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From Basic to Clinical Research: Toward Precision Medicine for Metabolic...
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From Basic to Clinical Research: Toward Precision Medicine for Metabolic Diseases

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 19238

Special Issue Editors

Prof. Dr. Nikolaos Perakakis

E-Mail Website
Guest Editor
Chair of Metabolic and Vascular Medicine, Department of Endocrinology, University of Dresden, 01307 Dresden, Germany
Interests: NAFLD; diabetes; obesity; nutrition; exercise; omics
Prof. Dr. Barbara Ludwig

E-Mail Website
Guest Editor
Chair of Pancreas Islet Transplantation, Department of Endocrinology, University of Dresden, 01307 Dresden, Germany
Interests: diabetes; transplantation; pancreas

Special Issue Information

Dear Colleagues,

Metabolic diseases have become a major health hazard of the modern world, affecting a great part of the population and demonstrating a continuously increasing prevalence. Remarkable advancements in recent decades in diagnostic procedures and in available treatments have led to profound improvements in patient care. However, increasing evidence from extensive research in recent decades has shown that disease and population heterogeneity have a major impact on diagnostic success, on the prediction of the course of metabolic diseases and on treatment response.    

This Special Issue focuses on cutting-edge developments in the diagnosis, understanding and treatment of metabolic diseases, such as obesity, diabetes, hyperlipidemia, hypertension and non-alcoholic fatty liver disease. We invite the submission of original research (basic, clinical and epidemiological studies), review and meta-analysis articles on the latest advances toward understanding and combatting metabolic diseases in the era of precision medicine. Topics of particular interest include: a) Novel diagnostic, prognostic and preventive approaches (including, but not limited to patient-subphenotyping, biomarker discovery, risk score development), b) Novel approaches of treatment, including pharmacologic and non-pharmacological interventions (e.g., nutritional, exercise, transplantation, operation) as well as combination therapies, c) Targeted treatment, i.e., treatment of groups with unique characteristics, d) Novel pathophysiological mechanisms. 

Prof. Dr. Nikolaos Perakakis
Prof. Dr. Barbara Ludwig
Guest Editors

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. Journal of Personalized Medicine is an international peer-reviewed open access monthly 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.

Keywords

  • obesity
  • diabetes
  • NAFLD
  • NASH
  • hyperlipidemia
  • hypertension
  • omics
  • nutrition
  • exercise

Published Papers (6 papers)

