Lindsey D Bogachus1,2, Melena D Bellin3, Adrian Vella4, R Paul Robertson1,2,3. 1. Pacific Northwest Diabetes Research Institute, Seattle, Washington. 2. Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington. 3. Department of Medicine and Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Minnesota, Minneapolis, Minnesota. 4. Mayo Clinic College of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Rochester, Minnesota.
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 [1-13C]-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.
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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