超声定义的脂肪肝与从临床前肥胖进展为临床肥胖的风险：一项前瞻性队列研究

文献信息

中文摘要

背景： 根据2025年发表在《柳叶刀糖尿病与内分泌学》上的国际共识，肥胖可被概念化为一种具有两个阶段的进展性疾病：临床前肥胖，其特征为脂肪过多但无已确立的器官功能障碍；以及临床肥胖，定义为存在肥胖相关器官损害。然而，从临床前肥胖向临床肥胖转变的决定因素仍知之甚少。脂肪肝是代谢功能障碍的常见表现，可能代表这一进展的早期指标。
方法： 我们分析了开滦研究中18,955名基线时患有临床前肥胖但无临床肥胖的成年人。脂肪肝通过腹部超声诊断，并分为轻度或中重度。临床肥胖定义为随访期间出现至少一种肥胖相关器官功能障碍。在多变量调整后，使用加权Cox回归估计基线脂肪肝与 incident 临床肥胖之间的平均关联，同时使用带时变系数的扩展Cox模型评估随访期间关联的变化。
结果： 在中位随访7.8年期间，11,463名参与者发生了临床肥胖。超声定义的脂肪肝与进展为临床肥胖的风险增加独立相关（完全调整HR：1.59，95% CI：1.50-1.68），并呈严重程度依赖性梯度（轻度：HR 1.55，95% CI：1.45-1.65；中重度：HR 1.70，95% CI：1.59-1.82）。患有中重度脂肪肝的女性风险最高（HR：1.77，95% CI：1.56-2.01）。敏感性分析结果一致。高血压、阻塞性睡眠呼吸暂停综合征和高血糖-血脂异常综合征是导致临床肥胖的最常见器官功能障碍。
结论： 超声定义的脂肪肝与从临床前肥胖进展为临床肥胖的风险显著增加相关。这些发现提示，超声定义的脂肪肝可能有助于识别进展为临床肥胖风险增加的临床前肥胖个体，并可能支持有针对性的代谢监测。

英文摘要

BACKGROUND: According to the 2025 international consensus published in The Lancet Diabetes & Endocrinology, obesity can be conceptualized as a progressive disease with two stages: preclinical obesity, characterized by excess adiposity without established organ dysfunction, and clinical obesity, defined by the presence of obesity-related organ damage. However, determinants of the transition from preclinical to clinical obesity remain poorly understood. Fatty liver, a common manifestation of metabolic dysfunction, may represent an early indicator of this progression.
METHODS: We analyzed 18,955 adults with preclinical obesity but without clinical obesity at baseline from the Kailuan Study. Fatty liver was diagnosed by abdominal ultrasound and categorized as mild or moderate-to-severe. Clinical obesity was defined as the development of at least one obesity-related organ dysfunction during follow-up. Weighted Cox regression was used to estimate the average association between baseline fatty liver and incident clinical obesity after multivariable adjustment, while extend Cox models with time-varying coefficients were used to evaluate changes in the association over follow-up.
RESULTS: During a median follow-up of 7.8 years, 11,463 participants developed clinical obesity. Ultrasound-defined fatty liver was independently associated with an increased risk of progression to clinical obesity (fully adjusted HR: 1.59, 95% CI: 1.50-1.68), with a severity-dependent gradient (mild: HR 1.55, 95% CI: 1.45-1.65; moderate-to-severe: HR 1.70, 95% CI: 1.59-1.82). Women with moderate-to-severe fatty liver had the highest risk (HR: 1.77, 95% CI: 1.56-2.01). Results were consistent in sensitivity analyses. Hypertension, obstructive sleep apnea syndrome, and hyperglycemia-dyslipidemia syndrome were the most common organ dysfunctions contributing to clinical obesity.
CONCLUSIONS: Ultrasound-defined fatty liver is associated with a significantly increased risk of progressing from preclinical to clinical obesity. These findings suggest that ultrasound-defined fatty liver may help identify individuals with preclinical obesity who are at increased risk of progressing to clinical obesity and may support targeted metabolic surveillance.