Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Effect of 8 hours of hyperinsulinaemia on haemostatic parameters in healthy man

  • 71 Accesses

  • 3 Citations


The role of variations in plasma insulin concentrations as a factor possibly involved in abnormalities of haemostatic functions, and (or) the development of arterial disease, has been the subject of controversy. This study examines the “in vivo” effect of hyperinsulinaemia on haemostatic parameters in seven healthy men. Two studies were carried out in random order: (a) Hyperinsulinaemia study. Human insulin was infused by a calibrated infusion pump (0.7 mU kg−1 min−1, for 8 h) during a euglycaemic glucose clamp, and (b) Control study 0.15 mmol/l NaCl solution was infused over 8 h. Plasma epinephrine and norepinephrine concentrations remained constant throughout the studies. Mean insulin levels during the hyperinsulinaemia study were 46.2±1.6 μU/ml, i.e. approximately eightfold higher than those at baseline, whereas plasma glucose levels remained constant at 4.9±0.1 mmol/l. During the control study, mean insulinaemia was 5.0±0.9 μU/ml, and plasma glucose 5.2±0.1 mmol/l. No statistically significant changes were observed during, or after insulin or 0.15 mmol/l NaCl infusions with regard to platelet parameters, blood coagulation, and coagulation inhibitors. These data suggest that abnormalities of the haemostatic function described during insulin-induced hypoglycaemia or in hyperinsulinaemic patients are not due to a direct action of insulin.


  1. 1.

    Osterman H, van de Loo J (1986) Factors of the hemostatic system in diabetic patients. A survey of controlled studies. Haemostasis 16: 386–416

  2. 2.

    Paton RC (1981) Haemostatic changes in diabetic coma. Diabetologia 21: 172–177

  3. 3.

    Juhan-Vague I, Vague P, Poisson C, Aillaud MF, Mendez C, Collen D (1984) Effect of 24 hours of normoglycaemia on tissue-type plasminogen activator plasma levels in insulin-dependent diabetes. Thromb Haemost 51: 97–98

  4. 4.

    Frier BM (1986) Hypoglycaemia and diabetes. Diab Med 3: 513–525

  5. 5.

    Trovati M, Anfossi G, Cavalot F, Vitali S, Masuco P, Mularoni E, Schinco P, Tamponi G, Emanuelli G (1986) Studies on mechanisms involved in hypoglycemia-induced platelet activation. Diabetes 35: 818–825

  6. 6.

    Hutton RA, Mikhailidis D, Dormandy KM, Ginsburg J (1979) Platelet aggregation studies during transient hypoglycaemia. A potential method for evaluating platelet function. J Clin Pathol 32: 434–438

  7. 7.

    Corrall RJM, Webber RG, Frier BM (1980) Increase in coagulation Factor VIII activity in man following acute hypoglycaemia: mediation via an adrenergic mechanism. Br J Haematol 44: 301–305

  8. 8.

    Dalsgaard-Nielsen J, Madsbad S, Hilsted J (1982) Changes in platelet function, blood coagulation and fibrinolysis during insulininduced hypoglycaemia in juvenile diabetics and normal subjects. Thromb Haemost 47: 254–258

  9. 9.

    Althoff PH, Rosak C, Ziemen M, Faβbinder W, Breddin K, Schöffling K (1986) Hypoglykämieinduzierte Hyperkoagualabilität — ein Risikofaktor für akute und chronische kardiovaskuläre Komplikationen bei Diabetikern. Akt Endokr Stoffw 7: 70

  10. 10.

    Hedlin AM (1973) Insulin and blood fibrinolytic activity. Thromb Diathes Haemorrh 29: 293–299

  11. 11.

    Hilsted J, Madsbad S, Dalsgaard-Nielsen J, Krarup T, Sestoft L, Gormsen J (1980) Hypoglycemia and hemostatic parameters in juvenile-onset diabetes. Diab Care 3: 675–678

  12. 12.

    Small M, Peterson KR, Flannigan P, Lowe GDO Forbes CHD, MacCuish AC (1986) Enhancement of fibrinolysis after insulin administration in NIDDM. Diab Care 2: 216–217

  13. 13.

    Vague P, Juhan-Vague I, Aillaud MF, Badier CH, Viard R, Alessi MCH, Collen D (1986) Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects. Metabolism 35: 250–253

  14. 14.

    Fuh MMT, Shieh SM, Wu DA, Chen YDI, Reaven GM (1987) Abnormalities of carbohydrate and lipid metabolism in patients with hypertension. Arch Intern Med 147; 1035–1038

  15. 15.

