Effect of exenatide on beta cell function after islet transplantation in type 1 diabetes.
BACKGROUND
Islet transplantation can reduce or eliminate the need for insulin in patients with type 1 diabetes. Exenatide is a long acting analogue of Glucagon-like peptide-1 (GLP-1) that augments glucose induced insulin secretion, and may increase beta cell mass. We evaluated the effect of exenatide on insulin secretion after islet transplantation.


METHODS
Eleven C-peptide positive islet cell recipients with elevated glucose levels were treated with exenatide for three months. Response was assessed by insulin requirements, meal tolerance tests, and hyperglycemic glucose clamps.


RESULTS
Ten patients responded to exenatide. Two patients who had not restarted insulin achieved good glycemic control and one patient who had received 5500 IE/kg in first islet infusion was able to stop insulin. Seven other patients decreased their insulin dose by 39% on exenatide. Hyperglycemic clamp studies showed a rise in second phase insulin release (before exenatide: 246+/-88 pM; during exenatide: 644+/-294 pM, P<0.01). Meal tolerance studies before and one month after stopping exenatide did not show a difference in glucose or C-peptide values. Nausea and vomiting were the major side effects.


CONCLUSIONS
Exenatide stimulates insulin secretion in islet transplant recipients. It reduces insulin dose in some patients and may delay the need to resume insulin in others. We did not find any evidence of a trophic effect on islets.
Ghofaili
Khalid Al
KA
Department of Medicine University of British Columbia, Vancouver, BC.
Fung
Michelle
M
Ao
Ziliang
Z
Meloche
Mark
M
Shapiro
R Jean
RJ
Warnock
Garth L
GL
Elahi
Dariush
D
Meneilly
Graydon S
GS
Thompson
David M
DM
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D014688:Venoms / Q000008:administration & dosage / Q000627:therapeutic use*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000077270:Exenatide