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Predominance of Insulin Resistance Over Beta-Cell Dysfunction as a Diabetes Risk Factor in Chinese Adults: Impact of Obesity in a Nationwide Prospective Study

36 Pages Posted: 20 Aug 2019

See all articles by Tiange Wang

Tiange Wang

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Jieli Lu

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Lixin Shi

Guizhou Medical University (Guiyang Medical University) - First Affiliated Hospital

Gang Chen

Fujian Medical University - Fujian Provincial Hospital

Min Xu

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Yu Xu

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Qing Su

Shanghai Jiao Tong University (SJTU) - Xinhua Hospital

Yiming Mu

Government of the People's Republic of China - Department of Endocrinology

Lulu Chen

Huazhong University of Science and Technology (Formerly Tongi Medical University) - Union Hospital

Ruying Hu

Zhejiang Provincial Center for Disease Control and Prevention - Department of Non-Communicable Disease Control and Prevention

Xulei Tang

Lanzhou University - Department of Endocrinology

Xuefeng Yu

Huazhong University of Science and Technology (Formerly Tongi Medical University) - Tongji Hospital

Mian Li

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Zhiyun Zhao

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Yuhong Chen

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Li Yan

Sun Yat-Sen University (SYSU) - Sun Yat-sen Memorial Hospital

Guijun Qin

Zhengzhou University - Division of Endocrinology

Qin Wan

Southwest Medical University - Affiliated Hospital

Meng Dai

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Di Zhang

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Zhengnan Gao

Dalian University - Dalian Municipal Central Hospital

Guixia Wang

Jilin University (JLU) - Department of Endocrinology and Metabolism

Feixia Shen

Wenzhou Medical University - First Affiliated Hospital

Zuojie Luo

Guangxi Medical University - First Affiliated Hospital

Yingfen Qin

Guangxi Medical University - Department of Endocrine

Li Chen

Shandong University - Qilu Hospital

Yanan Huo

Nanchang University - Jiangxi Medical School

Qiang Li

Harbin Medical University - Second Affiliated Hospital

Zhen Ye

Zhejiang Provincial Center for Disease Control and Prevention

Yinfei Zhang

Central Hospital of Shanghai Jiading District

Chao Liu

Jiangsu Province Hospital on Integration of Chinese and Western Medicine

Youmin Wang

Anhui Medical University - Department of Endocrinology

Shengli Wu

Government of the People's Republic of China - Karamay Municipal People's Hospital

Tao Yang

Nanjing Medical University - Nanjing Medical Hospital

Huacong Deng

Chongqing Medical University - First Affiliated Hospital

Jiajun Zhao

Shandong First Medical University - Department of Endocrinology and Metabolism; Shandong Academy of Clinical Medicine - Institute of Endocrinology; Shandong Clinical Medical Center of Endocrinology and Metabolism

Shenghan Lai

Johns Hopkins University - School of Medicine

Yufang Bi

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Ralph A. DeFronzo

University of Texas Health Science Center at San Antonio

Weiqing Wang

Shanghai Jiao Tong University (SJTU) - Shanghai Clinical Center for Endocrine and Metabolic Diseases

Guang Ning

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases; Shanghai Jiao Tong University (SJTU) - Shanghai Institute of Endocrine and Metabolic Diseases; Shanghai Jiao Tong University (SJTU) - Shanghai Clinical Center for Endocrine and Metabolic Diseases

4C Study Group

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Abstract

Background: National investigations on the interaction of insulin resistance, beta-cell dysfunction, and obesity with the development of diabetes are scarce in China.

Methods: In this prospective cohort study, we analyzed a nationwide sample of 97,828 adults aged 40 years or older, using data from the China Cardiometabolic Disease and Cancer Cohort Study, between 2011 and 2016. Glucose regulation status was defined according to the American Diabetes Association 2010 criteria. We examined the contributions of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) and beta-cell dysfunction (HOMA of beta-cell function [HOMA-B]) to diabetes risk, and evaluated the impact of obesity on these associations.

