Liraglutide Improved Cardiometabolic Parameters More in Obese than in Non-obese Patients with Type 2 Diabetes: A Real-World 18-Month Prospective Study

Introduction The glucagon-like peptide-1 agonist (GLP1-RA) liraglutide is currently approved for the treatment of both obesity and type 2 diabetes (T2DM). We investigated whether the effect of this agent on cardiometabolic parameters in subjects with T2DM varied in relation to the concomitant presence of obesity. Methods One hundred thirty-five subjects (78 men and 57 women; age: 62 +/- 10 years) naive to incretin-based therapies were treated with low-dose liraglutide (1.2 mg/day) as an add-on to metformin for 18 months. Patients were divided into two subgroups based on their body-mass index (BMI): (a) obese (BMI >= 30) and (b) non-obese (BMI < 30). Clinical and laboratory analyses were assessed at baseline and every 6 months. Results During follow-up, significant improvements were seen in both groups in fasting glycemia, glycated hemoglobin, waist circumference, and carotid intima-media thickness (cIMT), while body weight, BMI, total cholesterol, and low-density lipoprotein cholesterol decreased significantly in obese subjects only. Correlation analysis revealed that changes in subclinical atherosclerosis (assessed by cIMT) were associated with changes in triglycerides (r = 0.488, p < 0.0001) in the obese group only. Conclusion Liraglutide had beneficial actions on glycemic parameters and cardiometabolic risk factors in both non-obese and obese patients with T2DM, with a greater efficacy in the latter. These findings reinforce the benefits of liraglutide for the cardiometabolic outcomes of obese patients with T2DM in the real-world setting. This has critical importance during the current pandemic, since patients with diabetes and obesity are exposed globally to the most severe forms of COVID-19, related complications, and death

Liraglutide Reduces Oxidative Stress And Restores Heme Oxygenase-1 and Ghrelin Levels in Patients with Type 2 Diabetes: A Prospective Pilot Study

Context: Liraglutide is a glucagon-like peptide-1 analog and glucose-lowering agent whose effects on cardiovascular risk markers have not been fully elucidated. Objective: We evaluated the effect of liraglutide on markers of oxidative stress, heme oxygenase-1 (HO-1), and plasma ghrelin levels in patients with type-2 diabetes mellitus (T2DM). Design and Setting: A prospective pilot study of 2 months duration has been performed at the Unit of Diabetes and Cardiovascular Prevention at University of Palermo, Italy. Patients and Intervention(s): Twenty subjects with T2DM (10 men and 10 women; meanage: 57 +/- 13 y) were treated with liraglutide sc (0.6 mg/d for 2 wk, followed by 1.2 mg/d) in addition to metformin (1500 mg/d orally) for 2 months. Patients with liver disorders or renal failure were excluded. Main Outcome Measure(s): Plasma ghrelin concentrations, oxidative stress markers, and heat-shock proteins, including HO-1 were assessed. Results: The addition of liraglutide resulted in a significant decrease in glycated hemoglobin (HbA1c) (8.5 +/- 0.4 vs 7.5 +/- 0.4%, P LT .0001). In addition, plasma ghrelin and glutathione concentrations increased (8.2 +/- 4.1 vs 13.6 +/- 7.3 pg/ml, P = .0007 and 0.36 +/- 0.06 vs 0.44 +/- 0.07 nmol/ml, P = .0002, respectively), whereas serum lipid hydroperoxides and HO-1 decreased (0.11 +/- 0.05 vs 0.04 +/- 0.07 pg/ml, P = .0487 and 7.7 +/- 7.7 vs 3.6 +/- 1.8 pg/ml, P = .0445, respectively). These changes were not correlated with changes in fasting glycemia or HbA1c. Conclusions: In a 2-months prospective pilot study, the addition of liraglutide to metformin resulted in improvement in oxidative stress as well as plasma ghrelin and HO-1 concentrations in patients with T2DM. These findings seemed to be independent of the known effects of liraglutide on glucose metabolism

Vitamin D and Multiple Sclerosis: An Open-Ended Story

Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease of the Central Nervous System (CNS). Genetic, epigenetic and environmental factors interact together, contributing to the complex pathogenesis of the disease. In the last decades, the role of hypovitaminosis D on MS risk was hypothesised. Several factors drive the regulation of vitamin D status, including genetics. The current review summarises the literature evidence on the association between vitamin D and MS, with a focus on the genetic polymorphisms in vitamin D-related genes. The variants of the genes codifying Vitamin D Receptor (VDR), Vitamin D Binding Protein (VDBP) and CYP enzymes have been investigated, but the findings are controversial. Only a few studies have addressed the role of DHCR7 polymorphisms in MS risk

Genetic and Epigenetic Biomarkers For Diagnosis, Prognosis and Treatment Of Metabolic Syndrome

Background: Metabolic syndrome is a clinical condition that deserves special attention because it puts the individual at high cardiovascular risk, especially heart attack and stroke. Considering the precision medicine, it would be advisable to valuate the individual cardio-metabolic risk by estimating the coesistence of risk factors (abdominal obesity, low level of High- Density Lipoprotein Cholesterol, High Triglycerides, and small dense Low-Density Lipoproteins sub-classes, hypertension, and elevated fasting glycemia), which could engrave on metabolism increasing cardiovascular mortality. Objective: To identify genetic and epigenetic biomarkers may assist in the possibility of helping follow-up strategies and other measures of prevention, and in metabolic risk. Methods: We searched for studies which valued the combination between epigenetic biomarkers and all factors of cardio-metabolic risk. Results: Numerous researches have investigated the molecular start of metabolic alterations, focusing on the epigenetic mark, as methylation of DNA, histone modifications and non.coding RNAs. It has been found that DNA methylation is the most searched epigenetic sign in the human genome concerning the control of gene expression. Conclusion: For the screening, diagnosis, and prognosis of metabolic syndrome and the prescription of personalized medicine, the DNA methylation biomarkers specify for subjects have been recognized as an ensuring tool. While these results are promising, further investigations are needed to unravel the complicated synergic association of the genome, epigenome and the situations related to metabolic pathology

Effect of a Natural Supplement Containing Curcuma Longa, Guggul, and Chlorogenic Acid in Patients with Metabolic Syndrome

The impact of a natural supplement (Kepar; Rikrea, Italy), containing several plant extracts such as curcuma longa, silymarin, guggul, chlorogenic acid, and inulin, was evaluated in 78 patients with metabolic syndrome (MetS; 45 men; age: 62 ± 9 years). Kepar at a dose of 2 pills/d was given for 4 months as add-on therapy to the ongoing treatment, maintained at fixed doses for the entire study. Anthropometric variables, plasma lipids, glucose parameters, and oxidative stress were measured at baseline and after 4 months. We found significant reductions in body weight (from 81.1 ± 13.5 to 79.4 ± 12.5 kg, P <.0001), body mass index (from 29.6 [23.7] to 29.3 [21.9] kg/m2, P =.001), and waist circumference (from 105 ± 11 to 102 ± 10 cm, P =.0004) as well as in fasting glucose (from 6.5 [11.7] to 6.4 [7.6] mmol/L, P =.014) and total cholesterol (from 4.8 ± 1.4 to 4.5 ± 1.0 mmol/L, P =.03). No significant changes were found in the other appraised parameters, including oxidative stress. In conclusion, after few months of treatment Kepar seems to exert beneficial effects in patients with MetS. Larger studies with a longer follow-up period are needed to confirm these preliminary findings

A Nutraceutical Containing Chlorogenic Acid and Luteolin Improves Cardiometabolic Parameters in Subjects with Pre-Obesity: A 6-Month Randomized, Double-Blind, Placebo-Controlled Study

