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  • 1
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Kurzfassung: Joslin Medalist Study identified Retinol Binding Protein 3 (RBP3) as a potential protective factor against advanced diabetic retinopathy (DR) in the vitreous and retina of people with type 1 diabetes for 50 years or longer. There is emerging interest in DR biomarker identification in aqueous due to its easier access compared to vitreous. Quantitive aqueous RBP3 concentration, in a pilot study, correlated inversely with DR severity, but positively with vitreous RBP3, suggesting it may be a clinically useful DR biomarker. This study measured RBP3 concentration in 153 aqueous samples from patients undergoing cataract surgery at the Joslin Beetham Eye Institute to characterize RBP3 concentrations in relation to DR progression. DR progression was defined as ≥2-step worsening on the Early Treatment Diabetic Retinopathy Study severity scale. At baseline, DR severity distribution was 36% no DR, 38% mild and 26% moderate DR. The average follow-up was 5.6±3.6yrs. Aqueous RBP3 concentration was highest in patients with no visible signs of DR (median 2.1nM) compared to mild and moderate DR (1.5nM, P=0.04). There was no significant difference between aqueous RBP3 concentration in those with type 1 or type 2 diabetes (P=0.55). DR progression was present in 28.1% (N=45). Elevated aqueous RBP3 concentration was associated with less frequent diabetic macular edema (Odd Ratio (OR) 0.20, 95% Confidence Interval (CI) 0.07;0.56, P=0.002). In unadjusted analyses, less DR progression was associated with older age (OR 0.87, CI 0.79;0.96, P=0.006), lower HbA1c (OR 1.88, 95% CI 1.01;3.49, P=0.05), and elevated RBP3 concentration (OR 0.51, 95% CI 0.28;0.93, P=0.029). The performance of an Area Under the Curve model including RBP3 was 0.69 for predicting DR progression. These findings indicate that elevated aqueous RBP3 concentration is associated with less DR progression, supporting its potential as a protective factor and retinal-specific DR biomarker. Disclosure T. Chokshi: None. W. Fickweiler: None. S. Jangolla: None. I. Wu: None. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim, Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines. L.P. Aiello: Advisory Panel; Novo Nordisk. Stock/Shareholder; Kalvista. Other Relationship; Optos. Consultant; Ceramedix. G.L. King: None. Funding American Diabetes Association (7-21-PDF-022); National Eye Institute (R01EYE26080-01), the National Institute of Diabetes and Digestive and Kidney Diseases and National Institutes of Health (DP3- DK-094333-01); JDRF (17-2013-310); the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund
    Materialart: Online-Ressource
    ISSN: 0012-1797
    Sprache: Englisch
    Verlag: American Diabetes Association
    Publikationsdatum: 2024
    ZDB Id: 1501252-9
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Kurzfassung: Given the increasing prevalence of diabetes in the elderly, understanding factors that influence age-related macular degeneration (AMD) and diabetic retinopathy (DR) is crucial to target intervention for both. Previously, we found an inverse relationship between DR and AMD in the Joslin 50-Year Medalist Study composed of individuals who have had insulin-dependent diabetes for over 50 years. This study evaluated the relationship between AMD and DR in an age-matched cohort of people with type 1 diabetes from the Beetham Eye Institute (BEI) at Joslin Diabetes Center (N=1413) with the Medalist Study. The presence of AMD and DR severity were assessed from fundus photography. Advanced glycation endproducts (AGEs), specifically carboxymethyl-lysine, carboxyethyl-lysine, and methylglyoxal-derived hydroimidazolone 1, were quantified using high-performance liquid chromatography mass spectrometry and inflammatory cytokines by ELISA. We found an inverse association between DR severity and the presence of AMD in the BEI cohort (P & lt;0.0001), consistent with previous findings in Medalists. The presence of AMD was associated with less frequent diabetic macular edema (7.6% vs 16.7%, P=0.01). In Medalists, there was no correlation of plasma inflammatory cytokines including interleukin-6 with DR, AMD, or their vitreous concentrations, whereas serum AGE levels were positively associated with DR severity, but