All-Cause Mortality Differentials by Diabetes Status and Serum Neurofilament Light-Chain Levels in US General Adults

Abstract

Abstract Context Neurofilament light chains (sNFLs) increase in patients with diabetes (DM) and are associated with death. Objective This work aimed to examine whether sNFL mediates associations of DM with all-cause mortality and the extent of interaction or joint relations of sNFL and DM with mortality. Methods This population-based cohort study was conducted using the 2013 to 2014 cycle of the National Health and Nutrition Examination Survey. A total of 2071 adults aged 20 to 75 years with sNFL measurements were included. sNFL was lg-transformed (LgNfl). Participants were included whose LgNfl was higher than 1.48 pg/mL or who were diagnosed with DM. All-cause mortality was the primary outcome obtained through linkage to registries. Results During a median follow-up of 6.1years, 85 participants died. Incidence rates (per 1000 person-years [95% CI]) of all-cause mortality were 27.78 (19.98∼35.58) in adults with LgNfl greater than 1.48 pg/mL and DM, 9.01 (1.99∼16.03) in adults with LgNfl greater than 1.48 pg/mL but no DM, 3.07 (1.01∼5.13) in adults with DM and LgNfl less than or equal to 1.48 pg/mL, and 2.21 (1.15∼3.27) in adults without DM and LgNfl less than or equal to 1.48 pg/mL. Significant interaction but not mediation was observed between LgNfl and DM. Compared with adults without DM and LgNfl less than or equal to 1.48 pg/mL, those with DM and LgNfl greater than 1.48 pg/mL had higher risks of all-cause mortality (hazard ratio; 95% CI, 7.06; 3.52∼14.16). Conclusion In general US adults with DM, elevated sNFLs were associated with higher all-cause mortality specifically, supporting an important role of sNFLs in predicting health outcome in individuals with DM.