الفهرس 
Diabetic NephropathyOnly 14 pages are availabe for public view
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Abstract
D
iabetes mellitus is a chronic metabolic disorder characterized by high plasma glucose caused by an impairment of insulin production, insulin action or both.
The chronic hyperglycemia of diabetes is accompanied with long-term damage, failure, and dysfunction of many organs, particularly the kidneys, nerves, eyes, blood, and heart. Promotion of vascular damage and oxidative stress occurs due to prolonged hyperglycemia and dyslipidemia which also accelerates endothelial dysfunction which is associated with macro vascular and micro vascular complications.
Glucose overload may damage the cells through oxidative stress, clinical and experimental studies showed that oxidative stress plays a main role in the pathogenesis of type 1 and type 2 diabetes mellitus. Free radicals are formed excessively in diabetes by glucose oxidation, the subsequent oxidative degradation of glycated proteins and the non-enzymatic glycation of proteins.
Carnosine (β-alanyl-L-histidine) which is a natural polypeptide found in skeletal muscle, cardiac muscle and brain. Carnosine has antiglycating and antioxidant properties in addition to heavy metal sequestering and pH-buffering action.
Carnosine is recommended for patients under oxidative stress as an effective natural therapy that has no side effects.Moreover, carnosine decreases elevated blood sugar levels, lessens long-term formation of hazardous advanced glycation end-products, prevents protein cross-linking and reduces oxidant stress, not only in diabetic patients but also in other healthy aging adults. Further, it reduces the risk of diabetic kidney disease by protecting kidney cells from the effects of high levels of glucose.
In view of these data, we study the role of carnosine as an adjuvant therapy for diabetic nephropathy in children and adolescents with type 1 diabetes and assess its relation to oxidative stress, glycemic control and micro albuminuria
This study was carried out on 90 children and adolescents with type 1 diabetes mellitus (24males and 66 females) attending the Pediatric Diabetes Clinic, Pediatric Hospital, Ain Shams University. They were compared to 40 age- and sex-matched healthy subjects served as controls. The control group consisted of 13 males and 27 females. The mean age of patients was 12.8 ± 3.3 years (range, 9-18 years) while that of controls was 12.7 ± 3.1 years (range, 7-16 years).
Each of the eligible children was randomly assigned by simple randomization to either group I or group II.
group I (Study group): consists of 45 pediatric patients having type 1 diabetes and nephropathy. Patients received oral carnosine capsules (NOW FOODS ® Company for Natural products manufactured by GMP Pharma, Bloomingdale, IL 60108, USA). The capsules of L- carnosine contain 500 mg of β-alanyl-L-histidine administered orally in two divided doses for three months.
group II (DN control group): consists of 45 pediatric patients having type 1 diabetes and nephropathy without carnosine supplementation.
Patients in both groups received oral angiotensin-converting enzyme inhibitors (ACE-Is) captopril 25 mg tablet (manufactured by SmithKline Beecham-Egypt L.L.C. an affiliated company to GlaxoSmithKline) provided their blood pressure could be maintained within normal range for age.
group III (Healthy control group): consists of 40 age- and sex-matched healthy controls.
All included patients were subjected to i) detailed medical history with special emphasis on age of onset of diabetes and disease duration, family history: paternal or maternal diabetes, hypertension, and frequency of monitoring of blood glucose, insulin therapy, symptoms of diabetic complications, the frequency and severity of hypoglycemia (sweating, headache, blurring) and diabetic ketoacidosis and chronic complications; micro-vascular complications (nephropathy [puffy eye lids and lower limb edema], edema.
ii) thorough clinical examination laying stress on assessment of anthropometric measures including weight in kilograms (Kg), height in centimeters (cm) and body mass index (BMI SDS), blood pressure (mmHg), vital data: pulse, temperature, complete examination including chest, heart, abdomen and especial emphasis on neurological examination for evidence of any diabetic complications.
iii) Laboratory investigations including measurement of mean fasting blood glucose levels in the last 3 months prior to the study, routine liver and kidney function tests including serum creatinine, assessment of mean HbA1c%, urinary albumin excretion (UAE) in an early morning fasting urine sample as albumin-to-creatinine ratio, alpha 1-microglobulin, serum total antioxidant capacity (TAC) as a marker of oxidative, serum levels of MDA as a marker of lipid peroxidation by measuring the production of thiobarbituric Acid.
Upon comparison between baseline clinical data among diabetic nephropathy patients with and without carnosine supplementation, no significant difference was found as regards age, sex, disease duration, weight SDS, height SDS, BMI SDS, pubertal staging, blood pressure and insulin doses (p>0.05).
Comparison between markers of oxidative stress and alpha 1-microglobulin between the two diabetic groups and healthy controls showed that TAC and MDA, as well as alpha 1-microglobulin, were significantly higher among the two patients’ groups than healthy controls (p<0.001).
No significant difference was between baseline laboratory data among diabetic nephropathy patients with and without carnosine therapy (p>0.05).
Comparison between diabetic nephropathy patients with carnosine at baseline and post-therapy showed significantly lower FBG, HbA1c, MDA, UACR and alpha 1 microglobulin while TAC was significantly higher at the end of follow up (p<0.05).
No significant difference between diabetic nephropathy patients who did not receive carnosine at baseline and end of study as regards oxidative stress markers and renal markers (p>0.05).
Comparison between diabetic nephropathy patients with and without carnosine therapy at the end of the study revealed significantly lower FBG, HbA1c, UACR, alpha 1 miroglobulin and MDA while TAC was significantly increased in patients who received carnosine compared with the other group (p<0.05).
There were significant negative correlations between baseline TAC and HbA1c as well as alpha1-microglobulin among diabetic nephropathy patients with carnosine.
There were significant negative correlations between baseline TAC and FBG among diabetic nephropathy patients without carnosine supplementation.