【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 94952 participants (31517 men and 63435 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 (P interaction =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.
【中文摘要】
背景：中國糖尿病的有效防治，亟待找到近年來糖尿病持續攀升的根本原因。2型糖尿病的主要病理特徵是胰島素抵抗和β細胞功能障礙。本研究旨在中國人群中分析胰島素抵抗、β細胞功能障礙及二者的交互作用對2型糖尿病發生風險的作用，並探討肥胖對糖尿病病因的影響。
方法：研究人群來自中國心臟代謝疾病和癌症隊列研究（China Cardiometabolic Disease and Cancer Cohort Study, 4C），該研究是一項全國多中心前瞻性隊列研究。研究採用穩態模型評估的胰島素抵抗指數（HOMA-IR）和β細胞功能指數（HOMA-β）。
結果：該研究共納入94 952名基線無糖尿病的40歲及以上研究對象（31 517名男性和63 435名女性）。在340 443人年的隨訪中，新發糖尿病患者共6 484名（6.8%）。將HOMA-IR和HOMA-β按照性別特異性四分位後，與低HOMA-β（HOMA-β下四分位對上四分位：HR＝4.08，95%CI 3.72～4.48；Z值每下降一個單位：HR＝1.92，95%CI 1.85～2.00）相比，高HOMA-IR（HOMA-IR上四分位對下四分位：HR＝6.70，95%CI 6.08～7.39；Z值每上升一個單位：HR＝2.17，95%CI 2.10～2.24）與更高的糖尿病風險顯著相關。人群歸因風險（population-attributable risk percentage, PAR%）分析顯示，總研究對象中約24.4%（95%CI 23.6～25.2）的糖尿病發生風險歸因於胰島素抵抗，12.4%（95%CI 11.2～13.7）歸因於β細胞功能障礙。高HOMA-IR較低HOMA-β與更高的糖尿病風險顯著相關的模式在肥胖研究對象中更為顯著（P=0.0091），該結論在正常糖耐量及糖尿病前期研究對象中保持一致。
結論：相比β細胞功能障礙，肥胖影響的胰島素抵抗是中國糖尿病更重要的危險因素，提示肥胖是影響中國人胰島素抵抗與糖尿病之間關聯的主要原因，為重新審視中國糖尿病病因特點提供了科學證據。