    Isles C, Lowe GDO, Rankin BM, Forbes CD, Lucie N, Lever AF, Kennedy AC (1984) Abnormal haemostasis and blood viscosity in malignant hypertension. Thromb Haemost 52: 253–255

  16. 16.

    Janka HU, Standl E (1987) Hyperinsulinaemia as a possible risk factor of macrovascular disease in diabetes mellitus. An overview. Diabete Metab 13: 279–282

  17. 17.

    Singer P, Gödicke W, Voigt S, Hajdu I, Weiss M (1985) Postprandial hyperinsulinemia in patients with mild essential hypertension. Hypertension 7: 182–186

  18. 18.

    EASD (1978) The policy of the European Association for the Study of Diabetes on human investigation. Diabetologia 15: 431–432

  19. 19.

    Verdonk CA, Rizza RA, Westland RE; Nelson RL, Gerich JE, Service FJ (1980) Glucose clamping using the Biostator GCIIS. Horm Metab Res 12: 133–135

  20. 20.

    Scharf RE (1986) Thrombozyten und Mikrozirkulationsstörungen. Klinische und experimentelle Untersuchungen zum Sekretionsverhalten und Arachidonsäurestoffwechsel der Blutplättchen. Schattauer, Stuttgart

  21. 21.

    Scharf RE, Tsamaloukas A, Schneider W (1984) Inhibition of platelet alpha-granule release in vitro by forskolin. Thromb Res 33: 661–664

  22. 22.

    Clauss A (1957) Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 17: 237–246

  23. 23.

    Breckenridge RT, Ratnoff OD (1962) Studies on the nature of the circulatory anticoagulant directed against the antihaemophilic factor: with notes on an assay for antihaemophilic factor. Blood 20: 137–149

  24. 24.

    Rosove MH, Hocking WC, Harwig SSL, Perloff JK (1983) Studies of β-thromboglobulin, platelet factor 4, and fibrino-peptide A in erythrocytosis due to cyanotic congenital heart disease. Thromb Res 29: 225–235

  25. 25.

    Löbermann H, Kolde HJ, Deubel R, Peter R, Tourte E, Becker U (1986) Determination of Protein C in plasma. Behring Inst Mitt 79: 112–120

  26. 26.

    Abildgaard U, Lie M, Ødergärd OR (1977) Antithrombin (heparin cofactor) assay with “new” chromogenic substrates (S-2238 and Chromozym TH). Thromb Res 11: 549–553

  27. 27.

    Gram J, Jespersen J (1985) A functional plasminogen assay utilizing the potentiating effect of fibrinogen to correct for the overestimation of plasminogen in pathological plasma samples. Thromb Haemostas 53: 255–259

  28. 28.

    Teger-Nilsson AC, Friberger P, Gyzander E (1977) Determination of a new rapid plasmin inhibitor in human blood by means of a plasmin specific tripeptide substrate. Scand J Clin Lab Invest 37: 403–409

  29. 29.

    Kemmer FW, Bisping R, Steingrüber HJ, Baar H, Hardtmann F, Schlaghecke R, Berger M (1986) Psychological stress and metabolic control in patients with type I diabetes mellitus. N Engl J Med 314: 1078–1084

  30. 30.

    Nurjhan N, Campbell PJ, Kennedy FP, Miles JM, Gerich JE (1986) Insulin dose-response characteristics for suppression of glycerol release and conversion to glucose in humans. Diabetes 35: 1326–1331

  31. 31.

    Small M, Douglas JT, Lowe GDO, MacCuish AC, Forbes CD (1986) Effect of insulin therapy on coagulation and platelet function in type II (Non-insulin-Dependent) diabetes mellitus. Haemostasis 16: 417–423

  32. 32.

    Kishikawa H, Takeda H, Kiyota S, Sakakida M, Furashima H, Ichinose K, Matsuda H, Nakamura N, Uzawa H. Role of α2-adrenergic receptor in platelet activation during insulin-induced hypoglycemia in normal subjects. Diabetes 36: 407–412

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mauricio-Leguizamo, G., Heinemann, L., Scharf, R.E. et al. Effect of 8 hours of hyperinsulinaemia on haemostatic parameters in healthy man. Diabetologia 32, 606–610 (1989). https://doi.org/10.1007/BF00285335

Download citation

Key words

  • Haemostasis
  • hyperinsulinaemia
  • platelet function