Evaluation of the safety and efficacy of biosimilar recombinant growth hormone in children with growth hormone deficiency: non-inferiority, randomized, parallel, multicentric and Phase III trial.

OBJECTIVES: This study is designed in order to compare the efficacy and safety of recombinant human growth hormone (rhGH) with the reference brand. METHODS: According to the inclusion criteria, 85 people in 13 Iranian centers were randomly selected to receive biosimilar Somatropin (Somatin®) (44 people) and reference Somatropin (Norditropin®) (41 people) at a dose of 35 µg/kg/d, seven days/week for 12 months. The primary outcomes included height velocity (HV) was measured during 12 months of treatment. RESULTS: The two intervention groups' Height changes were similar. The mean HV was 10.96 cm/year in the biosimilar group and 10.05 cm/year in the reference groups after 12 months. Estimates of the lower bounds of 95% CI for mean height differences in the biosimilar intervention group compared to the reference intervention group did not exceed the 2 cm margin. Therefore, the non-inferiority of biosimilar intervention compared to the brand product is verified. Common ADRs in both groups were nausea in two patients (2.4%), diarrhea in two patients (2.4%), increased body temperature in one patient (1.2%), and headache in one patient (1.2%). CONCLUSIONS: The finding of this study indicated that Somatin® and Norditropin® have comparable efficacy and safety profiles. CLINICAL TRIAL REGISTRATION: www.IRCT.irIRCT20171122037571N1.

Usefulness of Doppler ultrasound for the early diagnosis of diabetic nephropathy in type 1 diabetes mellitus.

PURPOSE: Early diagnosis and management of diabetic nephropathy (DN) might prevent or delay its progression to end-stage renal disease. The purpose of this study was to investigate whether changes in the duplex Doppler resistivity index (RI) are useful for the early identification of renal involvement in children and adolescents with insulin-dependent diabetes mellitus and associated conditions. MATERIALS AND METHODS: A total of 49 diabetic patients (two groups: 21 with DN and 28 without DN) were included in this study. DN was defined as 30-300 mg/l of albumin excretion in a random urine sample. The RI of the main renal arteries and their intrarenal branches (arcuate, interlobar) were evaluated with duplex Doppler ultrasound and correlated with age, renal length, duration of diabetes, and laboratory examinations. RESULTS: The mean age did not significantly differ between the two groups. The patients with DN had a significantly longer duration of type 1 diabetes (p = 0.02). The majority of patients (90.5%) had mild renal involvement with microalbuminuria and normal renal function. The mean RI was normal in both groups of patients, with no significant difference between the two groups. CONCLUSION: The RI did not increase in the early clinical stage of DN and was not a reliable marker for the screening of DN in patients with type 1 diabetes mellitus.

Utility of Urine N-acetyl-ß-D-glucosaminidase for Prediction of Renal Damage in Obese Children.

The incidence of obesity has increased globally in children and adults. In addition, renal dysfunction is an important complication of childhood obesity. This study was performed to identify the diagnostic value of N-acetyl-ß-D-glucosaminidase (NAG), a renal injury marker, for the early determination of renal damage in childhood obesity. Totally, 115 obese children and 115 healthy normal weight controls were enrolled in a cross-sectional case-control study. Urine NAG was measured in sample urine and normalized by urine creatinine (CR). In addition, correlation of urine NAG with other variables such as blood pressure (BP), blood glucose, and urine albumin was evaluated. Mean systolic BP (P <0.001), serum glucose (P = 0.047), urine albumin/Cr (P = 0.049), and urine NAG/Cr (P = 0.037) were significantly higher in obese children, compared with normal healthy controls. There was no correlation between urine NAG and urine albumin excretion. Urinary NAG/Cr was a simple and safe screening test for early determination of renal damage in children with obesity.

Investigation of Five Common Mutations on Phenylalanine Hydroxylase Gene of Phenylketonuria Patients from Two Provinces in North of Iran.

BACKGROUND: There are more than 500 different mutations on phenylalanine hydroxylase (PAH) gene that is responsible for phenylketonuria (PKU) diseases and the spectrum of these mutations is varied in different populations. The main clinical manifestation of untreated patients is severe mental retardation. The PAH gene, that is 90 kb long, is consisted of 13 exons and 12 introns. The aim of the present study was to identify the frequency of five common mutations on PAH gene among patients with PKU in Mazandaran and Golestan provinces including c.1066-11G>A, p. R261Q, p. R252W, p. R261X, and c.1200 + 1G>C. METHODS: Forty unrelated PKU patients, that 22 of them, were from Mazandaran and 18 of them from Golestan provinces were enrolled in the study. Genomic DNA was extracted from leukocytes using Qiagen DNA extraction kit and polymerase chain reaction - restriction fragment length polymorphism method was applied to detect five common mutations. RESULTS: Three out of the 5 investigate mutations were identified among the patients. The c.1066-11G>A mutation has the highest frequency (27.5%) among the patients and the frequency of p. R261Q and p. R261X mutations were 3.75 and 1.25%, respectively. In Golestan province, only c.1066-11G>A mutation was observed in investigated alleles. CONCLUSIONS: The high frequency of c.1066-11G>A mutation in Golestan province may be related to genetic drift, founder effect, and consanguinity.

