Impaired Crosstalk between Pulsatile Insulin and Glucagon Secretion in Prediabetic Individuals

Introduction: Postprandial hyperglucagonemia is frequently found in patients with diabetes. Recently, a loss of the inverse relationship between pulsatile insulin and glucagon secretion has been reported in patients with type 2 diabetes. The crosstalk between pulsatile islet hormone secretion in prediabetic individuals has not yet been examined. Patients and Methods: Eleven individuals with impaired glucose tolerance and/or impaired fasting glucose and 13 nondiabetic controls were examined after mixed meal ingestion. Glucose, insulin, and glucagon levels were determined frequently and analyzed by deconvolution and cross-correlation methods. Results: Postprandial glucose levels were higher in prediabetic individuals (P = 0.017). Insulin concentrations were not different between the groups (P = 0.29). Postprandial glucagon levels were higher in the impaired glucose tolerance/impaired fasting glucose individuals (P = 0.039). Pulsatile insulin and glucagon secretion was apparent in both groups, but there were no differences in the frequency or mass of insulin and glucagon pulses between the groups. An inverse relationship between the insulin and glucagon concentration time curves was found in the control subjects (P < 0.05). This association was not detectable in the prediabetic individuals. Conclusions: Increased postprandial glucagon concentrations in prediabetic individuals are accompanied by a loss of the pulsatile insulin-glucagon crosstalk. This suggests that disturbances in islet hormone pulsatility precede the actual manifestation of hyperglycemia.