lean diabetes

This review synthesized the evidence from randomized controlled trials comparing the effect of meal replacements (MRs) as part of a weight loss intervention with conventional food-based weight loss diets on cardiometabolic risk in individuals with pre-diabetes and features of metabolic syndrome. MEDLINE, EMBASE, and Cochrane Library were searched through January 16, 2024. Data were pooled using the generic inverse variance method and expressed as mean difference [95% confidence intervals]. The overall certainty of the evidence was assessed using GRADE...

This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce ∼15-24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin...

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), often linked with obesity, can also affect individuals with normal weight, a condition known as "lean NAFLD", imposing comparable burdens and adverse effects. However, the impact of diet on lean NAFLD remains underexplored. The objective of this study is to investigate the correlation between the Dietary Inflammatory Index (DII) and NAFLD among Americans, stratified by waist-to-height ratio (WHtR) and body mass index (BMI). METHODS: Five thousand one hundred fifty-two participants from the National Health and Nutrition Examination Survey (NHANES) 2003-2018 were comprised in the final analysis...

Management of chronic obesity-associated metabolic disorders is a key challenge for biomedical researchers. During chronic obesity, visceral adipose tissue (VAT) undergoes substantial transformation characterized by a unique lipid-rich hypoxic AT microenvironment (ATenv) which plays a crucial role in VAT dysfunction, leading to insulin resistance (IR) and type 2 diabetes(T2D). Here, we demonstrate that obese ATenv triggers the release of miR-210-3p microRNA-loaded extracellular vesicles (EVs) from adipose tissue macrophages (ATMs), which disseminate miR-210-3p to neighboring adipocytes, skeletal muscle cells, and hepatocytes through paracrine and endocrine actions, thereby influencing insulin sensitivity...

During insulin resistance, the heart undergoes a metabolic shift in which fatty acids (FA) account for roughly about 99% of the ATP production. This metabolic shift is indicative of impaired glucose metabolism. A shift in FA metabolism with impaired glucose tolerance can increase reactive oxygen species (ROS), lipotoxicity, and mitochondrial dysfunction, ultimately leading to cardiomyopathy. Thyroid hormones (TH) may improve the glucose intolerance by increasing glucose reabsorption and metabolism in peripheral tissues, but little is known on its effects on cardiac tissue during insulin resistance...

Populational aging is marked by chronic noncommunicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels...

OBJECTIVE: Circulating exosome-enriched extracellular vesicles (EVs) have drawn considerable importance in obesity-related insulin-resistance (IR). We sought to compare the proteomics profile of serum exosomes from normal individuals and those with obesity and IR. METHODS: We isolated serum exosomes from male subjects with obesity and insulin resistance (Ob-IR, HOMA-IR > 2.0) and lean/overweight insulin-sensitive (Normal (N), HOMA-IR < 2.0) individuals. The differential protein expression between the two groups was detected by a label-free quantitative mass spectrometry analysis followed by GO annotation and ingenuity pathway analysis (IPA)...

BACKGROUND: Dysregulation of insulin and glucagon secretion alters the normal insulin:glucagon ratio (IGR) in type 2 diabetes mellitus, obesity, and metabolic syndrome. This study explores the scope of construing the role of these two diametrically opposing hormones on the glucose level not just in obesity but in different glucose tolerance states by looking at the hormone levels and at the insulin glucagon bipolar axis itself. MATERIALS AND METHODS: This is an analytical cross-sectional study of 60 healthy adults consisting of an equal number of adults who are lean and adults who are obese...

BACKGROUND AND AIMS: We aimed to investigate the correlation and to explore which MAFLD subtypes have the greatest influence on progression of arterial stiffness risk. METHODS AND RESULTS: Using data from a health examination-based cohort, a total of 12,129 participants who underwent two repeated health examinations that included brachial-ankle pulse wave velocity (baPWV) from 2012 to 2020 were enrolled. Participants were separated into non-MAFLD, overweight/obese (OW-MAFLD), lean/normal weight (lean-MAFLD) and diabetes (DM-MAFLD) groups...

Liver-expressed antimicrobial peptide 2 (LEAP2) and ghrelin have reciprocal effects on their common receptor, the growth hormone secretagogue receptor (GHSR). Ghrelin is considered a gastric hormone and LEAP2 a liver-derived hormone and both have been proposed to be involved in the pathophysiology of obesity and type 2 diabetes (T2D). We investigated the mRNA expression of LEAP2, ghrelin and GHSR along the intestinal tract of individuals with and without TD2, and in the liver of men with and without obesity...

OBJECTIVE: Glucose dependent insulinotropic polypeptide (GIP) is well established as an incretin hormone, boosting glucose-dependent insulin secretion. However, whilst anorectic actions of its sister-incretin glucagon-like peptide-1 (GLP-1) are well established, a physiological role for GIP in appetite regulation is controversial, despite the superior weight loss seen in preclinical models and humans with GLP-1/GIP dual receptor agonists compared with GLP-1R agonism alone. METHODS: We generated a mouse model in which GIP expressing K-cells can be activated through hM3Dq Designer Receptor Activated by Designer Drugs (DREADD, GIP-Dq) to explore physiological actions of intestinally-released GIP...

