Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man.

Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development.

Early-onset, coexisting autoimmunity and decreased HLA-mediated susceptibility are the characteristics of diabetes in Down syndrome.

OBJECTIVE: Down syndrome (DS) is associated with an increased risk of diabetes, particularly in young children. HLA-mediated risk is however decreased in children with DS and diabetes (DSD). We hypothesized that early-onset diabetes in children with DS is etiologically different from autoimmune diabetes. RESEARCH DESIGN AND METHODS: Clinical and immunogenetic markers of autoimmune diabetes were studied in 136 individuals with DSD and compared with 194 age- and sex-matched individuals with type 1 diabetes, 222 with DS, and 671 healthy controls. HLA class II was analyzed by sequence-specific primed PCR. Islet autoantibodies were measured by radioimmunoassay. RESULTS: Age at onset of diabetes was biphasic, with 22% of DS children diagnosed before 2 years of age, compared with only 4% in this age-group with type 1 diabetes in the general population (P < 0.0001). The frequency of the highest-risk type 1 diabetes-associated HLA genotype, DR3-DQ2/DR4-DQ8, was decreased in both early- and later-onset DSD compared with age-matched children with type 1 diabetes (P < 0.0001), although HLA DR3-DQ2 genotypes were increased (P = 0.004). Antibodies to GAD were observed in all five samples tested from children diagnosed at ≤2 years of age, and persistent islet autoantibodies were detected in 72% of DSD cases. Thyroid and celiac disease were diagnosed in 74 and 14%, respectively, of the DSD cohort. CONCLUSIONS: Early-onset diabetes in children with DS is unlikely to be etiologically different from autoimmune diabetes occurring in older DS children. Overall, these studies demonstrate more extreme autoimmunity in DSD typified by early-onset diabetes with multiple autoimmunity, persistent islet autoantibodies, and decreased HLA-mediated susceptibility.

Obesity in children and adolescents in Gulf countries: Facts and solutions / Obesidad en niños y adolescentes en países del Golfo: hechos y soluciones

The rapid pace of socioeconomic development in the Arabian Gulf nations and the rapidly changing environment are probably determining the altering scenario of child and adolescent nutrition in the developed societies. The rapid urbanization in everyday life, accompanied by decreased levels of physical activity and increased caloric intake of non-traditional food has become responsible for the emerging of obesity in children and adolescents as a major public health issue in these countries. The six Arabian Gulf nations are a good example for this developmental transition and its consequences. Prevalence is high among Kuwaiti and Saudi pre-school children (8-9%), and among the highest in the world among Kuwaiti adolescents (40-46%), taking into account that different standard of assessment of obesity are used. Although data on the prevalence of type 2 diabetes (T2DM) and metabolic syndrome (MS) in children in the region are sparse, both morbidities are expected to rise, knowing the strong association between obesity and T2DM in the adult population. Prevention strategies need the collaborative efforts of governmental and community-led agencies to establish long-term programs to improve health education, targeting young children and their families. Healthy eating and physical activity should be promoted and encouraged in schools, nurseries, and child care settings. This article gives an overview of overweight and obesity among children and adolescents in the 6-Arabian Gulf countries. It will also address possible strategies for the prevention and management of this major health epidemic

El frenético ritmo de los avances socioeconómicos en los países del Golfo Pérsico y el rápidamente cambiante entorno está probablemente definiendo el perturbador panorama de la nutrición de niños y adolescentes en las sociedades desarrolladas. La fugaz urbanización de la vida diaria, acompañada por unos niveles reducidos de actividad física y un aumento de la ingesta calórica en forma de alimentos no tradicionales, ha convertido la obesidad en los niños y adolescentes en un tema de salud pública de gran importancia en estos países. Los seis países del Golfo Pérsico son un buen ejemplo de esta transición en el desarrollo y de sus consecuencias. La prevalencia es elevada entre los niños preescolares kuwaitíes y saudíes (8%-9%), y entre los adolescentes kuwaitíes cuenta con una de las más elevadas en el mundo (40%-46%), de acuerdo con diferentes estándares para valorar la obesidad. Aunque los datos sobre la prevalencia de la diabetes tipo 2 (DMT2) y el síndrome metabólico (SM) en los niños de la región son escasos, se esperan que ambas morbilidades aumenten, debido a la existencia de una importante asociación entre la obesidad y la DMT2 en la población adulta. Las estrategias de prevención exigen una fuerte colaboración entre el gobierno y las agencias dirigidas por la comunidad para establecer programas a largo plazo para mejorar la educación sanitaria, centrada en los niños pequeños y sus familias. Es necesaria la promoción de una dieta saludable y de la actividad física tanto en colegios, como en guarderías y centros de puericultura. Este artículo aporta una visión general del sobrepeso y la obesidad en niños y adolescentes en los seis países que conforman el Golfo Pérsico. También se contemplan posibles estrategias para la prevención y la gestión de esta importante epidemia sanitaria