Endocrine Abstracts

JOINT686

Introduction: The metabolic consequences of obesity in adulthood are well-documented. While some children living with obesity maintain a healthy metabolic profile, others develop complications persisting into adulthood. Conversely, healthy-weight children can also exhibit an unhealthy phenotype.

Objectives: To describe metabolic phenotype evolutions from childhood to early adulthood and identify modifiable childhood determinants of unhealthy evolutions.

Methods: The QUALITY cohort included 630 children aged 8–10 years at baseline(V1), all with at least one parent living with obesity. Participants were reassessed at 10–12 years(V2), 15–17 years(V3), and 24–26 years (V4). Biological markers, physical activity, body composition, and screen time were assessed at each visit. Metabolic phenotypes were categorized into four groups: normal-weight metabolically healthy (NWMH), normal-weight metabolically unhealthy (NWMU), metabolically healthy living with obesity (MHO), and metabolically unhealthy living with obesity (MUO), based on IDF criteria. Descriptive analyses and Markov modeling assessed phenotype evolution and transition probabilities at each visit. Multiple logistic regressions among metabolically healthy participants at V1 estimated associations between transition to metabolically unhealthy phenotypes at V4 and childhood determinants. Inverse Probability Weighting was applied to adjust for missing data.

Results: A total of 169 participants with phenotype data at all four visits were analyzed. The prevalence of unhealthy phenotypes (NWMU + MUO) increased from 31% at V1 to 57% at V4, with a 20% rise occurring between V2 and V3. MUO prevalence steadily increased, from 12% at V1 to 35% at V4. Markov modeling showed that NWMH and MUO were the most stable phenotypes, with a high probability (67% and 69%, respectively) of remaining stable to the next visit. Among metabolically healthy children at V1, regardless of baseline weight status, boys (OR=3. 63, 95%CI:2. 0-6. 7) and those with a higher % body fat at V1 (OR=1. 05, 95%CI:1. 02-1. 08) had higher odds of transitioning to an unhealthy phenotype at V4. Additionally, when examining changes in lifestyle habits from V1 to V2, every 10-minute increase in moderate-to-vigorous physical activity between V1 and V2 was associated with 29% (95%CI: 15-42%) lower odds of transitioning to an unhealthy phenotype at V4, after adjusting for baseline physical activity.

Conclusion: The proportion of unhealthy phenotypes nearly doubled over 16 years in this high-risk population, with puberty being a critical period for transition to an unhealthy phenotype. Early interventions, especially for boys, with an emphasis on reducing adiposity early in childhood and promoting sustained physical activity appear important to preventing the progression towards unhealthy phenotypes.