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Towards Precision Medicine in Diabetes and Related Complications
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Towards Precision Medicine in Diabetes and Related Complications

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Omics/Informatics".

Deadline for manuscript submissions: closed (10 June 2023) | Viewed by 25048

Special Issue Editor

Dr. Claudia Menzaghi

E-Mail Website
Guest Editor
Research Unit of Diabetes and Endocrine Diseases, Scientific Institute "Casa Sollievo della Sofferenza", Viale Padre Pio, 71013 San Giovanni Rotondo, Italy
Interests: heritability; adipocytokines; inflammatory biomarkers; metabolomics; cardiovascular and renal diseases; mortality in type 2 diabetes

Special Issue Information

Dear Colleagues, 

Diabetes increases the risk of premature mortality and morbidity as a result of multisystem complications during the lifelong disease course. Due to the epidemic proportion that diabetes is assuming, this dramatic load is very likely to further surge over the next few decades, thus greatly contributing to an increase in economic, social and human costs worldwide. To tackle such a burden, the development of precision medicine approaches to predict the most high-risk patients to be targeted with the most aggressive, expensive and burdensome prevention strategies is mandatory.

The use of “omics” information leading to the discovery of novel biomarkers and their integration in prediction models that incorporate data from accurate phenotyping would help clinicians to stratify patients’ individual risk in order to choose the best follow-up and treatment strategies so as to maximize their effectiveness and minimize their costs. 

This Special Issue of the Journal of Personalized Medicine aims to highlight some of the latest studies in the field of “omics”, in the application of precision medicine for people with diabetes and coincidentally in addressing pathogenic pathways that are either unknown or poorly understood and that can eventually become the target of new treatments.

Dr. Claudia Menzaghi
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. 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

  • diabetes
  • precision diagnosis
  • prediction models
  • biomarker discovery
  • genetic risk score
  • nutrigenetics/nutrigenomics
  • metabolomics
  • pharmacogenomics
  • tailored intervention
  • immune therapies

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Published Papers (6 papers)

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Research

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14 pages, 3809 KiB  
Article
Interleaved Optical Coherence Tomography: Clinical and Laboratory Biomarkers in Patients with Diabetic Macular Edema
by Corina-Iuliana Suciu, Vlad-Ioan Suciu, Ancuţa Cuţaş and Simona Delia Nicoară
J. Pers. Med. 2022, 12(5), 765; https://doi.org/10.3390/jpm12050765 - 9 May 2022
Cited by 4 | Viewed by 3107
Abstract
(1) Background: The global burden of diabetes mellitus (DM) has been estimated to reach 600 million patients worldwide by 2040. Approximately 200 million people will develop diabetic retinopathy within this time frame. Diabetic macular edema (DME) is a severe, vision-threatening complication that can [...] Read more.
(1) Background: The global burden of diabetes mellitus (DM) has been estimated to reach 600 million patients worldwide by 2040. Approximately 200 million people will develop diabetic retinopathy within this time frame. Diabetic macular edema (DME) is a severe, vision-threatening complication that can develop at any stage of diabetic retinopathy, and it represents the main cause of vision loss in patients with DM. Its harmful consequences on visual function could be prevented with timely recognition and treatment. (2) Methods: This study assessed the clinical (demographic characteristics, diabetic evolution, and systemic vascular complications); laboratory (glycated hemoglobin, metabolic parameters, capillary oxygen saturation, and renal function); ophthalmologic exam; and spectral-domain optical coherence tomography (SD–OCT) (macular volume, central macular thickness, maximal central thickness, minimal central thickness, foveal thickness, superior inner, inferior inner, nasal inner, temporal inner, inferior outer, superior outer, nasal outer, and temporal outer thicknesses, disruption of the ellipsoid zone, and disruption of the inner retinal layers (DRIL) parameters in three groups of individuals: healthy controls (HC), patients with DME and type 1 DM (T1DM—group A), and patients with DME and type 2 DM (T2DM—group B) to identify novel correlations between them that would open a path to new pathogenetic hypotheses and, implicitly, to the identification of new therapeutic methods, as part of a tailored treatment within the concept of precision medicine. (3) Results: The duration of DM was significantly longer in group A as compared with group B, as were the prevalence of smoking and systemic vascular complications. Capillary oxygen saturation and estimated glomerular filtration rates were significantly lower, and serum creatinine levels were significantly higher in group A as compared to group B. Regarding the OCT findings, DME had a predominantly eccentric pattern, and the right eye was more severely affected in both groups of patients. Significantly higher values were obtained in group B as compared to group A for the following OCT biomarkers: macular volume, central macular thickness, maximal central thickness, minimal central thickness, foveal thickness, superior inner, inferior inner, nasal inner, inferior outer and nasal outer thickness. The disruption of the ellipsoid zone was significantly more prevalent within group A, whereas the overall disruption of the retinal inner layers (DRIL) was identified significantly more frequently in group B. (4) Conclusions: Whereas systemic and laboratory biomarkers were more severely affected in patients with DME and T1DM, the OCT quantitative biomarkers revealed significantly higher values in patients with DME and T2DM. Full article
(This article belongs to the Special Issue Towards Precision Medicine in Diabetes and Related Complications)
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10 pages, 1810 KiB  
Article
Predictive Assessment of Quantitative Ultra-Widefield Angiographic Features for Future Need for Anti-VEGF Therapy in Diabetic Eye Disease
by Alice C. Jiang, Duriye Damla Sevgi, Christopher Mugnaini, Jon Whitney, Sunil K. Srivastava, Katherine E. Talcott, Ming Hu, Jamie L. Reese and Justis P. Ehlers
J. Pers. Med. 2022, 12(4), 608; https://doi.org/10.3390/jpm12040608 - 10 Apr 2022
Cited by 3 | Viewed by 2075
Abstract
The objective of this study was to identify biomarkers that predict a future need for anti-VEGF therapy in diabetic retinopathy (DR). Eyes with DR that underwent ultra-widefield angiography (UWFA) and had at least a 1 year follow-up were grouped based on future anti-VEGF [...] Read more.
The objective of this study was to identify biomarkers that predict a future need for anti-VEGF therapy in diabetic retinopathy (DR). Eyes with DR that underwent ultra-widefield angiography (UWFA) and had at least a 1 year follow-up were grouped based on future anti-VEGF treatment requirements: (1) not requiring treatment, (2) immediate treatment (within 3 months of UWFA), and (3) delayed treatment (after 3 months of UWFA). Quantitative UWFA features and clinical factors were evaluated. Random forest models were built to differentiate eyes requiring immediate and delayed treatment from the eyes not requiring treatment. A total of 173 eyes were included. The mean follow-up was 22 (range: 11–43) months. The macular leakage index, panretinal leakage index, presence of DME, and visual acuity were significantly different in eyes requiring immediate (n = 38) and delayed (n = 34) treatment compared to eyes not requiring treatment (n = 101). Random forest model differentiating eyes requiring immediate treatment from eyes not requiring treatment demonstrated an AUC of 0.91 ± 0.07. Quantitative angiographic features have potential as important predictive biomarkers of a future need for anti-VEGF therapy in DR and may serve to guide the frequency of a follow-up. Full article
(This article belongs to the Special Issue Towards Precision Medicine in Diabetes and Related Complications)
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Review