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Research

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14 pages, 2506 KiB  
Article
Low Bone Turnover Due to Hypothyroidism or Anti-Resorptive Treatment Does Not Affect Whole-Body Glucose Homeostasis in Male Mice
by Franziska Lademann, Martina Rauner, Nicolas Bonnet, Lorenz C. Hofbauer and Elena Tsourdi
J. Pers. Med. 2022, 12(9), 1462; https://doi.org/10.3390/jpm12091462 - 6 Sep 2022
Cited by 1 | Viewed by 1440
Abstract
Bone is a large and dynamic tissue and its maintenance requires high amounts of energy as old or damaged bone structures need to be replaced during the process of bone remodeling. Glucose homeostasis is an essential prerequisite for a healthy bone and vice [...] Read more.
Bone is a large and dynamic tissue and its maintenance requires high amounts of energy as old or damaged bone structures need to be replaced during the process of bone remodeling. Glucose homeostasis is an essential prerequisite for a healthy bone and vice versa, the skeleton can act as an endocrine organ on energy metabolism. We recently showed that hypothyroidism in mice leads to an almost complete arrest of bone remodeling. Here, we aimed to investigate whether the profound suppression of bone remodeling affects whole-body glucose homeostasis. To that end, male C57BL/6JRj mice were rendered hypothyroid over 4 weeks using methimazole and sodium perchlorate in the drinking water. We confirmed trabecular bone gain due to decreased bone turnover in hypothyroid mice with decreased cortical but increased vertebral bone strength. Further, we found impaired glucose handling but not insulin resistance with hypothyroidism. In hypothyroid bone, glucose uptake and expression of glucose transporter Glut4 were reduced by 44.3% and 13.9%, respectively, suggesting lower energy demands. Nevertheless, hypothyroidism led to distinct changes in glucose uptake in muscle, liver, and epididymal white adipose tissue (eWAT). Reduced glucose uptake (−30.6%) and Glut1/Glut4 transcript levels (−31.9%/−67.5%) were detected in muscle tissue. In contrast, in liver and eWAT we observed increased glucose uptake by 25.6% and 68.6%, respectively, and upregulated expression of glucose transporters with hypothyroidism. To more specifically target bone metabolism and discriminate between the skeletal and systemic effects of hypothyroidism on energy metabolism, male mice were treated with zoledronate (ZOL), a bisphosphonate, that led to decreased bone turnover, trabecular bone gain, and reduced local glucose uptake into bone (−40.4%). However, ZOL-treated mice did not display alterations of systemic glucose handling nor insulin tolerance. Despite the close mutual crosstalk of bone and glucose metabolism, in this study, we show that suppressing bone remodeling does not influence whole-body glucose homeostasis in male mice. Full article
(This article belongs to the Special Issue From Basic to Clinical Research: Toward Precision Medicine for Metabolic Diseases)
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12 pages, 1959 KiB  
Article
Personalized Self-Monitoring of Energy Balance through Integration in a Web-Application of Dietary, Anthropometric, and Physical Activity Data
by Giada Bianchetti, Alessio Abeltino, Cassandra Serantoni, Federico Ardito, Daniele Malta, Marco De Spirito and Giuseppe Maulucci
J. Pers. Med. 2022, 12(4), 568; https://doi.org/10.3390/jpm12040568 - 2 Apr 2022
Cited by 11 | Viewed by 2508
Abstract
Self-monitoring of weight, diet and physical activity is a valuable component of behavioral weight loss treatment. The validation and user-friendliness of this approach is not optimal since users are selected from homogeneous pools and rely on different applications, increasing the burden and achieving [...] Read more.
Self-monitoring of weight, diet and physical activity is a valuable component of behavioral weight loss treatment. The validation and user-friendliness of this approach is not optimal since users are selected from homogeneous pools and rely on different applications, increasing the burden and achieving partial, generic and/or unrelated information about their metabolic state. Moreover, studies establishing type, time, duration, and adherence criteria for self-monitoring are lacking. In this study, we developed a digital web-based application (ArmOnIA), which integrates dietary, anthropometric, and physical activity data and provides a personalized estimation of energy balance. Moreover, we determined type, time, duration, and adherence criteria for self-monitoring to achieve significant weight loss in a highly heterogeneous group. A single-arm, uncontrolled prospective study on self-monitored voluntary adults for 7 months was performed. Hierarchical clustering of adherence parameters yielded three behavioral approaches: high (HA), low (LA), and medium (MA) adherence. Average BMI decrease is statistically significant between LA and HA. Moreover, we defined thresholds for the minimum frequencies and duration of dietary and weight self-monitoring. This approach can provide the correct clues to empower citizens with scientific knowledge, augmenting their self-awareness with the aim of achieving long-lasting results when pursuing a healthy lifestyle. Full article
(This article belongs to the Special Issue From Basic to Clinical Research: Toward Precision Medicine for Metabolic Diseases)
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Review

