Glycated hemoglobin: mechanisms of formation and clinical significance (literature review and own researches)
Keywords:glycated hemoglobin, diabetes mellitus, coronary artery disease, cardiovascular risk
Although the level of glycated hemoglobin (HbA1c) indicates the body content of the advanced glycation end products, its value is underestimated in clinical practice. In order to discuss the diagnostic and prognostic value of HbA1c, we conducted a comprehensive literature review and analyzed the results of own investigation that included clinical examination and laboratory testing of 116 patients with coronary artery disease, with a detailed analysis of carbohydrate metabolism and subsequent follow-up period of up to 40 months. It was found that HbA1c level tends to represent the content of advanced glycation end products, which stimulate free radical production and oxidative modification of multiple proteins and lipids, reduce cellular transport, activate pro-inflammatory cytokines and chemokines, cause immune responses and mutations, increase the activity of adhesion molecules, and cause malfunction of receptors. Nowadays, the role of advanced glycation end products is discussed in the pathophysiology of different diseases, such as arterial hypertension, diabetic vascular complications, nephropathy, atherosclerosis, Alzheimer’s disease, dementia, cataract, premature aging, loss of muscle mass, poor wound healing, malignant tumors, etc. According to our data, HbA1c not only indicates poor metabolic control within the preceding 3 months, but also is a sensitive marker of vascular diabetic complications, atherogenic dyslipidemia, insulin resistance, systemic inflammation, coronary events, and the risk of transformation to diabetes mellitus during the next 3 years. Besides, HbA1c is an effective tool for differentiation of stress hyperglycemia, which frequently occurs in patients with acute cardiovascular events, and chronic hyperglycemia caused by overt or latent glucose dysregulation. Blood HbA1c levels should be monitored not only in diabetic patients but also in elder people, smokers, patients with atherosclerotic arterial diseases, and Helicobacter pylori infection.
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020 Jan 7;41(2):255-323. doi: 10.1093/eurheartj/ehz486.
Radchenko OM. Glycosylated haemoglobin - metabolic marker of impairment. Problems of Endocrine Pathology. 2008;(1):104-107. (in Ukrainian).
Radchenko OM, Korolyuk OYa. Impaired glucose homeostasis in patients with coronary artery disease: changing views for 40 years. Mìžnarodnij endokrinologìčnij žurnal. 2015;(66):95-98. doi: 10.22141/2224-07220.127.116.115.75448. (in Ukrainian).
Korolyuk OYa, Radchenko OM, Horbach LО, Horbach МО. Pathogenetic mechanisms of glucose-insulin regulation in patients with coronary artery disease and concomitant disorders of carbohydrate metabolism. Medical Hydrology and Rehabilitation. 2010;(1):76-85. (in Ukrainian).
Office of Medical Products and Tobacco; Center for Devices and Radiological Health. Review criteria for assessment of glycohemoglobin (glycated or glycosylated) hemoglobin in vitro diagnostic devices. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/review-criteria-assessment-glycohemoglobin-glycated-or-glycosylated-hemoglobin-vitro-diagnostic. Accessed: March 22, 2018.
Alzahrani SH, Baig M, Aashi MM, Al-Shaibi FK, Alqarni DA, Bakhamees WH. Association between glycated hemoglobin (HbA1c) and the lipid profile in patients with type 2 diabetes mellitus at a tertiary care hospital: a retrospective study. Diabetes Metab Syndr Obes. 2019;12:1639-1644. doi:10.2147/DMSO.S222271.
Van Putte L, De Schrijver S, Moortgat P. The effects of advanced glycation end products (AGEs) on dermal wound healing and scar formation: a systematic review. Scars Burn Heal. 2016;2:2059513116676828. doi: 10.1177/2059513116676828.
Bruno CM, Meli S, Marcinno M, Ierna D, Sciacca C, Neri S. Plasma endothelin-1 levels and albumin excretion rate in normotensive, microalbuminuric type 2 diabetic patients. J Biol Regul Homeost Agents. 2002;16(2):114-117.
Bhutto AR, Abbasi A, Abro AH. Correlation of Hemoglobin A1c with Red Cell Width Distribution and Other Parameters of Red Blood Cells in Type II Diabetes Mellitus. Cureus. 2019;11(8):e5533. doi: 10.7759/cureus.5533.
