{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:47:50Z","timestamp":1785764870259,"version":"3.56.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Early detection of diabetic neuropathy is crucial for both health and economic stability. Clinically, timely diagnosis and intervention can prevent the progression to severe complications, significantly preserving a patient\u2019s quality of life and mobility. Economically, this proactive approach reduces the long-term burden on healthcare systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To assess and compare the early predictive value of different heart rate variability (HRV) parameters for the early detection of type 2 diabetes mellitus (T2DM)-induced neuropathy. And to evaluate their correlation with the novel serum parameters, Brain-Derived Neurotrophic Factor (BDNF), and Nesfatin-1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>HRV parameters showed early changes in type 2 diabetics, even before the development of overt neuropathy. We investigated early changes in heart rate variability parameters in a cohort of type 2 diabetic patients compared to age-matched healthy controls. We found that heart rate variability changes occur even before the development of neuropathic symptoms, suggesting that it can be used as an early detection measure in diabetic neuropathy. Also, we measured serum brain-derived neurotrophic factor and Nesfatine-1 in all study subjects and found brain-derived neurotrophic factor to show a stronger correlation with the HRV parameters than Nesfatine-1. This correlation was more significant in the diabetic patients than the healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>We concluded that the HRV metrics can serve as sensitive early biomarkers for detecting type 2 diabetes mellitus-induced neuropathy, especially cardiac autonomic neuropathy, even in T2DM patients without clinical signs of neuropathy. Additionally, BDNF is superior to Nesfatin-1 for early detection of visceral autonomic neuropathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/jfmpc.jfmpc_320_26","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:00:34Z","timestamp":1785182434000},"page":"2267-2276","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Comparative study of the early predictive values of the heart rate variability parameters, neurophysiological and metabolic markers for the early detection of type two diabetic visceral autonomic neuropathy"],"prefix":"10.4103","volume":"15","author":[{"given":"Omar A.","family":"Alfaifi","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed S.","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Al-Regaiey","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamir","family":"Al-Khlaiwi","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida A.","family":"Korish","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed M.","family":"Khalifa","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"R1-20260803","doi-asserted-by":"crossref","first-page":"758501","DOI":"10.3389\/fphar.2022.758501","article-title":"Advances in mechanism research on Polygonatum in prevention and treatment of diabetes","volume":"13","author":"Liu","year":"2022","journal-title":"Front Pharmacol"},{"key":"R2-20260803","doi-asserted-by":"crossref","first-page":"1202917","DOI":"10.3389\/fendo.2023.1202917","article-title":"Efficacy and safety of high-dose intramuscular vitamin D2 injection in type 2 diabetes mellitus with distal symmetric polyneuropathy combined with vitamin D insufficiency: Study protocol for a multicenter, randomized, double-blinded, and placebo-controlled trial","volume":"14","author":"Chen","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"R3-20260803","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3390\/diagnostics11020165","article-title":"Early detection of diabetic peripheral neuropathy: A focus on small nerve fibres","volume":"11","author":"Burgess","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"R4-20260803","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/pathophysiology31010001","article-title":"Similar patterns of dysautonomia in myalgic encephalomyelitis\/chronic fatigue and post-COVID-19 syndromes","volume":"31","author":"Ryabkova","year":"2024","journal-title":"Pathophysiology"},{"key":"R5-20260803","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1080\/00015385.2023.2177371","article-title":"Autonomic nervous system assessment using heart rate variability","volume":"78","author":"Gr\u00e9goire","year":"2023","journal-title":"Acta cardiologica"},{"key":"R6-20260803","doi-asserted-by":"crossref","first-page":"1584922","DOI":"10.3389\/fphys.2025.1584922","article-title":"Diabetes alters cardiorespiratory dynamics: Insights from short-term recurrence quantification analysis of pulse-respiration quotient","volume":"16","author":"Reyes-Lagos","year":"2025","journal-title":"Front Physiol"},{"key":"R7-20260803","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s11916-024-01243-5","article-title":"Diabetic neuropathy: Pathophysiology review","volume":"28","author":"Strand","year":"2024","journal-title":"Curr Pain Headache Rep"},{"key":"R8-20260803","doi-asserted-by":"crossref","first-page":"1265372","DOI":"10.3389\/fendo.2023.1265372","article-title":"Diabetic peripheral neuropathy: Pathogenetic mechanisms and treatment","volume":"14","author":"Zhu","year":"2024","journal-title":"Front Endocrinol"},{"key":"R9-20260803","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10286-022-00865-2","article-title":"Interpreting resting heart rate variability in complex populations: The role of autonomic reflexes and