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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.
Amino Acids 2014; 46(2):311-9AA

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).

Authors+Show Affiliations

Section of Diabetes, Endocrinology, and Metabolism, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH, 03756, USA, paul.j.beisswenger@dartmouth.edu.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24036985

Citation

Beisswenger, Paul J., 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, vol. 46, no. 2, 2014, pp. 311-9.
Beisswenger PJ, Howell SK, 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. 2014;46(2):311-9.
Beisswenger, P. J., Howell, S. K., Russell, G., Miller, M. E., Rich, S. S., & Mauer, M. (2014). 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(2), pp. 311-9. doi:10.1007/s00726-013-1533-x.
Beisswenger PJ, 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. 2014;46(2):311-9. PubMed PMID: 24036985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation. AU - Beisswenger,Paul J, AU - Howell,Scott K, AU - Russell,Greg, AU - Miller,Michael E, AU - Rich,Stephen S, AU - Mauer,Michael, Y1 - 2013/09/14/ PY - 2013/01/28/received PY - 2013/06/06/accepted PY - 2013/9/17/entrez PY - 2013/9/17/pubmed PY - 2014/10/8/medline SP - 311 EP - 9 JF - Amino acids JO - Amino Acids VL - 46 IS - 2 N2 - 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). SN - 1438-2199 UR - https://www.unboundmedicine.com/medline/citation/24036985/Detection_of_diabetic_nephropathy_from_advanced_glycation_endproducts__AGEs__differs_in_plasma_and_urine_and_is_dependent_on_the_method_of_preparation_ L2 - https://dx.doi.org/10.1007/s00726-013-1533-x DB - PRIME DP - Unbound Medicine ER -