Prediabetes May Alter HPA Axis Activity and Regulation: A Study on Patients with Prediabetes
Palesa Mosili1, Bongeka Cassandra Mkhize1, Phikelelani Sethu Ngubane1
1School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville 4000, South Africa.
International Journal of Molecular Sciences
|July 12, 2025
Summary
Prediabetes is linked to increased hypothalamic-pituitary-adrenal (HPA) axis activity, indicated by higher cortisol and ACTH levels. This suggests prediabetes may alter stress response regulation, impacting future health outcomes.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Neuroendocrinology
Background:
- A dysregulated hypothalamic-pituitary-adrenal (HPA) axis exacerbates hyperglycemia in type 2 diabetes (T2D), increasing depression risk.
- HPA axis activity and regulation during prediabetes remain unclear.
- Understanding prediabetes's impact on the HPA axis is crucial for early intervention.
Purpose of the Study:
- To investigate HPA axis activity in prediabetes.
- To assess HPA axis regulatory biomarkers and hormones in individuals with prediabetes.
- To determine if prediabetes alters HPA axis regulation.
Main Methods:
- Adult participants (25-45 years) were categorized into non-prediabetic (NPD), prediabetic (PD), and T2D groups (n=40 each).
- Plasma concentrations of cortisol (CORT), adrenocorticotropic hormone (ACTH), insulin, epinephrine (EPI), and norepinephrine (NE) were measured.
- Group classification was based on glycated haemoglobin percentage.
Main Results:
- Plasma CORT and ACTH concentrations were elevated in the PD group compared to the NPD group.
- Plasma insulin levels increased significantly only in the T2D group.
- Plasma EPI levels were higher in the T2D group versus NPD and PD groups.
Conclusions:
- Prediabetes is associated with heightened HPA axis activity.
- The prediabetic state may alter HPA axis regulation.
- These alterations may contribute to an altered stress response in individuals with prediabetes.
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