International Journal of Pharma and Bio Sciences
    ISSN 0975-6299

Int J Pharm Bio Sci Volume 15 Issue 3, July-September, Pages:10-15

Evaluation of Coagulation Profile in T2DM Patients On Metformin: A Cross-Sectional Study

Vyshnavi Shanbagh, Narendranath S, Renuka B G, Dr. Sushma H K, Vijayalakshmi Malya and Shashikala G H

The incidence of cardiovascular disease due to thrombosis is 2-4 folds greater in diabetic patients with diabetes. Prothrombin time, activated partial thromboplastin time, and platelet count are hematological indices that give an insight into the coagulation status. Decreased/deficient vitamin B12 levels are now considered a common side effect in patients on metformin treatment, especially in those receiving a higher dose or longer treatment duration, which leads to an increase in homocysteine and hyperhomocysteinemia levels are linked to thrombosis. Hence, this study aimed to assess the coagulation status of patients with type 2 diabetes on a higher dose of metformin and to compare it with that of patients with type 2 diabetes mellitus receiving a lower dose of metformin. A comparative cross-sectional study was conducted at Bapuji Hospital and Chigateri Government Hospital, attached to the JJM Medical College, Davangere. A total of 50 treated type II diabetes treated with metformin (>1500 mg/day and <1500 mg/day) were included. After obtaining informed consent, a structured questionnaire was used to collect the sociodemographic data. Following the interview, 4 ml of blood was collected to determine the two groups' PT(Prothrombin time), aPTT(activated partial thromboplastin time,) and INR (international normalized ratio )values. The data were analyzed using SPSS version 20. An unpaired "t" test was used to compare the mean PT, aPTT, and INR counts among the groups. A P significance was set at P < 0.05. The mean aPTT and PT of T2DM patients (>1500mf/day metformin) had a mean aPTT, PT, and INR of 26.97 ± 5.25, 11.93 ± 1.06, and 1.024 ± 0.1 and T2DM (< 1500 mg/day metformin) had mean aPTT, PT, and INR of 31.76 ± 6.25, 13.08 ± 1.36, and 1.148 ± 0.12, respectively. The odds ratio was 5.4, which revealed that the aPTT values were 5.4 times more in controls than in cases. There was a significant shortening of aPTT, PT, and INR in cases compared with controls (P < 0.05). Shortening of aPTT, PT, and INR in T2DM may be a useful marker. Therefore, monitoring aPTT and PT in T2DM patients receiving a higher metformin dose is important to prevent hypercoagulation.

