Chapter

Pathophysiology of type 2 diabetes mellitus

Hannele Yki-Järvinen

in Oxford Textbook of Endocrinology and Diabetes

Second edition

Published on behalf of Oxford University Press

ISBN: 9780199235292
Published online July 2011 | e-ISBN: 9780199608232 | DOI: http://dx.doi.org/10.1093/med/9780199235292.003.1336

Series: Oxford Textbooks

Pathophysiology of type 2 diabetes mellitus

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Insulin resistance, largely caused by obesity and physical inactivity, both precedes and predicts type 2 diabetes. The insulin resistance preceding type 2 diabetes is commonly referred to as the metabolic syndrome. The latter condition consists of a cluster of risk factors, which are thought to be either causes or consequences of insulin resistance. The development of type 2 diabetes, overt hyperglycaemia, also requires the presence of a relative defect in insulin secretion. This defect appears, at least in part, genetically determined.

Insulin resistance can be defined as the inability of insulin to produce its usual biological actions at circulating concentrations that are effective in normal subjects. This chapter is focused on defining and characterizing defects in insulin action and in insulin and glucagon secretion in patients with type 2 diabetes, and the effects that these defects have on the body. The causes of insulin resistance in different tissues is also discussed.

Hepatic insulin resistance and metabolic syndrome can be linked to atherosclerosis and cardiovascular disease, the main cause of the excess mortality in type 2 diabetes, by increased very-low-density lipoprotein production which leads to the generation of small, dense, and atherogenic LDL particles. Insulin resistance is also seen in adipose tissue and skeletal muscle, altering glucose and fatty acid handling in these tissues and the liver. The hepatic manifestation of insulin resistance in type 2 diabetes is nonalcoholic fatty liver disease (NAFLD). NFALD is defined as excess fat in the liver which is not due to excess alcohol use, and can lead to hepatic inflammation and even cirrhosis.

There are defects in both insulin and glucagon secretion in type 2 diabetes, the exact cause of which remains speculative. Whilst family history and genetic factors appear to play a significant role in determining the susceptibility to overt type 2 diabetes, the only certain aspect of its aetiology and pathogenesis is that its incidence can very significantly be reduced by increasing physical activity and avoiding obesity.

Chapter.  7205 words.  Illustrated.

Subjects: Endocrinology and Diabetes

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