الفهرس 
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Abstract
Type 1 diabetes mellitus (T1DM) is associated with an increased risk of vascular complications, and T1DM patients with proteinuria and/or retinopathy have a significantly increased risk of fatal coronary artery disease . Inflammation plays a pivotal role in all stages of atherosclerosis. The monocyte-macrophage, a crucial cell in atherogenesis, is readily accessible for study. Several researches had demonstrated that patients with T1DM exhibit increased inflammation as evidenced by increased monocyte activity, and these are more pronounced in T1DM with microvascular complications.
Members of the toll-like receptors (TLRs) family play a critical role in the inflammatory components of atherosclerosis. Toll-like receptors are a family of pattern recognition receptors that are important in the regulation of immune function and inflammation. Their activation by various ligands triggers a signaling cascade leading to cytokine production and initiation of an adaptive immune response.
The aim of this study was to asses expression of toll-like receptor 2 and 4 in monocytes in type 1 diabetes mellitus and its relation to presence of diabetic micro vascular complications
Our study was conducted on 80 subjects with age ranging from 18-35 years old, selected from the inpatient & outpatient clinic of internal medicine, endocrinology departments of Ain Shams University hospitals from March 2011 to August 2011 They were divided into the following groups: Group I: 20patients with type 1 diabetes mellitus above age of 18 years with duration of diabetes 1 year or more without any diabetic complications. Group II: 20 patients with type 1 diabetes mellitus and diabetic retinopathy and this group is divided into 2 sub groups: Group Iia:9 patients with non – proliferative diabetic retinopathy Group Iib:11 patients with proliferative diabetic retinopathy. Group III:20 patients with type 1 diabetes mellitus and diabetic nephropathy and this group is divided into 2 sub groups: Group IIIa: 7 patients with micro-albuminuria. Group IIIb: 13 patients with macro-albuminuria. Group IV: 20 healthy subjects above age of 18 years with no family history of diabetes or other chronic diseases.
The patients and control groups are matched as regard age and sex.
All subjects will be subjected to the following: Full medical history, clinical examination, laboratory investigation including: FPG (mg/dl), (HbA1c)%, Albumin / creatinine ratio (μg /ml) in random urine sample.TLR2 (%) and TLR4(%) using flowcytometry and fundus Examination.
The results were statistically analyzed and we observed the following:
TLR2 percent was higher in T1DM with microvascular complications (94.5+3.1)% and T1DM without micro-vascular complications (69.5+7.7)% than in healthy control subjects (49+4.7)% and the difference was highly statistically significant (p-value<0.01).
TLR4 percent was higher in T1DM with microvascular complication (86.5 + 3.5)% and T1DM without microvascular complication (53.5 + 6.2)% than in healthy control subjects (40.5 + 5.3)% and the difference was highly statistically significant (p-value<0.01).
Regarding albuminuria level there was a high statistical significant difference between the studied groups being higher in group III (396.5 ±186.5) µg/ml, than group II (26.5±2.9) µg/ml, followed by group I (24.5±2.1) µg/ml, and group IV (17.6±3.5) µg/ml (p-value < 0.01).
On comparing between diabetic patients with microalbuminuria and patients with macroalbuminuria: They were 7patients with microalbuminuria and 13 patients with macroalbuminuria.
There was no statistical significant difference between both groups regarding age (28.7 ± 1.3 vs. 30.4± 2.3) years respectively, gender and BMI (24.1±1.6 vs. 25.5±2) kg/m² respectively (p-value>0.05).
There was a highly significant statistical difference between both groups as regards age of onset of diabetes (13.7+1.1 vs.8.07+4.07) years old respectively, duration of diabetes (15+1.4 vs 22.3+4.07) years respectively, systolic blood pressure (125 + 5 vs.132.6 + 9.9) mm/Hg respectively and diastolic blood pressure (73.5 + 3.7 vs.83.8+ 8.2) mm/Hg respectively, fasting plasma glucose (162+15.3 vs. 220.3+42.6) mg/dl respectively .HbA1c (8.1+0.2 vs. 9.3+0.8) % respectively ,T LR2 (92.6+1.8 vs. 96.2 +3.01)% respectively and TLR4 (85.9+3.1 vs. 86.8+3.8)% respectively.(p –value <0.01). We found that 7 patients with microalbuminuria had non–proliferative diabetic retinopathy and 13 patients with macroalbuminuria had proliferative diabetic retinopathy.
On comparing between diabetic patients with non – proliferative diabetic retinopathy and patients with proliferative diabetic retinopathy: They were 19 patients with non–proliferative diabetic retinopathy and 21 patients with proliferative diabetic retinopathy.
There was no statistical significant difference between both groups regarding age (26.6± 3.4 vs. 27.7± 4) years respectively, gender and BMI (25±1.5vs. 25.1±2.2) kg/m² respectively (p-value>0.05).
There was a highly significant statistical difference between both groups as regards age of onset of diabetes (13.8+3vs.10.6+4.7) years old respectively, duration of diabetes (12.6+3.9 vs 17.5+6.5) years respectively, systolic blood pressure (121.5 + 7.4 vs.133.2 + 8.5) mm/Hg respectively and diastolic blood pressure (74.7+ 4.5 vs.83+7.1) mm/Hg respectively, fasting plasma glucose (170.3 + 18.6vs.211.7 +36) mg/dl respectively HbA1c (8.2 + 0.2 vs.9 + 0.8) % respectively, T LR2 (90.6+3.9 vs. 95.6 +3)% respectively and TLR4 (81.2+6 vs. 81 + 7.5)% respectively .(p –value <0.01).
We found that 7 patients with non – proliferative diabetic retinopathy had microalbuminuria and 3 patients with non – proliferative diabetic retinopathy had macroalbuminuria, we found that 9 patients had only non – proliferative diabetic retinopathy without albuminuria.10 patients with proliferative diabetic retinopathy had macroalbuminuria.11 patients had only proliferative diabetic retinopathy without albuminuria.
There was a high statistical significant positive correlation between TLR2 in all studied groups regarding age of onset of diabetes (r=0.68), and duration of diabetes (r=0.85), systolic blood pressure (r=0.85), diastolic blood pressure (r=0.85). FPG (r=0.84).HbA1c (r=0.88), and albuminuria (r=0.53) (p-value <0.01).
There was a high statistical significant positive correlation between TLR4 in all studied groups regarding age of onset of diabetes (r=0.57) and duration of diabetes (r=0.87), systolic blood pressure (r=0.57), diastolic blood pressure (r=0.27). FBG (r=0.77). HbA1c (r=0.83), and albuminuria (r=0.62) (p-value <0.01).
In conclusion, our results showed that type 1 diabetic patients with micro vascular complications had a significant increase expression of TLR2 and TLR4 on monocytes (vs matched controls). These finding suggest the need for ongoing evaluation of possible protective role of blocking TLR2 and TLR4 in the development of diabetic microvascular complications.