Does obesity independently influence mortality risk when accounting for systemic inflammation and hyperinsulinemia? A prospective population-representative cohort study published in Diabetes, Obesity and Metabolism evaluated the association of body mass index (BMI), C-reactive protein (CRP), and fasting insulin with all-cause mortality and incident non-communicable chronic disease (NCD).

The study included approximately 8,280 Canadian adults aged 18 years and older from the Canadian Health Measure Survey, with external validation in US and UK cohorts. At baseline, 24.4% had obesity (BMI ≥30 kg/m²), 56.5% had elevated CRP (>1 mg/L), and 36.6% had hyperinsulinemia (fasting insulin >75 pmol/L). Participants were followed for a median of 6.7 years; 3.1% died, and 7.4% developed an NCD, including 1.8% with cardiovascular disease.

After adjustment for age, sex, and smoking, CRP was positively associated with mortality (hazard ratio [HR] vs referent for 1st and 99th percentiles: 0.72 [95% CI 0.61-0.84] and 7.67 [95% CI 2.89-20.38]). Fasting insulin showed a similar pattern (0.88 [95% CI 0.78-0.99] and 3.22 [95% CI 1.12-9.29]). In contrast, BMI was negatively associated with mortality (HR for 1st and 95th percentiles: 1.45 [95% CI 1.11-1.88] and 0.46 [95% CI 0.22–0.97]), although the 99th percentile was not statistically significant (0.51 [95% CI 0.20–1.27]). All three exposures were mostly positively associated with incident NCD, with variation by disease type.

These findings indicate that after accounting for inflammation and hyperinsulinemia, higher BMI percentiles were associated with lower mortality risk but higher risk of developing chronic disease.