Assessment of the Effect of Timing of Insulin Glargine Administration (Bedtime versus Morning) on Glycemic Control in Children with Type 1 Diabetes in Cairo, Egypt: A Single Centre Experience.

BACKGROUND: Diabetes control without developing hypoglycemia is challenging in Type 1 diabetes (T1D) management, with few studies evaluating the effect of insulin glargine timing on glucoregulation. OBJECTIVES: The aim is to compare glycemic control using continuous glucose monitoring (CGM) in children with T1D receiving bedtime versus morning glargine and to assess CGM effect on glycemia. METHODS: This cross-sectional observational study was conducted on 30 pediatric patients with T1D receiving glargine (19 at bedtime and 11 in the morning). CGM sensor was applied for 3-5 days using the I-Pro2 blood glucose sensor. RESULTS: Total daily dose of glargine showed a significant correlation with HbA1C (p=0.006) and percentage of glucose readings within average (p=0.039). HbA1C correlated significantly with time in range (TIR) (p=0.049). Nocturnal hypoglycemia was significantly higher in the bedtime glargine group than in the morning one (p=0.016). The morning glargine group showed better control in terms of lower HbA1C and higher TIR, but these did not reach statistical significance. Follow- up after 3 months revealed significant improvement in the percentage of hyperglycemia, BG readings within average, as well as HbA1c (p:0.001). CONCLUSIONS: Bedtime glargine administration was associated with a higher frequency of occurrence of nocturnal hypoglycemia. No statistically significant difference in glycemic control between both groups was found. CGM use improved glycemic control.

Reference values for penile and clitoral lengths of healthy term Egyptian newborn infants.

AIM: Examination of the external genital organs is an integral part of the routine physical examination of the newborn. Early recognition of micropenis or clitoromegaly is important as they may be the only obvious manifestation of pituitary or hypothalamic hormonal deficiencies at birth. Studies suggest that differences in penile or clitoral anthropometry may exist between different populations. Therefore, reference values for genital organs dimensions should be available and well known to medical personnel. We aim to establish reference values for the penile length in Egyptian newborn boys and reference values for the clitoral length in Egyptian newborn girls and to define micropenis and clitoromegaly according to Egyptian reference values. METHODS: A total of 500 healthy term newborn boys and 500 healthy term newborn girls were enrolled in the study. Stretched penile length and clitoral length were measured during the first 7 days of postnatal life. Birth weight, length and head circumference were measured and recorded. RESULTS: The mean (±SD) stretched penile length was 3.16 ± 0.41 cm. The mean (±SD) clitoral length was 0.51 ± 0.13. There was no significant correlation between penile or clitoral length, and body weight, length or head circumference. CONCLUSION: Our study provides reference values for normal penile length and clitoral length in Egyptian newborns. Our study suggests that among healthy term Egyptian newborns, penile length of less than 2.13 cm may be considered micropenis and clitoral length of more than 0.83 cm may be considered clitoromegaly.

Categorization of differences of sex development among Egyptian children and the role of antimullerian hormone and inhibin B.

Background: Differences of sex development (DSD) are congenital conditions linked to atypical development of chromosomal, gonadal, or anatomical sex. Objective: The aim of this study was to demonstrate our experiences at the Diabetes Endocrine and Metabolism Pediatric Unit (DEMPU), Faculty of Medicine, Cairo University in the field of DSD by focusing on the clinical presentation, laboratory profile, classification, and etiological diagnosis of these conditions. In addition, the present study intended to delineate the importance of serum anti-Müllerian hormone (AMH) and inhibin B in detecting the presence of functioning testicular tissue. Methods: This cohort study included 451 infants and children with various clinical presentations of DSD. The study performed a retrospective analysis on medical records of established DSD cases to evaluate the clinical importance of AMH and inhibin B. In addition, newly diagnosed patients were prospectively analyzed. Results: Three hundred thirty-six (74.5%) patients were 46,XY DSD, 98 (21.7%) were 46,XX DSD, 14 patients had other karyotypes and 3 had missing karyotypes. Among the 46XY DSD patients, the most common cause was partial androgen insensitivity. In contrast, congenital adrenal hyperplasia constituted the most common diagnosis in 46,XX DSD cases. The cut off value of serum AMH was 14.5 ng/ml with 100% sensitivity and 55.1% specificity. Conclusion: Partial androgen insensitivity was the most important cause of 46,XY DSD in Egyptian children, and congenital adrenal hyperplasia was the most common cause of 46,XX DSD. AMH was valuable in detecting functioning testicular tissue.

