A high proportion of subjects with diabetes were previously undiagnosed, consequently, the prevalence of diabetes in patients with acute heart failure is higher than previously recognized, occurring in more than half of the patients studied. Furthermore, the study established that patients with undiagnosed diabetes, despite having less cardiovascular risk factors and comorbidities, had a similar increased mortality as that of subjects with clinical diabetes.
Prevalence of undiagnosed diabetes
The prevalence of diabetes in this study was higher than previously reported, which ranged from 23% to 43% [
10‐
13]. This wide range reflects the diverse criteria used to identify patients with diabetes and the differences between heart failure populations analyzed. Most studies and registries of heart failure have only included patients with clinical diabetes, based on medical history or antidiabetic drug use [
10‐
13]. This may exclude up to 20% of the population with diabetes following dietary advice only, as well as those with undiagnosed diabetes. In the present study, systematic "review" of fasting blood glucose levels resulted in an undiagnosed diabetes prevalence of 16%, which means that 30% of diabetes cases were not detected. This figure is consistent with the undiagnosed diabetes prevalence reported in subjects with established cardiovascular disease [
16,
17,
21,
22]. In patients with stable chronic heart failure, Kistorp et al [
18] described a clinical diabetes prevalence of 21%, while that of undiagnosed diabetes was 6%. Furthermore, most diabetes prevalence studies in heart failure have been conducted in outpatient clinics, while the present study only included those requiring hospitalization for acute decompensated heart failure. In the large US ADHERE registry of patients with acute decompensated heart failure, 40% of the patients had clinical diabetes [
13], similar to the 37% prevalence reported in the present study. Therefore, the prevalence of diabetes in heart failure patients seems to be increased in those requiring hospitalization for acute decompensation.
Long-term mortality of patients with undiagnosed diabetes
Patients with undiagnosed diabetes were 1.69 times (95% CI: 1.16-2.35) more likely to die during follow-up than those without diabetes. The excess in mortality appears to be mainly due to increased cardiovascular mortality. The present study demonstrates this relationship in a cohort of heart failure patients and the results are similar to those found in patients with coronary artery disease [
21,
22]. The association between undiagnosed diabetes and increased mortality existed despite the relative preservation of left ventricular ejection fraction. This finding is in agreement with Suskin et al [
19], who found undiagnosed diabetes to be related to worse symptomatic status, but not worsening of left ventricular ejection fraction.
It is known that increased cardiovascular mortality in type 2 diabetes is related, at least in part, with comorbidities such as hypertension, dyslipidaemia and other cardiovascular diseases. However, in the present study, patients with undiagnosed diabetes had a mortality risk similar to those with clinical diabetes despite having lower fasting blood glucose and HbA1c levels at admission and a lower prevalence of hypertension, dyslipidaemia, coronary heart disease and peripheral vascular disease. Thus, the increased mortality in subjects with undiagnosed diabetes must be attributed to factors other than those usually associated with diabetes.
In this respect, previous studies showed heart failure to be an insulin-resistant state that may predispose to diabetes [
28,
29]. Amato et al [
30] demonstrated in a longitudinal study that chronic heart failure was associated with an increased incidence of non-insulin-dependent diabetes mellitus. Moreover, previous evidence supports the idea that insulin resistance progresses within the natural course of heart failure [
31]. Based on these findings, undiagnosed diabetes identified in the present study could reflect a "hyperglycemia" developed in patients with more severe heart failure, as reflected by its association with more previous hospitalizations for acute heart failure. Therefore, rather than being the cause of poor clinical outcomes, undiagnosed diabetes could represent a prognostic marker of heart failure severity.
To our knowledge, this is the first study to describe the prevalence of undiagnosed diabetes in patients with acute heart failure and to analyze the impact of this condition on long-term mortality. The clinical relevance of our findings is that more attention should be paid in diagnosing glucose abnormalities in patients admitted with heart failure, as this simple, cost-effective intervention allows identification of high-risk patients who could benefit from more aggressive therapeutic interventions.
Our study has some limitations that need to be acknowledged. The retrospective collection of clinical data precluded gathering information that might have been used to more accurately assess the relationship between diabetes and mortality in patients with heart failure, such as diabetes duration, complete data on HbA1c and microangiopathic complications. However, the retrospective collection of clinical data allowed evaluation of the impact of undiagnosed diabetes; a prospective study would have prevented this analysis on ethical grounds. Furthermore, the cohort of the present study was restricted to patients with acute decompensated heart failure that required hospitalization, and thus the data observed here cannot be extrapolated to the whole heart failure population. Finally, we do not have information regarding the possible diagnosis and treatment of diabetes during the seven-year follow-up period in those patients with undiagnosed diabetes at the time of admission, and thus can not analyze potential differences. Therefore, further studies will be needed to ascertain whether early diagnosis and treatment of diabetes can improve clinical outcomes in these patients.