Findings: High HOMA-IR was associated with a greater risk of diabetes (hazard ratio [HR] per unit increase in z score, 2·17; 95% CI, 2·10-2·24) than low HOMA-B (HR per unit decrease in z score: HR, 1·91; 95% CI, 1·84-1·99). The HRs for diabetes were 1·84 (95% CI, 1·74-1·96) per unit increase in z score of HOMA-IR and 2·04 (95% CI, 1·87-2·22) per unit decrease in z score of HOMA-B among participants with normal weight; the corresponding HRs for diabetes were 2·01 (95% CI, 1·92-2·10) and 1·88 (95% CI, 1·78-1·97) among participants with obesity (P[interaction] =0·006). The stronger association of HOMA-IR with diabetes than that of HOMA-B was diminished after adjusting for BMI. These associations and interactions were similar for participants with normal glucose regulation or prediabetes.

Interpretation: Insulin resistance exhibited a stronger association with diabetes risk than beta-cell dysfunction; such association pattern was mainly modified by obesity.

Funding Statement: This work was funded by the Chinese Ministry of Finance. It is also supported by the 973 Foundation (grant 2015CB553601), National Key R&D Program of China (grants 2016YFC1305600, 2016YFC1305202, 2016YFC0901200, 2016YFC1304904, 2017YFC1310700, and 2018YFC1311800), National Natural Science Foundation of China (grants 81622011 and 81621061), Shanghai Pujiang Program (grant 18PJ1409600), and the Shanghai Municipal Education Commission–Gaofeng Clinical Medicine Grant Support from Shanghai Jiao Tong University School of Medicine (grant 20171901).

Declaration of Interests: Dr Ralph A. DeFronzo has been a member of the Advisory Board for Astra Zeneca, Novo Nordisk, Janssen, Boehringer-Ingelheim, Intarcia, and Elcelyx; a speaker for Novo Nordisk and Astra Zeneca; and an investigator for Boehringer-Ingelheim, Astra Zeneca, Janssen, and Merck. No other conflicts of interest relevant to this article were reported.

Ethics Approval Statement: This study was approved by the Medical Ethics Committee of Ruijin Hospital, Shanghai Jiao Tong University. All study participants provided written informed consent.

Keywords: Diabetes, insulin resistance, beta-cell dysfunction, obesity, nationwide investigation

Suggested Citation

Wang, Tiange and Lu, Jieli and Shi, Lixin and Chen, Gang and Xu, Min and Xu, Yu and Su, Qing and Mu, Yiming and Chen, Lulu and Hu, Ruying and Tang, Xulei and Yu, Xuefeng and Li, Mian and Zhao, Zhiyun and Chen, Yuhong and Yan, Li and Qin, Guijun and Wan, Qin and Dai, Meng and Zhang, Di and Gao, Zhengnan and Wang, Guixia and Shen, Feixia and Luo, Zuojie and Qin, Yingfen and Chen, Li and Huo, Yanan and Li, Qiang and Ye, Zhen and Zhang, Yinfei and Liu, Chao and Wang, Youmin and Wu, Shengli and Yang, Tao and Deng, Huacong and Zhao, Jiajun and Lai, Shenghan and Bi, Yufang and DeFronzo, Ralph A. and Wang, Weiqing and Ning, Guang and Group, 4C Study, Predominance of Insulin Resistance Over Beta-Cell Dysfunction as a Diabetes Risk Factor in Chinese Adults: Impact of Obesity in a Nationwide Prospective Study (August 15, 2019). Available at SSRN: https://ssrn.com/abstract=3437795 or http://dx.doi.org/10.2139/ssrn.3437795

Tiange Wang

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Shanghai
China

Jieli Lu

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Shanghai
China

Lixin Shi

Guizhou Medical University (Guiyang Medical University) - First Affiliated Hospital

Guiyang, Guizhou 550004
China

Gang Chen

Fujian Medical University - Fujian Provincial Hospital

Fuzhou
China

Min Xu

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases ( email )

