Biological ageing and the risks of all-cause and cause-specific mortality among people with diabetes: a prospective cohort study

Abstract

Background: The aetiology of diabetes is complex with limited treatment strategies. Growing animal studies have shown that targeted antiageing can improve the outcomes of diabetes. However, population evidence is limited. This study aims to evaluate the associations of biological ageing with all-cause and cause-specific mortality among people with diabetes.

Methods: A total of 5278 people with diabetes from the National Health and Nutrition Examination Survey 1999-2014 were included. Biological ageing was measured from different perspectives, including phenotypic age, biological age, telomere length and klotho concentration. Phenotypic/biological age acceleration was the residual resulting from a linear model when regressing phenotypic/biological age on chronological age. Cox proportional hazards models were used to examine the relationships between ageing and all-cause, cardiovascular disease (CVD), and cancer mortality.

Results: Over median follow-up for 7.3 years, 1355 diabetics died. There was a positive and linear association of mortality with phenotypic age acceleration (HR_all-cause 1.04; HR_CVD 1.04; HR_cancer 1.04, p<0.001) and biological age acceleration (HR_all-cause 1.03; HR_CVD 1.04; HR_cancer 1.03, p<0.001). Telomere length was inversely associated with all-cause mortality (tertile (T)3 vs T1: HR 0.67, p<0.05). The concentration of klotho had a U-shaped relationship with mortality (T2 vs T1: HR_all-cause 0.62; HR_CVD 0.48; HR_cancer 0.47, p<0.05). Further, stratified analysis by age and sex found that the associations of ageing-related markers with mortality were more significant in the aged and female subgroup.

Conclusions: Biological ageing was positively associated with mortality among people with diabetes, indicating therapies targeting antiageing could be encouraged to halt the progression of diabetes.

Keywords: aging; death; diabetes mellitus.