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Special Issue "Diabetes: Comorbidities, Therapeutics and Insights"

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 31 March 2024 | Viewed by 4681

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Special Issue Editor

Dr. Tomislav Bulum
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Guest Editor

1. Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia
2. School of Medicine, University of Zagreb, Zagreb, Croatia
Interests: diabetes; endocrinology; metabolic disease

Special Issue Information

Dear Colleagues,

Diabetes is one of the most challenging health problems in the 21st century, being projected to affect 700 million people by 2045. In the last 15 years, the number of people diagnosed with type 1 diabetes increased by 45%, and those diagnosed with type 2 diabetes increased by 95%. The most devastating effects of diabetes are its chronic complications, which confer a high risk of morbidity and mortality and an increased health system cost burden. Although there is increased awareness and new therapeutic options in the treatment of diabetes, it is still the leading cause of blindness in working-age adults, the leading cause of kidney failure and dialysis, and the leading cause of nontraumatic lower-limb amputations. People with diabetes have a 2 to 4 times higher risk of developing cardiovascular disease, which remains the most common cause of death in people with diabetes. Diabetes is a very heterogenous and complex disease and in addition to the traditional risk factors, such as hyperglycemia, hypertension, and dyslipidemia, multiple cellular pathways and potential molecular mechanisms are also implicated in diabetes-induced complications.

Considering this context, we welcome submissions to this Special Issue focusing on diabetes comorbidities, therapeutics, and insights into this disease. Detailed knowledge of this harmful disease is needed to prevent chronic complications and cardiovascular disease/death and optimize quality of life.

Dr. Tomislav Bulum
Guest Editor

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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. Biomedicines 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
complications
diabetic retinopathy
diabetic neuropathy
diabetic nephropathy
biomarkers

Published Papers (7 papers)

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Research

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17 pages, 1715 KiB

Open AccessArticle

Serum Cytokines and Growth Factors in Subjects with Type 1 Diabetes: Associations with Time in Ranges and Glucose Variability

Vadim V. Klimontov

Kamilla R. Mavlianova

Nikolai B. Orlov

Julia F. Semenova

and

Anton I. Korbut

Biomedicines 2023, 11(10), 2843; https://doi.org/10.3390/biomedicines11102843 - 19 Oct 2023

Viewed by 532

Abstract

The detrimental effect of hyperglycemia and glucose variability (GV) on target organs in diabetes can be implemented through a wide network of regulatory peptides. In this study, we assessed a broad panel of serum cytokines and growth factors in subjects with type 1 diabetes (T1D) and estimated associations between concentrations of these molecules with time in ranges (TIRs) and GV. One hundred and thirty subjects with T1D and twenty-seven individuals with normal glucose tolerance (control) were included. Serum levels of 44 cytokines and growth factors were measured using a multiplex bead array assay. TIRs and GV parameters were derived from continuous glucose monitoring. Subjects with T1D compared to control demonstrated an increase in concentrations of IL-1β, IL-1Ra, IL-2Rα, IL-3, IL-6, IL-7, IL-12 p40, IL-16, IL-17A, LIF, M-CSF, IFN-α2, IFN-γ, MCP-1, MCP-3, and TNF-α. Patients with TIR ≤ 70% had higher levels of IL-1α, IL-1β, IL-6, IL-12 p70, IL-16, LIF, M-CSF, MCP-1, MCP-3, RANTES, TNF-α, TNF-β, and b-NGF, and lower levels of IL-1α, IL-4, IL-10, GM-CSF, and MIF than those with TIR > 70%. Serum IL-1β, IL-10, IL-12 p70, MCP-1, MCP-3, RANTES, SCF, and TNF-α correlated with TIR and time above range. IL-1β, IL-8, IL-10, IL-12 p70, MCP-1, RANTES, MIF, and SDF-1α were related to at least one amplitude-dependent GV metric. In logistic regression models, IL-1β, IL-4, IL-10, IL-12 p70, GM-CSF, HGF, MCP-3, and TNF-α were associated with TIR ≤ 70%, and MIF and PDGF-BB demonstrated associations with coefficient of variation values ≥ 36%. These results provide further insight into the pathophysiological effects of hyperglycemia and GV in people with diabetes. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights)

