Effect of poor glycaemic control on plasma levels and activity of protein C, protein S, and antithrombin III in type 2 diabetes mellitus

Autoři: Otchere Addai-Mensah aff001;  Max Efui Annani-Akollor aff002;  Frederick Obeng Nsafoah aff001;  Linda Ahenkorah Fondjo aff002;  Eddie-Williams Owiredu aff002;  Kwabena Owusu Danquah aff001;  Richard Vikpebah Duneeh aff003;  Francis Agyei Amponsah aff004
Působiště autorů: Department of Medical Diagnostics, Faculty of Allied Health Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana aff001;  Department of Molecular Medicine, School of Medical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana aff002;  Department of Haematology, Komfo Anokye Teaching Hospital, Kumasi, Ghana aff003;  St. John of God Hospital, Duayaw Nkwanta, Sunyani, Ghana aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223171



Type 2 diabetes mellitus (T2DM) patients are predisposed to several diabetes-related complications. Dysregulation of the haemostatic mechanisms have been implicated. There are however no current studies assessing the levels and activity of protein C (PC), protein S (PS), and antithrombin III (AT III), which are essential in haemostatic regulation, in a single cohort of T2DM patients. This study evaluated the effect of poorly-managed T2DM on the levels and activity of PC, PS, and AT III.


This cross-sectional study was conducted at the Diabetes Clinic, Cocoa Clinic in Kumasi, Ghana. A total of 242 T2DM patients, comprising 152 patients with poorly-managed diabetes and 90 well-managed diabetes patients, were recruited for the study. Fasting blood glucose, liver function tests and lipid profile were performed for each respondent. Glycated haemoglobin (HbA1c) was estimated by turbidimetric inhibition immunoassay. The levels and activity of PC, PS and AT III were measured by solid phase sandwich ELISA method.


There was a negative correlation between HbA1c and the levels and activity of PC, PS and AT III. The levels and activity of PC [(5.78 vs 4.64 μg/ml, p<0.0001) and (42.22 vs 36.21 U/ml, p = 0.01) respectively], PS [(22.55 vs 20.29 μg/ml, p = 0.010) and (235.94 vs 211.67 U/ml, p<0.0001) respectively] and AT III [(16.28 vs 14.41μg/ml, p<0.0001) and (176.01 vs 160.09 U/ml, p = 0.03) respectively] were significantly increased in patients with well-managed T2DM compared to the poorly-managed diabetes patients. Likewise, the levels and activity of PC, PS, and AT III was higher among T2DM patients using statins than patients who were statin-naïve. Among patients with well-managed T2DM, those who were on statins had significantly higher levels and activities of PC, PS, and AT III compared to well-managed T2DM patients not on statins. However, there no statistically significant differences between the level and activity of PC, PS, and AT III among poorly-managed T2DM patients with respect to statin status.


Poorly-managed type 2 diabetes mellitus is associated with reduced levels and activity of PC, PS and AT III compared to well-managed T2DM. Though use of statins may improve the levels and activity of the PC, PS and AT III in T2DM, their effect is limited in the presence of poorly-controlled T2DM. Proper management of diabetes is essential to reduce the likelihood of thrombotic events among T2DM patients.

Klíčová slova:

Blood plasma – Blood pressure – Blood sugar – Cholesterol – Statins


1. Fondjo LA, Sakyi SA, Owiredu WKBA, Laing EF, Owiredu EW, Awusi EK et al. Evaluating Vitamin D Status in Pre- and Postmenopausal Type 2 Diabetics and Its Association with Glucose Homeostasis. BioMed Research International. 2018;2018:12.

2. Kaiser A, Zhang N, Der Pluijm W. Global Prevalence of Type 2 Diabetes over the Next Ten Years (2018–2028). Diabetes. 2018;67:202-LB.

3. Fondjo LA, Owiredu WKBA, Sakyi SA, Laing EF, Adotey-Kwofie MA, Antoh EO et al. Vitamin D status and its association with Insulin resistance among type 2 diabetics:A case-control study in Ghana. PloS one. 2017;12(4).

4. Nazimek-Siewniak B, Moczulski D, Grzeszczak W. Risk of macrovascular and microvascular complications in Type 2 diabetes: results of longitudinal study design. J Diabetes Complications. 2002;16:271–6. 12126785

5. Yamada T, Sato A, Nishimori T, Mitsuhashi T, Terao A, Sagai H et al. Importance of hypercoagulability over hyperglycemia for vascular complication in type 2 diabetes. Diabetes research and clinical practice. 2000;49:23–31. doi: 10.1016/s0168-8227(00)00134-0 10808060

6. Carr M. Diabetes mellitus: a hypercoagulable state. J Diabetes Complications. 2001;15:44–54. 11259926

7. Sowers J, Epstein M, Frohlich E. Diabetes, hypertension, and cardiovascular disease: an update. Hypertension. 2001;37:1053–9. doi: 10.1161/01.hyp.37.4.1053 11304502

8. Aslan B, Eren N, Ciğerli Ş, Müldür F, Yücel N. Evaluation of Plasma Protein C Antigen, Protein C Activity and Thrombomodulin Levels in Type 2 Diabetic Patients. Turkish Journal of Medical Sciences. 2005;35:305–10.

9. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114(6):597–605. doi: 10.1161/CIRCULATIONAHA.106.621854 16894049

10. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovascular research. 2004;63(4):582–92. doi: 10.1016/j.cardiores.2004.05.001 15306213

11. Goh S-Y, Cooper ME. The role of advanced glycation end products in progression and complications of diabetes. The Journal of Clinical Endocrinology & Metabolism. 2008;93(4):1143–52.

12. Tripodi A, Mannucci P. Laboratory investigation of thrombophilia. Clinical chemistry. 2001;47:1597–606. 11514392

13. Kim HK, Kim JE, Park SH, Kim YI, Nam-Goong IS, Kim ES. High coagulation factor levels and low protein C levels contribute to enhanced thrombin generation in patients with diabetes who do not have macrovascular complications. Journal of Diabetes and its Complications. 2014;28(3):365–9. doi: 10.1016/j.jdiacomp.2014.01.006 24560421

14. Fattah MA, Shaheen MH, Mahfouz MH. Disturbances of haemostasis in diabetes mellitus. Disease markers. 2004;19(6):251–8.

15. Jax TW, Peters AJ, Plehn G, Schoebel F-C. Hemostatic risk factors in patients with coronary artery disease and type 2 diabetes-a two year follow-up of 243 patients. Cardiovascular diabetology. 2009;8(1):48.

16. Sommeijer D, Hansen H, Van Oerle R, Hamulyak K, Van Zanten A, Meesters E et al. Soluble tissue factor is a candidate marker for progression of microvascular disease in patients with type 2 diabetes. Journal of thrombosis and haemostasis. 2006;4(3):574–80. doi: 10.1111/j.1538-7836.2005.01763.x 16371118

17. Verkleij CJ, Bruijn REd, Meesters EW, Gerdes VE, Meijers JC, Marx PF. The hemostatic system in patients with type 2 diabetes with and without cardiovascular disease. Clinical and applied thrombosis/hemostasis. 2011;17(6):E57–E63. doi: 10.1177/1076029610384112 21078616

18. Erem C, Hacıhasanoğlu A, Çelik Ş, Ovalı E, Ersöz H, Ukinç K et al. Coagulation and fibrinolysis parameters in type 2 diabetic patients with and without diabetic vascular complications. Medical principles and practice. 2005;14:22–30. doi: 10.1159/000081919 15608477

19. Hernández-Espinosa D, Ordóñez A, Miñano A, Martínez-Martínez I, Vicente V, Corral J. Hyperglycaemia impairs antithrombin secretion: possible contribution to the thrombotic risk of diabetes. Thrombosis research. 2009;124:483–9. doi: 10.1016/j.thromres.2009.05.020 19573895

20. Service GS, Ghana, Research NMIfM, Legon GaOm, Calverton, Maryland et al. Ghana demographic health Survey2003.

21. Owusu-Ansah A, Panyin AB, Obirikorang C, Agyare C, Acheampong E, Kwofie S et al. Metabolic Syndrome among Schizophrenic Patients: A Comparative Cross-Sectional Study in the Middle Belt of Ghana. Schizophrenia Research and Treatment. 2018;2018.

22. Gatimu S, Milimo B, San Sebastian M. Prevalence and determinants of diabetes among older adults in Ghana. BMC public health. 2016;16.

23. Amoah A, Owusu S, Adjei S. Diabetes in Ghana: a community based prevalence study in Greater Accra. Diabetes Res Clin Pract. 2002;56:197–205. doi: 10.1016/s0168-8227(01)00374-6 11947967

24. Danquah I, Bedu-addo G, Terpe K, Micah F, Amoako YA, Awuku YA et al. Diabetes mellitus type 2 in urban Ghana: characteristics and associated factors. BMC Public Health. 2012;12(1):210.

25. Owiredu E-W, Dontoh E, Essuman SE, Bazanfara BB. Demographic and Lifestyle Predictors of Prehypertension: A Cross-Sectional Study among Apparently Healthy Adults in Kumasi, Ghana. BioMed Research International. 2019;2019.

