Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestr

Sugar and Type 2 diabetes

Background: Consumption of sugar, specifically sugar-sweetened beverages, has been widely held responsible by the media for the global rise in Type 2 diabetes (T2DM). Sources of data: Systematic reviews and dietary guidelines relating dietary sugars to T2DM. Areas of agreement: Weight gain and T2DM incidence are associated with diet and lifestyle patterns characterized by high consumptions of any sweetened beverages. High sugar intakes impair risk factors for macrovascular complications of T2DM. Areas of controversy: Much of the association between sugars and T2DM is eliminated by adjusting data for body mass index (BMI). However, BMI adjustment does not fully account for adiposity (r2=0.65–0.75). Excess sugar can promote weight gain, thus T2DM, through extra calories, but has no unique diabetogenic effect at physiological levels. Growing points: Ethical concerns about caffeine added to sweetened beverages, undetectable by consumers, to increase consumption. Areas timely for developing research: Evidence needed for limiting dietary sugar below 10% energy intake

The importance of diet and exercise in preventing type 2 diabetes

Diabetes is reaching epidemic proportions globally with estimates of 374 million people worldwide (WHO 2014 ) and impacts on the people with the condition, their families and on health service resources. While type 1 diabetes is an autoimmune disease, the causes of type 2 diabetes are more multi-factorial. In the UK there are about 2.9 million with diabetes of whom approximately 90% will have type 2. It is also estimated that there are about 850,000 people in the UK who have type 2 diabetes but have not as yet been diagnosed ( NHS UK 2014). Coupled with this, there are people who have known risk factors for developing diabetes. This article aims to consider the role of diet in adults in preventing those who are at high risk of developing type 2 diabetes and to present the evidence and practical application for nurses

Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

Weight loss in type 2 diabetes

Support from nurses is crucial to help obese and overweight patients achieve and maintain weight loss, explains Nicky Kim

Interventions for prevention of type 2 diabetes in relatives:A systematic review

The relatives and partners of people with type 2 diabetes are at increased risk of developing type 2 diabetes. This systematic review examines randomized controlled trials, written in English that tested an intervention, which aimed to modify behaviors known to delay or prevent type 2 diabetes, among the relatives or partners of people with type 2 diabetes. Study quality was assessed using the Cochrane Collaboration’s tool for assessing risk of bias. Seven studies met the inclusion criteria. The majority of studies were at low risk of bias. Six studies tested an intervention in first-degree relatives of people with type 2 diabetes and one in partners. Intervention components and intervention intensity across studies varied, with those targeting diet and physical activity reporting the most significant changes in primary outcomes. Only one study did not observe significant changes in primary outcomes. There were three main recruitment approaches: advertising in the community, recruiting people through their relatives with diabetes, or identifying people as high risk by screening of their own health care contacts. Some evidence was found for potentially successful interventions to prevent type 2 diabetes among the relatives and partners of people with type 2 diabetes, although finding simple and effective methods to identify and recruit them remains a challenge. Future studies should explore the effect of patients’ perceptions on their family members’ behavior and capitalize on family relationships in order to increase intervention effectiveness

Association of a Low-Frequency Variant in HNF1A With Type 2 Diabetes in a Latino Population

Importance: Latino populations have one of the highest prevalences of type 2 diabetes worldwide. Objectives: To investigate the association between rare protein-coding genetic variants and prevalence of type 2 diabetes in a large Latino population and to explore potential molecular and physiological mechanisms for the observed relationships. Design, Setting, and Participants: Whole-exome sequencing was performed on DNA samples from 3756 Mexican and US Latino individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from 1993 to 2013. One variant was further tested for allele frequency and association with type 2 diabetes in large multiethnic data sets of 14 276 participants and characterized in experimental assays. Main Outcome and Measures: Prevalence of type 2 diabetes. Secondary outcomes included age of onset, body mass index, and effect on protein function. Results: A single rare missense variant (c.1522G>A [p.E508K]) was associated with type 2 diabetes prevalence (odds ratio [OR], 5.48; 95% CI, 2.83-10.61; P = 4.4 × 10−7) in hepatocyte nuclear factor 1-α (HNF1A), the gene responsible for maturity onset diabetes of the young type 3 (MODY3). This variant was observed in 0.36% of participants without type 2 diabetes and 2.1% of participants with it. In multiethnic replication data sets, the p.E508K variant was seen only in Latino patients (n = 1443 with type 2 diabetes and 1673 without it) and was associated with type 2 diabetes (OR, 4.16; 95% CI, 1.75-9.92; P = .0013). In experimental assays, HNF-1A protein encoding the p.E508K mutant demonstrated reduced transactivation activity of its target promoter compared with a wild-type protein. In our data, carriers and noncarriers of the p.E508K mutation with type 2 diabetes had no significant differences in compared clinical characteristics, including age at onset. The mean (SD) age for carriers was 45.3 years (11.2) vs 47.5 years (11.5) for noncarriers (P = .49) and the mean (SD) BMI for carriers was 28.2 (5.5) vs 29.3 (5.3) for noncarriers (P = .19). Conclusions and Relevance: Using whole-exome sequencing, we identified a single low-frequency variant in the MODY3-causing gene HNF1A that is associated with type 2 diabetes in Latino populations and may affect protein function. This finding may have implications for screening and therapeutic modification in this population, but additional studies are required.publishedVersio

Obesity and diabetes in New Zealand

Obesity is a risk factor for diabetes, cardiovascular disease, musculoskeletal disorders, and some cancers. Introduction It is estimated that 1.1 million adults are obese in New Zealand (that is, they have a BMI or Body Mass Index of 30 or more). Obesity in New Zealand places a considerable strain on the health care system: a study in 2006 estimated that health care costs attributable to overweight and obese persons was $686 million or 4.5% of New Zealand’s total health care expenditure. Obesity is a risk factor for diabetes, cardiovascular disease, musculoskeletal disorders, and some cancers. There are two main types of diabetes: type 1 (insulin-dependent diabetes mellitus) and type 2 (adult-onset diabetes mellitus). Type 2 is more common in the population than type 1 (approximately 90% of diabetes cases worldwide are type 2). Individuals who are obese increase their risk of developing type 2 diabetes. The Ministry of Health estimated (when looking at the mortality burden of nutrition-related risk factors in New Zealand) that, in 1997, 80% of deaths from type 2 diabetes were attributable to a high BMI. Complications from diabetes include an increased risk of cardiovascular disease, nerve damage, and kidney failure. There were 768 deaths from diabetes in New Zealand in 2010

Latent Autoimmune Diabetes in Adults in the United Arab Emirates: Clinical Features and Factors Related to Insulin-Requirement

AIMS: To describe and to characterize clinical features of latent autoimmune diabetes in adults (LADA) compared to type 1 and type 2 diabetes in the UAE. METHODS: In this cross-sectional study a dataset including 18,101 subjects with adult-onset (>30 years) diabetes was accessed. 17,072 subjects fulfilled the inclusion/exclusion criteria. Data about anthropometrics, demographics, autoantibodies to Glutamic Acid Decarboxylase (GADA) and to Islet Antigen 2 (anti-IA2), HbA1c, cholesterol and blood pressure were extracted. LADA was diagnosed according to GADA and/or anti-IA2 positivity and time to insulin therapy. RESULTS: 437 (2.6%) patients were identified as LADA and 34 (0.2%) as classical type 1 diabetes in adults. Mean age at diagnosis, BMI, waist circumference, systolic blood pressure and HbA1c significantly differed between, LADA, type 2 and type 1 diabetes, LADA showing halfway features between type 2 and type 1 diabetes. A decreasing trend for age at diagnosis and waist circumference was found among LADA subjects when subdivided by positivity for anti-IA2, GADA or for both antibodies (p=0.013 and p=0.011 for trend, respectively). There was a gradual downward trend in autoantibody titre in LADA subjects requiring insulin within the first year from diagnosis to subjects not requiring insulin after 10 years of follow-up (p<0.001). CONCLUSIONS: This is the first study describing the clinical features of LADA in the UAE, which appear to be different from both type 1 and type 2 diabetes. Furthermore, we showed that the clinical phenotype of LADA is dependent on different patterns of antibody positivity, influencing the time to insulin requirement