Journal of Kerman University of Medical Sciences

Evaluation of the Relationship between Serum ACTH and Uric Acid Levels and Insulin Resistance in Patients with Type 2 Diabetes

Document Type : Original Article

Authors

Amjad Oraibi hasan Matrood 1
Dariyuosh Hamidi Alamdari 2
Masoud Homayouni Tabrizi 1
Vahid Pouresmaeil 3, 4

1 Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran

2 Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Biochemistry, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran

4 Innovative Medical Research Center, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran

https://doi.org/10.34172/jkmu.2884
Abstract
Background: Research indicates that high levels of uric acid (UA) are linked to insulin resistance (IR), which may elevate the risk of diabetes development. Adrenocorticotropic hormone (ACTH) regulates cortisol, a hormone essential for glucose metabolism. This study examined the relationship between ACTH, uric acid (UA) levels, and IR in diabetic patients.
Methods: This case-control study involved thirty individuals with type 2 diabetes (T2D) and 30 healthy controls (45% male and 55% female) in Iran. Demographic data were collected, and serum levels of ACTH and insulin were assessed using ELISA; serum UA levels were measured through spectrophotometry. The data were analyzed using SPSS version 24.
Results: Significant differences were observed in body mass index (BMI), fasting blood sugar (FBS), HbA1c, and IR, with higher mean values in the T2D group compared to the control group (P<0.05). UA levels were significantly elevated in all patients (P=0.004), particularly males (P=0.009), compared to controls. Moreover, increased UA levels were linked to greater disease risk (P=0.007). ACTH levels were also significantly higher in T2D individuals than in healthy individuals (P<0.001), and elevated ACTH levels correlated with an increased disease risk (P=0.002). Additionally, the relationship between ACTH and UA levels and IR in the T2D group was significant compared to the control group.
Conclusion: The findings indicate a relationship between ACTH, UA, IR, and T2D, suggesting that these factors may serve as important indicators for diagnosing the progression of the disease.

Highlights

Vahid Pouresmaeil (Google Scholar) (PubMed)