Pre-obesity is a condition that predisposes to the risk of developing obesity, cardiovascular diseases (CVD), and diabetes. Our previous study demonstrated that a Cynara cardunculus (L.) based nutraceutical named Altilix® (Bionap, Italy), containing chlorogenic acid and luteolin extracts, was able to improve several hepatic and cardio-metabolic parameters. Given this background, we conducted a post-hoc analysis of the Altilix® study in order to analyze the supplement’s effects in the subgroup of pre-obesity subjects on anthropometry (weight and waist circumference), glucose metabolism (HbA1C, HOMA-IR, and HOMA-β), lipid profile (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol), hepatic functionality (FLI, AST, ALT and AST/ALT), carotid-media thickness (CIMT) and endothelial function (FMD). Fifty subjects from the original study cohort (which consisted of 100 subjects) were chosen with BMI ≥ 25 and 2. All subjects received the Altilix® supplement (150 mg/day) or placebo using a computer-based random allocation system. After six months of treatment Altilix® significantly reduced body weight, glycemic, and lipid parameters (total cholesterol, triglycerides, LDL-cholesterol) and improved hepatic functionality, CIMT, and FMD. In conclusion, these results confirm that Altilix® supplementation has a significant effect on cardiometabolic parameters not only in obese subjects but also in pre-obesity subjects

A Nutraceutical Containing Chlorogenic Acid and Luteolin Improves Cardiometabolic Parameters in Subjects with Pre-Obesity: A 6-Month Randomized, Double-Blind, Placebo-Controlled Study

: Pre-obesity is a condition that predisposes to the risk of developing obesity, cardiovascular diseases (CVD), and diabetes. Our previous study demonstrated that a Cynara cardunculus (L.) based nutraceutical named Altilix® (Bionap, Italy), containing chlorogenic acid and luteolin extracts, was able to improve several hepatic and cardio-metabolic parameters. Given this background, we conducted a post-hoc analysis of the Altilix® study in order to analyze the supplement's effects in the subgroup of pre-obesity subjects on anthropometry (weight and waist circumference), glucose metabolism (HbA1C, HOMA-IR, and HOMA-β), lipid profile (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol), hepatic functionality (FLI, AST, ALT and AST/ALT), carotid-media thickness (CIMT) and endothelial function (FMD). Fifty subjects from the original study cohort (which consisted of 100 subjects) were chosen with BMI ≥ 25 and &lt; 30 kg/m2. All subjects received the Altilix® supplement (150 mg/day) or placebo using a computer-based random allocation system. After six months of treatment Altilix® significantly reduced body weight, glycemic, and lipid parameters (total cholesterol, triglycerides, LDL-cholesterol) and improved hepatic functionality, CIMT, and FMD. In conclusion, these results confirm that Altilix® supplementation has a significant effect on cardiometabolic parameters not only in obese subjects but also in pre-obesity subjects

The Prevalence of NAFLD and Fibrosis in Bariatric Surgery Patients and the Reliability of Noninvasive Diagnostic Methods

Background. Bariatric surgery patients have a higher prevalence of nonalcoholic fatty liver (NAFL) than the general population; however, its assessment and the accurate staging of fibrosis are often complicated because noninvasive tests are not very accurate in patients with morbid obesity, and liver biopsy cannot be performed as a routine exam. The aim of this study was to evaluate (A) the histological prevalence of NAFL, nonalcoholic steatohepatitis (NASH), and fibrosis in patients undergoing bariatric surgery; (B) the reliability of ultrasound (US) in diagnosing NAFL; and (C) the reliability of various fibrosis scoring systems for defining fibrosis. Methods. US and intraoperative liver biopsy results were reviewed in 57 bariatric surgery patients. NAFL, NASH, and fibrosis were diagnosed according to the Kleiner scoring system. US diagnosis of liver steatosis was based on the bright liver. Fibrosis scores used were (i) the BMI, AST/ALT Ratio, Diabetes (BARD) scoring system; (ii) the nonalcoholic fatty liver disease (NAFLD) fibrosis score; and (iii) the fibrosis-4 (FIB-4) index. Results. The prevalence of NAFL was 81%, NASH 61.4%, and fibrosis 94% (F3 5.7%, cirrhosis 2.8%). The sensitivity of US was 95%, specificity 50%, and likelihood ratio (LR+, LR-) 1.91 and 0.1. The reliability of fibrosis scores for F≥2 were as follows: BARD score: sensitivity 46%, specificity 54%, and area under the receiver-operating characteristics (AUROC) curve 0.5; NAFLD score: sensitivity 30%, specificity 89%, and AUROC 0.5; and FIB-4: sensitivity 68%, specificity 67%, and AUROC 0.7. Conclusions. In bariatric surgery patients, the prevalence of NAFL was 81%, NASH 61.4%, and fibrosis 94%. US is able to rule out the presence of NAFL, while the commonly used scores may be inaccurate in defining fibrosis in patients with morbid obesity

