Fibrinogen concentration correlates with glycemic control in patients with type 2 diabetes mellitus

Fibrinogen concentration correlates with glycemic control in patients with type 2 diabetes mellitus

Main Article Content

Pablo Aguirre-Villegas
Adriana Pedreáñez

Abstract

Cardiovascular disease is the main cause of morbidity and mortality in diabetic patients and elevated fibrinogen concentration has been described as an important risk factor. Objective: to determine the plasma concentration of fibrinogen and its association with glycated hemoglobin (HbA1c) levels in patients with DM2. Materials and methods: An observational, non-experimental, correlational, cross-sectional, cross-sectional research was conducted between November 2023 and August 2024. We selected 120 participants of both sexes diagnosed with DM2 who attended the Internal Medicine office of the Hospital Provincial General Docente Riobamba, Ecuador (90 patients with DM2 and 30 controls). Subjects with a diagnosis of DM2 were divided into three groups according to their HbA1c levels: group 1 (HbA 1c <6.5 %), group 2 (≥ 6.5% <10.0 %), and group 3 (HbA1c ≥ 10.0 %). Blood glucose levels, lipid profile, and plasma fibrinogen were evaluated. Results: Statistically significant differences were observed between subjects with DM2 and controls regarding age, BMI, serum glucose concentration, and triacylglycerides (p<0.05). Patients with DM2 showed higher mean plasma levels of fibrinogen than controls (P<0.001). A significant positive correlation was observed between fibrinogen and HbA1c (r=0.8380, P<0.0001). Conclusion: The correlation observed between fibrinogen concentration and HbA1c levels in the subjects with DM2 evaluated in this investigation, together with the increase in triacylglyceride concentration, supports the value of these markers for the early prediction of the main complications observed in diabetes, such as vascular dysfunction, the development of atherosclerosis and consequent cardiovascular damage.

References

Abdul Razak, M. K., & Sultan, A. A. (2019). The importance of measurement of plasma fibrinogen level among patients with type- 2 diabetes mellitus. Diabetes & Metabolic Syndrome, 13(2), 1151–1158. https://doi.org/10.1016/j.dsx.2019.01.049

Aguirre-Villegas, P., & Pedreañez, A. (2024). Could glycated hemoglobin be considered a marker of inflammation in patients with diabetes mellitus? International Journal of Medical and Surgical Sciences, 11(2), 1–13. https://doi.org/10.32457/ijmss.v11i2.2619

American Diabetes Association (2021). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2021. Diabetes Care, 44(Suppl 1), S15–S33. https://doi.org/10.2337/dc21-S002.

Cerit, L. (2017). Fibrinogen and Atherosclerosis. Arquivos Brasileiros de Cardiologia, 108(2), 189–190. https://doi.org/10.5935/abc.20170017

Clauss, A. (1957). Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens [Rapid physiological coagulation method in determination of fibrinogen]. Acta Haematol, 17(4), 237-46. https://doi.org/10.1159/000205234

Daugaard, N., Bladbjerg, E. M., Maat, M. P. M., & Münster, A. B. (2024). Effect of Plasma Fibrinogen Levels on the Risk of Stroke in Patients with Type 2 Diabetes: A Systematic Review. TH Open: Companion Journal to Thrombosis and Haemostasis, 8(1), e72–e80. https://doi.org/10.1055/s-0043-1777344

de Oliveira Dos Santos, A. R., de Oliveira Zanuso, B., Miola, V. F. B., Barbalho, S. M., Santos Bueno, P. C., Flato, U. A. P., Detregiachi, C. R. P., Buchaim, D. V., Buchaim, R. L., Tofano, R. J., Mendes, C. G., Tofano, V. A. C., & Dos Santos Haber, J. F. (2021). Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions. International Journal of Molecular Sciences, 22(5), 2639. https://doi.org/10.3390/ijms22052639

de Vries, J. J., Snoek, C. J. M., Rijken, D. C., & de Maat, M. P. M. (2020). Effects of Post-Translational Modifications of Fibrinogen on Clot Formation, Clot Structure, and Fibrinolysis: A Systematic Review. Arteriosclerosis, Thrombosis, and Vascular Biology, 40(3), 554–569. https://doi.org/10.1161/ATVBAHA.119.313626

Di Pino, A., & DeFronzo, R. A. (2019). Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents. Endocrine Reviews, 40(6), 1447–1467. https://doi.org/10.1210/er.2018-00141

Domingueti, C. P., Dusse, L. M., Carvalho, M.d, de Sousa, L. P., Gomes, K. B., & Fernandes, A. P. (2016). Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. Journal of Diabetes and its Complications, 30(4), 738–745. https://doi.org/10.1016/j.jdiacomp.2015.12.018

Folsom, A. R., Wu, K. K., Rosamond, W. D., Sharrett, A. R., & Chambless, L. E. (1997). Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation, 96(4), 1102–1108.

https://doi.org/10.1161/01.cir.96.4.1102

GBD 2019 Diabetes Mortality Collaborators (2022). Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019. The Lancet. Diabetes & Endocrinology, 10(3), 177–192. https://doi.org/10.1016/S2213-8587(21)00349-1.

Gifford, J. L., Higgins, T., & Sadrzadeh, S. M. H. (2019). A high-throughput test for diabetes care: An evaluation of the next generation Roche Cobas c 513 hemoglobin A1C assay. Practical Laboratory Medicine, 17, e00147. https://doi.org/10.1016/j.plabm.2019.e00147

Hamidullah, Ahmad, I., Ashraf, Ali, M., Hussain, M., & Zakirullah (2024). Correlation between plasma fibrinogen levels and microvascular complications in type 2 diabetes. JPMA. The Journal of the Pakistan Medical Association, 74(8), 1441–1448. https://doi.org/10.47391/JPMA.10403

Henning R. J. (2018). Type-2 diabetes mellitus and cardiovascular disease. Future Cardiology, 14(6), 491–509. https://doi.org/10.2217/fca-2018-0045

Kane, J. P., Pullinger, C. R., Goldfine, I. D., & Malloy, M. J. (2021). Dyslipidemia and diabetes mellitus: Role of lipoprotein species and interrelated pathways of lipid metabolism in diabetes mellitus. Current Opinion in Pharmacology, 61, 21–27. https://doi.org/10.1016/j.coph.2021.08.013

Karim, F., Akter, Q. S., Khanom, A., Haque, S., & Rashid, M. S. (2022). Estimation of Serum Fibrinogen in Males with Type 2 Diabetes. Mymensingh Medical Journal: MMJ, 31(2), 395–399. https://pubmed.ncbi.nlm.nih.gov/35383756/

Khanam, A., Alouffi, S., Alyahyawi, A. R., Husain, A., Khan, S., Alharazi, T., Akasha, R., Khan, H., Shahab, U., & Ahmad, S. (2024). Generation of autoantibodies against glycated fibrinogen: Role in diabetic nephropathy and retinopathy. Analytical Biochemistry, 685, 115393. https://doi.org/10.1016/j.ab.2023.115393

Kotbi, S., Mjabber, A., Chadli, A., El Hammiri, A., El Aziz, S., Oukkache, B., Mifdal, H., Nourichafi, N., Kamal, N., Habbal, R., Ghalim, N., Farouqi, A., & Kabine, M. (2016). Correlation between the plasma fibrinogen concentration and coronary heart disease severity in Moroccan patients with type 2 diabetes. Prospective Study. Annales d’Endocrinologie, 77(5), 606–614. https://doi.org/10.1016/j.ando.2015.02.004

Liberale, L., Badimon, L., Montecucco, F., Lüscher, T. F., Libby, P., & Camici, G. G. (2022). Inflammation, Aging, and Cardiovascular Disease: JACC Review Topic of the Week. Journal of the American College of Cardiology, 79(8), 837–847. https://doi.org/10.1016/j.jacc.2021.12.017

Litvinov, R. I., Pieters, M., de Lange-Loots, Z., & Weisel, J. W. (2021). Fibrinogen and Fibrin. Sub-cellular Biochemistry, 96, 471–501. https://doi.org/10.1007/978-3-030-58971-4_15

Lominadze, D., Dean, W. L., Tyagi, S. C., & Roberts, A. M. (2010). Mechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular disease. Acta Physiologica (Oxford, England), 198(1), 1–13. https://doi.org/10.1111/j.1748-1716.2009.02037.x

Luyendyk, J. P., Schoenecker, J. G., & Flick, M. J. (2019). The multifaceted role of fibrinogen in tissue injury and inflammation. Blood, 133(6), 511–520. https://doi.org/10.1182/blood-2018-07-818211

Mitsios, J. P., Ekinci, E. I., Mitsios, G. P., Churilov, L., & Thijs, V. (2018). Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and MetaAnalysis. Journal of the American Heart Association, 7(11), e007858. https://doi.org/10.1161/JAHA.117.007858

Pedreanez, A., Mosquera, J., Munoz, N., Robalino, J., Tene, D. (2022). Diabetes, heart damage, and angiotensin II. What is the relationship link between them? A minireview. Endocr Regul., 56(1):55-65. https://doi.org/10.2478/enr-2022-0007.

