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Anstalt \u00f6ffentlichen Rechts"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>Our aim was to detect early structural and functional changes in the macular capillaries using optical coherence tomography angiography during the course of type 1 or 2 diabetes mellitus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this cross-sectional study, individuals with type 1 diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      =143) or type 2 diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      =197) from the German Diabetes Study (ClinicalTrials.gov registration no. NCT01055093) underwent clinical examination and cluster analysis to identify phenotype-based diabetes subtypes, using BMI, age, HbA\n                      <jats:sub>1c<\/jats:sub>\n                      , homoeostasis model estimates and islet autoantibodies. Colour fundus photography, optical coherence tomography and optical coherence tomography angiography were performed within the first year of diabetes diagnosis (baseline) and at 5 year intervals up to year 10. Age- and sex-adjusted participants served as control participants (\n                      <jats:italic>n<\/jats:italic>\n                      =105). Perfusion density, vessel density, presence of retinal microaneurysms in superficial, intermediate and deep capillary plexus (SCP, ICP, DCP), choriocapillaris flow deficit density (CC FD) and the foveal avascular zone (FAZ) of the macula as well as retinal layer thickness, visual acuity and contrast sensitivity were analysed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Perfusion density and vessel density of SCP were already reduced at baseline in type 2 diabetes (expected difference compared with control participants: \u22120.0071,\n                      <jats:italic>p<\/jats:italic>\n                      =0.0276, expected difference: \u22120.0034,\n                      <jats:italic>p<\/jats:italic>\n                      =0.0184, respectively), especially in participants with severe insulin-deficient and mild obesity-related diabetes. At year 10 only perfusion density of the SCP and DCP was reduced in both type 1 and 2 diabetes (\n                      <jats:italic>p<\/jats:italic>\n                      =0.0365,\n                      <jats:italic>p<\/jats:italic>\n                      =0.0062, respectively). The FAZ was enlarged and the CC FD within the first year increased in type 1 (\n                      <jats:italic>p<\/jats:italic>\n                      =0.0327,\n                      <jats:italic>p<\/jats:italic>\n                      =0.0474, respectively) and more markedly in type 2 diabetes (\n                      <jats:italic>p<\/jats:italic>\n                      =0.0006,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001). The occurrence of microaneurysms in SCP and DCP was significant at year 5 (\n                      <jats:italic>p<\/jats:italic>\n                      =0.0209,\n                      <jats:italic>p<\/jats:italic>\n                      =0.0279, respectively) and year 10 (\n                      <jats:italic>p<\/jats:italic>\n                      =0.0220,\n                      <jats:italic>p<\/jats:italic>\n                      =0.0007). Presence of microaneurysms in SCP and DCP was associated with decreases in perfusion density and vessel density in both SCP and ICP. Furthermore, microaneurysms were associated with decreased ganglion cell layer and inner plexiform layer thickness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Type 2 diabetes already reduces macular perfusion SCP at time of clinical diagnosis, while long-standing diabetes affects both SCP and DCP. The FAZ of the SCP and the CC FD are early indicators of diabetic alterations, with more pronounced changes observed in type 2 diabetes. Microaneurysms in the macular plexus are associated with a decrease of ganglion cell layer and inner plexiform layer. Subclinical microangiopathy occurs prior to manifestation of diabetic retinopathy, disease-related visual acuity impairment or inner retinal layer thinning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-025-06407-5","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T06:36:47Z","timestamp":1743575807000},"page":"1140-1156","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Macular perfusion alterations in people with recent-onset diabetes and novel diabetes subtypes"],"prefix":"10.1007","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1320-5717","authenticated-orcid":false,"given":"Sema","family":"Kaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ala","family":"Khamees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Geerling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Strzalkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Gontscharuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Szendroedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"M\u00fcssig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Roden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Guthoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the GDS Cohort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"issue":"14","key":"6407_CR1","doi-asserted-by":"publisher","first-page":"e93751","DOI":"10.1172\/jci.insight.93751","volume":"2","author":"EJ Duh","year":"2017","unstructured":"Duh EJ, Sun JK, Stitt AW (2017) Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. 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We would also like to thank our study coordinators J. Benga and S. Jansen (Department of Ophthalmology, University Hospital D\u00fcsseldorf) for their organisational and technical support. This work was initially exclusively supported by the German Diabetes Center (DDZ), which is funded by the German Federal Ministry of Health (BMG, Berlin, Germany) and the Ministry of Culture and Science of Northrhine-Westphalia (MKW-NRW, D\u00fcsseldorf, Germany) and as a multicentre study now receives additional funding by the German Federal Ministry of Education and Research (BMBF, Berlin, Germany) through the German Center for Diabetes Research (DZD e.V.). Some of the data were presented as an abstract at the ARVO Annual Meeting, June 2021, Vol. 62, Issue 8, \u2018Detection of early microvascular changes in diabetic patients with OCTA\u2019.List of GDS Study Group members: The GDS Study Group consists of M. Roden (speaker), H. Al-Hasani, B. Belgardt, G. J. B\u00f6nhof, G. Geerling, C. Herder, A. Icks, K. Jandeleit-Dahm, J. Kotzka, O. Ku\u00df, E. Lammert, W. Rathmann, S. Schlesinger, V. Schrauwen-Hinderling, J. Szendroedi, S. Trenkamp, R. Wagner and their co-workers, who contributed to the design and conduct of the GDS.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"All data supporting the findings of this study are available within the paper and its electronic supplementary material (\n                      \n                      ). The datasets are available from the corresponding author upon reasonable request and after discussion of the request within the GDS steering committee. The study protocol and the individual methods have been published in the cohort profile [\n                      \n                      ] and are unrestrictedly available.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Open Access funding enabled and organized by Projekt DEAL. This work was initially exclusively supported by the German Diabetes Center (DDZ), which is funded by the German Federal Ministry of Health (BMG, Berlin, Germany) and the Ministry of Culture and Science of Northrhine-Westphalia (MKW-NRW, D\u00fcsseldorf, Germany) and as a multicenter study now receives additional funding by the German Federal Ministry of Education and Research (BMBF, Berlin, Germany) through the German Center for Diabetes Research (DZD e.V.), which is supported by a grant (01GI0925) from the German Federal Ministry of Education and Research (BMBF).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"SK has participated in the scientific advisory board of Johnson & Johnson. GG has participated in consulting for and\/or scientific advisory boards of Santen, Holostem\/Chiesi, Novartis, Thea Pharma and Med1 Ventures. PS received speaker honoraria from Bayer. MR received fees for consulting, lecturing or serving on advisory boards from Astra Zeneca, Boehringer Ingelheim, Echosens, Eli Lilly, Merck-MSD, Madrigal, Novo Nordisk, Madrigal, Synlab and Target RWE, and has performed investigator-initiated research with support from Boehringer Ingelheim and Novo Nordisk to the DDZ. The research of MR is also supported by grants from the German Research Foundation (DFG; RTG\/GRK 2576), the European Community (HORIZON-HLTH-2022-STAYHLTH-02-01: Panel A) to the INTERCEPT-T2D consortium and the Schmutzler-Stiftung. RG has participated in consulting for and\/or scientific advisory boards of BayerHealthCare, RochePharmaAG and Abbvie.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors' relationships and activities"}},{"value":"SK and RG conceived the pilot study and evaluation, and all authors contributed to the design and operational delivery. VG performed the statistical analysis. All authors contributed to the drafting and critical review of the manuscript, and to the final approval of the submitted version. SK and RG are the guarantors of this work and are responsible for the integrity of the work as a whole.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}