30-Year Cardiovascular Disease in Type 1 Diabetes: Risk and Risk Factors Differ by Long-Term Patterns of Glycemic Control

Objective: We hypothesized that there is heterogeneity in long-term patterns of glycemic control with respect to cardiovascular disease (CVD) development in type 1 diabetes and that risk factors for CVD differ by glycemic control pattern. Thus, we estimated associations between data-derived latent HbA1c trajectories and 30-year CVD risk in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood-onset (<17 years old) type 1 diabetes.

Research Design and Methods: Participants (n=536 with ≥2 HbA1c measurements [median 6] and CVD-free at baseline; mean age 27 and diabetes duration 18 years) were followed from 1986-88 to 2016-18 to ascertain CVD incidence (CVD death, myocardial infarction, stroke, coronary revascularization or blockage ≥50%, ischemic ECG, or angina). Latent HbA1c trajectories and their association with time-to-CVD incidence were simultaneously assessed using Joint Latent Class Mixed Models.

Results: Two HbA1c trajectories with respect to differential CVD risk were identified: Low (HbA1c ~8% [64 mmol/mol] and improving over follow-up, 76% of cohort) and High (HbA1c ~10% [86 mmol/mol] and stable, 24%). Overall, 30-year CVD incidence was 47.4% (n=253); MACE incidence 31.0% (n=176). High HbA1c was associated with 3-fold increased CVD risk versus Low HbA1c. Both groups had similar age and diabetes duration. Non-HDLc and estimated glomerular filtration rate were associated with CVD risk only in Low HbA1c; albumin excretion rate was associated with CVD risk only in High HbA1c.

Conclusions: These risk factor differences suggest that pathways to CVD may differ by glycemic control, potentially resulting in important implications for prognosis in type 1 diabetes.