Insulin resistance, a condition associated with type 2 diabetes, results from the interaction of environmental and genetic factors. Objective: We examined the influence of the intestinal fatty acidbinding protein 2 (FABP2) Ala54Thr polymorphism on insulin sensitivity. Design: Fifty-nine healthy young subjects (28 were Ala54/Ala54, 27 were Ala54/Thr54, and 4 were Thr54/Thr54) completed 3 diets, each of which lasted 4 wk. The first diet, which all subjects consumed, was a high-saturated fatty

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... (SFA) diet (38% of energy as fat and 20% of energy as SFAs). The second and third diets were administered according to a randomized crossover design, and they consisted of a low-fat and high-carbohydrate diet (CHO diet; 28% of energy from fat and 10% of energy from SFAs) and a high-monounsaturated fatty acid (MUFA) diet (called the Mediterranean diet; 38% of energy from fat and 22% of energy from MUFAs). All food and drinks were prepared and provided in the research kitchen. We determined in vivo insulin resistance by using the insulin suppression test with somatostatin. Results: Steady state plasma glucose concentrations were significantly higher in Ala54Thr subjects after the SFA diet than after the CHO diet or the Mediterranean diet. The plasma free fatty acid concentrations in these subjects were significantly lower after the CHO and Mediterranean diets than after the SFA diet. However, no significant differences between the 3 diets were observed in the Ala54 allele homozygotes. Conclusion: Insulin sensitivity decreased in subjects with the Thr54 allele of the FABP2 polymorphism when SFAs were replaced by MUFAs and carbohydrates. Am J Clin Nutr 2005;82:196 -200. KEY WORDS Ala54Thr polymorphism, steady state plasma glucose, Mediterranean diet, insulin sensitivity, dietary fat