Nutritional studies in patients with ß-thalassemia major: A short review.

BACKGROUND: Patients with ß-thalassemia major (BTM) had variable prevalence of undernutrition and abnormal body composition.  Methods: We performed an electronic search in PubMed, Scopus, Research gate, and Web of Sciences to evaluate the prevalence of nutritional disorders in patients with BTM worldwide in relation to their body composition and possible etiological factors. In addition, we reviewed the published nutritional intervention studies.  Results: 22 studies on the prevalence of undernutrition (12 countries) and 23 nutritional intervention studies were analyzed.  Undernutrition occurred in a considerable number of patients but varied greatly among different countries (from 5.2% to 70%). The lower middle income (LMI) countries (India, Pakistan, Iran, Egypt) had higher prevalence, while (high -middle and high income (Turkey, Greece, North America, USA, Canada) had lower prevalence.  Even in patients with normal BMI, abnormalities of body composition are common with decreased muscle mass, lean-body mass, and bone mineral density. 65% to 75% of them had lower energy intake with low levels of circulating nutrients, minerals (zinc, selenium, and copper), and vitamins (D, E) versus controls. Increased macro and micronutrient requirements decreased absorption and /or increased loss or excretion are etiologic factors. Undernutrition was associated with short stature and lower quality of life (QOL). High prevalence of endocrinopathies, poor transfusion regimen (tissue hypoxia), improper chelation, and lack of maternal education, represented important risk factors in the production of poor growth in weight and stature. CONCLUSIONS: Timely detection of undernutrition in patients with BTM and proper nutritional intervention could prevent growth delay and comorbidities.

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.

Risk of Breast Cancer Progression after Treatment in the Western Region of Saudi Arabia.

Background: The risk of breast cancer progression is one of the most difficult factors to predict as it is studied in different populations, patient groups, or time frames, resulting in conflicting estimates of incidence rates reported in the literature. The purpose of this study is to identify predictive factors for breast cancer recurrences in a sample of the Middle Eastern population. Methodology: A cohort retrospective study included all eligible breast cancer patients at the National Guard Health Affairs (NGHA) Hospital in Jeddah, Western region, from 2015 to 2021. Our primary outcome was the progression status of the patients; we adjusted for demographic, clinical, and molecule characteristics of the population. From 2015 to 2021, there were 319 patients diagnosed with breast cancer. Multiple logistic regression analysis was used to estimate predictors of breast cancer progression. Results: One of five breast cancer patients had breast cancer progression (20.83%), while 66.15% of the progression patients were between the ages of 41-65. In multivariate analysis, age, progesterone receptor (PR), family history, and tumor size were significant predictors of breast cancer progression. The age group of 20-40 years was a protective predictor of breast cancer progression, patients in the young age group were less likely to be diagnosed with progression (OR = 0.35; CI = 0.15, 0.81). While negative PRs and tumor size greater than 2 cm were significant predictor factors of breast cancer progression (OR = 2.07; CI = 1.09, 3.91, OR = 2.02; CI = 1.9, 3.78). Conclusion: Although the effect of young age as a protective factor for the progression of breast cancer remains controversial, our study revealed that patients between 41 and 60 years of age had a higher rate of progression. Future larger prospective studies are needed to delineate the role of age and PR hormone receptors in determining the best treatment options for women with breast cancer in the Saudi population.

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 long-term (five years) effects of prednisone therapy in children with frequently relapsing nephrotic syndrome: A controlled study of anthropometric parameters and metabolic abnormalities.

BACKGROUND: Steroids are the main drugs used for the treatment of nephrotic syndrome (NS) in children. AIM OF THE STUDY: We investigated the steroid effect on linear growth and weight gain as well as the prevalence of different metabolic components and dysglycemia in children with NS with multiple relapses for 5 years in relation to the cumulative dose of steroids. Study population and sample size: Data of 30 children with NS were analyzed retrospectively. They received prednisolone treatment as advised by international guidelines. The cumulative dose of prednisolone (CDP) over the 5 years was calculated for each child. Their growth and different metabolic criteria, including impaired fasting glucose (IFG), high LDL and cholesterol, lower HDL, and high blood pressure studied over this period and compared with the data for 66 age-matched obese non-nephrotic children. RESULTS: The mean CDP was 100 ± 63 mg /kg/yr given over an average duration of 5 years.  The height-SDS was not affected after 3 years but decreased by -0.4 SD after 5 years. The body mass index-SDS increased from 0.65 to 0.97 and 1.1 after 3 and 5 years, respectively. Obesity and overweight increased from 25% pre-treatment to 59.2% after 5 years of treatment. After 5 years of treatment, IFG was detected in 35 %, hypertension in 40%, high LDL in 77%, and high cholesterol in 80%. CONCLUSION: In children with frequently relapsing NS, long-term steroid therapy was associated with a higher rate of obesity, short stature as well as the occurrence of different metabolic syndrome (MetS.

