METABOLIC AND HEMOSTATIC PARAMETERS IN PRE-DIABETES AND NEWLY DIAGNOSED TYPE 2 DIABETES

Metabolic changes in diabetes mellitus are associated with hemostatic disorders. However, the sequence of hemostatic events in the early stages of disease remains unclear.

Aim. To assess metabolic and hemostatic parameters and their interaction in pre-diabetes and newly diagnosed type 2 diabetes mellitus (ND T2DM).

Material and methods. The study enrolled volunteers of 40 to 65 years who considered themselves healthy and did not get any medication therapy. Of 170 examined individuals, 46 had impaired carbohydrate exchange (ICE) — 13 with impaired fasting glucose, 17 — impaired glucose tolerance and 16 with ND T2DM. The control group comprised healthy volunteers with normal body mass index and without signs of metabolic abnormalities. The metabolic (carbohydrate, lipid, protein exchange, hepatic transaminase), platelet and plasma hemostatic parameters (mean platelet volume, ADP- &collagen-induced platelet aggregation, coagulation profile, fibrinogen, plasminogen) were investigated. We identified the peculiarities initiating impact of changed parameters on different hemostatic components in patients with pre-diabetes and ND T2DM.

Results. Concentration of insulin, C-peptide, Homa-IR, total cholesterol demonstrated increase in groups with ICE. ADP-induced platelet aggregation, fibrinogen increased in ICE, however these changes were not statistically significant. Mean platelet volume and plasminogen had the tendency to be elevated in pre-diabetes and demonstrated significant increase in ND T2DM.

Conclusion. Metabolic disorders in prediabetic stage initiate changes in platelet hemostasis and fibrinolysis. The increase of MPV and higher concentrations of plasminogen are considered to be significant in ND T2DM.

1. Yusuf S, Wood D., Ralston J, Reddy K.S. The World Heart Federation’s vision for worldwide cardiovascular disease prevention. Lancet 2015; 386: 399–402.

2. International Diabetes Federation. Diabetes Atlas 2014. https://www.idf.org/sites/default/files/attachments/2014_4_Makaroff.pdf

3. Ferreiro JL, Gómez-Hospital1 JA, Angiolillo AJ. Platelet abnormalities in diabetes mellitus. Diabetes & Vascular Disease Research 2010; 7(4): 251–9.

4. Tabit CE, Chung WB, Hamburg NM,Vita JA.Endothelialdysfunction in diabetes mellitus: molecular mechanisms and clinical. Reviews in Endocrine and Metabolic Disorders 2010; 11(1): 61–74.

5. Vazzana N, Ranalli P, Cuccurullo C, Davi G. Diabetes mellitus and thrombosis. Thromb Res 2012; 129: 371-7.

6. World Health Organization: Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications: Report of a WHO Consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus. Geneva, World Health Org., 1999.

7. World Health Organization (WHO), Abbreviated report of aWHO consultation. Use of glycated hemoglobin (HbA1c) in the diagnosis if diabetes mellitus. 2011.

8. American Diabetes Association. Classification and Diagnosis of Diabetes. Diabetes Care 2015; 38(Suppl 1): S8-16.

9. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension. Eur Heart J. 2013; 34: 2159–219.

10. Kronenberg HM, Melmed S, Polonsky KS, Larsen PR. Williams Texbook of Endocrinology, 11th edition. Elsevier Ltd., 2008: 1589-631.

11. Bloomgarden ZT. Cardiovascular Disease in Diabetes. Diabetes Care. 2010; 33: 49–54.

12. Ryden L., Co-Chairperson, Standl E. et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text. Eur Heart J. 2013; 34: 3035-87.

13. Lyon CJ, Hsueh WA. Effect of plasminogen activator inhibitor-1 in diabetes mellitus and cardiovascular disease. Am.J. Med. 2003; 115(8A): 62-8.

