Effect of Glomerular Hyperfiltration on Incident Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus

Key Points Patients with type 2 diabetes mellitus who had glomerular hyperfiltration (GHF) were younger and had fewer comorbid metabolic disorders, despite poor glycemic control. The relationship between eGFR and incident cardiovascular disease showed an inverted J-shaped pattern, which was highest among low filtration, followed by GHF. GHF was associated with a higher risk of cardiovascular disease, particularly myocardial infarction and heart failure. Background The effects of glomerular hyperfiltration (GHF) on cardiovascular disease (CVD) risk in patients with type 2 diabetes mellitus were explored. Methods This retrospective cohort study enrolled 1,952,053 patients with type 2 diabetes mellitus from the Korean National Health Insurance Service database between 2015 and 2016. On the basis of age- and sex-specific eGFR percentiles, patients were classified into five groups: <5 (low filtration), 5–40, 40–60, 60–95, and >95 (GHF). Patients with incident CVD (myocardial infarction [MI], stroke, and hospitalization for heart failure) were followed up until December 2022. Results CVD occurred in 214,111 patients (11%). The incidence rates were 36.1, 20.8, 18.3, 18.7, and 19.3 per 1000 person-years for the eGFR groups, respectively. Low filtration (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.53 to 1.59) and GHF (HR, 1.13; 95% CI, 1.10 to 1.15) were associated with higher CVD risk adjusted for covariates than that of the eGFR 40–60 percentile, showing an inverted J-shaped relationship. GHF was associated with a higher risk of MI (HR, 1.06; 95% CI, 1.01 to 1.11) and heart failure (HR, 1.17; 95% CI, 1.14 to 1.20) and with a higher risk of stroke. eGFR was associated with CVD risk across subgroups of age, sex, obesity, hypertension, and dyslipidemia. The effect of GHF on CVD may be greater in younger patients (HR=1.30, 1.17, and 1.05 in <40, 40–60, and ≥65 years old, respectively). Conclusions GHF was associated with CVD, particularly MI and heart failure. Screening for GHF in the early stages of type 2 diabetes mellitus may be beneficial.