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Commencing Volume 19, Issue 1, MedReviews has ceased the publication of this journal. Reviews in Cardiovascular Medicine will continue to be published by IMRPress, Ltd. (www.imrpress.com)

Volume 7, Supplement 2, 2006

Volume 7, Supplement 2, 2006

Table of Contents

From Hyperglycemia to the Risk of Cardiovascular Disease From Hyperglycemia to the Risk of Cardiovascular Disease Diabetes, Hyperglycemia, and the Cardiologist
Blood glucose is a continuous, progressive risk factor for cardiovascular disease (CVD) throughout the dysglycemic range. There is also evidence that post-prandial hyperglycemia may be a better predictor of CVD risk than fasting plasma glucose or A1C. Targeting normoglycemia appears to reduce CVD events in diabetes mellitus (DM), although definitive studies in type 2 DM, as well as in prediabetes, are ongoing. Prediabetes has some, but not total, overlaps with the metabolic syndrome. Patients with the metabolic syndrome are at a significantly increased risk for both CVD and DM. Although the individual components of the syndrome predict risk for CVD to approximately equal degree, increased blood glucose, perhaps not surprisingly, is the best predictor of diabetes. Finally, there are multiple mechanisms by which hyperglycemia can increase the risk for CVD. [Rev Cardiovasc Med. 2006;7(suppl 2):S3-S9]
Management of Diabetes in the Hospital Diabetes, Hyperglycemia, and the Cardiologist
Hyperglycemia is a common complication in hospitalized patients, particularly among patients with acute myocardial infarction. It is an independent predictor of cardiovascular mortality and morbidity. Management of hyperglycemia with intensive insulin therapy has been shown to improve survival, reduce length of stay in intensive care, and decrease complications such as renal failure or prolonged mechanical ventilation in critically ill patients. Insulin infusions are now recommended for the treatment of hyperglycemia in several groups of patients, including patients in the intensive care unit and those undergoing major surgery. Implementation of protocols and standard orders may be useful to ensure the optimal use of insulin in the management of hyperglycemia. Fewer data are available to guide the management of hyperglycemia outside the intensive care setting. A variety of subcutaneous insulin regimens are now available with different pharmacokinetic profiles. These agents are preferred to controlling blood sugar with sliding scale regimens alone. Oral therapies may also have a role, but many agents may be contraindicated in the acute setting. As hyperglycemia has been shown to have significant adverse impact on patient outcomes in a variety of settings, cardiologists need to play a role in efforts to achieve adequate glycemic control in hospitalized patients with hyperglycemia in an effort to improve patient outcomes. [Rev Cardiovasc Med. 2006;7(suppl 2):S10-S17]
Prevalence of Newly Diagnosed Diabetes in Clinical Settings Diabetes, Hyperglycemia, and the Cardiologist
A substantial number of patients being evaluated or treated for cardiovascular disease are found to have glucometabolic disorders. Identification of such patients is important because treatment for coronary artery disease and stroke needs to be individualized. Hyperglycemia on admission or during hospitalization regardless of whether diabetes mellitus is known to exist in these patients is associated with increased morbidity and mortality. Despite the fact that this has been known for some time, various strategies to reduce hyperglycemia have had mixed results in cardiac outcomes. Another important factor is that a new diagnosis of diabetes mellitus in these patients should result in the patient’s triage to appropriate healthcare professionals to optimize glycemic control. The prevalence of hyperglycemia in patients admitted with acute cardiovascular disease and the effect of hyperglycemia on outcome are reviewed. [Rev Cardiovasc Med. 2006;7(suppl 2):S18-S24]
Anti-Inflammatory Effects of Insulin and Pro-Inflammatory Effects of Glucose: Relevance to the Management of Acute Myocardial Infarction and Other Acute Coronary Syndromes Diabetes, Hyperglycemia, and the Cardiologist
Hyperglycemia worsens morbidity and mortality for patients in intensive care or with acute myocardial infarction, stroke, or coronary artery bypass grafts. The control of hyperglycemia with insulin improves clinical outcomes for patients with these conditions. This article reviews the anti-inflammatory effects of insulin and proinflammatory effects of glucose and free fatty acids, and provides a mechanistic justification for maintaining euglycemia with insulin infusions. Hyperglycemia induced by infusions of a fixed dose of insulin with high rates of glucose may neutralize the benefit of insulin, and such regimens should be replaced by infusion of insulin to restore and maintain euglycemia. [Rev Cardiovasc Med. 2006;7(suppl 2):S25-S34]
Mechanism by Which Hyperglycemia Plays a Role in the Setting of Acute Cardiovascular Illness Diabetes, Hyperglycemia, and the Cardiologist
Acute hyperglycemia is associated with excess morbidity and mortality in acute cardiovascular illness in both diabetic and nondiabetic patients. Hyperglycemia is associated with altered myocardial energetics, but abnormalities in glucose oxidation and glycolysis do not fully account for this excess risk. Hyperglycemia leads to a pro-oxidative/ proinflammatory state that is associated with endothelial dysfunction, diminished coronary vasodilatory reserve, and a prothrombotic state. Hyperglycemia negates the protective effect of ischemic preconditioning and, most importantly, appears to interfere with the salutary effects of insulin in acute cardiovascular illness. Aggressive therapy with continuous infusion of insulin seems to improve a host of metabolic and physiologic effects associated with acute hyperglycemia and appears warranted if euglycemia can be maintained. [Rev Cardiovasc Med. 2006;7(suppl 2):S35-S43]
Glucose, Insulin, and Potassium for Metabolic Support in Acute Myocardial Infarction: Is the Jury Still Out? Diabetes, Hyperglycemia, and the Cardiologist
During ischemic and cardiomyopathic conditions, carbohydrate (glucose) metabolism in cardiomyocytes predominates over use of free fatty acids. The shift to glucose metabolism is a physiologic response to ischemia, which in many patients, particularly diabetics or those who are insulin-resistant, is blunted. Free fatty acid metabolism during ischemia produces higher levels of lactate and hydrogen ions within the ischemic cells. This in turn degrades myocardial contractility, induces diastolic dysfunction, and reduces the arrhythmogenic threshold of the cardiomyoctye. Suppression of free fatty acid uptake and oxidation by any means will increase myocardial glucose substrate utilization in ischemia. Theoretically, then, an insulin-glucose solution that can augment GLUT-1 and GLUT-4 translocation to the sarcolemmal membrane can assist cardiomyocyte survival during ischemia; however, study results have not supported metabolic therapy. It is essential for any investigation of glucose, insulin, potassium therapy to separate out the effect of hyperglycemia and glucose toxicity to make any meaningful comment on the effectiveness of metabolic support in myocardial infarction. [Rev Cardiovasc Med. 2006;7(suppl 2):S44-S50]