Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes

Aim To explore if novel non‐invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes. Methods Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross‐sectional analysis with optical coherence tomograp...

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Veröffentlicht in:	Diabetic medicine 2023-03, Vol.40 (3), p.e14952-n/a
Hauptverfasser:	Kirthi, Varo, Reed, Kate I., Alattar, Komeil, Zuckerman, Benjamin P., Bunce, Catey, Nderitu, Paul, Alam, Uazman, Clarke, Bronagh, Hau, Scott, Al‐Shibani, Fatima, Petropoulos, Ioannis N., Malik, Rayaz A., Pissas, Theodoros, Bergeles, Christos, Vas, Prashanth, Hopkins, David, Jackson, Timothy L.
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Sprache:	eng
Schlagworte:	Angiography Confocal microscopy Cornea Cross-Sectional Studies Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - diagnosis Diabetic retinopathy Electroretinograms Humans Medical diagnosis neuropathy‐somatic prediabetes Prediabetic State - diagnosis Research: Complications Retina Retinal Diseases Retinopathy
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creator	Kirthi, Varo Reed, Kate I. Alattar, Komeil Zuckerman, Benjamin P. Bunce, Catey Nderitu, Paul Alam, Uazman Clarke, Bronagh Hau, Scott Al‐Shibani, Fatima Petropoulos, Ioannis N. Malik, Rayaz A. Pissas, Theodoros Bergeles, Christos Vas, Prashanth Hopkins, David Jackson, Timothy L.
description	Aim To explore if novel non‐invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes. Methods Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross‐sectional analysis with optical coherence tomography angiography (OCT‐A), handheld electroretinography (ERG), corneal confocal microscopy (CCM) and evaluation of electrochemical skin conductance (ESC). Results Seventy‐five participants with normoglycaemia (n = 20), prediabetes (n = 29) and type 2 diabetes (n = 26) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16‐Td·s: 4.05 μV, 95% confidence interval [95% CI] 0.96–7.13) and high (32‐Td·s: 5·20 μV, 95% CI 1.54–8.86) retinal illuminance were lower in prediabetes, as were OCT‐A parafoveal vessel densities in superficial (0.051 pixels/mm2, 95% CI 0.005–0.095) and deep (0.048 pixels/mm2, 95% CI 0.003–0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA1c and peak ERG amplitude at 32‐Td·s (r = −0.256, p = 0.028), implicit time at 32‐Td·s (r = 0.422, p
doi_str_mv	10.1111/dme.14952
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Methods Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross‐sectional analysis with optical coherence tomography angiography (OCT‐A), handheld electroretinography (ERG), corneal confocal microscopy (CCM) and evaluation of electrochemical skin conductance (ESC). Results Seventy‐five participants with normoglycaemia (n = 20), prediabetes (n = 29) and type 2 diabetes (n = 26) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16‐Td·s: 4.05 μV, 95% confidence interval [95% CI] 0.96–7.13) and high (32‐Td·s: 5·20 μV, 95% CI 1.54–8.86) retinal illuminance were lower in prediabetes, as were OCT‐A parafoveal vessel densities in superficial (0.051 pixels/mm2, 95% CI 0.005–0.095) and deep (0.048 pixels/mm2, 95% CI 0.003–0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA1c and peak ERG amplitude at 32‐Td·s (r = −0.256, p = 0.028), implicit time at 32‐Td·s (r = 0.422, p < 0.001) and 16‐Td·s (r = 0.327, p = 0.005), OCT parafoveal vessel