title: Effects of pramlintide on postprandial glucose excursions and measures of oxidative stress in patients with type 1 diabetes.
abstract: OBJECTIVE
  Oxidative stress has been shown to be increased in the postprandial period in patients with diabetes and has been implicated in the pathogenesis of micro- and macrovascular complications. The aim of this post hoc analysis was to assess the effects of pramlintide, an amylin analog shown to reduce postprandial glucose excursions in patients with diabetes, on markers of oxidative stress in the postprandial period.
  
  
  METHODS
  In a randomized, single-blind, placebo-controlled, crossover study, 18 evaluable subjects with type 1 diabetes underwent two standardized breakfast meal tests and received pramlintide or placebo in addition to their preprandial insulin. The plasma concentrations of glucose and markers of oxidative stress (nitrotyrosine, oxidized LDL [ox-LDL], and total radical-trapping antioxidant parameter [TRAP]) were measured at baseline and during the 4-h postprandial period.
  
  
  RESULTS
  Compared with placebo, pramlintide treatment significantly reduced postprandial excursions of glucose, nitrotyrosine, and ox-LDL and prevented a decline in TRAP (P < 0.03 for all comparisons). Correlation analyses adjusted for treatment revealed a significant association between postprandial mean incremental area under the curve from 0 to 4 h (AUC(0-4 h)) for glucose and postprandial mean incremental AUC(0-4 h) for each measure of oxidative stress (r = 0.75, 0.54, and -0.63 for nitrotyrosine, ox-LDL, and TRAP, respectively; P < 0.001 for all correlations).
  
  
  CONCLUSIONS
  These findings indicate that the postprandial glucose-lowering effect of pramlintide in type 1 diabetes is associated with a significant reduction in postprandial oxidative stress.
authors.affiliation: Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
authors.forename: Ludovica
authors.initials: L
authors.lastname: Piconi
authors.forename: Lisa
authors.initials: L
authors.lastname: Quagliaro
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schnabel
authors.forename: James A
authors.initials: JA
authors.lastname: Ruggles
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Gloster
authors.forename: David G
authors.initials: DG
authors.lastname: Maggs
authors.forename: Christian
authors.initials: C
authors.lastname: Weyer
mesh_terms: D000328:Adult; D000682:Amyloid / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D058228:Islet Amyloid Polypeptide; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010919:Placebos; D019518:Postprandial Period; D012449:Safety; D016037:Single-Blind Method; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood*
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D008077:Lipoproteins, LDL; D010919:Placebos; D014443:Tyrosine; C099252:oxidized low density lipoprotein; C002744:3-nitrotyrosine; C105254:pramlintide