Premature Mortality in Type 2 Diabetes Mellitus Associated with Heart Failure and Chronic Kidney Disease: 20 Years of Real-World Data

Introduction: Type 2 diabetes mellitus (T2D) increases the risk of heart failure (HF) and chronic kidney disease (CKD). Nonetheless, evidence of cardiovascular (CV) prognosis is relatively scarce in young T2D patients. Purpose: To estimate the risk of all-cause death, CV death, and non-fatal major CV events (MACEs) in T2D patients younger than 65 years old. Methods: We designed a retrospective cohort study using incident cases of either T2D, HF, or CKD in the population aged 40-65 years, from 1st January 2000 to 31st December 2019. Each individual was followed for up to one year. The primary analysis consisted of survival analysis with Cox proportional hazards to compare one-year risk of all-cause death, CV death, and MACEs between T2D without HF or CKD (T2D), T2D with HF (T2D-HF), and T2D with CKD (T2D-CKD) groups. Results: A total of 14,986 incident adult diabetic patients from the last two decades in our institution were included with an average age at cohort inclusion of 55-58 years old. Glycemic control was similar among groups. The adjusted hazard ratio (HR) of one-year all-cause death was 2.77 (95% CI: 2.26-3.40) for T2D-HF and 3.09 (2.77-3.45) for T2D-CKD compared with the baseline T2D risk. The highest event rate (T2D-CKD) was 0.15 per person-year. The adjusted HR of one-year CV death was 2.75 (95% CI: 2.19-3.46) for T2D-CKD and 2.59 (1.72-3.91) for T2D-HF. The non-fatal MACE risk was significantly increased in T2D-HF or T2D-CKD compared with T2D (2.82 (CI95%: 2.34-3.41) for T2D-CKD vs. 1.90 (CI95%: 1.66-2.17) for T2D-CKD) with a 32% event rate in non-fatal MACEs. Conclusions: Coexistence of HF or CKD is associated with increased premature mortality as well as non-fatal CV events in T2D patients under 65 years old.