PDF herunterladen
Thromb Haemost 1999; 81(03): 367-372
DOI: 10.1055/s-0037-1614479
Review Article
Schattauer GmbH

A Randomised, Controlled Study of the Effects of Aerobic Exercise and Dietary Fish on Coagulation and Fibrinolytic Factors in Type 2 Diabetics

David W. Dunstan
1   From the Departments of Medicine and Human Movement, University of Western Australia, West Australian Heart Research Institute, Department of Diabetes and Endocrinology, Royal Perth Hospital, Australia
,
Trevor A. Mori
1   From the Departments of Medicine and Human Movement, University of Western Australia, West Australian Heart Research Institute, Department of Diabetes and Endocrinology, Royal Perth Hospital, Australia
,
Ian B. Puddey
1   From the Departments of Medicine and Human Movement, University of Western Australia, West Australian Heart Research Institute, Department of Diabetes and Endocrinology, Royal Perth Hospital, Australia
,
Lawrie J. Beilin
1   From the Departments of Medicine and Human Movement, University of Western Australia, West Australian Heart Research Institute, Department of Diabetes and Endocrinology, Royal Perth Hospital, Australia
,
Valerie Burke
1   From the Departments of Medicine and Human Movement, University of Western Australia, West Australian Heart Research Institute, Department of Diabetes and Endocrinology, Royal Perth Hospital, Australia
,
Alan R. Morton
1   From the Departments of Medicine and Human Movement, University of Western Australia, West Australian Heart Research Institute, Department of Diabetes and Endocrinology, Royal Perth Hospital, Australia
,
Kim G. Stanton
1   From the Departments of Medicine and Human Movement, University of Western Australia, West Australian Heart Research Institute, Department of Diabetes and Endocrinology, Royal Perth Hospital, Australia
› InstitutsangabenThis study was financially supported by grants from the West Australian Health Promotion Foundation (Healthway), the Royal Perth Hospital Medical Research Foundation and a program grant from the National Health and Medical Research Council of Australia.
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
09. Dezember 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Summary

Type 2 diabetes is associated with disturbances in coagulation and fibrinolysis. Prospective studies show that increased tissue plasminogen activator (tPA) antigen increases the risk of cardiovascular mortality. The present study examined the hypothesis that combining a regime of moderate aerobic exercise with one daily fish meal as part of a low-fat diet (30% total energy) would improve coagulation and fibrinolytic factors in dyslipidaemic type 2 diabetic patients. In a randomised, controlled, 8-week trial, 55 sedentary type 2 diabetic subjects with serum triglycerides >1.8 mmol/l and/or HDL-C <1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g ω3 fatty acids/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate <100 bpm) exercise program. Plasma levels of fibrinogen, coagulation factor VIIc, tPA and plasminogen activator inhibitor (PAI-1) antigen were measured before and after intervention. In the 49 subjects who completed the study, the fish diet alone, moderate exercise alone and the combination of fish and moderate exercise all led to significant reductions in tPA antigen concentrations (-2.1 ng/ml, p = 0.02, -1.9 ng/ml, p = 0.03, -2.0 ng/ml, p = 0.01, respectively) compared to controls. In multivariate regression, changes in fasting blood glucose (positively) and erythrocyte ω3 fatty acid composition (inversely) were independent predictors of the change in tPA antigen. The fish diet alone contributed to a significant rise in coagulation factor VIIc compared to controls (4.9%, p = 0.02), which was prevented by moderate exercise. No significant effects on PAI-1 antigen and fibrinogen were seen. In view of recent epidemiological findings, the reduction in tPA antigen with both fish and moderate exercise in these dyslipidaemic type 2 diabetic patients could reflect a reduced thrombotic potential and decreased cardiovascular risk. Furthermore, a small, albeit significant, increase in coagulation factor VIIc associated with fish can be prevented by a concomitant programme of moderate exercise.

 

  • References

  • 1 Pyorala K, Laasko M, Uusitupa M. Diabetes and atherosclerosis. Diabetes Metab Rev 1987; 3: 463-524.
    CrossrefPubMedGoogle Scholar
  • 2 De Wood M, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, Lange HT. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. New Engl J Med 1980; 303: 897-902.
    CrossrefPubMedGoogle Scholar
  • 3 Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: A meta-analysis and review of the literature. Ann Intern Med 1993; 118: 956-63.
