Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression
Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia which is further associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Several studies have shown that HPA axis hyperactivity is heightened in the chronic hyperglycemic state with severe hyperglyce...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-02-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/12/1/e003218.full |
| _version_ | 1797289462421520384 |
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| author | Andile Khathi Palesa Mosili Bongeka Cassandra Mkhize Ntethelelo Hopewell Sibiya Phikelelani Sethu Ngubane |
| author_facet | Andile Khathi Palesa Mosili Bongeka Cassandra Mkhize Ntethelelo Hopewell Sibiya Phikelelani Sethu Ngubane |
| author_sort | Andile Khathi |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia which is further associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Several studies have shown that HPA axis hyperactivity is heightened in the chronic hyperglycemic state with severe hyperglycemic events more likely to result in a depressive disorder. The HPA axis is also regulated by the immune system. Upon stress, under homeostatic conditions, the immune system is activated via the sympatho-adrenal-medullary axis resulting in an immune response which secretes proinflammatory cytokines. These cytokines aid in the activation of the HPA axis during stress. However, in T2DM, where there is persistent hyperglycemia, the immune system is dysregulated resulting in the elevated concentrations of these cytokines. The HPA axis, already activated by the hyperglycemia, is further activated by the cytokines which all contribute to a diagnosis of depression in patients with T2DM. However, the onset of T2DM is often preceded by pre-diabetes, a reversible state of moderate hyperglycemia and insulin resistance. Complications often seen in T2DM have been reported to begin in the pre-diabetic state. While the current management strategies have been shown to ameliorate the moderate hyperglycemic state and decrease the risk of developing T2DM, research is necessary for clinical studies to profile these direct effects of moderate hyperglycemia in pre-diabetes on the HPA axis and the indirect effects moderate hyperglycemia may have on the HPA axis by investigating the components of the immune system that play a role in regulating this pathway. |
| first_indexed | 2024-03-07T19:05:16Z |
| format | Article |
| id | doaj.art-67a43f96d5fc42b0b7b1cecf94408b14 |
| institution | Directory Open Access Journal |
| issn | 2052-4897 |
| language | English |
| last_indexed | 2024-03-07T19:05:16Z |
| publishDate | 2024-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj.art-67a43f96d5fc42b0b7b1cecf94408b142024-03-01T09:15:08ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972024-02-0112110.1136/bmjdrc-2022-003218Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depressionAndile Khathi0Palesa Mosili1Bongeka Cassandra Mkhize2Ntethelelo Hopewell Sibiya3Phikelelani Sethu Ngubane4Human Physiology, University of KwaZulu-Natal College of Health Sciences, Durban, KwaZulu-Natal, South AfricaHuman Physiology, University of KwaZulu-Natal College of Health Sciences, Durban, KwaZulu-Natal, South AfricaHuman Physiology, University of KwaZulu-Natal College of Health Sciences, Durban, KwaZulu-Natal, South AfricaPharmacy and Pharmacology, Rhodes University, Grahamstown, Eastern Cape, South AfricaHuman Physiology, University of KwaZulu-Natal College of Health Sciences, Durban, KwaZulu-Natal, South AfricaType 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia which is further associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Several studies have shown that HPA axis hyperactivity is heightened in the chronic hyperglycemic state with severe hyperglycemic events more likely to result in a depressive disorder. The HPA axis is also regulated by the immune system. Upon stress, under homeostatic conditions, the immune system is activated via the sympatho-adrenal-medullary axis resulting in an immune response which secretes proinflammatory cytokines. These cytokines aid in the activation of the HPA axis during stress. However, in T2DM, where there is persistent hyperglycemia, the immune system is dysregulated resulting in the elevated concentrations of these cytokines. The HPA axis, already activated by the hyperglycemia, is further activated by the cytokines which all contribute to a diagnosis of depression in patients with T2DM. However, the onset of T2DM is often preceded by pre-diabetes, a reversible state of moderate hyperglycemia and insulin resistance. Complications often seen in T2DM have been reported to begin in the pre-diabetic state. While the current management strategies have been shown to ameliorate the moderate hyperglycemic state and decrease the risk of developing T2DM, research is necessary for clinical studies to profile these direct effects of moderate hyperglycemia in pre-diabetes on the HPA axis and the indirect effects moderate hyperglycemia may have on the HPA axis by investigating the components of the immune system that play a role in regulating this pathway.https://drc.bmj.com/content/12/1/e003218.full |
| spellingShingle | Andile Khathi Palesa Mosili Bongeka Cassandra Mkhize Ntethelelo Hopewell Sibiya Phikelelani Sethu Ngubane Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression BMJ Open Diabetes Research & Care |
| title | Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression |
| title_full | Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression |
| title_fullStr | Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression |
| title_full_unstemmed | Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression |
| title_short | Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression |
| title_sort | review of the direct and indirect effects of hyperglycemia on the hpa axis in t2dm and the co occurrence of depression |
| url | https://drc.bmj.com/content/12/1/e003218.full |
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