title: Increased plasma amylin in type 1 diabetic patients after kidney and pancreas transplantation: A sign of impaired beta-cell function?
abstract: OBJECTIVE
  In response to hyperglycemia, beta-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all beta-cell hormones.
  
  
  METHODS
  Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, beta-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 +/- 1 kg/m2, 47 +/- 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 +/- 1 kg/m2, 50 +/- 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 +/- 1 kg/m2, 47 +/- 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance test (OGTT).
  
  
  RESULTS
  PKT patients had higher fasting amylin (19 +/- 3 vs. control subjects: 7 +/- 1 pmol/l) and insulin (20 +/- 2 vs. control subjects: 10 +/- 1 microU/ml; each P < 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P < 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9-31% higher (P < 0.05 vs. control subjects). Amylin clearance was comparable in all groups. Amylin's plasma concentrations and area under the concentration curve were up to twofold higher in PKT patients during OGTT (P < 0.05). OGIS was not significantly different between groups. beta-Cell sensitivity to glucose was reduced in PKT patients (-64%, P < 0.009). Fasting plasma amylin was inversely associated with beta-cell sensitivity to glucose (r = -0.543, P < 0.004).
  
  
  CONCLUSIONS
  After successful PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting and post-glucose load plasma amylin, which appears to be linked to impaired beta-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired beta-cell function in type 1 diabetic patients after PKT.
authors.affiliation: Ludwig Boltzmann Institute of Metabolic Diseases and Nutrition, Vienna, Austria.marietta.stadler@wienkav.at
authors.forename: Marietta
authors.initials: M
authors.lastname: Stadler
authors.forename: Christian
authors.initials: C
authors.lastname: Anderwald
authors.forename: Tina
authors.initials: T
authors.lastname: Karer
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.forename: Thomas
authors.initials: T
authors.lastname: Kästenbauer
authors.forename: Martin
authors.initials: M
authors.lastname: Auinger
authors.forename: Christian
authors.initials: C
authors.lastname: Bieglmayer
authors.forename: Oswald
authors.initials: O
authors.lastname: Wagner
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Nowotny
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Rudolf
authors.initials: R
authors.lastname: Prager
mesh_terms: D000328:Adult; D000682:Amyloid / Q000097:blood*; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000601:surgery; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000503:physiopathology*; D016030:Kidney Transplantation; D008875:Middle Aged; D016035:Pancreas Transplantation
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007328:Insulin; D058228:Islet Amyloid Polypeptide