Multilevel examination of diabetes in modernising China: what elements of urbanisation are most associated with diabetes?

Aims/hypothesis: The purpose of this study was to examine the association between urbanisation-related factors and diabetes prevalence in China.

Methods: Anthropometry, fasting blood glucose (FBG) and community-level data were collected for 7,741 adults (18-90 years) across 217 communities and nine provinces in the 2009 China Health and Nutrition Survey to examine diabetes (FBG ≥7.0 mmol/l or doctor diagnosis).

Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource.

Aims/hypothesis: Hyperglycaemia disproportionately affects African-Americans (AfAs). We tested the transferability of 18 single-nucleotide polymorphisms (SNPs) associated with glycaemic traits identified in European ancestry (EuA) populations in 5,984 non-diabetic AfAs.

Methods: We meta-analysed SNP associations with fasting glucose (FG) or insulin (FI) in AfAs from five cohorts in the Candidate Gene Association Resource.

New diabetes diagnostic threshold of hemoglobin A(1c) and the 3-year incidence of retinopathy.

The new diagnostic threshold of hemoglobin A(1c) was made based on evidence from cross-sectional studies, and no longitudinal study supports its validity. To examine whether hemoglobin A(1c) of 6.5% or higher defines a threshold for elevated risk of incident retinopathy, we analyzed longitudinal data of 19,897 Japanese adults who underwent a health checkup in 2006 and were followed up 3 years later.

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D.

A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study.

Aims/hypothesis: Genotype does not change over the life course and may thus facilitate earlier identification of individuals at high risk for type 2 diabetes. We hypothesised that a genotype score predicts incident type 2 diabetes from young adulthood and improves diabetes prediction models based on clinical risk factors alone.

Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) study followed young adults (aged 18-30 years, mean age 25) serially into middle adulthood.

Metabolic syndrome and inflammatory biomarkers: a community-based cross-sectional study at the Framingham Heart Study.

Background: Prior studies reported conflicting findings on the association between metabolic syndrome and inflammatory biomarkers. We tested the cross-sectional associations between metabolic syndrome and nine inflammatory markers.

Methods: We measured C-reactive protein, CD40 ligand, interleukin-6, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, osteoprotegerin, P-selectin, tumor necrosis factor-alpha, and tumor necrosis factor receptor-2 in 2570 Framingham Offspring Study participants free of diabetes and cardiovascular disease at examination 7.

Impact of common variation in bone-related genes on type 2 diabetes and related traits.

Exploring genetic pleiotropy can provide clues to a mechanism underlying the observed epidemiological association between type 2 diabetes and heightened fracture risk. We examined genetic variants associated with bone mineral density (BMD) for association with type 2 diabetes and glycemic traits in large well-phenotyped and -genotyped consortia. We undertook follow-up analysis in ∼19,000 individuals and assessed gene expression.

Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases.

Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m²) compared to obese cases (BMI≥30 Kg/m²).

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale.

Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system.

Background: Cardiovascular disease is increased among HIV-infected patients, but little is known regarding ischemic stroke rates. We sought to compare stroke rates and determine stroke risk factors in HIV-infected versus non-HIV-infected patients.

Methods: An HIV cohort and matched non-HIV comparator cohort seen between 1996 and 2009 were identified from a Boston health care system.

Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III).

Background: Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality.

Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA).

Genetic variants associated with fasting glucose in European ancestry populations are increasingly well understood. However, the nature of the associations between these single nucleotide polymorphisms (SNPs) and fasting glucose in other racial and ethnic groups is unclear. We sought to examine regions previously identified to be associated with fasting glucose in Caucasian genome-wide association studies (GWAS) across multiple ethnicities in the Multiethnic Study of Atherosclerosis (MESA).

Is genetic testing useful to predict type 2 diabetes?

The early identification of individuals at risk for type 2 diabetes (T2D) enables prevention. Recent genome-wide association studies (GWAS) have added at least 40 genetic variants to the list of already well characterized T2D risk predictors, including family history, obesity, and elevated fasting plasma glucose levels. Although these variants can significantly predict T2D alone and as a part of genotype risk scores, they do not yet offer clinical discrimination beyond that achieved with common clinical measurements.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.

Consistent directions of effect for established type 2 diabetes risk variants across populations: the population architecture using Genomics and Epidemiology (PAGE) Consortium.

Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S.

Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the Framingham Offspring Study.

Background: Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury.

Methods And Results: In 3127 stroke-free Framingham offspring (age, 59±10 years; 54% female), we related a panel of 8 biomarkers assessing inflammation (C-reactive protein), hemostasis (D-dimer and plasminogen activator inhibitor-1), neurohormonal activity (aldosterone-to-renin ratio, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptides), and endothelial function (homocysteine and urinary albumin/creatinine ratio) measured at the sixth examination (1995-1998) to risk of incident stroke/transient ischemic attack. In a subset of 1901 participants with available brain magnetic resonance imaging (1999-2005), we further related these biomarkers to total cerebral brain volume, covert brain infarcts, and large white-matter hyperintensity volume.

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels.

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown.

A risk score for chronic kidney disease in the general population.

Background: Stratification of individuals at risk for chronic kidney disease may allow optimization of preventive measures to reduce disease incidence and complications. We sought to develop a risk score that estimates an individual's absolute risk of incident chronic kidney disease.

Methods: Framingham Heart Study participants free of baseline chronic kidney disease, who attended a baseline examination in 1995-1998 and follow-up in 2005-2008, were included in the analysis (n = 2490).

Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.

Genetic counseling as a tool for type 2 diabetes prevention: a genetic counseling framework for common polygenetic disorders.

Advances in genetic epidemiology have increased understanding of common, polygenic preventable diseases such as type 2 diabetes. As genetic risk testing based on this knowledge moves into clinical practice, we propose that genetic counselors will need to expand their roles and adapt traditional counseling techniques for this new patient set. In this paper, we present a genetic counseling intervention developed for a clinical trial [Genetic Counseling/Lifestyle Change for Diabetes Prevention, ClinicalTrials.

Impact of literacy and numeracy on motivation for behavior change after diabetes genetic risk testing.

Background: Type 2 diabetes genetic risk testing might motivate at-risk patients to adopt diabetes prevention behaviors. However, the influence of literacy and numeracy on patient response to diabetes genetic risk is unknown.

Objective: The authors investigated the association of health literacy, genetic literacy, and health numeracy with patient responses to diabetes genetic risk.

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.

Plasma resistin, adiponectin, and risk of incident atrial fibrillation: the Framingham Offspring Study.

Background: We sought to investigate whether higher concentrations of resistin and lower concentrations of adiponectin relate to incident atrial fibrillation (AF) and whether this association is mediated by AF risk factors and inflammation. Resistin and adiponectin are adipokines that have been associated with multiple known risk factors for AF including diabetes, obesity, inflammation, and heart failure.

Methods: We studied the relations between circulating concentrations of both adipokines and incident AF in participants of the Framingham Offspring Study.

Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism.

Aims/hypothesis: Common genetic variants have been associated with type 2 diabetes. We hypothesised that a subset of these variants may have different effects on the transition from normal fasting glucose (NFG) to impaired fasting glucose (IFG) than on that from IFG to diabetes.

Methods: We identified 16 type 2 diabetes risk variants from the Illumina Broad Candidate-gene Association Resource (CARe) array genotyped in 26,576 CARe participants.