Impaired hyperglycemia-induced delay in gastric emptying in patients with type 1 diabetes deficient for islet amyloid polypeptide.
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.
Woerle
Hans J
HJ
Department of Internal Medicine II, Grosshadern, Clinical Research Unit, Ludwig Maximilians University, Munich, Germany. juergen.woerle@med.uni-muenchen.de
Albrecht
Max
M
Linke
Rainer
R
Zschau
Silvia
S
Neumann
Christoph
C
Nicolaus
Mathias
M
Gerich
John E
JE
Göke
Burkhard
B
Schirra
Joerg
J
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
D000682:Amyloid; D058228:Islet Amyloid Polypeptide