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Introduction The COVID-19 pandemic might have a multifaceted effect on children with type 1 diabetes (T1D), either directly through infection itself or indirectly due to measures implemented by health authorities to control the pandemic. Objective To compare data on children newly diagnosed with T1D in Kuwait during the COVID-19 pandemic to the pre-pandemic period. Research design and methods We analysed data on children aged 12 years or less registered in the Childhood-Onset Diabetes electronic Registry (CODeR) in Kuwait. Data were incidence rate (IR), diabetic ketoacidosis (DKA), and its severity and admission to the paediatric intensive care unit (PICU). Results The IR of T1D was 40.2 per 100,000 (95% CI; 36.0-44.8) during the COVID-19 pandemic period and was not statistically different from pre-pandemic. A higher proportion of incident T1D cases presented with DKA and were admitted to the PICU during the pandemic (52.2% vs. 37.8%: p ˂ 0.001, 19.8% vs. 10.9%; p = 0.002, respectively). The COVID-19 pandemic was positively associated with presentation of DKA and admission to PICU (AOR = 1.73; 95% CI, 1.13-2.65; p = 0.012, AOR = 2.04; 95% CI, 1.13-3.67; p = 0.018, respectively). Children of families with a positive history for diabetes were less likely to present with DKA and get admitted to the PICU during the COVID-19 pandemic (AOR = 0.38; 95% CI, 0.20-0.74; p = 0.004, AOR = 0.22; 95% CI, 0.08-0.61; p = 0.004, respectively). Conclusion High rates of DKA at presentation and admission to PICU in incident T1D cases during the COVID-19 pandemic warrant further studies and effective mitigation efforts through increasing awareness, early detection, and timely intervention.

Aim: To evaluate the efficacy and safety of once‑weekly exenatide (EQW) in youth with T2D. Methods: Participants (aged 10 to Results: Overall, 83 participants were randomized (exenatide: 59; placebo: 24); 72 completed 24-week treatment. Baseline characteristics were mostly balanced between groups. At 24 weeks, EQW was superior to placebo in lowering HbA1c; the least squares mean (LSM) change in HbA1c was −0.36% for EQW and +0.49% for placebo (between-group difference: −0.85%; P=0.012). Nonsignificant LSM differences from baseline to 24 weeks favoring EQW were observed for FG (−21.6 mg/dL; 95% CI: −49.0, 5.7; P=0.119), SBP (−2.8 mmHg; 95% CI: −8.0, 2.4; P=0.284), and body weight (−1.22 kg; 95% CI: −3.59, 1.15; P=0.307). EQW was well tolerated; AEs occurred in 61.0% and 73.9% and serious AEs in 3.4% and 4.3% of participants in the EQW and placebo groups, respectively. Conclusion: In youth with T2D sub-optimally controlled with current treatments, EQW was effective in improving metabolic control. EQW was well-tolerated and no AEs led to treatment discontinuation by the investigator. Disclosure W. V. Tamborlane: Consultant; Self; Medtronic, Sanofi, Other Relationship; Self; Tolerion, Inc. C. Sjostrom: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. R. Bishai: Employee; Self; AstraZeneca. D. Geller: None. N. Shehadeh: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Self; Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk, Sanofi. D. Al-abdulrazzaq: None. E. Karoly: None. O. Doehring: Employee; Self; AstraZeneca. D. Carter: Employee; Self; AstraZeneca. J. Monyak: Employee; Self; AstraZeneca.

