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20 pages, 3973 KiB

Open AccessArticle

Safety Profiles Related to Dosing Errors of Rapid-Acting Insulin Analogs: A Comparative Analysis Using the EudraVigilance Database

by Ioana Rada Popa Ilie, Andreea Loredana Vonica-Tincu, Carmen Maximiliana Dobrea, Anca Butuca, Adina Frum, Claudiu Morgovan, Felicia Gabriela Gligor and Steliana Ghibu

Biomedicines 2024, 12(10), 2273; https://doi.org/10.3390/biomedicines12102273 - 7 Oct 2024

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Abstract

Insulin is essential for treating type 1 diabetes and insulin-requiring type 2 diabetes. Background/Objectives: Diabetes is a widespread condition that can lead to multiple and severe complications. Rapid-acting insulin analogs (RAIAs) and long-acting insulin analogs are prescribed for the effective management of diabetes. [...] Read more.

Insulin is essential for treating type 1 diabetes and insulin-requiring type 2 diabetes. Background/Objectives: Diabetes is a widespread condition that can lead to multiple and severe complications. Rapid-acting insulin analogs (RAIAs) and long-acting insulin analogs are prescribed for the effective management of diabetes. RAIAs are expected to be associated with a higher number of dosing errors because of their rapid onset, short duration of action, and the need for frequent dosing, compared to other insulin analogs. There are three approved RAIAs on the market: insulin lispro (LIS), insulin aspart (ASP), and insulin glulisine (GLU). The aim of this study is to evaluate the real-world evidence on dosing errors reported for RAIAs in EudraVigilance (EV), an established pharmacovigilance database, in comparison to other insulin analogs and human insulins. Methods: A descriptive analysis and a disproportionality analysis were conducted. Results: ASP and LIS were associated with high percentages of adverse drug reactions (ADRs) (22% and 17%, respectively), with over 70% of the reports involving serious ADRs. A higher frequency of cardiac and eye disorder ADRs was observed for LIS compared with ASP and GLU. GLU showed a higher frequency of ADRs in the skin and subcutaneous tissue disorders category. LIS dosing errors accounted for 5% of the total number of cases, while dosing errors for ASP and GLU were less than 3%. The most frequently reported dosing errors involved improper dosing (49%). Conclusions: Although there were fewer dosing errors of RAIAs in comparison to other insulins, the severity of the potential outcome highlights the importance of precise dosing and timing. Improved the monitoring and reporting of these dosing errors could enhance diabetes patient care. Additionally, smart medical devices could improve therapeutic outcomes. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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13 pages, 738 KiB

Open AccessArticle

The Potential Diagnostic Utility of SMAD4 and ACCS in the Context of Inflammation in Type 2 Diabetes Mellitus Patients

by Habiba Khdair Abdalsada, Yusra Sebri Abdulsaheb, Samaneh Zolghadri, Hussein Kadhem Al-Hakeim and Agata Stanek

Biomedicines 2024, 12(9), 2015; https://doi.org/10.3390/biomedicines12092015 - 4 Sep 2024

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Abstract

The search for new parameters for the prediction of type 2 diabetes mellitus (T2DM) or its harmful consequences remains an important field of study. Depending on the low-grade inflammatory nature of diabetes, we investigated three proteins in T2DM patients: 1-aminocyclopropane-1-carboxylate synthase (ACCS), granulocyte–colony-stimulating [...] Read more.

The search for new parameters for the prediction of type 2 diabetes mellitus (T2DM) or its harmful consequences remains an important field of study. Depending on the low-grade inflammatory nature of diabetes, we investigated three proteins in T2DM patients: 1-aminocyclopropane-1-carboxylate synthase (ACCS), granulocyte–colony-stimulating factor (G-CSF), and Sma Mothers Against Decapentaplegic homolog-4 (SMAD4). In brief, sixty T2DM and thirty healthy controls had their serum levels of ACCS, G-CSF, SMAD4, and insulin tested using the ELISA method. The insulin resistance (IR) parameter (HOMA2IR), beta-cell function percentage (HOMA2%B), and insulin sensitivity (HOMA2%S) were all determined by the Homeostasis Model Assessment-2 (HOMA2) calculator. The predictability of these protein levels was investigated by neural network (NN) analysis and was associated with measures of IR. Based on the results, ACCS, G-CSF, and SMAD4 increased significantly in the T2DM group compared with the controls. Their levels depend on IR status and inflammation. The multivariate GLM indicated the independence of the levels of these proteins on the covariates or drugs taken. The receiver operating characteristic area under the curve (AUC) for the prediction of T2DM using NN analysis is 0.902, with a sensitivity of 71.4% and a specificity of 93.8%. The network predicts T2DM well with predicted pseudoprobabilities over 0.5. The model’s predictive capability (normalized importance) revealed that ACCS is the best model (100%) for the prediction of T2DM, followed by G-CSF (75.5%) and SMAD4 (69.6%). It can be concluded that ACCS, G-CSF, and SMAD4 are important proteins in T2DM prediction, and their increase is associated with the presence of inflammation. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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12 pages, 1229 KiB

