Dissociation between liver fat content and fasting metabolic markers of selective hepatic insulin resistance in humans.

Objective: Fasting hyperglycemia and hypertriglyceridemia are characteristic of insulin resistance (IR) and rodent work has suggested this may be due to selective hepatic IR, defined by increased hepatic gluconeogenesis and de novo lipogenesis (DNL), but this has not been shown in humans.

Design: Cross-sectional study in men and women across a range of adiposity.

Methods: Medication-free participants (n = 177) were classified as normoinsulinemic (NI) or hyperinsulinemic (HI) and as having low (LF) or high (HF) liver fat content measured by magnetic resonance spectroscopy.

Going beyond randomised controlled trials to assess treatment effect heterogeneity across target populations.

Methods have been developed for transporting evidence from randomised controlled trials (RCTs) to target populations. However, these approaches allow only for differences in characteristics observed in the RCT and real-world data (overt heterogeneity). These approaches do not recognise heterogeneity of treatment effects (HTE) according to unmeasured characteristics (essential heterogeneity).

Peptide-Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic β-Cell.

Targeting current therapies to treat or prevent the loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off-target effects. Current efforts to target the β-cell are limited by a lack of β-cell-specific targets and the inability to test multiple targeting moieties with the same delivery vehicle. Here, we fabricate a tailorable polycaprolactone nanocapsule (NC) in which multiple different targeting peptides can be interchangeably attached for β-cell-specific delivery.

Loss of electrical β-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes.

Diabetes mellitus involves both insufficient insulin secretion and dysregulation of glucagon secretion. In healthy people, a fall in plasma glucose stimulates glucagon release and thereby increases counter-regulatory hepatic glucose production. This response is absent in many patients with type-1 diabetes (T1D), which predisposes to severe hypoglycaemia that may be fatal and accounts for up to 10% of the mortality in patients with T1D.

Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial.

Background: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use.

Methods And Findings: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention.

Greater oxidation of dietary linoleate compared to palmitate in humans following an acute high-carbohydrate diet.

Background: We have previously demonstrated that dietary saturated fatty acids (SFA), when compared to polyunsaturated fatty acids (PUFA), are preferentially partitioned into oxidation pathways. However, it remains unclear if this preferential handling is maintained when hepatocellular metabolism is shifted toward fatty acid (FA) esterification and away from oxidation, such as when hepatic de novo lipogenesis (DNL) is upregulated.

Aim: To investigate whether an acute upregulation of hepatic DNL influences dietary FA partitioning into oxidation pathways.

Perlecan: An Islet Basement Membrane Protein with Protective Anti-Inflammatory Characteristics.

Throughout the isolation process, human islets are subjected to destruction of the islet basement membrane (BM) and reduced oxygen supply. Reconstruction of the BM represents an option to improve islet function and survival post-transplant and may particularly be relevant for islet encapsulation devices and scaffolds. In the present study, we assessed whether Perlecan, used alone or combined with the BM proteins (BMPs) Collagen-IV and Laminin-521, has the ability to protect isolated human islets from hypoxia-induced damage.

Sympathetic neuropeptide Y protects from obesity by sustaining thermogenic fat.

Human mutations in neuropeptide Y (NPY) have been linked to high body mass index but not altered dietary patterns. Here we uncover the mechanism by which NPY in sympathetic neurons protects from obesity. Imaging of cleared mouse brown and white adipose tissue (BAT and WAT, respectively) established that NPY sympathetic axons are a smaller subset that mostly maps to the perivasculature; analysis of single-cell RNA sequencing datasets identified mural cells as the main NPY-responsive cells in adipose tissues.

Glycaemic outcomes in people living with diabetes under 65 and over 65 years old using an intermittently scanned continuous glucose monitoring system.

Objective: Intermittently scanned continuous glucose monitoring (isCGM) has revolutionised the care of people with diabetes but its uptake and benefits in older adults are not well known. We examined the impact of isCGM (Freestyle Libre, FSL) on glycaemic outcomes in younger (⩽65 years) and older adults (>65 years) with diabetes.

Design And Methods: In total, 2260 adult patients registered on the Libreview account at University Hospitals Birmingham NHS Foundation Trust, UK, were included.

Postural asymmetry in low back pain - a systematic review and meta-analysis of observational studies.

Purpose: Systematic review and meta-analysis to examine common static postural parameters between participants with and without low back pain (LBP).

Methods: Systematic search on the PubMed, CINAHL, Embase and SCOPUS databases using keywords 'posture' and 'low back pain'. Observational studies comparing static postural outcomes (e.

Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms.

TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis.

International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents.

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork.

Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD.

Objectives: Currently, non-invasive scoring systems to stage the severity of non-alcoholic fatty liver disease (NAFLD) do not consider markers of glucose control (glycated haemoglobin, HbA1c); this study aimed to define the relationship between HbA1c and NAFLD severity in patients with and without type 2 diabetes.

Research Design And Methods: Data were obtained from 857 patients with liver biopsy staged NAFLD. Generalized-linear models and binomial regression analysis were used to define the relationships between histological NAFLD severity, age, HbA1c, and BMI.

Elevations in plasma glucagon are associated with reduced insulin clearance after ingestion of a mixed-macronutrient meal in people with and without type 2 diabetes.

Aims/hypothesis: The temporal suppression of insulin clearance after glucose ingestion is a key determinant of glucose tolerance for people without type 2 diabetes. Whether similar adaptations are observed after the ingestion of a mixed-macronutrient meal is unclear.

Methods: In a secondary analysis of data derived from two randomised, controlled trials, we studied the temporal responses of insulin clearance after the ingestion of a standardised breakfast meal consisting of cereal and milk in lean normoglycaemic individuals (n=12; Lean-NGT), normoglycaemic individuals with central obesity (n=11; Obese-NGT) and in people with type 2 diabetes (n=19).

A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion.

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB).

Loss of reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes.

There are multiple independent genetic signals at the () locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown that loss of in pancreatic beta cells reduces insulin content and impairs islet cell development and function. However, RREB1 is a widely expressed transcription factor and the metabolic impact of RREB1 loss remains unknown.

Body fat distribution and bone mineral density in a multi-ethnic sample of postmenopausal women in The Malaysian Cohort.

Unlabelled: In this study of postmenopausal women in Malaysia, total adiposity was inversely associated with total BMD, while regional associations varied. No differences were detected across Malay, Chinese, and Indian ethnicities. Low BMD contributes substantially to morbidity and mortality, and increasing adiposity levels globally may be contributing to this.