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12 pages, 299 KiB  
Review
Precision Medicine in Fatty Liver Disease/Non-Alcoholic Fatty Liver Disease
by Laura Valenzuela-Vallejo, Despina Sanoudou and Christos S. Mantzoros
J. Pers. Med. 2023, 13(5), 830; https://doi.org/10.3390/jpm13050830 - 14 May 2023
Cited by 7 | Viewed by 2358
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and is related to fatal and non-fatal liver, metabolic, and cardiovascular complications. Its non-invasive diagnosis and effective treatment remain an unmet clinical need. NAFLD is a heterogeneous disease that is most [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and is related to fatal and non-fatal liver, metabolic, and cardiovascular complications. Its non-invasive diagnosis and effective treatment remain an unmet clinical need. NAFLD is a heterogeneous disease that is most commonly present in the context of metabolic syndrome and obesity, but not uncommonly, may also be present without metabolic abnormalities and in subjects with normal body mass index. Therefore, a more specific pathophysiology-based subcategorization of fatty liver disease (FLD) is needed to better understand, diagnose, and treat patients with FLD. A precision medicine approach for FLD is expected to improve patient care, decrease long-term disease outcomes, and develop better-targeted, more effective treatments. We present herein a precision medicine approach for FLD based on our recently proposed subcategorization, which includes the metabolic-associated FLD (MAFLD) (i.e., obesity-associated FLD (OAFLD), sarcopenia-associated FLD (SAFLD, and lipodystrophy-associated FLD (LAFLD)), genetics-associated FLD (GAFLD), FLD of multiple/unknown causes (XAFLD), and combined causes of FLD (CAFLD) as well as advanced stage fibrotic FLD (FAFLD) and end-stage FLD (ESFLD) subcategories. These and other related advances, as a whole, are expected to enable not only improved patient care, quality of life, and long-term disease outcomes, but also a considerable reduction in healthcare system costs associated with FLD, along with more options for better-targeted, more effective treatments in the near future. Full article
(This article belongs to the Special Issue From Basic to Clinical Research: Toward Precision Medicine for Metabolic Diseases)
20 pages, 1007 KiB  
Review
Type 1 Diabetes Mellitus and Autoimmune Diseases: A Critical Review of the Association and the Application of Personalized Medicine
by Mihaela Simona Popoviciu, Nirja Kaka, Yashendra Sethi, Neil Patel, Hitesh Chopra and Simona Cavalu
J. Pers. Med. 2023, 13(3), 422; https://doi.org/10.3390/jpm13030422 - 26 Feb 2023
Cited by 24 | Viewed by 8273
Abstract
Type 1 Diabetes Mellitus (T1DM) is a common hyperglycemic disease characterized by the autoimmune destruction of insulin-producing beta cells of the pancreas. Various attempts have been made to understand the complex interplay of genetic and environmental factors which lead to the development of [...] Read more.
Type 1 Diabetes Mellitus (T1DM) is a common hyperglycemic disease characterized by the autoimmune destruction of insulin-producing beta cells of the pancreas. Various attempts have been made to understand the complex interplay of genetic and environmental factors which lead to the development of the autoimmune response in an individual. T1DM is frequently associated with other autoimmune illnesses, the most common being autoimmune thyroid disorders affecting more than 90% of people with T1D and autoimmune disorders. Antithyroid antibodies are present in around 20% of children with T1D at the start of the illness and are more frequent in girls. Patients with T1DM often have various other co-existing multi-system autoimmune disorders including but not limited to thyroid diseases, parathyroid diseases, celiac disease, vitiligo, gastritis, skin diseases, and rheumatic diseases. It is a consistent observation in clinics that T1DM patients have other autoimmune disorders which in turn affect their prognosis. Concomitant autoimmune illness might affect diabetes care and manifest itself clinically in a variety of ways. A thorough understanding of the complex pathogenesis of this modern-day epidemic and its association with other autoimmune disorders has been attempted in this review in order to delineate the measures to prevent the development of these conditions and limit the morbidity of the afflicted individuals as well. The measures including antibody screening in susceptible individuals, early identification and management of other autoimmune disorders, and adoption of personalized medicine can significantly enhance the quality of life of these patients. Personalized medicine has recently gained favor in the scientific, medical, and public domains, and is frequently heralded as the future paradigm of healthcare delivery. With the evolution of the ‘omics’, the individualization of therapy is not only closer to reality but also the need of the hour. Full article
(This article belongs to the Special Issue From Basic to Clinical Research: Toward Precision Medicine for Metabolic Diseases)
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20 pages, 751 KiB  
Review
Combination Therapies for Nonalcoholic Fatty Liver Disease
by Evangelia S. Makri, Eleftheria Makri and Stergios A. Polyzos
J. Pers. Med. 2022, 12(7), 1166; https://doi.org/10.3390/jpm12071166 - 18 Jul 2022
Cited by 20 | Viewed by 3020
Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered a highly prevalent disease associated with various co-morbidities that lead to socioeconomic burden. Despite large-scale investigation, no pharmacological treatment has been approved specifically for NAFLD to date. Lifestyle modifications and diet are regarded as highly beneficial [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is considered a highly prevalent disease associated with various co-morbidities that lead to socioeconomic burden. Despite large-scale investigation, no pharmacological treatment has been approved specifically for NAFLD to date. Lifestyle modifications and diet are regarded as highly beneficial for the management of NAFLD, albeit with poor compliance, thus rendering pharmacological treatment highly important. Based on the current failure to discover a “magic bullet” to treat all patients with NAFLD and considering the multifaceted pathophysiology of the disease, combination therapies may be considered to be a rational alternative approach. In this regard, several drug categories have been considered, including, but not limited to, lipid-lowering, anti-hypertensive, glucose-lowering, anti-obesity, anti-oxidant, anti-inflammatory and anti-fibrotic medications. The aim of this review is, in addition to summarizing some of the multiple factors contributing to the pathophysiology of NAFLD, to focus on the efficacy of pharmacological combinations on the management of NAFLD. This may provide evidence for a more personalized treatment of patients with NAFLD in the future. Full article
(This article belongs to the Special Issue From Basic to Clinical Research: Toward Precision Medicine for Metabolic Diseases)
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Other

