What does this research mean for the field?

Following total pancreatectomy with islet autotransplantation (TPIAT), counterregulatory hormone responses to hypoglycemia are largely preserved, with the exception of absent pancreatic polypeptide and blunted glucagon responses. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to determine the counterregulatory hormone responses after total pancreatectomy with islet autotransplantation (TPIAT).

June 7, 2026

1142-OR: Counterregulatory Hormone Responses to Hypoglycemia after Total Pancreatectomy with Islet Autotransplantation (TPIAT)

Key Points

This study aims to determine the counterregulatory hormone responses after total pancreatectomy with islet autotransplantation (TPIAT).
Nineteen subjects underwent stepped hypoglycemic clamps with mean nadir of 50 mg/dL, compared to healthy volunteers.
Counterregulatory hormone levels (C-peptide, glucagon, cortisol, epinephrine, norepinephrine) were measured during hypoglycemia.
Results were analyzed using t-tests to compare hormonal changes between groups.
TPIAT subjects showed appropriate C-peptide suppression but no pancreatic polypeptide response, with lower glucagon increase (p=0.006) compared to healthy volunteers.
TPIAT subjects off insulin had a higher glucagon response (p=0.057) compared to those on insulin.
Extrahepatic islet transplantation did not enhance glucagon responses in TPIAT subjects with intra + extrahepatic islets.

Abstract

Introduction and Objective: Insulin-independent hypoglycemia has been reported after TPIAT. Our objective was to determine counterregulatory hormone responses after TPIAT. Methods: Nineteen subjects, a mean of 9.17 (SD 3.36) years post-TPIAT (IEQ/kg 4617 (2022)), and 10 age-, sex-, and BMI-matched healthy volunteers (HV) underwent stepped hypoglycemic clamps (nadir 50 mg/dL), with serial measurements of C-peptide, pancreatic polypeptide (PP), cortisol, epinephrine (epi) and norepinephrine (NE). Mean changes from 70 mg/dL to 50 mg/dL steps were compared between groups with t-tests. Results: TPIAT subjects had an appropriate suppression of C-peptide, but absent PP, less increase in glucagon (p=0.006), and similar cortisol, epi, and NE responses to HV (Figure 1). Responses of TPIAT subjects off opioids (N=10) were similar to TPIAT on opioids (N=9). Compared to TPIAT subjects on insulin (N=10), TPIAT off insulin (N=9) had higher glucagon response (p=0.057), but no difference in cortisol, epi or NE. TPIAT subjects with intra + extrahepatic islets (N=7) had patterns suggesting lower responses for glucagon (p=0.074), cortisol (p=0.063), epi (p=0.088), and NE (p=0.1) vs those with intrahepatic islets alone (N=12), with similar patterns when restricted to insulin-independent TPIAT subjects. Conclusion: Other than glucagon and PP, counterregulatory responses were preserved in TPIAT. Extrahepatic islet transplantation did not improve glucagon response. Disclosure J.M. Ladd: None. A. Eaton: None. G. Beilman: None. M.R. Rickels: Consultant; Ended; Novo Nordisk. Consultant; Current; Vertex Pharmaceuticals Incorporated. Other - Invited speaker; Ended; Bayer AG. Consultant; Current; Sernova, Corp., Sanofi. Research Support; Current; Dompé, vTv Therapeutics, Hua Medicine. Research Support; Ended; Tandem Diabetes Care, Inc. M. Bellin: Other - DSMB member; Current; Vertex Pharmaceuticals Incorporated. Advisory Panel; Current; Novo Nordisk, Sana Biotechnology Inc., Sernova, Corp. Research Support; Current; Dexcom, Inc. Funding NIH (R01DK126728)

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Cite This Study

Ladd et al. (Fri,) studied this question.

synapsesocial.com/papers/6a250c7d7def13d035e1ca76 https://doi.org/https://doi.org/10.2337/db26-1142-or

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