Insulin Sensitivity and Hemostatic Factors in Clinically Healthy 58-year-old Men

Stefan Agewall; Lena Bokemark; John Wikstrand; Anders Lindahl; Björn Fagerberg

doi:10.1055/s-0037-1614069

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 84(04): 571-575
DOI: 10.1055/s-0037-1614069

Review Article

Schattauer GmbH

Insulin Sensitivity and Hemostatic Factors in Clinically Healthy 58-year-old Men

Authors

Stefan Agewall

¹From the Department of Cardiology, Sahlgrenska University Hospital, Göteborg University, Sweden
Lena Bokemark

²Department of Medicine, Sahlgrenska University Hospital, Göteborg University, Sweden
John Wikstrand

³Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg University, Sweden
Anders Lindahl

⁴Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg University, Sweden
Björn Fagerberg

²Department of Medicine, Sahlgrenska University Hospital, Göteborg University, Sweden

Abstract

Summary

The objective of this cross-sectional study was to investigate the relationship between factors of the coagulation- and fibrinolysis systems and insulin sensitivity in 104 clinically healthy, 58-years-old men. Insulin sensitivity (hyperinsulinemic euglycemic clamp) adjusted for lean body mass, the metabolic syndrome according to a suggested definition, and different factors in the coagulation- and fibrinolysis system were determined. Subjects with the metabolic syndrome were characterised by increases in PAI-1 activity, tPA antigen, protein C and protein S and low concentrations of tPA activity. Insulin sensitivity was independently and reversibly associated with PAI-1 (p = 0.014) and directly with tPA activity (p = 0.001). Insulin sensitivity was also significantly negatively associated with protein S and protein C and several components in the metabolic syndrome, however not remaining significant in multivariate analyses. Protein C and protein S were significantly associated with PAI-1 activity, tPA activity (negatively), tPA antigen and antithrombin III. In conclusion, the data indicated that insulin resistance and several of the clustering components in the metabolic syndrome are accompanied by increased plasma concentrations of the anticoagulatory proteins C and S which may represent a mechanism which counteracts the concomitantly occurring hypofibrinolysis.

Key words

Insulin sensitivity - plasminogen activator inhibitor activity - protein C - protein S - tissue plasminogen activator

Full Text

References

References
1 Wilhelmsen L, Svärdsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction: The study of men born in 1913. N Engl J Med 1984; 311: 501-5.
2 Kannel WB, Wolf PA, Castelli WP. D’Agostini RB Fibrinogen and risk of cardiovascular disease. JAMA 1987; 258: 1183-6.
3 Hamsten A, Wiman B, DeFaire U, Blombäck M. Increased plasma levels of rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-63.
4 Aznar J, Estelles A, Tormo G, Sapena P, Tormo V, Blanch S, Espana F. Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease. Br Heart J 1988; 59: 535-41.
5 Juhan-Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. Circulation 1996; 94: 2057-63.
6 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539-53.
7 Agewall S, Wikstrand J, Fagerberg B. Prothrombin fragment 1+2 is a risk factor for myocardial infarction in treated hypertensive men. J Hypertens 1998; 16: 537-41.
8 Agewall S, Wikstrand J, Suurkula M, Tengborn L, Fagerberg B. Carotid artery wall morphology, haemostatic factors and cardiovascular disease. An ultrasound study in men at high and low risk for atherosclerotic disease. Blood Coagul Fibrinolysis 1994; 05: 895-904.
9 Tataru MC, Heinrich J, Junker R, Schulte H, von Eckardstein A, Assmann G, Kochler E. D-dimers in relation to the severity of atherosclerosis in patients with stable angina pectoris after myocardial infarction. Eur Heart J 1999; 20: 1493-502.
10 Endre T, Mattiasson I, Berntorp E, Berglund G, Hulthén L. Coagulation and fibrinolytic factors in normotensive hypertension-prone men. J Hypertens 1996; 14: 629-34.
11 Byberg L, Siegbahn A, Berglund L, McKeigue P, Reneland R, Lithell H. Plasminogen activator inhibitor 1 activity is independently related to both insulin sensitivity and serum triglycerides in 70 year old men. Arterioscler Thromb Vasc Biol 1998; 18: 258-64.
12 Agewall S. Insulin sensitivity and haemostatic factors in men at high and low cardiovascular risk. J Int Med 1999; 246: 489-95.
13 Agewall S, Fagerberg B, Attvall S, Wendelhag I, Urbanavicius V, Wikstrand J. Carotid artery wall intima-media thickness is associated with insulin-mediated glucose disposal in men at high and low coronary risk. Stroke 1995; 26: 956-60.
14 Beckman MSuurküla, Wikstrand J, Berglund G, Sivertsson R. Body weight is more important than family history of hypertension for left ventricular function. Hypertension 1991; 17: 661-8.
15 Agewall S, Samuelsson O, Andersson OK, Persson B, Wikstrand J, Fagerberg B. The efficacy of multiple risk factor intervention in treated hypertensive men, during long term follow-up. J Int Med 1994; 236: 651-9.
16 DeFronzo R, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214-E223.
17 Bokemark L, Frödén A, Attvall S, Wikstrand J, Fagerberg B. The euglycemic hyperinsulinemic clamp examination: variability and reproducibility. Scand J Clin Lab Invest. (in press).
18 Pietrobelli A, Formica C, Wang Z, Heymsfield SB. Dual-energy X-ray absorptiometry body composition model: review of physical concepts. Am J Physiology. 1996; 271 (Endocrinol Metab 34): E941-E951.
19 In Thrombosis and hemorrhage. Ed Loscalzo J, Shafer AI. London: Williams & Wilkins; 2nd ed. 1998: 54-61.
20 Dart AM, Cooper B, Kay SB, Salem H. Relationships between protein C, protein S, von Willebrand factor and euglobulin lysis time and cardiovascular risk factors in subjects with and without coronary heart disease. Atheroclerosis 1998; 140: 55-64.
21 Yudkin JS. Abnormalities of coagulation and fibrinolysis in insulin resistance. Evidence for a common antecedent?. Diabetes Care 22 (Suppl. 03) C25-30.
22 Vigano S, Mannucci PM, D’Angelo A, Gelfi C, Gensini GF, Rostagno C, Neri GGSerneri. Protein C antigen is not an acute phase reactant and is often high in ischemic heart disease and diabetes. Thromb Haemost 1984; 52: 263-6.
23 Conlan MG, Folsom AR, Finch A, Davis CE, Marcucci G, Sorlie P, Wu KK. Antithrombin III: associations with age, race, sex and cardiovascular disease risk factor. Thromb Haemost 1994; 72: 551-6.
24 Lao TT, Yin JA, Ng WK, Yuen PM. Relationship between maternal antithrombin III and protein C/protein S levels before, during and after delivery. Gynecol Obstet Invest 1990; 30: 87-90.
25 Bertoli SV, di Belgiojoso GB, Trezzi M, Scorza D, Barone MT, Poggio M, Rossi E, Landriani N, Genderini A. Reduced levels of coagulation inhibitors in chronic hemodilysis compared with CAPD. Adv Perit Dial 1995; 11: 127-30.
26 Kluft C. Constitutive synthesis of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor types 1 (PAI-1): conditions and therapeutic targets. Fibrinolysis 1994; 08 (Suppl. 02) 1-7.
27 Juhan-Vague I, Morange P, Rennuci JF, Alessi MC. Fibrinogen, obesity and insulin resistance. Blood Coagul Fibrinolysis. 1999; 10 (Suppl. 01) 25-8.