الفهرس 
DIABETES MELLITUSOnly 14 pages are availabe for public view
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Abstract
Background: Plasminogen activator inhibitor 1 (PAI-1) is a fast-acting inhibitor of fibrinolysis that has been linked to increased risk of thrombosis. It plays a critical role in the insulin resistance syndrome, which leads to type 2 diabetes mellitus, and is associated with its side effects such as an increased risk of diabetic nephropathy and atherosclerotic cardiovascular disease. Objectives: We determined serum PAI-1 in children and adolescents with type 1 diabetes as a potential marker for vascular complications and assess its relation to glycemic control and carotid intima media thickness (CIMT) as synergistic risk factors for development of atherosclerosis. Materials and methods: This case control cross sectional study was carried out on 60 children and adolescents with type 1 diabetes (42 females and 18 males) with a mean age of 14.5 ± 2.8 years. Patients were recruited from pediatrics diabetes clinic, Ain shams university and compared with 25 age- and sex-matched healthy controls. Patients were subjected to detailed medical history with special emphasis on disease duration and insulin therapy, thorough clinical examination and laboratory assessment of fasting serum lipid profile, HbA1c and the presence of microvascular complications. PAI-1 was measured by enzyme linked immunosorbent assay (ELISA). CIMT of the common carotid artery was measured using high resolution ultrasonography. Results: PAI-1 levels were significantly elevated in all diabetic patients compared with controls (33.2 ± 8 versus 13.4 ± 4.1 ng/mL; p<0.001). When type 1 diabetic patients were classified into two subgroups according to the highest level of PAI-1 observed in healthy controls (23ng/mL), patients with high PAI-1 levels >23 ng/mL had higher HbA1c, serum lipids and CIMT compared with those with PAI-1 levels ≤ 23 ng/mL (p<0.05). Mean PAI-1 levels were also significantly increased in patients with microvascular complications (42.7 ± 8.8 ng/mL) and non-complicated patients (27.9 ± 6.1 ng/mL) compared with healthy controls with highest levels found in complicated patients (p<0.001). PAI-1 levels were also significantly increased in diabetic patients with microalbuminuria compared with normoalbuminuric group (p<0.001) and patients with peripheral neuropathy compared with those without (p<0.001). CIMT was significantly higher in patient group, particularly patients with microvascular complications, than controls or non-complicated patients. Significant positive correlations were found between PAI-1 levels and RBG, HbA1c, and CIMT (p<0.05). Conclusions: We suggest that PAI-1 levels are elevated in type 1 diabetic patients, particularly those with microvascular complications. Therefore, a hypercoagulable state, as indicated by elevated PAI-1 levels, may be one of the responsible factors for the development of microvascular complications in type 1 diabetes mellitus. Hyperglycemia, dyslipidemia and poor glycemic control may be significant factors contributing to increased PAI-1 levels. PAI-1 was positively correlated to CIMT suggesting a link between diabetic micro-and macro-angiopathy. Measurement of PAI-1 and CIMT, as early indicators of subclinical atherosclerosis in poorly controlled patients would help to identify those at high risk of developing cardiovascular complications or progression of renal disease who could benefit from intensive insulin therapy and reno-protective agents.
Keywords: Type 1 diabetes, plasminogen activator inhibitor-1, carotid intima media thickness.