Mechanisms of macrovascular disease in diabetes

Peter J. Grant and Mark T. Kearney

in Oxford Textbook of Endocrinology and Diabetes

Second edition

Published on behalf of Oxford University Press

Published in print July 2011 | ISBN: 9780199235292
Published online July 2011 | e-ISBN: 9780199608232 | DOI:

Series: Oxford Textbooks

Mechanisms of macrovascular disease in diabetes

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The virtual epidemic of diabetes that has appeared over the last couple of decades has highlighted the influence of Western lifestyles and obesity on the development of glucose intolerance and associated cardiovascular disease. Two important hypotheses need consideration in contemplating the strong clinical links that exist between diabetes and cardiovascular disease.

The thrifty genotype hypothesis proposed that the development of insulin resistance was an innate biochemical mechanism that acted to conserve energy in times of food shortage as obesity becomes chronic, as in modern life, insulin resistance would lead to the development of type 2 diabetes, thus introducing the concept of exposure as an important pathogenic factor.

The common soil hypothesis argued that diabetes and cardiovascular disease are the same condition underpinned by common genetic and environmental factors.

One of the great advances in understanding in the past 20 years has been the observation that insulin resistance is associated with inflammatory and atherothrombotic risk factor clustering to provide a risk ‘mirror’ for the changes observed in the vulnerable atheromatous plaque. This brings together the thrifty and the common soil hypotheses and indicates that physiological fluctuations in weight and insulin resistance seen in relation to variation in food availability become pathological with chronic exposure leading to both type 2 diabetes and cardiovascular disease. As insulin resistance cycles to type 2 diabetes, hyperglycaemia has further detrimental effects on vascular disease through the generation of reactive oxygen species, glycation of longlasting proteins, and direct effects of glucose. Epidemiological studies demonstrate a marked increase in vascular outcomes as individuals move from euglycaemic insulin resistance to type 2 diabetes to reflect this increased risk. Finally, the development of microvascular renal disease amplifies vascular risk further and the combination of hyperglycaemia and renal disease provides a common pathway for increased cardiovascular risk in both type 1 and type 2 diabetes.

Chapter.  4073 words. 

Subjects: Endocrinology and Diabetes

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