Al-Kindi SG, Refaat M, Jayyousi A, Asaad N, Al Suwaidi J, Abi Khalil C. Red cell distribution width is associated with all-cause and cardiovascular mortality in patients with diabetes. Biomed Res Int. 2017;2017:5843702. doi:10.1155/2017/5843702.
Xanthopoulos A, Giamouzis G, Melidonis A, et al. Red blood cell distribution width as a prognostic marker in patients with heart failure and diabetes mellitus. Cardiovasc Diabetol. 2017;16(1):81. doi: 10.1186/s12933-017-0563-1.
Berlanga-Acosta J, Schultz GS, López-Mola E, Guillen-Nieto G, García-Siverio M, Herrera-Martínez L. Glucose toxic effects on granulation tissue productive cells: the diabetics' impaired healing. Biomed Res Int. 2013;2013:256043. doi: 10.1155/2013/256043.
Morey M, O'Gaora P, Pandit A, Hélary C. Hyperglycemia acts in synergy with hypoxia to maintain the pro-inflammatory phenotype of macrophages. PLoS One. 2019;14(8):e0220577. doi: 10.1371/journal.pone.0220577.
Bucala R, Makita Z, Koschinsky T, Cerami A, Vlassara H. Lipid advanced glycosylation: pathway for lipid oxidation in vivo. Proc Natl Acad Sci U S A. 1993;90(14):6434-6438. doi: 10.1073/pnas.90.14.6434.
Kanaya AM, Barrett-Connor E, Gildengorin G, Yaffe K. Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med. 2004;164(12):1327-1333. doi: 10.1001/archinte.164.12.1327.
Korolyuk OYa, Radchenko OM, Horbach LО, Horbach МО. Diagnostic approach to patients with ischemic heart disease and newly detected hyperglycemia. Circulation and haemostasis. 2011;(3-4):23-28. (in Ukrainian).
Radchenko OM, Korolyuk OYa. Pecularities of ischemic heart disease course and treatment in patients with glucose metabolism impairment and diabetes mellitus. Mìžnarodnij endokrinologìčnij žurnal. 2015;(70):11-15. doi: 10.22141/2224-0718.104.22.1685.72632. (in Ukrainian).
Murray AL, Jimenez-Navarrete MF. Calidad del control glicemico segun la hemoglobina glicosidada vs la glicemia en ayunas; analisis en una poblacion urbana y otra rural de diabeticos costarricenses. AMC. 2004 Sept;46(3):139-144 (in Spanish).
Itoh M, Kazikawa H, Itoh Y, et al. 2704 The relationship between glycemic control and plasma VEGF and ET-1 concentration in diabetic patients. In: Abstracts of the 18th International Diabetes Federation Congress. 2003, August 24-29; Paris, France. Diabetes Metab. 2003;29(2 Spec):4S7-4S464.
Angulo J, Sanchez-Ferrer CF, Peiro C, Marin J, Rodríguez-Mañas L. Impairment of endothelium-dependent relaxation by increasing percentages of glycosylated human hemoglobin: possible mechanisms involved. Hypertension. 1996;28(4):583-592. doi: 10.1161/01.HYP.28.4.583.
James PE, Lang D, Tufnell-Barret T, Milsom AB, Frenneaux MP. Vasorelaxation by red blood cells and impairment in diabetes: reduced nitric oxide and oxygen delivery by glycated hemoglobin. Circ Res. 2004;94(7):976-983. doi: 10.1161/01.RES.0000122044.21787.01.
Ugalde-Canitrot A, Bajo-Martinez A, Bernal E. et al. 2703 Evaluation of endothelial function and extracellular matrix turnover in type 2 diabetic patients with elevated ambulatory blood pressure. In: Abstracts of the 18th International Diabetes Federation Congress. 2003, August 24-29; Paris, France. Diabetes Metab. 2003;29(2 Spec):4S7-4S464.
Strilchuk LM. Calculated parameters of the lipidogram: modern scientific views and correlations with laboratory and instrumental indexes. AML. 2017;23(3):72-78. doi: 10.25040/aml2017.03.072. (in Ukrainian).
Chen J, Xing Y, Zhao L, Ma H. The Association between Helicobacter pylori Infection and Glycated Hemoglobin A in Diabetes: A Meta-Analysis. J Diabetes Res. 2019 Sep;2019:3705264. doi: 10.1155/2019/3705264.
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