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Multicenter Study
. 2017 May;63(5):980-989.
doi: 10.1373/clinchem.2016.264135. Epub 2017 Mar 9.

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort

Stephanie J Loomis  1 , Yuan Chen  1 , David B Sacks  2 , Eric S Christenson  3 , Robert H Christenson  4 , Casey M Rebholz  1 , Elizabeth Selvin  5
Affiliations
Multicenter Study

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort

Stephanie J Loomis et al. Clin Chem. 2017 May.

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.

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Conflict of interest statement

Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:

Employment or Leadership: D.B. Sacks, Clinical Chemistry, AACC.

Consultant or Advisory Role: None declared.

Stock Ownership: None declared.

Honoraria: None declared.

Research Funding: The ARIC study is carried out as a collaborative study supported by the National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100 008C, HHSN268201100009C, HHSN268201100010C, HHSN268 201100011C, and HHSN268201100012C), R01HL087641, R01HL 59367, and R01HL086694; the National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200 625226C with the ARIC carotid MRI examination funded by U01 HL075572–01; infrastructure was partly supported by grant number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research (all of the preceding funding to the institution); American Heart Association; S.J. Loomis, institutional training grant from the NIH/NHLBI (T32 HL007024); E. Selvin, NIH/NIDDK grant K24DK106414.

Expert Testimony: None declared.

Patents: None declared.

References

    1. Yan SF, Ramasamy R, Schmidt AM. Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nat Clin Pract Endocrinol Metab. 2008;4:285–93. - PubMed
    1. Yan SF, Ramasamy R, Schmidt AM. The receptor for advanced glycation endproducts (RAGE) and cardiovascular disease. Expert Rev Mol Med. 2009;11:e9. - PMC - PubMed
    1. Song F, Schmidt AM. Glycation and insulin resistance: novel mechanisms and unique targets? Arterioscler Thromb Vasc Biol. 2012;32:1760–5. - PMC - PubMed
    1. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114:597–605. - PubMed
    1. Koyama H, Yamamoto H, Nishizawa Y. RAGE and soluble RAGE: potential therapeutic targets for cardiovascular diseases. Mol Med. 2007;13:625–35. - PMC - PubMed

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