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16 pages, 1876 KiB  
Systematic Review
Retinal Vascular Lesions in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
by Myrsini Orfanidou, Charikleia Ntenti, Kleo Evripidou, Asimina Mataftsi, Antonis Goulas and Stergios A. Polyzos
J. Pers. Med. 2023, 13(7), 1148; https://doi.org/10.3390/jpm13071148 - 17 Jul 2023
Cited by 1 | Viewed by 900
Abstract
Background: This systematic review and meta-analysis aimed to summarize and compare data on retinal vascular lesions between patients with nonalcoholic fatty liver disease (NAFLD) and individuals without the disease. Methods: Search was performed in PubMed, Scopus and Cochrane Library, complemented by handsearching (PROSPERO [...] Read more.
Background: This systematic review and meta-analysis aimed to summarize and compare data on retinal vascular lesions between patients with nonalcoholic fatty liver disease (NAFLD) and individuals without the disease. Methods: Search was performed in PubMed, Scopus and Cochrane Library, complemented by handsearching (PROSPERO ID: CRD42022345558). Thirty-six studies comprising 24,985 individuals (12,387 NAFLD patients and 12,598 controls) were selected for the meta-analysis. Results: Apart from retinopathy, no study with a different type of retinal vascular lesion was retrieved. Overall, there was no significant difference in the presence of retinopathy in NAFLD patients compared to controls (Odds Ratio (OR) = 1.20; 95% Confidence Interval (CI): 0.91–1.59). Heterogeneity among studies was high (I2 = 93%; p < 0.00001), while Egger’s test revealed no publication bias (p = 0.60). However, subgroup analysis showed positive association between retinopathy and NAFLD in type 1 diabetes mellitus (T1DM) (OR = 2.35; 95% CI: 1.53–3.60), but not in type 2 diabetes mellitus patients. Meta-regression analysis exploring potential confounders revealed no significant association. Conclusions: The presence of retinopathy was not overall different between individuals with and without NAFLD; however, T1DM patients with NAFLD had higher rates of retinopathy compared to T1DM patients without NAFLD, a finding warranting further research to show whether NAFLD may predict retinopathy in T1DM patients. Full article
(This article belongs to the Special Issue From Basic to Clinical Research: Toward Precision Medicine for Metabolic Diseases)
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