Hessa Alkandari

Aims: Kuwait has one of the highest global incidences of childhood type 1 diabetes (T1D), yet little is known about the burden of coeliac disease (CD) in this population. We aimed to determine the prevalence/incidence of CD in children newly diagnosed with T1D in Kuwait and identify associated risk factors. Methods: In this prospective cohort study, all 1938 children (≤ 14 years) diagnosed with T1D in Kuwait between 2011 and 2017 were enrolled and followed for 5 years post‐diagnosis. CD development was defined by intestinal biopsy confirmation. Cox univariable regression models quantified associations between several characteristics at T1D diagnosis (age, sex, DKA, height z‐score and BMI z‐score) and incident CD risk. Results: Four baseline CD cases were excluded. Of the remaining 1934 children, 65 (3.4%) developed CD during follow‐up. The median time to CD diagnosis was 1.5 years; 40% were diagnosed within the first year. The incidence rate within the first year following T1D diagnosis was 1.35 (95% CI 0.92–1.99) per 100 person‐years and generally declined over subsequent years of follow‐up. While age at diagnosis showed no clear effect shortly after T1D diagnosis, older age was associated with progressively lower CD risk over longer follow‐up, with the risk of CD being 33% lower per one‐year increase in age at diagnosis by 5 years of follow‐up; no other baseline factors investigated were significant. Conclusion: This nationwide prospective study highlights the burden and timing of biopsy‐confirmed CD after T1D onset. CD occurred most frequently during the early years after T1D diagnosis, with a higher risk among younger children, supporting particular attention to screening in these groups.

Background/Objectives: Multisystem inflammatory syndrome in children (MIS-C), a rare but serious post-acute hyperinflammatory condition that occurs in children 2–6 weeks after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection or exposure, varies between countries. Despite its serious nature, most children recover without any sequelae. The most frequently reported long-term sequelae are coronary artery aneurysms. This study aimed to describe the epidemiological profile, clinical characteristics (including cardiac manifestations), treatment, and outcomes of multisystem inflammatory syndrome in children (MIS-C) under 14 years of age with SARS-CoV-2 between February 2020 and November 2021 in Kuwait. Methods: Data on sociodemographic factors, co-morbidities, presenting signs and symptoms, as well as laboratory and echocardiography findings were retrieved from the Pediatric COVID registry (PCR-Q8 registry). Results: Of the one hundred and two patients with a provisional diagnosis of MIS-C, eighty-three patients fulfilled the WHO criteria of MIS-C. Thirty-nine of the MIS-C patients were admitted to the intensive care unit, and only one child died due to cardiogenic shock. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Most (63% (10/16)) of the patients had coronary abnormalities, nine patients (56%) had myocardial dysfunction, and six patients (38%) had dual pathologies. Pericarditis occurred in three patients only, whilst six patients (38%) had dual pathologies. Pericarditis occurred in three patients only. Conclusions: MIS-C appears to affect younger children in Kuwait than in other countries; however, the clinical pattern is consistent with other countries. Further studies of an analytical nature are recommended to identify the risk factors associated with MIS-C and its cardiac sequalae to allow for proactive risk reduction.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication arising from SARS-CoV-2 infection, with indications that rare inborn errors of immunity may play a role in its pathogenesis. Recent studies suggest that genetic predispositions, particularly monogenic forms, could significantly influence the immune responses to SARS-CoV-2 in MIS-C.Methods: We analysed 24 children under 12 years old, all of whom met the criteria provided by the World Health Organization, 2020 for MIS-C diagnosis, from the Paediatric COVID-19 Registry in Kuwait (PCR-Q8). Demographic and clinical data were collected from medical records, and exome sequencing was performed on the children and their parents to identify rare exonic variants. These variants were prioritized using two approaches: a candidate genes approach employing trio segregation analysis, and a candidate variants approach using a gene panel informed by previous studies on MIS-C-related genetic variants and datasets of differentially expressed genes in MIS-C patients.Results: The candidate genes approach identified 53 unique genes in 20 of the 24 probands, including DDX60 and TMEM154, which were also differentially expressed between MIS-C and control groups. The candidate variants approach identified 33 rare, predicted deleterious heterozygous variants across 19 unique genes in 19 of the 24 probands, including both previously described and novel candidate variants for MIS-C. Pathway analysis of the identified genes from both approaches revealed significant involvement in immune response, viral defence, and inflammatory pathways.Conclusion: This study underscores the monogenic susceptibility to MIS-C, enhancing the evidence base through comprehensive genetic analysis. The findings highlight the critical role of genetic predispositions in MIS-C and suggest that further functional genomics work is necessary to explore the mechanistic contributions of these genes, facilitating the development of targeted diagnostic strategies.

