The SstI polymorphism of the apolipoprotein C-III gene determines the insulin response to an oral-glucose-tolerance test after consumption of a diet rich in saturated fats.

The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-III gene has been associated with elevat- ed triacylglycerol concentrations, high blood pressure, and increased risk of coronary artery disease, all of which are charac- teristic of an insulin-resistant state. To study the effect of this mutation on carbohydrate metabolism in healthy persons, we gave 41 male subjects 3 consecutive diets. The first was rich in saturated fat (15% protein, 47% carbohydrate, 38% fat (20% sat- urated)), the second was a National Cholesterol Education Pro- gram Step 1 diet (15% protein, 57% carbohydrate, 28% fat (< 10% saturated)), and the last was rich in monounsaturated fat (15% protein, 47% carbohydrate, 38% fat (22% monounsaturat- ed, < 10% saturated)). At the end of each dietary period, subjects received an oral-glucose-tolerance test (OGTT). Apo C-III genotype significantly affected basal glucose concentrations (P < 0.045) and insulin concentrations after the OGTT (P < 0.012). APOC3*S1/APOC3*S2 subjects (n = 13) had higher insulin concentrations after the OGTT than APOC3*S1/APOC3*S1subjects (n = 28) in the 3 periods (diet 1: P < 0.0004; diet 2: P < 0.01; diet 3: P < 0.008). Multiple regres- sion analysis showed that this polymorphism predicted the insulin response to the OGTT (P < 0.031) and the difference between basal insulin concentrations and insulin concentrations after the OGTT (P < 0.002) with the saturated fat diet. In summary, our results suggest that the mutation in the apo C-III gene affects insulin response to an OGTT, which could result in reduced sen- sitivity to insulin, especially when persons consume diets rich in saturated fat. Am J Clin Nutr 1998;68:396-401.