Urinary markers for early detection of Diabetic Nephropathy in type 1 Diabetes Mellitus

Background: diabetic nephropathy [DN] is a serious complication of diabetic mellitus associated with increased risk of morbidity and mortality. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney functions and improve patient outcomes. N-acetyl Beta d-glucosaminidase [NAG] is a lysosomal enzyme, present in high concentrations in renal proximal tubular cells, Gamma-glutamyltransferase [GGT] is an enzyme which located along the proximal tubular brush border, Malondialdehyde [MDA] is a highly toxic product, formed in part by lipid oxidation derived free radicals, Reactive carbonyl derivatives [RCD[S]] is an oxidative stress marker in urine, as a measure of the oxidative modification of proteins and beta-2-microglobulin is filtered by the glomerulus, absorbed and catabolized by the proximal tubules. The aim of this study is to investigate the urinary outcome of these markers as early detectors of diabetic nephropathy in type 1 diabetic children

Subjects and methods: This case-control study included 67 children with type 1 diabetes mellitus [33 male; 34 female], age [11.03 +/- 1.05 years] and thirty one age [10.58 +/- 1.11 years] and sex [13 male; 18 female] matched healthy children [13 male; 18 female]. Type 1 diabetic children were further subdivided into microalbuminuric and normoalbuminuric subgroups according to microalbuminuria concentration [30 mg/ g creatinine]. Age, sex, diabetic duration and the current daily insulin dose, and family history of diabetes, weight, height, body mass index, systolic and diastolic blood pressure were recorded. Fasting plasma glucose, glycated hemoglobin, blood urea nitrogen, plasma creatinine, urinary creatinine, micoalbumin, N-acetyl-B-D glucosaminidase [NAG], Gama glutamyl transferase [GGT], Beta-2-microglobulin, Malondialdehyde [MDA] and Reactive carbonyl groups [RCDS[S]] were measured in all subjects

Results: a significant increase in tubular injury markers of diabetes [NAG, GGT, beta-2-microglobulin] and oxidative stress parameters [MDA, RCDS[S]] as compared to control subjects was found. Microalbuminuric subjects showed a significant elevatation in the urinary markers including NAG, GGT, beta-2-microglobulin, MDA, RCDS[S] as compared to normoalbuminuric subjects. The studied urinary tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta-2- microglobulin showed positive correlations with one another

Conclusion: The results of this study introduced the possibility of depending on tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta2 microglobulin as early, reliable, and sensitive predictors for diabetic nephropathy. The NAG activity index proved to be the most sensitive biomarker, then beta-2- microglobulin for early discovering the tubule cells damage

Retrospective epidemiological study, with focus on acute and chronic managements, of patients attended the pediatric outpatient clinic of National Institute of Diabetes and Endocrinology, Cairo, Egypt

Diabetes mellitus is the most common endocrine metabolic disorder of childhood. It is widely spread all over Egypt as its prevalence was found to be 1.09 per 1000 among school aged children. The aim of this work was to do a retrospective epidemiological study of the records of diabetic children attended the outpatient pediatric clinic in NIDE. The files of 851 diabetic children were examined retrospectively without any reference to the personal data. Out of them, the files of 200 diabetic patients were also studied for determination of chronic management results represented by the type of insulin regimen used and estimation of the daily insulin dose per kg. We also assessed the outcome management of acute ketoacidosis from the files of 200 patients admitted to the ICU and npatient departments. All the resulted data had been subjected to SPSS statistical program. The results showed that there is no statistical differences between male, [n = 424] to female, [n = 427] distribution. The results of this retrospective study showed that the mean age of onset of diabetes in children attended the outpatient pediatric clinic of National Institute of Diabetes was [mean = 8.37 10.96 y]. The present study showed also that there was a decrease of age of onset of diabetes among diabetic children as the age of onset between 5- <10 years were the highest percentage [46%]. As regards the insulin regimen used by the diabetic children, 17.5% used conventional insulin therapy, 11% used modified insulin therapy as they used regular insulin before lunch, and 71.5% used basal-bolus insulin regimen. The mean percentage of insulin unites per Kg. was 1.00 + 0.38 U/kg./day. The mean BMI was = 24.54 + 6.42, while the BMI distribution was: 56% were with normal weight = < 25, 27% were overweight = 25: < 30, 14% were obese = 30: < 40 and only 3% were with severe obesity where BMI = > 40. The results showed also that 34.8% of the diabetic patients were doing continues home blood glucose monitoring with glucose sensors, 25.8% were doing the monitoring only with visual strips, while 39.4% of the diabetic children were not doing home monitoring at all. The study of control of diabetes showed that the glycated HbA Ic was < 7% in 31%, 7-8% in 22%, > 8-9% in 14% and > 9% in 33%. As regards the diabetic patients with ketoacidosis, 39% of them were diagnosed as the first presentation of diabetes. The duration required, for ketoacidosis, to be resolved was < 6 hr. in 44%, 6-12 hr. in 38.6%, > 12-24 hr. in 12.6%, and > 24% in only 3.8%. The results showed, also, that only 4.3% of DKA-cases were with PH < 7.0, 8.7% were with PH = 7: 7.1, 7.7% were with PH> 7.1: 7.2, 32.4% were with PH > 7.2: 7.3 and 7.2% only were with PH > 7.3. The above results showed also that 13.0% of ketotic cases were with severe acidosis, 7.7% were with moderate acidosis, and 32.4% were with mild acidosis. The discussion of these results documented that it will be essential to follow the international guidelines of management of type 1 diabetes and it was recommended to do proper diagnosis of different types ol diabetes among diabetic children and to study the prevalence anc incidence of diabetes among Egyptian children as the prevalent L and incidence still uncertain till now

Study of various epidemiological and metabolic criteria in diabetic children and adolescence attending pediatric outpatient clinic of NIDE

Type 1 diabetes mellitus is one of the greatest challenges in public health and one of the most frequent chronic diseases in the pediatric age. The aim of this study was to study the epidemiological and metabolic criteria of 398 diabetic children who attended the outpatient pediatric clinic with determination of beta cell function of theses patients. Study of the age of onset of diabetes, sex distribution, residency, with other epidemiological factors among diabetic patients, attended the outpatient clinic of NIDE during year 2008, who accepted to participate in this study. All patients were subjected to full history taking, thorough clinical examination and full laboratory investigations including: CBC, liver enzymes, s. creatinine, lipid profile, including total cholesterol LDL-cholesterol, HDL-cholesterol and triglycerides, fasting c-peptide, Glycated HbA1c, and estimation of microalbuminuria. There was positive correlations between: Age [mean = 10.34 +/- 12.7 y.] and BMI [mean = 27.79 +/- 8.66 kg/m2], systolic B.P. [105.23 + 6.86 mmHg.] and total cholesterol [mean = 175.74 +/- 38.09 mg/dl] and systolic B.P. and triglycerides [mean = 83.88 +/- 47.46 mg/dl], and a highly positive correlations as regarding age [mean = 10.34 +/- 12.7 y.] and glycated HbA1c [mean = 9.79 +/- 2.38%]. There were no significant difference between diabetic group with c-peptide < 1 ng/ml and group with preserved beta cell function with c-peptide> 1 ng/ml as regards: Glycated HbA1c, s. cholesterol, s. cholesterol LDL, microalbuminuria, BMI and age. While there was a positive statistical difference between both groups as regards s. triglycerides [mean=75.27+31.17mg/ dl and 102.27+49.6 mg/dl]. There was no significant difference as regarding sex distribution as the female percentage was 51% while male represented 49%. The family history of diabetes was positive in 6.7% as regards father, 5.2% as regards mother, 4% as regards siblings. The study of beta cell function was done through estimation of fasting c-peptide levels. 93.7% were with fasting c-peptide level < 1 ng/ml, while 6.3% were preserved beta cell function as fasting c-peptide levels were > 1 ng/ml. Only 34.8% of the patients were doing continues home blood glucose monitoring with glucose sensors, 25.8% were doing the monitoring only with visual strips, while 39.4% of the diabetic children did not doing any home blood glucose monitoring. The glycated HbA1c was <7% in 31%, 7-8% in 22%, > 8-9% in 14% and >9% in 33%. The study of BMI of the patients showed that 56% were not overweight, [BMI <25], 27% started to be overweight, [BMI 25-30], 14% were obese, [BMI 30-<40] while 3% only were with severe obesity [BMI >40]. According to the definition of metabolic syndrome criteria, the study of the metabolic criteria of the study group showed that 112, [28.1%] patients were with positive one metabolic criteria, 56 patients, [14%] with 2 positive metabolic criteria and 36 patients, [9%] with 3 positive metabolic criteria. So, in addition to the presence of hyperglycemia, 23% of the young diabetic patients fulfilled the criteria of metabolic syndrome

Urinary N-acetyl-beta-D-glucosaminidase in children with diabetes as an early marker of diabetic nephropathy

We investigated urinary N-acetyl-beta-D-glucosaminidase [NAG] levels in children with type 1 diabetes as an early marker of tubular damage and studied its correlation with microalbuminuria and glycaemic control. The study group comprised 42 children with type 1 diabetes and 20 healthy children as control. Urinary NAG to urinary creatinine ratio, microalbuminuria, glycated haemoglobin [Hb A1c], blood urea and serum creatinine were estimated. Urinary NAG levels in the children with diabetes were significantly higher than those of controls. There were positive correlations between urinary NAG levels and microalbuminuria, Hb A1c and systolic and diastolic blood pressure values. We found that 59.5% of diabetic children were positive for urinary NAG, while 38.1% of them were positive for microalbuminuria

use of Amantadine in the treatment of pediatric patients with chronic hepatitis b and/or C

Amantadine, a drug developed in 1960. It is a synthetic antiviral agent that specifically used in the prevention of Influenza A virus infection Amantadine was shown to result in a sustained virological response in chronic hepatitis C patients who were unresponsive to interferon therapy. The present study was carried out to evaluate the safety and efficacy of this antiviral drug in pediatric patients with chronic hepatitis B and/or C. the study included 19 children with chronic viral hepatitis: 9 had HCV, 7 had HBV and 3 had both. Their ages ranged between 2-15 years. Eleven were males and 8 were females. They were treated with amantadine in a dose of 5-1 0 mg/kg daily orally for 6 months. Serum aminotransferase values decreased in 13 patients [68.4%], seven of whom showed normalization of ALT [P<0.001]. Two patients with chronic hepatitis C who were HCV RNA + ve became - ve by the end of therapy. Mild neurological symptoms in the form of insomnia and irritability were reported in 4 of our patients, however this did not necessitate stopping therapy.Amantadine appeared quite safe and effective in pediatric patients with chronic hepatitis B and / or C

Predictors for early diagnosis of CNS infiltration in acute lymphoblastic leukemia

The study was held to define the factors helping in prediction of CNS infiltration by leukemia [ALL], type and rate of relapse. Also studing clinical and laboratory diagnosis especially CSF analysis at the primary diagnosis. The study was done in pediatric oncology unit of Zagazig University Hospital on 24 cases of newly diagnosed ALL ranging from 1-14 years. Males were 16 cases and females were 8 cases with male to female ratio of 2: 1. L[1] represented 75% of cases, Patients were subjected to different tests e.g CBC with differential count, hemoglobin level and B[2] microglobulin, bone marrow aspiration, morphological and chemical tests. CNS relapses were 20.9% of cases, hematological relapses were 12.9% and testicular relapses were 4.2%. Serum B[2] microgIobulin, CSF B[2] microglobulin and CSF LDH are useful indicators for cytological diagnosis of CNS infiltration at time of presentation. Cases with elevated B[2] M and/or LDH levels at presentation should be subjected to intensive CNS prophylaxis and CSF monitoring and follow up for better diagnosis and prognosis

genetic epidemiological study of congenital malformations at birth in Sharkyia, Egypt

A total of 1500 consecutive neonates delivered in Zagazig University Hospitals were subjected to full clinical and genetic evaluation. Social data including parental consanguinity and social class were taken. The prevalence of congenital in malformations [CMs] in the 1500 hospital live births and still births were 3.2%. The malformed neonates [48] were classified into 13 groups according to world Health Organization classification of CMs. The most common anomalies were: central nervous system [29.1%], followed by musculoskeletal system [18.9%] and genetic syndromes [10.5%]. Parental consanguinity was found in [54.2%] of malformed cases, indicating the deleterious effects of consanguinity. Our study concludes that overall the inheritance rather than socio-environmental factors contributes significantly in the etiology of different congenital malformations. We further suggest that the basic information of this research might be useful foundation data in future analytic studies on CMs in Egypt

Comparison between the prophylaxis of rheumatic fever with benzathine penicillin G every four weeks versus every three weeks and oral penicillin

This study aimed to clarify the differences between prophylaxis of rheumatic fever by 4 weeks benzathine penicillin G versus 3 weeks regimen and also versus the prophylaxis with oral penicillin. The results of this study proved that, the 3 weeks program for the prophylaxis of rheumatic fever is much better than the 4 weeks program and in turn the 4 weeks program is better than the oral penicillin. The injection with benzathine penicillin produced better results than the oral penicillin. Although, the oral use of penicillin is more accepted for the children than the benzathine penicillin injection, which is very painful. Also, in spite that the injection is painful and needs to do sensitive test for every injection, but it gave better results if given every 3 weeks to give sustained accepted concentration of penicillin in the blood. The increased recurrence of B-hemolytic streptococci infection of throat in the 4 weeks program was more than the 3 weeks program

Prevalence of microalbuminuria in diabetic children as an early indicator of reversible diabetic nephropathy

Diabetic nephropathy is proved to be the most common cause of death in type I diabetes and microalbuminuria is the early sign in the reversible stage of diabetic nephropathy. 70 patients with insulin dependent diabetes mellitus with age ranged between 3-12 years were subjected to full clinical examinations and laboratory analysis for microalbuminuria estimation, kidney function tests and fasting and post-prandial blood sugar levels. Of these diabetic children, 26 patients [37%] showed microalbuminuria. There was significant difference between both groups with and without microalbuminuria as regarding duration and severity of diabetes. But there was insignificant difference as regarding age, sex and kidney function tests. There was also a positive correlation between level of microalbuminuria and both duration and severity of diabetes