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12 pages, 1646 KiB

Open AccessArticle

The Correlation between Islet β Cell Secretion Function and Gallbladder Stone Disease: A Retrospective Study Based on Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus

and

Biomedicines 2023, 11(10), 2840; https://doi.org/10.3390/biomedicines11102840 - 19 Oct 2023

Viewed by 415

Abstract

Background: This study aimed to analyze the correlation between islet β cell function and gallbladder stone (GBS) in newly diagnosed type 2 diabetes mellitus (T2DM) patients. Methods: A total of 438 newly diagnosed T2DM patients in Peking University International Hospital from January 2017 to August 2022 were retrospectively analyzed and divided into a non-GBS group and a GBS group. Results: (1) The homeostasis model assessment of the insulin resistance (HOMA-IR) of the GBS group was higher than that of the non-GBS group (p < 0.05), while the homeostasis model assessment of β cell (HOMA-β), disposition index (DI0), and Matsuda index of the GBS group were lower than those of the non-GBS group (all p < 0.05). (2) For male patients, HOMA-IR is an independent risk factor for GBS (OR = 2.00, 95% CI:1.03, 3.88, p < 0.05), and the Matsuda index value is a protective factor for GBS (OR = 0.76, 95% CI:0.60, 0.96, p < 0.05). For female patients, HOMA-IR is an independent risk factor for GBS (OR = 2.80, 95% CI:1.03, 7.58, p < 0.05) and the Matsuda index value is a protective factor for GBS (OR = 0.59, 95% CI:0.39, 0.90, p < 0.05). (3) For male patients, the area under curve (AUC) for predicting GBS was 0.77 (95% CI 0.67, 0.87), with a specificity of 75.26%, a sensitivity of 80.00%, and an accuracy of 75.64%. For female patients, the AUC for predicting GBS was 0.77 (95% CI 0.63, 0.88), with a specificity of 79.63%, a sensitivity of 71.43%, and an accuracy of 78.69%. Conclusions: Insulin resistance may be an independent risk factor for the incidence of GBS in patients with newly diagnosed T2DM, both male or female, which provides a new clinical basis and research direction for the prevention and treatment of GBS in patients with T2DM. This study has established a predictive model of GBS in T2DM and found it to be accurate, thus representing an effective tool for the early prediction of GBS in patients with T2DM. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights)

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12 pages, 433 KiB

Open AccessArticle

Progression of Diabetic Kidney Disease and Gastrointestinal Symptoms in Patients with Type I Diabetes

and

Jelizaveta Sokolovska

Biomedicines 2023, 11(10), 2679; https://doi.org/10.3390/biomedicines11102679 - 29 Sep 2023

Viewed by 542

Abstract

(1) Background: Little research is conducted on the link between diabetic kidney disease (DKD) progression and diabetic gastroenteropathy in type 1 diabetes (T1D). (2) Methods. We performed a cross-sectional study with 100 T1D patients; 27 of them had progressive DKD, defined as an estimated glomerular filtration rate (eGFR) decline ≥3 mL/min/year or increased albuminuria stage, over a mean follow-up time of 5.89 ± 1.73 years. A newly developed score with 17 questions on gastrointestinal (GI) symptoms was used. Faecal calprotectin was measured by ELISA. Lower GI endoscopies were performed in 21 patients. (3) Results: The gastrointestinal symptom score demonstrated high reliability (Cronbach’s α = 0.78). Patients with progressive DKD had higher GI symptom scores compared to those with stable DKD (p = 0.019). The former group demonstrated more frequent bowel movement disorders (p < 0.01). The scores correlated negatively with eGFR (r = −0.335; p = 0.001), positively with albuminuria (r = 0.245; p = 0.015), Hba1c (r = 0.305; p = 0.002), and diabetes duration (r = 0.251; p = 0.012). Faecal calprotectin levels did not differ between DKD groups significantly. The most commonly reported histopathological findings of enteric mucosa were infiltration with eosinophils, lymphocytes, plasmacytes, the presence of lymphoid follicles, and lymphoid aggregates. Conclusion: The progression of DKD is positively correlated with gastrointestinal symptoms; however, more research is needed to clarify the causal relationships of the gut-kidney axis in T1D. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights)