Linear growth and prevalence of the different components of the metabolic syndrome (MetS) in young obese nondiabetic children (below 5 years) in comparison to older obese children (6-12 years).

BACKGROUND: In Qatar, the prevalence of metabolic syndrome (MetS) in children and adults is increasing in parallel with the markedly increasing trends in obesity rates. OBJECTIVE: The aim of our study was to assess the prevalence of different components of MetS, measure plasma atherogenic indexes (AIP), and to evaluate linear growth in young obese nondiabetic children (< 5 years) in comparison to older obese children (6-12 years).  Methods:  We analysed the anthropometric and biochemical profile of 135 random sample obese children who attended to the Paediatric Clinic of Hamad Medical Centre (HGH) in Doha (Qatar) from January 2018 to December 2019. RESULTS: A large proportion of children presented with obesity, around the age of 5 years, were obese at the end of their first year of life (63.8%) and more were obese at the 2 years of age (82.6%). Significantly rapid gain in weight and linear growth occurred during the first 6 months of postnatal life. Moreover, some metabolic risk factors and high AIP occurred more frequently in older obese children compared to young obese children. CONCLUSIONS: This study documented the early occurrence of different components of the MetS in young obese children and the progressive increase of their prevalence in older prepubertal children. Most of obese children who presented at or below 5 years of age had significant obesity and rapid linear growth during the first two years (infancy). These two findings pointed out to the necessity to impose early detection and preventive measures on a national scale.

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.

Sib-pair subgroup familial type 1 diabetes mellitus in children in the state of Qatar.

BACKGROUND: Type 1 diabetes is the most common type of diabetes mellitus (DM) in children. It can be sporadic in onset or cluster in families, which comprises parent-offspring and sib-pair subgroups. The risk of developing DM in first-degree relatives of affected individuals is 8-15 fold higher. There is limited data about familial DM from the Gulf region. This study aims to describe the clinical, biochemical and genetic characteristics of sib-pair familial type 1 diabetes in Qatar. METHODS: Every child with DM following up at Sidra Medicine was recruited. Data was collected regarding clinical features, family history, type 1 diabetes autoantibodies and whole genome sequencing was performed. Genetic analysis for MODY genes and HLA association analysis was conducted. RESULTS: 44 families with sib-pair familial diabetes were identified. Of these, 2 families had 4 affected siblings and 5 families had 3 affected siblings. The majority are of Qatari ethnicity and the most common autoantibody was GAD65. The most common age of onset in the proband was 5-9 years while it was 10-14 years in subsequent siblings. The occurrence of DKA & HbA1c levels were lower in the second affected sibling. No relevant MODY gene variants were found. HLA analysis found 15 variants in at least 50% of the subjects. Most common were HLA-F*01*01*01G, HLA- DPA1*01*03*01G, HLA- DRB3*02*02*01G, HLA- E*01*01*01G & DRB4*03*01N. CONCLUSIONS: The prevalence of sib-pair diabetes is 3.64%. The second affected siblings were older. MODY is unlikely and Class I and II HLA genes was present in sib-pair diabetes.

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.

Understanding the complex role of mTORC as an intracellular critical mediator of whole-body metabolism in anorexia nervosa: A mini review.

Anorexia nervosa (AN) is a kind of malnutrition resulting from chronic self-induced starvation. The reported associated endocrine changes (adaptive and non-adaptive) include hypothalamic amenorrhea, a nutritionally acquired growth hormone resistance with low insulin like growth factor-1 (IGF-1) secretion, relative hypercortisolemia, decreased leptin and insulin concentrations, and increased ghrelin, PYY and adiponectin secretion. The combined effect of malnutrition and endocrinopathy may have deleterious effects on multi-organs including bone, gonads, thyroid gland, and brain (neurocognition, anxiety, depression, and other psychopathologies). The mammalian target of rapamycin (mTOR) is a kinase that in humans is encoded by the mTOR gene. Recent studies suggest an important role of mTOR complex in integration of nutrient and hormone signals to adjust energy homeostasis. In this review, we tried to elucidate the role/s of mTOR as critical mediator of the cellular response in anorexia nervosa.

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.

The Prevalence of the Different Components of the Metabolic Syndrome (MetS) in Obese Nondiabetic Children and Young Adolescents and their Anthropometric Data in Relation to Parents.

