The Metabolic Syndrome has been characterised in the United States in 1988 by G.M. Reaven. This adverse clustering of cardiovascular risk factors such as hypertension, glucose intolerance, high triglycerides, and low HDL-cholesterol concentrations was first proposedin the 1980’s as the syndrome X. ¹ Subsequently, several other metabolic abnormalities have been associated with this syndrome, including obesity, microalbuminuria, and abnormalities in fibrinolysis and coagulation. Insulin-resistance is thought to be the common denominator of the Metabolic Syndrome. Insulin-resistance is indeed a component of obesity, type 2 diabetes, and in many cases of hypertension, hypertriglyceridaemia with low levels of HDL-cholesterol. ^1,2

Obesity, and in particular the accumulation of central fat, also appears to play a key role in the pathophysiology of metabolic disorders. Abdominal obesity, measured either by waist circumference or waist-to-hip ratio, is associated with insulin-resistance and predicts the development of type 2 diabetes.³ In addition, abdominal obesity predicts subsequent coronary artery disease better than body mass index (BMI). ⁴ Central fat accumulation and presence of insulin-resistance have both been associated with a cluster of dyslipidaemic features, i.e., elevated plasma triglyceride level, an increase in very lowdensity lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), presence of small dense LDL particles, and a decrease in HDL-cholesterol.

These abnormalities of lipoprotein metabolism, which are more likely to occur together than separately, and in large part relate to insulin-resistance/ hyperinsulinaemia, have therefore been proposed to constitute key component traits of the Metabolic Syndrome. Insulin-resistance favouring the onset of type 2 diabetes develops commonly in association with correlated metabolic abnormalities recognised as cardiovascular risk factors and that are present prior to the onset of diabetes hypertriglyceridaemia, low HDL-cholesterol, increased intra-abdominal fat, hyperinsulinaemia, mild elevation of glycaemia and blood pressure.

Hyperglycaemia appears usually when pancreatic ß cell function can no longer compensate for insulin-resistance by increasing insulin release.³ Hence, type 2 diabetes has been recognised as the tip of an iceberg in which the antecedent and pivotal pathophysiological state was insulin-resistance and associated metabolic abnormalities. 3 Over the past decade, there has been an epidemic of diabetes world-wide. The incidence of type 2 diabetes has increased sharply in a number of countries around the world (Figure 1).

Adapted from Zimmet PZ. Diabetologia 1999;42:499-518 King H, et al. Diabetes Care 1998;21:1414-31
Figure 1. Global prevalence of type 2 diabetes estimates and projections

Diabetes is now common, affecting for instance more than 8% of the adult American population. This alarming increase is directly related to the parallel increase in sedentary lifestyle and the epidemic of obesity (Figure 2).

Source: Nature-Courtesy of the International Obesity Task Force 2003
Figure 2. Prevalence rates of obesity: history and projections from 1960 to 2025

Diabetic patients are not only affected by microvascular complications, but also by cardiovascular disease. Cardiovascular disease including coronary heart disease, cerebrovascular disease, and peripheral vascular disease represents the major cause of death in type 2 diabetic patients. The strong association between type 2 diabetes and cardiovascular disease suggests that they share a common physiologic antecedent, postulated to be insulin-resistance-related metabolic disorders. Mortality attributable to diabetes has alarmingly increased over the past two decades, emphasising the need to improve the management of macrovascular complications to alleviate the public health burden related to diabetes. The co-occurrence of risk factors for type 2 diabetes and metabolic abnormalities represents therefore a highly adverse metabolic state requiring early detection and aggressive risk factor intervention.

References

1. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-607.
2. Meigs JB. Epidemiology of the metabolic syndrome, 2002. Am J Manag Care 2002; 8 (11 suppl): S283-92.
3. Chan JM, Rimm EB, Colditz GA, et al. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994; 17: 961-9.
4. Ohlson LO, Larsson B, Svardsudd K, et al. The influence of body fat distribution on the incidence of diabetes mellitus. 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes 1985; 34: 1055-8.