    CrossrefPubMedGoogle Scholar
  • 4 Heinrich J, Balleisen L, Schulte H, Assman G, van de Loo J. Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM study in healthy men. Arterioscler Thromb 1994; 14: 54-9.
    CrossrefPubMedGoogle Scholar
  • 5 Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-9.
    CrossrefPubMedGoogle Scholar
  • 6 Jansson J, Olofsson B, Nilsson TK. Predictive value of tissue plasminogen activator mass concentration on long-term mortality in patients with coronary artery disease. A 7-year follow-up. Circulation 1993; 88: 2030-4.
    CrossrefPubMedGoogle Scholar
  • 7 Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 1165-8.
    CrossrefPubMedGoogle Scholar
  • 8 Ridker PM, Hennekens CH, Stampfer MJ, Manson JE, Vaughan DE. Prospective study of endogenous tissue plasminogen activator and risk of stroke. Lancet 1994; 343: 940-3.
    CrossrefPubMedGoogle Scholar
  • 9 Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. New Engl J Med 1995; 332: 635-41.
    CrossrefPubMedGoogle Scholar
  • 10 Brannstrom M, Jansson J, Boman K, Nilsson TK. Endothelial haemostatic factors may be associated with mortality in patients on long-term anticoagulant treatment. Thromb Haemost 1995; 74: 612-5.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 11 Hamsten A, Walldius G, Szamosi A, Blombäck M, De Faire U, Dahlen G, Landou C, Wiman B. Plasminogen activator inhibitor in plasma: Risk factor for recurrent myocardial infarction. Lancet 1987; II: 3-9.
    PubMedGoogle Scholar
  • 12 Auwerx J, Bouillon R, Collen D, Beboers J. Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 1988; 8: 68-72.
    CrossrefPubMedGoogle Scholar
  • 13 Morishita E, Asakura H, Jokaji H, Saito M, Uotani C, Kumabashiri I, Yamazaki M, Aoshima K, Hashimoto T, Matsuda T. Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus. Atherosclerosis 1996; 120: 7-14.
    CrossrefPubMedGoogle Scholar
  • 14 Juhan-Vague I, Alessi MC, Vague P. Increased plasma plasminogen activator inhibitor 1 levels: a possible link between insulin resistance and atherothrombosis. Diabetologia 1991; 34: 457-62.
    CrossrefPubMedGoogle Scholar
  • 15 Eliasson M, Asplund K, Evrin P, Lindahl B, Lundblad D. Hyperinsulinaemia predicts low tissue plasminogen activator activity in a healthy population: The Northern Sweden MONICA Study. Metabolism 1994; 43: 1579-86.
    CrossrefPubMedGoogle Scholar
  • 16 Hiraga T, Shimada M, Tsukada T, Murase T. Hypertriglyceridemia, but not hypercholesterolemia, is associated with the alterations of fibrinolytic system. Horm Metab Res 1996; 28: 603-6.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Dunstan DW, Mori TA, Puddey IB, Beilin LJ, Burke V, Morton AR, Stanton KG. The independent and combined effects of aerobic exercise and dietary fish intake on serum lipids and glycemic control in NIDDM. A randomised controlled study. Diabetes Care 1997; 20: 913-21.
    CrossrefPubMedGoogle Scholar
  • 18 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-46.
    CrossrefPubMedGoogle Scholar
  • 19 Dacie JV, Lewis SM. Practical Haematology. London, U.K: Churchill Livingstone; 1984
    Google Scholar
  • 20 Mori TA, Vandongen R, Beilin LJ, Burke V, Morris J, Ritchie J. Effects of varying dietary fat, fish, and fish oils on blood lipids in a randomized controlled trial in men at risk of heart disease. Am J Clin Nutr 1994; 59: 1060-8.
    CrossrefPubMedGoogle Scholar
  • 21 Chandler WL, Trimble SL, Loo WC, Mornin D. Effect of PAI-1 levels on the molar concentrations of active tissue plasminogen activator (t-PA) and t-PA/PAI-1 complex in plasma. Blood 1990; 76: 930-7.
    PubMedGoogle Scholar
  • 22 Nilsson TK. Analysis of factors affecting tissue plasminogen activator activity and antigen concentration before and after venous occlusion in 123 patients. Clin Chem Enzymol Commun 1989; 1: 335-41.
