Patients with type 2 diabetes are frequently dyslipidemic or hypertriglyceridemic. To assess whether increased intestinal triglyceride input leads to elevated fasting and postprandial triglycerides in type 2 diabetes, we used the codon 54 polymorphism of the fatty acid-binding protein 2 gene, which results in the substitution of threonine (Thr) for alanine and is associated with increased intestinal input of triglyceride. Of the 287 diabetic patients screened, 108 (37.6%) were heterozygous and 31 (10.8%) were homozygous for the Thr-54 allele. Mean (+/-SEM) fasting plasma triglyceride levels in patients with the wild-type (n = 80), those heterozygous for the Thr-54 allele (n = 57), and those homozygous for it (n = 18) were 2.0 +/- 0.09, 2.7 +/- 0.20, and 3.8 +/- 0.43 mmol/L, respectively. A linear relationship of mean fasting plasma triglyceride levels (r2 = 0.97) between the 3 groups was found. After fat ingestion, the postprandial area under the curve of plasma triglyceride (P = 0.025) and chylomicrons (Sf > 400, P = 0.013) was higher in the Thr-54/Thr-54 (n = 6) than in the wild-type (n = 9). Our results are consistent with the hypothesis that, in type 2 diabetes, increased intestinal input of triglyceride can lead to elevated fasting and postprandial plasma triglycerides.