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Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation

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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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Acknowledgments

Financial support was provided by the Juvenile Diabetes Research Foundation and the work was presented as an oral abstract at the “11th International Symposium on the Maillard Reaction”, in Nancy, France on Sept 19, 2012.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Section of Diabetes, Endocrinology, and Metabolism, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH, 03756, USA

    Paul J. Beisswenger

  2. Department of Medicine/Endocrinology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Paul J. Beisswenger & Scott K. Howell

  3. Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, NC, USA

    Greg Russell & Michael E. Miller

  4. Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA

    Stephen S. Rich

  5. Department of Pediatrics and Medicine, University of Minnesota, Minneapolis, MN, USA

    Michael Mauer

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  1. Paul J. Beisswenger
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  2. Scott K. Howell
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  3. Greg Russell
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  4. Michael E. Miller
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  5. Stephen S. Rich
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  6. Michael Mauer
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Correspondence to Paul J. Beisswenger.

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Beisswenger, P.J., Howell, S.K., Russell, G. et al. Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation. Amino Acids 46, 311–319 (2014). https://doi.org/10.1007/s00726-013-1533-x

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