Efficacy of oral insulin nanoparticles for the management of hyperglycemia in a rat model of diabetes induced with streptozotocin.

Insulin is the cornerstone of treatment in type 1 diabetes mellitus. However, because of its protein structure, insulin has to be administered via injection, and many attempts have been made to create oral formulations, especially using nanoparticles (NPs). The aim of this study was to compare the hypoglycemic effect of insulin-loaded NPs to that of subcutaneous insulin in an in vivo rat model of diabetes. We used biodegradable D-α-tocopherol polyethylene glycol succinate-emulsified, chitosan-capped poly(lactic-co-glycolic acid) NPs loaded with soluble human insulin in a dose of 20 IU/kg body weight, and examined the physical characteristics of NPs in vivo and in vitro. Serum glucose levels were reduced after 6 h, but the difference was not significant compared to subcutaneous insulin; at 12 h and 24 h, insulin levels were significantly higher in rats treated with NPs than in rats treated with subcutaneous insulin. There was no significant difference in serum insulin levels at 12 h and 24 h compared to non-diabetic rats. Our findings suggest that chitosan-based NPs are able to maintain good glycemic control for up to 24 h and can be considered a potential carrier for oral insulin delivery.

Long-term health consequences of central precocious/early puberty (CPP) and treatment with Gn-RH analogue: a short update.

BACKGROUND: The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors. METHODS: We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk. RESULTS: Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders. CONCLUSION: Monitoring and early diagnosis of these conditions are of paramount importance for successful management.

Qatar population-specific centile charts of placental weight in 80 722 newborns: relation to maternal age, gestational age, newborn birth weight, and gender, between the 37 th and 42 nd weeks of gestation.

BACKGROUND: Data about placental weight (PW) in relation to birth weight (BW) and gestational age (GA) are lacking in Arabic countries. AIMS OF THE STUDY: (a) to find out the national PW standards for babies born between 37th and 42nd weeks of gestation in male and female babies born in Qatar; (b) to study the relation, if any, between PW and maternal age, gestational age (GA), birth weight (BW), and gender of the newborn. MATERIALS AND METHODS: A National population-based retrospective chart review study was conducted between 1-2016 to 12-2019 (n = 80 722). Data of gestational age (GA) at delivery (in weeks), newborn birth weight (BW), PW, and gender at birth, were collected from singleton babies born between 37 th and 42nd weeks of gestation. RESULTS: The PW ranged from 440 to 860 grams (g) with a mean of 682 ± 96 g. at term for boys and 673 ± 94 g. for girls. The mean BW was 3 036 ± 448 g and BW/PW ratio was 0.203 ± 0.026. The PW continued to increase through 41 weeks' gestation, in boys and girls with a significant decrease at the 42nd week of gestation. PW was significantly correlated with BW (r = 0.596, P: < 0.001) and GA (r = 0.15, P: <0.001) and accounted for 43.4% of the explained variability in birth weight. CONCLUSIONS: PW was a significant predictor of BW with a consistent increase in PW until the 41st week of gestation in boys and girls and a positive correlation with BW and GA.

Trend in the incidence of type 1 diabetes (T1DM) among Qatari and Arab gulf children and adolescents over the past 20 years.

Letter to Editor.

A Short Review on Growth and Endocrine Long-term Complications in Children and Adolescents with ß-Thalassemia Major: Conventional Treatment versus Hematopoietic Stem Cell Transplantation.

The conventional treatment of ß-thalassemia (ß-TM) patients is based on the correction of anemia through regular blood transfusions and iron chelation therapy. However, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only currently available technique that has curative potential. Variable frequency and severity of long-term growth and endocrine changes after conventional treatment as well as after HSCT have been reported by different centers. The goal of this mini-review is to summarize and update knowledge about long-term growth and endocrine changes after HSCT in patients with ß-TM in comparison to those occurring in ß-TM patients on conventional treatment. Regular surveillance, early diagnosis, treatment, and follow-up in a multi-disciplinary specialized setting are suggested to optimize the patient's quality of life (www.actabiomedica.it).

Growth, bone maturation and ovarian size in girls with early and fast puberty (EFP) and effects of three years treatment with GnRH analogue (GnRHa).

INTRODUCTION: Early puberty (EP) in girls is defined as the onset of thelarche that begins after 6 years and before 8 years and/or acceleration in the tempo of pubertal development. The stage of puberty and the ovarian volume at presentation and the effect of treatment with GnRH analogue (GnRHa) on final adult height are still debated. PATIENTS AND METHODS: We analyzed the data of 22 girls, who presented early and fast puberty (FEP). The clinical stage of puberty, hormonal levels and the ovarian volume (OV) (measured by ovarian ultra-sonography) at presentation were studied. We recorded the effects of 3 years treatment with GnRHa on their growth in relation to their mid parental height, pubertal progression, and bone maturation. RESULTS AND CONCLUSION: GnRHa therapy decreased the fast progress of puberty, skeletal maturation, and GV/year. It was successful in increasing the predicted final adult height comparable to or surpassing their mid-parenteral height. A larger OV at presentation was associated with reduced Ht-SDS after 3 years of GnRHa treatment. Clearly, a definitive evaluation of the efficacy of GnRHa as treatment for EFP in girls will require expanded and concerted studies.

