Influence of Metabolic Control on Thromboxane Biosynthesis and Plasma Plasminogen Activator Inhibitor Type-1 in Non-insulin-dependent Diabetes mellitus

Summary

We have previously shown that tight metabolic control by insulin therapy reduced thromboxane-dependent platelet activation in noninsulin-dependent diabetes mellitus (NIDDM) patients. The present study was undertaken to determine whether a similar effect could be obtained without switching diabetics in secondary failure to insulin treatment. For this purpose, we gave strict diet and exercise advise program and adjusted on a weekly basis the oral antidiabetic therapy (glipizide) that 26 patients with NIDDM had been given over the previous months.

Basal measurements of urinary ll-dehydro-TXB₂ and PAI-1 confirmed previous findings of enhanced levels of these parameters in NIDDM patients with macrovascular disease in comparison to age-and sex-matched controls. After 2-6 weeks, 16 patients achieved tight metabolic control associated with significant reduction of both thromboxane biosynthesis and PAI-1 levels; 10 patients remained in poor control and no significant decrease of both parameters was observed.

We conclude that reduction of in-vivo platelet activation and PAI-1 antigen levels after metabolic improvement obtained by frequent reassessment of sulphonylurea therapy together with strict diet and exercise programs may have beneficial effects on the progression of diabetic micro- and macrovascular disease.

• References

• 1 Mustard JF, Packham MA. Platelets and diabetes mellitus. N Engl J Med 1984; 311: 665-667
• 2 Nathan MD. Long-term complications of diabetes mellitus. N Engl J Med 1993; 328: 1676-1685
• 3 Brownlee M. Glycation products and the pathogenesis of diabetic complications. Diabetes Care 1992; 15: 1835-1843
• 2 The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes in the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993 329. 977-986
• 5 Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes. Lancet 1993; 341: 1306-1309
• 6 Lasker RD. The diabetes control and complication trial implications for Policy and Practice. N Engl J Med 1993; 329: 1035-1036
• 7 Auwerk J, Bouillon R, Collen D, Geboers J. Tissue-type plasminogen antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 1988; 8: 68-72
• 8 Davi G, Catalano I, Avema M, Notarbartolo A, Strano A, Ciabattoni G, Patrono C. Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med 1990; 322: 1769-1774
• 9 Jokl R, Laimins M, Klein RL, Lyons TJ, Lopes-Virella MF, Colwell JA. Platelet plasminogen activator inhibitor 1 in patients with type II diabetes. Diabetes Care 1994; 171: 818-823
• 10 UK Prospective Diabetes Study Group. UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance. Diabetologia 1991 34. 877-901
• 11 National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979 28. 1039-1057
• 12 Ciabattoni G, Maclouf J, Catella F, FitzGerald GA, Patrono C. Radioimmunoassay of 11-dehydro-thromboxane B2 in human plasma and urine. Biochim Biophys Acta 1987; 918: 293-297
• 13 Siegel S. Nonparametric Statistics for the Behavioral Sciences. Me Graw-Hill Book Co: New York 1986; 184
• 14 Patrono C, Davi G. Antiplatelet agents in the prevention of diabetic vascular complications. Diabetes Metab Rev 1993; 9: 177-188
• 15 Davi G, Patrono C, Catalano I, Custro N, Giammarresi C, Ganci A, Cosen-tino F, Notarbartolo A. Inhibition of thromboxane biosynthesis and platelet function by indobufen in type II diabetes mellitus. Arterioscler Thromb 1993; 13: 1346-1349
• 16 Di Minno G, Silver MJ, Cerbone AM, Riccardi G, Rivellese A, Mancini M, Thiagarajan P. Increased binding of fibrinogen to platelets in diabetes: the role of prostaglandins and thromboxane. Blood 1985; 65: 156-162
• 17 Mayfield RK, Halushka PV, Wohltmann HJ, Lopes-Virella MF, Chambers JK, Loadholt CB, Colwell JA. Platelet function during continuous insulin infusion treatment in insulin-dependent diabetic patients. Diabetes 1985; 34: 1127-1133
• 18 Davi G, Avema M, Catalano I, Barbagallo CM, Giovenco E, Carroccio A, Notarbartolo A, Strano A. Platelet function in patients with type II diabetes mellitus: the effect of glycaemic control. Diabetes Res 1989; 10: 7-12
• 19 Kudlacek S, Schemthaner G. The effect of insulin treatment on HbAlc, body weight and lipids in type 2 diabetic patients with secondary-failure to sulfonylureas. A five-year follow-up study. Horm Metab Res 1992; 24: 455-500
• 20 Genuth S. Insulin use in NIDDM. Diabetes Care 1990; 13: 1240-1264
• 21 Donahue RP, Orchard TJ. Diabetes mellitus and macrovascular complications: an epidemiological perspective. Diabetes Care 1992; 15: 1141-1155
• 22 Birkeland KI, Furuseth K, Melander A, Mowinckel P, Vaaler S. Long term randomized placebo-controlled double-blind therapeutic comparison of glipizide and glyburide. Diabetes Care 1994; 17: 45-49
• 23 Ozaky Y, Yatoni Y, Kume S. Effects of oral hypoglycaemic agents on platelet functions. Biochem Pharmacol 1992; 44: 687-691
• 24 Vukovich T, Proidl S, Knobl P, Teufelsbauer H, Schnack C, Schemthaner 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
• 25 Knobl P, Schenhahaner G, Schnack C, Pietschmann P, Proidl S, Prager R, Vukovich T. Haemostatic abnormalities persist despite glycaemic improvement by insulin therapy in lean type 2 diabetic patients. Thromb Haemost 1994; 71: 692-697
• 26 Alessi MC, Juhan-Vague I, Kooistra T, Declerck PJ, Collen D. Insulin stimulates the synthesis of plasminogen activator inhibitor 1 by the human hepatocellular cell line Hep G2. Thromb Haemost 1988; 60: 491-494
• 27 Nordt TK, Klassen KJ, Schneider DJ, Sobel BE. 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