Subscribe to RSS
DOI: 10.1055/s-2004-817965
J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Enhancement of Fibrinolysis in Poorly Controlled, Hospitalized Type 2 Diabetic Patients by Short-Term Metabolic Control: Association with a Decrease in Plasminogen Activator Inhibitor 1
Publication History
Received: January 9, 2003
First decision: April 14, 2003
Accepted: October 6, 2003
Publication Date:
04 May 2004 (online)
Abstract
Impaired fibrinolysis in type 2 diabetes may be caused by an increased plasma concentration of plasminogen activator inhibitor 1 (PAI-1), although the effects of short-term hypoglycemic therapy on fibrinolytic activity are poorly understood. This study investigated the effects of metabolic improvement on fibrinolysis activity and plasma concentrations of PAI-1 in poorly controlled, hospitalized type 2 diabetic patients. Forty-eight poorly controlled type 2 diabetic patients were studied; 26 were subsequently treated with sulfonylurea (SU) and 22 with insulin. The plasma concentrations of plasmin-α2-antiplasmin (PAP), a measure of fibrinolytic activity, plasma PAI-1, and fasting triglycerides and glucoses were measured at the beginning and the end of hospitalization. The body mass index and fasting triglyceride decreased significantly after treatment (p < 0.0001). The plasma concentration of PAP increased significantly (p < 0.01), and the plasma PAI-1 decreased by 50 % after treatment. There was an inverse correlation between the changes in the plasma concentrations of PAP and PAI-1 (r= - 0.36, p = 0.023). Treatment with SU or insulin showed an increase in plasma PAP with a concomitant decrease in the plasma PAI-1 with equivalent glycemic control. In poorly controlled type 2 diabetic patients, the plasma PAP concentration can be significantly increased and the plasma PAI-1 antigen significantly reduced, even with short-term metabolic improvements including weight reduction, a better lipid profile, and tighter glycemic control with either SU or insulin therapy, and that enhanced fibrinolysis may be mediated partly through a decrease in the plasma PAI-1 after metabolic control.
Key words
Fibrinolysis - plasminogen activator inhibitor 1 - glycemic control - type 2 diabetes - plasmin-α2-antiplasmin
References
- 1 Alessi M C, Juhan-Vague I, Kooistra T, Declerck P J, Collen D. Insulin stimulates the synthesis of plasminogen activator inhibitor 1 by the human hepatocellular cell line HepG2. Thromb Haemost. 1988; 89 491-494
- 2 Alessi M C, Peiretti F, Morange P, Henry M, Nalbone G, Juhan-Vague I. Production of plasminogen activator inhibitor 1 by human adipose tissue. Possible link between visceral fat accumulation and vascular disease. Diabetes. 1997; 46 860-867
- 3 Aso Y, Matsumoto S, Fujiwara Y, Tayama K, Inukai T, Takemura Y. Impaired fibrinolytic compensation for hypercoagulability in obese patients with type 2 diabetes: association with increased plasminogen activator inhibitor 1. Metabolism. 2002; 51 471-476
- 4 Auwerx J, Bouillon R, Collen D, Geboers J. Tissue-type plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis. 1988; 8 68-72
- 5 Bagg W, Ferri C, Desideri G, Gamble G, Ockelford P, Braatvedt G D. The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes. J Clin Endocrinol Metab. 2001; 86 5491-5497
- 6 Bahru Y, Kesteven P, Alberti K G, Walker M. Decreased plasminogen activator inhibitor-1 activity in newly diagnosed type 2 diabetic patients following dietary modification. Diabetic Med. 1993; 10 802-806
- 7 Calles-Escadon J, Ballor D, Harvey-Berino J, Ades P, Tracy R, Sobel B. Amelioration of the inhibition of fibrinolysis in elderly, obese subjects by moderate energy intake restriction. Am J Clin Nutr. 1996; 64 7-11
- 8 Chen Y Q, Su M, Walia R R, Hao Q, Convington J W, Vaughan D E. Sp1 sites mediate activation of the plasminogen-activator inhibitor-1 promoter by glucose in vascular smooth muscle cells. J Biol Chem. 1998; 273 8225-8233
- 9 DeFronzo R A. Pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus: a balanced overview. Diabetologia. 1992; 35 389-397
- 10 Grant P J. The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. Diabetes Care. 1996; 19 64-66
- 11 Haffner S M, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and nondiabetic subjects and without prior myocardial infarction. N Engl J Med. 1998; 339 229-234
- 12 Jain S K, Nagi D K, Slavin B M, Lumb P J, Yudkin J S. Insulin therapy in type 2 diabetic subjects suppresses plasminogen activator inhibitor (PAI-1) activity and proinsulin-like molecules independently of glycemic control. Diabetic Med. 1993; 10 27-32
