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Metabolites
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Cardiometabolic Challenges-Present and Future
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Cardiometabolic Challenges-Present and Future

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 23489

Special Issue Editors

Prof. Dr. Manfredi Rizzo

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Guest Editor
Department of Internal Medicine and Medical Specialties (DIMIS), Università degli Studi di Palermo UNIPA, 90100 Palermo, Italy
Interests: cardiovascular risk; lipids; diabetes; prevention; therapy; metabolic syndrome; metabolism; lipoproteins; incretins; nutraceuticals
Special Issues, Collections and Topics in MDPI journals
Dr. Anca Pantea Stoian

E-Mail Website
Guest Editor
Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Str., 050474 Bucharest, Romania
Interests: diabetes; nutrition; metabolic diseases; chronic kidney disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular diseases represent the first cause of morbidity and mortality in most industrialised countries, and metabolic alterations are so strictly linked that is common to talk about the two as a whole, referring to them as cardiometabolic. Due to increasing sedentary habits and profound life habit changes, the cardiometabolic risk is an emerging problem in the entire planet, and it is crucial to identify the right targets of prevention and therapy. This Special Issue is dedicated to reviewing the current practical aspects of insulin resistance, and type-2 diabetes, atherogenic dyslipidemia, PCSK9 inhibition, hypertension, overweight and obesity, uric acid alteration, obstructive sleep apnea, chronic kidney disease, polycystic ovary syndrome ,and non-alcoholic fatty liver disease and will also highlight the most critical targets of prevention and therapy for an effective reduction of cardiometabolic risk. The triumvirate of metabolic syndrome, chronic kidney diseases, and coronary heart disease has as its mainstay oxidative stress and chronic inflammation. In the light of the determinations of new markers involved in this triad, as well as the new therapies focusing on cardio-renometabolic components, this edition aims to bring a modern approach to all innovations in this field.

Prof. Dr. Manfredi Rizzo
Prof. Dr. Anca Pantea Stoian
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiometabolic syndrome
  • cardiometabolic risk
  • cardio-renometabolic markers
  • insulin resistance
  • type-2 diabetes
  • chronic kidney disease

Published Papers (8 papers)