Postnatal Growth and Prevalence of Obesity in Infants Born Large-for-Gestational Age during the First 3 years of Life: Personal Experience and Exploration of Current Literature.

AIMS OF THE STUDY: We evaluated the growth patterns in a cohort of infants (n = 120) born large-for-gestational-age (LGA) [birth weight (Bwt) > 4 kg] from birth to age 3 years of age in comparison with normal age and sex-matched children (WHO). RESULTS: LGA infants had high weight for age Z score (WAZ) at birth that decreased significantly during the first 6 months of life (by a mean of - 0.67 SD) that was followed by significant gain during the following 6 months of life (around + 0.4 SD). These children grew on a higher centile of WAZ with no significant change during the second and third years of life.  The prevalence of obesity (WAZ > 2) increased markedly from 24% at the end of their first year to 34% and 36% at the end of their second and third years of life, respectively.  The mean length for age Z score (LAZ) decreased significantly during the first 6 months (by a mean of -0.9 SD) but was maintained at high centile (> 1 SD) during the second and 3rd years.  The weight for length SDS (WLZ) increased significantly during the first 18 months of life and decreases gradually during the second half of the 2nd year and the 3rd year.   Their head circumference SDS decreased significantly in the first 6 months and then sustained around the 70th centiles (+1 SD) in the following 18 months. CONCLUSION: Our study showed that in LGA babies obesity increased progressively after the first year of life to reach 36% at the end of the third year. Therefore, it is important to apply the early nutritional intervention to decrease the occurrence of obesity and reduce later cardiometabolic risks.

The epidemiology, clinical, biochemical, immunological and radiological features of youth onset type 2 diabetes mellitus in the state of Qatar.

Objectives: To describe the epidemiology, clinical, biochemical, immunological and radiological aspects of youth with type 2 diabetes. Methods: Patients under 18 year of age with type 2 diabetes were recruited from 2018 to 2020, clinical data collected, autoantibodies (GAD65, IAA, IA2 and ZnT8), insulin, ALT and c-peptide were measured. Hepatic ultrasound was performed for assessment of non-alcoholic fatty liver disease (NAFLD). Results: 104 patients were identified. The incidence in 2020 and prevalence per 100,000 was 2.51 and 23.7, respectively. The age of onset was between 8.5 and 18 years with 74% of the patients being of Qatari nationality. Males were more affected than females (1.5/1). Overweight/obesity was present in 98% of all the patients, a positive family history (either both parents or a single parent) in 71% and maternal gestational diabetes mellitus (GDM) in 60% of patients. More than 90% of the patients had acanthosis nigricans. 5 patients had 1 autoantibody positivity and hepatic ultrasound detected evidence of NAFLD in majority of patients. Conclusion: Obesity, maternal GDM and family history of diabetes were the key risk factors for the development of type 2 diabetes. Autoantibody positivity may be present in youth type 2 diabetes. As youth type 2 diabetes is associated with early onset microvascular and macrovascular complications, these findings have important social and health budget implications for Qatar. Tackling the burden of maternal GDM and childhood obesity and building programmes for early detection and intervention, are therefore, essential to reduce the risk of future complications.

Growth and Metabolic Syndrome (MetS) criteria in young children with classic Congenital Adrenal Hyperplasia (CAH) treated with corticosteroids (CS).

BACKGROUND: Treatment of children with congenital adrenal hyperplasia (CAH) with corticosteroids (CS) may increase the risk for developing different components of metabolic syndrome (MetS).  Aim: We assessed the occurrence of cardiometabolic risk factors in children with CAH on treatment with CS since early infancy. METHODS: Data of 30 children with CAH were analyzed retrospectively. They have received hydrocortisone (HC; n = 11) or prednisolone (P; n= 19) and fludrocortisone (0.1- 0.15 mg once daily) since early infancy. The different cardiometabolic criteria including blood pressure (BP), fasting glucose, low-density lipoprotein (LDL), and serum cholesterol concentrations were studied and compared with the data for 66 age-matched obese children. RESULTS: Children with CAH on treatment for > 5 years had a high rate of obesity and overweight (60%) and short stature (23.3%), respectively. They had higher occurrences of abnormal cardio-metabolic components including high LDL and triglyceride and BP as well as increased carotid intima-media thickness (CIMT). Females had higher body mass index (BMI) and BP compared to males. The less controlled group was older and had faster linear growth compared to the controls. In the CAH group, BP and CIMT were correlated significantly with BMI-SDS and weight-standard deviation score (Wt-SDS). Neither the level of 17-hydroxy-Progesterone (17-OHP), nor the HC dose was correlated with BP, CIMT or BMI. CONCLUSION: These findings suggest the role played by excessive weight gain on the increased cardiometabolic risk factors in children with CAH on treatment with CS.

