Metabolic Syndrome as a Link between Insulin Resistance and CVD

Metabolic syndrome refers to a constellation of risk factors that is apparently associated with risk for both CVD and type 2 diabetes (Figure 2.7). Although a clustering of risk factors had been recognized as early as the 1920s, Gerald Reaven's Banting lecture in 1988 (Reaven, 1988) disseminated the concept to a wider audience and stimulated considerable further research. Reaven linked 'upstream' insulin resistance to a 'downstream' clustering of risk factors potentially responsible for the excess vascular risk in diabetes. He included glucose intolerance, hypertriglyceridaemia, low HDL-cholesterol and hypertension in his clustering, which he termed 'syndrome X', but interestingly obesity was not included (Reaven, 1988). The syndrome has since been variably termed the insulin resistance syndrome, Reaven's syndrome and the dysmetabolic syndrome. However, as it is not a discrete entity caused by a single

Obesity

Insulin resistance

Type 2

Dietary excess Sedentary lifestyle Genetic predisposition Programming

Obesity

Insulin resistance

Type 2

diabetes

Figure 2.7 Scheme displaying the concept of metabolic syndrome as a link between obesity and insulin resistance (and related factors) with subsequent vascular disease and type 2 diabetes.

factor, but is likely caused by various factors in different individuals and racial groups, 'metabolic syndrome' has now become the preferred term. It should be stated at this point that some have questioned whether the collection of risk factors linked to obesity and insulin resistance truly constitutes a 'syndrome' (Kahn etal., 2005). Regardless of such arguments, criteria for metabolic syndrome have been used to try to demonstrate increased CVD in subjects with a constellation of insulin resistance-related features. These studies have universally demonstrated that individuals with the metabolic syndrome do indeed have a higher risk of CVD, with greater risk with each additional criterion fulfilled (Sattar etal., 2003b; Wilson etal., 2005). However, it remains contentious whether metabolic syndrome criteria will be used in clinical practice (Sattar, 2006b). At present, the available prospective data do not suggest that metabolic syndrome criteria enhance risk prediction beyond traditional risk factor charts based on the Framingham risk score (Sattar, 2006b). Nevertheless, with specific reference to diabetes, it is of interest that subjects with type 2 diabetes who do not fulfil the criteria for metabolic syndrome do not appear at elevated CVD risk, whereas those who do fulfil the criteria are at increased risk (Alexander etal., 2003). Such data concur with the observation that CVD risk is highest in the insulin-resistant patients with type 2 diabetes.

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