Association of Heart Failure Severity With Risk of Diabetes: A Danish Nationwide Cohort Study

Study Questions:

What is the relation between heart failure severity, defined by loop-diuretic dosage, and the risk of developing diabetes in a nationwide cohort of patients with heart failure?


The investigators followed all Danish patients discharged from hospitalization for first-time heart failure in 1997–2010, without prior use of hypoglycemic agents, until a claimed prescription for hypoglycemic agents, death, or December 31, 2010. The association of loop-diuretic dosage (furosemide equivalents) 90 days after discharge (study baseline) with risk of diabetes was estimated by multivariate Cox regression models.


In total, 99,362 patients were included and divided into five loop-diuretic dose groups: 30,838 (31%) used no loop diuretics; 24,389 (25%) used >0–40 mg/day; 17,355 (17%) used >40–80 mg/day; 11,973 (12%) used >80– 159 mg/day; and 14,807 (15%) used ≥160 mg/day. A total of 7,958 patients (8%) developed diabetes. Loop-diuretic dosages were associated with an increased risk of developing diabetes in a dose-dependent manner. Concomitant use of renin–angiotensin system inhibitors (RASis) attenuated the risk (p value for interaction < 0.0001). Compared with patients using no loop diuretics (group 1), the adjusted hazard ratios (95% confidence interval) for developing diabetes for groups 2–5, respectively, were 1.16 (1.07, 1.26), 1.35 (1.24, 1.46), 1.48 (1.35, 1.62), and 1.76 (1.61, 1.92) with RASi treatment, and 2.06 (1.83, 2.32), 2.28 (2.01, 2.59), 2.88 (2.52, 3.30), and 3.02 (2.66, 3.43) without RASi treatment.


The authors concluded that severity of heart failure was associated with a stepwise increased risk of developing diabetes.


This nationwide cohort of patients hospitalized for heart failure showed that increasing loop-diuretic dosage, used as a proxy for heart failure severity, was associated with increased risk of developing diabetes in a severity-dependent manner. Furthermore, patients developing diabetes were shown to be at increased risk of dying compared with patients who did not develop diabetes. These findings emphasize the need to monitor and treat patients with heart failure to prevent diabetes development. Future strategies for heart failure management should include increased awareness of risk of diabetes in patients with severe heart failure.

Clinical Topics: Heart Failure and Cardiomyopathies, Statins, Acute Heart Failure

Keywords: Proportional Hazards Models, Heart Failure, Renin-Angiotensin System, Hypoglycemic Agents, Sodium Potassium Chloride Symporter Inhibitors, Furosemide, Diabetes Mellitus

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