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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies

Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice

Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors B

Genetic Variation Within the HLA-DRA1 Gene Modulates Susceptibility to Type 1 Diabetes in HLA-DR3 Homozygotes

Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci encode HLA-DR and -DQ. Genetic heterogeneity and linkage disequilibrium in the highly polymorphic HLA region confound attempts to identify additional T1D susceptibility loci. To minimize HLA heterogeneity, T1D patients (N = 365) and control

Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women

Background and aims: Two Amerindian populations - Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women. Methods and results: Fasting plasm

Examining the causal association of fasting glucose with blood pressure in healthy children and adolescents: a Mendelian randomization study employing common genetic variants of fasting glucose.

The aim of the study was to determine whether genetically raised fasting glucose (FG) levels are associated with blood pressure (BP) in healthy children and adolescents. We used 11 common genetic variants of FG discovered in genome-wide association studies (GWAS), including the rs560887 single-nucleotide polymorphism (SNP) located in the G6PC2 locus found to be robustly associated with FG in child

Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality among Men with Type 2 Diabetes : A 22-Year Prospective Study

Objective - To examine select adipokines, including fatty acid-binding protein 4, retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in relation to cardiovascular disease (CVD) mortality among patients with type 2 diabetes mellitus. Approach and Results - Plasma levels of fatty acid-binding protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950 men with

Salt-inducible kinase 2 and -3 are downregulated in adipose tissue from obese or insulin-resistant individuals : implications for insulin signalling and glucose uptake in human adipocytes

AIMS/HYPOTHESIS: Salt-inducible kinases (SIKs) are related to the metabolic regulator AMP-activated protein kinase (AMPK). SIK2 is abundant in adipose tissue. The aims of this study were to investigate the expression of SIKs in relation to human obesity and insulin resistance, and to evaluate whether changes in the expression of SIKs might play a causal role in the development of disturbed glucose

Hypertensive disorders of pregnancy and offspring cardiac structure and function in adolescence

Background-Fetal exposure to preeclampsia is associated with higher blood pressure and later risk of stroke. We aimed to investigate the associations of maternal preeclampsia, gestational hypertension, and maternal blood pressure change in pregnancy with offspring cardiac structure and function in adolescence. Methods and Results-Using data from a prospective birth cohort study, we included offspr

Metformin ameliorates dysfunctional traits of glibenclamide- and glucose-induced insulin secretion by suppression of imposed overactivity of the islet nitric oxide synthase-no system

Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS)-NO system, a negative modulator of glucose-stimu

Predicting glycated hemoglobin levels in the non-diabetic general population : Development and validation of the DIRECTDETECT prediction model-a DIRECT study

Aims/hypothesis To develop a prediction model that can predict HbA1c levels after six years in the non-diabetic general population, including previously used readily available predictors. Methods Data from 5,762 initially non-diabetic subjects from three population-based cohorts (Hoorn Study, Inter99, KORA S4/F4) were combined to predict HbA1c levels at six year follow-up. Using backward selection

Lifestyle and precision diabetes medicine : will genomics help optimise the prediction, prevention and treatment of type 2 diabetes through lifestyle therapy?

Precision diabetes medicine, the optimisation of therapy using patient-level biomarker data, has stimulated enormous interest throughout society as it provides hope of more effective, less costly and safer ways of preventing, treating, and perhaps even curing the disease. While precision diabetes medicine is often framed in the context of pharmacotherapy, using biomarkers to personalise lifestyle

From association to function : MTNR1B

The discovery that variants in the melatonin receptor 2 (MTNR1B) gene were associated with glucose levels, insulin secretion, and risk for type 2 diabetes (T2D) in genome-wide association studies (GWAS) reinforced the previously suggested link between glucose homeostasis and circadian rhythmicity. Diurnal secretion of melatonin has reported to be altered in people with diabetes and rodent models o

Nutrigenetics of type 2 diabetes

Type 2 diabetes has become a leading health problem throughout the world. The escalating epidemic of type 2 diabetes is believed to result from a collision between inherent biological susceptibilities (genotypes) and a shift toward dietary habits and lifestyle that promote obesity over the past several decades; the transition from “traditional” to modern “obesogenic” lifestyles is characterized by

Genetics of type 2 diabetes : It matters from which parent we inherit the risk

Type 2 diabetes (T2D) results from a co-occurrence of genes and environmental factors. There are more than 120 genetic loci suggested to be associated with T2D, or with glucose and insulin levels in European and multi-ethnic populations. Risk of T2D is higher in the offspring if the mother rather than the father has T2D. Genetically, this can be associated with a unique parent-of-origin (PoO) tran

ω-3 Polyunsaturated fatty acid biomarkers and coronary heart disease : Pooling project of 19 cohort studies

Importance: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. Objective: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5 ω-3), docosapentaenoic acid (DPA; 22:5 ω-3), and docosahexaenoic acid (DHA; 22:6 ω-3) an

The heritable basis of gene–environment interactions in cardiometabolic traits

Aims/hypothesis: Little is known about the heritable basis of gene–environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype–environment interactions. Methods: Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adu

Increased DNA methylation variability in type 1 diabetes across three immune effector cell types

The incidence of type 1 diabetes (T1D) has substantially increased over the past decade, suggesting a role for non-genetic factors such as epigenetic mechanisms in disease development. Here we present an epigenome-wide association study across 406,365 CpGs in 52 monozygotic twin pairs discordant for T1D in three immune effector cell types. We observe a substantial enrichment of differentially vari