{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:05:30Z","timestamp":1778893530908,"version":"3.51.4"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["236360313-SFB 1118"],"award-info":[{"award-number":["236360313-SFB 1118"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013294","name":"Deutsches Forschungszentrum f\u00fcr Gesundheit und Umwelt, Helmholtz Zentrum M\u00fcnchen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013294","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background and aim<\/jats:title><jats:p>Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D).<\/jats:p><\/jats:sec><jats:sec><jats:title>Study design and methods<\/jats:title><jats:p>Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 \u00b1 1.3% [61.4 \u00b1 14.3 mmol\/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:uri>https:\/\/drks.de\/search\/en\/trial\/DRKS00014287<\/jats:uri>, identifier DRKS00014287.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1143799","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T06:38:13Z","timestamp":1683873493000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients"],"prefix":"10.3389","volume":"14","author":[{"given":"Zoltan","family":"Kender","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"von Rauchhaupt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios","family":"Tsilingiris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Schimpfle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannelore","family":"Bartl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valter D.","family":"Longo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bendszus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Kopf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Herzig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Heiland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Szendroedi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Sulaj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"B1","unstructured":"IDF diabetes atlas 2021 | IDF diabetes atlas"},{"key":"B2","unstructured":"Global report on diabetes"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2013.06.001","article-title":"Diabetic neuropathy","volume":"42","author":"Vinik","year":"2013","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B4","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1056\/NEJM199507133330203","article-title":"Natural history of peripheral neuropathy in patients with non-Insulin-Dependent diabetes mellitus","volume":"333","author":"Partanen","year":"1995","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.719356","article-title":"Gold standard for diagnosis of DPN","volume":"12","author":"Yu","year":"2021","journal-title":"Front Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41572-019-0092-1","article-title":"Diabetic neuropathy","volume":"5","author":"Feldman","year":"2019","journal-title":"Nat Rev Dis Primer."},{"key":"B7","doi-asserted-by":"publisher","first-page":"154867","DOI":"10.1016\/j.metabol.2021.154867","article-title":"Management of diabetic neuropathy","volume":"123","author":"Cernea","year":"2021","journal-title":"Metabolism"},{"key":"B8","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1080\/14656566.2020.1812578","article-title":"State-of-the-art pharmacotherapy for diabetic neuropathy","volume":"22","author":"Azmi","year":"2021","journal-title":"Expert Opin Pharmacother."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.cd007543.pub2","article-title":"Enhanced glucose control for preventing and treating diabetic neuropathy","author":"Callaghan","year":"","journal-title":"Cochrane Database Syst Rev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2005.07.005","article-title":"Exercise training can modify the natural history of diabetic peripheral neuropathy","volume":"20","author":"Balducci","year":"2006","journal-title":"J Diabetes Complications."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4253-z","article-title":"Effects of a long-term lifestyle modification programme on peripheral neuropathy in overweight or obese adults with type 2 diabetes: the look AHEAD study","volume":"60","year":"2017","journal-title":"Diabetologia"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.3390\/nu11102510","article-title":"Ketogenic diet and epilepsy","volume":"11","author":"U\u0142amek-Kozio\u0142","year":"2019","journal-title":"Nutrients"},{"key":"B13","doi-asserted-by":"publisher","first-page":"681289","DOI":"10.1155\/2015\/681289","article-title":"The therapeutic potential of the ketogenic diet in treating progressive multiple sclerosis","volume":"2015","author":"Storoni","year":"2015","journal-title":"Mult Scler Int"},{"key":"B14","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41394-018-0121-4","article-title":"Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: a pilot, randomized safety and feasibility trial","volume":"4","author":"Yarar-Fisher","year":"2018","journal-title":"Spinal Cord Ser Cases."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202969","article-title":"Ketogenic diet-mediated steroid metabolism reprogramming improves the immune microenvironment and myelin growth in spinal cord injury rats according to gene and co-expression network analyses","volume":"13","author":"Zeng","year":"2021","journal-title":"Aging"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1080\/19768354.2018.1490348","article-title":"Characterization of changes of pain behavior and signal transduction system in food-deprived mice","volume":"22","author":"Jang","year":"2018","journal-title":"Anim Cells Syst"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-35-11120.2003","article-title":"Analgesia induced by dietary restriction is mediated by the \u03ba-opioid system","volume":"23","author":"de los Santos-Arteaga","year":"2003","journal-title":"J Neurosci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1093\/brain\/awu307","article-title":"Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes","volume":"138","author":"Gibbons","year":"2015","journal-title":"Brain"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac197","article-title":"Six-month periodic fasting in patients with type 2 diabetes and diabetic nephropathy: a proof-of-Concept study","volume":"107","author":"Sulaj","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","volume-title":"Nationale VersorgungsLeitlinie neuropathie bei diabetes im erwachsenenalter - langfassung","year":"2011"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.671257","article-title":"Advances in screening, early diagnosis and accurate staging of diabetic neuropathy","volume":"12","author":"Carmichael","year":"2021","journal-title":"Front Endocrinol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab330","article-title":"Progression and regression of nerve fibre pathology and dysfunction early in diabetes over 5 years","volume":"144","author":"Ziegler","year":"2021","journal-title":"Brain"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-1303","article-title":"Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments","volume":"33","author":"Tesfaye","year":"2010","journal-title":"Diabetes Care"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.01.041","article-title":"Quantitative sensory testing in the German research network on neuropathic pain (DFNS): standardized protocol and reference values","volume":"123","author":"Rolke","year":"2006","journal-title":"PAIN"},{"key":"B25","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.diabres.2018.10.020","article-title":"Deep