Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study

Abstract

Aims/hypothesis Heart failure has been suggested to increase the risk of developing diabetes. We investigated 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. Methods We followed all Danish patients discharged from hospitalisation for first-time heart failure in 1997-2010, without prior use of hypoglycaemic agents, until a claimed prescription for hypoglycaemic agents, death or 31 December 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.Results 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 HRs (95% CI) for developing diabetes for groups 2-5 respectively were 1.16

Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology

“…13.6/1000 vs. 9.2/1000) over a 5‐year follow‐up . In a Danish nationwide cohort study, 8% of HF patients developed T2DM over 3 years, and the severity of HF was associated with a stepwise increased risk of developing T2DM . Similar incidence of T2DM was reported in clinical trials of HF patients, as demonstrated by the CHARM program, in which 7.8% of patients developed T2DM over 2.8 years .…”

“…Notably, HF treatment with angiotensin‐converting enzyme (ACE) inhibitors was shown to lower the incidence of T2DM in HFrEF patients; in a substudy of the SOLVD trial, 6% of patients in the enalapril arm developed T2DM over a mean follow‐up of 2.9 years as opposed to 22% in the placebo arm . Registry data corroborate that the use of renin–angiotensin system inhibitors is associated with attenuated risk for T2DM in HF patients receiving loop diuretics . Clinical trials also demonstrated that the severity of HF, as indicated by a higher New York Heart Association (NYHA) class, increases the likelihood of developing T2DM …”

Low-density-lipoprotein cholesterol concentrations and risk of incident diabetes: epidemiological and genetic insights from the Framingham Heart Study

“…We chose a priori to exclude people with prevalent cardiovascular disease and those using any antihypertensive medications (combined n =3,788 person-observations) because these conditions or the medications used to treat them have been associated with the risk of future diabetes in previous studies. [11–15] Additionally, we excluded people with missing data on key covariates (age, sex, blood pressure, antihypertensive medications, cholesterol treatment, lipid values and/or blood glucose concentrations; n = 3,209).…”

Severity of heart failure and risk of incident diabetes: a reverse causation?

“…Thus, the dosage of loop diuretic might be a proxy for metabolic disorder severity rather than heart failure severity. The higher proportion of patients with atrial flutter/ fibrillation, chronic obstructive pulmonary disease and renal disease in the higher diuretic dosage groups shown in Table 1 of the paper by Demant et al [1] not only frequently coexists with more severe heart failure, but also closely associates with more serious metabolic syndrome [6,7]. Thus, it is not clear whether more severe heart failure or more severe metabolic syndrome underlies the increased risk of diabetes in the patients receiving the higher diuretic dosage.…”

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To the Editor: We read with interest the article by Demant et al [1], which reported that severity of heart failure was associated with a graduated risk of new-onset diabetes. Demant et al underscored the importance of focusing on the underlying concomitant disease and its effect on future outcomes in patients with heart failure.

However, we think that it is premature to draw a conclusion on the cause-and-effect relationship between severity of heart failure and incident diabetes.

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