Keywords

Adrenocorticotropic hormone
Uric acid
Insulin resistance
Diabetes mellitus
Subjects
  1. Kruszynska YT. Type 2 diabetes mellitus: etiology, pathogenesis and clinical manifestations. In: Poretsky L, ed. Principles of Diabetes Mellitus. Boston, MA: Springer; 2004. p. 179-99. doi: 10.1007/978-1-4757-6260-0_10.
  2. El Ghorayeb N, Bourdeau I, Lacroix A. Role of ACTH and other hormones in the regulation of aldosterone production in primary aldosteronism. Front Endocrinol (Lausanne). 2016;7:72. doi: 10.3389/fendo.2016.00072.
  3. Ramamoorthy S, Cidlowski JA. Corticosteroids: mechanisms of action in health and disease. Rheum Dis Clin North Am. 2016;42(1):15-31. doi: 10.1016/j.rdc.2015.08.002.
  4. Ruggiero C, Lalli E. Impact of ACTH signaling on transcriptional regulation of steroidogenic genes. Front Endocrinol (Lausanne). 2016;7:24. doi: 10.3389/fendo.2016.00024.
  5. Schäcke H, Döcke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002;96(1):23-43. doi: 10.1016/s0163-7258(02)00297-8.
  6. Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017;17(4):233-47. doi: 10.1038/nri.2017.1.
  7. Haase M, Willenberg HS, Bornstein SR. Update on the corticomedullary interaction in the adrenal gland. Endocr Dev. 2011;20:28-37. doi: 10.1159/000321211.
  8. Iwata M, Oki Y, Okazawa T, Ishizawa S, Taka C, Yamazaki K, et al. A rare case of adrenocorticotropic hormone (ACTH)- independent macroadrenal hyperplasia showing ectopic production of ACTH. Intern Med. 2012;51(16):2181-7. doi: 10.2169/internalmedicine.51.7547.
  9. Vrezas I, Willenberg HS, Mansmann G, Hiroi N, Fritzen R, Bornstein SR. Ectopic adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) production in the adrenal gland: basic and clinical aspects. Microsc Res Tech. 2003;61(3):308-14. doi: 10.1002/jemt.10340.
  10. Thomas M, Keramidas M, Monchaux E, Feige JJ. Role of adrenocorticotropic hormone in the development and maintenance of the adrenal cortical vasculature. Microsc Res Tech. 2003;61(3):247-51. doi: 10.1002/jemt.10333.
  11. Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. Lancet. 2009;373(9678):1905-17. doi: 10.1016/s0140-6736(09)60326-3.
  12. Ferreira de Sá DS, Schulz A, Streit FE, Turner JD, Oitzl MS, Blumenthal TD, et al. Cortisol, but not intranasal insulin, affects the central processing of visual food cues. Psychoneuroendocrinology. 2014;50:311-20. doi: 10.1016/j. psyneuen.2014.09.006.
  13. Fink G. Stress Science: Neuroendocrinology. Oxford: Elselvier Inc; 2010.
  14. Salvador A, Suay F, González-Bono E, Serrano MA. Anticipatory cortisol, testosterone and psychological responses to judo competition in young men. Psychoneuroendocrinology. 2003;28(3):364-75. doi: 10.1016/s0306-4530(02)00028-8.
  15. Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev. 2000;21(1):55-89. doi: 10.1210/edrv.21.1.0389.
  16. Ziaja J, Cholewa K, Mazurek U, Cierpka L. [Molecular basics of aldosterone and cortisol synthesis in normal adrenals and adrenocortical adenomas]. Endokrynol Pol. 2008;59(4):330- 9. [Polish].
  17. Kamba A, Daimon M, Murakami H, Otaka H, Matsuki K, Sato E, et al. Association between higher serum cortisol levels and decreased insulin secretion in a general population. PLoS One. 2016;11(11):e0166077. doi: 10.1371/journal.pone.0166077.
  18. Morais JB, Severo JS, Beserra JB, de Oiveira AR, Cruz KJ, de Sousa Melo SR, et al. Association between cortisol, insulin resistance and zinc in obesity: a mini-review. Biol Trace Elem Res. 2019;191(2):323-30. doi: 10.1007/s12011-018-1629-y.
  19. Ortiz R, Kluwe B, Odei JB, Echouffo Tcheugui JB, Sims M, Kalyani RR, et al. The association of morning serum cortisol with glucose metabolism and diabetes: The Jackson Heart Study. Psychoneuroendocrinology. 2019;103:25-32. doi: 1016/j.psyneuen.2018.12.237.
  20. Yan YX, Xiao HB, Wang SS, Zhao J, He Y, Wang W, et al. Investigation of the relationship between chronic stress and insulin resistance in a Chinese population. J Epidemiol. 2016;26(7):355-60. doi: 10.2188/jea.JE20150183.
  21. Khaliq W, Großmann P, Neugebauer S, Kleyman A, Domizi R, Calcinaro S, et al. Lipid metabolic signatures deviate in sepsis survivors compared to non-survivors. Comput Struct Biotechnol J. 2020;18:3678-91. doi: 10.1016/j. csbj.2020.11.009.
