Alterations in one-carbon metabolism in metabolic dysfunction associated steatotic liver disease may be modified by semaglutide.

Introduction And Objectives: Disruptions in one-carbon metabolism (OCM) have been linked to cardiometabolic diseases. We evaluated alterations in OCM metabolites and enzymes and the impact of semaglutide in MASLD.

Materials And Methods: Using targeted metabolomics and bulk-transcriptomics, we analyzed components of OCM in plasma samples and liver biopsies from MASLD patients (n=100 with F0-F4 fibrosis, 51% type 2 diabetes) and healthy controls (n=50).

Diurnal rhythm of the human plasma proteome.

Background: Plasma is the most used clinical specimen, yet diurnal variation in plasma proteins remains largely unexplored. We aimed to identify diurnally-regulated proteins in healthy individuals and assess their potential diagnostic implications, and highlight how diurnal awareness can advance future biomarker research.

Methods: Twenty-four healthy young individuals were studied under highly controlled conditions.

Diagnostics of Autoimmune Hepatitis Enabled by Non-Invasive Clinical Proteomics.

Background: Autoimmune hepatitis (AIH) may be difficult to diagnose and distinguish clinically and biochemically from other chronic liver diseases like metabolic dysfunction-associated steatotic liver disease (MASLD).

Aims: To identify pathways involved in the pathogenesis and identify disease-specific biomarkers of AIH.

Methods: We recruited 19 newly diagnosed patients with AIH, 17 with MASLD, and 19 healthy controls.

The hepatic transcriptome is differentially regulated by a standardized meal in healthy individuals compared to patients with fatty liver disease.

The human liver is dynamic organ with minute to hourly adaptions in response to feeding. Patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis have altered transcriptomic features compared to controls but how and if food intake affects such is unknown in humans. Our aim was to investigate the hepatic transcriptome at both fasting and postprandial states in patients with NAFLD, cirrhosis, and healthy controls and secondly to develop a browsable resource enabling easy and unrestricted access to such data.

Six-year follow-up of glycemic control and cardiovascular risk factors after a one-year intensive lifestyle intervention in type 2 diabetes: An extension of the randomized U-TURN trial.

Purpose: This study aimed to describe the effects of a 1-year lifestyle intervention on hemoglobin A1c (HbA1c) and cardiovascular risk factors 5 years after cessation of the lifestyle intervention in persons with type 2 diabetes (T2D).

Methods: From April 2015 to August 2016, 98 persons with T2D (duration < 10 years) were randomly allocated (2:1, stratified by sex) to a 1-year lifestyle intervention group (INT) (n = 64) or a standard care group (StC) (n = 34). All participants received standard care with blinded, target-driven medical therapy.

Circulating and hepatic levels of growth differentiation factor 15 in patients with metabolic dysfunction-associated steatotic liver disease.

Aim: Increased growth differentiation factor 15 (GDF15) may reflect impaired metabolic health and an inflammatory state in metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the role of GDF15 in histologically verified MASLD in a meal test (discovery) cohort (n = 20) and a prospective (validation) cohort with 2 years of follow-up (n = 276).

Methods: Participants were evaluated clinically and histologically in both cohorts.

The Glucagon Receptor Is Expressed in the Frontal Cortex and Impaired Signaling Associates With Cognitive Decline.

Individuals with type 2 diabetes (T2D) have an elevated risk of cognitive decline, yet the mechanisms connecting these pathologies remain unclear. Altered glucagon and insulin signaling contribute to T2D, and insulin resistance may also be associated with cognitive decline. The role of glucagon in this context is unknown.

Differences in biomarker levels and proteomic survival prediction across two COVID-19 cohorts with distinct treatments.

Prognostic biomarkers have been widely studied in COVID-19, but their levels may be influenced by treatment strategies. This study examined plasma biomarkers and proteomic survival prediction in two unvaccinated hospitalized COVID-19 cohorts receiving different treatments. In a derivation cohort ( = 126) from early 2020, we performed plasma proteomic profiling and evaluated innate and complement system immune markers.

Targeted proteomics of serum IGF-I, -II, IGFBP-2, -3, -4, -5, -6 and ALS.

Objectives: The insulin-like growth factors (IGFs) regulate growth in humans. IGF-I and IGF binding protein (IGFBP)-3 are biomarkers in children with growth disorders. We investigate a targeted proteomics method for absolute quantitation of eight IGF protein family members in human serum, including the peptide hormones IGF-I and -II, and the six binding proteins IGFBP-2, -3, -4, -5, -6 and acid labile subunit (ALS).

Islet hormones at the intersection of glucose and amino acid metabolism.

The pancreatic islets of Langerhans are central to fine-tuning metabolism to ensure metabolic homeostasis during the transition between fasting and feeding. Insulin and glucagon, the principal hormones generated and secreted by islets, exert powerful control in various metabolic tissues to drive nutrient uptake, storage and metabolism. Their canonical actions on glycaemia have positioned these hormones in opposition, however, their metabolic actions extend beyond controlling blood levels of glucose.

Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men.

Dietary protein restriction increases energy expenditure and enhances insulin sensitivity in mice. However, the effects of a eucaloric protein-restricted diet in healthy humans remain unexplored. Here, we show in lean, healthy men that a protein-restricted diet meeting the minimum protein requirements for 5 weeks necessitates an increase in energy intake to uphold body weight, regardless of whether proteins are replaced with fats or carbohydrates.

