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Recent Advances in the Diagnosis of Metabolic Disorders

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 27327

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Special Issue Editor

Dr. Christina E. Kostara

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Guest Editor

Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Interests: metabolism; lipid metabolism; metabolic diseases; atherosclerosis; lipoproteins; lipids; cholesterol; lipid analysis; lipid biochemistry; NMR spectroscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic disorders, including type-2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), metabolic syndrome, obesity, etc., are pathogenically and clinically heterogeneous chronic conditions with increased cardiovascular (CVD) risk and incidence of all-cause mortality. Due to their rapid global escalating, hundreds of millions of individuals are now affected by these diseases and they exact a heavy clinical and financial burden. Metabolic disorders have been also observed in cancer patients, although the pathogenesis of these disturbances is poorly understood.

The phenotype of metabolic disorders is complex and dynamic due to the multiple interactions occurring between genetic and environmental factors. Regardless of their underlying etiology, the use of advanced diagnostic approaches such as imaging and sensitive and validated biomarkers for the early diagnosis of these disorders, monitoring their response to therapy, selecting those treatments most likely to be efficacious, and identifying and stratifying high-risk individuals remain necessary in clinical practice. The use of omics technologies, such as metabolomics, proteomics, lipidomics, etc., can provide a deeper insight into the molecular pathophysiological processes that lead to metabolic disorders, enhancing our understanding of their metabolic signature.

This Special Issue aims to review recent advances in the diagnosis of metabolic disorders such as T2D, NAFLD, metabolic syndrome, obesity, etc., as well as their associated complications. We welcome submissions (original articles, reviews, or short communications) from clinical, translational, and basic research.

Dr. Christina E. Kostara
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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.

Published Papers (12 papers)

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Research

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9 pages, 710 KiB

Open AccessArticle

Association of Fatty Liver Index with Incident Diabetes Risk in Patients Initiating Statin–Therapy: A 6-Year Retrospective Study

by Georgia Anastasiou, Evangelos Liberopoulos, Ermioni Petkou, Amalia Despoina Koutsogianni, Petros Spyridwnas Adamidis, George Liamis, Evangelia Ntzani and Fotios Barkas

Diagnostics 2023, 13(3), 503; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13030503 - 30 Jan 2023

Cited by 2 | Viewed by 1310

Abstract

Background: Statins are associated with new-onset type 2 diabetes (T2D), mainly in patients with metabolic syndrome (MetS). The fatty liver index (FLI) is used as a prognostic score for the diagnosis of non-alcoholic fatty liver disease (NAFLD), which is common in patients with MetS. We aimed to investigate the association of FLI with new-onset T2D in patients initiating statin therapy. Methods: A retrospective observational study including 1241 individuals with dyslipidemia and followed up for ≥3 years. Patients with T2D and those receiving lipid-lowering treatment at the baseline visit were excluded. Models with clinical and laboratory parameters were used to assess the association of FLI with incident T2D. Results: Among the 882 eligible subjects, 11% developed T2D during the follow-up (6 years; IQR: 4–10 years). After adjusting for sex, age and MetS parameters, a multivariate analysis revealed that age (HR:1.05; 95%CI: 1.01–1.09, p < 0.05), fasting plasma glucose (HR: 1.09; 95%CI: 1.06–1.13, p < 0.001) and FLI (HR: 1.02; 95%CI: 1.01–1.04, p < 0.01) were independently associated with T2D risk. The subjects with probable NAFLD (FLI ≥ 60) had a three-fold increased T2D risk compared with the subjects with FLI < 60 (HR: 3.14; 95%CI: 1.50–6.59, p = 0.001). A ROC curve analysis showed that FLI had a significant, although poor, predictive value for assessing T2D risk (C-Statistic: 0.67; 95%CI: 0.58–0.77, p = 0.001). Higher FLI values were associated with reduced T2D-free survival (log-rank = 15.46, p < 0.001). Conclusions: FLI is significantly and independently associated with new-onset T2D risk in patients initiating statin therapy. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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10 pages, 2111 KiB

