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 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.
Unidad de Lípidos y Arteriosclerosis, Hospital Universitario Reina Sofía, Córdoba, Spain.
J
J
Salas
S
S
Jansen
J
J
López-Miranda
J M
JM
Ordovás
P
P
Castro
C
C
Marín
M A
MA
Ostos
M D
MD
Bravo
J
J
Jiménez-Perepérez
A
A
Blanco
F
F
López-Segura
F
F
Pérez-Jiménez
D000284:Administration, Oral; D000328:Adult; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D015992:Body Mass Index; D050260:Carbohydrate Metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D011110:Polymorphism, Genetic
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D004041:Dietary Fats; D007328:Insulin