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17 pages, 377 KiB  
Review
Maturity-Onset Diabetes of the Young: Mutations, Physiological Consequences, and Treatment Options
by Hazar Younis, Se Eun Ha, Brian G. Jorgensen, Arushi Verma and Seungil Ro
J. Pers. Med. 2022, 12(11), 1762; https://doi.org/10.3390/jpm12111762 - 25 Oct 2022
Cited by 8 | Viewed by 3563
Abstract
Maturity-Onset Diabetes of the Young (MODY) is a rare form of diabetes which affects between 1% and 5% of diagnosed diabetes cases. Clinical characterizations of MODY include onset of diabetes at an early age (before the age of 30), autosomal dominant inheritance pattern, [...] Read more.
Maturity-Onset Diabetes of the Young (MODY) is a rare form of diabetes which affects between 1% and 5% of diagnosed diabetes cases. Clinical characterizations of MODY include onset of diabetes at an early age (before the age of 30), autosomal dominant inheritance pattern, impaired glucose-induced secretion of insulin, and hyperglycemia. Presently, 14 MODY subtypes have been identified. Within these subtypes are several mutations which contribute to the different MODY phenotypes. Despite the identification of these 14 subtypes, MODY is often misdiagnosed as type 1 or type 2 diabetes mellitus due to an overlap in clinical features, high cost and limited availability of genetic testing, and unfamiliarity with MODY outside of the medical profession. The primary aim of this review is to investigate the genetic characterization of the MODY subtypes. Additionally, this review will elucidate the link between the genetics, function, and clinical manifestations of MODY in each of the 14 subtypes. In providing this knowledge, we hope to assist in the accurate diagnosis of MODY patients and, subsequently, in ensuring they receive appropriate treatment. Full article
(This article belongs to the Special Issue Towards Precision Medicine in Diabetes and Related Complications)
14 pages, 1505 KiB  
Review
Pharmacogenetics of Cardiovascular Prevention in Diabetes: From Precision Medicine to Identification of Novel Targets
by Mario Luca Morieri, Caterina Pipino and Alessandro Doria
J. Pers. Med. 2022, 12(9), 1402; https://doi.org/10.3390/jpm12091402 - 29 Aug 2022
Cited by 4 | Viewed by 2826
Abstract
Pharmacogenetics—a branch of precision medicine—holds the promise of becoming a novel tool to reduce the social and healthcare burdens of cardiovascular disease (CVD) and coronary artery disease (CAD) in diabetes. The improvement in cardiovascular risk stratification resulting from adding genetic characteristics to clinical [...] Read more.
Pharmacogenetics—a branch of precision medicine—holds the promise of becoming a novel tool to reduce the social and healthcare burdens of cardiovascular disease (CVD) and coronary artery disease (CAD) in diabetes. The improvement in cardiovascular risk stratification resulting from adding genetic characteristics to clinical data has moved from the modest results obtained with genetic risk scores based on few genetic variants, to the progressively better performances of polygenic risk scores based on hundreds to millions of variants (CAD-PGRS). Similarly, over the past few years, the number of studies investigating the use of CAD-PGRS to identify different responses to cardio-preventive treatment has progressively increased, yielding striking results for lipid-lowering drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and statins. The use of CAD-PGRS to stratify patients based on their likely response to diabetes-specific interventions has been less successful, but promising results have been obtained with regard to specific genetic variants modulating the effects of interventions such as intensive glycemic control and fenofibrate. The finding of diabetes-specific CAD-loci, such as GLUL, has also led to the identification of promising new targets that might hopefully result in the development of specific therapies to reduce CVD burden in patients with diabetes. As reported in consensus statements from international diabetes societies, some of these pharmacogenetic approaches are expected to be introduced in clinical practice over the next decade. For this to happen, in addition to continuing to improve and validate these tools, it will be necessary to educate physicians and patients about the opportunities and limits of pharmacogenetics, as summarized in this review. Full article
