Prevalence and factors associated with thyroid autoimmunity among children newly diagnosed with type 1 diabetes before and during the COVID-19 pandemic: Evidence from Kuwait.

AIMS: This study reports the prevalence and characteristics related to the development of thyroid autoimmunity among children newly diagnosed with type I diabetes (T1D) during the COVID-19 pandemic in Kuwait. MATERIALS AND METHODS: This is a prospective observational study of all children under age 14 years newly diagnosed with T1D in Kuwait. We define the duration of the COVID-19 pandemic from the official declaration of the first identified positive COVID-19 case on 24 February 2020 until 31 December 2022. For comparison, we use the time period directly before the COVID-19 pandemic, 1 January 2017 to 23 February 2020. RESULTS: One thousand twenty-four (1024) children newly diagnosed with T1D in Kuwait during the study period were included. Among newly diagnosed children, 20.3% tested positive for thyroid antibodies during the COVID-19 pandemic, compared with 14.5% during the pre-pandemic period (p = 0.015). Children with positive COVID-19 status were more likely to present with thyroid antibodies (p = 0.035). After adjusting for other characteristics, patients diagnosed with T1D during the COVID-19 pandemic had double the odds of testing positive for thyroid antibodies (Adjusted odds ratio = 2.173, 95%CI: 1.108, 4.261, p = 0.024). CONCLUSIONS: Incident cases of T1D during the COVID-19 pandemic may be different in aetiology or contextual factors leading to a higher risk of thyroid autoimmunity. Longitudinal studies are needed to understand the role of COVID-19 in the onset and progression of T1D and on thyroid autoimmunity and disease.

Lessons Learned From COVID-19 Lockdown: An ASPED/MENA Study on Lifestyle Changes and Quality of Life During Ramadan Fasting in Children and Adolescents Living With Type 1 Diabetes.

Background: Lockdown was a unique experience that affected many aspects of life, particularly during the challenge of Ramadan fasting (RF). Studying this can increase understanding of the effects of lifestyle changes on quality of life (QoL) for children with type 1 diabetes (T1D) during RF. Methods: A cross-sectional study that assessed the effect of lockdown on lifestyle and QoL on fasting children living with T1D during Ramadan in the Middle East and North Africa region (2020-2021). We compared the child (self) and parent (proxy) reports using PEDQoL v3.0 disease specific questionnaire during lockdown and non-lockdown periods, and assessed correlations with lifestyle changes using regression and gap analyses. Results: A total of 998 reports from 499 children with T1D aged 8 to 18 years (study = 276, control = 223), and their parents during RF in lockdown and non-lockdown periods. Fathers were more involved in their children's care during lockdown (P = .019). Patients had better compliance with treatment (P = .002), a reversed sleep pattern (P = .033), increased food intake (P ⩽ .001), and less exercise (P < .001). Children and parents perceived better QoL during lockdown (P ⩽.001) with no differences between their reports in "Diabetes Symptoms", "Treatment Adherence," and "Communication" domains. Self and proxy reports were different in all domains during non-lockdown (P = <.001-.009). In gap analysis, although not statistically significant, the gap was approximated between children's and parents' perceptions in all domains during lockdown. Conclusion: COVID-19 lockdown had a positive impact on QoL of children living with T1D during RF, possibly due to lifestyle changes and superior psychosocial family dynamics.

Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children.

Type 1 diabetes (T1D) is a complex autoimmune disorder that is highly prevalent globally. The interactions between genetic and environmental factors may trigger T1D in susceptible individuals. HLA genes play a significant role in T1D pathogenesis, and specific haplotypes are associated with an increased risk of developing the disease. Identifying risk haplotypes can greatly improve the genetic scoring for early diagnosis of T1D in difficult to rank subgroups. This study employed next-generation sequencing to evaluate the association between HLA class II alleles, haplotypes, and amino acids and T1D, by recruiting 95 children with T1D and 150 controls in the Kuwaiti population. Significant associations were identified for alleles at the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci, including DRB1*03:01:01, DQA1*05:01:01, and DQB1*02:01:01, which conferred high risk, and DRB1*11:04:01, DQA1*05:05:01, and DQB1*03:01:01, which were protective. The DRB1*03:01:01~DQA1*05:01:01~DQB1*02:01:01 haplotype was most strongly associated with the risk of developing T1D, while DRB1*11:04-DQA1*05:05-DQB1*03:01 was the only haplotype that rendered protection against T1D. We also identified 66 amino acid positions across the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes that were significantly associated with T1D, including novel associations. These results validate and extend our knowledge on the associations between HLA genes and T1D in Kuwaiti children. The identified risk alleles, haplotypes, and amino acid variations may influence disease development through effects on HLA structure and function and may allow early intervention via population-based screening efforts.

