Microvascular complications at time of diagnosis of type 2 diabetes are similar among diabetic patients detected by targeted screening and patients newly diagnosed in general practice - The Hoorn Screening Study

OBJECTIVE - To investigate whether screening-detected diabetic patients differ from diabetic patients newly diagnosed in general practice with regard to the presence of microvascular complications. RESEARCH AND DESIGN METHODS - Diabetic patients, identified by a population-based targeted screening procedure consisting of a screening questionnaire and a fasting capillary whole-blood glucose measurement followed by diagnostic testing, were compared with patients newly diagnosed with diabetes in general practice. Retinopathy was assessed with fundus photography, impaired foot sensitivity was assessed with Semmes-Weinstein monofilaments, and the presence of microalbuminuria was measured by means of the albumin-to creatinine ratio (ACR). RESULTS - A total of 195 screening-detected type 2 diabetic patients and 60 patients newly diagnosed in general practice participated in the medical examination. The prevalence of retinopathy was higher in screening-detected type 2 diabetic patients than in patients newly diagnosed in general practice, but not significantly higher. The prevalence of retinopathy was 7.6% (95% CI 4.6-12.4) in screening-detected type 2 diabetic patients and 1.9% (0.3-9.8) in patients newly diagnosed in general practice. The prevalence of impaired foot sensitivity was similar in both groups, 48.1% (40.9-55.3) and 48.3% (36.2-60.7), respectively. The ACR was 0.61 (interquariile range 0.41-1.50) in screening-detected type 2 diabetic patients and 0.99 (0.53-2.49) in patients newly diagnosed in general practice. The difference in prevalence of microalbuminuria was not statistically significant. The prevalence of microalbuminuria was 17.2% (95% CI 12.5-23.2) and 26.7% (17.1-39.0) in screening-detected type 2 diabetic patients and patients newly diagnosed in general practice, respectively. CONCLUSIONS - Targeted screening for type 2 diabetes (with a screening questionnaire as a first step) resulted in the identification of previously undiagnosed diabetic patients with a considerable prevalence of microvascular complications

DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA(1c) levels:a systematic review and replication in a case-control sample of the Lifelines study

AIMS/HYPOTHESIS: Epigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels. Here we present a systematic review of these studies and attempt to replicate the CpG sites (CpGs) with the most significant associations from these EWASs in a case-control sample of the Lifelines study.METHODS: We performed a systematic literature search in PubMed and EMBASE for EWASs to test the association between DNA methylation and type 2 diabetes and/or glycaemic traits and reviewed the search results. For replication purposes we selected 100 unique CpGs identified in peripheral blood, pancreas, adipose tissue and liver from 15 EWASs, using study-specific Bonferroni-corrected significance thresholds. Methylation data (Illumina 450K array) in whole blood from 100 type 2 diabetic individuals and 100 control individuals from the Lifelines study were available. Multivariate linear models were used to examine the associations of the specific CpGs with type 2 diabetes and glycaemic traits.RESULTS: From the 52 CpGs identified in blood and selected for replication, 15 CpGs showed nominally significant associations with type 2 diabetes in the Lifelines sample (p &lt; 0.05). The results for five CpGs (in ABCG1, LOXL2, TXNIP, SLC1A5 and SREBF1) remained significant after a stringent multiple-testing correction (changes in methylation from -3% up to 3.6%, p &lt; 0.0009). All associations were directionally consistent with the original EWAS results. None of the selected CpGs from the tissue-specific EWASs were replicated in our methylation data from whole blood. We were also unable to replicate any of the CpGs associated with HbA1c levels in the healthy control individuals of our sample, while two CpGs (in ABCG1 and CCDC57) for fasting glucose were replicated at a nominal significance level (p &lt; 0.05).CONCLUSIONS/INTERPRETATION: A number of differentially methylated CpGs reported to be associated with type 2 diabetes in the EWAS literature were replicated in blood and show promise for clinical use as disease biomarkers. However, more prospective studies are needed to support the robustness of these findings.</p

Youth in transition:Study protocol of a prospective cohort study into the long-term course of addiction, mental health problems and social functioning in youth entering addiction treatment

BACKGROUND: Substance use disorders (SUDs) are prevalent in the general population, tend to follow a chronic course, are associated with many individual and social problems, and often have their onset in adolescence. However, the knowledge base from prospective population surveys and treatment-outcome studies on the course of SUD in adolescents is limited at best. The present study aims to fill this gap and focuses on a subgroup that is particularly at risk for chronicity: adolescents in addiction treatment. We will investigate the rate of persistent SUD and its predictors longitudinally from adolescence to young adulthood among youth with DSM-5 SUD from the start of their addiction treatment to 2 and 4 years following treatment-entry. In addition to SUD, we will investigate the course of comorbid mental disorders, social functioning, and quality of life and their association with SUD over time. METHODS/DESIGN: In a naturalistic, multi-center prospective cohort design, we will include youths (n = 420), who consecutively enter addiction treatment at ten participating organizations in the Netherlands. Inclusion is prestratified by treatment organization, to ensure a nationally representative sample. Eligible youths are 16 to 22 years old and seek help for a primary DSM-5 cannabis, alcohol, cocaine or amphetamine use disorder. Assessments focus on lifetime and current substance use and SUD, non-SUD mental disorders, family history, life events, social functioning, treatment history, quality of life, chronic stress indicators (hair cortisol) and neuropsychological tests (computerized executive function tasks) and are conducted at baseline, end of treatment, and 2 and 4 years post-baseline. Baseline data and treatment data (type, intensity, duration) will be used to predict outcome – persistence of or desistance from SUD. DISCUSSION: There are remarkably few prospective studies worldwide that investigated the course of SUD in adolescents in addiction treatment for longer than 1 year. We are confident that the Youth in Transition study will further our understanding of determinants and consequences of persistent SUD among high-risk adolescents during the critical transition from adolescence to young adulthood. TRIAL REGISTRATION: The Netherlands National Trial Register Trial NL7928. Date of registration January 17, 2019

