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 acute 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 hyperglycemic 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 first 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).

Mezza, T., Ferraro, P. M., Di Giuseppe, G., Moffa, S., Cefalo, C. M., Cinti, F., Impronta, F., Capece, U., Quero, G., Pontecorvi, A., Mari, A., Alfieri, S., Giaccari, A., Duodenopancreatectomy as a model to demonstrate the fundamental role of dysfunctional β cell in predicting diabetes, <<THE JOURNAL OF CLINICAL INVESTIGATION>>, 2021; 2021 (NA): N/A-N/A. [doi:10.1172/JCI146788] [http://hdl.handle.net/10807/179371]

Duodenopancreatectomy as a model to demonstrate the fundamental role of dysfunctional β cell in predicting diabetes

Mezza, Teresa
Primo
;
Ferraro, Pietro Manuel;Di Giuseppe, Gianfranco;Moffa, Simona;Cefalo, Chiara Ma;Impronta, Flavia;Capece, Umberto;Quero, Giuseppe;Pontecorvi, Alfredo;Alfieri, Sergio;Giaccari, Andrea
2021

Abstract

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 acute 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 hyperglycemic 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 first 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).
Inglese
Mezza, T., Ferraro, P. M., Di Giuseppe, G., Moffa, S., Cefalo, C. M., Cinti, F., Impronta, F., Capece, U., Quero, G., Pontecorvi, A., Mari, A., Alfieri, S., Giaccari, A., Duodenopancreatectomy as a model to demonstrate the fundamental role of dysfunctional β cell in predicting diabetes, <>, 2021; 2021 (NA): N/A-N/A. [doi:10.1172/JCI146788] [http://hdl.handle.net/10807/179371]
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