Diabetes Complications and Comorbidities as Risk Factors for MACE in People With Type 2 Diabetes and Their Development Over Time: A Danish Registry‐Based Case–Control Study

Aim This study aimed to investigate the association between cardiovascular risk factors and major adverse cardiovascular events (MACE) in people with type 2 diabetes, while assessing potential changes over time. Methods Utilizing data from Danish registries, this study identified people with type 2 diabetes between 2002 and 2021 ( n = 372 328) and subdivided them into two 10‐year time periods: TP1: 2002–2011 and TP2: 2012–2021, and further categorized into cases and controls. Cases were defined as having suffered a first‐time three‐point MACE ( n TP1 = 12 713, n TP2 = 8981) and matched 1:1 with controls on age, sex, and type 2 diabetes duration. Exposures were preselected diabetes complications and comorbidities. Results Fewer were affected by MACE during TP2 compared to TP1 ( p < 0.001). Diabetes complications associated with MACE were nephropathy (OR TP1 = 1.54, 95% CI 1.30–1.83, OR TP2 = 1.47, 95% CI 1.20–1.79), neuropathy (OR TP1 = 2.02, 95% CI 1.84–2.21 OR TP2 = 1.58, 95% CI 1.44–1.73) and retinopathy (OR TP1 = 1.10, 95% CI 0.98–1.23, OR TP2 = 1.38, 95% CI 1.17–1.63). Comorbidities associated with MACE included hypertension (OR TP1 = 1.30, 95% CI 1.22–1.38 OR TP2 = 1.31, 95% CI 1.22–1.41), atrial flutter or fibrillation (OR TP1 = 1.46, 95% CI 1.35–1.58, OR TP2 = 1.37, 95% CI 1.26–1.50), heart failure (OR TP1 = 1.53, 95% CI 1.401.67‐, OR TP2 = 1.37, 95% CI 1.23–1.54) and hypercholesterolemia (OR TP1 = 1.13, 95% CI 1.07–1.20, OR TP2 = 1.02, 95% CI 0.96–1.10). Hypercholesterolemia ( p = 0.038) and neuropathy ( p = 0.038) exhibited a significant decrease in association with MACE between the time periods. Conclusions The prevalence of first‐time MACE decreased over time, despite a relatively stable prevalence of type 2 diabetes. Several diabetes‐related complications and comorbidities were significantly associated with MACE. The associations of neuropathy and hypercholesterolemia with MACE lessened over time, suggesting potential improvements in risk management or treatment strategies.