Chang Yoosoo, Jung Hyun-Suk, Cho Juhee, Zhang Yiyi, Yun Kyung Eun, Lazo Mariana, Pastor-Barriuso Roberto, Ahn Jiin, Kim Chan-Won, Rampal Sanjay, Cainzos-Achirica Miguel, Zhao Di, Chung Eun Cheol, Shin Hocheol, Guallar Eliseo, Ryu Seungho
Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Am J Gastroenterol. 2016 Aug;111(8):1133-40. doi: 10.1038/ajg.2016.178. Epub 2016 May 17.
The risk of nonalcoholic fatty liver disease (NAFLD) among obese individuals without obesity-related metabolic abnormalities, a condition referred to as metabolically healthy obese (MHO), is largely unexplored. Therefore, we examined the association between body mass index (BMI) categories and the development of NAFLD in a large cohort of metabolically healthy men and women.
A cohort study was conducted in 77,425 men and women free of NAFLD and metabolic abnormalities at baseline, who were followed-up annually or biennially for an average of 4.5 years. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. The presence of fatty liver was determined using ultrasound.
During 348,193.5 person-years of follow-up, 10,340 participants developed NAFLD (incidence rate, 29.7 per 1,000 person-years). The multivariable adjusted hazard ratios (95% confidence intervals) for incident NAFLD comparing overweight and obese with normal-weight participants were 2.15 (2.06-2.26) and 3.55 (3.37-3.74), respectively. In detailed dose-response analyses, increasing baseline BMI showed a strong and approximately linear relationship with the incidence of NAFLD, with no threshold at no risk. This association was present in both men and women, although it was stronger in women (P for interaction <0.001), and it was evident in all clinically relevant subgroups evaluated, including participants with low inflammation status.
In a large cohort of strictly defined metabolically healthy men and women, overweight and obesity were strongly and progressively associated with an increased incidence of NAFLD, suggesting that the obese phenotype per se, regardless of metabolic abnormalities, can increase the risk of NAFLD.
在无肥胖相关代谢异常的肥胖个体（即代谢健康肥胖，MHO）中，非酒精性脂肪性肝病（NAFLD）的风险在很大程度上尚未得到研究。因此，我们在一大群代谢健康的男性和女性中，研究了体重指数（BMI）类别与NAFLD发生之间的关联。
对77425名基线时无NAFLD和代谢异常的男性和女性进行了队列研究，他们每年或每两年随访一次，平均随访4.5年。代谢健康定义为无任何代谢综合征组分且胰岛素抵抗的稳态模型评估<2.5。使用超声确定脂肪肝的存在。
在348193.5人年的随访期间，10340名参与者发生了NAFLD（发病率为每1000人年29.7例）。与正常体重参与者相比，超重和肥胖参与者发生NAFLD的多变量调整风险比（95%置信区间）分别为2.15（2.06 - 2.26）和3.55（3.37 - 3.74）。在详细的剂量反应分析中，基线BMI升高与NAFLD发病率呈强烈且近似线性关系，无无风险阈值。这种关联在男性和女性中均存在，尽管在女性中更强（交互作用P<0.001），并且在所有评估的临床相关亚组中都很明显，包括炎症状态低的参与者。
在一大群严格定义的代谢健康的男性和女性中，超重和肥胖与NAFLD发病率的增加呈强烈且逐渐增加的关联，表明肥胖表型本身，无论有无代谢异常，均可增加NAFLD的风险。
