TY - JOUR
T1 - Deficient Glucagon Response to Hypoglycemia during a Mixed Meal in Total Pancreatectomy/Islet Autotransplantation Recipients
AU - Bogachus, Lindsey D.
AU - Bellin, Melena D.
AU - Vella, Adrian
AU - Paul Robertson, R.
N1 - Publisher Copyright:
© 2018 Endocrine Society.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
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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U2 - 10.1210/jc.2017-02182
DO - 10.1210/jc.2017-02182
M3 - Article
C2 - 29351616
AN - SCOPUS:85045420251
SN - 0021-972X
VL - 103
SP - 1522
EP - 1529
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -