1555-P: Effects of 80% Pancreas Reduction on Beta-Cell Function and Glucose Metabolism

Introduction and Objectives: Diabetes typically develops when the endocrine pancreas fails to cope to insulin demand with adequate insulin secretion. Many studies have shown that diabetes appears when the loss of pancreatic β cell mass is approximately between 41% and 65% in humans. Near total pancreatectomy (NTP) is a surgical procedure that removes 80% of pancreatic mass.To investigate the metabolic effects of NTP in a cohort of nondiabetic subjects.

Methods: We recruited 7 subjects who underwent an oral glucose tolerance test (OGTT) and a hyperglycemic clamp (HC) followed by arginine stimulation, before and 3 months after NTP. We calculated the area under the curve of glucose (AUC-Glu) and insulin (AUC-Ins) responses during OGTT. Therefore, we estimated the β cell glucose sensitivity (βCGS), an index of β cell function, and rate sensitivity (RS), an index of first phase insulin secretion. Further, we calculated the total area under the curve of insulin responses (AUC-Itot) and the area under the of the arginine-stimulated insulin secretion (AUC-Arg) during HC.

Results: Compared to presurgical OGTT, we observed a 18% increase in the mean glucose levels during OGTT after surgery (AUC-Glu 19761 vs 23421 mg/dl·min) with a 57% reduction of the mean insulin concentration (AUC-Ins 6499 vs 2788 μU/ml·min p<0.05). Further, we observed a 36% reduction βCGS (61.2 vs 38.7 pmol min-1m-2mmol-1L) and a 82% reduction in the RS (763 vs 139 pmol m-2mmol-1L p<0.05) after surgery. Both total insulin secretion and arginine-stimulated insulin secretion during HC were reduced (AUC-Itot 15776 vs 6489 μU/ml·min) (AUC-Arg 7144 vs 2520 μU/ml·min), respectively by 58.8% and 64.7%. According to the ADA diagnostic criteria 3 of the 7 subjects developed diabetes.

Conclusion: In conclusion, despite previous reports, 80% β cell mass loss is not always sufficient to develop hyperglycemia. Additional studies will be necessary to understand what mechanisms play a compensating role in the preservation of glucose tolerance in those patients.