Deficient Glucagon Response to Hypoglycemia during a Mixed Meal in Total Pancreatectomy/Islet Autotransplantation Recipients

Lindsey D. Bogachus, Melena D Bellin, Adrian Vella, R. Paul Robertson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Context Total pancreatectomy and intrahepatic islet autotransplantation (TP/IAT) is performed to alleviate severe abdominal pain, avoid narcotic use, maintain islet function, and avoid diabetes in patients with chronic pancreatitis. However, many TP/IAT recipients complain of postprandial hypoglycemia. Objective This study was designed to discover the mechanisms of this problem. Design Participants consumed a triple-isotope mixed meal. Setting This study was performed in a hospital research unit. Participants We studied 10 TP/IAT recipients and 10 age- and body mass index-matched control subjects. Seven of 10 recipients had a history of postprandial hypoglycemia. Interventions Participants were given a [1- 13 C]-labeled mixed meal and two tracer infusions ([6,6- 2 H 2 ]- and [6- 3 H]-glucose). Main Outcome Measures Glucose kinetics and concentrations of regulatory hormones were determined. Results Immediately after the meal, peak glucose was elevated in recipients compared with control subjects [266 ± 20 mg/dL (14.8 ± 1.1 mmol/L) vs 185 ± 13 mg/dL (10.3 ± 0.7 mmol/L); P = 0.01]. However, mean Î " glucose for TP/IAT recipients between minutes 240 and 360 postprandially was significantly lower than for control subjects (P < 0.05); six of the seven recipients with a history of hypoglycemia experienced abnormally low postprandial Î " glucose. Î " Glucagon remained unchanged (minutes 240 to 360; P = 0.58) in TP/IAT recipients despite abnormal decreases in postprandial glucose. Radioisotopic studies revealed that meal appearance, glucose disappearance, and endogenous glucose production in TP/IAT recipients were not different from control subjects. Conclusion Initially high glucose levels followed by hypoglycemia with an absent glucagon response is a mechanistic sequence that contributes to postprandial hypoglycemia after TP/IAT.

Original languageEnglish (US)
Pages (from-to)1522-1529
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number4
DOIs
StatePublished - Apr 1 2018

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Pancreatectomy
Autologous Transplantation
Glucagon
Hypoglycemia
Meals
Glucose
Hospital Units
Narcotics
Chronic Pancreatitis
Medical problems
Isotopes
Abdominal Pain
Body Mass Index
Outcome Assessment (Health Care)
Hormones
Kinetics

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Deficient Glucagon Response to Hypoglycemia during a Mixed Meal in Total Pancreatectomy/Islet Autotransplantation Recipients. / Bogachus, Lindsey D.; Bellin, Melena D; Vella, Adrian; Paul Robertson, R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 103, No. 4, 01.04.2018, p. 1522-1529.

Research output: Contribution to journalArticle

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abstract = "Context Total pancreatectomy and intrahepatic islet autotransplantation (TP/IAT) is performed to alleviate severe abdominal pain, avoid narcotic use, maintain islet function, and avoid diabetes in patients with chronic pancreatitis. However, many TP/IAT recipients complain of postprandial hypoglycemia. Objective This study was designed to discover the mechanisms of this problem. Design Participants consumed a triple-isotope mixed meal. Setting This study was performed in a hospital research unit. Participants We studied 10 TP/IAT recipients and 10 age- and body mass index-matched control subjects. Seven of 10 recipients had a history of postprandial hypoglycemia. Interventions Participants were given a [1- 13 C]-labeled mixed meal and two tracer infusions ([6,6- 2 H 2 ]- and [6- 3 H]-glucose). Main Outcome Measures Glucose kinetics and concentrations of regulatory hormones were determined. Results Immediately after the meal, peak glucose was elevated in recipients compared with control subjects [266 ± 20 mg/dL (14.8 ± 1.1 mmol/L) vs 185 ± 13 mg/dL (10.3 ± 0.7 mmol/L); P = 0.01]. However, mean {\^I} {"} glucose for TP/IAT recipients between minutes 240 and 360 postprandially was significantly lower than for control subjects (P < 0.05); six of the seven recipients with a history of hypoglycemia experienced abnormally low postprandial {\^I} {"} glucose. {\^I} {"} Glucagon remained unchanged (minutes 240 to 360; P = 0.58) in TP/IAT recipients despite abnormal decreases in postprandial glucose. Radioisotopic studies revealed that meal appearance, glucose disappearance, and endogenous glucose production in TP/IAT recipients were not different from control subjects. Conclusion Initially high glucose levels followed by hypoglycemia with an absent glucagon response is a mechanistic sequence that contributes to postprandial hypoglycemia after TP/IAT.",
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AB - Context Total pancreatectomy and intrahepatic islet autotransplantation (TP/IAT) is performed to alleviate severe abdominal pain, avoid narcotic use, maintain islet function, and avoid diabetes in patients with chronic pancreatitis. However, many TP/IAT recipients complain of postprandial hypoglycemia. Objective This study was designed to discover the mechanisms of this problem. Design Participants consumed a triple-isotope mixed meal. Setting This study was performed in a hospital research unit. Participants We studied 10 TP/IAT recipients and 10 age- and body mass index-matched control subjects. Seven of 10 recipients had a history of postprandial hypoglycemia. Interventions Participants were given a [1- 13 C]-labeled mixed meal and two tracer infusions ([6,6- 2 H 2 ]- and [6- 3 H]-glucose). Main Outcome Measures Glucose kinetics and concentrations of regulatory hormones were determined. Results Immediately after the meal, peak glucose was elevated in recipients compared with control subjects [266 ± 20 mg/dL (14.8 ± 1.1 mmol/L) vs 185 ± 13 mg/dL (10.3 ± 0.7 mmol/L); P = 0.01]. However, mean Î " glucose for TP/IAT recipients between minutes 240 and 360 postprandially was significantly lower than for control subjects (P < 0.05); six of the seven recipients with a history of hypoglycemia experienced abnormally low postprandial Î " glucose. Î " Glucagon remained unchanged (minutes 240 to 360; P = 0.58) in TP/IAT recipients despite abnormal decreases in postprandial glucose. Radioisotopic studies revealed that meal appearance, glucose disappearance, and endogenous glucose production in TP/IAT recipients were not different from control subjects. Conclusion Initially high glucose levels followed by hypoglycemia with an absent glucagon response is a mechanistic sequence that contributes to postprandial hypoglycemia after TP/IAT.

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