Female glucagon receptor knockout mice are prone to steatosis but resistant to weight gain when fed a MASH-promoting GAN diet and a high-fat diet.

Glucagon is secreted from the pancreatic alpha cells and regulates not only hepatic glucose production, but also hepatic lipid and amino acid metabolism. Thus, glucagon provides a switch from hepatic glucose and lipid storage towards lipid and amino acid breakdown fueling glucose production during fasting. However, the effects of genetic deletion of the glucagon receptor on lipid metabolism are unclear.

Human subjects with impaired beta-cell function and glucose tolerance have higher levels of intra-islet intact GLP-1.

Aims: A number of studies have suggested that pancreatic α cells produce intact GLP-1, thereby constituting a gut-independent paracrine incretin system. However, the debate on whether human α cells contain intact GLP-1 and whether this relates to the presence of diabetes is still ongoing. This study aimed to determine the presence of proglucagon-derived peptides, including GLP-1 isoforms, in pancreas biopsies obtained during partial pancreatectomy from metabolically profiled human donors, stratified according to pre-surgery glucose tolerance.

Glucagon, Metabolic Dysfunction-Associated Steatotic Liver Disease and Amino Acids in Humans and Animals without Diabetes Mellitus-An Evidence Map.

Introduction: Health systems are confronted with not only the growing worldwide childhood obesity epidemic but also associated comorbidities. These subsequently cause variations in distinct metabolic pathways, leading to metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this evidence map is to systematically evaluate the evidence and to identify research gaps on glucagon-induced amino acid (AA) turnover and its metabolic interaction with MASLD.

Interfering antibodies may contribute to elevated D-dimer: a case report.

Background: Plasma levels of D-dimer are elevated in patients with thromboembolisms. Here we investigated the existence of interfering antibodies as a potential cause for elevated D-dimer levels.

Case Presentation: A 42-year-old white Caucasian woman with a prior history of pulmonary embolism during her first pregnancy (treated with heparin therapy for 6 weeks postnatally) and hypothyroidism had a persistent elevated D-dimer without any clinical or ultrasound-based signs of thromboembolic conditions during her second pregnancy.

Glucagon receptor activation contributes to the development of kidney injury.

The underlying causes of diabetic kidney disease are still largely unknown. New insights into the contributing causes of diabetic nephropathy are important to prevent this complication. Hyperglycemia and hypertension are some of the risk factors for diabetic nephropathy.

Hepatic steatosis and not type 2 diabetes, body mass index, or hepatic fibrosis associates with hyperglucagonemia in individuals with steatotic liver disease.

Increased plasma concentrations of glucagon (hyperglucagonemia) are reported in patients with type 2 diabetes (T2D) and are considered a diabetogenic risk factor. Emerging evidence suggests that hepatic steatosis in obesity is causing a condition of resistance toward glucagon's effects on amino acid metabolism, resulting in an amino acid-induced hyperglucagonemia. We investigated the presence of hyperglucagonemia in individuals with biopsy-verified metabolic dysfunction-associated steatotic liver disease (MASLD), and whether body mass index (BMI), T2D, hepatic steatosis, and/or fibrosis contribute to this relationship.

The role of glucagon-like peptide 1 in the postprandial effects of metformin in type 2 diabetes: a randomized crossover trial.

Aims: Although metformin is widely used for treatment of type 2 diabetes (T2D), its glucose-lowering mechanism remains unclear. Using the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) antagonist exendin(9-39)NH2, we tested the hypothesis that postprandial GLP-1-mediated effects contribute to the glucose-lowering potential of metformin in T2D.

Methods: In a randomized, placebo-controlled, double-blind, crossover study, 15 individuals with T2D (median HbA1c 50 mmol/mol [6.

Glucagon Resistance in Individuals With Obesity and Hepatic Steatosis Can Be Measured Using the GLUSENTIC Test and Index.

Increased plasma levels of glucagon (hyperglucagonemia) promote diabetes development but are also observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance toward amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated.

Impairments of insulin and glucagon sensitivity in Chinese women with gestational diabetes mellitus.

Aim: To evaluate insulin and glucagon sensitivity in Han Chinese women with and without gestational diabetes mellitus (GDM).

Methods: In total, 81 women with GDM and 81 age-matched healthy controls were evaluated with a 75 g oral glucose tolerance test (OGTT) at gestational weeks 24-28. Plasma glucose concentrations were measured at fasting and 1 h and 2 h post-OGTT.

The impact of short-term eucaloric low- and high-carbohydrate diets on liver triacylglycerol content in males with overweight and obesity: a randomized crossover study.

Background: Intrahepatic triacylglycerol (liver TG) content is associated with hepatic insulin resistance and dyslipidemia. Liver TG content can be modulated within days under hypocaloric conditions.

Objectives: We hypothesized that 4 d of eucaloric low-carbohydrate/high-fat (LC) intake would decrease liver TG content, whereas a high-carbohydrate/low-fat (HC) intake would increase liver TG content, and further that alterations in liver TG would be linked to dynamic changes in hepatic glucose and lipid metabolism.