Grant: Operating Grant

Diabetes and pre-diabetes are metabolic disorders affecting more than 15% of the world's population and their prevalences are on the increase due mainly to more sedentary lifestyles associated with rising obesity rates and aging of the population. Because diabetes and pre-diabetes are so closely associated with major health problems such as high blood pressure, high blood cholesterol and cardiovascular disease (CVD), they have a huge impact on the health care costs of our society. Major efforts should therefore be undertaken to tackle from a societal perspective this critical problem. Although elevated blood cholesterol levels observed in diabetes and pre-diabetes have largely been attributed to overproduction by the liver, recent studies from our group have indicated that the small intestine also contributes significantly to elevated blood cholesterol levels. Nutritional guidelines currently focus on substitution of saturated fatty acids (SFA) by polyunsaturated fatty acids (PUFA) and this is largely based on the evidence that consumption of PUFA in place of SFA reduces CVD risk. Recent data suggest that PUFA may exert beneficial effects on CVD risk by reducing intestinal cholesterol production but no studies have examined this issue in patients with diabetes or pre-diabetes. This study will allow us to investigate whether substitution of SFA by PUFA could reduce intestinal cholesterol production in patients with pre-diabetes. We will also examine the impact of PUFA on the expression of the major genes and proteins involved in the regulation of intestinal cholesterol metabolism. Identification of therapeutic strategies using non-pharmacologic agents such as PUFA is likely to lead to significant advances in our attempts to reduce CVD risk in this vulnerable population.