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Research

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8 pages, 1169 KiB  
Article
Possible Influence of Weight Gain and Creatinine Levels in Predicting Response to Nivolumab: A Multicenter Analysis
by Cornelia Nitipir, Cristina Orlov-Slavu, Lucian Alecu, Iulian Slavu, Anca Pantea-Stoian, Ionela Daniela Celmare, Mihaela Olaru, Valentin Calu, Andra-Iulia Suceveanu, Laura Mazilu, Andreea-Daniela Gheorghe, Adelina Silviana Gheorghe, Catalina Poiana, Razvan Hainarosie, Sanziana Octavia Ionescu and Dana Lucia Stanculeanu
Metabolites 2020, 10(12), 510; https://doi.org/10.3390/metabo10120510 - 14 Dec 2020
Cited by 5 | Viewed by 2238
Abstract
Literature suggests that high body mass index can be correlated with better response to immune checkpoint inhibitors. On the other hand, sarcopenia seems to be a negative predictive marker. The present analysis is a retrospective, multicenter trial that included patients with metastatic melanoma, [...] Read more.
Literature suggests that high body mass index can be correlated with better response to immune checkpoint inhibitors. On the other hand, sarcopenia seems to be a negative predictive marker. The present analysis is a retrospective, multicenter trial that included patients with metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma treated with nivolumab between 2018 and 2020. Patients were stratified by creatinine levels both at treatment initiation and at first follow-up (at three months) and by BMI for the same intervals, as recorded in the patients’ charts. Creatinine was considered a surrogate marker for sarcopenia. IBM SPSS version 20 was used for statistical analysis. A total of 57 (n = 57) patients were included in the trial. Overall response rate (ORR) for the entire population was 38.59% (p = 0.02). Patients with BMI lower than 25 had an ORR of 28.5% (p = 0.003), whereas patients with BMI higher than 25 had an ORR of 42.3% (p = 0.002). Patients who gained weight during treatment had a lower probability of having progressive disease (OR = 0.4 [95% CI; 0.4–1.2]), as did patients with creatinine higher than 0.9 (OR = 0.39 [95% CI: 0.13–1.14]). No superiority was found in progression-free survival (PFS) when patients were dichotomized for BMI = 25 or BMI = 18.5. Mean PFS in the BMI under 18.5 group was 10.2 months [95% CI: 5.8–23.1], versus 11.2 for BMI over 18.5 [95% CI: 5.3–25.3], p < 0.03. Mean PFS for the BMI under 25 was 11.2 months [95% CI: 7.2–20.1], vs. 13.3 months [95% CI: 6.4–22] for the BMI over 25, p < 0.001. There were also differences in PFS in the patients with baseline creatinine over 0.9 when compared with under 0.9 values. Mean PFS in the first group was 19.78 months [95% CI: 16.23–22.9] vs. 16.1 [95% CI: 12.2–20.3], p < 0.001. Patients treated with nivolumab who have weight gain during treatment have a better PFS than the ones who do not. Creatinine levels of over 0.9 at treatment initiation also have positive predictive value. Full article
(This article belongs to the Special Issue Cardiometabolic Challenges-Present and Future)
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18 pages, 1167 KiB  
Article
Genetic Variability in Antioxidative and Inflammatory Pathways Modifies the Risk for PCOS and Influences Metabolic Profile of the Syndrome
by Rok Herman, Mojca Jensterle, Andrej Janež, Katja Goričar and Vita Dolžan
Metabolites 2020, 10(11), 439; https://doi.org/10.3390/metabo10110439 - 29 Oct 2020
Cited by 17 | Viewed by 2245
Abstract
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder of multifactorial etiopathology likely to involve the interactions between genetics and lifestyle. Chronic inflammation and oxidative stress (OS) may participate in the pathophysiology of the syndrome. The question of the extent to [...] Read more.
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder of multifactorial etiopathology likely to involve the interactions between genetics and lifestyle. Chronic inflammation and oxidative stress (OS) may participate in the pathophysiology of the syndrome. The question of the extent to which OS and inflammation are causally related to the development of the syndrome and metabolic complications remains unanswered. By our knowledge, the role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome as an important trigger of inflammatory pathways and NLRP3 and CARD8 polymorphisms has never been addressed in PCOS yet. We conducted a case-control study conducting of total 169 Slovenian PCOS patients and 83 healthy blood donors. They were genotyped for polymorphisms in antioxidative (SOD2 rs4880, CAT rs1001179, PON1 rs854560, and rs662) and inflammatory pathways genes (NLRP3 rs35829419, CARD8 rs2043211, TNF rs1800629, IL1B rs1143623, and rs16944, IL6 rs1800795) using competitive allele-specific polymerase chain reaction (PCR). Logistic regression and the Mann–Whitney test were used in the statistical analysis. SOD2 rs4880, CARD8 rs2043211, and IL1B rs16944 were associated with the risk of developing PCOS. Furthermore, the interactions between CARD8 rs2043211 and IL6 rs1800795 and between IL1B rs1143623 and IL6 rs1800795 also significantly affected the risk for PCOS. With regard to glucose homeostasis, CAT rs1001179, SOD2 rs4880, PON1 rs854560, NLRP3 rs35829419, and TNF rs1800629 were significantly associated with response to the glycemic load. Our data indicate that the genetic variability in the antioxidative and inflammatory pathways influences the development of PCOS and glucose homeostasis in PCOS patients. Full article
