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First-time heart failure increases risk of diabetes mellitus

First-time heart failure increases risk of diabetes mellitus. Nat Rev Endocrinol. 2014 Aug;10(8):451-3. Introduction.

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First-time heart failure increases risk of diabetes mellitus

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  1. First-time heart failure increases risk of diabetes mellitus Nat Rev Endocrinol. 2014 Aug;10(8):451-3.

  2. Introduction • The severity of heart failure, categorized by loop-diuretic dosage, has previously been reported to predict the risk of developing type 2 diabetes mellitus (T2DM) after a myocardial infarction in a Danish register-based study • Now, a paper published by Demant and colleagues in Diabetologia extends this finding to show that patients with heart failure have a raised risk of developing T2DM that increases with increasing loop-diuretic dosage

  3. Methods • The study involved 99,362 Danish patients who had not previously used hypoglycaemic agents and who were discharged in 1997–2010 after hospitalization for first-time heart failure • The authors followed up these patients until a claimed prescription for hypoglycaemic agents, death or 31 December 2010

  4. Methods • Using multivariate Cox regression models, they estimated the association between the future risk of T2DM and loop-diuretic usage 90 days after discharge in five groups of patients who received different doses of loop diuretics • Dose groups were defined on the basis of the potency of loop-diuretic dosage equivalent to the following doses of furosemide: group 1, no loop diuretic; group 2, >0–40 mg per day; group 3, 40–80 mg per day; group 4, 80–159 mg per day; group 5, ≥160 mg per day

  5. Results • In the 7,958 patients (8%) who developed diabetes mellitus, loop-diuretic usage was associated with an increased risk of developing T2DM in a dose-dependent manner, which was attenuated by the concomitant use of renin–angiotensin system inhibitors (P <0.0001) • Patients who used β‑blockers had a lower risk of T2DM than those who did not (P <0.0001)

  6. Results • Compared with group 1 who used no loop diuretics, hazard ratios (HR) for developing T2DM in groups 2–5, adjusted for concomitant renin–angiotensin system inhibitor use, were: HR 1.16 (95% CI 1.07–1.26); HR 1.35 (95% CI 1.24–1.46); HR 1.48 (95% CI 1.35–1.62); and HR 1.76 (95% CI 1.61–1.92), respectively

  7. Results • In addition, increased loop-diuretic dosage was also associated with an increased risk of death, with HRs in groups 2–5 of 1.14 (95% CI 1.12–1.17), 1.17 (95% CI 1.14–1.20), 1.29 (95% CI 1.26–1.33) and 1.45 (95% CI 1.41–1.48), respectively • Of note, the patients who developed T2DM were at greater risk of death than those who did not develop T2DM, with an adjusted HR for death of 1.16 (95% CI 1.12–1.19)

  8. Results • The mean age of the patients increased with increasing loop-diuretic dosage (72 ± 13 years in group 1 versus 77 ± 11 years in group 5, P <0.0001) • Few patients had renal disease, but the proportion was greater in group 5 than in group 1 (9% versus 3%, P <0.0001) • The increased age and proportion of patients with renal disease in group 5 might accentuate their risk of developing T2DM • The proportion of patients taking thiazide diuretics was highest in group 1 (33%), reducing to 22% in group 5

  9. Discussion • A number of mechanisms have been suggested to explain why patients with heart failure might be at increased risk of developing diabetes mellitus, which are mainly related to increased insulin resistance that could be driven in part through neurohumoral activation

  10. Discussion • In patients with heart failure but not diabetes mellitus, insulin resistance correlates with worsening New York Heart Association functional class and with reduced exercise tolerance • Reduced exercise levels might provide another explanation for the increased risk of diabetes mellitus, but patients with more severe heart failure also tend to have a lower BMI than patients with less severe heart failure

  11. Conclusion • The data presented by Demant and colleagues not only remind us of the worsened prognosis of heart failure in people with diabetes mellitus, but also the need to be vigilant with respect to the increased risk of emergent diabetes mellitus in those who develop heart failure and to advise them accordingly

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