Open AccessArticle

Serotonin and Melatonin in Human Lower Gastrointestinal Tract

by Rosa Vaccaro, Arianna Casini, Carola Severi, Antonietta Lamazza, Annamaria Pronio and Rossella Palma

Diagnostics 2023, 13(2), 204; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13020204 - 05 Jan 2023

Cited by 3 | Viewed by 1764

Abstract

Background and Aims. Melatonin is a ubiquitous hormone produced not only by the pineal gland but also by other organs and tissues. It is involved in the regulation of several gastrointestinal functions. The main cells responsible for the production and release of extrapineal melatonin are the enterochromaffin (EC) cells that produce serotonin. They are involved in the pathogenesis of neuromotor disorders that characterize functional gastrointestinal disorders and in the pathophysiology of inflammatory intestinal diseases. Our aim was the immunohistochemical highlighting on biopsy samples of normal gastrointestinal mucosa and in ulcerative colitis (UC) of immunoreactive cells for melatonin and serotonin in order to identify any differences in their distribution. Materials and Methods. Our prospective case-control study involves the highlighting on human mucosal biopsies of immunoreactive cells for melatonin and serotonin. All patients undergoing colonoscopy + ileoscopy were considered eligible for the study, divided into two groups: 1. patients with active ulcerative colitis (UC); 2. control group consisting of patients undergoing endoscopic examination for colorectal cancer screening. Results. Twenty-one patients were enrolled. The controls had a higher concentration of EC cells containing 5HT particularly in the rectum (p value ≤ 0.05). In patients with active colitis the expression of 5-HT-iR was greater in all tracts of the colon. The correlation analysis in UC patients shows that a higher expression of 5-HT-iR+ cells corresponds to a lower extension of the disease and a greater severity of the same. Conclusions. 5HT+ cells decreased in the case of UC compared to healthy controls. In the severe disease, there was an increase in the expression of melatonin-secreting cells, probably as a compensatory response to the inflammation and oxidative stress. This increase is negatively correlated with the extent of the disease and positively with the severity of the same. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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17 pages, 1209 KiB

Open AccessArticle

A Study of the Metabolic Pathways Affected by Gestational Diabetes Mellitus: Comparison with Type 2 Diabetes

by Loukia Spanou, Aikaterini Dimou, Christina E. Kostara, Eleni Bairaktari, Eleni Anastasiou and Vasilis Tsimihodimos

Diagnostics 2022, 12(11), 2881; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12112881 - 21 Nov 2022

Cited by 2 | Viewed by 2037

Abstract

Background: Gestational diabetes mellitus (GDM) remains incompletely understood and increases the risk of developing Diabetes mellitus type 2 (DM2). Metabolomics provides insights etiology and pathogenesis of disease and discovery biomarkers for accurate detection. Nuclear magnetic resonance (NMR) spectroscopy is a key platform defining metabolic signatures in intact serum/plasma. In the present study, we used NMR-based analysis of macromolecules free-serum to accurately characterize the altered metabolic pathways of GDM and assessing their similarities to DM2. Our findings could contribute to the understanding of the pathophysiology of GDM and help in the identification of metabolomic markers of the disease. Methods: Sixty-two women with GDM matched with seventy-seven women without GDM (control group). ¹H NMR serum spectra were acquired on an 11.7 T Bruker Avance DRX NMR spectrometer. Results: We identified 55 metabolites in both groups, 25 of which were significantly altered in the GDM group. GDM group showed elevated levels of ketone bodies, 2-hydroxybutyrate and of some metabolic intermediates of branched-chain amino acids (BCAAs) and significantly lower levels of metabolites of one-carbon metabolism, energy production, purine metabolism, certain amino acids, 3-methyl-2-oxovalerate, ornithine, 2-aminobutyrate, taurine and trimethylamine N-oxide. Conclusion: Metabolic pathways affected in GDM were beta-oxidation, ketone bodies metabolism, one-carbon metabolism, arginine and ornithine metabolism likewise in DM2, whereas BCAAs catabolism and aromatic amino acids metabolism were affected, but otherwise than in DM2. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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11 pages, 878 KiB

