Official websites use .gov
A
.gov
website belongs to an official government organization in the
United States.
Secure .gov websites use HTTPS
A
lock
(
) or
https://
means you’ve safely connected to the .gov website. Share sensitive
information only on official, secure websites.
PubMed ID:
25187362
Public Release Type:
Journal
Publication Year: 2015
Affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH vmm3@cwru.edu smg15@case.edu.
DOI:
https://doi.org/10.2337/db14-0215
Authors:
Genuth S,
Sun W,
Cleary P,
Gao X,
Sell DR,
Lachin J,
DCCT/EDIC Research Group,
Monnier VM
Studies:
Diabetes Control and Complications Trial
Six skin collagen advanced glycation end products (AGEs) originally measured near to the time of the Diabetes Control and Complications Trial (DCCT) closeout in 1993 may contribute to the "metabolic memory" phenomenon reported in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. We have now investigated whether the addition of four originally unavailable AGEs (i.e., glucosepane [GSPNE], hydroimidazolones of methylglyoxal [MG-H1] and glyoxal, and carboxyethyl-lysine) improves associations with incident retinopathy, nephropathy, and neuropathy events during 13-17 years after DCCT. The complete 10-AGE panel is associated with three-step Early Treatment of Diabetic Retinopathy Study scale worsening of retinopathy (P ≤ 0.002), independent of either mean DCCT or EDIC study A1C level. GSPNE and fructose-lysine (furosine [FUR]) correlate with retinopathy progression, independently of A1C level. The complete panel also correlates with microalbuminuria (P = 0.008) and FUR with nephropathy independently of A1C level (P ≤ 0.02). Neuropathy correlates with the complete panel despite adjustment for A1C level (P ≤ 0.005). MG-H1 and FUR are dominant, independent of A1C level (P < 0.0001), whereas A1C loses significance after adjustment for the AGEs. Overall, the added set of four AGEs enhances the association of the original panel with progression risk of retinopathy and neuropathy (P < 0.04) but not nephropathy, while GSPNE and MG-H1 emerge as the principal new risk factors. Skin AGEs are robust long-term markers of microvascular disease progression, emphasizing the importance of early and sustained implementation of intensive therapy.