(This article belongs to the Special Issue Cardiometabolic Challenges-Present and Future)
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14 pages, 267 KiB  
Article
Pasta Supplemented with Opuntia ficus-indica Extract Improves Metabolic Parameters and Reduces Atherogenic Small Dense Low-Density Lipoproteins in Patients with Risk Factors for the Metabolic Syndrome: A Four-Week Intervention Study
by Rosaria Vincenza Giglio, Giuseppe Carruba, Arrigo F.G. Cicero, Maciej Banach, Angelo Maria Patti, Dragana Nikolic, Letizia Cocciadiferro, Maurizio Zarcone, Giuseppe Montalto, Anca Pantea Stoian, Yajnavalka Banerjee, Ali A. Rizvi, Peter P. Toth and Manfredi Rizzo
Metabolites 2020, 10(11), 428; https://doi.org/10.3390/metabo10110428 - 26 Oct 2020
Cited by 18 | Viewed by 2452
Abstract
Food supplementation with Opuntia ficus-indica (OFI) has been associated with a significant reduction in total cholesterol, body fat, hyperglycemia and blood pressure. Since OFI may also have antioxidant and anti-atherogenic properties, we hypothesized that its supplementation might reduce atherogenic lipoproteins, including small, dense [...] Read more.
Food supplementation with Opuntia ficus-indica (OFI) has been associated with a significant reduction in total cholesterol, body fat, hyperglycemia and blood pressure. Since OFI may also have antioxidant and anti-atherogenic properties, we hypothesized that its supplementation might reduce atherogenic lipoproteins, including small, dense low-density lipoproteins (sdLDL). Forty-nine patients (13 men and 36 women, mean age: 56 ± 5 years) with one or two criteria for the metabolic syndrome weekly consumed 500 g of pasta supplemented with 3% OFI extract (30% of insoluble polysaccharides with high antioxidant power) for 1 month. The full LDL subclass profile was assessed by gel electrophoresis (Lipoprint, Quantimetrix, Redondo Beach, CA, USA). After 1 month of pasta supplementation, waist circumference (p = 0.0297), plasma glucose (p < 0.0001), triglycerides (p = 0.0137), plasma creatinine (p = 0.0244), urea and aspartate transaminase (p < 0.0001 for each) significantly decreased. A percentage increase in larger, less atherogenic LDL-1 (p = 0.0002), with a concomitant reduction in smaller, denser LDL-2 (p < 0.0001) and LDL-3 (p = 0.0004), were found. LDL-4 and-5 decreased, although not significantly. This is the first intervention study suggesting that pasta enriched with an OFI extract may have beneficial effects on some metabolic parameters and the LDL particle sizes, reducing atherogenic sdLDL. Future studies will help to establish if these findings impact cardiovascular outcomes. Full article
(This article belongs to the Special Issue Cardiometabolic Challenges-Present and Future)
14 pages, 249 KiB  
Article
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
by Angelo M. Patti, Giuseppe Carruba, Arrigo F. G. Cicero, Maciej Banach, Dragana Nikolic, Rosaria V. Giglio, Antonino Terranova, Maurizio Soresi, Lydia Giannitrapani, Giuseppe Montalto, Anca Pantea Stoian, Yajnavalka Banerjee, Ali A. Rizvi, Peter P. Toth and Manfredi Rizzo
Metabolites 2020, 10(10), 392; https://doi.org/10.3390/metabo10100392 - 02 Oct 2020
Cited by 36 | Viewed by 4524
Abstract
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 [...] Read more.
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-α 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. Full article
(This article belongs to the Special Issue Cardiometabolic Challenges-Present and Future)
14 pages, 522 KiB  
Article
Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect
by Rosaria Vincenza Giglio, Dragana Nikolic, Giovanni Li Volti, Anca Pantea Stoian, Yajnavalka Banerjee, Antonio Magan-Fernandez, Giuseppa Castellino, Angelo Maria Patti, Roberta Chianetta, Carlo Castruccio Castracani, Giuseppe Montalto, Ali A. Rizvi, Giorgio Sesti and Manfredi Rizzo
Metabolites 2020, 10(10), 391; https://doi.org/10.3390/metabo10100391 - 30 Sep 2020
Cited by 10 | Viewed by 2158
Abstract
Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to [...] Read more.
Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to determine the effect of liraglutide on the serum levels of miRNA-27b, miRNA-130a and miRNA-210. Twenty-five subjects with type-2 diabetes mellitus (T2DM), naïve to incretin-based therapy, were treated with liraglutide (1.2 mg/day as an add-on to metformin) for 4 months. miRNAs were quantified using real-time polymerase chain reaction. After liraglutide treatment, we found significant reductions in fasting glucose (from 9.8 ± 5.3 to 6.7 ± 1.6 mmol/L, p = 0.0042), glycosylated haemoglobin (HbA1c) (from 8.1 ± 0.8 to 6.6 ± 1.0%, p = 0.0008), total cholesterol (from 5.0 ± 1.0 to 4.0 ± 0.7 mmol/L, p = 0.0011), triglycerides (from 1.9 ± 1.0 to 1.5 ± 0.8 mmol/L, p = 0.0104) and low-density lipoprotein cholesterol (from 2.9 ± 1.2 to 2.2 ± 0.6 mmol/L, p = 0.0125), while the serum levels of miRNA-27b, miRNA-130a and miRNA-210a were significantly increased (median (interquartile range, IQR) changes: 1.73 (7.12) (p = 0.0401), 1.91 (3.64) (p = 0.0401) and 2.09 (11.0) (p = 0.0486), respectively). Since the changes in miRNAs were independent of changes in all the metabolic parameters investigated, liraglutide seems to exert a direct epigenetic effect in T2DM patients, regulating microRNAs involved in the maintenance of endothelial cell homeostasis. These changes might be implicated in liraglutide’s benefits and may represent useful targets for cardiometabolic management. Full article
(This article belongs to the Special Issue Cardiometabolic Challenges-Present and Future)