Association of interleukin-4, interleukin-13 gene polymorphisms, HLA-DQ and DR genotypes with genetic susceptibility of type-1 Diabetes Mellitus in Kuwaiti children.

Background: Type-1 diabetes mellitus (T1DM) is a complex multifactorial disease with an autoimmune etiology and is thought to result from an interaction between genetic and non-genetic factors. Cytokines play a crucial role in the pathogenesis of autoimmune diseases due to their effector and regulatory functions in immune responses. Interleukin-4 (IL4) and Interleukin-13 (IL13) are anti-inflammatory cytokines and are considered as important mediators in pathology of the autoimmune diseases. Methods: We have determined the genotype frequency of IL4 gene promoter polymorphism (-590C/T, rs2243250), IL13 gene polymorphism p.(Arg130Glu, rs20541) and human leukocyte antigen, HLA-DQ and DR genotypes in Kuwaiti children with T1DM to investigate their role in genetic susceptibility. This study included 261 Kuwaiti children with T1DM and 214 healthy controls. The genotypes for IL4 (-590C/T) and IL13 p.(Arg130Glu) gene polymorphisms were detected by PCR-RFLP methods. HLA-DQ and DR genotypes were determined by sequence-specific PCR methods. Results: The CC genotype of IL4 gene polymorphism (-590C/T) was significantly related to the risk for T1DM in Kuwaiti patients (OR 1.64). The homozygous AA (QQ) and heterozygous AG (RQ) genotypes of IL13 gene polymorphism p.(Arg130Glu), also manifested a statistically significant association with T1DM (OR 2.92 and 4.79). In 55% T1DM patients, the HLA genotype was either DQ2/DQ2 or in combination with a DQ8 allele. Collectively, 91% Kuwaiti T1DM patients had either DQ2 or DQ8 alleles in different combinations highlighting them as the high risk-genotypes in comparison to the controls. In the case of HLA-DR, the genotypes DR3/DRB5, DR3/DR4, DR3/DR7 and DR4/DR4 showed highest frequency amongst the Kuwaiti T1DM patients and thus can be considered as high-risk genotypes when compared to the controls. A high degree of co-inheritance (>80%) was detected between IL4 and IL13 gene polymorphism genotypes (CC and QQ) and the high-risk HLA-DQ and DR genotypes amongst the Kuwaiti T1DM patients. Conclusions: We have identified the association of IL4 and IL13 gene polymorphisms with susceptibility to T1DM in Kuwaiti children and the co-inheritance of these polymorphisms with high-risk HLA genotypes. The findings may contribute to early identification of childhood diabetes.

Epidemiological trends in the presentation of diabetic ketoacidosis in children newly diagnosed with type 1 diabetes from 2011 to 2017 in Kuwait.

Background: Monitoring the trends in the presentation of T1D over decades cannot be underestimated as it provides a rich source of information on diabetes-related complications like DKA. DKA represents a medical emergency, with potentially fatal outcome, and thus the prevention of DKA is a priority in diabetes care. The aim of this study is to report on trends in the presentation of DKA in children newly diagnosed with T1D in Kuwait. Material and methods: This study is based on a retrospective review of children newly diagnosed with T1D aged 14 years or less at three Governmental Hospitals representing three health sectors out of the total six health sectors in the country during the period 2011-2017. Results: A total of 799 children (376 males and 423 females) were newly diagnosed with T1D. 287 children presented with DKA (35.9%) with only 73 children (9.1%) classified as severe. During the years 2011 to 2017, we note that the percentage of children older than 6 years of age presenting with severe DKA has decreased significantly (p=0.022). Unfortunately, this has not been replicated in children younger than 6 years. Conclusion: This study highlights the importance of continued monitoring of clinical characteristics of children at diagnosis of T1D specifically presenting with DKA to enable diabetes care professionals to appreciate the multifaceted aspects of T1D, in particular the importance of raising awareness of the early signs of the onset of T1D with special attention to DKA and its severe consequences.

Differentially methylated and expressed genes in familial type 1 diabetes.

There has recently been a growing interest in examining the role of epigenetic modifications, such as DNA methylation, in the etiology of type 1 diabetes (T1D). This study aimed to delineate differences in methylation patterns between T1D-affected and healthy individuals by examining the genome-wide methylation of individuals from three Arab families from Kuwait with T1D-affected mono-/dizygotic twins and non-twinned siblings. Bisulfite sequencing of DNA from the peripheral blood of the affected and healthy individuals from each of the three families was performed. Methylation profiles of the affected individuals were compared to those of the healthy individuals Principal component analysis on the observed methylation profiling based on base-pair resolution clustered the T1D-affected twins together family-wide. The sites/regions that were differentially methylated between the T1D and healthy samples harbored 84 genes, of which 18 were known to be differentially methylated in T1D individuals compared to healthy individuals in publicly available gene expression data resources. We further validated two of the 18 genes-namely ICA1 and DRAM1 that were hypermethylated in T1D samples compared to healthy samples-for upregulation in T1D samples from an extended study cohort of familial T1D. The study confirmed that the ICA1 and DRAM1 genes are differentially expressed in T1D samples compared to healthy samples.

HbA1c, blood pressure, and cholesterol control in adults with diabetes: A report card for Kuwait.

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 Pediatric COVID-19 Registry in Kuwait: Methodology and Results of Pilot Phase.

OBJECTIVE: Establishing a pediatric COVID-19 registry in Kuwait (PCR-Q8) was deemed imperative during the pandemic to study children infected with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) focusing on mode of presentation, therapeutic interventions, disease severity, and early outcomes. This manuscript describes the rapid establishment of the PCR-Q8 registry showcasing an infrastructure of the development process and presents the results of the pilot phase. SUBJECT AND METHODS: The registry was developed and implemented using the general key steps from a resource titled "Registries for Evaluating Patient Outcomes: A User's Guide" as a guide for best practice, experience from a previously established pediatric diabetes registry in Kuwait and several other COVID-19 registries developed globally. During the pilot phase, a convenience sample of 120 children was included, of whom 66 (55%) were male. RESULTS: Experience and expertise from other COVID-19 registries; guidance provided by the World Health Organization; and effective collaboration and cooperation between the stakeholders, study group, and data enterers during these challenging times were critical for the development and implementation of the registry. Our results were similar to international reports which showed that most children presented with mild disease (69.2%), majority (70.2%) had normal chest X-ray, and the most common symptom at presentation was fever (77%). CONCLUSION: We anticipate the development of PCR-Q8 to be a stepping-stone for more in-depth investigation of SARS-CoV-2 infection in children in Kuwait and for the establishment of other registries.

Urocortin Neuropeptide Levels Are Impaired in the PBMCs of Overweight Children.

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.

Health-related quality of life of children and adolescents with type 1 diabetes during the COVID-19 pandemic in Kuwait.

Background: With the rapid transmission of COVID-19 globally, countries have implemented strict governmental measures and social distancing rules that aimed to minimize the spread of the virus. School closures, quarantine orders, and social isolation, coupled with a surge in family stress and lack of peer interactions, are probable causes of mental health complications and psychological symptoms faced by children. This study aims at comparing the HRQoL of children and adolescents with type 1 diabetes (T1D) and affected by COVID-19 infection (personal or familial) and those who were not affected by COVID-19. Materials and methods: A random sample was selected from children and adolescents diagnosed with T1D at the six major governmental diabetes centers in Kuwait. To measure HRQoL, parent-proxy and self-reports from the Pediatric Quality of Life Inventory (PedsQLTM) 3.0 Diabetes Module were used. Results: A sample of 455 children and adolescents with T1D diabetes (44.6% male participants and 41.98% affected by COVID-19 infection) was studied. The total score of the HRQoL self-reports was significantly higher compared with parent-proxy reports (79.06 ± 15.19 vs. 73.79 ± 15.17, p < 0.01). Children reported significantly higher HRQoL scores in the "treatment I" domain and "worry" domain and lower scores in the "diabetes" symptoms domain, compared with their parents' reports (p < 0.01). In the COVID-19-affected group, a major difference was noticed between the total scores of children and parent-proxy reports (77.04 ± 15.81 vs. 72.80±14.90, p = 0.047). The affected children reported significantly lower scores in "diabetes" symptoms (59.50) (p < 0.01) and higher scores in the "treatment I" domain (81.43) than their parent-proxy reports (72.05) (p < 0.01). Conclusion: This is the first report on the health-related quality of life of children with T1D in Kuwait during the COVID-19 era. Parents' or caregivers' experience of caring for their children was negative, as they worried, and reported poorer HRQoL compared with their children's perceptions. There is a need to empower healthcare professionals to support parents and caregivers of children with chronic diseases such as T1D in promoting self-management, enhancing physical and psychological wellbeing, treatment adherence, and continuous health education during pandemics of any kind.

