LOSS OF THE 1ST 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 p rediabetic condition, therefore loss of first phase insulin secretion in subjects with IGT would suggest beta cell dysfunction as an early l esion 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 gluc ose tolerance at a repeat OGTT 6 months later), and 7 normal controls. First phase insulin secretion was studied using an intravenous glucos e tolerance test with arterialized blood sampling. Fasting, 3, 4 and 5 min samples were assayed for glucose and insulin (specific two-site i mmunoradiometric 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 subj ects with persistent impaired glucose tolerance demonstrated loss of t he first phase insulin response as an early indicator of beta cell dys function while subjects with transient IGT had a normal insulin respon se to intravenous glucose. During the OGTT, the 30 min glucose was not significantly different (p = 0.1) but the 30 min insulin to glucose r atio was significantly lower in subjects with persistent IGT (p < 0.03 ). In the whole group the 30 min insulin to glucose ratio during the O GTT showed a significant correlation with the peak insulin response du ring the IVGTT (r = 0.76, p < 0.001). This study suggests that beta ce ll dysfunction with impaired early insulin release is present before t he development of Type 2 diabetes.