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Abstract SUMMARY iabetes Mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia, resulting from defects in insulin secretion, insulin action or both. Type 1 diabetes mellitus is caused by deficiency of insulin secretion due to pancreatic β-cell damage. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs resulting in microvascular disease, such as nephropathy, retinopathy or neuropathy, and also macrovascular disease as atherosclerosis. In diabetes, microvascular disease may be mediated by disturbances in the levels of or balance of pro- and antiangiogenic factors, such as (anti-angiogenic) kallistatin. Kallistatin (KS) is a serine proteinase inhibitor (serpin), was first identified as a tissue kallikrein-binding protein. It has anti-angiogenic, anti-oxidant and anti-inflammatory effects, anti-tumor, vasodilator effects. KS is synthesized primarily in the liver, but it is also widely expressed in organs such as the kidney, heart, and blood vessels. It has been found elevated in serum samples of patients with diabetes. However, circulating kallistatin levels in type 1 diabetic children and adolescents have not been widely explored. Our study aimed to determine the level of serum Kallistatin in children and adolescents with type 1 diabetes as an early marker for micro-vascular complications as nephropathy, retinopathy or neuropathy and assess its relation to clinicolaboratory characteristics of the patients. Plasma Kallistatin levels were determined by immunosorbent assay (ELISA). This cross sectional study was carried out on 65 children and adolescents with type 1 DM, with disease duration 5 years or more, attending the Pediatric Diabetes Clinic, Ain Shams University, from from April 2012 to April 2013. Their mean age was 14.1 ± 2.6 years (range, 9-18years), with mean disease duration 6.9 ± 1.7 years. Another group of 35 age- and sexmatched healthy individuals was enrolled as controls with a mean age was 13.2 ± 3.4 years (range, 4-18 years). All included patients were subjected to detailed medical history (age of onset of diabetes, diabetes duration, insulin therapy, acute metabolic complications, symptomatic hypoglycemic attacks or episodes of diabetic ketoacidosis and chronic microvascular complications: retinopathy and neuropathy, thorough clinical examination stress on asessment of anthropometric measures and routine work up including; FBG, fasting lipid profile, mean HbA1c%, and CRP. Also, serum levels of Kallistatin were measured (ELISA). The studied diabetic patients were subdivided into 2 groups: patients with microvascular complication 49.2% (32 patients) and patients without 50.8% (33 patients). Among patients with complication the percentage of each complication was as follows: diabetic nephropathy (32.3%), retinopathy (10.7%), peripheral neuropathy (12.3%). The mean serum kallistatin levels were significantly increased in patients with micro-vascular complications (9.53 ± 1.9 ng/ml) and non-complicated patients (4.3 ± 1.54 ng/ml) compared to healthy controls (1.39 ± 0.55 ng/ml) (p<0.01). Furthermore, comparison of mean serum kallistatin levels between type 1 diabetic patients with different stages of albuminuria revealed that patients with microalbuminuria (9.05 ± 2.15 ng/ml) had increased levels than normoalbuminuric patients (6.48 ± 3.15 ng/ml ) (p<0.01). Also mean serum kallistatin levels was correlated to each single diabetic complication as follows, in nephropathy (9.5 ± 1.6), retinopathy (7.58 ± 1.59 ng/ml), peripheral neuropathy (10.7 ± 1.86 ng/ml). Patients with microvascular complications showed to have longer diabetes duration, higher systolic and diastolic blood pressure, mean fasting blood sugar, HbA1C, CRP, triglycerides, total cholesterol, LDL and serum kallistatin. And lower HDL than patients without complications. A significant positive correlation was found between mean serum kallistatin levels diabetes duration, systolic BP, diastolic BP, FBS, HbA1c, triglycerides, total cholesterol and LDL and a significant negative correlation with HDL it type 1 diabetic patients. Multiregression linear analysis showed that FBS, HbA1c, cholesterol and LDL were independently related to mean serum kallistatin levels in type 1 diabetics. ROC curve analysis revealed that the cutoff value of serum kallistatin at >6.0 ng/mL could differentiate complicated from non-complicated cases with a sensitivity of 96.87%, specificity of 93.75% and area under the curve was 0.979. |