Research Article: Ultrasound-defined fatty liver and the risk of progression from preclinical to clinical obesity: a prospective cohort study
Abstract:
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.
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.
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.
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.
Introduction:
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…
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