Background To evaluate the safety of fasting during the holy month of Ramadan among children and adolescent with type 1 diabetes (T1D). Methods A retrospective cohort study of 50 children and adolescents with T1D whose mean age was 12.7 ± 2.1 years was conducted. Twenty-seven patients (54%) were on multiple daily injections (MDI) insulin regimen and 23 (46%) were on insulin pump therapy. Before fasting for Ramadan, children and their families were evaluated and educated about diabetes management during Ramadan. Hemoglobin A1c (HbA1c), weight, number of days fasted, hypoglycemia and hyperglycemia episodes, and emergency hospital visits were collected and analyzed after completing the month. Participants were compared according to the insulin treatment regimen and their glycemic control level before Ramadan. Results The children were able to fast 20 ± 9.9 days of Ramadan, and the most common cause for breaking the fast was mild hypoglycemia (7.8% among all cases). There was no significant difference between the two insulin regimen groups in breaking fast days, frequency of hypo- or hyperglycemia, weight and HbA1c changes post Ramadan. Patients with HbA1c ≤ 8.5% were able to fast more days during Ramadan with significantly less-frequent hypoglycemic attacks as compared to patients with HbA1c > 8.5 (1.2 ± 1.5 vs. 3.3 ± 2.9 days of hypoglycemia, p = 0.01, respectively). Conclusions Fasting for children with T1D above the age of 10 years is feasible and safe in both pump and non-pump users, and well-controlled patients are less likely to develop complications. Education of the families and their children before Ramadan, along with intensive monitoring of fasting children during the month are crucial.

Aim To report on Rabson–Mendenhall Syndrome (RMS) diagnosed in Kuwait. Methods A toddler (18 months old) was referred with high plasma insulin and dysmorphic features suggestive of RMS including coarse facial features with globular nose, full lips and furrowed tongue. His skin was hyperkeratotic with hypertrichosis. His sister (aged 13.5 years) was diagnosed with diabetes at 9 years of age and treated with metformin and insulin. She presented with similar dysmorphic features, extensive acanthosis nigricans, dental abnormalities and bilateral nephrocalcinosis. The children were born to non-consanguineous parents. Blood samples were sent for genetic testing in a reference laboratory. Results Both children were found to be homozygous for the p.Arg141Trp missense variant (p.Arg114Trp if numbered according to pro-receptor sequence) in the alpha subunit of the insulin receptor. Conclusions These cases demonstrate the importance of raising awareness among healthcare professionals to ensure rapid referral of patients with characteristic physical features of RMS and severe insulin resistance for genetic testing. Unfortunately, treatment of RMS patients remains a challenge with poor prognosis and short life expectancy usually caused by diabetes-related complications. Genetic testing confirms the diagnosis and allows informed genetic counseling of parents considering future pregnancies.

Background: Type 2 Diabetes (T2D) in children and adolescents has become an important public health concern due to the increase in childhood obesity worldwide. The urgency to address T2D is evident as children and adolescents are at a higher risk of complications due to prolonged disease duration. We aimed to estimate the incidence rate (IR) of T2D in Kuwaiti children and adolescents aged 14 years and younger between 2011 and 2013 and to describe their clinical characteristics at the time of diagnosis. Material and Methods: All newly diagnosed patients were registered through the Childhood-Onset Diabetes electronic Registry implemented in Kuwait. Cases who met the 2018 ISPAD guidelines for diagnosis of T2D were included. Results: A total of 32 patients were included, equally distributed gender-wise, with a mean age 12.2 years (±1.7 SD), lower for females than males (11.5 vs. 12.2, p < 0.025). Data ascertainment was 94.1% (95%CI; 91.6–96.6%). Overall IR was 2.56 (95% CI; 1.78-3.56) per 100,000 Kuwaiti children and adolescents per year. Most of the patients (n = 30; 93.8%) presented with T2D between the ages 10–14 years, with age-specific IR of 8.0 (95%CI; 5.5–11.3). No statistically significant difference between males and females with regards to BMI z scores or HbA1C at diagnosis. Conclusion: The true incidence of T2D in Kuwaiti children and adolescents is expected to be considerably higher as we have reported only symptomatic cases. Future research should focus on screening children and adolescents at risk to enable accurate estimates. More efforts are needed to better understand the clinical course of T2D early in life to improve management, prevent complications and improve quality of life.