- 13 Jarvi A E, Karlstrom B E, Granfeldt Y E, Bjorck I E, Asp N G, Vessby B O. Improved glycemic control and lipid profile and normalized fibrinolytic activity on a low-glycemic index diet in type 2 diabetic patients. Diabetes Care. 1999; 22 10-18
- 14 Juhan-Vague I, Alessi M C, Vague P. Increased plasma plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia. 1991; 34 457-462
- 15 Juhan-Vague I, Alessi M C, Vague P. Involvement of the hemostatic system in the insulin resistance syndrome: a study of 1500 patients with angina pectoris. Arterioscler Thromb. 1993; 13 1865-1873
- 16 Juhan-Vague I, Roul C, Alessi M C, Ardissone J P, Heim M, Vague P. Increased plasminogen activator inhibitor activity in non insulin dependent diabetic patients-relationship with plasma insulin. Thromb Haemost. 1989; 61 370-373
- 17 Kannel W B, MacGee D L. Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study. Diabetes Care. 1979; 2 120-126
- 18 Kruithof E KO, Tran-Tang C, Bachman F. The fast acting inhibitor of tissue-type plasminogen activator in plasma is also the primary inhibitor of urokinase. Thromb Haemost. 1986; 55 65-69
- 19 Kruszynska Y T, Yu J G, Olefsky J M, Sobel B E. Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and lean and obese normal subjects. Diabetes. 2000; 49 633-639
- 20 Lormeau B, Aurousseau M H, Valensi P, Paries J, Attali J R. Hyperinsulinemia and hypofibrinolysis: effects of short-term optimized glycemic control with continuous insulin infusion in type II diabetic patients. Metabolism. 1997; 46 1074-1079
- 21 Marvi A, Stegnar M, Krebs M, Sentocnik J T, Geiger M, Binder B R. Impact of adipose tissue on plasma plasminogen activator inhibitor-1 in dieting obese women. Arteriorscler Thromb Vasc Biol. 1999; 19 1582-1587
- 22 McGill J B, Schneider D J, Arfken C L, Lucore C L, Sobel B E. Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients. Diabetes. 1994; 43 104-109
- 23 Nagi D K, Yudkin J S. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. Diabetes Care. 1993; 16 621-629
- 24 National Diabetes Data Group . Classification and diagnosis of diabetes mellitus and other categories of glucose tolerance. Diabetes. 1979; 28 1039-1057
- 25 Nordt T K, Klassen K J, Schneider D J, Sobel B E. Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial endothelial cells by glucose and its implications for local fibrinolysis. Arterioscler Thromb. 1993; 13 1822-1828
- 26 Nordt T K, Sawa H, Fujii S, Sobel B E. Induction of plasminogen activator inhibitor type-1 (PAI-1) by proinsulin and insulin in vivo. Circulation. 1995; 91 764-770
- 27 Panahloo A, Mohamed-Ali V, Andres C, Denver A E, Yudkin J S. Effect of insulin versus sulfonylurea therapy on cardiovascular risk factors and fibrinolysis in type II diabetes. Metabolism. 1998; 47 637-643
- 28 Relimpio F, Losada F, Pumar A, Garcia de Pesquera F, Morales F, Acosta D, Astorga R. Relationships of C-peptide levels and the C-peptide/blood sugar ratio with clinical/biochemical variables associated with insulin resistance in orally-treated, well-controlled type2 diabetic patients. Diabetes Res Clin Pract. 1997; 36 173-180
-
29 Rossetti L.
Glucose toxicity: effects of chronic hyperglycemia on insulin action. LeRoith D, Taylor SI, Olefsky JM Diabetes Mellitus - a Fundamental and Clinical Text. 2nd ed. Philadelphia; Lippincott Williams & Wilkin 2000: 641-651 - 30 Schneider D J, Nordt T K, Sobel B E. Attenuated fibrinolysis and accelerated atherogenesis in type II diabetic patients. Diabetes. 1993; 42 1-7
- 31 Schneider D J, Nordt T K, Sobel B E. Stimulation of proinsulin of expression of plasminogen activator inhibitor type-1 in endothelial cells. Diabetes. 1992; 41 890-895
- 32 Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaga K, Matsuzawa Y. Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease. Nature Med. 1996; 2 800-803
- 33 Vaughan D E. Plasminogen activator inhibitor-1: a common denominator in cardiovascular disease. J Invest Med. 1998; 46 370-376
- 34 Vukovich T, Proidl S, Knobl P, Teufelsbauer H, Schnack C, Schernthaner G. The effect of insulin treatment on the balance between tissue plasminogen activator and plasminogen activator inhibitor-1 in type 2 diabetic patients. Thromb Haemost. 1992; 68 253-256
- 35 Walmsely D, Hampton K K, Grant P J. Contrasting fibrinolytic responses in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes. Diabetic Med. 1991; 8 954-959
- 36 Wiman B, Hamsten A. The fibrinolytic enzyme system and its role in the etiology of thromboembolic disease. Semin Thromb Haemost. 1990; 26 207-216
M. D. Yoshimasa Aso
Department of Medicine, Koshigaya Hospital, Dokkyo University School of Medicine
2-1-50 Minami-Koshigaya
Koshigaya, Saitama 343-8555
Japan
Phone: + 81489651111
Fax: + 81 4 89 65 11 27
Email: yaso@dokkyomed.ac.jp