26. Yoon SS, Gu Q, Nwankwo T, Wright JD, Hong Y, Burt V. Trends in blood pressure among adults with hypertension: United States, 2003 to 2012. Hypertension. 2015;65(1):54–61. doi: 10.1161/HYPERTENSIONAHA.114.04012 25399687

27. Fleming JK. Evaluation of HbA1c on the Roche COBAS Integra 800 closed tube system. Clinical biochemistry. 2007;40(11):822–7. doi: 10.1016/j.clinbiochem.2007.03.017 17555737

28. Annani-Akollor ME, Laing EF, Osei H, Mensah E, Owiredu E-W, Afranie BO et al. Prevalence of metabolic syndrome and the comparison of fasting plasma glucose and HbA1c as the glycemic criterion for MetS definition in non-diabetic population in Ghana. Diabetology & Metabolic Syndrome. 2019;11(1):26.

29. Addai-Mensah O, Gyamfi D, Duneeh R, Danquah K, Annani-Akollor M, Boateng L et al. Determination of Haematological Reference Ranges in Healthy Adults in Three Regions in Ghana. BioMed Research International. 2019;2019.

30. Ji L, Su Q, Feng B, Shan Z, Hu R, Xing X et al. Glycemic control and self-monitoring of blood glucose in Chinese patients with type 2 diabetes on insulin: baseline results from the COMPASS study. Diabetes research and clinical practice. 2016;112:82–7. doi: 10.1016/j.diabres.2015.08.005 26775249

31. Li X, Xu X, Liu J, Yang J, Fang L, Miao L et al. HbA1c and survival in maintenance hemodialysis patients with diabetes in Han Chinese population. International urology and nephrology. 2014;46(11):2207–14. doi: 10.1007/s11255-014-0764-4 24966096

32. Qaseem A, Wilt TJ, Kansagara D, Horwitch C, Barry MJ, Forciea MA. Hemoglobin A1c targets for glycemic control with pharmacologic therapy for nonpregnant adults with type 2 diabetes mellitus: a guidance statement update from the American College of Physicians. Annals of internal medicine. 2018;168(8):569–76. doi: 10.7326/M17-0939 29507945

33. Annani-Akollor ME, Addai-Mensah O, Fondjo LA, Sallah L, Owiredu E-W, Acheampong E et al. Predominant Complications of Type 2 Diabetes in Kumasi: A 4-Year Retrospective Cross-Sectional Study at a Teaching Hospital in Ghana. Medicina. 2019;55. doi: 10.3390/medicina55050125 31075814

34. Onbaşı K, Efe B, Akalın A, Kebapçı N, Erenoğlu E. Diabetes mellitus and the natural anticoagulants. Turkish Journal of Endocrinology and Metabolism. 1999;2:53–63.

35. Thisiadou K, Karamouzis I, Arampatzi S, Lazaridou D, editors. Coagulation inhibitors in type 2 diabetes mellitus. 12th European Congress of Endocrinology; 2010: BioScientifica.

36. Raj D, Choudhury D, Welbourne T, Levi M. Advanced glycation end products: a Nephrologist’s perspective. American Journal of Kidney Diseases. 2000;35:365–80. doi: 10.1016/s0272-6386(00)70189-2 10692262

37. Kim H, Kim J, Park S, Kim Y, Naam-Goong I, Kim E. High coagulation factor levels and low protein C levels contribute to enhanced thrombin generation in patients with diabetes who do not have macrovascular complications. Journal of Diabetes And Its Complications. 2014;28:365–9. doi: 10.1016/j.jdiacomp.2014.01.006 24560421

38. Soares A, Sousa M, Fernandes A, Carvalho M. Hemostatic changes in patients with type 2 diabetes mellitus. Revista Brasileira de Hematologia e Hemoterapia. 2010;32:482–8.

39. Undas A, Brummel-Ziedins K, Mann K. Statins and blood coagulation. Arterioscler Thromb Vasc Biol. 2005;25:287–94. doi: 10.1161/01.ATV.0000151647.14923.ec 15569822

40. Aktaş Ş, Uçak S, Kurt F, Taşdemir M, Kutlu O, Eker P. Evaluation of protein C and protein S levels in patients with diabetes mellitus receiving therapy with statins and ACE inhibitors or angiotensin II receptor blockers. Diabetes research and clinical practice. 2018;135:88–92. doi: 10.1016/j.diabres.2017.11.004 29155121

Článek vyšel v časopise


2019 Číslo 9

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Zvyšte si kvalifikaci online z pohodlí domova

Antiseptika a prevence ve stomatologii
nový kurz
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Citikolin v neuroprotekci a neuroregeneraci: od výzkumu do klinické praxe nejen očních lékařů
Autoři: MUDr. Petr Výborný, CSc., FEBO

Zánětlivá bolest zad a axiální spondylartritida – Diagnostika a referenční strategie
Autoři: MUDr. Monika Gregová, Ph.D., MUDr. Kristýna Bubová

Diagnostika a léčba deprese pro ambulantní praxi
Autoři: MUDr. Jan Hubeňák, Ph.D

Význam nemocničního alert systému v době SARS-CoV-2
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D., prim. MUDr. Václava Adámková

Všechny kurzy
Kurzy Doporučená témata