In Qatar, the prevalence of metabolic syndrome (MetS) in children and adolescents is increasing in parallel with the increasing trends in obesity rates. In Qatar, the prevalence of obesity is relatively high. AIM: To assess the prevalence of the different components of MetS and plasma atherogenic indexes (AIP) in obese children and adolescents and to compare their anthropometric data with their parents (genetic background). METHODOLOGY: We analysed the anthropometric and biochemical profile of 91 randomly selected obese children and young adolescents (age: 10.5 ± 2.7 years) who attended to the Paediatric Clinic of Hamad Medical Center (HGH) in Doha (Qatar) form January 2017 to December 2019.  Data recorded included: age, gender, weight and height, body mass index (BMI), systolic and diastolic blood pressures. Biochemical data including lipid profile, glycated hemoglobin (A1C), and alanine transferase level (ALT) were recorded and compared with normal lab data for the same age group. RESULTS: Obese children had a high prevalence of dyslipidaemia, dysglycemia and non-alcoholic fatty liver disease (NAFLD). Using the modified adult MetS criteria, MetS was present in 30.2% of this obese cohort. AIP was high in 76.7% of the patients. Standing height standard deviation score (Ht-SDS) of obese children was significantly higher compared to Ht-SDS of their parents as well as to mid-parental height SDS (MPHt-SDS) (-0.37± 0.79). The BMI and BMI-SDS did not differ between obese children and their parents. CONCLUSION: The occurrence of MetS in 30% of our obese non-diabetic children and young adolescents pointed out to the necessity to impose early detection and preventive measures on a national scale.

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.

Epidemiology, genetic landscape and classification of childhood diabetes mellitus in the State of Qatar.

AIMS/INTRODUCTION: To study the epidemiology, genetic landscape and causes of childhood diabetes mellitus in the State of Qatar. MATERIALS AND METHODS: All patients (aged 0-18 years) with diabetes mellitus underwent biochemical, immunological and genetic testing. American Diabetes Association guidelines were used to classify types of diabetes mellitus. The incidence and prevalence of all the different types of diabetes mellitus were calculated. RESULTS: Total number of children with diabetes mellitus was 1,325 (type 1 n = 1,096, ≥1 antibody; type 2 n = 104, type 1B n = 53; maturity onset diabetes of the young n = 20; monogenic autoimmune n = 4; neonatal diabetes mellitus n = 10;, syndromic diabetes mellitus n = 23; and double diabetes mellitus n = 15). The incidence and prevalence of type 1 diabetes were 38.05 and 249.73 per 100,000, respectively, and for type 2 were 2.51 and 23.7 per 100,000, respectively. The incidence of neonatal diabetes mellitus was 34.4 per 1,000,000 live births, and in indigenous Qataris the incidence was 43.6 per 1,000,000 live births. The prevalence of type 1 diabetes and type 2 diabetes in Qatari children was double compared with other nationalities. The prevalence of maturity onset diabetes of the young in Qatar was 4.56 per 100,000. CONCLUSIONS: This is the first prospective and comprehensive study to document the epidemiology and genetic landscape of childhood diabetes mellitus in this region. Qatar has the fourth highest incidence of type 1 diabetes mellitus, with the incidence and prevalence being higher in Qatari compared with non-Qatari. The prevalence of type 2 diabetes mellitus is also higher in Qatar than in Western countries. The incidence of neonatal diabetes mellitus is the second highest in the world. GCK is the most common form of maturity onset diabetes of the young, and a large number of patients have type 1B diabetes mellitus.

Clinical features, epidemiology, autoantibody status, HLA haplotypes and genetic mechanisms of type 1 diabetes mellitus among children in Qatar.

To describe the clinical features, epidemiology, autoantibody status, HLA haplotypes and genetic mechanisms of type 1 diabetes mellitus (T1DM). Patients (0-18 years) with diabetes were recruited. Clinical data was collected, autoantibodies and c-peptide were measured. Whole Genome Sequencing was performed. Genomic data analysis was compared with the known genes linked with T1DM and HLA alleles were studied. 1096 patients had one or more antibody positivity. The incidence of T1DM in 2020 was 38.05 per 100,000 children and prevalence was 249.73. GADA was the most common autoantibody followed by IAA. Variants in GSTCD, SKAP2, SLC9B1, BANK1 were most prevalent. An association of HLA haplotypes DQA1*03:01:01G (OR = 2.46, p value = 0.011) and DQB1*03:02:01G (OR = 2.43, p value = 0.022) was identified. The incidence of T1DM in Qatar is the fourth highest in the world, IA2 autoantibody was the most specific with some patients only having ZnT8 or IA2 autoantibodies thus underlining the necessity of profiling all 4 autoantibodies. The genes associated with T1DM in the Arab population were different from those that are common in the Caucasian population. HLA-DQ was enriched in the Qatari patients suggesting that it can be considered a major risk factor at an early age.