Open AccessArticle

Divergent Effects of Glycemic Control and Bariatric Surgery on Circulating Concentrations of TMAO in Newly Diagnosed T2D Patients and Morbidly Obese

by Marina Canyelles, Antonio Pérez, Alexandra Junza, Inka Miñambres, Oscar Yanes, Helena Sardà, Noemí Rotllan, Josep Julve, José Luis Sánchez-Quesada, Mireia Tondo, Joan Carles Escolà-Gil and Francisco Blanco-Vaca

Diagnostics 2022, 12(11), 2783; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12112783 - 14 Nov 2022

Cited by 1 | Viewed by 1227

Abstract

High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, γ-butyrobetaine (γBB), in newly diagnosed T2D patients and morbidly obese subjects following a within-subject design. Based on HbA1c concentrations, T2D patients achieved glycemic control. However, the plasma TMAO and γBB concentrations were significantly increased, without changes in estimated glomerular filtration rate. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma γBB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Considering these results, an additional experiment was carried out in male C57BL/6J mice fed a Western-type diet for twelve weeks. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and γBB concentrations in these genetically defined mice strains. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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13 pages, 2728 KiB

Open AccessArticle

Intra-Individual Changes in Total Procollagen-Type 1 N-terminal Propeptide in a Korean Adult Population

by Rihwa Choi, Sang Gon Lee and Eun Hee Lee

Diagnostics 2022, 12(10), 2399; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12102399 - 02 Oct 2022

Cited by 1 | Viewed by 1188

Abstract

We aimed to investigate intra-individual changes in total procollagen-type 1 N-terminal pro-peptide (P1NP), a biochemical marker of bone turnover, to understand patient populations and test utilization in a Korean adult population while considering different definitions of least significant changes by sex, age, and medical institution type. Overall, 31,501 P1NP tests were performed on 24,644 Korean adults (3389 men and 21,255 women) with a median age of 68.9 years (interquartile range, IQR, 61.2–77.2) for osteoporosis evaluation. Among these, 1331 (5.4%) patients (127 men and 1204 women) underwent ≥3 follow-up P1NP measurements. The median follow-up period was 12.5 months (IQR, 11.7–15.9). Among 1331 patients, 64.4% experienced a decrease in P1NP and 35.6% experienced an increase in P1NP during follow-up. Among these, the proportion of patients who experienced serum P1NP changes ≥14.4% from baseline was 92.3%, and the proportion of patients who achieved ≤40 ng/mL (a median level of premenopausal Korean women) during follow-up was 31.8%. The overall proportion of patients that experienced a serum P1NP change exceeding the least significant change during follow-up was not significantly different by the type of medical institution. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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19 pages, 1644 KiB

Open AccessArticle

Glucose-Dependent Insulinotropic Polypeptide Plasma Level Influences the Effect of n-3 PUFA Supplementation

by Joanna Goralska, Urszula Razny, Philip C. Calder, Anna Gruca, Caroline E. Childs, Piotr Zabielski, Aldona Dembinska-Kiec, Maciej Banach, Bogdan Solnica and Malgorzata Malczewska-Malec

Diagnostics 2022, 12(8), 1984; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12081984 - 16 Aug 2022

Viewed by 1334

Abstract

Elevated glucose-dependent insulinotropic peptide (GIP) levels in obesity may predict the metabolic benefits of n-3 PUFA supplementation. This placebo-controlled trial aimed to analyze fasting and postprandial GIP response to 3-month n-3 PUFA supplementation (1.8 g/d; DHA:EPA, 5:1) along with caloric restriction (1200–1500 kcal/d) in obese subjects. Compliance was confirmed by the incorporation of DHA and EPA into red blood cells (RBCs). Blood analyses of glucose, insulin, non-esterified fatty acids (NEFAs), GIP and triglycerides were performed at fasting, and during an oral glucose tolerance test and a high fat mixed-meal tolerance test. Fatty acid composition of RBC was assessed by gas chromatography and total plasma fatty acid content and composition was measured by gas–liquid chromatography. The DHA and EPA content in RBCs significantly increased due to n-3 PUFA supplementation vs. placebo (77% vs. −3%, respectively). N-3 PUFA supplementation improved glucose tolerance and decreased circulating NEFA levels (0.750 vs. 0.615 mmol/L), as well as decreasing plasma saturated (1390 vs. 1001 µg/mL) and monounsaturated (1135 vs. 790 µg/mL) fatty acids in patients with relatively high GIP levels. The effects of n-3 PUFAs were associated with the normalization of fasting (47 vs. 36 pg/mL) and postprandial GIP levels. Obese patients with elevated endogenous GIP could be a target group for n-3 PUFA supplementation in order to achieve effects that obese patients without GIP disturbances can achieve with only caloric restriction. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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11 pages, 2247 KiB