Stretched penile length and anogenital distance in Egyptian boys aged one month to five years.

BACKGROUND: In children with isolated unilateral undescended testis mechanical anomalies are commonly implicated and a diagnosis of simple hypospadius implies that the rest of the external genitalia are normal. Patients with disorders of sexual development, by contrast, have other associated genital anomalies including micropenis and should be referred to the endocrinologist for hormonal assessment before surgical correction of undescended testis or hypospadius. Early diagnosis of abnormal penile size is important but proper assessment begins with defining the normal population-specific age-appropriate reference range. Anogenital distance (AGD) reflects prenatal and early postnatal testosterone levels. OBJECTIVE: The aim of our study was to establish mean reference values and percentile curves for strtetched penile length (SPL) and AGD in healthy Egyptian males from the age of one month to five years and to determine the mean monthly increase in SPL and AGDs from 1 to 13 months of age (a reflection of mini-puberty). STUDY DESIGN: This was a descriptive cross-sectional study conducted in Cairo University and Mataria Hosptals, Egypt to determine SPL and AGD in 2972 Egyptian males aged from one month to five years from October 2016-December 2018. In addition, we measured length/height, weight and body mass index. RESULTS: SPL increased gradually from a mean ± SD of 3.55 ± 0.51 cm in the first year of life to 5.52 ± 0.67 cm by five years of age with a growth from 1 to 12 months of life of 0.6 cm. SPL showed smaller values in infants 6-9 months old compared to younger infants. AGD increased from 7.48 ± 1.47 cm in the first year of life to 12.83 ± 0.58 cm by 5 years of age with a growth from 1 to 12 months of 4.34 cm. SPL and AGD Z-scores correlated positively with each other and with age (months), and Z-scores of height/length, weight and BMI (p < 0.001). DISCUSSION: The rapid increases in SPL and AGD observed in our study group in the first few months of life reflect the effects of mini-puberty. The fact that SPL and AGD correlated positively with other anthropometric measurements suggests that SPL and AGD may be controlled by nutritional and/or hormonal factors. We suggest that waning testosterone levels marking the end of minipuberty might explain smaller values for SPL in our group of 6-9 month old infants compared with younger infants. LIMITATION: We have not included children under one month old. CONCLUSION: It is important for each country to develop its own national percentile curves for all growth parameters. This will allow the physician to identify normal differences in the population and to pick up disorders at an age when intervention may yield better results We have developed percentile curves for SPL and AGD that can be used as references for Egyptian male infants and young children.

Metabolic syndrome in a sample of Egyptian adolescent girls and its association with apolipoprotein E.

AIM: Obesity and its metabolic complications are increasing in childhood and extend to adulthood. The aims of this study were to assess the prevalence of metabolic syndrome (MS) in a sample of Egyptian adolescent girls and investigate its association with apolipoprotein E. METHODS: A cross-sectional study design was used, including 200 Egyptian adolescent girls aged between 12 and 18 years. They were subjected to blood pressure (BP) measurement, anthropometric measurements (weight, height and waist circumference (WC)), laboratory investigations (fasting glucose and lipid profile) and molecular analysis (Apo E). RESULTS: Overweight/obese girls were suffering significantly, more than normal-weight girls, from hypertension (66.7 vs. 40.8%), diabetes diagnosed by elevated fasting blood glucose (46.7 vs. 31.2%) and low high-density lipoprotein (HDL) (64 vs. 59.2%). Girls with MS had significantly higher values of body mass index Z-score, WC, BP, cholesterol and triglycerides and significantly lower HDL. Allele E3 (59.1 vs. 55.1%) was more frequent among girls with MS, while allele E4 (41 vs. 36.4) was more frequent among girls without MS. MS was the most prominent among girls with the E3/E4 genotype (35.7%), who had the highest frequency of elevated cholesterol, triglycerides, low-density lipoprotein and blood glucose, while girls with the E2/E4 genotype, which was rare among both groups, had the highest frequency of elevated BP (68.8%) and low HDL (71.4%). CONCLUSION: MS was significantly more prominent among overweight/obese adolescent girls with the E3/E4 genotype, who had the highest frequency of disturbed lipid profile and blood glucose.

