Renin-independent aldosteronism and metabolic dysfunction-associated steatotic liver disease and cirrhosis: A genetic association study.

Background & Aims: Renin-independent aldosteronism (RIA) refers to a spectrum of autonomous aldosterone hypersecretion. We aimed to explore the genetical relationship between RIA and metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis.

Methods: We included 125357 participants from the cohort of United Kingdom Biobank.

Lipoprotein (a) in the Full Spectrum of MASLD; Evidence from Histologically and Genetically Characterized Cohorts.

Background And Aims: Lipoprotein(a) (Lp(a)) is an emerging biomarker for cardiometabolic factors. We studied the role of Lp(a) in the full spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Three independent analyses were implemented using a multi-center, cross-sectional, liver biopsy-based study (n=332) (Study 1) and the UK Biobank prospective study (n=270,004) (Study 2, median follow-up=12.

Regulation of proglucagon derived peptides by carbohydrate and protein ingestion in young healthy males-A randomized, double-blind, cross-over trial.

Background & Aims: The ingestion of macronutrients triggers the release of several incretin peptides from the gastrointestinal system, which have both insulinotropic and satiety-inducing properties. The effect of the meal's macronutrient content on the secretion of these peptides has not been adequately studied, particularly concerning the secretion of the newly characterized proglucagon-derived peptides (PGDPs). We aimed to examine the effect of a meal's macronutrient content, specifically its protein versus carbohydrate content, on postprandial PGDPs responses in healthy men.

Accurate non-invasive detection of MASH with fibrosis F2-F3 using a lightweight machine learning model with minimal clinical and metabolomic variables.

Background: There are no known non-invasive tests (NITs) designed for accurately detecting metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis stages F2-F3, excluding cirrhosis-the FDA-defined range for prescribing Resmetirom and other drugs in clinical trials. We aimed to validate and re-optimize known NITs, and most importantly to develop new machine learning (ML)-based NITs to accurately detect MASH F2-F3.

Methods: Clinical and metabolomic data were collected from 443 patients across three countries and two clinic types (metabolic surgery, gastroenterology/hepatology) covering the entire spectrum of biopsy-proven MASH, including cirrhosis and healthy controls.

Inflammation in atherosclerosis: pathophysiology and mechanisms.

Atherosclerosis imposes a heavy burden on cardiovascular health due to its indispensable role in the pathogenesis of cardiovascular disease (CVD) such as coronary artery disease and heart failure. Ample clinical and experimental evidence has corroborated the vital role of inflammation in the pathophysiology of atherosclerosis. Hence, the demand for preclinical research into atherosclerotic inflammation is on the horizon.

Noninvasive Hepatic Steatosis and Fibrosis Indices Differentially Predict Mortality in the Adult Korean Population.

Background & Aims: Because the association of hepatic fibrosis and steatosis non-invasive indices with mortality remain controversial, their association with all-cause, cardiovascular-, cancer-, and liver-related mortality was evaluated in the Korean population.

Methods: In this registry-based, cohort study, data were retrieved from the Korea National Health and Nutrition Examination Survey and mortality data from the Korean Cause of Death data registry; 40,491 individuals followed-up for a median of 8.6 years.

Evidence from clinical studies of leptin: current and future clinical applications in humans.

Leptin has been established as the prototype adipose tissue secreted hormone and as a major regulator of several human physiology functions. Here, we are primarily reviewing the findings from studies in humans involving leptin administration. We are describing the metabolic, endocrine and immunologic effects of leptin replacement in conditions of leptin deficiency, such as short-term fasting in healthy individuals, relative energy deficiency in sports (REDS), congenital leptin deficiency (CLD), generalized (GL) and partial lipodystrophy (PL), HIV-associated lipodystrophy (HIV-L) and of leptin treatment in conditions of leptin excess (common obesity, type 2 diabetes, steatotic liver disease).

The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation.

Similar to bariatric surgery, incretin receptor agonists have revolutionized the treatment of obesity, achieving up to 15-25 % weight loss in many patients, i.e., at a rate approaching that achieved with bariatric surgery.

Leptin physiology and pathophysiology in energy homeostasis, immune function, neuroendocrine regulation and bone health.

Since its discovery and over the past thirty years, extensive research has significantly expanded our understanding of leptin and its diverse roles in human physiology, pathophysiology and therapeutics. A prototypical adipokine initially identified for its critical function in appetite regulation and energy homeostasis, leptin has been revealed to also exert profound effects on the hypothalamic-pituitary-gonadal, thyroid, adrenal and growth hormone axis, differentially between animals and humans, as well as in regulating immune function. Beyond these roles, leptin plays a pivotal role in significantly affecting bone health by promoting bone formation and regulating bone metabolism both directly and indirectly through its neuroendocrine actions.

Apolipoprotein C-III in association with metabolic-dysfunction associated steatotic liver disease: A large, multicenter study.

Background & Aims: The available literature on the effect of apolipoprotein C-III (ApoC-III) inhibition in MASLD reveals inconsistencies. The aim of the present work was to examine levels of ApoC-III in the entire spectrum of metabolic-dysfunction associated steatotic liver disease (MASLD).

Methods: This is a multicenter study involving patients enrolled in two gastroenterology-hepatology clinics (Greece and Australia) and in a bariatric-metabolic surgery clinic (Italy), with liver biopsy before and after bariatric surgery or lifestyle modification.

Enhancing severe hypoglycemia prediction in type 2 diabetes mellitus through multi-view co-training machine learning model for imbalanced dataset.

Patients with type 2 diabetes mellitus (T2DM) who have severe hypoglycemia (SH) poses a considerable risk of long-term death, especially among the elderly, demanding urgent medical attention. Accurate prediction of SH remains challenging due to its multifaced nature, contributed from factors such as medications, lifestyle choices, and metabolic measurements. In this study, we propose a systematic approach to improve the robustness and accuracy of SH predictions using machine learning models, guided by clinical feature selection.

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The history of anti-obesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the conviction that excess body weight signifies a lack of willpower. However, categories of emerging pharmacotherapies generate hope to reduce obesity rates. This systematic review of phase 2 and phase 3 trials in adults with overweight/obesity investigates the effect of novel weight loss pharmacotherapies, compared to placebo/control or Food and Drug Administration-approved weight loss medication, through searching Medline, Embase, and ClinicalTrials.

Global burden of metabolic diseases, 1990-2021.

Background: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex.

Methods: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD).