The Complex Etiology of Childhood Obesity in Arabs Is Highlighted by a Combination of Biological and Socio-Economic Factors

Objectives: To identify predictors of childhood and adolescent obesity in Kuwaitis with Arab ethnicity.Methods: A cross-sectional sample of 6–18 year-old schoolchildren was randomly selected from 244 public schools across all six governorates in the State of Kuwait. Anthropometric data were measured from 6,574 Arab Kuwaiti schoolchildren, and a structured questionnaire was used to collect information on possible risk factors associated with obesity. Overweight and obesity were defined in accordance with the Center for Disease Control and Prevention criteria.Results: The prevalence of overweight and obesity in children (aged 6–18 years) were 17.7% and 33.7%, respectively. The likelihood of childhood obesity increased with birth weights >4.0 Kg [odds ratio (OR) = 2.3; p < 0.0001], maternal employment (OR = 1.26, p = 0.0006), maternal age at pregnancy >30 years (OR = 1.24; p = 0.0016) and family size of <6 members (OR = 1.16, p = 0.0106).Conclusions: Public health professionals should be aware that advanced maternal age, maternal employment, smaller family size, and high birthweight may predict the risk of obesity in Kuwaiti Arab children and adolescents

Ethnic differences in association of high body mass index with early onset of Type 1 diabetes – Arab ethnicity as case study

<div><p>Objective</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>BMI z-score was seen inversely associated with onset age (r,-0.28; p-value<0.001). Children with BMI z-score>0 (<i>i</i>.<i>e</i>. BMI >national average) showed a stronger correlation (r,-0.38; p-value<0.001) than those with BMI z-score<0 (r,-0.19; p-value<0.001); the former group showed significantly lower mean onset age than the latter group (9.6±2.4 <i>versus</i> 10.5±2.7; p-value<0.001). Observed inverse correlation was consistent with that seen in Anglo-saxon, central european, caucasian, and white children while inconsistent with that seen in Indian, New Zealander, and Australian children.</p><p>Conclusions</p><p>The accelerator hypothesis generalizes in Arab pediatric population from Kuwait.</p></div

Multiple linear regression models for association between BMI z-score and age at onset of T1D in the cohort of 6 to 18 years stratified by BMI z-score >0 and <0.

<p>Multiple linear regression models for association between BMI z-score and age at onset of T1D in the cohort of 6 to 18 years stratified by BMI z-score >0 and <0.</p

Summary of findings from previous studies on association between age- and sex-adjusted BMI z-scores and age at onset of T1D in various populations.

<p>Summary of findings from previous studies on association between age- and sex-adjusted BMI z-scores and age at onset of T1D in various populations.</p

Flowchart depicting the filtering steps used to derive the data sets on children and adolescents with age at onset of T1D during 2 to <6 years, and during 6 to18 years.

<p>Flowchart depicting the filtering steps used to derive the data sets on children and adolescents with age at onset of T1D during 2 to <6 years, and during 6 to18 years.</p

Linkage analysis using whole exome sequencing data implicates SLC17A1, SLC17A3, TATDN2 and TMEM131L in type 1 diabetes in Kuwaiti families

Abstract Type 1 diabetes (T1D) is characterized by the progressive destruction of pancreatic β-cells, leading to insulin deficiency and lifelong dependency on exogenous insulin. Higher estimates of heritability rates in monozygotic twins, followed by dizygotic twins and sib-pairs, indicate the role of genetics in the pathogenesis of T1D. The incidence and prevalence of T1D are alarmingly high in Kuwait. Consanguineous marriages account for 50–70% of all marriages in Kuwait, leading to an excessive burden of recessive allele enrichment and clustering of familial disorders. Thus, genetic studies from this Arab region are expected to lead to the identification of novel gene loci for T1D. In this study, we performed linkage analyses to identify the recurrent genetic variants segregating in high-risk Kuwaiti families with T1D. We studied 18 unrelated Kuwaiti native T1D families using whole exome sequencing data from 86 individuals, of whom 37 were diagnosed with T1D. The study identified three potential loci with a LOD score of ≥ 3, spanning across four candidate genes, namely SLC17A1 (rs1165196:pT269I), SLC17A3 (rs942379: p.S370S), TATDN2 (rs394558:p.V256I), and TMEM131L (rs6848033:p.R190R). Upon examination of missense variants from these genes in the familial T1D dataset, we observed a significantly increased enrichment of the genotype homozygous for the minor allele at SLC17A3 rs56027330_p.G279R accounting for 16.2% in affected children from 6 unrelated Kuwaiti T1D families compared to 1000 genomes Phase 3 data (0.9%). Data from the NephQTL database revealed that the rs1165196, rs942379, rs394558, and rs56027330 SNPs exhibited genotype-based differential expression in either glomerular or tubular tissues. Data from the GTEx database revealed rs942379 and rs394558 as QTL variants altering the expression of TRIM38 and IRAK2 respectively. Global genome-wide association studies indicated that SLC17A1 rs1165196 and other variants from SLC17A3 are associated with uric acid concentrations and gout. Further evidence from the T1D Knowledge portal supported the role of shortlisted variants in T1D pathogenesis and urate metabolism. Our study suggests the involvement of SLC17A1, SLC17A3, TATDN2, and TMEM131L genes in familial T1D in Kuwait. An enrichment selection of genotype homozygous for the minor allele is observed at SLC17A3 rs56027330_p.G279R variant in affected members of Kuwaiti T1D families. Future studies may focus on replicating the findings in a larger T1D cohort and delineate the mechanistic details of the impact of these novel candidate genes on the pathophysiology of T1D