1345-P: Insulin and C-Peptide “Bursts” Characterise Secretory Dynamics of Human Insulinomas during Prolonged Fasts

Introduction and Objective: Insulinomas are characterized by autonomous secretion of (pro-)insulin. We wanted to explore secretory dynamics of insulinomas during prolonged fasting. Methods: Prolonged fasts lasting 48 h or until discontinuation (hypoglycemia), with plasma glucose, insulin and C-peptide measured at least every 4 h were analyzed from 49 insulinoma patients (I), 69 control subjects (C), and 11 insulinoma patients after surgical cure (SCI). “Bursts” of insulin secretion were defined as a rise in insulin or C-peptide concentrations between any peak over its preceding nadir (insulin: > 1.5 mU/l; C-peptide: > 0.05 nmol/l). Timing and burst sizes were compared between I, C, and SCI. Results: Insulinoma patients discontinued prolonged fasting after 19 (95% CI: 16; 22) h, C and SCI after 48 h. Insulin “bursts” were found in 46 (94%) and 53 (77%), and C-peptide “bursts” in 43 (88%) and 66 (96 %) for I and C, respectively. The averahge number of bursts per prolonged fast were 1.7 and 1.2 for insulin and 1.7 and 1.6 for C-peptide in I and C, respectively. “Burst” size was 12.2 (9.3; 15.1) vs. 3.7 (3.2; 4.1) mU/l insulin, and 0.31 (0.24; 0.37) vs. 0.14 (0.13; 0.16) nmo/l C-peptide for I and C, respectively. Insulin and C-peptide “bursts” observed concomitantly (within 1 h) were significantly correlated (p <0.0001). Last insulin and C-peptide “bursts” occurred 3 (2; 4) and 10 (7; 13) h. and 3 (1; 4) and 8 (6; 10) h before discontinuation, respectively. After a last insulin “burst,” the slope of decline in plasma glucose was significantly greater in I than in C (p = 0.013), and slopes were significantly correlated to the insulin “burst” size (p = 0.0005). Results in SCI were similar to C. Conclusion: In the majority of insulinoma patients, insulin and C-peptide display sizable, often concomitant “bursts”. Last “bursts” often occur late during prolonged fasts, and may often precipitate hypoglycemia and a need for discontinuation. “Bursts” may become a novel confirmatory diagnostic criterion for insulinomas. Disclosure M.A. Nauck: Advisory Panel; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Pfizer Inc., Regor. Consultant; Current; Structure Therapy. Speaker's Bureau; Current; Eli Lilly and Company, Novo Nordisk, Medscape, Medical Learning Institute. Advisory Panel; Current; Sun Pharmaceutical Industries Ltd.