Visit-to-visit variability of creatinine levels associated with proteinuria progression in Chinese patients with type 2 diabetes mellitus

doi:10.4239/wjd.119913

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World Journal of Diabetes

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1948-9358

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

Prospective Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Diabetes. Jun 15, 2026; 17(6): 119913
Published online Jun 15, 2026. doi: 10.4239/wjd.119913

Visit-to-visit variability of creatinine levels associated with proteinuria progression in Chinese patients with type 2 diabetes mellitus

Yu-Hang Ma, Xiao-Hui Wei, Yue Liu, Li-Ping Gu, Ting-Ting Shen, Ting-Ting Fan, Qin Qin, Ai-Fang Zhang, Rui-Ping Wang, Yu-Fan Wang

Yu-Hang Ma, Xiao-Hui Wei, Yue Liu, Li-Ping Gu, Ting-Ting Shen, Ting-Ting Fan, Qin Qin, Ai-Fang Zhang, Yu-Fan Wang, Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China

Rui-Ping Wang, Clinical Research Center, Shanghai Skin Disease Hospital, Skin Disease Hospital of Tongji University, Shanghai 200072, China

Co-first authors: Yu-Hang Ma and Xiao-Hui Wei.

Co-corresponding authors: Rui-Ping Wang and Yu-Fan Wang.

Author contributions: Wang YF, Wang RP, Ma YH, and Wei XH designed the study; Wang RP, Ma YH, and Wei XH analyzed the data; Zhang AF, Fan TT, Qin Q, and Shen TT collected blood samples and collected anthropometric measurements; Liu Y and Gu LP contributed to clinical data collection and information verification; Ma YH, Wei XH and Liu Y drafted the manuscript; Wang YF and Wang RP have primary responsibility for final content and are the guarantors of this work; Ma YH and Wei XH contributed equally to this manuscript and are co-first authors; Wang YF and Wang RP contributed equally to this manuscript and are co-corresponding authors; all authors contributed to data acquisition, revised the manuscript for important intellectual content and approved the manuscript, read and approved the final version to be published.

Supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project, No. 2023ZD0508104; Shanghai Science and Technology Commission Foundation, No. 23ZR1451500; National Health Commission Medical Health Science and Technology Development Research Center “Innovative Medicine Post-Marketing Clinical Research Project”, No. WKZX2023CX150002; and the Fourth Round of “Committee and Hospital Cooperation” (Shanghai Songjiang District Health Commission and Shanghai General People’s Hospital); Joint Research Project and the Chronic Disease Management Research Project of National Health Commission Capacity Building and Continuing Education Center, No. GWJJMB202510024038.

Institutional review board statement: This study was approved by the Ethics Committee of the Shanghai General Hospital affiliated with Shanghai Jiao Tong University School of Medicine (No. 2017KY209).

Clinical trial registration statement: The study cohort was acquired from the database of the Shanghai General Hospital; a branch of the National Standardized Management Center for Metabolic Diseases in China (ClinicalTrials.gov ID: NCT03811470).

Informed consent statement: Written informed consent was obtained from all participants prior to their involvement in the study.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Corresponding author: Yu-Fan Wang, MD, Doctor, Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China. yyffwang@sina.com

Received: February 10, 2026
Revised: March 12, 2026
Accepted: April 10, 2026
Published online: June 15, 2026
Processing time: 121 Days and 20.8 Hours

Abstract

BACKGROUND

Proteinuria is a critical therapeutic target in the early management of diabetic kidney disease in individuals with type 2 diabetes mellitus (T2DM). The relationship between metabolic parameter variability and proteinuria in T2DM remains unclear. Few studies have focused on the stability of serum creatinine in diabetic patients and its relationship with the development of proteinuria.

AIM

To explore the relationship between metabolic parameter variability and the development of proteinuria in patients with T2DM.

METHODS

A total of 3297 patients were recruited into this prospective study at Shanghai General Hospital. Ultimately, 1453 patients with T2DM were analyzed (median follow-up time 26 months). Variability was assessed using standard deviation (SD) of serial measurements. The means and SDs of metabolic indicators were categorized into four percentiles to analyze their impact on proteinuria progression. Logistic regression analysis was used to identify the independent risk factors for proteinuria progression.

RESULTS

Proteinuria progression was observed in 26.84% of patients. The SDs of body mass index, systolic blood pressure, diastolic blood pressure, uric acid, fasting blood glucose, and creatinine were greater in patients with proteinuria progression during follow-up. Multivariable logistic regression analysis revealed that the SD of creatinine during follow-up was an independent risk factor for proteinuria progression in T2DM patients [creatinine SD: Above percentiles 75 (P75^th) vs below P75^th, odds ratio (OR) = 1.47, 95% confidence interval (CI): 1.07-2.03; above P67^th vs below P67^th, OR = 1.39, 95%CI: 1.03-1.87] after adjusting for confounding factors. The results were consistent in subgroup analysis according to different albumin-to-creatinine ratio stages at baseline.

CONCLUSION

Creatinine level fluctuations independently predicted proteinuria development and progression in T2DM. Dynamic creatinine variability may serve as a valuable adjunct to static indicators in refining proteinuria risk assessment for T2DM.

Keywords: Metabolic parameters; Creatinine; Proteinuria; Progression; Type 2 diabetes mellitus

Core Tip: This was a prospective cohort study to comprehensively analyze the relationship between variability of metabolic parameters and proteinuria in type 2 diabetes mellitus (T2DM). Variability in creatinine levels during follow-up was an independent risk factor for proteinuria progression, and this finding was consistent across patients stratified by different baseline urinary albumin-to-creatinine ratio. These results offer a reference for incorporating dynamic creatinine variability into proteinuria risk monitoring strategies in T2DM patients.