Evaluación de inhibidores fisiológicos de la coagulación en pacientes diabéticos tipo 2 / Evaluation about coagulation physiological inhibitors in type 2 diabetic patients

La diabetes mellitus está asociada a disturbios en la hemostasis que pueden contribuir al desarrollo de enfermedad vascular diabética. El objetivo de este trabajo fue estudiar la coagulación en una población diabética de Uruguay y compararla con una población de referencia normal. Se trabajó con 100 pacientes diabéticos tipo 2, de ambos sexos (49 mujeres y 51 hombres), con edades comprendidas entre 42 y 79 años, y una población control representada por 130 individuos aparentemente sanos (73 mujeres y 57 hombres) cuyas edades oscilaron entre 37 y 78 años, los que fueron tomados como referencia. Se realizaron las determinaciones de tiempo de protrombina (TP), fibrinógeno (Fib), proteína C (PC), proteína S (PS), antitrombina III (ATIII) e inhibidor del activador de plasminógeno (PAI) en plasma citratado. El TP y el Fib se realizaron por nefelometría, la PC, ATIII y PAI se midieron cromogénicamente y la PS se determinó por coagulometría. Se encontró que los inhibidores fisiológicos de la coagulación PS y ATIII son significativamente menores en la población diabética, en tanto que los factores procoagulantes Fib y PAI son significativamente mayores, comparados con la población de referencia. De los hallazgos precedentes se confirma una tendencia a un disbalance hemostático que contribuiría al estado protrombótico que acompaña a un alto porcentaje de la población diabética.

Diabetes mellitus is associated with disturbances in hemostasis, which may contribute to the development of diabetic vascular disease. Coagulation tests were performed both in diabetic patients and healthy individuals in Uruguay. The results obtained were compared. Diabetic patients were 100, with ages between 42 and 79 years, 49 females and 51 males. Reference population were 130 healthy individuals between 37 and 78 years, 73 females and 57 males. Prothrombin time (PT), fibrinogen( Fib), protein C (PC), protein S (PS), antithrombin III (ATIII) and plasminogen activator inhibitor (PAI) were measured on citrated plasma. PT and Fib were determined nephelometrically, PC, ATIII y PAI were measured cromogenically and PS was determined by coagulometry. Coagulation physiological inhibitors outcomes such as PS and ATIII showed significantly lower levels in the diabetic patient than in the healthy person, and at the same time, Fib and PAI, which are procoagulant factors, have significantly higher concentrations in the diabetic patient than in the healthy person. These findings permit to assess that an impaired haemostatic balance is present in the diabetic population, which may contribute to the hypercoagulability that accompanies a high percentage of these patients.

Potential role of thrombin-activatable fibrinolysis inhibitor [TAFI] in diabetic nephropathy and its relation to degree of albuminuria and to dialysis modality

Diabetic nephropathy has become the most prevalent cause of end-stage renal disease [ESRD] in many countries, and about one third of patients with diabetic nephropathy progress to end stage renal disease. Patients with end-stage renal disease dialyzed due to diabetic nephropathy are at higher risk of death due to cardiovascular complications than dialyzed non-diabetic patients. Hypofibrinolysis is a common finding in patients with diabetes mellitus and a risk factor for diabetic nephropathy and may play a role in the vascular complications in dialyzed diabetic patients. A new potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor [TAFI], has been isolated from human plasma. However, the relation between plasma TAFI level and diabetic nephropathy has not been well appraised. In the present study, we investigated the plasma levels of TAFI in 50 type 2 diabetic patients: 10 with normoalbuminuria, 10 with microalbuminuria, 10 with macroalbuminuria, 10 with ESRD on haemodialysis, and 10 with ESRD on peritoneal dialysis. Also, we assessed albumin/creatinine ratio in albumiuric patients, blood urea, serum creatinine, serum lipids, and ECG. The plasma level of TAFI in diabetic patients with macroalbuminuria was significantly higher than the level in diabetic patients with microalbuminuria [P < 0.00l], and higher in micro-albuminuric patients than in normolbuminuric patients[P < 0.00l]. Plasma TAFI level was correlated to albumin/craetinine ratio[P < 0.00l], blood urea[P < 0.00l] and serum creatinine[P < 0.00l] in patients with micro-albuminuria [non dialyzed patients]. Moreover, it was significantly higher in patients with diabetic nephropathy and on peritoneal dialysis than those on haemodialysis [P < 0.01] and it was correlated positively with triglycerides [P < 0.05] and negatively with HDL-c[P < 0.05]. These data suggest that TFAI level was increased by the progression of diabetic nephropathy as it was significantly higher in. patients reaching ESRD [haemodialysis and peritoneal dialysis groups]than in those still in the stages of micro and rnacro-albuminuria and higher in macroalbuminuric patients than in microalbuminuric patients. Also TAFI level was significantly positive correlated with tile indicators of decline in renal function [blood urea, serum creatinine, urinary albumin and urinary albumin/creatinine ratio]. So we can concluded that increased plasma level of TAFI may contribute to the pathogenesis and progression of diabetic nephropathy and may have role in tile cardiovascular complications of dialyzed diabetic patients, especially those under peritoneal dialysis