Background: There is limited information about the management of cardiovascular (CV) risk in patients with type 2 diabetes (T2D) in the Middle East and Africa. For patients with T2D and established atherosclerotic cardiovascular disease (eASCVD) or those at risk for ASCVD, global guidelines recommend the use of antidiabetic medications with proven cardiovascular and kidney benefit (glucagon-like peptide-1 receptor agonists [GLP-1 RAs] and sodium-glucose cotransporter-2 inhibitors [SGLT2is]), in addition to lipid lowering, blood pressure lowering, and antiplatelet therapy, independent of baseline HbA1c or metformin use. Purpose: To determine the use of pharmacotherapy among a population of patients with T2D and eASCVD or high/very high ASCVD risk in seven countries across the Middle East and Africa. Methods: Adult patients with T2D were enrolled in a cross-sectional, observational study in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa, and United Arab Emirates. Pharmacotherapy data extracted from the medical charts of patients during a routine scheduled clinic visit in 2022 were analysed. Descriptive statistics were used to characterize patients with T2D and their glucose-lowering pharmacotherapy use by age, diabetes duration, body mass index, HbA1c, microvascular complications, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR). Results: Of the 3726 patients in the overall study sample (mean age, 58 ± 12; male, 53%), one in five had eASCVD (21%) and nearly all were classified as being at high (69%)/very high risk (30%, includes eASCVD), according to European Society of Cardiology (ESC) 2021 guidelines. About one-third (36%) of patients were taking SGLT2is (Table 1, range across countries: 20%-64%). Use of SGLT2is was similar across age and BMI but more patients with T2D for ≥10 years (40%) received these medications than those with T2D for <10 years (31%). More males than females were on SGLT2is (40% vs 32%). Use of SGLT2is was also higher among patients with HbA1c ≥7% (42% vs 33%, Table 2). SGLT2i use was similar by eGFR and UACR levels. Few (13%) of the overall sample of patients with T2D received GLP-1 RAs (Table 1, range across countries: 3%-25%), the use of which declined with age. More females than males were taking GLP1-RAs (16% vs 11%). More patients with obesity (BMI ≥30 kg/m2) received GLP-1 RAs than those without obesity (18% vs 8%); use was also higher among patients with eGFR ≥60 (14% vs 9%, Table 2). Conclusions: Despite availability of cardio-renal therapy in each of the seven participating countries in the Middle East and Africa, few patients with T2D who had eASCVD or were at high/very high risk for ASCVD received SGLT2is or GLP-1 RAs, as recommended by guidelines. Active prioritization of cardio-renal protective therapies based on CV risk and renal target organ damage should be addressed given the high burden of disease and complications in the region.Table 1Table 2

