Elevation of Factor Xla—α₁-Antitrypsin Complex Levels in NIDDM Patients With Diabetic Nephropathy

Abstract

Excess activated FXIa in plasma indicates hypercoagulability in the early contact phase. We have already developed methods for detecting the hypercoagulable state in clinical samples by our ELISA for complexed FXIa and α₁AT, which has been confirmed to be the predominant inhibitor of FXIa. Indiabetes, whether the activation of FXI is associated with the development of vascular complications remains unknown, although various hemostatic abnormalities have been described. We tested the complexed FXIa-α₁AT level in 45 NIDDM patients, who were divided into three groups according to the development of diabetic nephropathy, as assessed by UAE. Normoalbuminuria was defined as UAE <15 μg/min, microalbuminuria as UAE in the range of 15–200 μg/min, and albuminuria as UAE >200 μg/min. In the patients as a whole, FXIa-α₁AT and TAT levels were significantly increased compared with these levels in age-matched control subjects (17.3 ± 5.7 vs. 12.4 ± 2.4 ng/ml and 2.67 ± 1.23 vs. 1.93 ± 0.45 ng/ml, respectively). No significant difference was observed between FXIa-α₁AT levels in the control subjects and in the normoalbuminuric group (13.0 ± 2.1 ng/ml; n = 19). However, in the microalbuminuric (17.9 ± 3.9 ng/ml; n = 16) and albuminuric (24.1 ± 5.4 ng/ml; n = 10) groups, FXIa-α₁AT levels were significantly increased compared with those in the control and normoalbuminuric group. The TAT level was not correlated with FXIa-α₁AT, and no significant differences in its levels were found among these diabetic groups. We agree with the widely held belief that diabetic nephropathy is strongly related to widespread microangiopathy, and suggest that the FXIa-α₁AT level reflects vascular complications that occur concomitantly with such nephropathy. Therefore, we conclude that plasma FXIa-α₁AT levels may be of potential pathophysiological or clinical importance for detecting early diabetic microangiopathy.