BACKGROUND.The appearance of hyperglycemia is due to insulin resistance, functional deficits in the secretion of insulin and a reduction of β-cell mass. There is a long-standing debate as to the relative contribution of these factors to clinically manifest β-cell dysfunction. The aim of this study was to verify the effect of one of these factors, the reduction of β-cell mass, on the subsequent development of hyperglycemia. METHODS. To pursue this aim, non-diabetic patients, scheduled for identical pancreaticoduodenectomy surgery, underwent oral glucose tolerance tests (OGTT) and hyperglycaemic clamps (HC), followed by arginine stimulation before and after surgery. Based on post-surgery OGTT, subjects were divided into 3 groups depending on glucose tolerance: normal (post-NGT), impaired (post-IGT) or diabetic (post-DM). RESULTS. At baseline the three groups showed similar fasting glucose and insulin levels, however, examining the various parameters, we found that reduced first-phase insulin secretion and reduced glucose sensitivity and rate sensitivity were predictors of eventual post-surgery development of impaired glucose tolerance and diabetes. CONCLUSION. Despite comparable functional mass and fasting glucose and insulin levels at baseline, and the very same 50% mass reduction, only reduced 1st phase insulin secretion and glucose sensitivity predicted the appearance of hyperglycemia. These functional alterations could be pivotal to the pathogenesis of type 2 diabetes (T2DM). TRIAL REGISTRATION. ClinicalTrials.gov Identifier: NCT02175459. FUNDING. Università Cattolica del Sacro Cuore; the Italian Ministry of Education, University and Research, European Foundation for the Study of Diabetes.
Teresa Mezza, Pietro Manuel Ferraro, Gianfranco Di Giuseppe, Simona Moffa, Chiara M.A. Cefalo, Francesca Cinti, Flavia Impronta, Umberto Capece, Giuseppe Quero, Alfredo Pontecorvi, Andrea Mari, Sergio Alfieri, Andrea Giaccari