Impact of Mycobacterium tuberculosis Infection on Human B Cell Compartment and Antibody Responses

Tuberculosis (TB) remains one of the most important health challenges worldwide. Control of the TB epidemic has not yet been achieved because of the lack of an effective vaccine and rapid and sensitive diagnostic approaches, as well as the emergence of drug-resistant forms of M. tuberculosis. Cellular immunity has a pivotal role against M. tuberculosis infection, but the role of humoral immunity is still controversial. We analyzed the frequency, absolute counts, and phenotypic and functional subsets of B lymphocytes in the peripheral blood of patients with active TB and subjects with latent infection compared to healthy donors. Moreover, we analyzed serum levels of total Ig and their IgA, IgM, and IgG isotypes and the titers of preexisting antibodies against a pool of common viral pathogens. FlowCT and unsupervised clusterization analysis show that patients with active TB and LTBI subjects have modest non-significant reduction in the numbers of circulating B lymphocytes as compared to healthy donors. Moreover, LTBI subjects had high percentages of atypical B cell population and lower percentages of naive and switched memory B cells. These findings were supported by gene expression and GSEA analysis. Moreover, there were no differences between active TB patients, LTBI subjects and HD, either in serum levels of total Ig isotypes or in preexisting IgG antibody titers, to ten different antigens from eight common pathogenic viruses, clearly demonstrating that either active or latent M. tuberculosis infection preserves the antibody production capacity of long-lived plasma cells. Thus, our results agree with previous studies reporting unaltered B cell frequencies in the blood of active TB patients and LTBI individuals as compared to healthy controls

Daily Use of Extra Virgin Olive Oil with High Oleocanthal Concentration Reduced Body Weight, Waist Circumference, Alanine Transaminase, Inflammatory Cytokines and Hepatic Steatosis in Subjects with the Metabolic Syndrome: A 2-Month Intervention Study

Extra virgin olive oil (EVOO) intake is associated with reduced cardiovascular risk, and its phenolic compound oleocanthal (OC) has anti-oxidant and anti-inflammatory properties. The cardiometabolic effects of EVOO with a high OC concentration have not been fully elucidated. We administered EVOO with a high OC concentration daily to 23 subjects with the metabolic syndrome (MetS) and hepatic steatosis (15 men and 8 women, age: 60 +/- 11 years) for 2 months. Anthropometric data, metabolic parameters, hepatic steatosis (by fatty liver index, FLI), abdominal fat distribution (by ultrasound), and pro- and anti-inflammatory cytokines were assessed before and after the intervention. EVOO supplementation was associated with a reduction in body weight, waist circumference, body mass index (BMI), alanine transaminase and FLI, as well as interleukin (IL)-6, IL-17A, tumor necrosis factor-alpha and IL-1B, while IL-10 increased. Maximum subcutaneous fat thickness (SFT max) also increased, with a concomitant decrease in the ratio of visceral fat layer thickness/SFT max. Correlation analysis revealed positive associations between changes in body weight and BMI and those in SFT max, along with an inverse association between changes in IL-6 and those in SFT max. In conclusion, ingestion of EVOO with a high OC concentration had beneficial effects on metabolic parameters, inflammatory cytokines and abdominal fat distribution in MetS subjects with hepatic steatosis, a category of patients at high cardiometabolic risk