14. Juhan-Vague I, Roul C, Alessi MC, et al. Increase plasminogen activator inhibitor activity in non-insulin-dependent diabetic patients: relationship with plasma insulin. Thromb. Haemost. 1989; 61:370-3.

15. Geiger M, Binder BR. Plasminogen activation in diabetes mellitus. Enzyme 1988; 40: 149-57.

16. Meigs JB, O’donnell CJ, Tofler GH et al. Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes : the Framingham Offspring Study. Diabetes. 2006; 55: 530–7.

17. Folsom A, Wu K, Rasumussen M. Determinants of population changes in fibrinogen and factor VII over 6 year. Arteriosclerosis, Trombosis and Vasculare Biology. 2000; .20: 601-6.

18. Corrado E, Rizzo M, Muratori I. Assotiation of elevated fibrinogen and CRP levels with carotid lesions in patiets with newly diagnosed hypertensionor type 2 diabetes. Arch Med Res. 2006; 3798: 1004-9.

19. Dunn E, Ariens R, Grant P. The influence of type 2 diabetes on fibrin structure and function. Diabetologia. 2005; 48: 1198–1206.

20. Coban E, Yazicioglu G, Ozdogan M. Platelet activation in subjects with subclinical hypothyroidism. Med SciMonit. 2007; 13: 211-4.

21. Tavassoli M. Megakaryocyte-platelet axis and the process of platelet formation and release. Blood. 1980; 55: 537-45.

22. Michno A, Bielarezyk H, Pawetczyk T, Jan Kowska-Kulawy A. Alterations of adenine nuckleotide metabolism and function of blood platelets in patients with diabetes. Diabetes. 2007: 56: 462-7.

23. Negrev N. The effect of insulin in thrombocytopoiesis and thrombocytopoietin biosynthesis in rats. Exp.Med.Morfol. 1990; 29(4): 24-7.

24. Vinik AI, Tomris E, Roger N. Platelet disfunction in type 2 diabetes. Diabetes. 2001; 24 (8): 1476-85.

25. Keating FK, Sobel B E, Schneider DJ. Effects of increased concentrations of glucose on platelet reactivity in healthy subjects and in patients with and without diabetes. Am. J. Cardiol. 2003; 92:1362–5.

26. Schneider DJ. Factors Contributing to Increased Platelet Reactivity in People With Diabetes. Diabetes Care. 2009; 32: 525-7.

27. Michelson A. Platelets. Second Edition.— Amsterdam, Boston, Heidelberg et al.: Academic Press. Elserver Inc., 2007: 697-712.

28. McLeod AJ, Johnson M. Suckling KE, Walton P. Enchanced phospholipase A2 activity in cholesterol-enriched platelets from rabbits FED a cholesterdenriched platelets from rebbi tsFEDacholesterolenricheddiet. Throm. Haemost. 1981; 46(1): 278.

29. Dutu A, Gligore V, Hincu N, Podut A. Aspeetecorelativeintrelipidelesericefunctiiletrombocit aresiangiopatic in diabotulzaharef. Med.interna (Buc.) — 1972; 24(1): 81-6

30. Jovan M, Dusan D, Dragan M.et al. Agregacijathrombocita u bolesnika s diabetes mellitus ihyperlipoproteinemiajomtipa IV. Diabetol. Croat. 1979; 8(3): 227-49.

31. Dunn EJ, Grant PJ. Type 2 diabetes: an atherothrombotic syndrome. CurrMol Med. 2005; 5: 323-32.

32. Barillari G, Fabbro E, Pasca S, Bigotto E. Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population. Blood Coagul. Fibrinolysis. 2009; 20: 290-6.

33. Maschirow L, Khalaf K, Al-Aubaidy HA, Jelinek HF. Inflammation, coagulation, endothelial dysfunction and oxidative stress in prediabetes.— Biomarkers as a possible tool for early disease detection for rural screening. ClinBiochem. 2015;48(9): 581-5.