Dietary protein with adequate essential amino acids effectively stimulates protein synthesis and improves muscle mass. Musculoskeletal disorders in lower or upper limbs are not uncommon among patients with type II diabetes mellitus (T2DM). Therefore, this study primarily examines the effects of chronic dietary protein manipulation on amino acids' profile and position sense in the elderly suffering from T2DM. A total of 26 individuals suffering from non-insulin-dependent T2DM (age > 55 years old) participated in a 12 week nutritional intervention...

PURPOSE OF REVIEW: The purpose of this review article was to describe recent advances in our knowledge about how diabetes and metabolic syndrome are changing the face of familial hypercholesterolemia. RECENT FINDINGS: Heterozygous familial hypercholesterolemia, most commonly caused by disruption to LDL receptor function, leads to lifelong elevation of LDL cholesterol and increased risk of atherosclerotic cardiovascular disease. Familial hypercholesterolemia was originally described as a form of 'pure' hypercholesterolemia, in the sense that levels of LDL were uniquely affected...

OBJECTIVE: We aimed to examine the effects of a 5:2 regimens diet (2 days per week of energy restriction by formula diet) or an exercise (2 days per week of high-intensity interval training and resistance training) intervention compared with routine lifestyle education (control) on glycemic control and cardiometabolic health among adults with overweight/obesity and type 2 diabetes. RESEARCH DESIGN AND METHODS: This two-center, open-label, three-arm, parallel-group, randomized controlled trial recruited 326 participants with overweight/obesity and type 2 diabetes and randomized them into 12 weeks of diet intervention (n = 109), exercise intervention (n = 108), or lifestyle education (control) (n = 109)...

Detailed knowledge regarding the associations between intake of different types of seafood and meat and the risk of type 2 diabetes (T2D), and insight into possible mechanisms are warranted. In this study we aimed to evaluate the associations between intake of different types of seafood and meat and the subsequent risk of T2D using the Norwegian Mother, Father, and Child Cohort Study (MoBa), and furthermore, by using a mouse model to gain further insight into possible molecular mechanisms contributing to the associated metabolic changes...

AIMS: Hypertriglyceridemia is a risk factor for developing type 2 diabetes (T2D) and might contribute to its pathogenesis either directly or through elevation of non-esterified fatty acids (NEFAs). This study aimed at comparing the glucometabolic effects of acute hypertriglyceridemia alone or combined with NEFA elevation in non-diabetic subjects. METHODS: Twenty-two healthy lean volunteers underwent two 5-h intravenous infusions of either saline or Intralipid, without (n=12) or with heparin (I+H; n=10) to activate the release of NEFAs...

BACKGROUND: Type 2 diabetes mellitus (T2DM) is known to have obesity as a risk factor. Body mass index cannot distinguish between lean mass and fat mass. We aimed to examine the association between predicted fat mass, predicted lean mass, predicted percent fat and risk of T2DM in Japanese adults. We also explored whether these three new parameters could predict T2DM better than other obesity markers. METHODS: This present study is a secondary data analysis. The study enrolled 20,944 Japanese individuals who participated in the NAGALA medical assessment program between 2004 and 2015...

Spinophilin is an F-actin binding and protein phosphatase 1 (PP1) targeting protein that acts as a scaffold of PP1 to its substrates. Spinophilin knockout (Spino-/- ) mice have decreased fat mass, increased lean mass, and improved glucose tolerance, with no difference in feeding behaviors. While spinophilin is enriched in neurons, its roles in non-neuronal tissues, such as beta cells of the pancreatic islets, are unclear. We have corroborated and expanded upon previous studies to determine that Spino-/- mice have decreased weight gain and improved glucose tolerance in two different models of obesity...

INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor agonist, is associated with significant weight loss, yet its impact on lean body mass remains insufficiently understood. This review investigates the effect of semaglutide on lean mass in the context of obesity management. METHODOLOGY: This study investigates through different databases (PubMed, Elsevier, and Google Scholar) from 2016 for randomized control trials (RCTs) or observational studies that assessed the use of semaglutide in overweight or obese patients, regardless of whether they have type 2 diabetes or not...

Type 2 diabetes mellitus (T2DM) is one of the world's principal metabolic diseases characterized by chronic hyperglycemia. The gut incretin hormones, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), which has been proposed as a new treatment for T2DM, are extensively metabolized by Dipeptidyl peptidase 4 (DPP-4). Inhibitors of DPP-4 block the degradation of GLP-1 and GIP and may increase their natural circulating levels, favoring glycemic control in T2DM. A novel and potent selective inhibitor of DPP-4 with an 8-purine derived structure ( 1 ) has been developed and tested in vitro and in vivo in Zücker obese diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome and T2DM to assess the inhibitory activity using vildagliptin as reference standard...