title: Impaired hyperglycemia-induced delay in gastric emptying in patients with type 1 diabetes deficient for islet amyloid polypeptide.
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.
  
  
  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-(2)H(2)] and [1-(13)C]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 mumol . 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.
authors.affiliation: Department of Internal Medicine II, Grosshadern, Clinical Research Unit, Ludwig Maximilians University, Munich, Germany. juergen.woerle@med.uni-muenchen.de
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
authors.forename: Max
authors.initials: M
authors.lastname: Albrecht
authors.forename: Rainer
authors.initials: R
authors.lastname: Linke
authors.forename: Silvia
authors.initials: S
authors.lastname: Zschau
authors.forename: Christoph
authors.initials: C
authors.lastname: Neumann
authors.forename: Mathias
authors.initials: M
authors.lastname: Nicolaus
authors.forename: John E
authors.initials: JE
authors.lastname: Gerich
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Joerg
authors.initials: J
authors.lastname: Schirra
mesh_terms: D000328:Adult; D000682:Amyloid / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D005260:Female; D005746:Gastric Emptying / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D058228:Islet Amyloid Polypeptide; D008297:Male
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide