Loss of the First Phase Insulin Response to Intravenous Glucose in Subjects with Persistent Impaired Glucose Tolerance

Loss of the first phase insulin response to intravenous glucose is one of the earliest detectable defects of beta cell dysfunction in Type 2 diabetes mellitus. Impaired glucose tolerance (IGT) is considered a prediabetic condition, therefore loss of first phase insulin secretion in subjects with IGT would suggest beta cell dysfunction as an early lesion in the development of Type 2 diabetes. Three groups of subjects were studied, 7 subjects with persistent IGT (classified as having IGT at two 75 g oral glucose tolerance tests (OGTT) done 6 months apart), 6 subjects with transient IGT (IGT at the first OGTT, but normal glucose tolerance at a repeat OGTT 6 months later), and 7 normal controls. First phase insulin secretion was studied using an intravenous glucose tolerance test with arterialized blood sampling. Fasting, 3, 4 and 5 min samples were assayed for glucose and insulin (specific two‐site immunoradiometric assay). The fasting insulin was similar in all three groups, however the 3 min insulin response was significantly lower in those with persistent impaired glucose tolerance ( p < 0.02). Thus subjects with persistent impaired glucose tolerance demonstrated loss of the first phase insulin response as an early indicator of beta cell dysfunction while subjects with transient IGT had a normal insulin response to intravenous glucose. During the OGTT, the 30 min glucose was not significantly different ( p = 0.1) but the 30 min insulin to glucose ratio was significantly lower in subjects with persistent IGT ( p < 0.03). In the whole group the 30 min insulin to glucose ratio during the OGTT showed a significant correlation with the peak insulin response during the IVGTT ( r = 0.76, p < 0.001). This study suggests that beta cell dysfunction with impaired early insulin release is present before the development of Type 2 diabetes.