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Molecular Researches on Type 1 Diabetes and Its Complications

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 25 September 2024 | Viewed by 3041

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Dr. Jolanta Neubauer-Geryk

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Guest Editor

Clinical Physiology Unit, Medical Simulation Centre, Medical University of Gdańsk, Gdansk, Poland
Interests: endothelial dysfunction; microcirculation; macrocirculation; diabetes mellitus; cardiovascular diseases

Special Issue Information

Dear Colleagues,

The prevalence of type 1 diabetes is steadily increasing, especially in developed countries. Despite significant improvements in the diagnosis, prevention and treatment of diabetes complications based on interdisciplinary diabetes care, its chronic complications in the form of microangiopathies and macroangiopathies are a major cause of disability and reduced quality of life. In addition, mortality in type 1 diabetes remains two to eight times higher than in the general population. The main causes of mortality are cardiovascular complications, including cardiovascular and cerebrovascular events. The pathophysiological and morphological basis for the development of diabetic complications remains unclear. Endothelial damage during hyperglycemia and persistent inflammation in the microcirculation are responsible for microangiopathies such as retinopathy, neuropathy, nephropathy or cutaneous angiopathy. Another factor that increases inflammation in type 1 diabetes is the autoimmune nature of the disease. Many studies are devoted to investigating the impact of gene polymorphisms on the development of diabetic complications and searching for potential treatments. Personalization of preventive and therapeutic interventions is important. Undoubtedly, the future of type 1 diabetes treatment is linked to regenerative medicine.

This Special Issue of the International Journal of Molecular Sciences focuses on the latest research on the pathogenesis, early diagnosis or treatment of type 1 diabetes and its complications with both conventional and innovative technologies. This Special Issue welcomes in vitro and in vivo studies, as well as original research and reviews.

Dr. Jolanta Neubauer-Geryk
Guest Editor

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Keywords

type 1 diabetes mellitus
diabetic microangiopathy
diabetic macroangiopathy
continuous glucose monitoring
experimental diabetic models
biomarkers
endothelium dysfunction
diabetes-related diseases
comorbidities
pregnancy
pathophysiology
metabolic syndrome
treatment
precision medicine

Published Papers (3 papers)

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Research

18 pages, 3370 KiB

Open AccessArticle

The Impact of Metabolic Memory on Immune Profile in Young Patients with Uncomplicated Type 1 Diabetes

by Jolanta Neubauer-Geryk, Melanie Wielicka, Małgorzata Myśliwiec, Katarzyna Zorena and Leszek Bieniaszewski

Int. J. Mol. Sci. 2024, 25(6), 3190; https://doi.org/10.3390/ijms25063190 - 10 Mar 2024

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Abstract

Metabolic memory refers to the long-term effects of achieving early glycemic control and the adverse implications of high blood glucose levels, including the development and progression of diabetes complications. Our study aimed to investigate whether the phenomenon of metabolic memory plays a role in the immune profile of young patients with uncomplicated type 1 diabetes (T1D). The study group included 67 patients with uncomplicated type 1 diabetes with a mean age of 15.1 ± 2.3 years and a minimum disease duration of 1.2 years. The control group consisted of 27 healthy children and adolescents with a mean age of 15.1 ± 2.3 years. Patients were divided into three groups according to their HbA_1c levels at the onset of T1D, and the average HbA_1c levels after one and two years of disease duration. The subgroup A1 had the lowest initial HbA_1c values, while the subgroup C had the highest initial HbA_1c values. Cytokine levels (including TNF-α, IL-35, IL-4, IL-10, IL-18, and IL-12) were measured in all study participants. Our data analysis showed that subgroup A1 was characterized by significantly higher levels of IL-35 and IL-10 compared to all other groups, and significantly higher levels of IL-4 compared to group B. Additionally, a comparative analysis of cytokine levels between the groups of diabetic patients and healthy controls demonstrated that subgroup A1 had significantly higher levels of anti-inflammatory cytokines. The lipid profile was also significantly better in subgroup A1 compared to all other patient groups. Based on our findings, it appears that an inflammatory process, characterized by an imbalance between the pro- and anti-inflammatory cytokines, is associated with poor glycemic control at the onset of diabetes and during the first year of disease duration. These findings also suggest that both metabolic memory and inflammation contribute to the abnormal lipid profile in patients with type 1 diabetes. Full article

(This article belongs to the Special Issue Molecular Researches on Type 1 Diabetes and Its Complications)

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16 pages, 1767 KiB

Open AccessArticle

Suppression of B-Cell Activation by Human Cord Blood-Derived Stem Cells (CB-SCs) through the Galectin-9-Dependent Mechanism

by Wei Hu, Xiang Song, Haibo Yu, Sophia Fan, Andrew Shi, Jingyu Sun, Hongjun Wang, Laura Zhao and Yong Zhao

