Impaired Hyperglycemia-Induced Delay in Gastric Emptying in Patients With Type 1 Diabetes Deficient for Islet Amyloid Polypeptide
- Hans J. Woerle, MD1,
- Max Albrecht1,
- Rainer Linke, MD2,
- Silvia Zschau, MD3,
- Christoph Neumann, MD3,
- Mathias Nicolaus, MD1,
- John E. Gerich, MD4,
- Burkhard Göke, MD1 and
- Joerg Schirra, MD1
- 1Department of Internal Medicine II, Grosshadern, Clinical Research Unit, Ludwig Maximilians University, Munich, Germany
- 2Department of Nuclear Medicine, Grosshadern, Ludwig Maximilians University, Munich, Germany
- 3Outpatient Diabetes Center, Munich, Germany
- 4Department of Medicine, University of Rochester School of Medicine, Rochester, New York
- Corresponding author: Hans J. Woerle, juergen.woerle{at}med.uni-muenchen.de
Abstract
OBJECTIVE—Slowing of gastric emptying by hyperglycemia, a physiological response to minimize postprandial hyperglycemia, may be impaired in patients with type 1 diabetes. The causes and consequences on glucose homeostasis are unknown.
RESEARCH DESIGN AND METHODS—Consequences of euglycemia- and hyperglycemia-induced changes in gastric emptying on postprandial glucose fluxes and excursions were studied in 10 healthy subjects and 15 type 1 diabetic subjects after ingestion of a mixed meal using the double isotope approach ([6,6-2H2] and [1-13C]glucose) and scintigraphic measurements of gastric emptying.
RESULTS—Gastric emptying was greater in type 1 diabetic subjects (90–120 min, P < 0.03), and 50% retention times were comparable in healthy subjects and type 1 diabetic subjects (167 ± 8 vs. 152 ± 10, P = 0.32). Hyperglycemia markedly delayed gastric emptying in healthy subjects but did not alter it in type 1 diabetic subjects (50% retention time 222 ± 18 vs. 167 ± 8 min, P = 0.003 and 148 ± 9 vs. 152 ± 10 min, P = 0.51). Plasma islet amyloid polypeptide (IAPP) increased approximately fourfold in healthy subjects (P < 0.001), whereas it was undetectable in type 1 diabetic subjects. IAPP replacement, using the analog pramlintide, in type 1 diabetic subjects slowed gastric emptying to a comparable extent, as did hyperglycemia in healthy subjects (P < 0.14), and greatly reduced postprandial hyperglycemia (P < 00.1). Meal-derived glucose appearance in plasma (10.7 ± 0.5 vs. 6.8 ± 0.7 μmol · kg−1 · min−1, P < 0.001) was reduced, and splanchnic glucose sequestration increased (14.0 ± 3.0 vs. 25.0 ± 6.0%, P = 0.04).
CONCLUSIONS—In patients with type 1 diabetes the ability to delay gastric emptying in response to hyperglycemia is impaired. This impairment contributes to exaggerated rates of meal-derived glucose appearance and, ultimately, postprandial glucose excursions.
Footnotes
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See accompanying editorial, p. 2410.
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- Accepted August 5, 2008.
- Received January 5, 2008.
- DIABETES CARE
