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Epigenetic variation in human adipose tissue has been linked to type 2 diabetes and its related risk factors including age and obesity. Insulin resistance, a key risk factor for type 2 diabetes, may also be associated with altered DNA methylation in visceral and subcutaneous adipose tissue. Furthermore, linking epigenetic variation in target tissues to similar changes in blood cells may identify n
Elevated basal insulin secretion under fasting conditions together with insufficient stimulated insulin release is an important hallmark of type 2 diabetes, but the mechanisms controlling basal insulin secretion remain unclear. Membrane rafts exist in pancreatic islet cells and spatially organize membrane ion channels and proteins controlling exocytosis, which may contribute to the regulation of i
Type 2 diabetes (T2D) is a complex disease with widespread physiological insults to the regulation of metabolic homeostasis, above all glycaemic regulation. The pathogenesis of T2D and its progression is broadly understood to be through a gradual decrease in peripheral insulin sensitivity, a compensatory rise in insulin secretion, and a gradual decline in beta-cell function, resulting in glycaemic
MOTIVATION: Depletion of loss-of-function (LoF) mutations may provide a rank of genic functional intolerance and consequently susceptibility to disease.RESULTS: Here we have studied LoF mutations in 60 706 unrelated individuals and show that the most intolerant quartile of ranked genes is enriched in rare and early onset diseases and explains 87% of de novo haploinsufficient OMIM mutations, 17% mo
Purpose To study prevalence of diabetic retinopathy (DR) at diagnosis (DRAD) and to estimate contributing risk by sociodemographic, cardiovascular and metabolic characteristics present in patients recently diagnosed with type 2 diabetes (T2D) or latent autoimmune diabetes in the adult (LADA). Methods Patients (n = 2174) recently diagnosed T2D (93%) or LADA (7%) were included upon arrival for their
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
Previous research has shown that it is possible to decarbonise Sweden's road transport sector. This study develops a scenario based method and analyses the influence of external factors on energy security, focusing on passenger and freight transport. It does so by analysing the vulnerabilities and capabilities of five different climate mitigation strategies, investigating previous security scenariPrevious research has shown that it is possible to decarbonise Sweden's road transport sector. This study develops a scenario based method and analyses the influence of external factors on energy security, focusing on passenger and freight transport. It does so by analysing the vulnerabilities and capabilities of five different climate mitigation strategies, investigating previous security scenari
The last decade has witnessed a revolution in genetic technology, where genome-wide analyses, covering the majority of genetic variation, were thought to explain disease-causing mechanisms in common metabolic disorders. However, these genetic data only explain a modest proportion of the estimated heritability of type 2 diabetes and obesity and hence suggest a potential role for epigenetic variatio
Aim: To define the genomic distribution and function of DNA methylation changes during human adipogenesis. Methods: We isolated adipocyte-derived stem cells from 13 individuals and analyzed genome-wide DNA methylation and gene expression in cultured adipocyte-derived stem cells and mature adipocytes. Results: We observed altered DNA methylation of 11,947 CpG sites and altered expression of 11,830
AIMS/HYPOTHESIS: Impaired glucose tolerance and impaired insulin secretion have been reported in families with PAX6 mutations and it is suggested that they result from defective proinsulin processing due to lack of prohormone convertase 1/3, encoded by PCSK1. We investigated whether a common PAX6 variant would mimic these findings and explored in detail its effect on islet function in man. METHODS
Several new oral antidiabetic agents, known as 'gliptins' or 'enzyme dipeptidyl peptidase-IV (DPP-4) inhibitors', have been developed for the treatment of type 2 diabetes and a key clinical use of the gliptins is in combination with metformin. There are important differences in the kinetics of the interaction of different gliptins with the catalytic site of DPP-4, which may lead to varying pharmac
Incretin-based therapy for type 2 diabetes is based on the antidiabetic effects of glucagon-like peptide-1 (GLP-1) and instituted by GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors targeting the key islet defects of the disease. The treatment is clinically efficient and safe, and associated with a low risk of adverse events. It can be used both in early and late stages of the disease
Although it is well established that the pancreatic islets are innervated by autonomic nerves, the detailed islet innervation pattern is still unclear. In this issue of Diabetologia (DOI: 10.1007/s00125-012-2699-6 ) novel details of the islet neuroanatomy and its plasticity in experimental diabetes are described. By using a 3-dimensional (3-D) imaging technique, it has been shown that, in islets f
It is hoped that information garnered from studies on population genetics will one day be translated into a form in which it meaningfully improves the prediction, prevention or treatment of type 2 diabetes. Type 2 diabetes genetics researchers have made extraordinary progress in identifying common genetic variants that are associated with type 2 diabetes, which has shed light on the biological pat
AIMS/HYPOTHESIS: To study the heritability and familiality of type 2 diabetes and related quantitative traits in families from the Botnia Study in Finland. METHODS: Heritability estimates for type 2 diabetes adjusted for sex, age and BMI are provided for different age groups of type 2 diabetes and for 34 clinical and metabolic traits in 5,810 individuals from 942 families using a variance compone
α1-antitrypsin (AAT) is a serine protease inhibitor, which recently has been shown to prevent type 1 diabetes (T1D) development, to prolong islet allograft survival and to inhibit β-cell apoptosis in vivo. It has also been reported that T1D patients have significantly lower plasma concentrations of AAT suggesting the potential role of AAT in the pathogenesis of T1D. We have investigated whether pl
Achieving tight glycaemic control remains an unmet need for many patients with type 2 diabetes, despite improved treatments. In order to meet glycaemic targets, attempts have been made to improve existing drugs and to develop new classes of drugs. Recent advances include insulin analogues that more closely mimic physiologic insulin levels, and incretin-based therapies, which capitalise on the gluc
Type 1 diabetes (T1D) is an autoimmune disease caused by the T cell-mediated destruction of the pancreatic insulin-producing beta cells. Currently there are no widely accepted and standardized assays available to analyse the function of autoreactive T cells involved in T1D. The development of such an assay would greatly aid efforts to understand the pathogenesis of T1D and is also urgently require
Autoimmune T cell responses directed against insulin-producing β cells are central to the pathogenesis of type 1 diabetes (T1D). Detection of such responses is therefore critical to provide novel biomarkers for T1D 'immune staging' and to understand the mechanisms underlying the disease. While different T cell assays are being developed for these purposes, it is important to optimize and standardi
