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

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

Starch-Based Diet and Type 2 Diabetes

The starch based diet was discovered and developed by Dr. John McDougal who claimed that a diet consisting of 70% starch, 20% vegetable and 10% fruit while eliminating meat, fat and diary products has helped his patients reverse their diabetes. In this study, we will re-examine the effect of this diet on blood glucose in people with type 2 diabetes. We hypothesize that eating on a starch-based diet improves insulin sensitivity in individuals with type 2 diabetes. A survey of 10 selected type 2 diabetes diagnosed individuals was conducted. Each individual was interviewed and given the option to participate in the study. 7 consented to participate and are put on the starch-based diet for 4 weeks. At the end of each week their blood glucose and other vital readings are to be taken. The participants are given instructions on how to go on the diet. The expected outcome will come from the analysis of the result after the end of 4 weeks on the diet. We expect similar conclusions with that of Dr. McDougal’s findings on the starch-based diet. At this time, it is early to draw conclusions because the instruments required for this project arrived late from the vendors. Therefore, it is appropriate to state that conclusion will be finalized after the end of the four weeks

Circulating miRNAs as predictive biomarkers of type 2 diabetes mellitus development in coronary heart disease patients fromt he CORDIOPREV study

Circulating microRNAs (miRNAs) have been proposed as type 2 diabetes biomarkers, and they may be a more sensitive way to predict development of the disease than the currently used tools. Our aim was to identify whether circulating miRNAs, added to clinical and biochemical markers, yielded better potential for predicting type 2 diabetes. The study included 462 non-diabetic patients at baseline in the CORDIOPREV study. After a median follow-up of 60 months, 107 of them developed type 2 diabetes. Plasma levels of 24 miRNAs were measured at baseline by qRT-PCR, and other strong biomarkers to predict diabetes were determined. The ROC analysis identified 9 miRNAs, which, added to HbA1c, have a greater predictive value in early diagnosis of type 2 diabetes (AUC = 0.8342) than HbA1c alone (AUC = 0.6950). The miRNA and HbA1cbased model did not improve when the FINDRISC was included (AUC = 0.8293). Cox regression analyses showed that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p and miR-150 circulating levels have a higher risk of disease (HR = 11.27; 95% CI = 2.61–48.65). Our results suggest that circulating miRNAs could potentially be used as a new tool for predicting the development of type 2 diabetes in clinical practice

Ethnicity, Obesity, and Type 2 Diabetes of Adults in Urban Populations of Central America

The purpose of this meta-analysis was to examine the impact of ethnicity and obesity as it relates to Type-2 Diabetes (T2D) in specific Central American countries. A meta-analysis was conducted to determine the association of ethnicity, obesity, and T2D. Four studies that qualified for inclusion were identified by searching MEDLINE and PubMed databases. The studies on the association of ethnicity and T2D had a combined population resulted in 265,858 study participants. Two studies on the association of obesity and T2D had 197,899 participants. An analysis of the data was conducted utilizing the relative risk ration, odds ratio, and forest plots. The comparison of the relative risk of T2D across ethnic categories by studies range for Blacks was 1.59 to 2.74, Asians was 1.43 to 2.08, and Hispanics .92 to 2.91. The ethnic difference in the prevalence of diabetes was almost two-fold higher in all ethnic groups than among the Caucasians with a significance level of 95%. A comparison of relative risk of T2D across weight categories was significantly higher among those with a diagnosed of diabetes in all reported areas. The odds ratio was very close to the risk ratio in both ethnicity and obesity to the development of T2D.The meta-analysis findings documented that an association does exist between ethnicity and obesity to the development of type 2 diabetes

Ethnic differences in adiposity and diabetes risk – insights from genetic studies

Type 2 diabetes is more common in non-Europeans and starts at a younger age and at lower BMI cut-offs. This review discusses the insights from genetic studies about pathophysiological mechanisms which determine risk of disease with a focus on the role of adiposity and body fat distribution in ethnic disparity in risk of type 2 diabetes. During the past decade, genome-wide association studies (GWAS) have identified more than 400 genetic variants associated with the risk of type 2 diabetes. The Eurocentric nature of these genetic studies have made them less effective in identifying mechanisms that make non-Europeans more susceptible to higher risk of disease. One possible mechanism suggested by epidemiological studies is the role of ethnic difference in body fat distribution. Using genetic variants associated with an ability to store extra fat in a safe place, which is subcutaneous adipose tissue, we discuss how different ethnic groups could be genetically less susceptible to type 2 diabetes by developing a more favourable fat distribution

Gender and diet management in type 2 diabetes

Introduction Type 2 diabetes is a chronic health condition that requires ongoing self-management. This often includes changes in diet, which may be open to influences from relatives. Family support in terms of diet may be linked with gender and the assumption that meal preparation is a traditionally female activity. This article looks at the role of gender in diet management in people with type 2 diabetes and their relatives. Methods Seventeen semi-structured interviews were conducted with 23 participants (10 people with type 2 diabetes, 13 relatives of people with type 2 diabetes) in Scotland, UK. The aim was to uncover changes people have made to their diet following diagnosis of type 2 diabetes in oneself or a family member. Data were analysed using Framework Approach. Findings: Female relatives were more likely to manage the patient’s diet while male relatives provided support but were less likely to monitor the person’s diet. Female patients may prioritise the needs of their family while male patients are more likely to rely on their female relatives in terms of diet management. Discussion The study findings have implications for family-based interventions as gender may play a crucial role in the management of type 2 diabetes.Output Status: Forthcoming/Available Onlin