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14 pages, 301 KiB  
Article
Evolution of Inflammatory and Oxidative Stress Markers in Romanian Obese Male Patients with Type 2 Diabetes Mellitus after Laparoscopic Sleeve Gastrectomy: One Year Follow-Up
by Ariana Picu, Laura Petcu, Diana Simona Ştefan, Grațiela Grădișteanu Pîrcălăbioru, Manuela Mitu, Daiana Bajko, Daniela Lixandru, Cristian Guja, Octavian Savu, Anca Pantea Stoian, Alina Constantin, Bogdan Smeu, Cătălin Copăescu, Mariana Carmen Chifiriuc, Elena Ionica and Constantin Ionescu-Tîrgovişte
Metabolites 2020, 10(8), 308; https://doi.org/10.3390/metabo10080308 - 28 Jul 2020
Cited by 1 | Viewed by 2262
Abstract
Geography is one of the key drivers of the significant variation in the etiopathogenic profile and prevalence of type 2 diabetes mellitus (T2DM) and obesity, therefore geographically based data are fundamental for implementing the appropriate interventions. Presently, the selection criteria of T2DM and [...] Read more.
Geography is one of the key drivers of the significant variation in the etiopathogenic profile and prevalence of type 2 diabetes mellitus (T2DM) and obesity, therefore geographically based data are fundamental for implementing the appropriate interventions. Presently, the selection criteria of T2DM and obesity patients for laparoscopic sleeve gastrectomy (LSG) have not reached a worldwide consensus—highlighting the need for sharing experts’ guidance in the preoperative evaluation, choice of the interventional procedure, perioperative management and patient long-term care. The aim of the current study was to evaluate the impact of LSG on T2DM (T2DM) remission in Romanian obese male patients, based on a multiparametric, prospective investigation. We have conducted a randomized controlled study on 41 obese male participants with the body mass index (BMI) ≥ 30 kg/m2, aged 30–65 years, which were randomly divided in two study groups: one receiving conventional treatment and the second undergoing LSG. The clinical and anthropometrical parameters, resting metabolic rate, general biochemical status, adipocytes profile, gastrointestinal hormones levels, proinflammatory, oxidant and antioxidant profiles were determined at three time points: V1 (baseline), V2 (after six months) and V3 (after 12 months). Glycated hemoglobin (HbA1c), blood glucose levels, BMI, weight, visceral fat level, HDL-cholesterol, incretin hormones, proinflammatory and the oxidative stress status were significantly improved in the LSG versus conventional treatment group. This is the first study reporting on the evaluation of metabolic surgery impact on Romanian obese male patients with T2DM. Our results confirm that LSG could contribute to T2DM remission in patients with diabesity, but this beneficial effect seems to be critically influenced by the duration of T2DM rather than by the obesity status. Our results show that, in addition to the parameters included in the prediction algorithm, the proinsulin levels, proinsulin/insulin ratio and the visceral fat percentage could bring added value to the assessment of metabolic status. Full article
(This article belongs to the Special Issue Cardiometabolic Challenges-Present and Future)
11 pages, 813 KiB  
Article
Dyslipidemia: A Trigger for Coronary Heart Disease in Romanian Patients with Diabetes
by Mihnea-Alexandru Găman, Matei-Alexandru Cozma, Elena-Codruța Dobrică, Nicolae Bacalbașa, Ovidiu Gabriel Bratu and Camelia Cristina Diaconu
Metabolites 2020, 10(5), 195; https://doi.org/10.3390/metabo10050195 - 14 May 2020
Cited by 38 | Viewed by 3779
Abstract
Previous studies have reported age and gender disparities in the occurrence and therapeutic approach of dyslipidemia and (or) coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate these differences in Romanian patients with T2DM. A cross-sectional, [...] Read more.
Previous studies have reported age and gender disparities in the occurrence and therapeutic approach of dyslipidemia and (or) coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate these differences in Romanian patients with T2DM. A cross-sectional, observational, retrospective study was conducted using the medical records of T2DM patients who attended the outpatient facility of the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest, Romania for routine check-ups in a six-month period. We analyzed the records of 217 diabetic patients (mean age 69 ± 11 years; 51.15% women). We found no significant gender differences in the occurrence of dyslipidemia, CHD or CHD + dyslipidemia or in terms of statin prescription. However; patients aged 65 years or older were significantly more affected by dyslipidemia, CHD or CHD + dyslipidemia, versus subjects aged <65 years. Further, they were more likely to be prescribed statin therapy (p < 0.0001 for all). Statins were prescribed to 67.24% of the patients with dyslipidemia; 61.01% of the subjects with CHD; and to 91.48% of the patients who had both conditions. e recorded no gender differences in the occurrence of CHD and (or) dyslipidemia in Romanian T2DM patients. Patients aged 65 years or older had a higher prevalence of CHD and/or dyslipidemia, and were more likely to be prescribed statins, versus younger counterparts. However, many T2DM patients with CHD and (or) dyslipidemia were undertreated: Nearly 33% of the subjects with dyslipidemia, and nearly 40% of the ones with CHD were not prescribed statins. Full article
(This article belongs to the Special Issue Cardiometabolic Challenges-Present and Future)
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Review

