The truism that blood sugar is elevated in people with diabetes has dominated mechanistic thinking about this terrible disease for more than a century. Diabetes frequently leads to myocardial infarction, the consequence of chronic inflammation associated with lipid deposition in coronary arteries. Atherosclerotic lesions causing macrovascular (cardiovascular) complications are similar whether hyperglycemia occurs in type 1 diabetes (absolute insulin deficiency) or type 2 diabetes (relative insulin deficiency and insulin resistance). Despite a lack of supporting evidence, it was assumed that lowering glucose would decrease macrovascular complications as it does for microvascular complications such as retinopathy.
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Albert Einstein is credited with defining insanity as doing the same thing over and over again and expecting different results. It was not irrational to test the hypothesis that lowering glucose prevents heart disease, but careful studies have done just that over and over again. The data indicate that glucose is a powerful biomarker but not the major mechanistic mediator of atherosclerosis in diabetes. Developing new approaches to diabetic cardiovascular disease will require pursuing glucose-independent mechanisms at the bench encompassing the broad spectrum of abnormalities that plague patients with the most common metabolic disorder in the world.
Nature Medicine, Abril 2009
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