Stephanie J Loomis1, Yuan Chen1, David B Sacks2, Eric S Christenson3, Robert H Christenson4, Casey M Rebholz1, Elizabeth Selvin5. 1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 2. Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD. 3. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 4. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD. 5. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; eselvin@jhu.edu.
Abstract
BACKGROUND: Advanced glycation end products (AGEs) and their receptors are regarded as central to the development of diabetic complications, but associations with diabetes and cardiometabolic outcomes in previous studies are mixed. METHODS: Using ELISA assays, we measured N(6)-carboxymethyllysine (AGE-CML), soluble receptor for AGEs (sRAGE), and endogenous secreted receptor for AGEs (esRAGE) in 1874 participants from the Atherosclerosis Risk in Communities study. We conducted a cross-sectional analysis to evaluate associations of these biomarkers with demographics, diabetes, hyperglycemia, cardiometabolic measures, and genetic variants in the gene encoding RAGE, AGER (advanced glycosylation end-product specific receptor). RESULTS: After adjustment for demographics and body mass index (BMI), there were no significant differences in AGE-CML, sRAGE, or esRAGE by diabetes or hemoglobin A1c. Black race and AGER genetic variants were strongly associated with lower sRAGE and esRAGE even after adjustment [percent difference (95% CI) in black vs whites in sRAGE: -29.17 (-34.86 to -23.48), esRAGE: -26.97 (-33.11 to -20.84); with rs2070600 in sRAGE: -30.13 (-40.98 to -19.29), and esRAGE: -30.32 (-42.42 to -18.21); with rs2071288 in sRAGE: -20.03 (-34.87 to -5.18), and esRAGE: -37.70 (-55.75 to -19.65)]. Estimated glomerular filtration rate and albuminuria significantly correlated with sRAGE and esRAGE. BMI and C-reactive protein significantly negatively correlated with AGE-CML, sRAGE, and esRAGE. AGE-CML was modestly correlated with fructosamine and glycated albumin. CONCLUSIONS: AGE-CML, sRAGE, and esRAGE were more related to genetic, kidney, and inflammatory measures than to diabetes in this community-based population. Our results suggest that, when measured by ELISA, these biomarkers lack specificity and are of limited value in evaluating the role of these compounds in diabetes.
BACKGROUND: Advanced glycation end products (AGEs) and their receptors are regarded as central to the development of diabetic complications, but associations with diabetes and cardiometabolic outcomes in previous studies are mixed. METHODS: Using ELISA assays, we measured N(6)-carboxymethyllysine (AGE-CML), soluble receptor for AGEs (sRAGE), and endogenous secreted receptor for AGEs (esRAGE) in 1874 participants from the Atherosclerosis Risk in Communities study. We conducted a cross-sectional analysis to evaluate associations of these biomarkers with demographics, diabetes, hyperglycemia, cardiometabolic measures, and genetic variants in the gene encoding RAGE, AGER (advanced glycosylation end-product specific receptor). RESULTS: After adjustment for demographics and body mass index (BMI), there were no significant differences in AGE-CML, sRAGE, or esRAGE by diabetes or hemoglobin A1c. Black race and AGER genetic variants were strongly associated with lower sRAGE and esRAGE even after adjustment [percent difference (95% CI) in black vs whites in sRAGE: -29.17 (-34.86 to -23.48), esRAGE: -26.97 (-33.11 to -20.84); with rs2070600 in sRAGE: -30.13 (-40.98 to -19.29), and esRAGE: -30.32 (-42.42 to -18.21); with rs2071288 in sRAGE: -20.03 (-34.87 to -5.18), and esRAGE: -37.70 (-55.75 to -19.65)]. Estimated glomerular filtration rate and albuminuria significantly correlated with sRAGE and esRAGE. BMI and C-reactive protein significantly negatively correlated with AGE-CML, sRAGE, and esRAGE. AGE-CML was modestly correlated with fructosamine and glycated albumin. CONCLUSIONS: AGE-CML, sRAGE, and esRAGE were more related to genetic, kidney, and inflammatory measures than to diabetes in this community-based population. Our results suggest that, when measured by ELISA, these biomarkers lack specificity and are of limited value in evaluating the role of these compounds in diabetes.
Authors: M C Thomas; J Söderlund; M Lehto; V-P Mäkinen; J L Moran; M E Cooper; C Forsblom; P-H Groop Journal: Diabetologia Date: 2011-05-24 Impact factor: 10.122
Authors: Elizabeth Selvin; Michael W Steffes; Christie M Ballantyne; Ron C Hoogeveen; Josef Coresh; Frederick L Brancati Journal: Ann Intern Med Date: 2011-03-01 Impact factor: 25.391
Authors: W C Willett; L Sampson; M J Stampfer; B Rosner; C Bain; J Witschi; C H Hennekens; F E Speizer Journal: Am J Epidemiol Date: 1985-07 Impact factor: 4.897
Authors: Marci Laudenslager; Mariana Lazo; Dan Wang; Elizabeth Selvin; Po-Hung Chen; James S Pankow; Jeanne M Clark Journal: Dig Liver Dis Date: 2021-02-24 Impact factor: 5.165
Authors: Ligia Maria Claro; Andrea N Moreno-Amaral; Ana Carolina Gadotti; Carla J Dolenga; Lia S Nakao; Marina L V Azevedo; Lucia de Noronha; Marcia Olandoski; Thyago P de Moraes; Andréa E M Stinghen; Roberto Pécoits-Filho Journal: Toxins (Basel) Date: 2018-09-23 Impact factor: 4.546