Effect of vitamin d3 supplement in glycemic control of pediatrics with type 1 diabetes mellitus and vitamin d deficiency.

BACKGROUND: Glycemic control prevents microvascular complications in patients with type I diabetes mellitus such as retinopathy, nephropathy and neuropathy that influences quality of life. Some studies show the immunomodulatory effect of vitamin D in synthesis and secretion of insulin. AIMS: In this study we evaluate glycemic changes after vitamin D3 supplement in children with type I diabetes mellitus and vitamin D deficiency. MATERIALS AND METHODS: In children with type I diabetes mellitus, level of vitamin D and HbA1C was measured. Patients with type I diabetes mellitus who had vitamin D deficiency (25OHD < 50 nmol/lit) treated with 300,000 units of vitamin D3. Calcium supplement (40mg/kg/day) divided in two doses in order to avoid hungry bone was also used. After three months, 25OHD and HbA1C were measured again. Differences, in mean ± SD HbA1C and 25OHD were evaluated before and after the study. RESULTS: Mean ± SD HbA1C was 9.73±1.85 before the study which was diminished to 8.55±1.91 after vitamin D3 supplement treatment. This decline has a significant difference (p-value < 0.0001). Mean ± SD 25OHD was 17.33±8.97 nmol/lit before the study which is increased to 39.31±14.38 nmol/lit after treatment with vitamin D3 supplement. This increase also has a significant difference (p-value < 0.0001). Vitamin D3 supplement causes the improvement of HbA1C in all groups of glycemic control including HbA1C <7.8, 7.8-9.9, and >9.9. This supplement transfer patients toward better glycemic control for the entire group (p-value < 0.0001). CONCLUSION: Vitamin D3 supplement improves HbA1C in pediatrics with type I diabetes mellitus and vitamin D deficiency.

Relationship between 25-Hydroxy Vitamin-D and Obesity in 2-7 years old Children Referred to a Paediatric Hospital in Iran.

BACKGROUND: Obesity is increasing in children and it can cause many complications in adulthood, such as Diabetes mellitus (DM) and metabolic syndrome. In observational studies, vitamin-D was one of the factors which were found to be associated with obesity. AIMS: To determine the association between body mass index (BMI) and serum level of vitamin-D in children who were outpatients at Taleghani Paediatric Hospital, Iran. SETTINGS AND DESIGN: This was a cross-sectional observational study done on 215 children who were 2 to 7 y old, who were referred to Taleghani Hospital in winter (1391 solar calendar) 2013. MATERIALS AND METHODS: In this cross-sectional study, anthropometric indices: weight, height and waist circumference were measured by using identical instruments. BMI was also determined as per CDC 2000 criteria. Vitamin-D levels were estimated by ELISA. STATISTICAL ANALYSIS: Vitamin-D levels which were less than 20 nmol/L were considered as a deficiency, levels which were 20-30 nmol\L were considered as inadequate and those which were equal to or greater than 30 nmol\L were considered as sufficient. t-test, ANOVA and Pearson's correlation coefficient at a significant level of 0.05 were applied and data were analysed by using SPSS (version 16). RESULTS: One hundred and twenty five children (47.4%) were males and the rest were females. One hundred eighty four children (85.6%) had vitamin-D deficiency and only 31 had adequate levels of vitamin-D. The prevalence of obesity and overweight were 27%, but considering the vitamin-D status, it was found to be insignificant. However, there was a linear relationship between waist circumference and serum vitamin-D (p<0.01). The means and standard deviations of serum vitamin-D levels in girls and boys were 22.76 ±11.62 and 23.46 ± 9.30 nmol/L and this difference was not significant. Vitamin-D levels found in the three ethnic groups of Fars, Turkmen and Sistani showed significant differences (p<0.002). CONCLUSIONS: There was a high prevalence of vitamin-D deficiency in 2 to 7 year olds. There was no significant relationship between BMI and vitamin-D, but it was recorded in ethnic groups, and there was a correlation between waist circumference and vitamin-D levels. More exposure to sunlight and prescription of vitamin supplements were recommended.