ALBUMINURIA IS DIRECTLY ASSOCIATED WITH INCREASED PLASMA PAI-1 AND FACTOR-VII LEVELS IN NIDDM PATIENTS

Increased plasma plasminogen activator inhibitor type 1 (PAI-1), coagu lation factor VII (FVII) and fibrinogen levels have been recognized as risk factors for cardiovascular disease. Because a substantially high incidence of cardiovascular disease has been reported in diabetic pat ients with nephropathy compared with those without nephropathy, we mea sured plasma levels of PAI-1, FVII activity and fibrinogen in non-insu lin-dependent diabetic patients (NIDDM) with normoalbuminuria (without nephropathy), microalbuminuria (incipient nephropathy) and macroalbum inuria (overt nephropathy). PAI-1 and FVII levels were significantly i ncreased in NIDDM with overt nephropathy compared with NIDDM without n ephropathy. Fibrinogen levels were comparable between the patients wit h normo-, micro- and macro-albuminuria. Univariate regression analysis indicated that PAI-1 and FVII levels were significantly correlated wi th the albumin excretion rate (AER) in urine. PAI-1, FVII and fibrinog en levels were significantly correlated with the degree of insulin res istance estimated by the steady state plasma glucose concentration (SS PG) during the continuous infusion of glucose, insulin and octreotide. PAI-1 levels were correlated with plasma triglyceride (TG) levels. Mu ltiple regression analysis revealed that AER was significantly associa ted with PAI-1 and FVII levels, whereas TG lost significant correlatio n with PAI-1 when AER, SSPG and plasma TG were entered as independent variables. SSPG retained an independent correlation with fibrinogen, P AI-1 and FVII levels. These results suggest that elevated plasma level s of PAI-1 and FVII in NIDDM patients with nephropathy are directly as sociated with renal damage, whereas insulin resistance widely regulate s hemostatic components in NIDDM patients, irrespective of the presenc e of nephropathy. (C) 1997 Elsevier Science Ireland Ltd.