[Risk factors associated with obesity: a metabolic perspective]

Abstract

Obesity, especially visceral obesity, is associated with a cluster of metabolic complications increasing the risk of type 2 diabetes and coronary heart disease. It has been shown that obese patients characterized by a high accumulation of visceral adipose tissue have increased glycemic and insulinemic responses to an oral glucose load compared to normal weight individuals or to obese individuals with a low accumulation of visceral adipose tissue. Viscerally obese patients are also characterized by an unfavourable plasma lipid profile which includes elevated triglyceride and apolipoprotein B concentrations, reduced HDL-cholesterol levels as well as an increased proportion of small, dense LDL particles. Such alterations in the lipid profile are often observed even in the absence of elevated LDL-cholesterol concentrations. Our work has clearly shown that this cluster of metabolic abnormalities found among viscerally obese patients was associated with a substantial increase in coronary heart disease risk. Our work has also shown that the "metabolic triad" of non-traditional risk factors (hyperinsulinemia, elevated apolipoprotein B levels, increased proportion of small, dense LDL particles) was associated with a 20-fold increase in the risk of coronary heart disease. In this regard, we have been interested in developing simple tools which would allow clinicians to identify at an early stage and at low cost individuals who would be carriers of the atherogenic metabolic triad. We have noted that the measurement and interpretation of waist circumference and of fasting plasma triglyceride levels could allow the identification of a high proportion of carriers of the metabolic triad. Indeed, less than 10% of men with a waist circumference below 90 cm and triglyceride concentrations below 2 mmol/l were characterized by the features of the metabolic triad. However, more than 80% of individuals with a waist circumference above 90 cm and triglyceride levels above 2 mmol/l were carriers of the metabolic triad. Finally, an elevated visceral adipose tissue accumulation has also been associated with a thrombogenic and a pro-inflammatory metabolic profile which would be predictive of an unstable atherosclerotic plaque. Therefore, the stabilisation of the atherosclerotic plaque may represent a legitimate therapeutic objective to reduce the risk of coronary heart disease among patients with visceral obesity. It is proposed that a rather modest weight loss (approximately 10%) could contribute to substantially improve the risk profile of these patients.