Orbital textures and charge density waves in transition metal dichalcogenides

Low-dimensional electron systems, as realized naturally in graphene or created artificially at the interfaces of heterostructures, exhibit a variety of fascinating quantum phenomena with great prospects for future applications. Once electrons are confined to low dimensions, they also tend to spontaneously break the symmetry of the underlying nuclear lattice by forming so-called density waves; a state of matter that currently attracts enormous attention because of its relation to various unconventional electronic properties. In this study we reveal a remarkable and surprising feature of charge density waves (CDWs), namely their intimate relation to orbital order. For the prototypical material 1T-TaS2 we not only show that the CDW within the two-dimensional TaS2-layers involves previously unidentified orbital textures of great complexity. We also demonstrate that two metastable stackings of the orbitally ordered layers allow to manipulate salient features of the electronic structure. Indeed, these orbital effects enable to switch the properties of 1T-TaS2 nanostructures from metallic to semiconducting with technologically pertinent gaps of the order of 200 meV. This new type of orbitronics is especially relevant for the ongoing development of novel, miniaturized and ultra-fast devices based on layered transition metal dichalcogenides

Left ventricular mass increases with deteriorating glucose tolerance, especially in women: Independence of increased arterial stiffness or decreased flow-mediated dilation - The Hoorn Study

OBJECTIVE - Type 2 diabetes and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease (CVD) risk. Increased left ventricular mass (LVM) is thought to increase CVD risk through several unfavorable cardiac changes. Type 2 diabetes and IGM are associated with increased LVM, but the underlying mechanism is unclear. We investigated the association between glucose tolerance status (GTS) and LVM and explored whether any such association could be mediated through increased arterial stiffness, impaired endothelial function, or the presence of atherosclerosis. RESEARCH DESIGN AND METHODS - We used ultrasound to measure LVM, carotid and femoral stiffness, carotid-femoral transit time, and flow-mediated vasodilation (FMD) and tonometry to estimate compliance and augmentation index. The study population (n = 780) consisted of 287 individuals with normal glucose metabolism (NGM), 179 with IGM, and 314 with type 2 diabetes, and the mean age was 68.4 years. RESULTS - In women, after adjusting for age, height, BMI, and mean arterial pressure, LVM increased significantly with deteriorating GTS (LVM 157 g in NGM, 155 g in IGM, and 169 g in type 2 diabetes, P for trend <0.018). Additional adjustment for arterial stiffness, FMD, or the presence of atherosclerosis did not materially alter the results, even though these variables were significantly associated with both GTS and LVM. Indexes of hyperglycemia/-insulinemia or insulin resistance explained at most 7% of the association between GTS and LVM. In men, no statistically significant associations were observed. CONCLUSIONS - Our data expand the conceptual view of the pathogenesis of GTS-related changes in LVM because we show that the increase in LVM in women is independent of increased arterial stiffness, impaired FMD, or the presence of atherosclerosis. In addition, we show that this increase in LVM is only minimally explained by indexes of hyperglycemia/-insulinemia or insulin resistance. Our data may, in part, explain the increased CVD risk seen in women with deteriorating GTS

Flicker Light–Induced Retinal Vasodilation in Diabetes and Diabetic Retinopathy

10.2337/dc09-0075Diabetes Care32112075-2080DICA

Inflammatory, Hemostatic, and Other Novel Biomarkers for Diabetic Retinopathy: The Multi-Ethnic Study of Atherosclerosis

Objective&#8212; There are conflicting data regarding relationships of systemic biomarkers of inflammation, hemostasis, and homocysteine with diabetic retinopathy. We examined these relationships in the Multi-Ethnic Study of Atherosclerosis. Research design and methods&#8212; A total of 921 participants with diabetes were included. Diabetic retinopathy was graded from retinal photographs. We defined two outcomes: any diabetic retinopathy and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse). Systemic markers analyzed were C-reactive protein, homocysteine, fibrinogen, plasmin- 2-antiplasmin complex (PAP), interleukin-6, D-dimer, factor VIII, serum creatinine, and urinary albumin-to-creatinine (UAC) ratio. Results&#8212; Prevalence of diabetic retinopathy was 33.2% and vision-threatening diabetic retinopathy 7.1%. After adjusting for established risk factors (diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, and use of diabetes medications), fibrinogen (odds ratio 1.14 [95% CI 1.01&#8211;1.32], P 0.05) and PAP (1.25 [1.05&#8211;1.50], P0.01) were associated with any diabetic retinopathy, while PAP (1.54 [1.13&#8211;2.11], P 0.007) and homocysteine (1.57 [1.16&#8211; 2.11], P 0.003) were associated with vision-threatening diabetic retinopathy. Only PAP remained significant after additional adjustment for serum creatinine and UAC ratio. Area under receiver-operator characteristic curve (AUROC) for diabetic retinopathy was constructed for established and novel risk factors. Established risk factors accounted for a 39.2% increase of the AUROC, whereas novel markers (fibrinogen, PAP, homocysteine, serum creatinine, and UAC ratio) only accounted for an additional 2.2%. Conclusions&#8212; There were few associations of novel markers of inflammation, hemostasis, and homocysteine with diabetic retinopathy after controlling for established risk factors. These data suggest that there is limited clinical use of these biomarkers for prediction of diabetic retinopathy