Stress etiology of type 2 diabetes
Abstract
Stress creates disharmony in the body's natural environment and thus causes an imbalance in the normal physiological system. The term diabetes describes a group of metabolic disorders, characterized and identified by the presence of hyperglycemia. Essential factors identified to initiate hyperglycemia are excess body weight, high cholesterol, high blood pressure, and lifestyle changes like stress, genetics, etc. Different types of stress and related conditions like depression, anxiety, etc., cause pancreatic β-cell dysfunction and insulin resistance, the prime risk factors in the progression of type 2 diabetes. The neuroendocrine system plays a pivotal role in countering psychological stress is the hypothalamus-pituitary-adrenal (HPA) axis, which secretes glucocorticoids (GCs), e.g., cortisol is the principal stress-responsive natural steroid hormone. The stress system essentially hampers the body's homeostasis and develops serious clinical manifestations. Glucocorticoids exert a strong physiological impact on glucose metabolism directly or indirectly, cause hyperglycemic effect and play an important role in the development of type 2 diabetes observed in patients suffering from chronic stress, Cushing's syndrome, or patients on long term GCs therapy. This review provides a clear outline on the pathways and mechanisms of stress-linked type 2 diabetes.
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Hypercortisolism plays a significant role in the development of diabetes in patients subject to chronic stress, Cushing's syndrome, or long-term GCs treatment.
“Hypercortisolism is a clinical state attributed to over-exposure to excessive GCs and plays a significant role in the development of diabetes observed in patients subject to chronic stress, Cushing’s syndrome, or long-term GCs treatment (8).”
From The progression of secondary diabetes: A review of modeling studies (2022) · cites this paper as [8]
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Stress and the CRH System, Norepinephrine, Depression, and Type 2 Diabetes
Perrelli, M., Goparaju, P., Postolache, T. T., del Bosque‐Plata, L., & Gragnoli, C. (2024) · Biomedicines · doi:10.3390/biomedicines12061187 · Cited by 35 · see citing works
“In fact, the etiology of stress in the pathogenesis of T2D has been reported [20,21].”
BackgroundChronic stress, gut microbiota, and immunity: interconnections and implications for health
Jia, H., Guo, X., Wei, Y., Can, C., He, N., Zhang, H., Yang, X., Wu, H., Liu, W., & Ma, D. (2025) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-025-05376-y · Cited by 14 · see citing works
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“Recently, chronic stress has also been increasingly recognized as a potential risk factor for T2D (12,13).”
BackgroundThe progression of secondary diabetes: A review of modeling studies
Yang, B., Li, J., Haller, M. J., Schatz, D. A., & Rong, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1070979 · Cited by 6 · see citing works
“Hypercortisolism is a clinical state attributed to over-exposure to excessive GCs and plays a significant role in the development of diabetes observed in patients subject to chronic stress, Cushing’s syndrome, or long-term GCs treatment (8).”
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“Additionally, GCs are known to have negative effects on insulin sensitivity [8].”
BackgroundChen, R., Wang, Q., Wang, Y. Y., Wang, Y., Liu, J., Liao, Z., & Xiao, X. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1094458 · Cited by 5 · see citing works
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“Stress has become an inevitable component of modern human life that is growing in quantity to alarming and qualitatively threatening levels.[1] Stress impacts the neuroendocrine system by stimulating the hypothalamus‐pituitary‐adrenal (HPA) and axis the sympathetic nervous system.”
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Makvandi, M., Khodabakhshi, Z., Liu, Y., Li, W., & Yuan, P. F. (2025) · Sustainability · doi:10.3390/su17156973 · Cited by 3 · see citing works
Environmental and Lifestyle Determinants of Type 2 Diabetes MellitusPreprint
Siddiqui, I., Baig, M. M., & Khan, N. A. (2024) · Research Square · doi:10.21203/rs.3.rs-4738489/v1 · Cited by 9 · see citing works
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“70 A study was conducted to examine the role of stress responses in the prediabetic condition in Latino adults.”
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Diurnal cortisol cycle and cognitive performance in older people with Type 2 diabetes
Vallejo, L., Zapater‐Fajarí, M., Montoliu, T., Hidalgo, V., & Salvador, A. (2025) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2025.107718 · Cited by 1 · see citing works
A 2-es típusú cukorbetegség kapcsolata a szorongásos és az affektív zavarokkal
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“Second, steroid hormones may induce hypertension (Dodic et al., 1999) and hyperglycemia (Sunena and Mishra, 2022), along with peptic ulcers and various metabolic disorders (Conn and Poynard, 1994), thereby complicating diseases further.”
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A Mathematical Modeling Approach to Estimate Blood Glucose Behavior in Individuals with Prediabetes
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“These hormones directly impair insulin sensitivity and stimulate hepatic glucose output, contributing to hyperglycemia through a pathway that operates independently of behavioral self-care [24].”
Ковальчук, А., Zinych, О. В., Shyshkan-Shyshova, К. О., Кушнарьова, Н. М., Prybyla, О. В., & Шупрович, А. (2026) · INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) · doi:10.22141/2224-0721.22.4.2026.1722
- Authors
- Sunena, & Mishra, D. N.
- Affiliations
- Geeta Institute of Pharmacy, Panipat -132145, Haryana, India
- Department of Pharmceutical Sciences, Chaudhary Bansi Lal University, Bhiwani -127021, India
- Corresponding author
- Sunena
- ORCID
- Sunena
- Venue
- Current Diabetes Reviews
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2022-11
- Volume
- 18
- Issue
- 9
- Pages
- e240222201413-e240222201413
- ISSN
- 1573-3998 (ISSN-L)
- OpenAlex
- W4214552559
- Cited by
- 22
- References
- 0
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 1
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Diabetes Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- type 2 diabetes, psychological stress, chronic stress, hyperglycemia, insulin resistance, beta-cell dysfunction, hypothalamic-pituitary-adrenal axis, glucocorticoids, cortisol, Cushing's syndrome, glucocorticoid therapy, depression, anxiety, glucose metabolism
- MeSH terms
- Diabetes Mellitus, Type 2, Glucocorticoids, Humans, Hyperglycemia, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Stress, Physiological
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