phenotyping neuropathy: an underestimated complication in patients with pre-diabetes and type 2 diabetes associated with albuminuria","volume":"146","author":"Kopf","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0197","article-title":"Understanding diabetic neuropathy\u2013from subclinical nerve lesions to severe nerve fiber deficits: a cross-sectional study in patients with type 2 diabetes and healthy control subjects","volume":"69","author":"Groener","year":"2020","journal-title":"Diabetes"},{"key":"B27","doi-asserted-by":"publisher","first-page":"7593","DOI":"10.1038\/s41598-020-64585-1","article-title":"Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength","volume":"10","author":"Schwarz","year":"2020","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-0224","article-title":"Lifestyle intervention for pre-diabetic neuropathy","volume":"29","author":"Smith","year":"2006","journal-title":"Diabetes Care"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00929","article-title":"New perspective in diabetic neuropathy: from the periphery to the brain, a call for early detection, and precision medicine","volume":"10","author":"Yang","year":"2020","journal-title":"Front Endocrinol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0746","article-title":"Conduction slowing in diabetic sensorimotor polyneuropathy","volume":"36","author":"Dunnigan","year":"2013","journal-title":"Diabetes Care"},{"key":"B31","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.mcn.2007.10.004","article-title":"Hyperglycaemia inhibits schwann cell proliferation and migration and restricts regeneration of axons and schwann cells from adult murine DRG","volume":"37","author":"Gumy","year":"2008","journal-title":"Mol Cell Neurosci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4008-2","article-title":"The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes","volume":"59","author":"Cherney","year":"2016","journal-title":"Diabetologia"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.05.009","article-title":"A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms","volume":"15","author":"Choi","year":"2016","journal-title":"Cell Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-019-00607-x","article-title":"Physical activity and dietary interventions in diabetic neuropathy: a systemic review","volume":"29","author":"Zilliox","year":"2019","journal-title":"Clin Auton Res Off J Clin Auton Res Soc"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21952","article-title":"Treatment-induced diabetic neuropathy: a reversible painful autonomic neuropathy","volume":"67","author":"Gibbons","year":"2010","journal-title":"Ann Neurol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2012.05.007","article-title":"The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy","volume":"26","author":"Kluding","year":"2012","journal-title":"J Diabetes Complications."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0352-x","article-title":"A network meta-analysis on the comparative efficacy of different dietary approaches on glycaemic control in patients with type 2 diabetes mellitus","volume":"33","author":"Schwingshackl","year":"2018","journal-title":"Eur J Epidemiol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.01.010","article-title":"Analgesic effects of dietary caloric restriction in adult mice","volume":"114","author":"Hargraves","year":"2005","journal-title":"Pain"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.1493","article-title":"Impact of caloric restriction on peripheral nerve injury-induced neuropathic pain during ageing in mice","volume":"24","author":"De Angelis","year":"2020","journal-title":"Eur J Pain."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0208596","article-title":"Effects of caloric restriction on neuropathic pain, peripheral nerve degeneration and inflammation in normometabolic and autophagy defective prediabetic Ambra1 mice","volume":"13","author":"Coccurello","year":"2018","journal-title":"PloS One"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24243","article-title":"Proficiency of nerve conduction using standard methods and reference values (Cl. NPhys trial 4)","volume":"50","author":"Litchy","year":"2014","journal-title":"Muscle Nerve."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21661","article-title":"Signs and symptoms versus nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy: cl vs. NPhys trial","volume":"42","author":"Dyck","year":"2010","journal-title":"Muscle Nerve."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)02478-7","article-title":"Effect of angiotensin-converting-enzyme (ACE) inhibitor trandolapril on human diabetic neuropathy: randomised double-blind controlled trial","volume":"352","author":"Malik","year":"1998","journal-title":"Lancet Lond Engl"},{"key":"B44","doi-asserted-by":"publisher","first-page":"596","DOI":"10.2337\/dc15-2068","article-title":"Long-acting c-peptide and neuropathy in type 1 diabetes: a 12-month clinical trial","volume":"39","author":"Wahren","year":"2016","journal-title":"Diabetes Care"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199004123221503","article-title":"Effects of pancreatic transplantation on diabetic neuropathy","volume":"322","author":"Kennedy","year":"1990","journal-title":"N Engl J Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.11.013","article-title":"Test-retest and interobserver reliability of quantitative sensory testing according to the protocol of the German research network on neuropathic pain (DFNS): a multi-centre study","volume":"152","author":"Geber","year":"2011","journal-title":"Pain"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.642589","article-title":"Diffusion tensor imaging of the sciatic nerve as a surrogate marker for nerve functionality of the upper and lower limb in patients with diabetes and prediabetes","volume":"15","author":"Jende","year":"2021","journal-title":"Front Neurosci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049742","article-title":"MR neurography in ulnar neuropathy as surrogate parameter for the presence of disseminated neuropathy","volume":"7","author":"B\u00e4umer","year":"2012","journal-title":"PloS One"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24524","article-title":"Magnetic resonance neurography detects diabetic neuropathy early and with proximal predominance","volume":"78","author":"Pham","year":"2015","journal-title":"Ann Neurol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25182","article-title":"Diabetic neuropathy differs between type 1 and type 2 diabetes: insights from magnetic resonance neurography","volume":"83","author":"Jende","year":"2018","journal-title":"Ann Neurol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.125","article-title":"Exercise increases cutaneous nerve density in diabetic patients without neuropathy","volume":"1","author":"Singleton","year":"2014","journal-title":"Ann Clin Transl Neurol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1143799\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T06:38:18Z","timestamp":1683873498000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1143799\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,12]]},"references-count":51,"alternative-id":["10.3389\/fendo.2023.1143799"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1143799","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,12]]},"article-number":"1143799"}}