In patients with diabetic renal failure, attention must be paid to the prevention of atherosclerosis as well as the preservation of renal function. Insulin resistance is one of the important risk factors of atherosclerosis and the involvement of tumor necrosis factor-α (TNF-α) has been shown in the pathogenesis of insulin resistance in some diseases. A low-protein diet (LPD) is recommended for patients with advanced renal disease, but a large proportion of the total caloric intake is supplied from carbohydrates and fat in LPD. Therefore, we designed a study to determine : (1) the effect of TNF-α on insulin sensitivity, and (2) the effect of LPD on the TNF-α response and the risk factors of atherosclerosis, such as insulin sensitivity and lipid metabolism, in patients with diabetic renal failure. Insulin sensitivity was measured by an euglycemic hyperinsulinemic clamp technique and serum TNF-α level and in vitro release of TNF-α from peripheral blood mononuclear cells (PBMCs) was measured in patients with diabetic renal failure. A significant negative correlation was observed between lipopolysaccharide-stimulated TNF-α release from PBMCs and insulin sensitivity (r=-0.58. p&lt
0.05). Secondly, risk factors of atherosclerosis were measured before and two weeks after the introduction of LPD in patients with diabetic renal failure. LPD did not have any significant effect on insulin sensitivity, the production of TNF-α by PBMCs, lipid metabolism and glucose metabolism. These results indicate that : (1) TNF-α derived from PBMCs might affect insulin sensitivity in patients with diabetic renal failure, and (2) LPD does not have any significant effect on the risk factors of atherosclerosis.