Volume 2, Number 3, October 2005

EDITORIALDiabetes and acute coronary syndromes – a cardiologist’s view
Nikolaus Marx

Diabetes Vasc Dis Res 2005;2:101-102.

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TOPICEDITORIALDiabetes and acute coronary syndromes – a diabetologist’s view
Peter J Grant

Diabetes Vasc Dis Res 2005;2:103-104.

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TOPICREVIEWAll obese individuals are not created equal: insulin resistance is the major determinant of cardiovascular disease in overweight/obese individuals
Gerald Reaven

The ability of insulin to mediate glucose disposal varies more than six-fold in an apparently healthy population, and approximately one third of the most insulin-resistant of these individuals are at increased risk to develop cardiovascular disease. Differences in degree of adiposity account for approximately 25% of this variability, and another 25% varies as a function of level of physical fitness. The more overweight/obese the person, the more likely they are to be insulin-resistant and at increased risk of cardiovascular disease, but substantial numbers of overweight/obese individuals remain insulin-sensitive, and not all insulin-resistant persons are obese.
Of greater clinical relevance is evidence that the metabolic benefit and decrease in risk of cardiovascular disease following weight loss occurs primarily in those overweight/obese individuals that are also insulin resistant. The relationship between insulin resistance and overall obesity, as assessed by measurement of body mass index, is essentially the same as the relationship between insulin action and abdominal obesity as quantified by determining waist circumference.
Finally, there appears to be a comparable relationship between insulin-mediated glucose disposal and amount of visceral fat, subcutaneous fat, and total fat as quantified by various imaging techniques, and the magnitude of these relationships is no greater than that between insulin action and simple measure of body mass index.

Diabetes Vasc Dis Res 2005;2:105-112.

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TOPICREVIEWInflammation, thrombosis and acute coronary syndromes
Angela M Carter

Inflammation plays a central role in the pathogenesis of acute coronary syndromes, the prevalence of which is increased in individuals with diabetes. Monocytes and macrophages, T cells and mast cells contribute to the initiation, development and rupture of atherosclerotic plaques by synthesising a variety of pro-inflammatory cytokines, including interleukin 1b, interleukin 6 and tumour necrosis factor a. Cytokines upregulate endothelial cell adhesion molecules, recruit leukocytes and induce smooth muscle cell migration and proliferation. Cytokines act systemically to initiate the acute phase response, up-regulating proteins involved in inflammation and haemostasis and resulting in a pro-inflammatory and pro-thrombotic state. Expression of tissue factor by inflammatory cells potently induces thrombus formation upon plaque rupture, leading to acute coronary syndromes. Inflammatory biomarkers, including C-reactive protein, complement proteins, interleukin 6 and white blood cell count, predict development of acute coronary syndromes. C-reactive protein has been widely studied and consistently predicts future acute coronary syndrome events.

Diabetes Vasc Dis Res 2005;2:113-121.

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TOPICREVIEWBiomarkers in acute coronary syndromes and their role in diabetic patients
Christopher Heeschen

Diabetic patients with acute coronary syndromes are at high risk for cardiovascular complications but risk stratification in these patients remains challenging. Regularly, diabetic patients have a less typical clinical presentation, which could lead to delayed diagnosis and subsequent delayed initiation of treatment. Since diabetic patients derive particular benefit from aggressive anti-platelet therapy, early diagnostic and therapeutic risk stratification of these patients is of critical importance to improve their adverse outcome.
Although the electrocardiogram remains a pivotal diagnostic tool in the evaluation of patients suspected of having an acute coronary syndrome, only significant ST-segment changes provide reasonable prognostic information. Therefore, repeated assessment of circulating protein biomarkers represents a valuable diagnostic tool for improving efficacy and safety of decision-making in these patients. The combined use of biomarkers reflecting distinct pathophysiological aspects, such as myocardial necrosis, vascular inflammation, oxidative stress and neurohumoral activation, may significantly improve triage of patients with chest pain. These tools may identify those patients that are at particularly high risk for short-term and/or long-term cardiovascular events. Eventually, tailored medical and interventional treatment of diabetic patients should help to prevent these cardiac events in a cost-effective manner.

Diabetes Vasc Dis Res 2005;2:122-127.

REVIEWDiabetes and percutaneous coronary intervention in the setting of an acute coronary syndrome
David M Safley, Steven P Marso

Diabetes mellitus has reached epidemic proportions worldwide. Patients with diabetes are at increased risk for acute coronary syndromes, and these syndromes lead to frequent morbidity and cardiovascular mortality. Emerging adjunctive pharmacological strategies coupled with the drug-eluting stent platform have resulted in improved adverse event rates for this high-risk group. This review will concentrate on the historical data associated with acute coronary syndromes in diabetes mellitus, focusing on revascularisation, drug-eluting stents and antiplatelet therapies.

Diabetes Vasc Dis Res 2005;2:128-135.

REVIEWThe acute reperfusion management of STEMI in patients with impaired glucose tolerance and type 2 diabetes
Jean-Philippe Collet, Gilles Montalescot

Diabetes mellitus (DM) remains an important predictor for mortality in patients with ST-segment Elevation Myocardial Infarction (STEMI) although the use of reperfusion therapy has resulted in a considerable improvement of survival. Of importance, newly diagnosed diabetic patients and those with fasting glycaemia in the diabetes range have even worse outcomes compared to patients with known diabetes. Overall, 50% of all patients presenting with STEMI have abnormal glucose metabolism of which fewer than 50% are known diabetics. Obviously, the efficacy of reperfusion therapy in reopening the occluded artery is similar in STEMI patients with or without impaired fasting glycaemia, while the pre-existing decreased myocardial perfusion in STEMI patients with impaired fasting glycaemia persists after successful epicardial revascularisation. There is no doubt that improving microvascular perfusion within the ischaemic myocardium remains the ultimate goal of managing STEMI patients with impaired glucose metabolism. Identification of defective myocardial perfusion together with an aggressive antithrombotic regimen, reduction of the inflammatory response of the ischaemic myocardium and improvement of glycaemia control represent promising therapeutic approaches that deserve additional specific clinical investigations. This review examines all these important issues.

Diabetes Vasc Dis Res 2005;2:136-143.

REVIEWManagement of patients with type 2 diabetes after acute coronary syndromes
Malgorzata Bartnik, Klas Malmberg, Lars Rydén

Acute coronary syndromes are associated with a high risk for subsequent major cardiovascular events and with a risk for mortality that remains substantially increased for many months following the acute phase. Patients with type 2 diabetes mellitus are especially vulnerable and encounter excessive long-term mortality. Effective management of patients with type 2 diabetes following acute coronary syndromes requires aggressive multidisciplinary efforts for reduction of several risk factors, including meticulous control of blood glucose. The evidence for different medication and treatment strategies capable of improving the outcomes is reviewed and the currently available recommendations are summarised.

Diabetes Vasc Dis Res 2005;2:144-154.