Cardio-cerebrovascular Outcomes in MODY, Type 1 Diabetes, and Type 2 Diabetes: A Prospective Cohort Study.

Abstract

The cardio-cerebrovascular events are severe complications of diabetes. We aim to compare the incident risk of cardio-cerebrovascular events in maturity onset diabetes of the young (MODY), type 1 diabetes, type 2 diabetes. Type 1 diabetes, type 2 diabetes and MODY were diagnosed by whole exome sequencing (WES). The primary endpoint was the occurrence of the first major adverse cardiovascular events (MACE), including acute myocardial infarction, heart failure, stroke, unstable angina pectoris and cardio-cerebrovascular related mortality. Cox proportional hazards models were applied and adjusted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the incident risk of MACE in type 1 diabetes, type 2 diabetes, MODY and MODY subgroups in comparison with people without diabetes (control group). Type 1 diabetes, type 2 diabetes and MODY accounted for 2.7%, 68.1% and 11.4% of 26198 diabetic participants from UK Biobank. During a median follow-up of 13 years, 1028 MACEs occurred in control group, contrasting with 70 events in type 1 diabetes patients (HR 2.15, 95% CI 1.69-2.74, p<0.05), 5020 events in type 2 diabetes patients (HR 7.02, 95% CI 6.56-7.51, p<0.05) and 717 events in MODY (HR 5.79, 95% CI 5.26-6.37, p<0.05). The hazard OF MACE in HNF1B-MODY was highest among MODY subgroups (HR 11.00, 95% CI 5.47-22.00, p=1.5e-11).. MODY diagnosed by genetic analysis represents higher prevalence than the clinical diagnosis in UK Biobank. The risk of incident cardio-cerebrovascular events in MODY ranks between type 1 diabetes and type 2 diabetes.