Correlation between coagulation and inflammation state in patients with diabetes mellitus type 2 in relation to gender differences: is there any impact of eight-week exercise training?
Abstract
Abstract
Background/Aim. The hypercoagulable state and inflammation state in diabetics has been widely studied by previous researchers, but there is a lack of research about a possible impact of exercise training on this relationship. The aim of this study was to assess and compare correlation between the coagulation and inflammation status in patients with type 2 diabetes mellitus taking into account the gender differences as well as an impact of the 8-week exercise training on the correlation coefficient and parameters of the inflammation and coagulation state. Methods. A total of 60 patients in stable clinical condition and well-regulated diabetic status passed through all phases of the study. The exercise training included the exercise program as interval training with estimated intensity uphill to 75% of a maximal heart rate in particular individual, 5 times a week for 8 weeks, and walking for 30 minutes with a speed of 5 km/h, 5 times a week for 8 weeks. Further fibrinolytic, coagulation and inflammatory parameters were analyzed before and after the study: D-dimer, von Willebrand factor (vWF), fibrinogen, high sensitivity CRP (hs-CRP), leukocytes, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and coagulation factors: FII, FV, FVII and FX. Results. Our research showed a statistically significant reduction in the mean vWF levels after intervention both at the males (p < 0.001) and females (p < 0.001). According to a correlation analysis between hs-CRP and fibrinogen, there was a positive correlation as baseline both at the males (p < 0.05, r = 0.492) and females (p < 0.01, r = 0.516) which became weaker in the males (p < 0.01, r = 0.449) and disappeared in the females (p < 0.05, r = 0.059) after intervention. The correlation which existed as baseline in the males between D-dimer and either hs-CRP (p < 0.01, r = 0.633) or fibrinogen (p < 0.01, r = 0.673) as well as the correlation between hs-CRP and FII (p < 0.01, r = 0.728), FV (p < 0.05, r = 0.366), FVII (p < 0.05, r = 0.373) coagulation as well as between D-dimer and FII (p < 0.01, r = 0.851), FVII (p < 0.05, r = 0.367)was absent in the females. Our research demonstrated a weakening correlations in the males after intervention between D-dimer and hs-CRP (p < 0.05, r = 0.378), between hs-CRP and FII (p < 0.01, r = 0.501), FV (p < 0.05, r = 0.298), FVII (p < 0.05, r = 0.351) as well as between D-dimer and FII (p < 0.01, r = 0.759), and FVII (p < 0.05, r = 0.296). The increase of the FX values (p < 0.05) in the females after intervention suggested the possible antiinflammatory effect of exercise training. Conclusion. According to previous research, the higher levels of vWF was associated with a risk of cardiovascular disease in people with type 2 diabetes mellitus and vWF may be a risk factor unique to these populations. We demonstrated that the 8-week exercise training can significantly reduce the value of vWF in the males and females, suggesting a potential beneficial effect on the endothelial function parameters. Our research demonstrated a stronger correlation between the coagulation and inflammation parameters as baseline in the males than in the females with type 2 diabetes mellitus. According to our results, the 8-week exercise training lead to a weakening of the strength of correlation between the coagulation and inflammation parameters in the males and complete disappearance of this correlation in the females, suggesting a unique effect of exercise training that should be explored in future research.
References
REFERENCES
Cheng D. Prevalence, predisposition and prevention of type II diabetes. Nutr Metab (Lond) 2005; 2: 29.
Hilberg T, Eichler E, Gläser D, Schmidt V, Gabriel HH. Platelet activity, reactivity and platelet-leukocyte conjugate formation before and after exhaustive or moderate exercise in patients with IDDM. Platelets 2004; 15(2): 101–8.
Malý J. Diabetes mellitus and prothrombotic activity. Vnitr Lek 2010; 56(4): 284–8.
Dayer MR, Mard-Soltani M, Dayer MS, Alavi SM. Interpreta-tion of correlations between coagulation factors FV, FVIII and vWF in normal and type 2 diabetes mellitus patients. Pak J Biol Sci 2011; 14(9): 552–7.
Stoppa-Vaucher S, Dirlewanger MA, Meier CA, de Moerloose P, Reber G,Roux-Lombard P, et al. Inflammatory and prothrombotic states in obese children of European descent. Obesity (Silver Spring) 2012; 20(8): 1662–8.
Previtali E, Bucciarelli P, Passamonti SM, Martinelli I. Risk factors for venous and arterial thrombosis. Blood Transfus 2011; 9(2): 120–38.