    PubMedGoogle Scholar
  • 23 Eliasson M, Evrin PE, Lundblad D, Asplund K, Ranby M. Influence of gender, age and sampling time on plasma fibrinolytic variables and fibrinogen. A population study. Fibrinolysis 1993; 7: 316-23.
    PubMedGoogle Scholar
  • 24 Folsom AR, Qamhieh HT, Wing RR, Jeffrey RW, Stinson VL, Kuller LH, Wu KK. Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adults. Arterioscler Thromb Vasc Biol 1993; 13: 162-9.
    CrossrefPubMedGoogle Scholar
  • 25 Gough SCL, Grant PJ. The fibrinolytic system in diabetes mellitus. Diabetic Med 1991; 8: 898-905.
    CrossrefPubMedGoogle Scholar
  • 26 Hornsby WG, Boggess KA, Lyons TJ, Barnwell WH, Lazarchick J, Colwell JA. Hemostatic alterations with exercise conditioning in NIDDM. Diabetes Care 1990; 13: 87-92.
    CrossrefPubMedGoogle Scholar
  • 27 Schneider SH, Kim HC, Khachadurian AK, Ruderman NB. Impaired fibrinolytic response to exercise in Type 2 diabetes: Effects of exercise and physical training. Metabolism 1988; 37: 924-9.
    CrossrefPubMedGoogle Scholar
  • 28 Williams RS, Logue EE, Lewis JL, Barton T, Stead NW, Wallace AG, Pizzo SV. Physical conditioning augments the fibrinolytic response to venous occlusion in healthy adults. New Engl J Med 1980; 302: 987-91.
    CrossrefPubMedGoogle Scholar
  • 29 Stratton JR, Chandler WL, Schwartz RS, Cerqueira MD, Levy WC, Kahn SE, Larson VG, Cain KC, Beard JC, Abrass IB. Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old adults. Circulation 1991; 83: 1692-7.
    CrossrefPubMedGoogle Scholar
  • 30 De Geus EJC, Kluft C, De Bart ACW, Van Doornen LJP. Effects of exercise training on plasminogen activator inhibitor activity. Med Sci Sports Exerc 1992; 24: 1210-9.
    PubMedGoogle Scholar
  • 31 Rankinen T, Rauramaa R, Vaisanen S, Halonen P, Penttila IM. Blood coagulation and fibrinolytic factors are unchanged by aerobic exercise or fat modified diet. Randomized clinical trial in middle-aged men. Fibrinolysis 1994; 8: 48-53.
    PubMedGoogle Scholar
  • 32 Anderssen SA, Haaland A, Hjermann I, Urdal P, Gjesdal K, Holme I. Oslo diet and exercise study: a one-year randomized intervention trial. Effect on hemostatic variables and other coronary risk factors. Nutr Metab Cardiovasc Dis 1995; 5: 189-200.
    PubMedGoogle Scholar
  • 33 Pandolfi A, Iacoviello L, Capani F, Vitacolonna E, Donati MB, Consoli A. Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture. Diabetologia 1996; 39: 1425-31.
    CrossrefPubMedGoogle Scholar
  • 34 Nordt TK, Klassen KJ, Schneider DJ, Sobel BE. Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial cells by glucose and its implications for local fibrinolysis. Arterioscler Thromb 1993; 13: 1822-8.
    CrossrefPubMedGoogle Scholar
  • 35 Mehta J, Lawson D, Saldeen T. Reduction in plasminogen activator inhibitor-1 (PAI-1) with omega-3 polyunsaturated fatty acids (PUFA) intake. Am Heart J 1989; 116: 1201-6.
    PubMedGoogle Scholar
  • 36 Hellsten G, Boman K, Saarem K, Hallmans G. Effects on fibrinolytic activity of corn oil and a fish oil preparation enriched with omega-3-polyunsaturated fatty acids in a long-term study. Curr Med Res Opin 1993; 13: 133-9.
    CrossrefPubMedGoogle Scholar
  • 37 Toft I, Bonaa KH, Ingebretsen OC, Nordoy A, Jenssen T. Fibrinolytic function after dietary supplementation with ω3 fatty acids. Arterioscler Thromb Vasc Biol 1997; 17: 814-9.
