| Authors |
Beisswenger PJ, Howell SK, Russell G, Miller ME, Rich SS, Mauer M
|
| Submitted By |
Michael Mauer on 4/15/2014 |
| Status |
Published |
| Journal |
Amino acids |
| Year |
2014 |
| Date Published |
2/1/2014 |
| Volume : Pages |
46 : 311 - 319 |
| PubMed Reference |
|
| Abstract |
Increased advanced glycation endproducts (AGEs) and oxidation products (OPs)
have been proposed as pathogenic for diabetic nephropathy (DN). We investigated
the relationship between AGEs and OPs measured in different plasma and urine
preparations, and progression of DN in 103 young, normoalbuminuric, normotensive
participants with type 1 diabetes in the Natural History of Diabetic Nephropathy
Study. The primary endpoint was electron microscopy-measured change in
glomerular basement membrane (GBM) width from baseline to 5 years; change in
mesangial fractional volume was a secondary endpoint. Fast progressors (FP) were
defined as the upper quartile (n = 24) of rate of GBM thickening; slow
progressors (SP) were the remainder (n = 79). Four AGEs [3-deoxyglucosone and
methylglyoxal hydroimidazolones (DG3H1, MGH1) and carboxymethyl and ethyl lysine
(CML, CEL)], and two oxidation products methionine sulfoxide and aminoadipic
acid were measured by liquid chromatography, triple quadrupole mass
spectrometry. Measurements were done on 10 K plasma filtrates and plasma
proteolytic digests (PPD) at year 5, and at four time points over 5 years for
urinary 10 K filtrates. Urinary filtrate CEL levels were significantly higher in
FP, but not after adjustment for HbA1c, sex, and duration of diabetes. MGHI,
CEL, and CML plasma filtrate levels were significantly higher in FP relative to
SP (p < 0.05). In PPD, only MGHI showed borderline significantly higher levels
in FP relative to SP (p = 0.067), while no other product showed correlation. AGE
and OP measurements were not correlated with mesangial expansion. In plasma
filtrates, HbA1c at year 5 accounted for 4.7 % of the variation in GBM width.
The proportion of variation in GBM width was increased to 11.6 % when MGHI, CEL,
and CML were added to the model (6.9 % increase).
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