Prelipcean CC, Fierbinteanu-Braticevici C, Drug VL, Lăcătuşu C, Mihai B, Mihai C. Liver cirrhosis-procoagulant stasis. Rev Med Chir Soc Med Nat Iasi 2011; 115(3): 678–85. (Romanian)
Lelakowski J, Rydlewska A, Domagała TB, Piekarz J, Karkowski G, Januszek R, et al. Venous thrombosis as a complication of pacemaker implantation--own observations. Pol Merkur Le-karski 2011; 30(176): 102–10. (Polish)
Coban E, Ozdoğan M, Akçit F. Levels of plasma fibrinogen and D-dimer in subjects with white-coat hypertension. J Hum Hypertens 2004; 18(4): 291–2.
Ruszkowska-Ciastek B, Sokup A, Wernik T, Rhone P, Góralczyk K, Bielawski K, et al. Low-grade risk of hypercoagulable state in patients suffering from diabetes mellitus type 2. J Zhejiang Univ Sci B 2015; 16(9): 788–95.
Koh GC, Meijers JC, Maude RR, Limmathurotsakul D, Day NP, Peacock SJ, et al. Diabetes does not influence activation of coa-gulation, fibrinolysis or anticoagulant pathways in Gram-negative sepsis (melioidosis). Thromb Haemost 2011; 106(6): 1139–48.
Kafle DR, Shrestha P. Study of fibrinogen in patients with di-abetes mellitus. Nepal Med Coll J 2010; 12(1): 34–7.
Verkleij CJ, Bruijn RE, Meesters EW, Gerdes VE, Meijers JC, Marx PF. The hemostatic system in patients with type 2 di-abetes with and without cardiovascular disease. Clin Appl Thromb Hemost 2011; 17(6): E57–63.
Lim SC, Caballero AE, Smakowski P, LoGerfo FW, Horton ES, Veves A. Soluble intercellular adhesion molecule, vascular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 diabetic individuals without microalbuminuria. Diabetes Care 1999; 22(11): 1865–70.
Zareba W, Pancio G, Moss AJ, Kalaria VG, Marder VJ, Weiss HJ, et al. Increased level of von Willebrand factor is significantly and independently associated with diabetes in postinfarction patients. THROMBO Investigators. Thromb Haemost 2001; 86(3): 791–9.
Domingueti CP, Dusse LM, Fóscolo RB, Reis JS, Annichino-Bizzacchi JM, Orsi FL, et al. Von Willebrand Factor, ADAMTS13 and D-Dimer Are Correlated with Different Levels of Nephropathy in Type 1 Diabetes Mellitus. PLoS One 2015; 10(7): e0132784.
de Meirelles LR, Matsuura C, Resende Ade C, Salgado AA, Pereira NR, Coscarelli PG, et al. Chronic exercise leads to antiaggregant, antioxidant and anti-inflammatory effects in heart failure patients. Eur J Prev Cardiol 2014; 21(10): 1225–32.
Lockard MM, Gopinathannair R, Paton CM, Phares DA, Hagberg JM. Exercise training-induced changes in coagulation factors in older adults. Med Sci Sports Exerc 2007; 39(4): 587–92.
Ribeiro J, Almeida-Dias A, Oliveira AR, Mota J, Appell H, Duarte JA. Exhaustive exercise with high eccentric components induces prothrombotic and hypofibrinolytic responses in boys. Int J Sports Med 2007; 28(3): 193–6.
Frankel DS, Meigs JB, Massaro JM, Wilson PWF, O'Donnell CJ, D'Agostino RB, et al. Von Willebrand factor, type 2 diabetes mellitus, and risk of cardiovascular disease: The framingham offspring study. Circulation 2008; 118(24): 2533–9.
Creighton BC, Kupchak BR, Aristizabal JC, Flanagan SD, Dunn-Lewis C, Volk BM, et al. Influence of training on markers of platelet activation in response to a bout of heavy resistance exercise. Eur J Appl Physiol 2013; 113(9): 2203–9.
Androulakis NE, Koundourakis NE, Nioti E, Spatharaki P, Hatzi-symeon D, Miminas I, et al. Preseason preparation training and endothelial function in elite professional soccer players. Vasc Health Risk Manag 2015; 11: 595–9.
Jahangard T, Torkaman G, Ghoosheh B, Hedayati M, Dibaj A. The effect of short-term aerobic training on coagulation and fibrinolytic factors in sedentary healthy postmenopausal women. Maturitas 2009; 64(4): 223–7.