Shanghai
China

Yu Xu

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Shanghai
China

Qing Su

Shanghai Jiao Tong University (SJTU) - Xinhua Hospital

Shanghai
China

Yiming Mu

Government of the People's Republic of China - Department of Endocrinology

Beijing, 100853
China

Lulu Chen

Huazhong University of Science and Technology (Formerly Tongi Medical University) - Union Hospital

China

Ruying Hu

Zhejiang Provincial Center for Disease Control and Prevention - Department of Non-Communicable Disease Control and Prevention ( email )

Hangzhou
China

Xulei Tang

Lanzhou University - Department of Endocrinology

Lanzhou, Gansu 730000
China

Xuefeng Yu

Huazhong University of Science and Technology (Formerly Tongi Medical University) - Tongji Hospital

1239 Siping Road
Shanghai, 200092
China

Mian Li

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Shanghai
China

Zhiyun Zhao

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Shanghai
China

Yuhong Chen

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Shanghai
China

Li Yan

Sun Yat-Sen University (SYSU) - Sun Yat-sen Memorial Hospital

107 Yanjiang W Rd
Guangzhou
China

Guijun Qin

Zhengzhou University - Division of Endocrinology ( email )

Qin Wan

Southwest Medical University - Affiliated Hospital

China

Meng Dai

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Shanghai
China

Di Zhang

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Shanghai
China

Zhengnan Gao

Dalian University - Dalian Municipal Central Hospital

Dalian
China

Guixia Wang

Jilin University (JLU) - Department of Endocrinology and Metabolism ( email )

China

Feixia Shen

Wenzhou Medical University - First Affiliated Hospital

Zhejiang Province
China

Zuojie Luo

Guangxi Medical University - First Affiliated Hospital

Guangxi, 530021
China

Yingfen Qin

Guangxi Medical University - Department of Endocrine

Nanning, Guangxi 530021
China

Li Chen

Shandong University - Qilu Hospital

Jinan
China

Yanan Huo

Nanchang University - Jiangxi Medical School

Nanchang, 330000
China

Qiang Li

Harbin Medical University - Second Affiliated Hospital

Harbin
China

Zhen Ye

Zhejiang Provincial Center for Disease Control and Prevention

Binjiang
Hangzhou, Zhejiang 310051
China

Yinfei Zhang

Central Hospital of Shanghai Jiading District

Shanghai
China

Chao Liu

Jiangsu Province Hospital on Integration of Chinese and Western Medicine

Nanjing
China

Youmin Wang

Anhui Medical University - Department of Endocrinology

Hefei, Anhui 230000
China

Shengli Wu

Government of the People's Republic of China - Karamay Municipal People's Hospital

Xinjiang
China

Tao Yang

Nanjing Medical University - Nanjing Medical Hospital

Nanjing
China

Huacong Deng

Chongqing Medical University - First Affiliated Hospital

China

Jiajun Zhao

Shandong First Medical University - Department of Endocrinology and Metabolism ( email )

China

Shandong Academy of Clinical Medicine - Institute of Endocrinology ( email )

China

Shandong Clinical Medical Center of Endocrinology and Metabolism ( email )

China

Shenghan Lai

Johns Hopkins University - School of Medicine

733 North Broadway
Suite G-49
Baltimore, MD 21205-2196
United States

Yufang Bi

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases

Shanghai
China

Ralph A. DeFronzo

University of Texas Health Science Center at San Antonio ( email )

315 N. San Saba
Suite 201
San Antonio, TX 78248
United States

Weiqing Wang

Shanghai Jiao Tong University (SJTU) - Shanghai Clinical Center for Endocrine and Metabolic Diseases ( email )

Shanghai
China

Guang Ning (Contact Author)

Shanghai Jiao Tong University (SJTU) - Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases ( email )

Shanghai
China

Shanghai Jiao Tong University (SJTU) - Shanghai Institute of Endocrine and Metabolic Diseases ( email )

No.999, Xiwang Road
Malu Town, Shanghai
China

Shanghai Jiao Tong University (SJTU) - Shanghai Clinical Center for Endocrine and Metabolic Diseases ( email )

Shanghai
China

No contact information is available for 4C Study Group

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