Diabetes mellitus correlates with increased biological age as indicated by clinical biomarkers

Abstract

Chronological age (CA) is determined by time of birth, whereas biological age (BA) is based on changes on a cellular level and strongly correlates with morbidity, mortality, and longevity. Type 2 diabetes (T2D) associates with increased morbidity and mortality; thus, we hypothesized that BA would be increased and calculated it from biomarkers collected at routine clinical visits. Deidentified data was obtained from three cohorts of patients (20–80 years old)—T2D, type 1 diabetes (T1D), and prediabetes—and compared to gender- and age-matched non-diabetics. Eight clinical biomarkers that correlated with CA in people without diabetes were used to calculate BA using the Klemera and Doubal method 1 (KDM1) and multiple linear regression (MLR). The phenotypic age (PhAge) formula was used with its predetermined biomarkers. BA of people with T2D was, on average, 12.02 years higher than people without diabetes (p < 0.0001), while BA in T1D was 16.32 years higher (p < 0.0001). Results were corroborated using MLR and PhAge. The biomarkers with the strongest correlation to increased BA in T2D using KDM were A1c (R2 = 0.23, p < 0.0001) and systolic blood pressure (R2 = 0.21, p < 0.0001). BMI had a positive correlation to BA in non-diabetes subjects but disappeared in those with diabetes. Mortality data using the ACCORD trial was used to validate our results and showed a significant correlation between higher BA and decreased survival. In conclusion, BA is increased in people with diabetes, irrespective of pathophysiology, and to a lesser extent in prediabetes.