(This article belongs to the Special Issue Towards Precision Medicine in Diabetes and Related Complications)
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17 pages, 2267 KiB  
Review
Personalized Immunotherapies for Type 1 Diabetes: Who, What, When, and How?
by Claire Deligne, Sylvaine You and Roberto Mallone
J. Pers. Med. 2022, 12(4), 542; https://doi.org/10.3390/jpm12040542 - 29 Mar 2022
Cited by 15 | Viewed by 6434
Abstract
Our understanding of the immunopathological features of type 1 diabetes (T1D) has greatly improved over the past two decades and has shed light on disease heterogeneity dictated by multiple immune, metabolic, and clinical parameters. This may explain the limited effects of immunotherapies tested [...] Read more.
Our understanding of the immunopathological features of type 1 diabetes (T1D) has greatly improved over the past two decades and has shed light on disease heterogeneity dictated by multiple immune, metabolic, and clinical parameters. This may explain the limited effects of immunotherapies tested so far to durably revert or prevent T1D, for which life-long insulin replacement remains the only therapeutic option. In the era of omics and precision medicine, offering personalized treatment could contribute to turning this tide. Here, we discuss how to structure the selection of the right patient at the right time for the right treatment. This individualized therapeutic approach involves enrolling patients at a defined disease stage depending on the target and mode of action of the selected drug, and better stratifying patients based on their T1D endotype, reflecting intrinsic disease aggressiveness and immune context. To this end, biomarker screening will be critical, not only to help stratify patients and disease stage, but also to select the best predicted responders ahead of treatment and at early time points during clinical trials. This strategy could contribute to increase therapeutic efficacy, notably through the selection of drugs with complementary effects, and to further develop precision multi-hit medicine. Full article
(This article belongs to the Special Issue Towards Precision Medicine in Diabetes and Related Complications)
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20 pages, 663 KiB  
Review
Epigenetics in Precision Nutrition
by Xiang Li and Lu Qi
J. Pers. Med. 2022, 12(4), 533; https://doi.org/10.3390/jpm12040533 - 28 Mar 2022
Cited by 20 | Viewed by 5889
Abstract
Precision nutrition is an emerging area of nutrition research, with primary focus on the individual variability in response to dietary and lifestyle factors, which are mainly determined by an individual’s intrinsic variations, such as those in genome, epigenome, and gut microbiome. The current [...] Read more.
Precision nutrition is an emerging area of nutrition research, with primary focus on the individual variability in response to dietary and lifestyle factors, which are mainly determined by an individual’s intrinsic variations, such as those in genome, epigenome, and gut microbiome. The current research on precision nutrition is heavily focused on genome and gut microbiome, while epigenome (DNA methylation, non-coding RNAs, and histone modification) is largely neglected. The epigenome acts as the interface between the human genome and environmental stressors, including diets and lifestyle. Increasing evidence has suggested that epigenetic modifications, particularly DNA methylation, may determine the individual variability in metabolic health and response to dietary and lifestyle factors and, therefore, hold great promise in discovering novel markers for precision nutrition and potential targets for precision interventions. This review summarized recent studies on DNA methylation with obesity, diabetes, and cardiovascular disease, with more emphasis put in the relations of DNA methylation with nutrition and diet/lifestyle interventions. We also briefly reviewed other epigenetic events, such as non-coding RNAs, in relation to human health and nutrition, and discussed the potential role of epigenetics in the precision nutrition research. Full article
(This article belongs to the Special Issue Towards Precision Medicine in Diabetes and Related Complications)
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