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Frontline stories - caring for non-covid patients

As the pandemic plays out - hospitals are reconfigured to increase critical care capacity, outpatient clinics become virtual, and elective procedures delayed. How are these affecting care for those who are in hospital but don't have covid-19? In this podcast, Matt Morgan,honorary senior research fellow at Cardiff University, consultant in...




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Wellbeing – coping with Covid fatigue

We are more than six weeks into the lockdown and if you were to gauge the mood of the nation, it would be one of fatigue. It started as an all-hands-on-deck emergency situation, but it now transpires that the current work situation for healthcare professionals is not going to change any time soon. This is a marathon rather than a sprint. So how...




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Talk evidence covid-19 update: natural history of covid, include patients in guidelines

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give you...




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Glucose-Induced Reactive Oxygen Species Cause Apoptosis of Podocytes and Podocyte Depletion at the Onset of Diabetic Nephropathy

Katalin Susztak
Jan 1, 2006; 55:225-233
Complications




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Fuel selection in human skeletal muscle in insulin resistance: a reexamination

DE Kelley
May 1, 2000; 49:677-683
Articles




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5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle

EJ Kurth-Kraczek
Aug 1, 1999; 48:1667-1671
Articles




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Morbidity and Mortality in Diabetics In the Framingham Population: Sixteen Year Follow-up Study

Mariano J Garcia
Feb 1, 1974; 23:105-111
Original Contribution




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Endothelial Progenitor Cell Dysfunction: A Novel Concept in the Pathogenesis of Vascular Complications of Type 1 Diabetes

Cindy J.M. Loomans
Jan 1, 2004; 53:195-199
Complications




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Thiazolidinediones in the Treatment of Insulin Resistance and Type II Diabetes

Alan R Saltiel
Dec 1, 1996; 45:1661-1669
Perspectives in Diabetes




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Relation Between Antioxidant Enzyme Gene Expression and Antioxidative Defense Status of Insulin-Producing Cells

Markus Tiedge
Nov 1, 1997; 46:1733-1742
Original Article




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Are the {beta}-Cell Signaling Molecules Malonyl-CoA and Cystolic Long-Chain Acyl-CoA Implicated in Multiple Tissue Defects of Obesity and NIDDM?

Marc Prentki
Mar 1, 1996; 45:273-283
Original Article




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Cell-Permeable Peptide Inhibitors of JNK: Novel Blockers of {beta}-Cell Death

Christophe Bonny
Jan 1, 2001; 50:77-82
Islet Studies




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Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes: Results of the Prospective Population-Based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology




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A Lesson in Metabolic Regulation Inspired by the Glucokinase Glucose Sensor Paradigm

Franz M Matschinsky
Feb 1, 1996; 45:223-241
Banting Lecture 1995




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The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization

R A DeFronzo
Dec 1, 1981; 30:1000-1007
Original Contribution




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Mechanisms of Pancreatic {beta}-Cell Death in Type 1 and Type 2 Diabetes: Many Differences, Few Similarities

Miriam Cnop
Dec 1, 2005; 54:S97-S107
Section III: Inflammation and beta-Cell Death




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Nonalcoholic Fatty Liver Disease: A Feature of the Metabolic Syndrome

Giulio Marchesini
Aug 1, 2001; 50:1844-1850
Pathophysiology




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Evidence for 5'AMP-Activated Protein Kinase Mediation of the Effect of Muscle Contraction on Glucose Transport

Tatsuya Hayashi
Aug 1, 1998; 47:1369-1373
Rapid Publications




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High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells

T Inoguchi
Nov 1, 2000; 49:1939-1945
Articles




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Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance

Eve Van Cauter
Mar 1, 1992; 41:368-377
Original Article




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From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus

Ralph A. DeFronzo
Apr 1, 2009; 58:773-795
Banting Lecture




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Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action

D A Pan
Jun 1, 1997; 46:983-988
Original Article




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Protein kinase C activation and the development of diabetic complications

D Koya
Jun 1, 1998; 47:859-866
Articles




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Lipotoxicity in the Pathogenesis of Obesity-Dependent NIDDM: Genetic and Clinical Implications

Roger H Unger
Aug 1, 1995; 44:863-870
Perspectives in Diabetes




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Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and I{kappa}B-{alpha}

Samar I. Itani
Jul 1, 2002; 51:2005-2011
Rapid Publications




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Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats

G Xu
Dec 1, 1999; 48:2270-2276
Articles




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Banting Lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes

J. Denis McGarry
Jan 1, 2002; 51:7-18
Banting Lecture 2001




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Method for the Isolation of Intact Islets of Langerhans from the Rat Pancreas

Paul E Lacy
Jan 1, 1967; 16:35-39
Original Contribution




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Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications




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Hypoglycemia in the Diabetes Control and Complications Trial

The Diabetes Control and Complications Trial Research Group
Feb 1, 1997; 46:271-286
Original Article




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The Relationship of Glycemic Exposure (HbA1c) to the Risk of Development and Progression of Retinopathy in the Diabetes Control and Complications Trial

