Tiange Wang1, Jieli Lu1, Lixin Shi2, Gang Chen3, Min Xu1, Yu Xu1, Qing Su4, Yiming Mu5, Lulu Chen6, Ruying Hu7, Xulei Tang8, Xuefeng Yu9, Mian Li1, Zhiyun Zhao1, Yuhong Chen1, Li Yan10, Guijun Qin11, Qin Wan12, Meng Dai1, Di Zhang1, Zhengnan Gao13, Guixia Wang14, Feixia Shen15, Zuojie Luo16, Yingfen Qin16, Li Chen17, Yanan Huo18, Qiang Li19, Zhen Ye7, Yinfei Zhang20, Chao Liu21, Youmin Wang22, Shengli Wu23, Tao Yang24, Huacong Deng25, Jiajun Zhao26, Shenghan Lai27, Yufang Bi1, Ralph A DeFronzo28, Weiqing Wang29, Guang Ning1. 1. Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 2. Affiliated Hospital of Guiyang Medical College, Guiyang, China. 3. Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China. 4. Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. 5. Chinese People's Liberation Army General Hospital, Beijing, China. 6. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 7. Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China. 8. The First Hospital of Lanzhou University, Lanzhou, China. 9. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 10. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. 11. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 12. The Affiliated Hospital of Southwest Medical University, Luzhou, China. 13. Dalian Municipal Central Hospital, Dalian, China. 14. The First Hospital of Jilin University, Changchun, China. 15. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 16. The First Affiliated Hospital of Guangxi Medical University, Nanning, China. 17. Qilu Hospital of Shandong University, Jinan, China. 18. Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China. 19. The Second Affiliated Hospital of Harbin Medical University, Harbin, China. 20. Central Hospital of Shanghai Jiading District, Shanghai, China. 21. Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China. 22. The First Affiliated Hospital of Anhui Medical University, Hefei, China. 23. Karamay Municipal People's Hospital, Xinjiang, China. 24. The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 25. The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 26. Shandong Provincial Hospital, Shandong First Medical University, Jinan, China. 27. Johns Hopkins University School of Medicine, Baltimore, MD, USA. 28. Diabetes Division, UT Health San Antonio, San Antonio, TX, USA. 29. Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: wqingw61@163.com.
Abstract
BACKGROUND: National investigations on the interaction of insulin resistance, β-cell dysfunction, and obesity with the development of diabetes are scarce in China. We aimed to investigate the individual and joint associations of insulin resistance and β-cell dysfunction with incident diabetes, and to examine the modifying effect of BMI and waist circumference on these associations among adults with normal glucose tolerance and with prediabetes. METHODS: In this nationwide, population-based, prospective cohort study, we analysed data from the China Cardiometabolic Disease and Cancer Cohort Study, which recruited adults aged 40 years or older during 2011-12 (baseline) and invited participants to attend follow-up visits in 2014-16. Patients with diabetes at baseline, missing data for baseline measures of glucose tolerance status, missing data for baseline homoeostasis model assessment (HOMA) indexes, missing data for baseline covariates, and missing data for measures of glucose tolerance status at follow-up visits were excluded. At baseline and follow-up visits, a comprehensive set of questionnaires, clinical measurements, oral glucose tolerance tests, and laboratory examinations were carried out following standardised protocols. Glucose tolerance status and prediabetes were defined according to the American Diabetes Association 2010 criteria. In the main analysis, we examined the contributions of insulin resistance (HOMA of insulin resistance [HOMA-IR]) and β-cell dysfunction (HOMA of β-cell function [HOMA-B]) to diabetes risk, and evaluated the impact of obesity on these associations. FINDINGS: 94 952 participants (31 517 men and 63 435 women) were included in the analysis. High HOMA-IR was associated with a greater hazard of diabetes (quartile 4 vs 1: hazard ratio [HR] 6·70, 95% CI 6·08-7·39; per unit increase in Z score: HR 2·17, 95% CI 2·10-2·24) than low HOMA-B (quartile 1 vs 4: 4·08, 3·72-4·48; per unit decrease in Z score: 1·92, 1·85-2·00). Approximately 24·4% (95% CI 23·6-25·2) of the incident diabetes could be attributed to insulin resistance and 12·4% (11·2-13·7) could be attributed to β-cell dysfunction. The HRs for diabetes were 1·83 (95% CI 1·72-1·95) per unit increase in Z score of HOMA-IR and 2·03 (1·86-2·21) per unit decrease in Z score of HOMA-B among participants with normal weight; the corresponding HRs for diabetes were 2·02 (1·93-2·11) and 1·88 (1·79-1·98) among participants with obesity (pinteraction=0·0091). These associations and interactions were similar for participants with normal glucose tolerance or prediabetes. INTERPRETATION: Insulin resistance shows a stronger association with incident diabetes than does β-cell dysfunction in Chinese adults, and this association pattern was more prominent among adults with obesity. Given the limitations of HOMA indexes as surrogate measures of insulin resistance and β-cell dysfunction, these findings should be interpreted with caution. FUNDING: National Natural Science Foundation of China.
