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Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to ide

Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes

Genome sequencing can identify individuals in the general population who harbor rare coding variants in genes for Mendelian disorders1-7 and who may consequently have increased disease risk. Previous studies of rare variants in phenotypically extreme individuals display ascertainment bias and may demonstrate inflated effect-size estimates8-12. We sequenced seven genes for maturity-onset diabetes o

Health-related quality of life 5 years after carpal tunnel release among patients with diabetes: a prospective study with matched controls.

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy encountered in diabetes. The short-term improvement after carpal tunnel release has previously been demonstrated not to differ between patients with and without diabetes, despite a marked impairment in health-related quality of life (HRQL) among the former. In this study, we compare HRQL 5 years after carpal tunnel release betwe

Between-Monitor Differences in Step Counts Are Related to Body Size: Implications for Objective Physical Activity Measurement

Background: The quantification of the relationships between walking and health requires that walking is measured accurately. We correlated different measures of step accumulation to body size, overall physical activity level, and glucose regulation. Methods: Participants were 25 men and 25 women American Indians without diabetes (Age: 20-34 years) in Phoenix, Arizona, USA. We assessed steps/day du

Complement activation and plasma levels of C4b-binding protein in critical limb ischemia patients.

OBJECTIVE: Critical limb ischemia (CLI) is a peripheral arterial disease manifested by drastically diminished blood flow to the legs, pain at rest, nonhealing wounds, and gangrene caused by atherosclerosis. Significant tissue necrosis is associated with late stage CLI and the patients have a poor prognosis. Necrotic and apoptotic cells activate complement and bind complement inhibitor C4b-binding

Targeting Expression of the Leukemogenic PML-RAR alpha Fusion Protein by Lentiviral Vector-Mediated Small Interfering RNA Results in Leukemic Cell Differentiation and Apoptosis

Acute promyelocytic leukemia (APL) results from a chromosomal translocation that gives rise to the leukemogenic fusion protein PML-RAR alpha (promyelocytic leukemia-retinoic acid alpha receptor). Differentiation of leukemic cells and complete remission of APL are achieved by treatment of patients with pharmacological doses of all-trans retinoic acid (ATRA), making APL a model disease for different

Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS-We have conducted a meta-analysis of genome-wide as

Updated Genetic Score Based on 34 Confirmed Type 2 Diabetes Loci Is Associated With Diabetes Incidence and Regression to Normoglycemia in the Diabetes Prevention Program

OBJECTIVE Over 30 loci have been associated with risk of type 2 diabetes at genome-wide statistical significance. Genetic risk scores (GRSs) developed from these loci predict diabetes in the general population. We tested if a GRS based on an updated list of 34 type 2 diabetes-associated loci predicted progression to diabetes or regression toward normal glucose regulation (NGR) in the Diabetes Prev

Subsequent Type 2 Diabetes in Patients with Autoimmune Disease.

Immunological data show that type 2 diabetes (T2D) manifests autoimmune features. We wanted to test the association epidemiologically by assessing subsequent diagnosis of T2D following diagnosis of autoimmune disease (AId) and subsequent AId after T2D in the same individuals. Patients were identified from three Swedish health databases. A total of 32 different AId were included. Standardized incid

Association between plasma leptin and blood pressure in two population-based samples of children and adolescents

Objectives In this study we examined the association between leptin and blood pressure in a population-based study of Danish and Norwegian children and adolescents. Because of the putative bidirectional relationship between leptin and adiposity we formally tested (i) the mediating effect of body mass index in the association between leptin and blood pressure, and (ii) the mediating effect of lepti

Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study

OBJECTIVE-Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up. RESEARCH DESIGN AND METHODS-The randomized double-blind clinical trial of metformin or placebo followed by a 7-8-year open-label ex

Perinatal risk factors for premature ischaemic heart disease in a Swedish national cohort.

Several studies have reported associations between restricted fetal development, as shown by birth weight or birth length, and later ischaemic heart disease (IHD). However, few studies have examined the importance of these perinatal factors when taking into account gestational age at birth, hereditary factors, sociodemographic factors and comorbidities. This study investigated the importance of pe

Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body size The EPIC-InterAct study

Beulens JWJ, van der Schouw YT, Bergmann MM, Rohrmann S, B Schulze M, Buijsse B, Grobbee DE, Arriola L, Cauchi S, Tormo M-J, Allen NE, van der A DL, Balkau B, Boeing H, Clavel-Chapelon F, de Lauzon-Guillan B, Franks P, Froguel P, Gonzales C, Halkjaer J, Huerta JM, Kaaks R, Key TJ, Khaw KT, Krogh V, Molina-Montes E, Nilsson P, Overvad K, Palli D, Panico S, Ramon Quiros J, Ronaldsson O, Romieu I, Ro

Single InAs/GaSb Nanowire Low-Power CMOS Inverter

III − V semiconductors have so far predom- inately been employed for n-type transistors in high-frequency applications. This development is based on the advantageous transport properties and the large variety of heterostructure combinations in the family of III − V semiconductors. In contrast, reports on p-type devices with high hole mobility suitable for complementary metal − oxide − semiconducto

Risk of Second Primary Cancers in Multiple Myeloma Survivors in German and Swedish Cancer Registries.

We aimed at investigating the distribution and risk of second primary cancers (SPCs) in multiple myeloma (MM) survivors in Germany and Sweden to provide etiological understanding of SPCs and insight into their incidence rates and recording practices. MM patients diagnosed in 1997-2010 at age ≥15 years were selected from the Swedish (nationwide) and 12 German cancer registries. Standardized inciden

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identifi