Abstract
BACKGROUND: We sought to investigate the association between biological age (BA) acceleration and mortality among adults with diabetes or prediabetes and to assess whether physical activity mediates this association. METHODS: We included 7,337 participants with diabetes or prediabetes from the 1999-2018 National Health and Nutrition Examination Survey. BA was estimated using the Klemera-Doubal method (KDM). BA acceleration was defined as the residual difference between the estimated BA and chronological age. Cox proportional hazards models were used to examine the association between KDM-BA acceleration and mortality. The mediating effect of physical activity were evaluated to investigate the potential mechanism of the associations between BA acceleration and mortality. RESULTS: Over a median follow-up period of 94 months, 1,445 deaths occurred. Participants in the high tertile of KDM-BA acceleration had a 35% higher risk of all-cause mortality compared to those in the low tertile (HR = 1.35, 95% CI: 1.18-1.54, P < 0.0001). Participants engaging in ≥ 600 MET-minutes/week of physical activity had a lower risk of all-cause mortality compared to those with < 600 (HR = 0.86, 95% CI: 0.77-0.95, P = 0.0047). Mediation analysis indicated that physical activity accounted for 17.53% (P < 0.0001) of the association between KDM-BA acceleration and all-cause mortality. Similar patterns were observed for cardiovascular mortality. CONCLUSION: Elevated BA acceleration is associated with an increased risk of mortality in adults with diabetes or prediabetes. Higher levels of physical activity are linked to reduced mortality risk and partially mediate the relationship between BA acceleration and mortality.