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Thrombin generation and factor VIII:C levels in patients with type 1 diabetes complicated by nephropathy
S H Ibbotson1, H Rayner, M H Stickland
1Academic Unit of Medicine, Leeds General Infirmary, UK.
Insights
Elevated Factor VIII:C levels are linked to diabetic nephropathy in Type 1 diabetes patients, correlating with kidney function but not blood sugar control. Plasma coagulant activity did not show increased enhancement.
Area of Science:
- Endocrinology and Metabolism
- Nephrology
- Hematology
Background:
- Diabetic nephropathy is a serious complication of Type 1 diabetes.
- Understanding the role of coagulation factors in diabetic nephropathy is crucial for risk assessment and management.
Purpose of the Study:
- To investigate the association between plasma coagulant activity, specifically Factor VIII:C (FVIII:C) and thrombin generation, and the presence of diabetic nephropathy in Type 1 diabetes patients.
- To explore the relationship of FVIII:C with glycaemic control and renal function.
Main Methods:
- Studied 31 Type 1 diabetes patients (12 with nephropathy, 19 without) and 11 healthy controls.
- Assessed thrombin generation using a computer-assisted chromogenic method (T50).
- Measured Factor VIII:C levels and correlated them with age, renal function (urinary albumin excretion, creatinine clearance), and glycaemic control (HbA1c).
Main Results:
- Median FVIII:C concentration was significantly increased in patients with diabetic nephropathy compared to those without and healthy controls (p < 0.01).
- FVIII:C levels correlated with age and were related to urinary albumin excretion and creatinine clearance, indicating a link with renal impairment.
- No significant differences in thrombin generation (T50) were observed between groups, and FVIII:C and T50 were not related to HbA1c levels.
Conclusions:
- Factor VIII:C levels are elevated in Type 1 diabetes patients with nephropathy and are associated with the degree of renal impairment.
- Increased FVIII:C in diabetic nephropathy does not appear to be driven by glycaemic control.
- No overall enhancement of plasma procoagulant activity was detected despite elevated FVIII:C in nephropathy.
Abstract:
The association between plasma coagulant activity and the presence of diabetic nephropathy was investigated in 31 patients with Type 1 diabetes, 12 with and 19 without nephropathy, and in 11 healthy subjects. Thrombin generation was assessed by computer assisted chromogenic method and expressed as time (in seconds) to 50% maximal thrombin activity (T50). Factor VIII:C levels related to thrombin activity, glycaemic control, and renal function. Median (IQ) FVIII:C concentration was increased in patients with nephropathy (1590 (1130-1900) IU l-1) compared to those without renal disease and with controls (960 (750-1090); 1020 (810-1100) IU l-1, p < 0.01, respectively). There were no significant differences in T50 values between the groups. FVIII:C correlated with age in all subjects and in the diabetic group (r = 0.33, p = 0.036; r = 0.39, p = 0.031) and inversely with T50 in all subjects and in controls (r = -0.35, p = 0.02; r = -0.62, p = 0.04). In all subjects and in patients, FVIII:C was related to urinary albumin excretion and creatinine clearance. FVIII:C and T50 were not related to HbA1c. The results show that FVIII:C levels are increased in Type 1 diabetes complicated by nephropathy and are related to degree of renal impairment but not levels of glycaemia. No associated enhancement of plasma procoagulant activity was detected.