comorbidities","volume":"32","author":"Kwon","year":"2022","journal-title":"Clin Auton Res"},{"key":"R10-20260803","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.neuroscience.2024.12.004","article-title":"The intricate brain-heart connection: The relationship between heart rate variability and cognitive functioning","volume":"565","author":"Forte","year":"2025","journal-title":"Neuroscience"},{"key":"R11-20260803","doi-asserted-by":"crossref","first-page":"1055445","DOI":"10.3389\/fnins.2023.1055445","article-title":"The connection between heart rate variability (HRV), neurological health, and cognition: A literature review","volume":"17","author":"Arakaki","year":"2023","journal-title":"Front Neurosci"},{"key":"R12-20260803","first-page":"224","article-title":"Cardiac autonomic dysfunctions in type 2 diabetes mellitus: An investigative study with heart rate variability measures","volume":"12","author":"John","year":"2022","journal-title":"Am J Cardiovasc Dis"},{"key":"R13-20260803","doi-asserted-by":"crossref","first-page":"153","DOI":"10.22141\/2224-0721.18.3.2022.1162","article-title":"A study of heart rate variability in diabetic mellitus patients","volume":"18","author":"Jayachandra","year":"2022","journal-title":"Int J Endocrinol (Ukraine)"},{"key":"R14-20260803","doi-asserted-by":"crossref","first-page":"1249709","DOI":"10.3389\/fcvm.2023.1249709","article-title":"Real-time heart rate variability according to ambulatory glucose profile in patients with diabetes mellitus","volume":"10","author":"Im","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"R15-20260803","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12933-025-02666-z","article-title":"Heart rate variability tests for diagnosing cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus in advanced stages of kidney disease","volume":"24","author":"Fel\u00edcio","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"R16-20260803","doi-asserted-by":"crossref","first-page":"13773","DOI":"10.1038\/s41598-021-93271-z","article-title":"A systematic review and meta-analysis of association between brain-derived neurotrophic factor and type 2 diabetes and glycemic profile","volume":"11","author":"Davarpanah","year":"2021","journal-title":"Sci Rep"},{"key":"R17-20260803","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1007\/s11845-024-03716-3","article-title":"Brain-derived neurotrophic factor (BDNF) and other neurotrophic factors in type 2 diabetes mellitus and their association with neuropathy","volume":"193","author":"Gaur","year":"2024","journal-title":"Ir J Med Sci"},{"key":"R18-20260803","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/IAE.0000000000002355","article-title":"Relationship between stages of diabetic retinopathy and levels of brain-derived neurotrophic factor in aqueous humor and serum","volume":"40","author":"Uzel","year":"2020","journal-title":"Retina"},{"key":"R19-20260803","doi-asserted-by":"crossref","first-page":"978143","DOI":"10.1155\/2014\/978143","article-title":"Relationship between levels of brain-derived neurotrophic factor and metabolic parameters in patients with type 2 diabetes mellitus","volume":"2014","author":"Boyuk","year":"2014","journal-title":"J Diabetes Res"},{"key":"R20-20260803","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.metabol.2006.02.012","article-title":"Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus","volume":"55","author":"Suwa","year":"2006","journal-title":"Metabolism"},{"key":"R21-20260803","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4183\/aeb.2019.69","article-title":"Serum nesfatin-1 level in healthy subjects with weight-related abnormalities and newly diagnosed patients with type 2 diabetes mellitus; A case-control study","volume":"5","author":"Mirakhor Samani","year":"2019","journal-title":"Acta Endocrinol (Buchar)"},{"key":"R22-20260803","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s43162-022-00106-y","article-title":"Serum nesfatin-1 is a biomarker of pre-diabetes and interplays with cardiovascular risk factors","volume":"34","author":"Matta","year":"2022","journal-title":"Egypt J Intern Med"},{"key":"R23-20260803","doi-asserted-by":"crossref","first-page":"882686","DOI":"10.3389\/fpubh.2022.882686","article-title":"Influence of circulating nesfatin-1, GSH and SOD on insulin secretion in the development of T2DM","volume":"10","author":"Huang","year":"2022","journal-title":"Front Public Health"},{"key":"R24-20260803","first-page":"883","article-title":"Increased nucleobindin-2 (NUCB2) transcriptional activity links the regulation of insulin sensitivity in Type 2 diabetes mellitus","volume":"36","author":"Guo","year":"2013","journal-title":"J Endocrinol Invest"},{"key":"R25-20260803","doi-asserted-by":"crossref","first-page":"7687098","DOI":"10.1155\/2017\/7687098","article-title":"Circulating nesfatin\u20101 levels and type 2 diabetes: A systematic review and meta\u2010analysis","volume":"2017","author":"Zhai","year":"2017","journal-title":"J Diabetes Res"}],"container-title":["Journal of Family Medicine and Primary Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/jfmpc.jfmpc_320_26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:06:32Z","timestamp":1785762392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/jfmpc.jfmpc_320_26"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/jfmpc.jfmpc_320_26","relation":{},"ISSN":["2249-4863","2278-7135"],"issn-type":[{"value":"2249-4863","type":"print"},{"value":"2278-7135","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2026-02-15","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-21","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}