Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy.
BACKGROUND
Formation of advanced glycation endproducts (AGEs), endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and nephropathy.


METHODS
Patients with type 2 diabetes and urinary albumin excretion in the high-normal and microalbuminuric range (15-300 mg/24h) were randomized to receive benfotiamine (n = 39) or placebo (n = 43). Plasma and urinary AGEs (N(ε)-(carboxymethyl) lysine [CML], N(ε)-(Carboxyethyl) lysine [CEL], and 5-hydro-5-methylimidazolone [MG-H1]) and plasma markers of endothelial dysfunction (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1], soluble E-selectin) and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid-A [SAA], myeloperoxidase [MPO]) were measured at baseline and after 6 and 12 weeks.


RESULTS
Compared to placebo, benfotiamine did not result in significant reductions in plasma or urinary AGEs or plasma markers of endothelial dysfunction and low-grade inflammation.


CONCLUSIONS
Benfotiamine for 12 weeks did not significantly affect intermediate pathways of hyperglycemia-induced vascular complications.  TRIAL REGRISTRATION: ClinicalTrials.gov NCT00565318.
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. a.alkhalaf@isala.nl
Alaa
A
Alkhalaf
Nanne
N
Kleefstra
Klaas H
KH
Groenier
Henk J G
HJ
Bilo
Reinold O B
RO
Gans
Peter
P
Heeringa
Jean L
JL
Scheijen
Casper G
CG
Schalkwijk
Gerjan J
GJ
Navis
Stephan J L
SJ
Bakker
D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015815:Cell Adhesion Molecules / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000652:urine; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000652:urine; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D013831:Thiamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D013831:Thiamine; C013835:benphothiamine