Aging and the risks of all-cause and cause-specific mortality among diabetics: a prospective cohort study

Abstract BackgroundAging is an important driver for age-related diseases and death, but the evidence regarding the effects of aging on diabetics is limited. This study aims to evaluate the associations of aging with all-cause and cause-specific mortality among diabetics.MethodsA total of 5,278 diabetics from the National Health and Nutrition Examination Survey 1999-2014 were included. The aging status was measured from different perspectives, including Phenotypic Age, Biological Age, telomere length, and Klotho concentration. Cox proportional hazards models were used to examine the relationships between aging and all-cause, cardiovascular disease (CVD), and cancer mortality. Mediation analysis was performed to elucidate the role of aging in associations of metformin with mortality.Results Over median follow-up for 7.3 years, 1,355 diabetics died. There was a positive and linear association of mortality with Phenotypic Age (hazard ratio (HR)all-cause 1.05, 95% confidence interval (CI) 1.05-1.06; HRCVD 1.05, 95%CI 1.04-1.07; HRcancer 1.05, 95%CI 1.04-1.07; all P<0.001) and Biological Age (HRall-cause 1.07, 95%CI 1.05-1.08; HRCVD 1.08, 95%CI 1.05-1.10; HRcancer 1.05, 95%CI 1.03-1.08; all P<0.001). Telomere length was inversely associated with all-cause mortality (tertile (T)3 vs. T1: HR 0.67, 95%CI 0.45-0.98; Ptrend=0.036). The concentration of Klotho had a U-shaped relationship with mortality (T2 vs. T1: HRall-cause 0.62, 95%CI 0.43-0.88; HRCVD 0.48, 95%CI 0.26-0.86; HRcancer 0.47 95%CI 0.25-0.88). Additionally, metformin users had a lower HR for mortality compared to those without use (HRall-cause 0.64, 95%CI 0.56-0.73; HRCVD 0.51, 95%CI 0.37-0.70; HRcancer 0.65, 95%CI 0.44-0.95; all P<0.001), which was partly mediated by Phenotypic Age and Biological Age. ConclusionsThese findings suggested aging was a noteworthy risk factor of mortality for diabetics and therapies targeting anti-aging could be encouraged to halt the progression of diabetes.