Postprandial C-peptide is more relevant to hemoglobin A1c levels and diabetic microvascular complications than fasting C-peptide in type 2 diabetes

doi:10.4239/wjd.v16.i9.109414

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World Journal of Diabetes

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Diabetes. Sep 15, 2025; 16(9): 109414
Published online Sep 15, 2025. doi: 10.4239/wjd.v16.i9.109414

Postprandial C-peptide is more relevant to hemoglobin A1c levels and diabetic microvascular complications than fasting C-peptide in type 2 diabetes

Zheng Wang, Ming-Qun Deng, Li-Xin Guo, Qi Pan

Zheng Wang, Ming-Qun Deng, Li-Xin Guo, Qi Pan, Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China

Zheng Wang, Department of Endocrinology, Beijing Dongcheng District First People's Hospital, Beijing 100075, China

Co-first authors: Zheng Wang and Ming-Qun Deng.

Author contributions: Wang Z was responsible for collecting clinical data, organizing, and analyzing the data; Deng MQ was responsible for data analysis and drafting the initial manuscript; Wang Z and Deng MQ have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper; Guo LX and Pan Q were responsible for reviewing and revising the entire manuscript; all authors have read and approved the final version to be published.

Supported by National High Level Hospital Clinical Research Funding, No. BJ-2022-145; and China Endocrinology and Metabolism Young Scientific Talent Research Project, No. 2021-N-03.

Institutional review board statement: The study protocol was approved by the Institutional Review Board and Ethics Committee of Beijing Hospital. The study was conducted in accordance with the Declaration of Helsinki.

Informed consent statement: A waiver of informed consent was applied for and granted by the Ethics Committee.

Conflict-of-interest statement: All authors declare no conflict of interest.

STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.

Data sharing statement: All original data available from the corresponding author at panqi621@126.com.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Qi Pan, Professor, Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Dahua Road, Dongcheng District, Beijing 100730, China. panqi621@126.com

Received: May 12, 2025
Revised: June 19, 2025
Accepted: July 28, 2025
Published online: September 15, 2025
Processing time: 124 Days and 19.7 Hours

Abstract

BACKGROUND

Type 2 diabetes mellitus (T2DM), driven by insulin resistance and β cell dysfunction, necessitates reliable assessment of β cell function. C-peptide (CP) measurement, a stable marker of endogenous insulin secretion, is useful for this clinically as it avoids interference from exogenous insulin. While fasting CP (FCP) and postprandial CP (PCP), along with glucose-adjusted indices and ratios, such as FCP/fasting plasma glucose (FPG), 2 hours postprandial CP (2hCP)/postprandial blood glucose (PBG) and CP ratio, are used, their comparative efficacy in reflecting β cell function remains unclear. Hemoglobin A1c (HbA1c), a key glycemic control indicator, theoretically links β cell function to complications, but limited studies have explored the associations between diverse CP indices, HbA1c, and diabetic microvascular complications.

AIM

To investigate the relationships between different CP indices and HbA1c as well as diabetic microvascular complications in T2DM.

METHODS

T2DM patients admitted to Department of Endocrinology at Beijing Hospital between July 1, 2021 and December 31, 2021 were included in the study. Clinical and laboratory data were collected, including CP levels, glucose levels, HbA1c levels and diabetic microvascular complications. Statistical analysis was performed using Statistical Package for the Social Sciences 24.0.

RESULTS

A total of 453 patients were included in the final analysis. Adjusted by confounding factors, CP ratio and CP/blood glucose (BG) ratio were not relevant to HbA1c, but FCP, 2hCP, delta CP, FCP/FPG, 2hCP/PBG and delta CP/BG were still negatively correlated to HbA1c_, of which 2hCP/PBG showed the strongest negative correlation (r = -0.485,P < 0.001). Independent of HbA1c and other confounding factors, 2hCP, 2hCP/PBG, delta CP and delta CP/BG were protective factors of diabetic retinopathy while 2hCP, delta CP and FCP/FPG were protective factors of diabetic peripheral neuropathy.

CONCLUSION

This study indicates that higher levels of CP indices suggest better glucose control and a lower prevalence of diabetic microvascular complications, and PCP indices, particularly 2hCP/PBG, were more relevant to HbA1c and diabetic microvascular complications than FCP indices. These results suggest CP-related indices could be useful biomarkers for diabetes management, warranting further research.

Keywords: C-peptide; Hemoglobin A1c; Diabetic microvascular complications; Type 2 diabetes mellitus; Observational study

Core Tip: This study highlights postprandial C-peptide, particularly 2 hours postprandial C-peptide (2hCP)/postprandial blood glucose (PBG), as the strongest predictor of hemoglobin A1c in type 2 diabetes mellitus, surpassing fasting C-peptide. Higher C-peptide (CP) levels correlate with improved glycemic control. Notably, 2hCP independently reduces the risk of diabetic retinopathy and diabetic peri-neuropathy, suggesting that β cell function preservation benefits both glucose management and complications. These findings advocate prioritizing stimulated CP assessments and exploring 2hCP/PBG as a biomarker for tailored diabetes therapies.