Anti-Müllerian hormone levels in patients with turner syndrome: Relation to karyotype, spontaneous puberty, and replacement therapy.

Most girls with Turner syndrome (TS) suffer from incomplete sexual development, premature ovarian failure, and infertility due to abnormal ovarian folliculogenesis. Serum anti-Müllerian hormone (AMH) levels reflect the ovarian reserve in females, even in childhood. Thus, we aimed to assess serum AMH levels in girls with TS and its relation to karyotype, spontaneous puberty, and growth hormone (GH) therapy. Fifty TS were compared to 50 age- and sex-matched controls. All subjects were subjected to history, anthropometric assessment, Tanner pubertal staging and measurement of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and AMH. Karyotype results were obtained from patients' records. Serum AMH was measurable in 12 TS patients (24%). The lowest frequency of measurable AMH was in patients with a karyotype of 45,X. The measurable AMH was associated with spontaneous breast development (p = .003) and spontaneous menarche (p = .001). AMH correlated negatively with FSH (r = -.846, p = .000) and LH (r = -.83, p = .034). GH therapy increased the odds of having measurable AMH in TS girls (p = .002). In conclusion, AMH was associated with karyotype, spontaneous pubertal development, LH, and FSH in TS girls and may serve as a useful marker of ovarian function and ongoing follicular development in prepuberty.

Left ventricular diastolic dysfunction without left ventricular hypertrophy in obese children and adolescents: a Tissue Doppler Imaging and Cardiac Troponin I Study.

BACKGROUND: Obesity increases the risk for various cardiovascular problems. Increase in body mass index is often an independent risk factor for the development of elevated blood pressure and clustering of various cardiovascular risk factors. OBJECTIVE: To determine early markers of left ventricular affection in obese patients before the appearance of left ventricular hypertrophy. METHODS: In this cross-sectional study, we evaluated 42 obese patients and 30 healthy controls. Their ages ranged from 6 to 19 years. Studied children were subjected to anthropometric, lipid profile, and serum Troponin I level measurements. Echocardiographic evaluation performed to assess the left ventricle included left ventricular dimension measurement using motion-mode echocardiography, based on which patients with left ventricular hypertrophy (10 patients) were eliminated, as well as conventional and tissue Doppler imaging. RESULTS: Tissue Doppler findings in the study groups showed that the ratio of transmitral early diastolic filling velocity to septal peak early diastolic myocardial velocity (E/e') was significantly higher in cases compared with controls [6.9±1.4 versus 9.0±1.6, p (Pearson's coefficient)=0.001, respectively]. The level of cardiac troponin I was significantly higher in cases compared with controls [0.14±0.39 ng/ml versus 0.01±0.01 ng/ml, p (Pearson's coefficient)=0.047, respectively] and there was a significant correlation between troponin I and transmitral early diastolic filling velocity to septal peak early diastolic myocardial velocity ratio (E/e') [R (correlation coefficient)=0.6]. CONCLUSION: Tissue Doppler Imaging and Troponin I evaluation proved useful tools to detect early affection of the left ventricle in obese patients even in the absence of left ventricular hypertrophy.

Identification of insulin gene variants in neonatal diabetes.

OBJECTIVES: Permanent neonatal diabetes (PNDM) is caused by mutations in the genes responsible for the synthesis of different proteins that are important for the normal behavior of beta cells in the pancreas. Mutations in the insulin gene (INS) are considered as one of the causes of diabetes in neonates. This study aimed to investigate the genetic variations in the INS gene in a group of Egyptian infants diagnosed with PNDM. METHODS: We screened exons 2 and 3 with intronic boundaries of the INS gene by direct gene sequencing in 30 PNDM patients and 20 healthy controls. A detailed clinical phenotyping of the patients was carried out to specify the diabetes features in those found to carry an INS variant. RESULTS: We identified five variants (four SNPs and one synonymous variant), c(0).187 + 11T > C, c.-17-6T > A, c.*22A > C, c.*9C > T, and c.36G > A (p.A12A), with allelic frequencies of 96.7%, 80%, 75%, 5%, and 1.7%, respectively. All showed no statistically significance difference compared with the controls, with the exception of c.*22A > C. CONCLUSION: Genetic screening for the INS gene did not reveal an evident role in the diagnosis of PNDM.