Higher rates of diabetic ketoacidosis and admission to the paediatric intensive care unit among newly diagnosed children with type 1 diabetes in Kuwait during the COVID-19 pandemic.

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 Ë‚ 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.

Identification of Maturity-Onset-Diabetes of the Young (MODY) mutations in a country where diabetes is endemic.

Genetic variants responsible for Maturity-Onset-Diabetes of the Young (MODY) in Kuwait were investigated. A newly established a National Referral Clinic, the Dasman Diabetes Institute (DDI-NRC), assessed forty-five members from 31 suspected MODY families by whole exome sequencing. Thirty-three of the 45 samples were independently sequenced at the DDI-NRI, Exeter University, UK ( https://www.diabetesgenes.org/ ) using targeted 21-gene panel approach. Pathogenic mutations in GCK, HNF1A, HNF1B, HNF4A, and PDX1 confirmed MODY in 7 families, giving an overall positivity rate of 22.6% in this cohort. Novel variants were identified in three families in PDX1, HNF1B, and HNF1B. In this cohort, Multiplex Ligation-dependent Probe Amplification assay did not add any value to MODY variant detection rate in sequencing negative cases. In highly selected familial autoantibody negative diabetes, known MODY genes represent a minority and 77.3% of the familial cases have yet to have a causal variant described.

Cultural Adaptation of Health Literacy Measures: Translation Validation of the Newest Vital Sign in Arabic-Speaking Parents of Children With Type 1 Diabetes in Kuwait.

PURPOSE: The purpose of the study was to assess the feasibility of use and reliability of the Arabic version of the Newest Vital Sign (NVS-Ar) in parents of children with type 1 diabetes (T1D). METHODS: The final translated version of NVS-Ar was administered to 175 adult caregivers of children with T1D who are native Arabic speakers. The association between NVS-Ar scores for the parents/legal guardians and A1C for their children was assessed. The internal consistency was evaluated by Cronbach's α, and reliability was assessed by test-retest method. RESULTS: The median (interquartile range) score was 4.0 (3-5). The internal consistency of the NVS-Ar was moderate (α = .58). The intraclass correlation coefficient was .61. There was no correlation between NVS-Ar score and A1C (Spearman's ρ = .055; P = .62). Furthermore, there was significant inverse association between adequate health literacy and optimal glycemic control among the children, which remained evident even after adjusting for the duration of T1D, age, or education of the parents/guardians. However, it lost statistical significance after adjustment for treatment regimen. CONCLUSION: Study findings indicate that the NVS is unlikely to be a predictive tool for functional health literacy in Arabic settings and that there is a need to properly translate and validate other tools such as the Test of Functional Health Literacy in Adults or, alternatively, to develop a reliable tool.

Diagnosis and management of X-linked hypophosphatemia in children and adolescent in the Gulf Cooperation Council countries.

INTRODUCTION: X-linked hypophosphatemia (XLH) is a rare inherited cause of hypophosphatemic rickets and osteomalacia. It is caused by mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX). This results in increased plasma fibroblast growth factor-23 (FGF23), which leads to loss of renal sodium-phosphate co-transporter expression leading to chronic renal phosphate excretion. It also leads to low serum 1,25-dihydroxyvitamin D (1,25(OH)2D), resulting in impaired intestinal phosphate absorption. Chronic hypophosphatemia in XLH leads to impaired endochondral mineralization of the growth plates of long bones with bony deformities. XLH in children and adolescents also causes impaired growth, myopathy, bone pain, and dental abscesses. XLH is the most frequent inherited cause of phosphopenic rickets/osteomalacia. Hypophosphatemia is also found in calcipenic rickets/osteomalacia as a result of secondary hyperparathyroidism. Thus, chronic hypophosphatemia is a common etiologic factor in all types of rickets. RESULTS: There is considerable overlap between symptoms and signs of phosphopenic and calcipenic rickets/osteomalacia. Wrong diagnosis leads to inappropriate treatment of rickets/osteomalacia. Nutritional rickets and osteomalacia are common in the Gulf Cooperation Council countries which include Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman. Due to high levels of consanguinity in the region, genetic causes of phosphopenic and calcipenic rickets/osteomalacia are also common. CONCLUSION: This guideline was developed to provide an approach to the diagnosis of XLH, especially where there is no family history of the disease, and that other related conditions are not mistaken for XLH. We also guide the medical management of XLH with conventional treatment and with burosumab, a recombinant human IgG1 monoclonal antibody to FGF23.

