Number 25, 2004
Heart failure in diabetes

Heart failure in diabetes

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M. Marber
St Thomas's Hospital, London, UK
Correspondence: M. Marber, Department of Cardiology, The Rayne Institute, St Thomas's Hospital, London SE1 7EH.
E-mail: mike.marber@kcl.ac.uk

All of us are now aware that type 2 (noninsulin-dependent) diabetes is pandemic in the developed world. Furthermore, even conservative estimates suggest further significant growth in its prevalence, with an approximate twofold increase, over the next two decades. Amongst patients with coronary artery disease, abnormal glucose regulation is extremely common. For example, in the recent EURO Heart Survey on Diabetes presented at the annual meeting of ESC in 2004, more than 50% of the 4196 patients with ischemic heart disease had abnormal glucose metabolism. In addition, many of the patients with newly diagnosed diabetes that was detected during a formal glucose tolerance test would have been missed on the basis of a random glucose test. Given the high prevalence of diabetes in the general population and the fact that most of our patients with coronary artery disease have diabetes or prediabetes, this issue of Heart and Metabolism is timely and topical.
In the Basic Article, Danielle Feuvray explains the actions of insulin through its effects on known glucose transporters and signaling intermediates. Although the influences of insulin on glycolysis and β-oxidation in the heart have been known for decades, our increased understanding of the underlying biology have added further layers of complexity. As Dr Feuvray explains, insulin resistance, increased circulating insulin concentrations, or dysregulation of glucose per se injure the myocardium. In its most extreme form, this injury manifests as true diabetic cardiomyopathy, with severe contractile dysfunction in the absence of angiographically visible obstructions within the epicardial coronary arteries. The hope is that an increased understanding of the actions of insulin, especially through mouse models, will reveal novel therapeutic targets for this invidious disease.
In the Main Clinical Article, Vivienne Ezzat and Mark Kearney explain that the treatment of patients with heart failure and diabetes is similar to the treatment of patients with heart failure without diabetes, only more so! As the presence of diabetes further increases the risk of events, the absolute benefit of proven pharmacological interventions is likely to be even greater. Furthermore, tight glycemic control may reduce injury to the heart through the mechanisms explained in the Basic Article. Interestingly, agents that target the renin–angiotensin system (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) not only reduce the complications seen with diabetes, but also reduce the incidence of new cases of diabetes. The mechanism for this robust observation, seen in the Heart Outcomes Prevention Evaluation, European Trial on Reduction of Cardiac Events with Perindopril in stable coronary Artery Disease (EUROPA) and Valsartan Antihypertensive Long-term Use Evaluation trials, is not known, but presumably would reduce the incidence of prediabetes in addition to the conversion of prediabetes to overt diabetes. Drs Ezzat and Kearney emphasize the need for treatments individually tailored to a patient's needs – a refreshing physicianly philosophy in practices increasingly moulded by evidence-base, care pathways, and quality of care measures. What is without doubt is that diabetic patients merit the most meticulous management and control of all modifiable risk factors.
The Metabolic Imaging article emphasizes the complexity of measuring substrate utilization in the hearts of patients with diabetes. Juhani Knuuti explains that, once the abnormalities in circulating glucose, insulin, and free fatty acid concentrations are controlled, quantitative positron emission tomography can no longer reliably demonstrate impaired glucose uptake/oxidation. In other words, there is no intrinsic cardiac abnormality but, rather, disordered substrate preference is the result of disordered substrate availability, and in particular the increases in free fatty acids.
Romualdo Belardinelli provides a very balanced perspective of new treatments available for diabetes, with an emphasis on the multifactorial benefits of exercise and lifestyle intervention. In addition, findings from his own research suggest that there may be some benefits from therapeutic agents that address the metabolic imbalance in diabetes and improve glucose oxidation at the expense of free fatty acids. Similar hope is offered in the Refresher Corner, in which Lazaros Nikolaidis and Barry Levine discuss the transcriptional changes that accompany diabetes and the benefits that may accrue from peroxisome proliferator-activated receptor-α or -γ agonists such as the thiazolidinediones. These insulin-sensitizing agents have the potential to reverse many of the derangements that accompany diabetic heart disease but, as pointed out by various authors within this issue of Heart and Metabolism, their use is complicated by fluid retention apparently worsening heart failure. In essence, we await further guidance from clinical trials as to how to use these disease-modifying drugs in patients with diabetes and coincident left ventricular dysfunction.
I hope you enjoy this issue of Heart and Metabolism, and I trust that its reading does not accompany an energy-dense meal! I'm sure you will find the content educational and that, in response to the question, “Do you want that supersized?”, the response will now always be, “No!”. ▪