Lamprecht M, Moussalli H, Ledinski G, Leschnik B, Schlagenhauf A, Koestenberger M, et al. Effects of a single bout of walking exercise on blood coagulation parameters in obese women. J Appl Physiol 2013; 115(1): 57–63.
Beltan E, Chalabi T, Tripette J, Chout R, Connes P. Coagulation responses after a submaximal exercise in sickle cell trait carri-ers. Thromb Res 2011; 127(2): 167–9.
el-Sayed MS. Effects of exercise on blood coagulation, fibrinolysis and platelet aggregation. Sports Med 1996; 22(5): 282–98.
Bizheh N, Jaafari M. The Effect of a Single Bout Circuit Resis-tance Exercise on Homocysteine, hs-CRP and Fibrinogen in Sedentary Middle Aged Men. Iran J Basic Med Sci 2011; 14(6): 568–73.
Mongirdienė A, Kubilius R. Effect of physical training on indices of platelet aggregation and fibrinogen concentration in patients with chronic heart failure. Medicina (Kaunas) 2015; 51(6): 343–50.
Crop MJ, Siemes C, Berendes P, van der Straaten F, Willemsen S, Levin M. Influence of C-reactive protein levels and age on the value of D-dimer in diagnosing pulmonary embolism. Eur J Haematol 2014; 92(2): 147–55.
Lowe GD, Yarnell JW, Rumley A, Bainton D, Sweetnam PM. C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell study: Are inflammation and fibrin turnover linked in pathogenesis? Arterioscler Thromb Vasc Biol 2001; 21(4): 603–10
Topçiu-Shufta V, Haxhibeqiri V, Begolli L, Baruti-Gafurri Z, Veseli S, Haxhibeqiri S, et al. Correlation of Inflammation and Lipoprotein (a) with Hypercoagulability in Hemodialysis Pa-tients. Med Arch 2015; 69(4): 232–5.
Long ZF, Qu GY, Xu M. Relationship between the level of plasma D-dimer and diabetic microangiopathy. Hunan YiKe Da Xue Xue Bao 2001; 26(5): 434–6. (Chinese)
Levinger I, Goodman C, Peake J, Garnham A, Hare DL, Jerums G, et al. Inflammation, hepatic enzymes and resistance training in individuals with metabolic risk factors. Diabet Med 2009; 26(3): 220–7.
Dayer MR, Mard-Soltani M, Dayer MS, Alavi SM. Causality relationships between coagulation factors in type 2 diabetes mellitus: Path analysis approach. Med J Islam Repub Iran 2014; 28: 59.
Fu Y, Jiang H, Li LX, Chen J, Niu Q, Li RX. Correlation of coagulation indicators with inflammatory markers for sepsis in the patients with hematological malignancies. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2014; 22(5): 1381–5. (Chinese)
Thor M, Yu A, Swedenborg J. Markers of inflammation and hypercoagulability in diabetic and nondiabetic patients with lower extremity ischemia. Thromb Res 2002; 105(5): 379–83.
Alehagen U, Dahlström U, Lindahl TL. Low plasma concentra-tions of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure. Blood Coa-gul Fibrinolysis 2010; 21(1): 62–9.
Ruiz-Saez A. Occurrence of thrombosis in rare bleeding dis-orders. Semin Thromb Hemost 2013; 39(6): 684–92.
El-Hagracy RS, Kamal GM, Sabry IM, Saad AA, Abou El Ezz NF, Nasr HA. Tissue Factor, Tissue Factor Pathway Inhibitor and Factor VII Activity in Cardiovascular Complicated Type 2 Diabetes Mellitus. Oman Med J 2010; 25(3): 173–8.
Ip H, Chan AY, Ng K, Soo YO, Wong LK. Case report: A 70-year-old man with undiagnosed factor VII deficiency pre-sented with acute ischemic stroke. J Stroke Cerebrovasc Dis 2013; 22(8): e664–6
Ku SK, Bae JS. Inhibitory Effect of FXa on Secretory Group IIA Phospholipase A2. Inflammation 2015; 38(3): 987–94.
Bukowska A, Zacharias I, Weinert S, Skopp K, Hartmann C, Huth C, et al. Coagulation factor Xa induces an inflammatory signalling by activation of protease-activated receptors in human atrial tissue. Eur J Pharmacol 2013; 718(1–3): 114–23.
Gleeson EM, O'Donnell JS, Hams E, Ní Áinle F, Kenny BA, Fallon PG, et al. Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from lipopolysaccharide-stimulated myeloid cells. Haematologica 2014; 99(1): 185–93.