Insulin secretion and insulin sensitivity in relation to fasting glucose in healthy subjects

OBJECTIVE—This study evaluated insulin secretion and insulin sensitivity in healthy subjects with normal fasting glucose. RESEARCH DESIGN AND METHODS—A total of 148 healthy women (aged 53–70 years) underwent a glucose-dependent arginine stimulation test and a 2-h euglycemic-hyperinsulinemic clamp. In the arginine test, arginine (5 g) was injected intravenously under baseline (fasting) conditions and after raising the glucose levels to 15 and >28 mmol/l. From this test, the acute insulin response (AIR) to arginine during the three glucose levels (AIR1, AIR2, and AIR3) were estimated. The subjects were divided into quartiles of fasting glucose (n = 37 in each group [range RESULTS—The results show that 1) AIR1 was higher in subjects in the two highest quartiles (P = 0.004), 2) AIR3 was higher in the quartile with the highest fasting glucose (P = 0.012), and 3) insulin sensitivity was reduced in subjects in the highest quartile (P = 0.026) compared with the lower quartiles. The results also show, in contrast, that AIR2 did not show a similar trend to be increased at higher fasting glucose. CONCLUSIONS—It is concluded that 1) raised fasting glucose (albeit still within normal values) augments baseline and maximal arginine-induced insulin secretion in healthy subjects, and 2) this is associated with reduced insulin sensitivity. This suggests that high, but still normal, fasting glucose may contribute to the augmented insulin secretion in subjects with low insulin sensitivity.