Open AccessArticle

Salivary Neurotrophins Brain-Derived Neurotrophic Factor and Nerve Growth Factor Associated with Childhood Obesity: A Multiplex Magnetic Luminescence Analysis

by Vaithinathan Selvaraju, Jeganathan R. Babu and Thangiah Geetha

Diagnostics 2022, 12(5), 1130; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12051130 - 03 May 2022

Cited by 2 | Viewed by 1683

Abstract

Obesity is linked with higher inflammatory markers and is characterized by chronic low-grade inflammation. Neurotrophins brain-derived neurotrophic factor (BDNF) and β-nerve growth factor (β-NGF), in addition to their neuronal functions, act on several immune cells and have been recently designated as metabokines due to their regulatory role in energy homeostasis and food intake. The current study evaluates the salivary BDNF and β-NGF and their association with anthropometric measurement, blood pressure, and salivary insulin in children. Anthropometric measurements and saliva samples were obtained from 76 children, aged 6–10 years. Multiplex analysis was carried out for the salivary analysis of BDNF, NGF, and insulin by human magnetic Luminex performance assay. Statistical analysis was performed to analyze the best fit diagnostic value for biomarkers and the relationship of the neurotrophic levels of BDNF and NGF with obesity measures and blood pressure. Salivary BDNF and β-NGF showed a significantly higher concentration in obese children than normal-weight children. Both neurotrophins are positively associated with obesity anthropometric measures, blood pressure, and salivary insulin. Multinominal regression analysis reported a significant association between salivary BDNF, β-NGF, insulin, and systolic pressure adjusted for age, gender, income, and maternal education. The salivary concentration of BDNF and NGF was higher in obese children, and it is positively associated with anthropometric measures, suggesting that neurotrophins can be used as a non-invasive predictor of obesity-related complications in children. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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Graphical abstract

12 pages, 1346 KiB

Open AccessArticle

Compliance with Cardiovascular Prevention Guidelines in Type 2 Diabetes Individuals in a Middle-Income Region: A Cross-Sectional Analysis

by Joaquim Barreto, Beatriz Luchiari, Vaneza L. W. Wolf, Isabella Bonilha, Ticiane G. Bovi, Barbara S. Assato, Ikaro Breder, Sheila T. Kimura-Medorima, Daniel B. Munhoz, Thiago Quinaglia, Otavio R. Coelho-Filho, Luiz Sergio F. Carvalho, Wilson Nadruz and Andrei C. Sposito

Diagnostics 2022, 12(4), 814; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12040814 - 26 Mar 2022

Cited by 1 | Viewed by 1690

Abstract

Stricter control of risk factors has been pursued as a compelling strategy to mitigate cardiovascular events (CVE) in type 2 diabetes (T2D) individuals. However, the achievement rate of the recommended goals has remained low in clinical practice. This study investigated the 2019 ESC guideline recommendation attainment among T2D individuals enrolled in a national cohort held in Brazil. Data from 1030 individuals (mean age: 58 years old; 54% male; mean T2D duration: 9.7 years) were analyzed. The control rates were 30.6% for SBP, 18.8% for LDL-C, and 41% for A1c, and only 3.2% of the study participants met all three targets. Statins and high-intensity lipid-lowering therapy prescription rates were 45% and 8.2%, respectively. Longer T2D duration and those at higher CV risk were less likely to be controlled. Longer diabetes duration and higher CV risk were inversely related to the chance of achieving the recommended targets. Treatment escalation using conventional therapies would be sufficient to gain optimal control in most of the study sample. In conclusion, a minimal proportion of T2D individuals comply with guidelines-oriented CV prevention targets. Given the significant burden of the disease, and the substantial effect size predicted for these therapies, bridging this gap between guidelines and clinical practice should be considered an urgent call to public health managers. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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Review

