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TCF7L2 is a master regulator of insulin production and processing.

Genome-wide association studies have revealed >60 loci associated with type 2 diabetes (T2D), but the underlying causal variants and functional mechanisms remain largely elusive. Although variants in TCF7L2 confer the strongest risk of T2D among common variants by presumed effects on islet function, the molecular mechanisms are not yet well understood. Using RNA-sequencing, we have identified a TC

Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis.

Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80%) and to atherosclerosis regression

Dairy products and risk of hepatocellular carcinoma: The European Prospective Investigation into Cancer and Nutrition

Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/ yogurt) and their components (calcium/vitamin D/fats/prote

Circulating triacylglycerol signatures and insulin sensitivity in NAFLD associated with the E167K variant in TM6SF2

Background & Aims: The Glu167Lys (E167K) variant in the transmembrane 6 superfamily member 2 protein (TM6SF2) was recently shown to influence liver fat (LFAT) content. We aimed at studying how this variant influences circulating triacylglycerol (TAG) signatures and whether it influences hepatic or adipose tissue insulin sensitivity. Methods: We genotyped 300 Finnish subjects for the E167K (rs5

High glucose enhances store-operated calcium entry by upregulating ORAI/STIM via calcineurin-NFAT signalling

ORAI and stromal interaction molecule (STIM) are storeoperated channel molecules that play essential roles in human physiology through a coupling mechanism of internal Ca2+ store to Ca2+ influx. However, the roles of ORAI and STIMin vascular endothelial cells under diabetic conditions remain unknown. Here, we investigated expression and signalling pathways of ORAI and STIM regulated by high glucos

A dedicated investigation unit improves management of syncopal attacks (Syncope Study of Unselected Population in Malmo--SYSTEMA I).

Aims To investigate whether a systematic approach to unexplained syncopal attacks based on the European Society of Cardiology guidelines would improve the diagnostic and therapeutic outcomes. Methods and results Patients presenting with transient loss of consciousness to the Emergency Department of Skåne University Hospital in Malmö were registered by triage staff. Those with established cardiac,

Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to

Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Background:There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell c

Does high sugar consumption exacerbate cardiometabolic risk factors and increase the risk of type 2 diabetes and cardiovascular disease?

Consumption of sugar has been relatively high in the Nordic countries; the impact of sugar intake on metabolic risk factors and related diseases has been debated. The objectives were to assess the effect of sugar intake (sugar-sweetened beverages, sucrose and fructose) on association with type 2 diabetes, cardiovascular disease and related metabolic risk factors (impaired glucose tolerance, insuli

Enhancement of glucagon secretion in mouse and human pancreatic alpha cells by protein kinase C (PKC) involves intracellular trafficking of PKCalpha and PKCdelta.

AIMS/HYPOTHESIS: Protein kinase C (PKC) regulates exocytosis in various secretory cells. Here we studied intracellular translocation of the PKC isoenzymes PKCalpha and PKCdelta, and investigated how activation of PKC influences glucagon secretion in mouse and human pancreatic alpha cells. METHODS: Glucagon release from intact islets was measured in static incubations, and the amounts released were

Early Revascularization after Admittance to a Diabetic Foot Center Affects the Healing Probability of Ischemic Foot Ulcer in Patients with Diabetes.

There is limited information about whether time from recognition of decreased perfusion to revascularization affects the probability of healing in a patient with a diabetic foot ulcer. The aim of the present study was to examine whether time to revascularization after referral to a multidisciplinary foot center was related to the outcome of foot ulcers in patients with diabetes and severe peripher

Food intake of individuals with and without diabetes across different countries and ethnic groups

Background/Objectives: Given the importance of nutrition therapy in diabetes management, we hypothesized that food intake differs between individuals with and without diabetes. We investigated this hypothesis in two large prospective studies including different countries and ethnic groups. Subjects/Methods: Study populations were the European Prospective Investigation into Cancer and Nutrition Stu

Mendelian randomization of blood lipids for coronary heart disease

Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholestero

Liver Fat Content and Hepatic Insulin Sensitivity in Overweight Patients With Type 1 Diabetes

Objectives: Patients with type 1 diabetes mellitus (T1DM) lack the portal/peripheral insulin gradient, which might diminish insulin stimulation of hepatic lipogenesis and protect against development of nonalcoholic fatty liver disease (NAFLD). We compared liver fat content and insulin sensitivity of hepatic glucose production and lipolysis between overweight T1DM patients and nondiabetic subjects.

Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study.

Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Isocaloric substitution of carbohydrates with protein: the association with weight change and mortality among patients with type 2 diabetes.

The health impact of dietary replacement of carbohydrates with protein for patients with type 2 diabetes is still debated. This study aimed to investigate the association between dietary substitution of carbohydrates with (animal and plant) protein and 5-year weight change, and all-cause and cardiovascular (CVD) mortality risk in patients with type 2 diabetes.

Genetic Variation in SULF2 Is Associated with Postprandial Clearance of Triglyceride-Rich Remnant Particles and Triglyceride Levels in Healthy Subjects

Context: Nonfasting (postprandial) triglyceride concentrations have emerged as a clinically significant cardiovascular disease risk factor that results from accumulation of remnant triglyceride-rich lipoproteins (TRLs) in the circulation. The remnant TRLs are cleared from the circulation by hepatic uptake, but the specific mechanisms involved are unclear. The syndecan-1 heparan sulfate proteoglyca

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously