{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:48:11Z","timestamp":1787014091603,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To explore if novel non\u2010invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross\u2010sectional analysis with optical coherence tomography angiography (OCT\u2010A), handheld electroretinography (ERG), corneal confocal microscopy (CCM) and evaluation of electrochemical skin conductance (ESC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventy\u2010five participants with normoglycaemia (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a020), prediabetes (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a029) and type 2 diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a026) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16\u2010Td\u00b7s: 4.05\u2009\u03bcV, 95% confidence interval [95% CI] 0.96\u20137.13) and high (32\u2010Td\u00b7s: 5\u00b720\u2009\u03bcV, 95% CI 1.54\u20138.86) retinal illuminance were lower in prediabetes, as were OCT\u2010A parafoveal vessel densities in superficial (0.051\u2009pixels\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , 95% CI 0.005\u20130.095) and deep (0.048\u2009pixels\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , 95% CI 0.003\u20130.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA\n                      <jats:sub>1c<\/jats:sub>\n                      and peak ERG amplitude at 32\u2010Td\u00b7s (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.256,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.028), implicit time at 32\u2010Td\u00b7s (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.422,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and 16\u2010Td\u00b7s (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.327,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.005), OCT parafoveal vessel density in the superficial (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.238,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.049) and deep (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.3,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.017) retinal layers, corneal nerve fibre length (CNFL) (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.293,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.017), and ESC\u2010hands (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.244,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.035) were observed. HOMA\u2010IR was a predictor of CNFD (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a0\u22120.94, 95% CI \u22121.66 to \u22120.21,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.012) and CNBD (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a0\u22125.02, 95% CI \u221210.01 to \u22120.05,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.048).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2010A) and function (ERG) may precede retinopathy in prediabetes, which require confirmation in larger, adequately powered studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dme.14952","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T11:04:38Z","timestamp":1661857478000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4322-1017","authenticated-orcid":false,"given":"Varo","family":"Kirthi","sequence":"first","affiliation":[{"name":"King's College London  London UK"},{"name":"King's College Hospital NHS Foundation Trust  London 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