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17 pages, 905 KiB

Open AccessReview

Fatty Acid Profile and Genetic Variants of Proteins Involved in Fatty Acid Metabolism Could Be Considered as Disease Predictor

by Raja Chaaba, Aicha Bouaziz, Asma Ben Amor, Wissem Mnif, Mohamed Hammami and Sounira Mehri

Diagnostics 2023, 13(5), 979; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13050979 - 04 Mar 2023

Cited by 2 | Viewed by 3247

Abstract

Circulating fatty acids (FA) have an endogenous or exogenous origin and are metabolized under the effect of many enzymes. They play crucial roles in many mechanisms: cell signaling, modulation of gene expression, etc., which leads to the hypothesis that their perturbation could be the cause of disease development. FA in erythrocytes and plasma rather than dietary FA could be used as a biomarker for many diseases. Cardiovascular disease was associated with elevated trans FA and decreased DHA and EPA. Increased arachidonic acid and decreased Docosahexaenoic Acids (DHA) were associated with Alzheimer’s disease. Low Arachidonic acid and DHA are associated with neonatal morbidities and mortality. Decreased saturated fatty acids (SFA), increased monounsaturated FA (MUFA) and polyunsaturated FA (PUFA) (C18:2 n-6 and C20:3 n-6) are associated with cancer. Additionally, genetic polymorphisms in genes coding for enzymes implicated in FA metabolism are associated with disease development. FA desaturase (FADS1 and FADS2) polymorphisms are associated with Alzheimer’s disease, Acute Coronary Syndrome, Autism spectrum disorder and obesity. Polymorphisms in FA elongase (ELOVL2) are associated with Alzheimer’s disease, Autism spectrum disorder and obesity. FA-binding protein polymorphism is associated with dyslipidemia, type 2 diabetes, metabolic syndrome, obesity, hypertension, non-alcoholic fatty liver disease, peripheral atherosclerosis combined with type 2 diabetes and polycystic ovary syndrome. Acetyl-coenzyme A carboxylase polymorphisms are associated with diabetes, obesity and diabetic nephropathy. FA profile and genetic variants of proteins implicated in FA metabolism could be considered as disease biomarkers and may help with the prevention and management of diseases. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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15 pages, 299 KiB

Open AccessReview

The Triglyceride/High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio as a Risk Marker for Metabolic Syndrome and Cardiovascular Disease

by Constantine E. Kosmas, Shanna Rodriguez Polanco, Maria D. Bousvarou, Evangelia J. Papakonstantinou, Edilberto Peña Genao, Eliscer Guzman and Christina E. Kostara

Diagnostics 2023, 13(5), 929; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13050929 - 01 Mar 2023

Cited by 21 | Viewed by 5679

Abstract

Atherosclerosis is an immunoinflammatory pathological procedure in which lipid plaques are formed in the vessel walls, partially or completely occluding the lumen, and is accountable for atherosclerotic cardiovascular disease (ASCVD). ACSVD consists of three components: coronary artery disease (CAD), peripheral vascular disease (PAD) and cerebrovascular disease (CCVD). A disturbed lipid metabolism and the subsequent dyslipidemia significantly contribute to the formation of plaques, with low-density lipoprotein cholesterol (LDL-C) being the main responsible factor. Nonetheless, even when LDL-C is well regulated, mainly with statin therapy, a residual risk for CVD still occurs, and it is attributable to the disturbances of other lipid components, namely triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Increased plasma TG and decreased HDL-C levels have been associated with metabolic syndrome (MetS) and CVD, and their ratio, TG/HDL-C, has been proposed as a novel biomarker for predicting the risk of both clinical entities. Under these terms, this review will present and discuss the current scientific and clinical data linking the TG/HDL-C ratio with the presence of MetS and CVD, including CAD, PAD and CCVD, in an effort to prove the value of the TG/HDL-C ratio as a valuable predictor for each aspect of CVD. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

