Type 2 Diabetes Risk Alleles Are Associated With Reduced Size at Birth

OBJECTIVE: Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight. RESEARCH DESIGN AND METHODS: We genotyped single-nucleotide polymorphisms (SNPs) at five recently identified type 2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2, and SLC30A8) in 7,986 mothers and 19,200 offspring from four studies of white Europeans. We tested the association between maternal or fetal genotype at each locus and birth weight of the offspring. RESULTS: We found that type 2 diabetes risk alleles at the CDKAL1 and HHEX-IDE loci were associated with reduced birth weight when inherited by the fetus (21 g [95% CI 11-31], P = 2 x 10(-5), and 14 g [4-23], P = 0.004, lower birth weight per risk allele, respectively). The 4% of offspring carrying four risk alleles at these two loci were 80 g (95% CI 39-120) lighter at birth than the 8% carrying none (P(trend) = 5 x 10(-7)). There were no associations between birth weight and fetal genotypes at the three other loci or maternal genotypes at any locus. CONCLUSIONS: Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers

Context, Complexity and Contestation: Birmingham's Agreed Syllabuses for Religious Education since the 1970s

publication-status: AcceptedThis is an Author's Original Manuscript of an article whose final and definitive form, the Version of Record, has been published in the Journal of Beliefs and Values, September 2011. Available online at: http://www.tandfonline.com/ or DOI: 10.1080/13617672.2011.600823The present article offers an historical perspective on the 1975, 1995 and 2007 Birmingham Agreed Syllabuses for Religious Education. It draws upon historical evidence uncovered as part of ‘The hidden history of curriculum change in religious education in English schools, 1969–1979’ project, and curriculum history theories, especially David Labaree’s observations about the distance between the ‘rhetorical’ and ‘received’ curricula. We argue that, contrary to the existing historiography, curriculum change in religious education (RE) has been evolutionary not revolutionary. Multiple reasons are posited to explain this, not least among which is the capacity and agency of teachers. Furthermore, we argue that ongoing debates about the nature and purpose of RE, as exemplified in the Birmingham context, reflect the multiple expectations that religious educators and other stakeholders had, and continue to have, of the curriculum subject. These debates contribute to the inertia evident in the implementation of RE curriculum reforms. A consciousness of the history of RE enables curriculum contestations to be contextualised and understood, and, thereby, provides important insights which can be applied to ongoing and future debates and developments

The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge

BACKGROUND AND AIM:The first genome-wide association study on birth weight was recently published and the most significant associated birth weight lowering variant was the rs900400 C-allele located near LEKR1 and CCNL1. We aimed to replicate the association with birth weight in the Danish Inter99 study and furthermore to evaluate associations between rs900400 and indices of insulin secretion and insulin sensitivity obtained by oral glucose tolerance tests in adults from the Danish Inter99 study and the Finnish, Metabolic Syndrome in Men (METSIM) sample. METHODS:For 4,744 of 6,784 Inter99 participants, midwife journals were traced through the Danish State Archives and association of rs900400 with birth weight was examined. Associations between rs900400 and fasting serum insulin, fasting plasma glucose, insulinogenic index, homeostasis model assessment of insulin resistance (HOMA-IR) and disposition index were studied in 5,484 Danish and 6,915 Finnish non-diabetic individuals and combined in meta-analyses. RESULTS:The C-allele of rs900400 was associated with a 22.1 g lower birth weight ([-41.3;-3.0], P = 0.024) per allele. Moreover, in combined analyses of the Danish Inter99 study and the Finnish METSIM study we found that the birth weight lowering allele was associated with increased insulin release measured by the insulinogenic index (β = 2.25% [0.59; 3.91], P = 0.008) and with an increased disposition index (β = 1.76% [0.04; 3.49], P = 0.05). CONCLUSION:The birth weight lowering effect of the C-allele of rs900400 located near LEKR1 and CCNL1 was replicated in the Danish population. Furthermore the C-allele was associated with increased insulin response following oral glucose stimulation in a meta-analysis based on Danish and Finnish non-diabetic individuals

Spending time, spending money: passenger segmentation in an international airport

Changes within the air transport sector have required many European airports to either develop or expand their commercial activities. Strategies have included the expansion of retail space, a broadening of the tenant and merchandise mix and the development of a passenger segmentation strategy. This paper explores the efficacy of this approach by identifying the behaviour of different passenger segments while in an international airport. Using a framework of strategic market segmentation, it identifies how travellers allocate their time having entered 'airside' and details any purchases made. Using observational research and a face to face quantitative survey, 301 passengers were tracked and interviewed. Through a broad based, a priori form of segmentation, significant differences in shopping behaviour are identified. Such findings assist with the development of the airport's commercial strategy and allow a number of observations to be made about the value of market segmentation from both a theoretical and managerial perspective

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: common genetic variants in GCK and TCF7L2 are associated with fasting and postchallenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes mellitus from the International Association of Diabetes and Pregnancy Study Groups.

OBJECTIVE: Common genetic variants in GCK and TCF7L2 are associated with higher fasting glucose and type 2 diabetes in nonpregnant populations. However, their associations with glucose levels from oral glucose tolerance tests (OGTTs) in pregnancy have not been assessed in a large sample. We hypothesized that these variants are associated with quantitative measures of glycemia in pregnancy. RESEARCH DESIGN AND METHODS: We analyzed the associations between variants rs1799884 (GCK) and rs7903146 (TCF7L2) and OGTT outcomes at 24-32 weeks' gestation in 3,811 mothers of European (U.K. and Australia) and 1,706 mothers of Asian (Thailand) ancestry from the HAPO cohort. We also tested associations with offspring birth anthropometrics. RESULTS: The maternal GCK variant was associated with higher fasting glucose in Europeans (P = 0.001) and Thais (P 0.05). In both populations, both variants were associated with higher odds of gestational diabetes mellitus according to the new International Association of Diabetes and Pregnancy Study Groups recommendations (P = 0.001-0.08). CONCLUSIONS: Maternal GCK and TCF7L2 variants are associated with glucose levels known to carry an increased risk of adverse pregnancy outcome in women without overt diabetes. Further studies will be important to determine the variance in maternal glucose explained by all known genetic variants

Physiologic Characterization of Type 2 Diabetes–Related Loci

For the past two decades, genetics has been widely explored as a tool for unraveling the pathogenesis of diabetes. Many risk alleles for type 2 diabetes and hyperglycemia have been detected in recent years through massive genome-wide association studies and evidence exists that most of these variants influence pancreatic β-cell function. However, risk alleles in five loci seem to have a primary impact on insulin sensitivity. Investigations of more detailed physiologic phenotypes, such as the insulin response to intravenous glucose or the incretion hormones, are now emerging and give indications of more specific pathologic mechanisms for diabetes-related risk variants. Such studies have shed light on the function of some loci but also underlined the complex nature of disease mechanism. In the future, sequencing-based discovery of low-frequency variants with higher impact on intermediate diabetes-related traits is a likely scenario and identification of new pathways involved in type 2 diabetes predisposition will offer opportunities for the development of novel therapeutic and preventative approaches

Do Gene Variants Influencing Adult Adiposity Affect Birth Weight? A Population-Based Study of 24 Loci in 4,744 Danish Individuals

Several obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn.Midwife records from the Danish State Archives provided information on mother's age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10(th) percentile), normal (10(th)-90(th) percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI.24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life