1] Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea [2] Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.
Am J Gastroenterol. 2013 Dec;108(12):1861-8. doi: 10.1038/ajg.2013.349. Epub 2013 Oct 8.
No study has evaluated an association between non-alcoholic fatty liver disease (NAFLD) severity and the incidence of diabetes. We examined whether NAFLD and its severity-using the NAFLD fibrosis score (NFS)-predict the development of diabetes.
A cross-sectional study was performed in 43,166 apparently healthy Koreans aged 30-59 years, who underwent a health checkup in 2005 and 2006. Of these, 38,291 subjects without diabetes were followed annually or biennially until December 2011 for the cohort study. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or other identifiable causes. The NFS was used to categorize the severity of fibrosis. Diabetes was defined as fasting serum glucose ≥126 mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or medication use for diabetes.
During 175,996 person-years of follow-up, 2,025 participants developed diabetes. An increase across NAFLD categories was positively associated with an increased risk of diabetes in both the cross-sectional and cohort studies in a dose-response manner (P-trend <0.001). In multivariate-adjusted models, the hazard ratios (95% confidence intervals) for diabetes comparing NAFLD with low NFS and NAFLD with intermediate or high NFS vs. no NAFLD were 2.00 (1.79-2.24) and 4.74 (3.67-6.13), respectively. This association remained significant even in subjects with fasting glucose <100 mg/dl and subjects with HbA1c <5.8%.
In this cohort study of a healthy Korean population, NAFLD and its severity using NFS were independently and strongly associated with increased incidence of diabetes in men and women-even with a euglycemic range of glucose and HbA1c.
目前尚无研究评估非酒精性脂肪性肝病（NAFLD）严重程度与糖尿病发病之间的关系。本研究旨在探讨 NAFLD 及其严重程度（采用 NAFLD 纤维化评分[NFS]）是否可预测糖尿病的发生。
本研究为横断面研究，纳入了 2005 年至 2006 年期间于韩国接受健康体检的 43166 名 30-59 岁的貌似健康人群。其中，38291 名无糖尿病的受试者在随访期间每年或每 2 年接受一次随访，直至 2011 年 12 月进行队列研究。NAFLD 通过超声检查在无过量饮酒或其他可识别病因的情况下定义为肝脂肪变性。采用 NFS 对纤维化严重程度进行分类。糖尿病的定义为空腹血糖≥126mg/dl、糖化血红蛋白（HbA1c）≥6.5%或使用降糖药物。
在 175996 人年的随访期间，2025 名受试者发生了糖尿病。在横断面和队列研究中，NAFLD 各分类与糖尿病风险呈正相关，且呈剂量-反应关系（趋势 P<0.001）。在校正多变量模型后，与无 NAFLD 相比，NAFLD 伴低 NFS 和 NAFLD 伴中/高 NFS 患者发生糖尿病的风险比（95%置信区间）分别为 2.00（1.79-2.24）和 4.74（3.67-6.13）。即使在空腹血糖<100mg/dl 和 HbA1c<5.8%的受试者中，这种相关性仍然显著。
在这项针对韩国健康人群的队列研究中，NAFLD 及其严重程度（采用 NFS）与男性和女性糖尿病的发生率增加独立且密切相关，即使在血糖和 HbA1c 处于正常范围时也是如此。