AIMS This study had 2 aims: to report data on the incidence of childhood-onset type 1 diabetes in Kuwaiti children aged 0-14 years during 2011 to 2013 and to compare the recent data with those collected during 1992 to 1997. METHODS All newly diagnosed patients were registered through the Childhood-Onset Diabetes eRegistry (CODeR) in 2011-2013, based on the DiaMond protocol used in 1992-1997. RESULTS A total of 515 Kuwaiti children (247 boys and 268 girls) aged 0-14 years newly diagnosed with type 1 diabetes were registered from 1 January 2011 to 31 December 2013. Data ascertainment were 96.7%. The mean age ± SD at diagnosis was 8.7 ± 3.4 years in boys and 7.9 ± 3.1 years in girls. The crude incidence rate (95% CI) was 40.9 (37.4-44.6) and the age standardized rate 41.7 (95% 38.1-45.4) per 100,000 per year, 39.3 (34.6-44.4) among boys and 44.1 (39.0-49.7) among girls. A statistically significant increasing trend in incidence was observed as the overall crude incidence rose from 17.7 in 1992-1994 to 40.9 per 100,000 per year in 2011-2013. The Poisson regression model depicting the trend in incidence revealed that, the incidence rates adjusted for age and sex in 2011 to 2013 was 2.3 (95% CI 1.9-2.7) times higher than 1992-1997. CONCLUSIONS The incidence of type 1 diabetes in Kuwaiti children 0-14 years has doubled in the last 2 decades. The reasons for this increase requires further investigation.

Objective: In recent decades, the Arab population has experienced an increase in the prevalence of type 2 diabetes (T2DM), particularly within the Gulf Cooperation Council. In this context, early intervention programmes rely on an ability to identify individuals at risk of T2DM. We aimed to build prognostic models for the risk of T2DM in the Arab population using machine-learning algorithms vs. conventional logistic regression (LR) and simple non-invasive clinical markers over three different time scales (3, 5, and 7 years from the baseline). Design: This retrospective cohort study used three models based on LR, k-nearest neighbours (k-NN), and support vector machines (SVM) with five-fold cross-validation. The models included the following baseline non-invasive parameters: age, sex, body mass index (BMI), pre-existing hypertension, family history of hypertension, and T2DM. Setting: This study was based on data from the Kuwait Health Network (KHN), which integrated primary health and hospital laboratory data into a single system. Participants: The study included 1,837 native Kuwaiti Arab individuals (equal proportion of men and women) with mean age as 59.5 ± 11.4 years. Among them, 647 developed T2DM within 7 years of the baseline non-invasive measurements. Analytical methods: The discriminatory power of each model for classifying people at risk of T2DM within 3, 5, or 7 years and the area under the receiver operating characteristic curve (AUC) were determined. Outcome measures: Onset of T2DM at 3, 5, and 7 years. Results: The k-NN machine-learning technique, which yielded AUC values of 0.83, 0.82, and 0.79 for 3-, 5-, and 7-year prediction horizons, respectively, outperformed the most commonly used LR method and other previously reported methods. Comparable results were achieved using the SVM and LR models with corresponding AUC values of (SVM: 0.73, LR: 0.74), (SVM: 0.68, LR: 0.72), and (SVM: 0.71, LR: 0.70) for 3-, 5-, and 7-year prediction horizons, respectively. For all models, the discriminatory power decreased as the prediction horizon increased from 3 to 7 years. Conclusions: Machine-learning techniques represent a useful addition to the commonly reported LR technique. Our prognostic models for the future risk of T2DM could be used to plan and implement early prevention programmes for at risk groups in the Arab population.

Intensive glycemic control reduces the risk of microvascular and macrovascular complications. Furthermore, optimal glycemic control is essential for normal growth and development. Thus, there is a need to monitor and evaluate glycemic control in patients with type 1 diabetes (T1D). Our aim was to audit glycemic control in patients with T1D in a specialized center as per the Society of Pediatric and Adolescent Diabetes (ISPAD) Hemoglobin A1C (HbA1C) target recommendations published in 2014.This is a retrospective cross-sectional study reporting on glycemic control (HbA1C) of patients younger than 21 years of age and with T1D treated at Dasman Diabetes Institute (DDI) between January 2013 and December 2015.A total of 470 patients with T1D (250 males and 220 females) were included. Only 53 (11.3%) patients met the ISPAD target for optimal glycemic control with HbA1C 7.5% (58 mmol/mol). Older age was positively associated with poor glycemic control (p = 0.001) while Continuous Subcutaneous Insulin Infusion (CSII) therapy was negatively associated with poor glycemic control, adjusted Odds Ratio (OR) 0.33 (95% confidence interval (CI): 0.16-0.66) for CSII and adjusted OR 0.42 (95% CI: 0.27-0.64) for shifting to CSII (p 0.001).Achieving optimal glycemic control is a significant challenge for young patients with T1D. Glycemic control goals should be individualized to achieve such goals safely, realistically and with a better quality of life for patients with T1D.

