Background and aims: Postprandial lipoprotein abnormalities in type 2 diabetes are associated with insulin resistance. The role of other diabetes-related factors is stilt not clear. The aim of this study is to differentiate the effects of whole-body insulin resistance, obesity, and type 2 diabetes on postprandial dyslipidaemia and lipoprotein lipase (LPL) in adipose tissue. Methods and results: Ten subjects with obesity and diabetes (OD), 11 with obesity alone (0), and 11 normal-weight controls (C) - mates, aged 26-59 years, with fasting normo-triglyceridaemia underwent measurements of cholesterol, triglycerides, apo B-48 and apo B-100 concentrations in plasma lipoproteins separated by density gradient ultracentrifugation before and after a fat-rich meal. Fasting and postprandial (6 h) LPL activity was determined in abdominal subcutaneous adipose tissue biopsy samples. Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp. OD and 0 subjects had similar degrees of adiposity (BMI, waist circumference, fat mass) and insulin resistance (insulin stimulated glucose disposal and M//). They also showed a similarly higher postprandial increase in large VLDL lipids (triglyceride incremental AUC 188 +/- 28 and 135 +/- 22 mg/dl.6 h) than C (87 +/- 13 mg/dl.6 h, M +/- SEM, p < 0.05). CD had an increased chylomicron response compared to 0 (triglyceride incremental AUC 132 +/- 23 vs. 75 +/- 14 mg/dl.6 h, p < 0.05). OD had significantly lower fasting and postprandial adipose tissue heparin-releasable LPL activity than O and C. Conclusions: In insulin-resistant conditions of obesity, with and without diabetes, large VLDL are increased after a fat-rich meat. In addition, diabetic patients compared to obese subjects have an increased postprandial chylomicron response and a reduced adipose tissue LPL activity. (C) 2008 Elsevier B.V. All rights reserved.