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10 pages, 813 KiB  
Review
NLRP3 Inflammasome Biomarker—Could Be the New Tool for Improved Cardiometabolic Syndrome Outcome
by Andra-Iulia Suceveanu, Laura Mazilu, Niki Katsiki, Irinel Parepa, Felix Voinea, Anca Pantea-Stoian, Manfredi Rizzo, Florin Botea, Vlad Herlea, Dragos Serban and Adrian-Paul Suceveanu
Metabolites 2020, 10(11), 448; https://doi.org/10.3390/metabo10110448 - 06 Nov 2020
Cited by 26 | Viewed by 2750
Abstract
Metabolomics, the research area studying chemical processes involving metabolites, finds its utility in inflammasome biomarker discovery, thus representing a novel approach for cardiometabolic syndrome pathogeny acknowledgements. Metabolite biomarkers discovery is expected to improve the disease evolution and outcome. The activation of abundantly expressed [...] Read more.
Metabolomics, the research area studying chemical processes involving metabolites, finds its utility in inflammasome biomarker discovery, thus representing a novel approach for cardiometabolic syndrome pathogeny acknowledgements. Metabolite biomarkers discovery is expected to improve the disease evolution and outcome. The activation of abundantly expressed NLRP3 inflammasome represents the background process of the diabetes mellitus disturbances like hyperglycemia and insulin resistance, as well as for myocardial cell death and fibrosis, all of them being features characteristic for cardiometabolic syndrome. Many molecules like troponins, brain natriuretic protein (BNP), ST2/IL-33, C-reactive protein (CRP), TNF, IL-1β, and IL-18 cytokines have been already examined as molecular markers for diagnosing or predicting different cardiac disturbances like myocardial infarction, heart failure, or myocarditis. In addition, metabolomics research comes with new findings arguing that NLRP3 inflammasome becomes a promising molecular tool to use for clinical and therapeutical management providing new targets for therapies in cardiometabolic syndrome. Inflammasome markers analyses, along with other molecular or genetic biomarkers, will result in a better understanding of cardiometabolic syndrome pathogenesis and therapeutic targets. Screening, diagnostic, and prognostic biomarkers resulted from inflammasome biomarker research will become standard of care in cardiometabolic syndrome management, their utility becoming the first magnitude. Full article
(This article belongs to the Special Issue Cardiometabolic Challenges-Present and Future)
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