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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Association of β-cell function and insulin resistance with pediatric type 2 diabetes among Chinese children
Zhen-Ran Xu, Hong-Wei Du, Lan-Wei Cui, Rong-Xiu Zheng, Gui-Mei Li, Hai-Yan Wei, Fei-Yu Lu, Li-Li Chen, Chu-Shan Wu, Shu-Xin Zhang, Shu-Le Zhang, Fang Liu, Miao-Ying Zhang, Zhou Pei, Cheng-Jun Sun, Jing Wu, Fei-Hong Luo
Zhen-Ran Xu, Miao-Ying Zhang, Zhou Pei, Cheng-Jun Sun, Jing Wu, Fei-Hong Luo, Department of Pediatric Endocrinology and Inherited Metabolic Diseases, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai 201102, China
Hong-Wei Du, Fei-Yu Lu, Department of Pediatric Endocrinology and Inherited Metabolic Diseases, The First Bethune Hospital of Jilin University, Changchun 130021, Jilin Province, China
Lan-Wei Cui, Li-Li Chen, Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
Rong-Xiu Zheng, Chu-Shan Wu, Shu-Xin Zhang, Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin 300052, China
Gui-Mei Li, Shu-Le Zhang, Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
Hai-Yan Wei, Fang Liu, Department of Endocrinology, Henan Children's Hospital, Zhengzhou 450052, Henan Province, China
Author contributions: Luo FH and Xu ZR conceived the idea and designed the study; Luo FH, Li GM, Zheng RX, Du HW, Cui LW, and Wei HY were the local principal investigators and supervised the study; Xu ZR, Liu F, Lu FY, Chen LL, Wu CS, Zhang SX, and Zhang SL were responsible for data collection; Xu ZR, Zhang MY, and Sun CJ did the statistical analysis; Zhang MY, Wu J, Pei Z, and Xu ZR did the literature review; Xu ZR wrote the first draft; Luo FH gave critical comments and contributed to the writing of the manuscript; Luo FH had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. All authors agreed to submit and publish the manuscript.
Supported by the National Key Research and Development Program of China, No. 2016YFC1305302; the National Natural Science Fund of China, No. 81600608; and the Key Research and Development Program of Shandong Province, No. 2017GSF18118.
Institutional review board statement: This study was reviewed and approved by the Ethics Committees of all included hospitals.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflict of interest for this manuscript.
Data sharing statement: Data are available on request from the authors.
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:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Fei-Hong Luo, MD, PhD, Chief Doctor, Department of Pediatric Endocrinology and Inherited Metabolic Diseases, National Children’s Medical Center, Children's Hospital of Fudan University, No. 399 Wan Yuan Road, Min Hang District, Shanghai 201102, China. luofh@fudan.edu.cn
Received: November 11, 2020
Peer-review started: November 11, 2020
First decision: June 5, 2021
Revised: June 15, 2021
Accepted: July 13, 2021
Article in press: July 13, 2021
Published online: August 15, 2021
Processing time: 270 Days and 19.4 Hours
BACKGROUND
In addition to insulin resistance, impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus (T2DM). Scarce clinical data exist for pediatric T2DM.
AIM
To investigate the association of β-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study.
METHODS
This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019. Children with normal glycemic levels (n = 1935) were included as healthy control subjects. The homeostasis models (HOMAs) were used to assess the β-cell function (HOMA2-%B) and insulin resistance (HOMA2-IR) levels. The HOMA index was standardized by sex and age. We performed logistic regression analysis to obtain odds ratios (ORs) for T2DM risk using the standardized HOMA index, adjusted for confounding factors including sex, Tanner stage, T2DM family history, body mass index z-score, and lipid profile.
RESULTS
The male-female ratio of newly diagnosed T2DM patients was 1.37:1 (OR = 2.20, P = 0.011), and the mean ages of onset for boys and girls were 12.5 ± 1.9 years and 12.3 ± 1.7 years, respectively. The prevalence of related comorbidities including obesity, elevated blood pressure, and dyslipidemia was 58.2%, 53.2%, and 80.0%, respectively. The T2DM group had lower HOMA2-%B levels (P < 0.001) and higher HOMA2-IR levels (P < 0.001) than the control group. Both the decrease in HOMA2-%B z-score (OR = 8.40, 95%CI: 6.40–11.02, P < 0.001) and the increase in HOMA2-IR z-score (OR = 1.79, 95%CI: 1.60–2.02, P < 0.001) were associated with a higher risk of T2DM, and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors.
CONCLUSION
Besides insulin resistance, β-cell function impairment is also strongly associated with Chinese pediatric T2DM. Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.
Core Tip: This multicenter cross-sectional study described the clinical characteristics of Chinese type 2 diabetes (T2DM) children in detail, and characterized the association of β-cell function and insulin resistance with T2DM among children and adolescents. This study showed that β-cell dysfunction, compared with insulin resistance, is a stronger risk factor associated with pediatric T2DM among Chinese children, regardless of obesity status. Our results suggested that pediatricians should pay more attention to children with relatively low β-cell function regardless of insulin resistance during pediatric T2DM screening and emphasize the protection and improvement of β-cell function in T2DM children in clinical practice.