density in the superficial (r = −0.238, p = 0.049) and deep (r = −0.3, p = 0.017) retinal layers, corneal nerve fibre length (CNFL) (r = −0.293, p = 0.017), and ESC‐hands (r = −0.244, p = 0.035) were observed. HOMA‐IR was a predictor of CNFD (β = −0.94, 95% CI −1.66 to −0.21, p = 0.012) and CNBD (β = −5.02, 95% CI −10.01 to −0.05, p = 0.048). Conclusions The glucose threshold for the diagnosis of diabetes is based on emergent retinopathy on fundus examination. We show that both abnormal retinal neurovascular structure (OCT‐A) and function (ERG) may precede retinopathy in prediabetes, which require confirmation in larger, adequately powered studies.</description><identifier>ISSN: 0742-3071</identifier><identifier>EISSN: 1464-5491</identifier><identifier>DOI: 10.1111/dme.14952</identifier><identifier>PMID: 36054221</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Angiography ; Confocal microscopy ; Cornea ; Cross-Sectional Studies ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - diagnosis ; Diabetic retinopathy ; Electroretinograms ; Humans ; Medical diagnosis ; neuropathy‐somatic ; prediabetes ; Prediabetic State - diagnosis ; Research: Complications ; Retina ; Retinal Diseases ; Retinopathy</subject><ispartof>Diabetic medicine, 2023-03, Vol.40 (3), p.e14952-n/a</ispartof><rights>2022 The Authors. published by John Wiley & Sons Ltd on behalf of Diabetes UK.</rights><rights>2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.</rights><rights>2022. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4442-782c268cf0cb289b6c882878258d64e4d83cf29cf32a23c2251b125764bf0b073</citedby><cites>FETCH-LOGICAL-c4442-782c268cf0cb289b6c882878258d64e4d83cf29cf32a23c2251b125764bf0b073</cites><orcidid>0000-0002-8309-086X ; 0000-0001-7618-1555 ; 0000-0002-2427-0449 ; 0000-0001-6913-6107 ; 0000-0001-7448-2995 ; 0000-0003-4322-1017 ; 0000-0002-3190-1122 ; 0000-0002-0935-3713 ; 0000-0002-8571-0751 ; 0000-0002-9152-3194 ; 0000-0002-7188-8903 ; 0000-0002-0451-0900 ; 0000-0002-1126-7638 ; 0000-0002-0077-6074 ; 0000-0002-4112-4881 ; 0000-0001-9500-7085</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdme.14952$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdme.14952$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36054221$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kirthi, Varo</creatorcontrib><creatorcontrib>Reed, Kate I.</creatorcontrib><creatorcontrib>Alattar, Komeil</creatorcontrib><creatorcontrib>Zuckerman, Benjamin P.</creatorcontrib><creatorcontrib>Bunce, Catey</creatorcontrib><creatorcontrib>Nderitu, Paul</creatorcontrib><creatorcontrib>Alam, Uazman</creatorcontrib><creatorcontrib>Clarke, Bronagh</creatorcontrib><creatorcontrib>Hau, Scott</creatorcontrib><creatorcontrib>Al‐Shibani, Fatima</creatorcontrib><creatorcontrib>Petropoulos, Ioannis N.</creatorcontrib><creatorcontrib>Malik, Rayaz A.</creatorcontrib><creatorcontrib>Pissas, Theodoros</creatorcontrib><creatorcontrib>Bergeles, Christos</creatorcontrib><creatorcontrib>Vas, Prashanth</creatorcontrib><creatorcontrib>Hopkins, David</creatorcontrib><creatorcontrib>Jackson, Timothy L.