We examined the frequency and severity of diabetic ketoacidosis (DKA) in 679 children and adolescents (0–14 years) at diagnosis of Type 1 Diabetes Mellitus (T1DM) in Kuwait. Between 1st January 2011 and 31st December 2013, all newly diagnosed children with diabetes were registered prospectively in a population-based electronic register. DKA was diagnosed using standard criteria based on the levels of venous pH and serum bicarbonate. At the time of diagnosis, mild/moderate DKA was present in 24.8% of the children, while severe DKA was present in 8.8%. Incidence of ketoacidosis was significantly higher in young children less than 2 (60.7% vs 32.4% p =

BACKGROUND The aim of the study was to describe the referral pattern, baseline characteristics, and etiological profile of children referred with short stature in Kuwait. METHODS This is a cross-sectional retrospective review of children referred to the Endocrine Clinic with short stature. Short stature was defined as height or length below the 3rd centile or

Background Recombinant Growth hormone (rGH) therapy is approved in many countries for treatment of short stature in a number of childhood diagnoses. Despite the increasing body of international literature on rGH use, there is paucity of data on rGH use in Kuwait and the broader Middle-East which share unique ethnic and socio-cultural backgrounds. This study aimed to describe the pattern of use and treatment outcomes of rGH therapy in Kuwait. Methods This is a cross-sectional retrospective review of children treated with rGH in the Department of Pediatrics, in a major hospital in Kuwait between December 2013 and December 2014. Data were extracted using standard data extraction form and the response to rGH therapy was defined as a gain of ≥ 0.3 standard deviation score (SDS) of height per year. Results A total of 60 children were treated with rGH in the center. Their Median (Interquartile) age at rGH initiation was 9.0 (6.2, 10.7) years. The most common indications for rGH therapy were Growth Hormone Deficiency (GHD) 23 (38.3 %), Idiopathic Short Stature (ISS) 12 (20.0 %) and Small for Gestational Age (SGA) 9 (15.0 %). After excluding patients with TS, no significant differences were found in gender of those who received rGH therapy in all indications combined or in each group (p ≥ 0.40). At 1-year follow-up, children in all groups had median height SDS change of ≥ 0.3 SDS except for children with ISS. Age at rGH initiation was negatively associated with 1-year treatment response, Adjusted odds ratio (AOR) 0.56 (95 % CI: 0.04–1.49); p = 0.011). Conclusions GHD is the most common indication of rGH therapy. All indications except for ISS showed significant 1-year treatment response to therapy. Treatment outcomes in patients with ISS should be further investigated in Kuwait. Younger age at initiation of rGH therapy was independently associated with significant response to therapy suggesting the importance of identifying children with short stature and prompt initiation of rGH therapy.

Objective: Continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) are two methods currently used to manage type I diabetes mellitus (T1DM). Here we compare our experiences with CSII and MDI in a large cohort of pediatric patients in Kuwait. Methods: Data on 326 patients with T1DM who were started on CSII between 2007 and 2012 were retrospectively compared with those of 326 patients on MDI. They were matched for sex, age at diagnosis, T1DM duration, glycemic control, insulin requirement, and body mass index (BMI). Data were collected at baseline and every three months and included glycated hemoglobin (HbA1c), insulin dose, and adverse events (severe hypoglycemia, diabetic ketoacidosis, and skin problems). Results: The main reason for switching to CSII was to achieve better glycemic control (37%), followed by reducing hypoglycemia, and improving the quality of life (13.3% each). Although HbA1c decrease was most significant in the first year, it continued to be significantly lower in the CSII group compared to the MDI throughout the study period. Total daily insulin requirements were significantly lower in the CSII group. BMI increased in both groups, but the difference was significant only at the end of the fifth year. There was no significant change in the rate of diabetic ketoacidosis in either group. The CSII patients had more severe hypoglycemic episodes at baseline; however, it significantly decreased throughout the study period. Only five patients discontinued CSII therapy and two of these restarted within three months. Conclusion: CSII is a safe intensive insulin therapy in youngsters with T1DM and achieved markedly fewer severe hypoglycemic episodes and lower daily insulin requirements

