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

• Published in: The American journal of clinical nutrition Vol. 68; no. 2; pp. 396 - 401
• Main Authors: SALAS, J, JANSEN, S, LOPEZ-SEGURA, F, PEREZ-JIMENEZ, F, LOPEZ-MIRANDA, J, ORDOVAS, J. M, CASTRO, P, MARIN, C, OSTOS, M. A, BRAVO, M. D, JIMENEZ-PEREPEREZ, J, BLANCO, A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.08.1998
• Subjects: Administration, Oral; Adult; Apolipoprotein C-III; Apolipoproteins C - genetics; Biological and medical sciences; Body Mass Index; Carbohydrate Metabolism; Carbohydrates; Dietary Fats - administration & dosage; Fundamental and applied biological sciences. Psychology; Glucose Tolerance Test; Humans; Insulin - pharmacology; Male; Metabolisms and neurohumoral controls; Polymorphism, Genetic; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Apolipoprotein C; Gene; Saturated fatty acid; Lipids; Carbohydrate; Glucose tolerance test; Supplemented diet; Metabolism; Insulin; Feeding; Polymorphism
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/68.2.396

The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-III gene has been associated with elevated triacylglycerol concentrations, high blood pressure, and increased risk of coronary artery disease, all of which are characteristic 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% saturated)], the second was a National Cholesterol Education Program 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% monounsaturated, < 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*S1 subjects (n = 28) in the 3 periods (diet 1: P < 0.0004; diet 2: P < 0.01; diet 3: P < 0.008). Multiple regression 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 sensitivity to insulin, especially when persons consume diets rich in saturated fat.