</creatorcontrib><title>Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes</title><title>Diabetic medicine</title><addtitle>Diabet Med</addtitle><description>Aim To explore if novel non‐invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes. Methods Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross‐sectional analysis with optical coherence tomography angiography (OCT‐A), handheld electroretinography (ERG), corneal confocal microscopy (CCM) and evaluation of electrochemical skin conductance (ESC). Results Seventy‐five participants with normoglycaemia (n = 20), prediabetes (n = 29) and type 2 diabetes (n = 26) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16‐Td·s: 4.05 μV, 95% confidence interval [95% CI] 0.96–7.13) and high (32‐Td·s: 5·20 μV, 95% CI 1.54–8.86) retinal illuminance were lower in prediabetes, as were OCT‐A parafoveal vessel densities in superficial (0.051 pixels/mm2, 95% CI 0.005–0.095) and deep (0.048 pixels/mm2, 95% CI 0.003–0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA1c and peak ERG amplitude at 32‐Td·s (r = −0.256, p = 0.028), implicit time at 32‐Td·s (r = 0.422, p < 0.001) and 16‐Td·s (r = 0.327, p = 0.005), OCT parafoveal vessel density in the superficial (r = −0.238, p = 0.049) and deep (r = −0.3, p = 0.017) retinal layers, corneal nerve fibre length (CNFL) (r = −0.293, p = 0.017), and ESC‐hands (r = −0.244, p = 0.035) were observed. HOMA‐IR was a predictor of CNFD (β = −0.94, 95% CI −1.66 to −0.21, p = 0.012) and CNBD (β = −5.02, 95% CI −10.01 to −0.05, p = 0.048). Conclusions The glucose threshold for the diagnosis of diabetes is based on emergent retinopathy on fundus examination. We show that both abnormal retinal neurovascular structure (OCT‐A) and function (ERG) may precede retinopathy in prediabetes, which require confirmation in larger, adequately powered studies.</description><subject>Angiography</subject><subject>Confocal microscopy</subject><subject>Cornea</subject><subject>Cross-Sectional Studies</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - diagnosis</subject><subject>Diabetic retinopathy</subject><subject>Electroretinograms</subject><subject>Humans</subject><subject>Medical diagnosis</subject><subject>neuropathy‐somatic</subject><subject>prediabetes</subject><subject>Prediabetic State - diagnosis</subject><subject>Research: Complications</subject><subject>Retina</subject><subject>Retinal Diseases</subject><subject>Retinopathy</subject><issn>0742-3071</issn><issn>1464-5491</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kc1vFCEYh4mxsWv14D9gSLzUxG35moE5GVPrR9LGi54Jw7yzS8PACsM2e_Q_l-22jZrIhcD78PDCD6FXlJzROs6HCc6o6Br2BC2oaMWyER19ihZECrbkRNJj9DznG0Io63j3DB3zljSCMbpAv66Ln90UB-PxDHl2YYUTbMH4jHPprXfB2VoLUFLcmmyLNwkPuzyWYGcXA3YBbxIMzvRQBe-wXRvvIaz2pnkNuFZWIVazrcsEeR39gOOIH068QEdjvQ1e3s8n6Meny-8XX5ZX3z5_vfhwtbRC1GdIxSxrlR2J7Znq-tYqxVTdbdTQChCD4nZknR05M4xbxhraU9bIVvQj6YnkJ-j9wbsp_QSDhTAn4_UmucmknY7G6b8rwa31Km41JURJwlU1nN4bUvxZ6mfpyWUL3psAsWTNJOkkbzq6R9_8g97EkkJ9X6Wk4KLmsKfeHiibYs4JxsduKNH7ZHVNVt8lW9nXf7b_SD5EWYHzA3DrPOz-b9Ifry8Pyt-2k7Ax</recordid><startdate>202303</startdate><enddate>202303</enddate><creator>Kirthi, Varo</creator><creator>Reed, Kate I.</creator><creator>Alattar, Komeil</creator><creator>Zuckerman, Benjamin P.</creator><creator>Bunce, Catey</creator><creator>Nderitu, Paul</creator><creator>Alam, Uazman</creator><creator>Clarke, Bronagh</creator><creator>Hau, Scott</creator><creator>Al‐Shibani, Fatima</creator><creator>Petropoulos, Ioannis N.</creator><creator>Malik, Rayaz A.</creator><creator>Pissas, Theodoros</creator><creator>Bergeles, Christos</creator><creator>Vas, Prashanth</creator><creator>Hopkins, David</creator><creator>Jackson, Timothy L.