An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference

Aims - A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. Methods - We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged = 40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case–control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. Results - In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95% CI 0.24–0.67) kg/m2 per A-allele (P = 3.0 × 10-5) and with waist circumference was 0.88 (95% CI 0.36–1.41) cm per A-allele (P = 0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95% CI) 1.18 (1.07–1.30); P = 0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95% CI 1.14–1.31); P = 1.07 × 10-8] even after adjusting for BMI [1.18 (95% CI 1.10–1.27); P = 1.02 × 10-5] or waist circumference [1.18 (95% CI 1.10–1.27); P = 3.97 × 10-5]. Conclusions - The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

Debate : arm's- length bodies and alternative models of service delivery

This article reflects on the UK coalition government’s ‘alternative models’ agenda, specifically in terms of the adoption of new models of service delivery by arm’s-length bodies (ALBs). It provides an overview of the alternative models agenda and discusses barriers to implementation. These include practical challenges involved in the set up of alternative models, the role of sponsor departments, and the effective communication of best practice. Finally, the article highlights some issues for further discussion.

Delegation in hard times:the financial management of arm's length bodies in the UK

This paper explores the effectiveness of financial management tools in regulating the use of resources by arm’s length bodies (ALBs) in a period of fiscal stress. The paper presents research undertaken into the implementation of a new financial management tool for ALBs in the UK since the 2008 financial crisis. Drawing on conflict ambiguity theory, the paper shows how the effectiveness of such tools is affected by deep-rooted tensions implicit within arm’s length governance. This gives rise to micro-level conflict over the means of achieving fiscal regulation, underpinned by macro-level ambiguity over the logic of governance pursued by the government.

High frequency inverter topologies integrated with the coupled inductor bridge arm

A new topology of the high frequency alternating current (HFAC) inverter bridge arm is proposed which comprises a coupled inductor, a switching device and an active clamp circuit. Based on it, new single-phase and threephase inverters are proposed and their operating states are analysed along with the traditional H-bridge inverter. Multiphase and multi-level isolated inverters are also developed using the HFAC bridge arm. Furthermore, based on the proposed HFAC, a front-end DC-DC converter is also developed for photovoltaic systems to demonstrate the application of the proposed HFAC converter. Simulation and experimental results from prototype converters are carried out to validate the proposed topologies which can be utilised widely in high frequency power conversion applications such as induction heating and wireless power transfer.