{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T18:35:23Z","timestamp":1783794923186,"version":"3.55.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"The German Diabetes Study"},{"name":"German Diabetes Center"},{"name":"German Federal Ministry of Health"},{"name":"Ministry of Innovation, Science, Research and Technology"},{"name":"North Rhine-Westphalia"},{"name":"German Federal Ministry of Education and Research"},{"name":"German Center for Diabetes Research"},{"name":"European Funds for Regional Development","award":["EFRE-0400191"],"award-info":[{"award-number":["EFRE-0400191"]}]},{"name":"EUREKA Eurostars-2"},{"name":"German Science Foundation"},{"DOI":"10.13039\/100004807","name":"DFG","doi-asserted-by":"publisher","award":["CRC\/SFB 1116\/2 B12"],"award-info":[{"award-number":["CRC\/SFB 1116\/2 B12"]}],"id":[{"id":"10.13039\/100004807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Schmutzler Stiftung"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>It has traditionally been suggested that the early development of diabetic sensorimotor polyneuropathy (DSPN) is characterized by predominant and progressive injury to small nerve fibres followed by large fibre impairment. We alternatively hypothesized that small and large fibre damage due to DSPN in type 1 and type 2 diabetes could develop in parallel and may not only be progressive but also reversible.<\/jats:p>\n               <jats:p>Participants from the German Diabetes Study baseline cohort with recent-onset type 1\/type 2 diabetes (n\u2009=\u2009350\/570) and age-matched glucose-tolerant control individuals (Control 1\/Control 2: n\u2009=\u2009114\/190) were assessed using nerve conduction studies, thermal detection thresholds, vibration perception thresholds, neuropathy symptom scores, neuropathy disability scores and intraepidermal nerve fibre density (IENFD) in skin biopsies (type 1\/type 2 diabetes: n\u2009=\u2009102\/226; Control 1\/Control 2: n\u2009=\u2009109\/208). Subsets of participants with type 1\/type 2 diabetes were followed for 5\u2009years (n\u2009=\u2009184\/307; IENFD subset: n\u2009=\u200918\/69). DSPN was defined by the Toronto Consensus criteria.<\/jats:p>\n               <jats:p>At baseline, DSPN was present in 8.1% and 13.3% of the type 1 and type 2 diabetes groups, respectively. The most frequently abnormal tests in the lower limbs below or above the 2.5th and 97.5th centiles of the controls were the IENFD (13.7%) and individual nerve conduction studies (up to 9.4%) in type 1 diabetes participants and IENFD (21.8%), malleolar vibration perception thresholds (17.5%), and individual nerve conduction studies (up to 11.8%) in those with type 2 diabetes, whereas thermal detection threshold abnormalities did not differ between the control and diabetes groups. After 5\u2009years, the highest progression rates from the normal to the abnormal range in type 2 diabetes participants were found for IENFD (18.8%) by \u22124.1\u2009\u00b1\u20092.8 fibres\/mm, malleolar vibration perception threshold (18.6%) by 9.1\u2009\u00b1\u200920.2\u2009\u00b5m and nerve conduction studies (15.0%) by 3.7\u2009\u00b1\u20091.5 points, while vice versa the highest regression rates were observed for neuropathy disability scores (11.2%) by \u22123.1\u2009\u00b1\u20091.3 points, sural nerve amplitudes (9.1%) by 4.7\u2009\u00b1\u20093.0\u2009\u00b5V, IENFD (8.7%) by 1.4\u2009\u00b1\u20091.3 fibres\/mm, and neuropathy symptom scores (8.2%) by \u22125.8\u2009\u00b1\u20091.6 points. In type 1 diabetes participants, no major progression was seen after 5\u2009years, but subclinical DSPN regressed in 10.3%.<\/jats:p>\n               <jats:p>These findings point to early parallel damage to both small and large nerve fibres in well-controlled recent-onset type 2 and, to a lesser extent, type 1 diabetes. After 5\u2009years, peripheral nerve morphology and function and clinical measures progress to the abnormal range in type 2 diabetes, but initial nerve alterations are also reversible to a meaningful degree.<\/jats:p>","DOI":"10.1093\/brain\/awab330","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T11:36:32Z","timestamp":1631100992000},"page":"3251-3263","source":"Crossref","is-referenced-by-count":38,"title":["Progression and regression of nerve fibre pathology and dysfunction early in diabetes over 5 years"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8956-3552","authenticated-orcid":false,"given":"Dan","family":"Ziegler","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Department of Endocrinology and Diabetology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research, Partner D\u00fcsseldorf, 85764 M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gidon J","family":"B\u00f6nhof","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Department of Endocrinology and Diabetology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Strom","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research, Partner D\u00fcsseldorf, 85764 M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Stra\u00dfburger","sequence":"additional","affiliation":[{"name":"Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanislava","family":"Karusheva","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5185-8168","authenticated-orcid":false,"given":"Julia","family":"Szendroedi","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Department of Endocrinology and Diabetology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research, Partner D\u00fcsseldorf, 85764 M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-6382","authenticated-orcid":false,"given":"Michael","family":"Roden","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Department of Endocrinology and Diabetology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University\u00a0D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research, Partner D\u00fcsseldorf, 85764 M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"issue":"1","key":"2021120109193163200_awab330-B1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.2337\/dc16-2042","article-title":"Diabetic neuropathy. 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