</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8309-086X</orcidid><orcidid>https://orcid.org/0000-0001-7618-1555</orcidid><orcidid>https://orcid.org/0000-0002-2427-0449</orcidid><orcidid>https://orcid.org/0000-0001-6913-6107</orcidid><orcidid>https://orcid.org/0000-0001-7448-2995</orcidid><orcidid>https://orcid.org/0000-0003-4322-1017</orcidid><orcidid>https://orcid.org/0000-0002-3190-1122</orcidid><orcidid>https://orcid.org/0000-0002-0935-3713</orcidid><orcidid>https://orcid.org/0000-0002-8571-0751</orcidid><orcidid>https://orcid.org/0000-0002-9152-3194</orcidid><orcidid>https://orcid.org/0000-0002-7188-8903</orcidid><orcidid>https://orcid.org/0000-0002-0451-0900</orcidid><orcidid>https://orcid.org/0000-0002-1126-7638</orcidid><orcidid>https://orcid.org/0000-0002-0077-6074</orcidid><orcidid>https://orcid.org/0000-0002-4112-4881</orcidid><orcidid>https://orcid.org/0000-0001-9500-7085</orcidid></search><sort><creationdate>202303</creationdate><title>Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes</title><author>Kirthi, Varo ; Reed, Kate I. ; Alattar, Komeil ; Zuckerman, Benjamin P. ; Bunce, Catey ; Nderitu, Paul ; Alam, Uazman ; Clarke, Bronagh ; Hau, Scott ; Al‐Shibani, Fatima ; Petropoulos, Ioannis N. ; Malik, Rayaz A. ; Pissas, Theodoros ; Bergeles, Christos ; Vas, Prashanth ; Hopkins, David ; Jackson, Timothy L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4442-782c268cf0cb289b6c882878258d64e4d83cf29cf32a23c2251b125764bf0b073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Angiography</topic><topic>Confocal microscopy</topic><topic>Cornea</topic><topic>Cross-Sectional Studies</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - diagnosis</topic><topic>Diabetic retinopathy</topic><topic>Electroretinograms</topic><topic>Humans</topic><topic>Medical diagnosis</topic><topic>neuropathy‐somatic</topic><topic>prediabetes</topic><topic>Prediabetic State - diagnosis</topic><topic>Research: Complications</topic><topic>Retina</topic><topic>Retinal Diseases</topic><topic>Retinopathy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kirthi, Varo</creatorcontrib><creatorcontrib>Reed, Kate I.</creatorcontrib><creatorcontrib>Alattar, Komeil</creatorcontrib><creatorcontrib>Zuckerman, Benjamin P.</creatorcontrib><creatorcontrib>Bunce, Catey</creatorcontrib><creatorcontrib>Nderitu, Paul</creatorcontrib><creatorcontrib>Alam, Uazman</creatorcontrib><creatorcontrib>Clarke, Bronagh</creatorcontrib><creatorcontrib>Hau, Scott</creatorcontrib><creatorcontrib>Al‐Shibani, Fatima</creatorcontrib><creatorcontrib>Petropoulos, Ioannis N.</creatorcontrib><creatorcontrib>Malik, Rayaz A.</creatorcontrib><creatorcontrib>Pissas, Theodoros</creatorcontrib><creatorcontrib>Bergeles, Christos</creatorcontrib><creatorcontrib>Vas, Prashanth</creatorcontrib><creatorcontrib>Hopkins, David</creatorcontrib><creatorcontrib>Jackson, Timothy L.</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetic medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kirthi, Varo</au><au>Reed, Kate I.</au><au>Alattar, Komeil</au><au>Zuckerman, Benjamin P.</au><au>Bunce, Catey</au><au>Nderitu, Paul</au><au>Alam, Uazman</au><au>Clarke, Bronagh</au><au>Hau, Scott</au><au>Al‐Shibani, Fatima</au><au>Petropoulos, Ioannis N.</au><au>Malik, Rayaz A.