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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

Minimal Entanglement Witness from Electrical Current Correlations

Despite great efforts, an unambiguous demonstration of entanglement of mobile electrons in solid state conductors is still lacking. Investigating theoretically a generic entangler-detector setup, we here show that a witness of entanglement between two flying electron qubits can be constructed from only two current cross correlation measurements, for any nonzero detector efficiencies and noncolline

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

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

Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program

Background-We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (versus placebo control) on lipid and lipid subfraction levels in the Diabetes Prevention Program randomized controlled trial. Methods and Results-We tested gene treatment interactions in relation to baseline-adjusted follow-up blood lipid concentrations

Exposing the exposures responsible for type 2 diabetes and obesity

The rising prevalences of type 2 diabetes and obesity constitute major threats to human health globally. Powerful social and economic factors influence the distribution of these diseases among and within populations. These factors act on a substrate of individual predisposition derived from the composite effects of inherited DNA variation and a range of environmental exposures experienced througho

Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G×E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (Pv), G×E interaction effects (with smoking and physical activity), and marginal genetic e

FTO genotype and weight loss : systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials

OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.ELIGIBILITY CRITERIA FOR S

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) <5%) coding variants asso

Rates of glycaemic deterioration in a real-world population with type 2 diabetes

Aims/hypothesis: There is considerable variability in how diabetes progresses after diagnosis. Progression modelling has largely focused on ‘time to failure’ methods, yet determining a ‘coefficient of failure’ has many advantages. We derived a rate of glycaemic deterioration in type 2 diabetes, using a large real-world cohort, and aimed to investigate the clinical, biochemical, pharmacological and

Does the Timing of Integrating New Skills Affect Start-up Growth?

Research SummaryGrowth often requires start‐ups to recruit new skills not present in the founding team. We analyze if the relationship between integrating new skills and growth depends on timing. Should new skills be recruited as early as possible, or can start‐ups add them as needed along the way? Using a unique panel dataset covering Sweden's population of start‐ups from 1997 to 2012, our analys

An investigation of causal relationships between prediabetes and vascular complications

Prediabetes is a state of glycaemic dysregulation below the diagnostic threshold of type 2 diabetes (T2D). Globally, ~352 million people have prediabetes, of which 35–50% develop full-blown diabetes within five years. T2D and its complications are costly to treat, causing considerable morbidity and early mortality. Whether prediabetes is causally related to diabetes complications is unclear. Here

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which

Human postprandial responses to food and potential for precision nutrition

Metabolic responses to food influence risk of cardiometabolic disease, but large-scale high-resolution studies are lacking. We recruited n = 1,002 twins and unrelated healthy adults in the United Kingdom to the PREDICT 1 study and assessed postprandial metabolic responses in a clinical setting and at home. We observed large inter-individual variability (as measured by the population coefficient of

Precision medicine in diabetes : a Consensus Report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

The convergence of advances in medical science, human biology, data science and technology has enabled the generation of new insights into the phenotype known as ‘diabetes’. Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence and how best practice in treatment varies between populations.

Association of changes in inflammation with variation in glycaemia, insulin resistance and secretion based on the KORA study

Aims: Subclinical systemic inflammation may contribute to the development of type 2 diabetes, but its association with early progression of glycaemic deterioration in persons without diabetes has not been fully investigated. Our primary aim was to assess longitudinal associations of changes in pro-inflammatory (leukocytes, high-sensitivity C-reactive protein (hsCRP)) and anti-inflammatory (adipone