Effects of pramlintide on postprandial glucose excursions and measures of oxidative stress in patients with type 1 diabetes.
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.
Ceriello
Antonio
A
Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Italy.
Piconi
Ludovica
L
Quagliaro
Lisa
L
Wang
Yan
Y
Schnabel
Catherine A
CA
Ruggles
James A
JA
Gloster
Maurice A
MA
Maggs
David G
DG
Weyer
Christian
C
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*
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