Dietary fat and insulin action in humans.

A high intake of fat may increase the risk of obesity. Obesity, especially abdominal obesity, is an important determinant of the risk of developing insulin resistance and non-insulin-dependent diabetes mellitus. It is suggested that a high proportion of fat in the diet is associated with impaired insulin sensitivity and an increased risk of developing diabetes, independent of obesity and body fat localization, and that this risk may be influenced by the type of fatty acids in the diet. Cross-sectional studies show significant relationships between the serum lipid fatty acid composition, which at least partly mirrors the quality of the fatty acids in the diet, and insulin sensitivity. Insulin resistance, and disorders characterized by insulin resistance, are associated with a specific fatty acid pattern of the serum lipids with increased proportions of palmitic (16:0) and palmitoleic acids (16:1 n-7) and reduced levels of linoleic acid (18:2 n-6). The metabolism of linoleic acid seems to be disturbed with increased proportions of dihomo-gamma linolenic acid (20:3 n-6) and a reduced activity of the delta 5 desaturase, while the activities of the delta 9 and delta 6 desaturases appear to be increased. The skeletal muscle is the main determinant of insulin sensitivity. Several studies have shown that the fatty acid composition of the phosholipids of the skeletal muscle cell membranes is closely related to insulin sensitivity. An increased saturation of the membrane fatty acids and a reduced activity of delta 5 desaturase have been associated with insulin resistance. There are several possible mechanisms which could explain this relationship. The fatty acid composition of the lipids in serum and muscle is influenced by diet, but also by the degree of physical activity, genetic disposition, and possibly fetal undernutrition. However, controlled dietary intervention studies in humans investigating the effects of different types of fatty acids on insulin sensitivity have so far been negative.