Wafa'a Al-Qabandi,1 Eman Buhamrah,2 Dalia Al-Abdulrazzaq,1 Khaled Hamadi,2 Fawaz Al Refaee3 1Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait; 2Department of Pediatrics, Al Amiri Hospital, Kuwait; 3Department of Pediatrics, Al Adan Hospital, Kuwait All authors contributed equally to the study Background: Celiac disease (CD) is a chronic inflammatory disease of the small intestine triggered by gluten ingestion. The objective of this study is to describe our experience with CD children in Kuwait. Methods: The records of children with CD seen in the pediatric gastroenterology unit between February 1998 and December 2010 were retrospectively reviewed. Patients were referred because of symptoms or positive CD antibody screening of a high-risk group (type 1 diabetes and Down syndrome). Results: Forty-seven patients were diagnosed: 53% were symptomatic and 47% were identified by screening. The median age at diagnosis was 66 (range 7–189) months. All cases were biopsy-proven except one. The symptomatic patients were significantly younger than those identified following screening (P

Hyperparathyroidism Jaw-Tumour Syndrome (HPT-JT) is characterized by primary hyperparathyroidism (PHPT), maxillary/mandible ossifying fibromas and by parathyroid carcinoma in 15% of cases. Inactivating mutations of the tumour suppressor CDC73/HRPT2 gene have been found in HPT-JT patients and also as genetic determinants of sporadic parathyroid carcinoma/atypical adenomas and, rarely, typical adenomas, in familial PHPT. Here we report the genetic and molecular analysis of the CDC73/HRPT2 gene in three patients affected by PHPT due to atypical and typical parathyroid adenomas, in one case belonging to familial PHPT. Flag-tagged WT and mutant CDC73/HRPT2 proteins were transiently transfected in HEK293 cells and functional assays were performed in order to investigate the effect of the variants on the whole protein expression, nuclear localization and cell overgrowth induction. We identified four CDC73/HRPT2 gene mutations, three germline (c.679_680delAG, p.Val85_Val86del and p.Glu81_Pro84del), one somatic (p.Arg77Pro). In three cases the mutation was located within the Nucleolar Localisation Signals (NoLS). The three NoLS variants led to instability either of the corresponding mutated protein or mRNA or both. When transfected in HEK293 cells, NoLS mutated proteins mislocalized with a predeliction for cytoplasmic or nucleo-cytoplasmic localization and, finally, they resulted in overgrowth, consistent with a dominant negative interfering effect in the presence of the endogenous protein.

Objective The “accelerator hypothesis” predicts early onset of Type 1 diabetes (T1D) in heavier children. Studies testing direction of correlation between body mass index (BMI) and age at onset of T1D in different continental populations have reported differing results–inverse, direct, and neutral. Evaluating the correlation in diverse ethnic populations is required to generalize the accelerator hypothesis. Methods The study cohort comprised 474 Kuwaiti children of Arab ethnicity diagnosed with T1D at age 6 to 18 years during 2011–2013. Age- and sex-adjusted BMI z-scores were calculated by comparing the BMI measured at diagnosis with Kuwaiti pediatric population reference data recorded during comparable time-period. Multiple linear regression and Pearson correlation analyses were performed. Results BMI z-score was seen inversely associated with onset age (r,-0.28; p-value0 (i.e. BMI >national average) showed a stronger correlation (r,-0.38; p-value