{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:22:57Z","timestamp":1791400977694,"version":"4.3.3"},"reference-count":73,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation (NRF)","award":["121435"],"award-info":[{"award-number":["121435"]}]},{"name":"College of Health Science (CHS) of the University of KwaZulu-Natla (UKZN)","award":["121435"],"award-info":[{"award-number":["121435"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A dysregulated hypothalamic\u2013pituitary\u2013adrenal (HPA) axis in patients with type 2 diabetes (T2D), a condition preceded by prediabetes, has been shown to exacerbate the hyperglycaemic state, increasing the risk of depression. However, HPA axis activity in a prediabetic state\u2014as well as whether the prediabetic state affects HPA axis regulation\u2014is not fully understood. This study investigated the activity of the HPA axis in selected biomarkers and hormones related to HPA axis regulation in individuals with prediabetes. The study used samples obtained from adults aged between 25 and 45 of all ethnicities from the King Edward VIII Hospital. The samples were divided into three groups\u2014non-prediabetic (NPD) (n = 40), prediabetic (PD) (n = 40), and T2D (n = 40)\u2014based on the participant\u2019s glycated haemoglobin percentage. The cortisol (CORT), adrenocorticotropic hormone (ACTH), insulin, epinephrine (EPI), and norepinephrine (NE) concentrations of the samples were measured. The plasma CORT and ACTH concentrations in the PD group were higher compared to the NPD group. Plasma insulin concentration was increased only in the T2D group. There was also an increase in the plasma epinephrine concentration in the T2D group as compared to the NPD and PD groups. These observations collectively suggest that prediabetes is associated with heightened HPA axis activity and may alter HPA axis regulation, which may cause an altered stress response.<\/jats:p>","DOI":"10.3390\/ijms26136231","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:28Z","timestamp":1751347708000},"page":"6231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Prediabetes May Alter HPA Axis Activity and Regulation: A Study on Patients with Prediabetes"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9971-1854","authenticated-orcid":false,"given":"Palesa","family":"Mosili","sequence":"first","affiliation":[{"name":"School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9032-8303","authenticated-orcid":false,"given":"Bongeka Cassandra","family":"Mkhize","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phikelelani Sethu","family":"Ngubane","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5894-8935","authenticated-orcid":false,"given":"Ntethelelo Hopewell","family":"Sibiya","sequence":"additional","affiliation":[{"name":"Pharmacology Division, Faculty of Pharmacy, Rhodes University, Grahamstown 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2246-0038","authenticated-orcid":false,"given":"Andile","family":"Khathi","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.30773\/pi.2017.08.17","article-title":"Stress and heart rate variability: A meta-analysis and review of the literature","volume":"15","author":"Kim","year":"2018","journal-title":"Psychiatry Investig."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Janssen, J.A. 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