Japanese IGT subjects with high insulin response are far more frequently associated with the metabolic syndrome than those with low insulin response

Abstract

Impaired glucose tolerance (IGT) represents a prediabetic state positioned somewhere between normal glucose tolerance and diabetes, which is also assumed to make individuals in this state highly susceptible to atherosclerotic disease. IGT also accounts for a highly heterogeneous population, with the condition varying from individual to individual. In this study, we stratified subjects with IGT by their insulin response and compare the pathology of IGT when it is associated with high or low insulin response to gain insight into the diverse pathology of IGT. Of the male corporate employees who underwent 75 g OGTT at the corporation's healthcare center, 150 individuals diagnosed with IGT (isolated IGT, combined IGT and IFG) comprised our study subjects. The study subjects were stratified into four quartiles by percentile AUC for insulin, and those in the 25th or less percentile were defined as the low insulin response group (n = 37), vs those in the 76th or greater percentile defined as the high insulin response group (n = 38), and these groups were compared. There was no significant difference observed between the two groups in regard to post-OGTT glucose response and area under the glucose curve. However, the high insulin response group was associated with higher BMI, subcutanesous fat area, uric acid levels, HOMA-beta cell values, and delta insulin/delta glucose (30 min) than the low insulin response group. The number of risk factors for the metabolic syndrome detected (as defined by the ATPIII diagnostic criteria) per subject was 2.84 +/- 0.17 and 2.08 +/- 0.20, respectively, in the high insulin response group and in the low insulin response group, with the number significantly (p < 0.05) higher in the high insulin response group. Furthermore, the incidence of the metabolic syndrome as defined by the ATPIII diagnostic criteria was 63.2% (24/38) in the high insulin response group vs 32.4% (12/27) in the low insulin response group, with the incidence significantly (p < 0.01) higher in the high insulin response group. Likewise, the incidence of the metabolic syndrome as defined by the Japanese diagnostic criteria was found to be significantly (p < 0.05) higher in the high insulin response group at 50% (19/38) compared to 27.0% (10/37) in the low insulin response group. Our study findings suggest that IGT subjects with high insulin response and those with low insulin response vary greatly in regard to the number of atherosclerotic risk factors complicated and the frequency with which they are associated with the metabolic syndrome. It is also shown in middle-aged Japanese males that of the two forms of IGT, IGT with high insulin response is more closely linked to the pathogenesis of atherosclerotic cardiovascular disease.