  22. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9. doi: 10.1007/bf00280883.
  23. Aljanabi MA, Homayouni Tabrizi M, Pouresmaeil V. Correlation between cytochrome P450, 5-alpha reductase, and androgen receptor levels in patients with type 2 diabetes mellitus. Iran J Diabetes Obes. 2022;14(1):20-8. doi: 10.18502/ijdo.v14i1.8738.
  24. Gorgani-Firuzjaee S, Khodabandehloo H. Circulating levels of C1q/TNF-related protein-12 (CTRP-12) in patients with type 2 diabetes: a case-control study. J Kerman Univ Med Sci. 2020;27(3):262-9. doi: 10.22062/jkmu.2020.90645.
  25. Pouresmaeil V, Mashayekhi S, Sarafraz Yazdi M. Investigation of serum level relationship anti-glutamic acid decarboxylase antibody and inflammatory cytokines (IL1-β, IL-6) with vitamins D in type 2 diabetes. J Diabetes Metab Disord. 2022;21(1):181-7. doi: 10.1007/s40200-021-00956-3.
  26. Pouresmaeil V, Al Abudi AH, Mahimid AH, Sarafraz Yazdi M, Es-Haghi A. Evaluation of serum selenium and copper levels with inflammatory cytokines and indices of oxidative stress in type 2 diabetes. Biol Trace Elem Res. 2023;201(2):617-26. doi: 10.1007/s12011-022-03191-w.
  27. Gordon L, Ragoobirsingh D, Morrison EY, Choo-Kang E, McGrowder D, Martorell E. Lipid profile of type 2 diabetic and hypertensive patients in the Jamaican population. J Lab Physicians. 2010;2(1):25-30. doi: 10.4103/0974-2727.66709.
  28. Shahwan MJ, Jairoun AA, Farajallah A, Shanabli S. Prevalence of dyslipidemia and factors affecting lipid profile in patients with type 2 diabetes. Diabetes Metab Syndr. 2019;13(4):2387- 92. doi: 10.1016/j.dsx.2019.06.009.
  29. Bakov L, Milanov S. [Basal blood level of adrenocorticotropic hormone in diabetes mellitus patients]. Vutr Boles. 1984;23(1):69-74. [Bulgarian].
  30. Dehghan A, van Hoek M, Sijbrands EJ, Hofman A, Witteman JC. High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care. 2008;31(2):361-2. doi: 10.2337/ dc07-1276.
  31. van der Schaft N, Brahimaj A, Wen KX, Franco OH, Dehghan A. The association between serum uric acid and the incidence of prediabetes and type 2 diabetes mellitus: the Rotterdam Study. PLoS One. 2017;12(6):e0179482. doi: 10.1371/ journal.pone.0179482.
  32. Bombelli M, Quarti-Trevano F, Tadic M, Facchetti R, Cuspidi C, Mancia G, et al. Uric acid and risk of new-onset metabolic syndrome, impaired fasting glucose and diabetes mellitus in a general Italian population: data from the Pressioni Arteriose Monitorate E Loro Associazioni study. J Hypertens. 2018;36(7):1492-8. doi: 10.1097/hjh.0000000000001721.
  33. Tassone EJ, Cimellaro A, Perticone M, Hribal ML, Sciacqua A, Andreozzi F, et al. Uric acid impairs insulin signaling by promoting Enpp1 binding to insulin receptor in human umbilical vein endothelial cells. Front Endocrinol (Lausanne). 2018;9:98. doi: 10.3389/fendo.2018.00098.
  34. Yokoyama K, Yamada T, Mitani H, Yamada S, Pu S, Yamanashi T, et al. Relationship between hypothalamic-pituitary-adrenal axis dysregulation and insulin resistance in elderly patients with depression. Psychiatry Res. 2015;226(2-3):494-8. doi: 10.1016/j.psychres.2015.01.026.
  35. Oltmanns KM, Dodt B, Schultes B, Raspe HH, Schweiger U, Born J, et al. Cortisol correlates with metabolic disturbances in a population study of type 2 diabetic patients. Eur J Endocrinol. 2006;154(2):325-31. doi: 10.1530/eje.1.02074.
  36. Muscogiuri G, Sorice GP, Prioletta A, Mezza T, Cipolla C, Salomone E, et al. The size of adrenal incidentalomas correlates with insulin resistance. Is there a cause-effect relationship? Clin Endocrinol (Oxf). 2011;74(3):300-5. doi: 10.1111/j.1365-2265.2010.03928.x.
  37. Katsiki N, Papanas N, Fonseca VA, Maltezos E, Mikhailidis DP. Uric acid and diabetes: is there a link? Curr Pharm Des. 2013;19(27):4930-7. doi: 10.2174/1381612811319270016.
  38. Yoo TW, Sung KC, Shin HS, Kim BJ, Kim BS, Kang JH, et al. Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome. Circ J. 2005;69(8):928-33. doi: 10.1253/circj.69.928.
Journal of Kerman University of Medical Sciences
Volume 32
Pages 1-6

Home

Editorial Board

Guide for Authors

Submit Manuscript

Guide for Reviewers

Contact Us