Int. J. Mol. Sci. 2024, 25(3), 1830; https://doi.org/10.3390/ijms25031830 - 02 Feb 2024

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Abstract

We developed the Stem Cell Educator therapy among multiple clinical trials based on the immune modulations of multipotent cord blood-derived stem cells (CB-SCs) on different compartments of immune cells, such as T cells and monocytes/macrophages, in type 1 diabetes and other autoimmune diseases. However, the effects of CB-SCs on the B cells remained unclear. To better understand the molecular mechanisms underlying the immune education of CB-SCs, we explored the modulations of CB-SCs on human B cells. CB-SCs were isolated from human cord blood units and confirmed by flow cytometry with different markers for their purity. B cells were purified by using anti-CD19 immunomagnetic beads from human peripheral blood mononuclear cells (PBMCs). Next, the activated B cells were treated in the presence or absence of coculture with CB-SCs for 7 days before undergoing flow cytometry analysis of phenotypic changes with different markers. Reverse transcription-polymerase chain reaction (RT-PCR) was utilized to evaluate the levels of galectin expressions on CB-SCs with or without treatment of activated B cells in order to find the key galectin that was contributing to the B-cell modulation. Flow cytometry demonstrated that the proliferation of activated B cells was markedly suppressed in the presence of CB-SCs, leading to the downregulation of immunoglobulin production from the activated B cells. Phenotypic analysis revealed that treatment with CB-SCs increased the percentage of IgD⁺CD27⁻ naïve B cells, but decreased the percentage of IgD⁻CD27⁺ switched B cells. The transwell assay showed that the immune suppression of CB-SCs on B cells was dependent on the galectin-9 molecule, as confirmed by the blocking experiment with the anti-galectin-9 monoclonal antibody. Mechanistic studies demonstrated that both calcium levels of cytoplasm and mitochondria were downregulated after the treatment with CB-SCs, causing the decline in mitochondrial membrane potential in the activated B cells. Western blot exhibited that the levels of phosphorylated Akt and Erk1/2 signaling proteins in the activated B cells were also markedly reduced in the presence of CB-SCs. CB-SCs displayed multiple immune modulations on B cells through the galectin-9-mediated mechanism and calcium flux/Akt/Erk1/2 signaling pathways. The data advance our current understanding of the molecular mechanisms underlying the Stem Cell Educator therapy to treat autoimmune diseases in clinics. Full article

(This article belongs to the Special Issue Molecular Researches on Type 1 Diabetes and Its Complications)

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18 pages, 2505 KiB

Open AccessArticle

The Complex Network of Cytokines and Chemokines in Pediatric Patients with Long-Standing Type 1 Diabetes

by Anna Wołoszyn-Durkiewicz, Dorota Iwaszkiewicz-Grześ, Dominik Świętoń, Mariusz J. Kujawa, Anna Jankowska, Agata Durawa, Paulina Glasner, Piotr Trzonkowski, Leopold Glasner, Edyta Szurowska and Małgorzata Myśliwiec

Int. J. Mol. Sci. 2024, 25(3), 1565; https://doi.org/10.3390/ijms25031565 - 26 Jan 2024

Viewed by 847

Abstract

Type 1 diabetes (T1D) is a progressive disorder leading to the development of microangiopathies and macroangiopathies. Numerous cytokines and chemokines are involved in the pathogenesis of T1D complications. The study aimed to assess the presence of complications in patients with long-standing T1D and its relationship with serum biomarker concentrations. We examined 52 T1D subjects, with a disease duration ≥4 years and 39 healthy controls. The group of T1D patients was further divided into subgroups based on the duration of the disease (<7 years and ≥7 years) and the metabolic control assessed by the HbAlc level (<8% and ≥8%). We used Luminex Technology to assess a wide range of biomarker concentrations. A 24 h urine test was done to evaluate the rate of albuminuria. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Subclinical atherosclerosis was assessed by measuring the carotid intima–media thickness (IMT). T1D patients showed remarkably higher concentrations of EGF, eotaxin/CCL11, MDC/CCL22, sCD40L, TGF-α, and TNF-α. Moreover, we reported statistically significant correlations between cytokines and IMT. Biomarker concentrations depend on numerous factors such as disease duration, metabolic control, and the presence of complications. Although the majority of pediatric T1D patients do not present signs of overt complications, it is indispensable to conduct the screening for angiopathies already in childhood, as its early recognition may attenuate the further progression of complications. Full article

(This article belongs to the Special Issue Molecular Researches on Type 1 Diabetes and Its Complications)

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