Assessment of endothelial dysfunction and inflammation in type 2 diabetic postmenopausal women
Article Sidebar
Main Article Content
Abstract
Objective: Vascular complications in type 2 diabetes mellitus are an important cause of morbidity and mortality. Also, endothelial dysfunction arises with vascular ageing during the postmenopausal period. Our objective in this study was to evaluate inflammation and endothelial function parameters and their possible diagnostic roles in type 2 diabetic postmenopausal patients.
Material and Methods: The study was conducted on four groups, including type 2 diabetic premenopausal (n:20), non-diabetic premenopausal (n:20), type 2 diabetic postmenopausal (n:20), and non-diabetic postmenopausal subjects (n:20). Serum endothelin-1 (ET-1), endothelial nitric oxide synthetase (eNOS), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and chitinase-3-like protein 1 (YKL-40) levels were determined as inflammatory and endothelial function markers using ELISA kits.
Results: Serum ET-1, IL-6, and YKL-40 levels were higher in the type 2 diabetic postmenopausal group compared to the non-diabetic premenopausal group (p<0.01, p<0.05, and p<0.01, respectively). ET-1, IL-6, and YKL-40 levels were higher in the type 2 diabetic postmenopausal group compared to the non-diabetic postmenopausal group (p<0.001, p<0.05, and p<0.01 respectively). ROC analysis revealed serum ET-1 (AUC 0.933, sensitivity 87.5%, specificity 85.7%), IL-6 (AUC 0.812, sensitivity 56.3%, specificity 92.8%), and YKL-40 (AUC 0.880, sensitivity 81.2%, specificity 92.8%), as good diagnostic parameters, especially in the type 2 diabetic premenopausal vs. non-diabetic premenopausal cohorts.
Conclusion: Serum ET-1, IL-6, and YKL-40 levels were at the highest levels in the 2 diabetic postmenopausal group, and the increase in these markers was remarkable in diabetes compared with menopausal periods. Also, ET-1, IL-6, and YKL-40 were good diagnostic parameters for detecting endothelial function and inflammation in type 2 diabetic postmenopausal and non-diabetic premenopausal cohorts.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Accepted 2023-01-23
Published 2023-01-24
References
Özşahin AK, Asma S, Aksoyek A, Gereklioğlu Ç, Korur A. Obesity-Insulin Resistance and Diabetes. Turkish Journal of Family Medicine and Primary Care. 2015;9(2):36-9.
Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics. 2005;115(4):e500-e3.
Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Jama. 2001;286(3):327-34.
Cioffi M, Esposito K, Vietri MT, Gazzerro P, D'Auria A, Ardovino I, et al. Cytokine pattern in postmenopause. Maturitas. 2002;41(3):187-92.
July M, Faiz S, Yaqub A, Santhanam P, Douglas J, Stanek R, et al. Role of adipokines and inflammatory markers in postmenopausal hypertension. Minerva endocrinologica. 2017;43(2):101-8.
Kaur R, Kaur M, Singh J. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovascular diabetology. 2018;17(1):1-17.
Takahashi K, Ghatei M, Lam H-C, O'halloran D, Bloom S. Elevated plasma endothelin in patients with diabetes mellitus. Diabetologia. 1990;33(5):306-10.
Ferri C, Pittoni V, Piccoli A, Laurenti O, Cassone MR, Bellini C, et al. Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo. The Journal of Clinical Endocrinology & Metabolism. 1995;80(3):829-35.
Takeda Y, Miyamori I, Yoneda T, Takeda R. Production of endothelin-1 from the mesenteric arteries of streptozotocin-induced diabetic rats. Life sciences. 1991;48(26):2553-6.
Fernandez-Cruz A, Martin P, Fernandez L, Sanchez J, Ibarra J, Moya J, et al. Plasma endothelin is increased in young essential hypertensives but not in elderly essential or diabetic hypertensives. Journal of Hypertension. 1993;11:S146-S7.
Wang M, Sui J, Wang S, Wang X. Correlations of carotid intima-media thickness with endothelial function and atherosclerosis degree in patients with type 2 diabetes mellitus. Clinical hemorheology and microcirculation. 2019;72(4):431-9.
Wilcox JG, Hatch IE, Gentzschein E, Stanczyk FZ, Lobo RA. Endothelin levels decrease after oral and nonoral estrogen in postmenopausal women with increased cardiovascular risk factors. Fertility and sterility. 1997;67(2):273-7.