Rabson-Mendenhall Syndrome in a brother-sister pair in Kuwait: Diagnosis and 5 year follow up.

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.

Incidence of Type 2 Diabetes in Kuwaiti Children and Adolescents: Results From the Childhood-Onset Diabetes Electronic Registry (CODeR).

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.

Audit of glycemic control in patients with type 1 diabetes referred to a pediatric clinic in a specialized center in Kuwait.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Relationship of four vitamin D receptor gene polymorphisms with type 1 diabetes mellitus susceptibility in Kuwaiti children.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore, VDR gene may be considered a candidate for T1DM susceptibility. METHODS: The genotypes of four VDR gene polymorphisms were determined in 253 Kuwaiti Arab T1DM patients and 214 healthy controls by PCR-RFLP analysis. Serum concentrations of three autoantibodies i.e. ICA (Islet cell autoantibody), GADA (Glutamic acid decarboxylase) and INS (Insulin autoantibody) were determined by radio-immunoassays. RESULTS: Statistically significant differences were detected between the genotypes of two VDR gene polymorphisms (FokI, C > T, rs10735810 and TaqI, C > T, rs731236) between T1DM patients and controls (P < 0.0001). In both, the frequency of variant alleles was considerably high in T1DM than in the controls. In contrast, the VDR gene ApaI (G > T, rs7975232) and BsmI (A > G, rs1544410) polymorphisms did not show association with T1DM. The homozygous variant genotypes of FokI, ApaI and TaqI polymorphisms show significant differences between various age-of-onset subgroups while no such association was detected in the case of BsmI polymorphism. Significant differences were also noted between heterozygous genotypes of all four polymorphisms especially between 4-6y and > 6y age-of-onset subgroups of T1DM patients. Three autoantibodies, ICA (Islet cell), GADA (glutamate decarboxylase) and INS (insulin) were positively associated to, varying degrees, with T1DM in Kuwaiti Arabs harboring different VDR gene polymorphism genotypes. CONCLUSIONS: Our results demonstrate a significant effect of two VDR gene polymorphisms (FokI and TaqI) and three autoantibodies on genetic susceptibility of T1DM in Kuwaiti Arabs along with other factors.

Association of protein tyrosine phosphatase non-receptor type 22 gene functional variant C1858T, HLA-DQ/DR genotypes and autoantibodies with susceptibility to type-1 diabetes mellitus in Kuwaiti Arabs.

The incidence of type-1 Diabetes Mellitus (T1DM) has increased steadily in Kuwait during recent years and it is now considered amongst the high-incidence countries. An interaction between susceptibility genes, immune system mediators and environmental factors predispose susceptible individuals to T1DM. We have determined the prevalence of protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene functional variant (C1858T; R620W, rs2476601), HLA-DQ and DR alleles and three autoantibodies in Kuwaiti children with T1DM to evaluate their impact on genetic predisposition of the disease. This study included 253 Kuwaiti children with T1DM and 214 ethnically matched controls. The genotypes of PTPN22 gene functional variant C1858T (R620W; rs2476601) were detected by PCR-RFLP method and confirmed by DNA sequencing. HLA-DQ and DR alleles were determined by sequence-specific PCR. Three autoantibodies were detected in the T1DM patients using radio-immunoassays. A significant association was detected between the variant genotype of the PTPN22 gene (C1858T, rs2476601) and T1DM in Kuwaiti Arabs. HLA-DQ2 and DQ8 alleles showed a strong association with T1DM. In T1DM patients which carried the variant TT-genotype of the PTPN22 gene, 93% had at least one DQ2 allele and 60% carried either a DQ2 or a DQ8 allele. Amongst the DR alleles, the DR3-DRB5, DR3-3, DR3-4 and DR4-4 showed a strong association with T1DM. Majority of T1DM patients who carried homozygous variant (TT) genotype of the PTPN22 gene had either DR3-DRB5 or DRB3-DRB4 genotypes. In T1DM patients who co-inherited the high risk HLA DQ, DR alleles with the variant genotype of PTPN22 gene, the majority were positive for three autoantibodies. Our data demonstrate that the variant T-allele of the PTPN22 gene along with HLA-DQ2 and DQ8 alleles constitute significant determinants of genetic predisposition of T1DM in Kuwaiti children.