30704ecc1894904fc0bdb5b474581761 pmc_34945815.pdf e3f6585b73604ba83271a625862c0fb7c1bd6f1a pmc_34945815.pdf f2fb357bf3bf0f3c6ec3a54ab18f6a0b04382828c25ebce8fbec1f6f4df215a1 pmc_34945815.pdf Title: Diabetic Retinopathy and Skin Tissue Advanced Glycation End Products Are Biomarkers of Cardiovascular Events in Type 2 Diabetic Patients Subject: Risk of cardiovascular events is not homogeneous in subjects with type 2 diabetes; therefore, its early identification remains a challenge to be met. The aim of this study is to evaluate whether the presence of diabetic retinopathy and accumulation of advanced glycation end-products in subcutaneous tissue can help identify patients at high risk of cardiovascular events. For this purpose, we conducted a prospective study (mean follow-up: 4.35 years) comprising 200 subjects with type 2 diabetes with no history of clinical cardiovascular disease and 60 non-diabetic controls matched by age and sex. The primary outcome was defined as the composite of myocardial infarction, coronary revascularization, stroke, lower limb amputation or cardiovascular death. The Cox proportional hazard multiple regression analysis was used to determine the independent predictors of cardiovascular events. The patients with type 2 diabetes had significantly more cardiovascular events than the non-diabetic subjects. Apart from the classic factors such as age, sex and coronary artery calcium score, we observed that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue were independent predictors of cardiovascular events. We conclude that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue could be useful biomarkers for selecting type 2 diabetic patients in whom the screening for cardiovascular disease should be prioritized, thereby creating more personalized and cost-effective medicine. Keywords: cardiovascular disease; advanced glycation end-products; diabetic retinopathy; cardiovascular disease biomarkers; type 2 diabetes; diabetic complications Author: Alejandra Planas, Olga Simó-Servat, Cristina Hernández, Ángel Ortiz-Zúñiga, Joan Ramón Marsal, José R. Herance, Ignacio Ferreira-González and Rafael Simó Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 10 06:52:58 2021 CET ModDate: Fri Dec 10 06:58:58 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 646092 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QODWNV+VnURWPalladioL Type 1 Custom yes yes no 10 0 IQQDBZ+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 VJHZAS+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 EQEMBW+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 RUGTHW+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 UIJACC+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 61 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 65 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 69 0 UWJUYN+CMSY10 Type 1 Builtin yes yes no 84 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 91 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 98 0 ABCDEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 110 0 ABCDEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 114 0 ABCDEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 118 0 ABCDEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 122 0 ABCDEE+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes no 129 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-11-23 05:25:55 CET RepresentationInformation: pmc_34945815.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:06:36 CEST Size: 646092 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 268 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design and Subjects Destination: subsection.2.1 Item: Title: Data Collection and Laboratory Tests Destination: subsection.2.2 Item: Title: Fundus Eye Examination Destination: subsection.2.3 Item: Title: Measurement of Skin Autofluorescence Destination: subsection.2.4 Item: Title: CT-CAC Scanning Destination: subsection.2.5 Item: Title: Outcome Destination: subsection.2.6 Item: Title: Statistical Analysis Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Basal Characteristics of the Sample Destination: subsection.3.1 Item: Title: Follow-Up Destination: subsection.3.2 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: Destination: section.A. Children: Item: Title: Anthropometric Data, Assessment of the Classic Risk Factors and Laboratory Test Destination: subsection.A.1 Item: Title: Measurement of Skin Autofluorescence Destination: subsection.A.2 Item: Title: Destination: section.B. Item: Title: References Destination: specialtable.caption.5 Info: Title: Diabetic Retinopathy and Skin Tissue Advanced Glycation End Products Are Biomarkers of Cardiovascular Events in Type 2 Diabetic Patients Author: Alejandra Planas, Olga Simó-Servat, Cristina Hernández, Ángel Ortiz-Zúñiga, Joan Ramón Marsal, José R. Herance, Ignacio Ferreira-González and Rafael Simó Subject: Risk of cardiovascular events is not homogeneous in subjects with type 2 diabetes; therefore, its early identification remains a challenge to be met. The aim of this study is to evaluate whether the presence of diabetic retinopathy and accumulation of advanced glycation end-products in subcutaneous tissue can help identify patients at high risk of cardiovascular events. For this purpose, we conducted a prospective study (mean follow-up: 4.35 years) comprising 200 subjects with type 2 diabetes with no history of clinical cardiovascular disease and 60 non-diabetic controls matched by age and sex. The primary outcome was defined as the composite of myocardial infarction, coronary revascularization, stroke, lower limb amputation or cardiovascular death. The Cox proportional hazard multiple regression analysis was used to determine the independent predictors of cardiovascular events. The patients with type 2 diabetes had significantly more cardiovascular events than the non-diabetic subjects. Apart from the classic factors such as age, sex and coronary artery calcium score, we observed that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue were independent predictors of cardiovascular events. We conclude that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue could be useful biomarkers for selecting type 2 diabetic patients in whom the screening for cardiovascular disease should be prioritized, thereby creating more personalized and cost-effective medicine. 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