ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 12 S33

What role for adipocytokines in insulin resistance and diabetes prediction? From genes to epidemiology

N Sattar

Glasgow Royal Infirmary, Glasgow, United Kingdom.

Excess weight/obesity is a major risk factor for type 2 diabetes. Mechanisms linking obesity to insulin resistance in other liver and skeletal muscle are of considerable interest and the role of adipokines, in particular adiponectin, has come under considerable interest. Adiponectin is exclusively produced by fat cells but its circulating levels are paradoxically reduced in obesity. Current weight of evidence from prospective studies suggest that high adiponectin levels are protective against diabetes. Potential mechanisms have been described and include adiponectin’s ability to enhance fatty acid oxidation. However, other evidence suggests the picture is more complex than originally considered since elevated adiponectin does not appear to be associated with protection from CHD events, and higher levels predict greater mortality in those with heart failure.

There is also considerable interest in the inflammatory hypothesis for diabetes. BMI/waist circumference are major correlates of low grade inflammation although higher circulating levels of inflammatory parameters predict new-onset diabetes independently of BMI. Adipocytes and/or associated macrophages in fat depots may release inflammatory factors into the circulation, thereby contributing to insulin resistance in other tissues by a variety of potential mechanisms. Many insulin sensitising agents (e.g. glitazones) are also apparently anti-inflammatory. Although such insights may eventually lead to new therapies for diabetes, further research, including genetic studies, are needed to unravel genuine causal pathways for diabetes.

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