BACKGROUND: National investigations on the interaction of insulin resistance, β-cell dysfunction, and obesity with the development of diabetes are scarce in China. We aimed to investigate the individual and joint associations of insulin resistance and β-cell dysfunction with incident diabetes, and to examine the modifying effect of BMI and waist circumference on these associations among adults with normal glucose tolerance and with prediabetes. METHODS: In this nationwide, population-based, prospective cohort study, we analysed data from the China Cardiometabolic Disease and Cancer Cohort Study, which recruited adults aged 40 years or older during 2011-12 (baseline) and invited participants to attend follow-up visits in 2014-16. Patients with diabetes at baseline, missing data for baseline measures of glucose tolerance status, missing data for baseline homoeostasis model assessment (HOMA) indexes, missing data for baseline covariates, and missing data for measures of glucose tolerance status at follow-up visits were excluded. At baseline and follow-up visits, a comprehensive set of questionnaires, clinical measurements, oral glucose tolerance tests, and laboratory examinations were carried out following standardised protocols. Glucose tolerance status and prediabetes were defined according to the American Diabetes Association 2010 criteria. In the main analysis, we examined the contributions of insulin resistance (HOMA of insulin resistance [HOMA-IR]) and β-cell dysfunction (HOMA of β-cell function [HOMA-B]) to diabetes risk, and evaluated the impact of obesity on these associations. FINDINGS: 94 952 participants (31 517 men and 63 435 women) were included in the analysis. High HOMA-IR was associated with a greater hazard of diabetes (quartile 4 vs 1: hazard ratio [HR] 6·70, 95% CI 6·08-7·39; per unit increase in Z score: HR 2·17, 95% CI 2·10-2·24) than low HOMA-B (quartile 1 vs 4: 4·08, 3·72-4·48; per unit decrease in Z score: 1·92, 1·85-2·00). Approximately 24·4% (95% CI 23·6-25·2) of the incident diabetes could be attributed to insulin resistance and 12·4% (11·2-13·7) could be attributed to β-cell dysfunction. The HRs for diabetes were 1·83 (95% CI 1·72-1·95) per unit increase in Z score of HOMA-IR and 2·03 (1·86-2·21) per unit decrease in Z score of HOMA-B among participants with normal weight; the corresponding HRs for diabetes were 2·02 (1·93-2·11) and 1·88 (1·79-1·98) among participants with obesity (pinteraction=0·0091). These associations and interactions were similar for participants with normal glucose tolerance or prediabetes. INTERPRETATION:Insulin resistance shows a stronger association with incident diabetes than does β-cell dysfunction in Chinese adults, and this association pattern was more prominent among adults with obesity. Given the limitations of HOMA indexes as surrogate measures of insulin resistance and β-cell dysfunction, these findings should be interpreted with caution. FUNDING: National Natural Science Foundation of China.
Authors: Qinying Zhao; Li Ding; Ying Yang; Jinhong Sun; Min Wang; Xin Li; Ming Liu Journal: Front Endocrinol (Lausanne) Date: 2022-06-20 Impact factor: 6.055
Authors: Riku Klén; Miikka-Juhani Honka; Jarna C Hannukainen; Ville Huovinen; Marco Bucci; Aino Latva-Rasku; Mikko S Venäläinen; Kari K Kalliokoski; Kirsi A Virtanen; Riikka Lautamäki; Patricia Iozzo; Laura L Elo; Pirjo Nuutila Journal: J Endocr Soc Date: 2020-03-11