Clinical and metabolic characteristics of children with hybrid diabetes mellitus (HD) compared to children with type 2 diabetes mellitus (T2DM): A preliminary comparative study.

BACKGROUND: The term double diabetes or "Hybrid Diabetes (HD)" describes diabetes with combined features of type 1 and type 2 diabetes (T2DM). PATIENTS AND METHODS: We report the clinical and biochemical characteristics of 7 children with HD and the course of their disease including the response to treatment. The data were compared to 59 children with a diagnosis of T2DM. Variables examined included age, height, weight, body mass index (BMI), triglycerides (Tg), high-density lipoprotein (HDL), and blood pressure. The Weiss criteria were used to diagnose metabolic syndrome (MetS). The atherogenic index of plasma (AIP) was calculated from the standard lipid profile. Four autoantibodies against pancreatic ß-cell were measured in all patients. RESULTS: Significant clinical and biochemical differences were detected among children with HD versus T2DM. The mean BMI of children with T2DM was significantly higher than for the HD group. At presentation, the mean C peptide level was significantly lower in HD versus T2DM group and 28% presented with diabetic ketoacidosis (DKA). The percentage of those with full criteria of MetS was significantly higher in T2DM versus HD group as well as the percentage of children with high atherogenic index. After a mean duration of 2.3 months from diagnosis, 4/7 of HD patients stopped insulin therapy and 3 patients had a marked reduction in the insulin requirement. During the follow-up (after 15 ±5 months), 5/7 HD patients required an increase in their insulin dose, one was controlled on a markedly low dose of basal insulin and the last patient did not require any insulin therapy for 40 months. CONCLUSION: Appropriate assessment of HD is necessary for early and correct diagnosis. Increasing awareness of HD among the general population and primary care practitioners is necessary for successfully and properly treating this complex disease.

Early and Long-term Consequences of Nutritional Stunting: From Childhood to Adulthood.

Linear growth failure (stunting) in childhood is the most prevalent form of undernutrition globally. The debate continues as to whether children who become stunted before age 24 months can catch up in growth and cognitive functions later in their lives. The potentially irreparable physical and neurocognitive damage that accompanies stunted growth is a major obstacle to human development. This review aims at evaluation and summarizing the published research covering the different aspects of stunting from childhood to adulthood.

A rare case of Ovarian Juvenile Granulosa Cell Tumor in an Infant with Isosexual Pseudo Puberty and a Revision of Literature.

Juvenile ovarian granulosa cell tumors (JGCTs) are described infrequently in pediatrics, and their finding in infants is exceptional. We highlight the presenting symptoms, radiologic images, operative management, and histopathologic findings of a 9-month-old female with isosexual pseudopuberty. An updated revision of literature in infants below the age of 12 months is also reported.

Defective Cortisol Secretion in Response to Spontaneous Hypoglycemia but Normal Cortisol Response to ACTH stimulation in neonates with Hyperinsulinemic Hypoglycemia (HH).

INTRODUCTION: Hyperinsulinemic Hypoglycaemia (HH) is the most common cause of recurrent and persistent hypoglycemia in the neonatal period. Cortisol and GH play an important role as a counterregulatory hormone during hypoglycemia. Both antagonize the peripheral effects of insulin and directly influences glucose metabolism Patients and Methods: We studied cortisol and GH secretion in newborn infants with HH during spontaneous hypoglycemia. In addition, their basal ACTH level and cortisol response to a standard dose ACTH was performed. RESULTS: Nine newborns with HH were studied during the first 2 weeks of life. During HH, their mean glucose concentration was 1.42 ± 0.7 mmol/L, mean beta hydroxybutyrate level was 0.08 ± 0.04 mmol/L, and mean serum insulin level was 17.78 ± 9.7 µU/mL. Their cortisol and GH levels at the time of spontaneous hypoglycemia were 94.7 ± 83.1 nmol/L and 82.4 ± 29 m IU/L respectively. They had relatively low level of ACTH (range: 14 :72 pg/ml, mean: 39.4 ± 20 pg/mL) during hypoglycemia. All infants had GH concentration > 20 mIU/L at the time of hypoglycemia. All infants underwent ACTH test. Their basal serum cortisol levels did not differ compared to cortisol levels during hypoglycemia, and all had a normal peak cortisol response (> 500 nmol/L) in response to i.v. ACTH stimulation test. CONCLUSION: Infants with HH have low cortisol response to spontaneous hypoglycemia with normal response to exogenous standard-dose ACTH. Checking hypothalamic-pituitary axis (HPA) axis later in infancy using low dose ACTH may be useful to diagnose persistent HPA abnormalities in these infants. All HH infants had appropriate elevation of GH during hypoglycemia.