Assessing the Shape of the Glucose Curve During an Oral Glucose Tolerance Test

Abstract

OBJECTIVE—The oral glucose tolerance test (OGTT) is used to define the status of glucose tolerance based on the plasma glucose level at 120 min. The purpose of the present study was to identify parameters that determine the shape of the plasma glucose course measured at 0, 30, 60, 90, and 120 min during an OGTT. RESEARCH DESIGN AND METHODS—OGTT data from 551 subjects (485 with normal glucose tolerance [NGT] and 66 with impaired glucose tolerance [IGT]) were analyzed. We distinguished between “monophasic,” “biphasic,” and unclassified glucose shapes. A “shape” index based on the extent and the direction of the plasma glucose change in the second hour allowed us to treat shape as a continuous variable. RESULTS—In the biphasic group, the NGT-to-IGT ratio was slightly higher (173/20 vs. 209/40, P = 0.08) and the male-to-female ratio was lower (60/133 vs. 120/129, P = 0.0003). Subjects with a biphasic shape had significantly lower age, BMI, waist-to-hip ratio (WHR), HbA1c, plasma glucose, and area under the insulin curve (insulinAUC) and a better estimated insulin sensitivity and secretion (using validated indexes) than monophasic subjects (all P < 0.05). By adjusting this shape index for glucoseAUC (as continuous measure of glucose tolerance), correlations with age, BMI, WHR, HbA1c, and insulinAUC were completely abolished. The adjusted shape index was still higher in female than in male subjects but lower in IGT than in NGT subjects (both P = 0.0003). Finally, we tested common polymorphisms in insulin receptor substrate (IRS)-1, IRS-2, calpain-10, hepatic lipase, and peroxisome proliferator-activated receptor-γ for association with the shape index. CONCLUSIONS—We conclude that the plasma glucose shape during an OGTT depends on glucose tolerance and sex. In addition, genetic factors seem to play a role. The shape index may be a useful metabolic screening parameter in epidemiological and genetic association studies.