Nature study validates clinical and preclinical obesity framework across four global cohorts

A study published in Nature on 11 November 2026 validates a diagnostic framework proposed by a 2025 Lancet Commission that distinguishes clinical obesity from preclinical obesity. The research, led by An Pan and colleagues, used data from 844,108 adults across four cohorts: the Kailuan Study in China (137,795 participants), the UK Biobank (436,203), the All of Us Research Program in the USA (218,841) and the SIDIAP database in Spain (51,269).

Classification changes when waist measures are added

The Lancet Commission framework recommends supplementing body mass index (BMI) with waist circumference (WC) and waist-to-height ratio (WHtR) to confirm obesity status. The study found that BMI alone both overestimated and underestimated obesity across all four cohorts. The proportions classified as obese by BMI but without elevated WC or WHtR were 3.1% in the Kailuan Study, 1.9% in the UK Biobank, 1.9% in the All of Us Research Program and 1.2% in the SIDIAP database. Meanwhile, 6.6%, 5.2%, 7.5% and 8.6% of individuals with BMI-defined overweight met both WC and WHtR criteria for obesity-level adiposity in those same cohorts.

Using the combined anthropometric definition of obesity (CAD-obesity), overall obesity prevalence increased from 17.8% to 21.3% in the Kailuan Study, 24.0% to 27.3% in the UK Biobank, 42.5% to 48.1% in the All of Us Research Program and 18.7% to 26.1% in the SIDIAP database. Overall, CAD-obesity yielded a net increase in obesity prevalence of 3.5% in China, 3.3% in the UK, 5.6% in the USA and 7.4% in Spain.

Clinical and preclinical obesity distribution

Clinical obesity was defined as CAD-obesity accompanied by at least one of 18 adult diagnostic criteria specified by the Lancet Commission, representing organ dysfunction or functional impairment across cardiovascular, respiratory, metabolic, hepatic, renal, neurological, musculoskeletal, reproductive, urological and lymphatic systems, together with limitations in daily activities. The researchers applied an attributable fraction approach to estimate the proportion of organ dysfunction plausibly attributable to obesity.

AF-adjusted clinical obesity accounted for 26.3% of total obesity in the Kailuan Study, 30.5% in the UK Biobank, 22.7% in the All of Us Research Program and 31.3% in the SIDIAP database. The overall population prevalence of AF-adjusted clinical obesity was 5.6% in the Kailuan Study, 8.3% in the UK Biobank, 10.9% in the All of Us Research Program and 8.2% in the SIDIAP database.

Ten-year stability and mortality risk

Among individuals with preclinical obesity at baseline, the AF-adjusted 10-year incidence of clinical obesity was 21.2% in the Kailuan Study, 8.7% in the UK Biobank and 22.6% in the SIDIAP database. Because of shorter follow-up, the All of Us Research Program showed an AF-adjusted 4-year incidence of 8.5%. The authors state that approximately 70–90% of individuals with preclinical obesity remained stable over a decade.

Mortality analyses excluded the All of Us cohort because of limited follow-up. Median follow-up was 15.3 years in the Kailuan Study (17,642 deaths), 13.8 years in the UK Biobank (31,812 deaths) and 11.2 years in the SIDIAP database (2,338 deaths). Compared with individuals with no overweight or obesity, participants with BMI-defined overweight or obesity but without CAD-obesity had a lower all-cause mortality risk (pooled HR 0.88 [95% CI: 0.86–0.90] and 0.93 [0.86–0.99], respectively). Individuals with CAD-obesity had a higher mortality risk (pooled HR 1.06 [1.03–1.10] and 1.07 [1.05–1.10], respectively).

Clinical obesity was associated with substantially higher all-cause mortality (hazard ratio 1.69, 95% confidence interval 1.64–1.73), whereas preclinical obesity conferred only modest risk (1.19, 1.14–1.24). Increased mortality risk was associated with the combined anthropometric definition of obesity, but not with BMI-only obesity.

Why it matters

The findings support the global adoption of the Lancet Commission diagnostic framework to improve obesity care and policy. The authors write that the absence of a clinically grounded definition has impeded recognition of obesity as a distinct disease, contributing to gaps in care, inconsistent prevention, misallocated resources and persistent stigma.

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Sources

• nature.com: Validation of clinical and preclinical obesity across global cohorts | Nature

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