Relatives of subjects with type 2 diabetes carry an increased risk for diabetes and cardiovascular disease. Oxidative modification of low-density lipoprotein (LDL) and proinflammatory processes are believed to have central roles in atherogenesis. We have investigated the susceptibility of LDL to oxidation and circulating cell adhesion molecules in healthy, glucose-tolerant adults (aged 18 to 38 years) with (12 men, 2 women) and without (controls; 12 men, 2 women) a parental history of type 2 diabetes. From fasting blood samples, oxidation of LDL was initiated with copper ions and adhesion molecules were measured using immunoassays. Groups were similar with respect to age, body mass index (BMI), blood pressure, plasma glucose, and serum lipids. Resistance of LDL to oxidation was reduced in offspring of parents with type 2 diabetes (time to Vmax, 80.1 +/- 2.2 v 91.4 +/- 2.6 minutes, P =.003). Plasma hydroperoxides did not differ between groups (1.2 +/- 0.1 v 1.1 +/- 0.1 micromol/L). Soluble intracellular adhesion molecule-1 (sICAM1) was elevated in offspring compared with controls (571 +/- 20 v 447 +/- 20 microg/L, P =.0002). Soluble vascular cell adhesion molecule-1 (sVCAM-1) (1,184 +/- 76 v 1084 +/- 56 microg/L, P =.31) and E-selectin (53 +/- 8 v 53 +/- 7 microg/L, P =.98) did not differ between groups. Reduced resistance of LDL to oxidation and increased circulating sICAM-1 in young healthy adult offspring of parents with type 2 diabetes may be intrinsic to increased risk of atherosclerosis in these subjects.