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11 pages, 811 KiB

Open AccessArticle

Relationship between β-Cell Autoantibodies and Their Combination with Anthropometric and Metabolic Components and Microvascular Complications in Latent Autoimmune Diabetes in Adults

Tomislav Bulum

Marijana Vučić Lovrenčić

Jadranka Knežević Ćuća

Martina Tomić

Sandra Vučković-Rebrina

and

Lea Duvnjak

Biomedicines 2023, 11(9), 2561; https://doi.org/10.3390/biomedicines11092561 - 18 Sep 2023

Viewed by 549

Abstract

Aims: Our study aimed to investigate the relationship between three autoantibodies and their combination with anthropometric and metabolic components and microvascular complications in patients with latent autoimmune diabetes in adults (LADA). Methods: Our study included 189 LADA patients divided into four subgroups according to the autoantibodies present: glutamic acid decarboxylase autoantibodies (GADA) only; zinc transporter-8 autoantibodies (ZnT8A)+GADA; insulinoma-associated-2 autoantibodies (IA-2)+GADA; and ZnT8+IA-2+GADA. Results: Compared to GADA positivity only, patients with ZnT8+GADA positivity and ZnT8+IA-2+GADA positivity had a shorter diabetes duration and lower body mass index (BMI); patients with ZnT8+GADA positivity were younger and showed an increase in glomerular filtration rate, while those with ZnT8+IA-2+GADA positivity had lower C-peptide and lower insulin resistance measured with HOMA2-IR. In a multiple regression analysis, ZnT8 positivity was associated with lower BMI (p = 0.0024), female sex (p = 0.0005), and shorter duration of disease (p = 0.0034), while IA-2 positivity was associated with lower C-peptide levels (p = 0.0034) and shorter diabetes duration (p = 0.02). No association between antibody positivity and microvascular complications of diabetes, including retinopathy, neuropathy, and microalbuminuria, as well as with variables of glucose control and β-cell function were found. Conclusion: The results of our study suggest that ZnT8 and IA-2 autoantibodies are present in a significant number of LADA patients and associated with clinical and metabolic characteristics resembling classic type 1 diabetes. Due to increased LADA prevalence, earlier identification of patients requiring frequent monitoring with the earlier intensification of insulin therapy might be of special clinical interest. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights)

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24 pages, 25892 KiB

Open AccessArticle

Identifying Aging-Related Biomarkers and Immune Infiltration Features in Diabetic Nephropathy Using Integrative Bioinformatics Approaches and Machine-Learning Strategies

Tao Liu

Xing-Xing Zhuang

and

Jia-Rong Gao

Biomedicines 2023, 11(9), 2454; https://doi.org/10.3390/biomedicines11092454 - 04 Sep 2023

Cited by 1 | Viewed by 755

Abstract

Background: Aging plays an essential role in the development of diabetic nephropathy (DN). This study aimed to identify and verify potential aging-related genes associated with DN using bioinformatics analysis. Methods: To begin with, we combined the datasets from GEO microarrays (GSE104954 and GSE30528) to find the genes that were differentially expressed (DEGs) across samples from DN and healthy patient populations. By overlapping DEGs, weighted co-expression network analysis (WGCNA), and 1357 aging-related genes (ARGs), differentially expressed ARGs (DEARGs) were discovered. We next performed functional analysis to determine DEARGs’ possible roles. Moreover, protein–protein interactions were examined using STRING. The hub DEARGs were identified using the CytoHubba, MCODE, and LASSO algorithms. We next used two validation datasets and Receiver Operating Characteristic (ROC) curves to determine the diagnostic significance of the hub DEARGs. RT-qPCR, meanwhile, was used to confirm the hub DEARGs’ expression levels in vitro. In addition, we investigated the relationships between immune cells and hub DEARGs. Next, Gene Set Enrichment Analysis (GSEA) was used to identify each biomarker’s biological role. The hub DEARGs’ subcellular location and cell subpopulations were both identified and predicted using the HPA and COMPARTMENTS databases, respectively. Finally, drug–protein interactions were predicted and validated using STITCH and AutoDock Vina. Results: A total of 57 DEARGs were identified, and functional analysis reveals that they play a major role in inflammatory processes and immunomodulation in DN. In particular, aging and the AGE-RAGE signaling pathway in diabetic complications are significantly enriched. Four hub DEARGs (CCR2, VCAM1, CSF1R, and ITGAM) were further screened using the interaction network, CytoHubba, MCODE, and LASSO algorithms. The results above were further supported by validation sets, ROC curves, and RT-qPCR. According to an evaluation of immune infiltration, DN had significantly more resting mast cells and delta gamma T cells but fewer regulatory T cells and active mast cells. Four DEARGs have statistical correlations with them as well. Further investigation revealed that four DEARGs were implicated in immune cell abnormalities and regulated a wide range of immunological and inflammatory responses. Furthermore, the drug–protein interactions included four possible therapeutic medicines that target four DEARGs, and molecular docking could make this association practical. Conclusions: This study identified four DEARGs (CCR2, VCAM1, CSF1R, and ITGAM) associated with DN, which might play a key role in the development of DN and could be potential biomarkers in DN. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights)

