Understanding the relationship between stress and diabetes.

Stress has a significant impact on blood sugar levels, particularly for individuals with diabetes. Recent studies have provided insights into how stress affects glucose metabolism and diabetes management.

STRESS AND GLUCOSE METABOLISM

• Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to the release of cortisol, a glucocorticoid hormone. Elevated cortisol levels can increase blood glucose levels by promoting gluconeogenesis (the production of glucose from non-carbohydrate sources) and reducing insulin sensitivity.¹
• Chronic stress can lead to sustained high levels of cortisol, which may contribute to the development of insulin resistance and type 2 diabetes (T2D).²

IMPACT OF STRESS ON DIABETES MANAGEMENT

• Stress and glucocorticoids are linked to the risk of developing alcohol use disorders and relapse, which can complicate diabetes management due to poor lifestyle choices and inconsistent medication adherence.³
• Sleep deprivation, a common consequence of stress, potentiates HPA axis stress reactivity, leading to higher cortisol levels and subsequently higher blood glucose levels.⁴

PSYCHOSOCIAL STRESS AND BLOOD SUGAR LEVELS

• Chronic stress, as measured by hair cortisol concentrations (HCC), is associated with elevated blood glucose levels. This method of measuring long-term cortisol exposure provides a more accurate picture of the chronic stress-blood sugar relationship.⁵
• A link between PTSD symptoms, stress, and inflammation has been found in several studies, indicating that severe stress can exacerbate blood glucose dysregulation through inflammatory pathways.^6,7

BEHAVIOURAL AND ENVIRONMENTAL FACTORS:

• Studies have shown that individuals experiencing weight stigma or discrimination have higher cortisol levels, which can lead to increased blood glucose levels. Jackson et al. found that obese individuals who experienced weight-related discrimination had higher HCC levels than those who did not, suggesting that social stressors can directly impact metabolic health.^8,9
• Environmental factors such as poor sleep,¹⁰ high glycaemic index diets,¹¹ and excessive alcohol use¹² can exacerbate stress responses and lead to higher blood glucose levels.

GENETIC AND INDIVIDUAL DIFFERENCES

Interindividual differences in glucocorticoid sensitivity, which can be partly genetically determined, may lead to varying responses to stress. Some individuals may have a higher vulnerability to stress-induced hyperglycaemia due to genetic variations in glucocorticoid receptor sensitivity.^13,14

CLINICAL IMPLICATIONS

Understanding the relationship between stress and blood sugar levels can lead to more effective and individualised treatment strategies for managing diabetes. Integrating stress management techniques, such as mindfulness, cognitive-behavioural therapy, and lifestyle modifications, can help improve blood glucose control in individuals with diabetes.

REFERENCES 

1. Seal SV, Turner JD. The 'Jekyll and Hyde' of Gluconeogenesis: Early Life Adversity, Later Life Stress, and Metabolic Disturbances. Int J Mol Sci. 2021 Mar 25;22(7):3344. doi: 10.3390/ijms22073344. PMID: 33805856; PMCID: PMC8037741. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037741/. 
2. Joseph JJ, Golden SH. Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus. Ann N Y Acad Sci. 2017 Mar;1391(1):20-34. doi: 10.1111/nyas.13217. Epub 2016 Oct 17. PMID: 27750377; PMCID: PMC5334212. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334212/. 
3. Blaine SK, Sinha R. Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders. Neuropharmacology. 2017 Aug 1;122:136-147. doi: 10.1016/j.neuropharm.2017.01.037. Epub 2017 Feb 1. PMID: 28159647; PMCID: PMC5479733. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479733/. 
4. Minkel J, Moreta M, Muto J, Htaik O, Jones C, Basner M, Dinges D. Sleep deprivation potentiates HPA axis stress reactivity in healthy adults. Health Psychol. 2014 Nov;33(11):1430-4. doi: 10.1037/a0034219. Epub 2014 May 12. PMID: 24818608. Available from: https://pubmed.ncbi.nlm.nih.gov/24818608/. 
5. Stalder T, Steudte-Schmiedgen S, Alexander N, et al. Stress-related and basic determinants of hair cortisol in humans: A meta-analysis, Psychoneuroendocrinology. 2017;77:261-274, ISSN 0306-4530. Available from: https://doi.org/10.1016/j.psyneuen.2016.12.017. 
6. Katrinli, S., Oliveira, N.C.S., Felger, J.C. et al. The role of the immune system in posttraumatic stress disorder. Transl Psychiatry 2022;12(313). Available from: https://doi.org/10.1038/s41398-022-02094-7. 
7. Quinones, M.M., Gallegos, A.M., Lin, F.V. et al. Dysregulation of inflammation, neurobiology, and cognitive function in PTSD: an integrative review. Cogn Affect Behav Neurosci 2020;20:455-480. Available from: https://doi.org/10.3758/s13415-020-00782-9. 
8. Jackson SE, Kirschbaum C, Steptoe A. Perceived weight discrimination and chronic biochemical stress: A population-based study using cortisol in scalp hair. Obesity (Silver Spring). 2016 Dec;24(12):2515-2521. doi: 10.1002/oby.21657. Epub 2016 Oct 14. PMID: 27740706; PMCID: PMC5132135. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5132135/. 
9. Jackson SE, Steptoe A. Obesity, perceived weight discrimination, and hair cortisol: a population-based study. Psychoneuroendocrinology. 2018 Dec;98:67-73. doi: 10.1016/j.psyneuen.2018.08.018. Epub 2018 Aug 11. PMID: 30118922. Available from: https://www.sciencedirect.com/science/article/abs/pii/S030645301830502X?via%3Dihub. 
10. Martire VL, Caruso D, Palagini L, Zoccoli G, Bastianini S. Stress & sleep: A relationship lasting a lifetime. Neuroscience & Biobehavioral Reviews. 2020;17:65-77. ISSN 0149-7634. Available from: https://doi.org/10.1016/j.neubiorev.2019.08.024. 
11. Al-Dujaili EAS, Ashmore S, Tsang C. A Short Study Exploring the Effect of the Glycaemic Index of the Diet on Energy intake and Salivary Steroid Hormones. Nutrients. 2019 Jan 24;11(2):260. doi: 10.3390/nu11020260. PMID: 30682835; PMCID: PMC6413178. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6413178/. 
12. Ramchandani VA, Stangl BL, Blaine SK, et al. Stress vulnerability and alcohol use and consequences: From human laboratory studies to clinical outcomes. Alcohol. 2018;72:75-88. ISSN 0741-8329. Available from: https://doi.org/10.1016/j.alcohol.2018.06.001. 
13. Lengton R, Iyer AM, van der Valk ES, Hoogeveen EK, Meijer OC, van der Voorn B, van Rossum EFC. Variation in glucocorticoid sensitivity and the relation with obesity. Obes Rev. 2022 Mar;23(3):e13401. doi: 10.1111/obr.13401. Epub 2021 Nov 27. PMID: 34837448; PMCID: PMC9285588. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9285588/. 
14. Kokkinopoulou I, Diakoumi A, Moutsatsou P. Glucocorticoid Receptor Signaling in Diabetes. Int J Mol Sci. 2021 Oct 16;22(20):11173. doi: 10.3390/ijms222011173. PMID: 34681832; PMCID: PMC8537243. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8537243/.