The Epidemiology of Diabetes Mellitus in Heart Failure
Patients with heart failure demonstrate impaired glucose metabolism and insulin resistance is common.16 The altered glucose metabolism places them at increased risk for developing diabetes, 29 % vs 18 %, compared to the general population.17 Data from multiple randomised studies and registries agree that the prevalence ranges from 20 %18 to 26 %.19 In fact nearly one quarter of all HF patients have concomitant diabetes and this number rises drastically to 40 % in patients admitted with ADHF.20 In the SOLVD (Studies of Left Ventricular Dysfunction) trial 6 % of patients developed DM within three years of enrollment.17 The overall prevalence of DM in heart failure is significantly higher than in the general population, 25 % compared to 9 %. While the overall prevalence of DM is 25 % in heart failure, patients with Heart Failure with Preserved Ejection Fraction (HFpEF) have a slightly higher prevalence of DM reaching nearly 40 %.21
Outcomes in Heart Failure with Concomitant Diabetes
The co-existence of heart failure and diabetes has significant impact on outcomes and confers a worse prognosis than heart failure alone.22 The diagnosis of diabetes in heart failure patients results in increased cardiovascular mortality, higher readmission rates23 and increased hospital lengths of stay.24 Data from ALLHAT (The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) demonstrated significantly higher risk for heart failure admissions or death in diabetics, nearly twice as high than in those patients without diabetes.25 The presence of diabetes in heart failure confers a significantly higher rate of mortality compared to those without diabetes, 45 % versus 24 % respectively, at 5 years.11
The poor prognosis of concomitant DM and HF is more prominent in two sub-groups of patients with heart failure. The SOLVD trial showed an increased risk for HF admissions (RR:2.16) or a composite of death or symptoms in HF (RR:1.56) in patients with asymptomatic ischaemic cardiomyopathy26 and in the Framingham Heart Study 34 % of diabetic patients died within 1 year of the diagnosis of heart failure.27 The other sub-group of heart failure patients that experience worse outcomes
with DM are patients with HFpEF. As previously demonstrated, patients with HFpEF have a higher prevalence of DM. In the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Morbidity and mortality) study patients with HFpEF and concomitant diabetes had higher rates of CV death and hospitalisations for heart failure compared to those with reduced EF.28
As was previously shown HgbA1c is directly related to the risk of developing heart failure. It has also been demonstrated that it directly impacts outcome in heart failure. In heart failure, the effect of HgbA1c on morality is U-shaped. Morality decreases with decreasing glycosylated haemoglobin until a nadir is reached, then the mortality begins to creep upwards again. The highest mortality is seen in patients with HgbA1c > 7.8 % and < 7.1 %,indicating that the optimal HgbA1c goal in DM to reduce the risk of death in heart failure is approximately 7.5 %.29 Glycaemic control has been thought to be paramount to reducing the risk and impact of DM on the development and prognosis of heart failure. Achieving adequate glycaemic control requires the use of hypoglycaemic agents and often exogenous insulin. However therapies utilised to improve glycaemic control are often a double-edged sword, especially in heart failure. Randomised controlled trials have failed to show a benefit of tighter glycaemic control on the incidence of heart failure.30,31 The use of insulin in heart failure is controversial, while excellent glycaemic control can be achieved, it has been associated with increased mortality in HF.32 The use of metformin is cautioned due to the increased risk of metabolic acidosis and is not recommended in advanced heart failure. Trials with thiazolidinediones (pioglitazone and rosiglitazone) have demonstrated adverse outcomes in heart failure, increasing the risk of heart failure and hospitalisations by nearly 2-fold.33,34 It is thought that these medicines promote fluid retention and alter sodium handling resulting in worsening heart failure. In a recent analysis of the dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin its use was associated with a significant increase in heart failure admissions.35 Sulfonylureas, which increase endogenous insulin production, have not been shown to negatively impact the development of heart failure. Clearly the optimal therapeutic strategy remains elusive.