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Albuminuria is directly associated with increased plasma PAI-1 and factor VII levels in NIDDM patients
T Hirano1, K Kashiwazaki, Y Moritomo
1First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Insights
In patients with non-insulin-dependent diabetes mellitus (NIDDM), elevated plasminogen activator inhibitor type 1 (PAI-1) and coagulation factor VII (FVII) are linked to kidney damage. Insulin resistance broadly influences clotting factors, regardless of nephropathy.
Area of Science:
- Endocrinology
- Nephrology
- Cardiovascular Medicine
Background:
- Cardiovascular disease (CVD) risk is elevated in diabetic patients with nephropathy.
- Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), coagulation factor VII (FVII), and fibrinogen are recognized CVD risk factors.
Purpose of the Study:
- To investigate plasma levels of PAI-1, FVII activity, and fibrinogen in non-insulin-dependent diabetic mellitus (NIDDM) patients with varying degrees of nephropathy (normoalbuminuria, microalbuminuria, macroalbuminuria).
- To determine the association between these hemostatic factors, albumin excretion rate (AER), insulin resistance (estimated by steady state plasma glucose concentration - SSPG), and plasma triglyceride (TG) levels.
Main Methods:
- Plasma levels of PAI-1, FVII activity, and fibrinogen were measured in NIDDM patients across different albuminuria categories.
- Univariate and multiple regression analyses were performed to assess correlations between hemostatic factors, AER, SSPG, and TG.
Main Results:
- PAI-1 and FVII levels were significantly higher in NIDDM patients with overt nephropathy (macroalbuminuria) compared to those without nephropathy (normoalbuminuria).
- Fibrinogen levels did not differ significantly across albuminuria groups.
- PAI-1 and FVII levels correlated significantly with AER.
- PAI-1, FVII, and fibrinogen levels correlated with insulin resistance (SSPG).
- Multiple regression indicated AER was associated with PAI-1 and FVII, while insulin resistance (SSPG) independently correlated with PAI-1, FVII, and fibrinogen.
Conclusions:
- Elevated PAI-1 and FVII in NIDDM patients with nephropathy are directly associated with renal damage.
- Insulin resistance plays a significant role in regulating hemostatic components in NIDDM patients, irrespective of the presence or severity of nephropathy.
Abstract:
Increased plasma plasminogen activator inhibitor type 1 (PAI-1), coagulation 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 patients with nephropathy compared with those without nephropathy, we measured plasma levels of PAI-1, FVII activity and fibrinogen in non-insulin-dependent diabetic patients (NIDDM) with normoalbuminuria (without nephropathy), microalbuminuria (incipient nephropathy) and macroalbuminuria (overt nephropathy). PAI-1 and FVII levels were significantly increased in NIDDM with overt nephropathy compared with NIDDM without nephropathy. Fibrinogen levels were comparable between the patients with normo-, micro- and macro-albuminuria. Univariate regression analysis indicated that PAI-1 and FVII levels were significantly correlated with the albumin excretion rate (AER) in urine. PAI-1, FVII and fibrinogen levels were significantly correlated with the degree of insulin resistance estimated by the steady state plasma glucose concentration (SSPG) during the continuous infusion of glucose, insulin and octreotide. PAI-1 levels were correlated with plasma triglyceride (TG) levels. Multiple regression analysis revealed that AER was significantly associated with PAI-1 and FVII levels, whereas TG lost significant correlation with PAI-1 when AER, SSPG and plasma TG were entered as independent variables. SSPG retained an independent correlation with fibrinogen, PAI-1 and FVII levels. These results suggest that elevated plasma levels of PAI-1 and FVII in NIDDM patients with nephropathy are directly associated with renal damage, whereas insulin resistance widely regulates hemostatic components in NIDDM patients, irrespective of the presence of nephropathy.