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18 pages, 1446 KiB

Open AccessArticle

The Impact of GLP-1 RAs and DPP-4is on Hospitalisation and Mortality in the COVID-19 Era: A Two-Year Observational Study

and

Biomedicines 2023, 11(8), 2292; https://doi.org/10.3390/biomedicines11082292 - 18 Aug 2023

Viewed by 598

Abstract

Novel antidiabetic drugs have the ability to produce anti-inflammatory effects regardless of their glucose-lowering action. For this reason, these molecules (including GLP-1 RAs and DPP-4is) were hypothesized to be effective against COVID-19, which is characterized by cytokines hyperactivity and multiorgan inflammation. The aim of our work is to explore the potential protective role of GLP-1 RAs and DPP-4is in COVID-19 (with the disease intended to be a model of an acute stressor) and non-COVID-19 patients over a two-year observation period. Retrospective and one-versus-one analyses were conducted to assess the impact of antidiabetic drugs on the need for hospitalization (in both COVID-19- and non-COVID-19-related cases), in-hospital mortality, and two-year mortality. Logistic regression analyses were conducted to identify the variables associated with these outcomes. Additionally, log-rank tests were used to plot survival curves for each group of subjects, based on their antidiabetic treatment. The performed analyses revealed that despite similar hospitalization rates, subjects undergoing home therapy with GLP-1 RAs exhibited significantly lower mortality rates, even over a two-year period. These individuals demonstrated improved survival estimates both within hospital and non-hospital settings, even during a longer observation period. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights)

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Review

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15 pages, 1383 KiB

Open AccessReview

Role of Oxidative Stress in Tuberculosis Meningitis Infection in Diabetics

and

Vishwanath Venketaraman

Biomedicines 2023, 11(9), 2568; https://doi.org/10.3390/biomedicines11092568 - 19 Sep 2023

Viewed by 654

Abstract

Tuberculosis meningitis (TBM) is a result of the invasion of the meninges with the bacilli of Mycobacterium tuberculosis (Mtb), leading to inflammation of the meninges around the brain or spinal cord. Oxidative stress occurs when the body’s cells become overwhelmed with free radicals, particularly reactive oxygen species (ROS). ROS plays a significant role in the pathogenesis of TBM due to their toxic nature, resulting in impairment of the body’s ability to fight off infection. ROS damages the endothelial cells and impairs the defense mechanisms of the blood–brain barrier (BBB), which contributes to CNS susceptibility to the bacteria causing TBM. Diabetes mellitus (DM) is a common condition that is characterized by the impairment of the hormone insulin, which is responsible for modulating blood glucose levels. The increased availability of glucose in individuals with diabetes results in increased cellular activity and metabolism, leading to heightened ROS production and, in turn, increased susceptibility to TBM. In this review, we summarize our current understanding of oxidative stress and its role in both TBM and DM. We further discuss how increased oxidative stress in DM can contribute to the likelihood of developing TBM and potential therapeutic approaches that may be of therapeutic value. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights)

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