The Diabetes Control and Complications Trial Research Group
Aug 1, 1995; 44:968-983
Original Article




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A Preprandial Rise in Plasma Ghrelin Levels Suggests a Role in Meal Initiation in Humans

David E. Cummings
Aug 1, 2001; 50:1714-1719
Rapid Publications




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Role of oxidative stress in diabetic complications: a new perspective on an old paradigm

JW Baynes
Jan 1, 1999; 48:1-9
Articles




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PPAR{gamma} Ligands Increase Expression and Plasma Concentrations of Adiponectin, an Adipose-Derived Protein

Norikazu Maeda
Sep 1, 2001; 50:2094-2099
Pathophysiology




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Preservation of Pancreatic {beta}-Cell Function and Prevention of Type 2 Diabetes by Pharmacological Treatment of Insulin Resistance in High-Risk Hispanic Women

Thomas A. Buchanan
Sep 1, 2002; 51:2796-2803
Pathophysiology




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Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade

ME Griffin
Jun 1, 1999; 48:1270-1274
Articles




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Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM

Guenther Boden
Jan 1, 1997; 46:3-10
Perspectives in Diabetes




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Role of Oxidative Stress in Development of Complications in Diabetes

John W Baynes
Apr 1, 1991; 40:405-412
Perspectives in Diabetes




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The Triumvirate: {beta}-Cell, Muscle, Liver: A Collusion Responsible for NIDDM

Ralph A DeFronzo
Jun 1, 1988; 37:667-687
Lilly Lecture 1987




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Quantification of the Relationship Between Insulin Sensitivity and {beta}-Cell Function in Human Subjects: Evidence for a Hyperbolic Function

Steven E Kahn
Nov 1, 1993; 42:1663-1672
Original Article




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Triggering and amplifying pathways of regulation of insulin secretion by glucose

JC Henquin
Nov 1, 2000; 49:1751-1760
Articles




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PPAR-gamma: adipogenic regulator and thiazolidinedione receptor

BM Spiegelman
Apr 1, 1998; 47:507-514
Articles




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Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion

HE Hohmeier
Mar 1, 2000; 49:424-430
Articles




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Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice

Patrice D. Cani
Jun 1, 2008; 57:1470-1481
Metabolism




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The Pathobiology of Diabetic Complications: A Unifying Mechanism

Michael Brownlee
Jun 1, 2005; 54:1615-1625
Banting Lecture 2004




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Metabolic Endotoxemia Initiates Obesity and Insulin Resistance

Patrice D. Cani
Jul 1, 2007; 56:1761-1772
Obesity Studies




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Classification and Diagnosis of Diabetes Mellitus and Other Categories of Glucose Intolerance

National Diabetes Data Group
Dec 1, 1979; 28:1039-1057
Articles




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Assessment of MTNR1B Type 2 Diabetes Genetic Risk Modification by Shift Work and Morningness-Eveningness Preference in the UK Biobank

Night shift work, behavioral rhythms, and the common MTNR1B risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes; however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (N = 189,488), we aimed to test the cross-sectional independent associations and joint interaction effects of these risk factors on odds of type 2 diabetes (n = 5,042 cases) and HbA1c levels (n = 175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk allele associated with type 2 diabetes and HbA1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between self-reported morningness-eveningness preference and rs10830963 on risk of type 2 diabetes was seen, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when accelerometer-derived sleep midpoint was used as an objective measure of morningness-eveningness preference. Our findings suggest that MTNR1B risk allele carriers who carry out shift work or have more extreme morningness-eveningness preference may not have enhanced risk of type 2 diabetes.




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Predictive Modeling of Type 1 Diabetes Stages Using Disparate Data Sources

This study aims to model genetic, immunologic, metabolomics, and proteomic biomarkers for development of islet autoimmunity (IA) and progression to type 1 diabetes in a prospective high-risk cohort. We studied 67 children: 42 who developed IA (20 of 42 progressed to diabetes) and 25 control subjects matched for sex and age. Biomarkers were assessed at four time points: earliest available sample, just prior to IA, just after IA, and just prior to diabetes onset. Predictors of IA and progression to diabetes were identified across disparate sources using an integrative machine learning algorithm and optimization-based feature selection. Our integrative approach was predictive of IA (area under the receiver operating characteristic curve [AUC] 0.91) and progression to diabetes (AUC 0.92) based on standard cross-validation (CV). Among the strongest predictors of IA were change in serum ascorbate, 3-methyl-oxobutyrate, and the PTPN22 (rs2476601) polymorphism. Serum glucose, ADP fibrinogen, and mannose were among the strongest predictors of progression to diabetes. This proof-of-principle analysis is the first study to integrate large, diverse biomarker data sets into a limited number of features, highlighting differences in pathways leading to IA from those predicting progression to diabetes. Integrated models, if validated in independent populations, could provide novel clues concerning the pathways leading to IA and type 1 diabetes.




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Interplay of Placental DNA Methylation and Maternal Insulin Sensitivity in Pregnancy

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.