
[49] Gao, L., Qin, J., Chen, Y., Jiang, W., Zhu, D., Zhou, X., et al. (2024) Risk Factors for Subclinical Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus. Diabetes, Metabolic Syndrome and Obesity, 17, 417-426. [Google Scholar] [CrossRef] [PubMed]
[50] Zuo, A., Wang, C., Li, L., Qu, J., Cao, J., Chen, L., et al. (2020) The Association of Fasting C-Peptide with Corneal Neuropathy in Patients with Type 2 Diabetes. Journal of Diabetes Research, 2020, 1-8. [Google Scholar] [CrossRef] [PubMed]
[51] Chung, J.O., Park, S.Y., Cho, D.H., et al. (2020) Association between Serum C-Peptide Level and Cardiovascular Autonomic Neuropathy According to Estimated Glomerular Filtration Rate in Individuals with Type 2 Diabetes. Experimental and Clinical Endocrinology & Diabetes, 128, 607-614. [Google Scholar] [CrossRef] [PubMed]
[52] Wang, L., Lin, P., Ma, A., Zheng, H., Wang, K., Li, W., et al. (2015) C-Peptide Is Independently Associated with an Increased Risk of Coronary Artery Disease in T2DM Subjects: A Cross-Sectional Study. PLOS ONE, 10, e0127112. [Google Scholar] [CrossRef] [PubMed]
[53] Kumar, S. and Valliyot, B. (2024) Serum C-Peptide as a Predictor of Coronary Artery Disease in Middle-Aged Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Analytical Study. Cureus, 16, e74422. [Google Scholar] [CrossRef] [PubMed]
[54] Zha, X.Y., Wei, C.S., Dong, J.J., et al. (2025) Elevated Fasting C-Peptide Levels Correlate with Increased 10-Year Risk of Atherosclerotic Cardiovascular Disease in Newly Diagnosed Type 2 Diabetes Patients. Diabetes, Metabolic Syndrome and Obesity, 18, 51-59. [Google Scholar] [CrossRef] [PubMed]
[55] Marx, N., Silbernagel, G., Brandenburg, V., Burgmaier, M., Kleber, M.E., Grammer, T.B., et al. (2013) C-Peptide Levels Are Associated with Mortality and Cardiovascular Mortality in Patients Undergoing Angiography: The LURIC Study. Diabetes Care, 36, 708-714. [Google Scholar] [CrossRef] [PubMed]
[56] Liu, Y., Zhao, X., Yang, Z., Wang, S., Han, C. and Zhang, H. (2022) Correlation between Serum C-Peptide-Releasing Effects and the Risk of Elevated Uric Acid in Type 2 Diabetes Mellitus. Endocrine Journal, 69, 773-784. [Google Scholar] [CrossRef] [PubMed]
[57] Huang, Y., Wang, Y., Liu, C., Zhou, Y., Wang, X., Cheng, B., et al. (2022) C-Peptide, Glycaemic Control, and Diabetic Complications in Type 2 Diabetes Mellitus: A Real-World Study. Diabetes/Metabolism Research and Reviews, 38, e3514. [Google Scholar] [CrossRef] [PubMed]
[58] Wang, Y., Zou, X., Cai, X., Liu, W., Chen, L., Zhang, R., et al. (2021) Urinary C-Peptide/Creatinine Ratio: A Useful Biomarker of Insulin Resistance and Refined Classification of Type 2 Diabetes Mellitus. Journal of Diabetes, 13, 893-904. [Google Scholar] [CrossRef] [PubMed]
[59] Landgraf, W., Bigot, G., Hess, S., Asplund, O., Groop, L., Ahlqvist, E., et al. (2022) Distribution and Characteristics of Newly-Defined Subgroups of Type 2 Diabetes in Randomised Clinical Trials: Post Hoc Cluster Assignment Analysis of over 12,000 Study Participants. Diabetes Research and Clinical Practice, 190, Article 110012. [Google Scholar] [CrossRef] [PubMed]
[60] Iwamoto, Y., Kimura, T., Morimoto, Y., Kimura, Y., Komi, M., Watanabe, Y., et al. (2026) C-Peptide Index under Non-Fasting Conditions Can Predict the Likelihood of Future Insulin Therapy in Outpatients with Type 2 Diabetes Mellitus Not Receiving Insulin at Baseline. Internal Medicine, Article ID: 6495-25. [Google Scholar] [CrossRef
[61] Dario, T., Riccardo, G., Silvia, P., Mikiko, W., Daria, M., Andrea, P., et al. (2021) The Utility of Assessing C-Peptide in Patients with Insulin-Treated Type 2 Diabetes: A Cross-Sectional Study. Acta Diabetologica, 58, 411-417. [Google Scholar] [CrossRef] [PubMed]
[62] Sugita-Hamada, M., Yokoo, T., Nakajima, N., Takahashi, Y., Osaki, A., Maruyama, M., et al. (2025) Simultaneous Evaluation of Shear Wave Elastography and C-Peptide Index for Predicting Need of Insulin Therapy in Type 2 Diabetes: A Pilot Study. Journal of Personalized Medicine, 15, Article 277. [Google Scholar] [CrossRef] [PubMed]
[63] Wei, Y., Quan, L., Zhou, T., Du, G. and Jiang, S. (2021) The Relationship between Different C-Peptide Level and Insulin Dose of Insulin Pump. Nutrition & Diabetes, 11, Article No. 7. [Google Scholar] [CrossRef] [PubMed]
[64] Mu, P., Liu, D., Lin, Y., Liu, D., Zhang, F., Zhang, Y., et al. (2018) The Postprandial-to-Fasting Serum C-Peptide Ratio Is a Predictor of Response to Basal Insulin-Supported Oral Antidiabetic Drug(s) Therapy: A Retrospective Analysis. Diabetes Therapy, 9, 963-971. [Google Scholar] [CrossRef] [PubMed]