Introduction: Mucopolysaccharidosis type I (MPSI) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and nonspecific symptoms resulting in high morbidity and mortality. The incidence of MPSI in US is estimated to be 0.26:100,000, however, it is unknown in Kuwait. This pilot study was undertaken to screen MPSI in all Kuwaiti neonates born at Farwaniya Hospital over a period of 12-months. This study examined the incidence of MPSI in a major center in Kuwait for inclusion in the national newborn screening program to enable its early detection and adequate treatment. Methods: All Kuwaiti neonates born at Farwaniya Hospital, Kuwait from December 2021 to December 2022, were screened for MPSI. The screening consisted of determining IDUA enzyme activity in dried blood spots (DBS)-derived samples by Tandem Mass Spectrometry. A follow-up genetic analysis of IDUA gene is planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. Results: A total of 618 newborns, including 331 (54%) males and 287 (46%) females, were screened. Twenty of them had deficient IDUA enzyme activity but showed negative genetic testing for IDUA. However, we have diagnosed one additional female baby with MPSI, who belonged to Farwaniya Hospital, but the parents chose to deliver in a private hospital. She presented at age three months with recurrent upper airway infections, snoring and extensive Mongolian spots. The molecular study revealed previously reported pathogenic nonsense variant in IDUA c.1882C>T; p.(Arg628Ter), associated with severe phenotype. That being included, MPSI is estimated to be about 0.3% among tested females and 0.2% of all screened cases in Kuwait. Conclusion: Our study is the first to evaluate the incidence of MPSI in Kuwait. Given the single center, small number of screened babies and the short study duration thus far, it is premature to calculate the incidence of MPSI. It is anticipated that as the study continues and more infants are examined, we would be able to estimate the incidence of this disease in our population correctly. Further studies including screening newborns in all maternity hospitals in Kuwait are needed to calculate the actual incidence of MPSI. Our data supports including MPSI in national newborn screening program to allow early initiation of treatment and thus improve disease outcome.

Aim: To assess the level of glycemic, blood pressure, and cholesterol control (the ‘ABCs’) nationally amongst adults with diabetes living in Kuwait.Materials and Methods: Using data from two national cross‐sectional surveys, the levels of risk factor control were assessed in 1,801 adults with diabetes, aged 18–82 years. Glycemic control was defined as HbA1c < 7%, blood pressure control as systolic and diastolic blood pressures of <140/90 mmHg, and non‐HDL cholesterol control as <3.4 mmol/L.Results: The percentage of adults with diabetes achieving control was 39.2% (95% CI, 37.0–41.5) for glycemia, 58.4% (95% CI, 56.0–60.7) for blood pressure, and 28.3% (95% CI, 26.3–30.4) for non‐HDL cholesterol. The percentage of adults who were non‐smokers was 77.6% (95%, CI 75.6–79.4). The percentage of adults with diabetes achieving control on all three risk factors was 7.4% (95% CI, 6.3–8.8), and only 5.8% (95% CI, 4.8–7.0) achieved ABC control and were nonsmokers. ABC control was 30% higher in women compared with men. Non‐Kuwaitis were almost twice as likely to have uncontrolled ABC factors compared with Kuwaitis.Conclusions: Only 1 in 13 people with diabetes in Kuwait achieved good control of glycemia, blood pressure, and cholesterol. Only 2 in 5 achieved glycemic control, 6 in 10 blood pressure control, and 2 in 7 cholesterol control. A national diabetes quality improvement program is urgently needed to improve the quality of care and to prevent long‐term complications.

The corticotropin-releasing hormone (CRH) and urocortins (UCNs) have been implicated in energy homeostasis and the cellular stress response. However, the expression of these neuropeptides in children remains unclear. Therefore, we determined the impact of obesity on their expression in 40 children who were normal weight, overweight, and had obesity. Peripheral blood mononuclear cells (PBMCs) and plasma were used to assess the expression of neuropeptides. THP1 cells were treated with 25 mM glucose and 200 µM palmitate, and gene expression was measured by real-time polymerase chain reaction (RT-PCR). Transcript levels of neuropeptides were decreased in PBMCs from children with increased body mass index as indicated by a significant decrease in UCN1, UCN3, and CRH mRNA in overweight and obese children. UCN3 mRNA expression was strongly correlated with UCN1, UCN2, and CRH. Exposure of THP1 cells to palmitate or a combination of high glucose and palmitate for 24 h increased CRH, UCN2, and UCN3 mRNA expression with concomitant increased levels of inflammatory and endoplasmic reticulum stress markers, suggesting a crosstalk between these neuropeptides and the cellular stress response. The differential impairment of the transcript levels of CRH and UCNs in PBMCs from overweight and obese children highlights their involvement in obesity-related metabolic and cellular stress.