The link between obesity and Type 2 diabetes has long been established and a visit to any diabetes clinic will confirm the alarming statistic that 90% of those with Type 2 diabetes are also estimated to be obese (18). It is not currently known whether insulin resistance is the cause of obesity, the result of obesity, or whether the two conditions arise independently from each other (19). It is known that the prevalence of insulin resistance is greater among the obese, however, there are normal weight individuals who are equally insulin resistant
(20). Without question, reduction in weight is associated with improvements in insulin sensitivity (21,22). It is also clear that regular physical activity improves insulin action, although the exact mechanisms involved are not clear.
Several mechanisms have been proposed to explain how excessive body weight is associated with Type 2 diabetes. In general, the accumulation of fat mass is associated with a decline in whole body insulin sensitivity. The distribution of obesity is important, with resistance to the action of insulin and glucose intolerance most closely associated with excess abdominal adipose tissue. As visceral adipose tissue increases plasma triglyceride (TG) concentrations are elevated, high-density lipoprotein (HDL) cholesterol decreases and low-density lipoprotein (LDL) cholesterol increases with a greater proportion of the more atherogenic small dense LDL particles (LDL subclass III). Other associated characteristics include an elevated plasma non-esterified fatty acid (NEFA) concentration, an increased plasminogen activator inhibitor 1 (PAI-1) concentration, hyperuricaemia and hypertension. Abdominal obesity is also associated with specific changes in skeletal muscle morphology, namely a reduction in capillary density and an increase in the proportion of 'white' or 'glycolytic' fibres which are less insulin sensitive than the red (oxidative) fibres (23). Within the adipocyte an increase in the expression of products such as tumour necrosis factor-a (TNF-a) and leptin may also contribute to the deterioration in insulin sensitivity. More recently a novel protein known as resistin has been reported as providing the missing link in explaining the molecular link between diabetes and obesity. Resistin is secreted by adipocytes. Its circulating levels correlate with obesity and it has been shown to cause insulin resistance in target tissues (24).
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