    CrossrefPubMedGoogle Scholar
  • 38 Emeis JJ, van Houwelingen AC, van den Hoogen CM, Hornstra G. A moderate fish intake increases plasminogen activator inhibitor type-1 in human volunteers. Blood 1989; 74: 233-237.
    PubMedGoogle Scholar
  • 39 Fumeron F, Brigant L, Ollivier V, de Prost D, Driss F, Darcet P, Bard J, Parra H, Fruchart J, Apfelbaum M. n-3 polyunsaturated fatty acids raise low-density lipoproteins, high-density lipoprotein 2, and plasminogen-activator inhibitor in healthy young men. Am J Clin Nutr 1991; 54: 118-22.
    CrossrefPubMedGoogle Scholar
  • 40 Eritsland J, Seljeflot I, Abdelnoor M, Arnesen H. Long-term influence of omega-3 fatty acids on fibrinolysis, fibrinogen, and serum lipids. Fibrinolysis 1994; 8: 120-5.
    PubMedGoogle Scholar
  • 41 Oosthuizen W, Vorster HH, Jerling JC, Barnard HC, Smuts CM, Silvis N, Kruger A, Venter CS. Both fish oil and olive oil lowered plasma fibrinogen in women with high baseline fibrinogen levels. Thromb Haemost 1994; 72: 557-62.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 42 Miller GJ. Lipoproteins and the haemostatic system in atherothrombotic disorders. Baillières Clin Haematol 1994; 7: 713-32.
    CrossrefPubMedGoogle Scholar
  • 43 Hendra TJ, Britton ME, Roper DR, Wagaine-Twabwe D, Jeremy JY, Dandona P, Haines AP, Yudkin JS. Effects of fish oil supplements in NIDDM subjects. Controlled study. Diabetes Care 1990; 13: 821-9.
    CrossrefPubMedGoogle Scholar
  • 44 Boberg M, Pollare T, Siegbahn A, Vessby B. Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus. Eur J Clin Invest 1992; 22: 645-50.
    CrossrefPubMedGoogle Scholar
  • 45 Ceriello A, Giugliano D, Quatraro A, Dello Russo P, Torella R. Blood glucose may condition factor VII levels in diabetic and normal subjects. Diabetologia 1988; 31: 889-91.
    PubMedGoogle Scholar
  • 46 Westerveld HT, De Graaf JC, van Breugel I HHF, Akkerman JWN, Sixma JJ, Erkelens DW, Banga JD. Effects of low-dose EPA-E on glycemic control, lipid profile, lipoprotein(a), platelet aggregation, viscosity, and platelet and vessel wall interaction in NIDDM. Diabetes Care 1993; 16: 683-7.
    CrossrefPubMedGoogle Scholar
  • 47 Haines AP, Sanders TAB, Imeson JD, Mahler RF, Martin J, Mistry M, Vickers M, Wallace PG. Effects of a fish oil supplement on platelet function, hemostatic variables and albuminuria in insulin-dependent diabetics. Thromb Res 1986; 43: 643-55.
    CrossrefPubMedGoogle Scholar
  • 48 Radack K, Deck C, Huster G. Dietary supplementation with low-dose fish oils lowers fibrinogen levels: A randomized, double-blind controlled study. Ann Intern Med 1989; 111: 757-8.
    CrossrefPubMedGoogle Scholar
  • 49 Hwang DH, Chanmugam PS, Ryan DH, Boudreau MD, Windhauser MM, Tulley RT, Brooks ER, Bray GA. Does vegetable oil attenuate the beneficial effects of fish oil in reducing risk factors for cardiovascular disease?. Am J Clin Nutr 1997; 66: 89-96.
    CrossrefPubMedGoogle Scholar
  • 50 Wosornu D, Allardyce W, Tansey P. Influence of power and aerobic exercise training on haemostatic factors after coronary artery surgery. Br Heart J 1992; 68: 181-6.
    CrossrefPubMedGoogle Scholar
  • 51 Schuit AJ, Schouten EG, Kluft C, de Maat M, Menheere PPCA, Kok FJ. Effect of strenuous exercise on fibrinogen and fibrinolysis in healthy elderly men and women. Thromb Haemost 1997; 78: 845-51.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 52 Mori TA, Beilin LJ, Burke V, Morris J, Ritchie J. Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 1997; 17: 279-86.
    CrossrefPubMedGoogle Scholar