Impact of Impaired Pancreatic β-Cell Function on Cardiovascular Prognosis in Heart Failure Patients Without Diabetes Mellitus

Abstract

Introduction: Insulin resistance (homeostasis model assessment ratio; HOMA-R) is associated with latent myocardial damage in apparently healthy subjects in health check. Meanwhile, diabetes mellitus is a well-known unfavourable prognostic risk factor in patients with heart failure (HF). However, it is still unclear whether beta cell function is associated with HF. HOMA-beta is reported to estimate beta cell function based on fasting plasma glucose and insulin concentration. We examined the impact of beta cell dysfunction on clinical outcomes in HF patients without diabetes mellitus (DM). Methods and Results: This study enrolled 312 HF patients without DM. Beta cell dysfunction was defined as HOMA-beta less than 30%. There were 90 cardiovascular events (29%) including 25 cardiovascular deaths and 65 rehospitalizations. There were 108 patients (35%) who showed beta cell dysfunction. Serum heart type fatty acid-binding protein (H-FABP) levels were higher in patients with beta cell dysfunction compared with those without (14.1 vs. 7.1 ng/ml, P< 0.001), whereas there was no significant difference between patients with and without insulin resistance. Plasma brain natriuretic peptide (BNP) levels were higher in patients with beta cell dysfunction compared with those without (625.2 vs. 399.0 pg/ml, P<0.001). HOMA-beta (r = -0.26, P < 0.001) was negatively correlated with log-BNP levels, whereas there was no correlation between HOMA-R and log- BNP levels. Kaplan-Meier analysis revealed significantly higher cardiovascular events rate was observed in patients with beta cell dysfunction (log-rank test p=0.001). However, there was no significant difference in cardiovascular events rates between patients with and without insulin resistance. Cox hazard analysis showed that beta cell dysfunction was independently associated with cardiovascular events after adjustment for confounding factors (hazard ratio 1.58, 95% confidence interval 1.02- 2.45), whereas insulin resistance was not associated with cardiovascular events. Conclusion(s): Beta cell dysfunction, but not insulin resistance, was associated with unfavorable outcomes in HF patients without DM. Our results provide an important insight into impairment of insulin secretion in patients with HF.