The effect of metabolic dysfunction-associated fatty liver disease and diabetic kidney disease on the risk of hospitalization of heart failure in type 2 diabetes: a retrospective cohort study

Abstract

Background: Diabetes mellitus is a major risk factor for heart failure. A recent consensus statement recommended annual cardiac biomarker testing (e.g. natriuretic peptide or high-sensitivity cardiac troponin) for all patients with diabetes. We aimed to identify patients at a higher risk of hospitalization for heart failure among patients with type 2 diabetes to prioritize those who would require screening.

Methods: Overall, 1,189,113 patients who underwent two medical health checkup cycles (2009-2012 and 2011-2014) and had stable diabetic kidney disease (DKD) phenotype in the Korean National Health Insurance Service database were included in this study. After excluding those with concurrent proteinuria (PU) and reduced estimated glomerular filtration rate, three groups (no-DKD, PU⁺DKD, and PU^-DKD) were identified. A fatty liver index of ≥ 60 was defined as metabolic dysfunction-associated fatty liver disease (MAFLD). Patients were followed up until December 2018 or until outcomes developed. The Cox proportional hazard model was used to compare the risk of hospitalization for heart failure across groups.

Results: During an average of 6.6 years of follow-up, 5781 patients developed hospitalization for heart failure. After adjusting for covariates, the risk of hospitalization for heart failure was highest in the PU⁺DKD group [HR 3.12, 95% CI (2.75-3.55)], followed by the PU^-DKD group [HR 1.85, 95% CI (1.73-1.99)] using the no-DKD group as the reference category. The risk of hospitalization for heart failure was comparable regardless of MAFLD status in patients who already had DKD. However, in the no-DKD group, the risk of hospitalization for heart failure was 1.4 times higher in patients with MAFLD than in those without [HR 1.41, 95% CI (1.31-1.52)].

Conclusions: In lines with the international consensus statement, we suggest that annual cardiac biomarker testing should be conducted at least in patients with DKD and/or MAFLD.

Keywords: Diabetic kidney disease; Heart failure; Hospitalization for heart failure; Metabolic dysfunction–associated fatty liver disease.

Fig. 1

Cumulative incidence plot of hospitalization for heart failure according to the DKD/MAFLD phenotype. The black, blue, and red lines indicate the no-DKD, PU⁺DKD, and PU⁻DKD groups, respectively. The bold line indicates MAFLD and the dashed line indicates no MAFLD

Fig. 2

HRs and 95% CI of HHF according to DKD/MAFLD phenotype. DKD: diabetic kidney disease; HHF: hospitalization for heart failure; MAFLD: metabolic dysfunction–associated fatty liver disease; PU: proteinuria. no-DKD: normal eGFR (eGFR ≥ 60) with negative PU; PU⁺DKD: normal eGFR with positive PU; PU⁻DKD: reduced eGFR (eGFR < 60) with negative PU. HRs were adjusted for age, sex, smoking, alcohol, exercise, hypertension, dyslipidemia, atrial fibrillation, ischemic heart disease, fasting plasma glucose, diabetes duration, hemoglobin levels, and insulin usage

Fig. 3

Subgroup analyses among no-DKD patients stratified by age, sex, and previous HF. DKD: diabetic kidney disease; FLI: fatty liver index; HR: hazard ratio; HF: heart failure; IR: incidence rate. HRs were adjusted for age, sex, smoking, alcohol, exercise, hypertension, dyslipidemia, atrial fibrillation, ischemic heart disease, fasting plasma glucose, diabetes duration, hemoglobin levels, and insulin usage