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Cardiovascular Dysfunction in Chronic Diabetes

Published Online: June 6th 2011 US Endocrinology, 2005;(1):35-8 DOI: http://doi.org/10.17925/USE.2005.00.01.35
Authors: Naranjan S Dhalla
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Overview

Background
Diabetes is one of several risk factors for ischemic heart disease and is a major killer.1–3 This complex disease affected around 171 million people all over the world in 2000 and is estimated to affect 366 million people by 2030. Of these, about 13 million cases have been diagnosed with diabetes in the US, and another 5.2 million people are unaware that they have the disease.

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It is generally thought that about 30% of the population with diabetes remains undiagnosed in industrialized nations, whereas the impact of diabetes is considerably less in developing countries because people die young due to malnutrition and infectious diseases. Nonetheless, the financial burden is too great for treating diabetes-induced complications such as heart attack, stroke, blindness, kidney disease, and limb amputations. The cost of treating diabetes and its complications worldwide was estimated to be well over US$132 billion in 2002.

It is generally thought that about 30% of the population with diabetes remains undiagnosed in industrialized nations, whereas the impact of diabetes is considerably less in developing countries because people die young due to malnutrition and infectious diseases. Nonetheless, the financial burden is too great for treating diabetes-induced complications such as heart attack, stroke, blindness, kidney disease, and limb amputations. The cost of treating diabetes and its complications worldwide was estimated to be well over US$132 billion in 2002. It has been noted that ethnicity seems to play a major role in diabetes— aboriginal people have five to six times higher incidence of diabetes in comparison with others. In fact, it has been reported that African-Americans, Asians, Indians, and Hispanics have a genetic propensity toward diabetes.

There are two major forms of diabetes: type 1 diabetes is seen in 5% to 10% of the patients, whereas 85% to 90% of patients are affected by type 2 diabetes.4 Although the plasma level of glucose is markedly elevated in diabetic patients, type 1 diabetes is considered to be due to insufficiency of insulin and type 2 diabetes is related to insulin resistance. It is commonly held that the onset of type 1 diabetes occurs in children, while type 2 diabetes occurs in adulthood; however, recent observations have revealed that type 1 diabetes is stalking adults and type 2 diabetes has been detected in children and teenagers. Thus, it would be prudent to characterize diabetics on the basis of insulin insufficiency and insulin resistance rather than in terms of type 1 and type 2 diabetes. It should be noted that diabetic patients show different symptoms, such as fatigue, irritability, blurry vision, extreme hunger, weight loss, frequent urination, and excessive thirst. In addition to hyperglycemia and dyslipidemia, several biochemical markers, including increased plasminogen activator inhibitor, serum C-reactive protein level, advanced glycation end products, and hexosamine production, are used to identify the severity of diabetes. Management of Diabetes
Since the discovery of insulin by Frederick Banting and Charles Best in 1920, no major breakthrough has occurred for the treatment of diabetes. Because the immune system destroys insulin-producing cells in the pancreas, transplantation of insulin-producing islets in the pancreas is becoming a valuable intervention. Several attempts are also being made to generate insulin-producing cells by employing stem cells under a wide variety of experimental conditions. However, it should be emphasized that although insulin is a life support mechanism, it is not a cure for diabetes. This is based on the fact that insulin resistance rather than insulin insufficiency is the main problem confronting most diabetics. Accordingly, several types of insulin sensitizers, such as metformin and thiazolidinediones, with different sites of action, are being developed as drugs of choice for the treatment of diabetes. Because the control of diet, exercise, and behavior are cornerstones for the management of diabetes, a great deal of emphasis is placed on changes in the lifestyle of patients.With approximately 90% of diabetics with insulin resistance being overweight, obesity is considered to complicate the overall management of diabetes.With regard to this, physical activity has been shown to reduce the risk of diabetes due to insulin resistance by about 50%.

Cardiovascular Complications
Heart disease is by far the leading cause of death among people with diabetes;5–9 it accounts for 40% to 50% of all deaths. In view of the invariable presence of dyslipidemia and atherosclerosis,10 coronary artery disease (CAD) is a common manifestation in diabetic patients; however, the direct effects of high cholesterol cannot be ruled out. In view of abnormalities in the endothelial and vascular functions, diabetes is often linked to hypertension. Because about 15% to 25% of patients with congestive heart failure are diabetics, it has been suggested that diabetes may predispose patients to congestive heart failure as a consequence of specific diabetic cardiomyopathy. Different mechanisms, such as microangiopathy, metabolic defects resulting from an imbalance of glucose and free fatty acid utilization, as well as fibrosis, have been suggested for the development of congestive heart failure, independent of CAD, in chronic diabetes.

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