JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
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Deficient Glucagon Response to Hypoglycemia During a Mixed Meal in Total Pancreatectomy/Islet Autotransplantation Recipients.

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 [1-13C]-labeled mixed meal and two tracer infusions ([6,6-2H2]- and [6-3H]-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 Δ 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 Δ glucose. Δ 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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