Perween, S., Abidi, M., Faizy, A. F., & Moinuddin (2019). Post-translational modifications on glycated plasma fibrinogen: A physicochemical insight. International Journal of Biological Macromolecules, 126, 1201–1212. https://doi.org/10.1016/j.ijbiomac.2019.01.018

Pieters, M., van Zyl, D. G., Rheeder, P., Jerling, J. C., Loots, duT., van der Westhuizen, F. H., Gottsche, L. T., & Weisel, J. W. (2007). Glycation of fibrinogen in uncontrolled diabetic patients and the effects of glycaemic control on fibrinogen glycation. Thrombosis Research, 120(3), 439–446. https://doi.org/10.1016/j.thromres.2006.10.016

Robinson, P. W., Jury, D. R., & Langdon, A. G. (1991). The relative clotting activity of glycated and non-glycated forms of fibrinogen. Annals of Clinical Biochemistry, 28 (Pt 6), 618–619. https://doi.org/10.1177/000456329102800613

Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022). Inflammation in obesity, diabetes, and related disorders. Immunity, 55(1), 31–55. https://doi.org/10.1016/j.immuni.2021.12.013

Saito, I., Folsom, A. R., Brancati, F. L., Duncan, B. B., Chambless, L. E., & McGovern, P. G. (2000). Nontraditional risk factors for coronary heart disease incidence among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Annals of Internal Medicine, 133(2), 81–91. https://doi.org/10.7326/0003-4819-133-2-200007180-00007

Shrestha, B., & Dunn, L. (2020). The Declaration of Helsinki on Medical Research involving Human Subjects: A Review of Seventh Revision. Journal of Nepal Health Research Council, 17(4), 548–552. https://doi.org/10.33314/jnhrc.v17i4.1042.

Singh, V. P., Bali, A., Singh, N., & Jaggi, A. S. (2014). Advanced glycation end products and diabetic complications. The Korean Journal of Physiology & Pharmacology: Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology, 18(1), 1–14. https://doi.org/10.4196/kjpp.2014.18.1.1

Sulimai, N. H., Brown, J., & Lominadze, D. (2022). Fibrinogen, Fibrinogen-like 1 and Fibrinogen-like 2 Proteins, and Their Effects. Biomedicines, 10(7), 1712. https://doi.org/10.3390/biomedicines10071712

Sulimai, N., & Lominadze, D. (2021). Fibrinogen and/or Fibrin as a Cause of Neuroinflammation. Online Journal of Neurology and Brain Disorders, 5(4), 217.

Ten Cate, H., & Meade, T. (2014). The Northwick Park Heart Study: evidence from the laboratory. Journal of Thrombosis and Haemostasis: JTH, 12(5), 587–592. https://doi.org/10.1111/jth.12545

Tene, D., Urdaneta, G., Robalino, J., & Pedreañez, A. (2021). Nitric oxide and fibrinogen in patients with subclinical hypothyroidism and their possible relation to cardiovascular damage. International Journal of Medical and Surgical Sciences, 8(4), 1–12. https://doi.org/10.32457/ijmss.v8i4.1735

Thygesen, L. C., & Ersbøll, A. K. (2014). When the entire population is the sample: strengths and limitations in register-based epidemiology. European Journal of Epidemiology, 29(8), 551–558. https://doi.org/10.1007/s10654-013-9873-0

Viigimaa, M., Sachinidis, A., Toumpourleka, M., Koutsampasopoulos, K., Alliksoo, S., & Titma, T. (2020). Macrovascular Complications of Type 2 Diabetes Mellitus. Current Vascular Pharmacology, 18(2), 110–116. https://doi.org/10.2174/1570161117666190405165151

Wan, Z., Guo, J., Pan, A., Chen, C., Liu, L., & Liu, G. (2021). Association of Serum 25-Hydroxyvitamin D Concentrations With All-Cause and Cause-Specific Mortality Among Individuals With Diabetes. Diabetes Care, 44(2), 350–357. https://doi.org/10.2337/dc20-1485

Wang, P., Yuan, D., Zhang, C., Zhu, P., Jia, S., Song, Y., Tang, X., Xu, J., Li, T., Zeng, G., Zhao, X., Yang, Y., Xu, B., Gao, R., & Yuan, J. (2022). High fibrinogen-to-albumin ratio with type 2 diabetes mellitus is associated with poor prognosis in patients undergoing percutaneous coronary intervention: 5-year findings from a large cohort. Cardiovascular Diabetology, 21(1), 46. https://doi.org/10.1186/s12933-022-01477-w

Wolberg A. S. (2023). Fibrinogen and fibrin: synthesis, structure, and function in health and disease. Journal of Thrombosis and Haemostasis: JTH, 21(11), 3005–3015. https://doi.org/10.1016/j.jtha.2023.08.014

Wong, N. D., & Sattar, N. (2023). Cardiovascular risk in diabetes mellitus: epidemiology, assessment and prevention. Nature Reviews. Cardiology, 20(10), 685–695. https://doi.org/10.1038/s41569-023-00877-z

Ząbczyk, M., Ariëns, R. A. S., & Undas, A. (2023). Fibrin clot properties in cardiovascular disease: from basic mechanisms to clinical practice. Cardiovascular Research, 119(1), 94–111. https://doi.org/10.1093/cvr/cvad017