inversely with AMD (P & lt;0.05). Higher triglyceride/high-density lipoprotein ratio and lower systemic insulin sensitivity were associated with DR severity, but inversely with AMD (P & lt;0.05). These findings suggest that metabolic control of hyperglycemia and lipidemia can delay DR, but may worsen the progression of AMD. The inverse risk of AMD and DR suggests accelerated aging is not likely a major cause of DR. Studies are needed urgently to evaluate the distinct effects of glucose and lipid metabolism on their contribution to inverse risks for DR and AMD. Disclosure W. Fickweiler: None. T. Chokshi: None. E. O'Doherty: None. S. Jangolla: None. N.A. Ziemniak: None. I. Wu: None. C. Jacoba: None. S. Gulkas: None. A. Talaspayeva: None. J.D. Cavallerano: None. L.P. Aiello: Advisory Panel; Novo Nordisk. Stock/Shareholder; Kalvista. Other Relationship; Optos. Consultant; Ceramedix. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim, Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines. G.L. King: None. Funding American Diabetes Association (7-21-PDF-022), National Eye Institute (R01EYE26080-01), the National Institute of Diabetes and Digestive and Kidney Diseases and National Institutes of Health (DP3- DK-094333-01); JDRF (17-2013-310); the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund
    Materialart: Online-Ressource
    ISSN: 0012-1797
    Sprache: Englisch
    Verlag: American Diabetes Association
    Publikationsdatum: 2024
    ZDB Id: 1501252-9
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Kurzfassung: Introduction & Objective: Our prior research has shown a clear distinction between two types of diabetic retinopathy (DR): predominantly exudative diabetic macular edema (DME) and predominantly proliferative diabetic retinopathy (PDR). These clinical presentations often occur separately, with a large percentage of patients (85% for PDR, 80% for DME) not showing signs of the other type. This suggests that DME and PDR may not be a single disease entity that progresses linearly but rather distinct diseases driven by different molecular mechanisms and genetic factors. Methods: We analyzed two distinct patient groups: i) only PDR and no signs of DME (n=182), and the other with only center-involving DME and no PDR (n =77). The severity of PDR was graded using the ETDRS standard protocol on ultrawide field retinal images. Whole-exome and whole-genome sequencing were performed to identify genetic factors, and a novel algorithm was used to evaluate the impact of coding variants in the cohort. Results: Comparative analysis of patients with exclusive manifestations of PDR compared to DME revealed a unique genetic framework differentiating the two cohorts. Notably, the prevalence of rare functional variants was significantly elevated in the PDR group (p & lt;0.05). We discovered functional variants in genes, including CD36, MMRN2, EPHB2, PLAUR, and RAPGEF3, which are enriched in the angiogenesis pathway. Phenotype-centric gene variant analysis underscored the role of MMRN2, a key player in angiogenesis (p & lt;0.001). MMRN2 (Multimerin-2) is a crucial regulator of endothelial cell movement, functioning as a negative modulator of angiogenesis by inhibiting KDR activation through its interaction with VEGFA. Conclusions: Rare functional variants may act as phenotype modifiers, potentially modulating the trajectory of DR into DME or PDR. Functional validation of these factors could represent new biomarkers and therapeutic targets for DR. Disclosure S. Rangasamy: None. F. Monickaraj: None. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim, Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines. L.P. Aiello: Advisory Panel; Novo Nordisk. Stock/Shareholder; Kalvista. Other Relationship; Optos. Consultant; Ceramedix. A. Das: None. Funding 5R01EY028606
    Materialart: Online-Ressource
    ISSN: 0012-1797
    Sprache: Englisch
    Verlag: American Diabetes Association
    Publikationsdatum: 2024
    ZDB Id: 1501252-9
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    In: Ophthalmology Science, Elsevier BV, Vol. 4, No. 5 ( 2024-09), p. 100521-
    Materialart: Online-Ressource
    ISSN: 2666-9145
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2024
    ZDB Id: 3065630-8
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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