One in three adults with ‘preclinical obesity’ progressed within five years

A large US cohort study has provided the first estimate of how often adults classified with “preclinical obesity” progress to “clinical obesity” under a recently proposed diagnostic framework. Among 92,396 participants with preclinical obesity, the estimated cumulative incidence of clinical obesity reached 34.3% at five years.

Published August 21 in the *International Journal of Obesity*, the observational analysis addresses a central question raised by the Lancet Diabetes & Endocrinology Commission’s 2025 effort to distinguish excess body fat from illness caused by excess body fat: How frequently does the ostensibly preclinical state progress?

The answer matters for healthspan because clinical obesity, as defined by the framework, involves impaired organ function, reduced physical function or limitations in daily activities—not merely a particular body-mass index. Preventing or delaying that transition could mean preserving metabolic health, mobility and independence. The new study, however, did not test a preventive intervention.

How the categories were applied

Researchers analyzed 319,815 participants in the National Institutes of Health’s All of Us Research Program. Obesity was defined by either a body-mass index of at least 40 or by meeting at least two of four thresholds covering BMI, waist circumference, waist-to-hip ratio and waist-to-height ratio.

Participants with excess adiposity but preserved self-reported physical function and no qualifying obesity-related condition were classified as having preclinical obesity. Those with related functional impairment or illness were classified as having clinical obesity. The primary endpoint was a transition to clinical obesity through the new onset of a qualifying condition during follow-up.

At baseline, 28.9% of the full cohort had preclinical obesity and 40.0% had clinical obesity. Among the 92,396 people in the preclinical group, 24,057—or 26.0%—transitioned during a median follow-up of 2.9 years. Estimated cumulative incidence was 12.7% after one year, 25.7% after three years and 34.3% after five years.

Risk markers, not proven causes

Older age, higher hemoglobin A1C, higher BMI, larger waist-related measurements and poorer self-rated health were independently associated with a greater likelihood of transition in adjusted models. Insurance coverage was also associated with progression.

Those relationships are predictive rather than causal. Higher A1C and central adiposity may identify participants already closer to metabolic dysfunction, while the insurance finding may partly reflect greater access to diagnosis and documentation. The study cannot show that changing any single measured factor would prevent clinical obesity.

The results nevertheless suggest that the preclinical category is not uniformly low risk. It includes people with substantially different prospects, supporting the Commission’s description of preclinical obesity as a heterogeneous state rather than an inevitable early stage of disease.

Why implementation remains unsettled

Several limitations separate this analysis from routine diagnosis. The researchers operationalized the Commission framework using available All of Us measurements, self-reported function and recorded health conditions. That is not equivalent to a comprehensive clinical assessment establishing that organ dysfunction was directly caused by excess adiposity.

All of Us is also a volunteer research cohort rather than a nationally representative sample. Clinical conditions may be detected unevenly, and residual confounding remains possible despite statistical adjustment. The findings have not yet been independently replicated under the same classification system.

For clinicians and health systems, the practical message is therefore about risk stratification, not an automatic treatment threshold. The study supplies an initial estimate of progression and identifies variables that may help design prospective validation studies. It does not determine which people with preclinical obesity benefit from medication, surgery or other interventions, nor does it replace individualized assessment of metabolic health, physical function and competing risks.