Prediabetes Linked to Higher Mortality in Younger Adults: JAMA
Researchers have found in a cohort study that prediabetes was significantly associated with increased mortality only among adults aged 20-54 years, possibly due to underlying metabolic or behavioral risk factors. Previous research on this link has shown conflicting results. The study was published in JAMA Network by Obinna E. and colleagues.
Prediabetes is generally accepted to be a risk factor for type 2 diabetes and is also associated with cardiovascular disease and increased risk of all-cause and cause-specific mortality. The contribution of demographic, lifestyle, and comorbidity factors in this relationship has not been well understood. This study demonstrates that controlling for these factors, the mortality risk remains significant only among young adults—laying emphasis on early intervention among young adults.
According to STROBE guidelines, this retrospective cohort study employed the data from NHANES linked to the National Death Index mortality records. The sample consisted of 38,093 adults aged 20 years and older who completed interviews and physical examinations between 2005 and 2018 and had valid mortality follow-up information.
Prediabetes was self-reported or defined as an HbA1c of 5.7% to 6.4%. Participants were sorted by demographics, lifestyle characteristics, and comorbidities. Race and ethnicity were reported by the participants and categorized as non-Hispanic Black, non-Hispanic White, or other.
Three increasingly adjusted Cox proportional hazards models were employed:
• Demographics only
• Demographics + lifestyle factors
• Demographics + lifestyle factors + comorbidities
Analyses were weighted to be representative of the U.S. adult population, and statistical significance was set at P < .05.
Results
• Of the 38,093 participants, 9,971 (26.2%) corresponding to more than 51 million U.S. adults had prediabetes. They were predominantly female and aged 20–54 years.
• Unadjusted association: Prediabetes was associated with an increased risk of mortality by 58% (HR = 1.58; 95% CI: 1.43–1.74).
• Fully adjusted model: After controlling for demographics, lifestyle, and comorbidities, the relationship was no longer statistically significant (HR = 1.04; 95% CI: 0.92–1.18).
• Age interaction: Hazard for mortality was still present only among adults 20–54 years old (HR = 1.64; 95% CI: 1.24–2.17).
• Race/ethnicity interaction: No statistically significant racial or ethnic differences in mortality were found.
This large US population-based cohort study demonstrates that prediabetes is only associated with increased risk of death in younger adults aged 20–54 years after adjusting for demographics, lifestyle, and comorbidities. In older adults, the excess risk of death seems to be accounted for by other comorbid conditions and not prediabetes. These findings emphasize the crucial need for early intervention among younger adults with prediabetes to avoid progression to diabetes and premature mortality.
Reference:
Ekwunife O, Wang X, Fraser R, et al. Demographics, Lifestyle, Comorbidities, Prediabetes, and Mortality. JAMA Netw Open. 2025;8(8):e2526219. doi:10.1001/jamanetworkopen.2025.26219