20 pages, 1568 KiB

Open AccessReview

Expanding the Molecular Disturbances of Lipoproteins in Cardiometabolic Diseases: Lessons from Lipidomics

by Christina E. Kostara

Diagnostics 2023, 13(4), 721; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13040721 - 15 Feb 2023

Cited by 2 | Viewed by 1671

Abstract

The increasing global burden of cardiometabolic diseases highlights the urgent clinical need for better personalized prediction and intervention strategies. Early diagnosis and prevention could greatly reduce the enormous socio-economic burden posed by these states. Plasma lipids including total cholesterol, triglycerides, HDL-C, and LDL-C have been at the center stage of the prediction and prevention strategies for cardiovascular disease; however, the bulk of cardiovascular disease events cannot be explained sufficiently by these lipid parameters. The shift from traditional serum lipid measurements that are poorly descriptive of the total serum lipidomic profile to comprehensive lipid profiling is an urgent need, since a wealth of metabolic information is currently underutilized in the clinical setting. The tremendous advances in the field of lipidomics in the last two decades has facilitated the research efforts to unravel the lipid dysregulation in cardiometabolic diseases, enabling the understanding of the underlying pathophysiological mechanisms and identification of predictive biomarkers beyond traditional lipids. This review presents an overview of the application of lipidomics in the study of serum lipoproteins in cardiometabolic diseases. Integrating the emerging multiomics with lipidomics holds great potential in moving toward this goal. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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Other

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14 pages, 2354 KiB

Open AccessCase Report

Familial Partial Lipodystrophy—Literature Review and Report of a Novel Variant in PPARG Expanding the Spectrum of Disease-Causing Alterations in FPLD3

by Lena Rutkowska, Dominik Salachna, Krzysztof Lewandowski, Andrzej Lewiński and Agnieszka Gach

Diagnostics 2022, 12(5), 1122; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12051122 - 30 Apr 2022

Cited by 5 | Viewed by 2447

Abstract

Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by the selective loss of adipose tissue. Its estimated prevalence is as low as 1 in 1 million. The deficiency of metabolically active adipose tissue is closely linked with a wide range of metabolic complications, such as insulin resistance, lipoatrophic diabetes, dyslipidemia with severe hypertriglyceridemia, hypertension or hepatic steatosis. Moreover, female patients often develop hyperandrogenism, hirsutism, polycystic ovaries and infertility. The two most common types are FPLD type 2 and 3. Variants within LMNA and PPARG genes account for more than 50% of all reported FPLD cases. Because of its high heterogeneity and rarity, lipodystrophy can be easily unrecognized or misdiagnosed. To determine the genetic background of FPLD in a symptomatic woman and her close family, an NGS custom panel was used to sequence LMNA and PPARG genes. The affected patient presented fat deposits in the face, neck and trunk, with fat loss combined with muscular hypertrophy in the lower extremities and hirsutism, all features first manifesting at puberty. Her clinical presentation included metabolic disturbances, including hypercholesterolemia with severe hypertriglyceridemia, diabetes mellitus and hepatic steatosis. This together with her typical fat distribution and physical features raised a suspicion of FPLD. NGS analysis revealed the presence of missense heterozygous variant c.443G>A in exon 4 of PPARG gene, causing glycine to glutamic acid substitution at amino acid position 148, p.(Gly148Glu). The variant was also found in the patient’s mother and son. The variant was not previously reported in any public database. Based on computational analysis, crucial variant localization within DNA-binding domain of PPARγ, available literature data and the variant cosegregation in the patient’s family, novel c.443G>A variant was suspected to be causative. Functional testing is needed to confirm the pathogenicity of the novel variant. Inherited lipodystrophy syndromes represent a heterogenous group of metabolic disorders, whose background often remains unclear. A better understating of the genetic basis would allow earlier diagnosis and targeted treatment implementation. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis of Metabolic Disorders)

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