Keywords: Type 2 diabetes mellitus, Metformin, Activated partial thromboplastin time, Platelet count, International normalized ratio
Full HTML:
  1. American Diabetes Association Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(S1):S81–S90. doi: 10.2337/dc14-S081.
  2. Pradeepa R, Mohan V. Epidemiology of type 2 diabetes in India. Indian journal of ophthalmology. 2021;69(11):2932. doi: 10.4103/ijo.IJO_1627_21.
  3. Carr ME. Diabetes mellitus: a hypercoagulable state. Journal of Diabetes and its Complications. 2001;15(1):44-54. doi: 10.1016/s1056-8727(00)00132-x.
  4. Pretorius E, Oberholzer HM, van der Spuy WJ, Swanepoel AC, Soma P. Qualitative scanning electron microscopy analysis of fibrin networks and platelet abnormalities in diabetes. Blood coagulation & fibrinolysis. 2011;22(6):463-7. doi: 10.1097/MBC.0b013e3283468a0d.
  5. Mushtak A, Khan FY, AlDehwe B, Al-Ani AA. Three different presentation of same pathophysiology. Acta Informatica Medica. 2012;20(3):190. doi: 10.5455/aim.2012.20.190-191.
  6. Venkatesh P, Shaikh N, Malmstrom MF, Kumar VR, Nour B. Portal, superior mesenteric and splenic vein thrombosis secondary to hyperhomocysteinemia with pernicious anemia: a case report. Journal of Medical Case Reports. 2014;8:1-5. doi: 10.1186/1752-1947-8-286.
  7. Lin HY, Chung CY, Chang CS, Wang ML, Lin JS, Shen MC. Hyperhomocysteinemia, deep vein thrombosis and vitamin B12 deficiency in a metformin-treated diabetic patient. Journal of the Formosan Medical Association. 2007;106(9):774-8. doi: 10.1016/S0929-6646(08)60039-X.
  8. Rena G, Lang CC. Repurposing metformin for cardiovascular disease. Circulation. 2018;137(5):422-4. doi: 10.1161/CIRCULATIONAHA.117.031735.
  9. Abdulrahaman Y, Dallatu MK. Evaluation of prothrombin time and activated partial thromboplastin in patients with diabetes mellitus. Nigerian journal of basic and applied sciences. 2012;20(1):60-3.
  10. CLSI. Collection t, and processing of blood specimens for testing plasma-based coagulation assays and molecular hemostasis assays; approved guideline. 5e edition. CLSI Document H21-A5. Ed. Wayne: PCaLSI, 2008.
  11. Sauls DL, Banini AE, Boyd LC, Hoffman M. Elevated prothrombin level and shortened clotting times in subjects with type 2 diabetes. Journal of thrombosis and haemostasis. 2007;5(3):638-9. 2007;5:638-9. doi: 10.1111/j.1538-7836.2006.02366.
  12. Zhao Y, Zhang J, Zhang J, Wu J. Diabetes mellitus is associated with shortened activated partial thromboplastin time and increased fibrinogen values. PLoS One. 2011;6:1–4. doi: 10.1371/journal.pone.0016470.
  13. Chavan PS, Afroz S, Jadhav S. A comparative study of coagulation tests in type 2 diabetes mellitus individuals and health individuals. Int J Med Sci. 2014;3(1):290-8.
  14. Acang N, Jalil FD. Hypercoagulation in diabetes mellitus. The Southeast Asian journal of tropical medicine and public health. 1993;24(Suppl 1):263–266. PMID 7886593.
  15. Ankalayya B, Sodhi HS, Modala S, Baghel M. A comparative study of coagulation time in type 2 diabetes mellitus and healthy individuals. International Journal of Contemporary Medical Research. 2016;3(11):3170–3171.
  16. Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, Coresh J, Brancati FL. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. New England Journal of Medicine. 2010;362(9):800-11. doi: 10.1056/NEJMoa0908359.
  17. Kim J, Ahn CW, Fang S, Lee HS, Park JS. Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes. Medicine. 2019;98(46). doi: 10.1097/MD.0000000000017918.
  18. Zhang Q, Li S, Li L, Li Q, Ren K, Sun X, Li J. Metformin treatment and homocysteine: a systematic Review and meta-analysis of randomized controlled trials. Nutrients. 2016;8(12):798. doi: 10.3390/nu8120798.
  19. Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, Johnston C, Engbaek F, Schneede J, McPartlin C, Scott JM. Facts and recommendations about total homocysteine determinations: an expert opinion. Clinical chemistry. 2004;50(1):3-2. doi: 10.1373/clinchem.2003.021634.
  20. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. Jama. 1993;270(22):2693-8. doi: 10.1001/jama.1993.03510220049033.
  21. Robinson K, Mayer EL, Miller DP, Green R, van Lente F, Gupta A, Kottke-Marchant K, Savon SR, Selhub J, Nissen SE, Kutner M. Hyperhomocysteinemia and low pyridoxal phosphate: common and independent reversible risk factors for coronary artery disease. Circulation. 1995;92(10):2825-30. doi: 10.1161/01.cir.92.10.2825.
  22. Dalery K, Lussier-Cacan S, Selhub J, Davignon J, Latour Y, Genest Jr J. Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate. The American journal of cardiology. 1995;75(16):1107-11. doi: 10.1016/s0002-9149(99)80739-5.
  23. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA. 1995;274(13):1049-57. doi: 10.1001/jama.1995.03530130055028.
  24. Sakyi SA, Laing EF, Mantey R, Kwarteng A, Owiredu EW, Dadzie RE, Amoani B, Opoku S, Afranie BO, Boakye D. Profiling immuno-metabolic mediators of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in Ghana. Plos one. 2021;16(3):e0249325. doi: 10.1371/journal.pone.0249325.
  25. Al-Maskari MY, Waly MI, Ali A, Al-Shuaibi YS, Ouhtit A. Folate and vitamin B12 deficiency and hyperhomocysteinemia promote oxidative stress in adult type 2 diabetes. Nutrition. 2012;28(7-8):e23-6. doi: 10.1016/j.nut.2012.01.005.
  26. Weikert C, Hoffmann K, Dierkes J, Zyriax BC, Klipstein-Grobusch K, Schulze MB, Jung R, Windler E, Boeing H. A homocysteine metabolism–related dietary pattern and the risk of coronary heart disease in two independent German study populations. The Journal of nutrition. 2005;135(8):1981-8. doi: 10.1093/jn/135.8.1981.
  27. Al-Daghri NM, Rahman S, Sabico S, Yakout S, Wani K, Al-Attas OS, Saravanan P, Tripathi G, McTernan PG, Alokail MS. Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects. Nutrients. 2016;8(9):460. doi: 10.3390/nu8090460.


[Download PDF]
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy
Pharmaceutical Fields
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Pharmaceutics
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Novel drug delivery system
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Nanotechnology
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Pharmacology
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Pharmacognosy
© Copyright 2009-2015 IJPBS, India. All rights reserved. Specialized online journals by ubijournal. Website by Ubitech Solutions
         Home I Contact I Terms & Conditions