Vural P, Akgul C, Canbaz M. Effects of hormone replacement therapy on plasma pro-inflammatory and anti-inflammatory cytokines and some bone turnover markers in postmenopausal women. Pharmacological research. 2006;54(4):298-302.
Khatun MT, Jesmin S, Rahman A, Ahsan HA, Islam M, Akter S, et al. Assessment of circulatory endothelin-1 level among pre-and post-menopausal rural women in Bangladesh: Result from a population-based study. Life Sciences. 2013;25(93):e68.
Fernández-Mejía C. Oxidative stress in diabetes mellitus and the role of vitamins with antioxidant actions. Oxidative stress and chronic degenerative diseases-a role for antioxidants. 2013;209.
Endres M, Laufs U, Liao JK, Moskowitz MA. Targeting eNOS for stroke protection. Trends in neurosciences. 2004;27(5):283-9.
Adela R, Nethi SK, Bagul PK, Barui AK, Mattapally S, Kuncha M, et al. Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients. PloS one. 2015;10(4):e0125270.
Yenisey Ç, Öge A, Serter M, Bolaman Z. Serum interleukin-1 (IL-1beta) and nitric oxide (NO) levels in diabetes mellitus. Medical Journal of Ege University. 2001;11(1):1-5.
Ghosh A, Sherpa ML, Bhutia Y, Pal R, Dahal S. Serum nitric oxide status in patients with type 2 diabetes mellitus in Sikkim. International Journal of Applied and Basic Medical Research. 2011;1(1):31.
Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP. The pathophysiologic roles of interleukin-6 in human disease. Annals of internal medicine. 1998;128(2):127-37.
Makino N, Maeda T, Sugano M, Satoh S, Watanabe R, Abe N. High serum TNF-α level in Type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells. Journal of Diabetes and its Complications. 2005;19(6):347-55.
Taleb-Belkadi O, Chaib H, Zemour L, Fatah A, Chafi B, Mekki K. Lipid profile, inflammation, and oxidative status in peri-and postmenopausal women. Gynecological Endocrinology. 2016;32(12):982-5.
Blank SE, Johnson EC, Weeks DK, Wysham CH. Circulating dendritic cell number and intracellular TNF-α production in women with type 2 diabetes. Acta diabetologica. 2012;49(1):25-32.
Doganay S, Evereklioglu C, Er H, Türköz Y, Sevinc A, Mehmet N, et al. Comparison of serum NO, TNF-α, IL-1β, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus. Eye. 2002;16(2):163-70.
Kim OY, Chae JS, Paik JK, Seo HS, Jang Y, Cavaillon J-M, et al. Effects of aging and menopause on serum interleukin-6 levels and peripheral blood mononuclear cell cytokine production in healthy nonobese women. Age. 2012;34(2):415-25.
Kamada M, Irahara M, Maegawa M, Ohmoto Y, Takeji T, Yasui T, et al. Postmenopausal changes in serum cytokine levels and hormone replacement therapy. American journal of obstetrics and gynecology. 2001;184(3):309-14.
Mascarenhas-Melo F, Marado D, Palavra F, Sereno J, Coelho Á, Pinto R, et al. Diabetes abrogates sex differences and aggravates cardiometabolic risk in postmenopausal women. Cardiovascular diabetology. 2013;12(1):1-14.
Mascarenhas-Melo F, Sereno J, Teixeira-Lemos E, Ribeiro S, Rocha-Pereira P, Cotterill E, et al. Markers of increased cardiovascular risk in postmenopausal women: focus on oxidized-LDL and HDL subpopulations. Disease Markers. 2013;35.
Rathcke CN, Vestergaard H. YKL-40-an emerging biomarker in cardiovascular disease and diabetes. Cardiovascular diabetology. 2009;8(1):1-7.
Nielsen AR, Erikstrup C, Johansen JS, Fischer CP, Plomgaard P, Krogh-Madsen R, et al. Plasma YKL-40: a BMI-independent marker of type 2 diabetes. Diabetes. 2008;57(11):3078-82.
Kaya M, Kaya D, Idiman E, Kocak N, Ozturk T, Ayhan Z, et al. A novel biomarker in diabetic macular edema with serous retinal detachment: serum chitinase-3-like protein 1. Ophthalmologica. 2019;241(2):90-7.
Kumari RD, Babu FM, Mahendran BK. Human cartilage glycoprotein 39 (YKL-40): a View in type 2 diabetes mellitus. International Journal of Pharmaceutical Sciences and Research. 2015;6(11):4852.