</au><au>Pissas, Theodoros</au><au>Bergeles, Christos</au><au>Vas, Prashanth</au><au>Hopkins, David</au><au>Jackson, Timothy L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes</atitle><jtitle>Diabetic medicine</jtitle><addtitle>Diabet Med</addtitle><date>2023-03</date><risdate>2023</risdate><volume>40</volume><issue>3</issue><spage>e14952</spage><epage>n/a</epage><pages>e14952-n/a</pages><issn>0742-3071</issn><eissn>1464-5491</eissn><abstract>Aim To explore if novel non‐invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes. Methods Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross‐sectional analysis with optical coherence tomography angiography (OCT‐A), handheld electroretinography (ERG), corneal confocal microscopy (CCM) and evaluation of electrochemical skin conductance (ESC). Results Seventy‐five participants with normoglycaemia (n = 20), prediabetes (n = 29) and type 2 diabetes (n = 26) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16‐Td·s: 4.05 μV, 95% confidence interval [95% CI] 0.96–7.13) and high (32‐Td·s: 5·20 μV, 95% CI 1.54–8.86) retinal illuminance were lower in prediabetes, as were OCT‐A parafoveal vessel densities in superficial (0.051 pixels/mm2, 95% CI 0.005–0.095) and deep (0.048 pixels/mm2, 95% CI 0.003–0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA1c and peak ERG amplitude at 32‐Td·s (r = −0.256, p = 0.028), implicit time at 32‐Td·s (r = 0.422, p < 0.001) and 16‐Td·s (r = 0.327, p = 0.005), OCT parafoveal vessel density in the superficial (r = −0.238, p = 0.049) and deep (r = −0.3, p = 0.017) retinal layers, corneal nerve fibre length (CNFL) (r = −0.293, p = 0.017), and ESC‐hands (r = −0.244, p = 0.035) were observed. HOMA‐IR was a predictor of CNFD (β = −0.94, 95% CI −1.66 to −0.21, p = 0.012) and CNBD (β = −5.02, 95% CI −10.01 to −0.05, p = 0.048). Conclusions The glucose threshold for the diagnosis of diabetes is based on emergent retinopathy on fundus examination. We show that both abnormal retinal neurovascular structure (OCT‐A) and function (ERG) may precede retinopathy in prediabetes, which require confirmation in larger, adequately powered studies.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36054221</pmid><doi>10.1111/dme.14952</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-8309-086X</orcidid><orcidid>https://orcid.org/0000-0001-7618-1555</orcidid><orcidid>https://orcid.org/0000-0002-2427-0449</orcidid><orcidid>https://orcid.org/0000-0001-6913-6107</orcidid><orcidid>https://orcid.org/0000-0001-7448-2995</orcidid><orcidid>https://orcid.org/0000-0003-4322-1017</orcidid><orcidid>https://orcid.org/0000-0002-3190-1122</orcidid><orcidid>https://orcid.org/0000-0002-0935-3713</orcidid><orcidid>https://orcid.org/0000-0002-8571-0751</orcidid><orcidid>https://orcid.org/0000-0002-9152-3194</orcidid><orcidid>https://orcid.org/0000-0002-7188-8903</orcidid><orcidid>https://orcid.org/0000-0002-0451-0900</orcidid><orcidid>https://orcid.org/0000-0002-1126-7638</orcidid><orcidid>https://orcid.org/0000-0002-0077-6074</orcidid><orcidid>https://orcid.org/0000-0002-4112-4881</orcidid><orcidid>https://orcid.org/0000-0001-9500-7085</orcidid><oa>free_for_read</oa></addata></record>
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subjects	Angiography Confocal microscopy Cornea Cross-Sectional Studies Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - diagnosis Diabetic retinopathy Electroretinograms Humans Medical diagnosis neuropathy‐somatic prediabetes Prediabetic State - diagnosis Research: Complications Retina Retinal Diseases Retinopathy
title	Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes
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