Open AccessArticle

Development of Liver Fibrosis Represented by the Fibrosis-4 Index Is a Specific Risk Factor for Tubular Injury in Individuals with Type 2 Diabetes

by Tomoyo Hara, Takeshi Watanabe, Hiroki Yamagami, Kohsuke Miyataka, Saya Yasui, Takahito Asai, Yousuke Kaneko, Yukari Mitsui, Shiho Masuda, Kiyoe Kurahashi, Toshiki Otoda, Tomoyuki Yuasa, Akio Kuroda, Itsuro Endo, Soichi Honda, Akira Kondo, Munehide Matsuhisa and Ken-ichi Aihara

Biomedicines 2024, 12(8), 1789; https://doi.org/10.3390/biomedicines12081789 - 7 Aug 2024

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Abstract

Although hyperglycemia and hypertension are well-known risk factors for glomerular injury in individuals with type 2 diabetes (T2D), specific risk factors for tubular injury remain unclear. We aimed to clarify the differences between risk factors for glomerular injury and risk factors for tubular [...] Read more.

Although hyperglycemia and hypertension are well-known risk factors for glomerular injury in individuals with type 2 diabetes (T2D), specific risk factors for tubular injury remain unclear. We aimed to clarify the differences between risk factors for glomerular injury and risk factors for tubular injury in individuals with T2D. We categorized 1243 subjects into four groups based on urinary biomarkers, including the albumin-to-creatinine ratio (uACR) and L-type fatty acid-binding protein-to-creatinine ratio (uL-ABPCR) as a normal (N) group (uACR < 30 mg/gCr and uL-FABPCR < 5 μg/gCr; n = 637), a glomerular specific injury (G) group (uACR ≥ 30 mg/gCr and uL-FABPCR < 5 μg/gCr; n = 248), a tubular specific injury (T) group (uACR < 30 mg/gCr and uL-FABPCR ≥ 5 μg/gCr; n = 90), and a dual injury (D) group (uACR ≥ 30 mg/gCr and uL-FABPCR ≥ 5 μg/gCr; n = 268). Logistic regression analysis referencing the N group revealed that BMI, current smoking, and hypertension were risk factors for the G group, creatinine (Cr) and Fibrosis-4 (FIB-4) index were risk factors for the T group, and BMI, hypertension, HbA1c, Cr, and duration of diabetes were risk factors for the D group. While hypertension was a distinct specific risk factor for glomerular injury, the FIB-4 index was a specific contributor to the prevalence of tubular injury. On the other hand, the logistic regression analysis revealed that the hepatic steatosis index (HSI) did not show any significant association with the G group, T group, or D group. Taken together, the development of liver fibrosis rather than liver steatosis is an inherent threat relating to tubular injury in individuals with T2D. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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11 pages, 1633 KiB

Open AccessArticle

SMAD3 rs17228212 Polymorphism Is Associated with Advanced Carotid Atherosclerosis in a Slovenian Population

by David Petrovič, Jernej Letonja and Danijel Petrovič

Biomedicines 2024, 12(5), 1103; https://doi.org/10.3390/biomedicines12051103 - 16 May 2024

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Abstract

Smad proteins influence the TGFβ signaling pathway, which plays an important role in the progression of atherosclerosis. The aim of our study was to investigate the association between the rs17228212 polymorphism of the SMAD3 gene and advanced carotid atherosclerosis in Slovenian subjects and [...] Read more.

Smad proteins influence the TGFβ signaling pathway, which plays an important role in the progression of atherosclerosis. The aim of our study was to investigate the association between the rs17228212 polymorphism of the SMAD3 gene and advanced carotid atherosclerosis in Slovenian subjects and to investigate the effect of the rs17228212 SMAD3 polymorphism on the expression of SMAD3 in endarterectomy sequesters. In this cross-sectional case-control study, 881 unrelated Caucasians were divided into two groups. The first group included 308 patients with advanced carotid atherosclerosis of the common or internal carotid artery with stenosis greater than 75% that underwent a revascularization procedure (cases). The control group consisted of 573 subjects without hemodynamically significant carotid atherosclerosis. We analyzed the rs17228212 polymorphism of the SMAD3 gene using the StepOne real-time polymerase chain reaction system and TaqMan SNP genotyping assay. The results in the two genetic models showed a statistically significant association, codominant (OR 4.05; CI 1.10–17.75; p = 0.037) and dominant (OR 3.60; CI 1.15–15.45; p = 0.045). An immunohistochemical analysis of SMAD3 expression was conducted for 26 endarterectomy specimens. The T allele of the rs17228212 SMAD3 gene was shown to be associated with an increased numerical area density of SMAD3-positive cells in carotid plaques. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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15 pages, 4260 KiB

Open AccessArticle

Glucose Promotes EMMPRIN/CD147 and the Secretion of Pro-Angiogenic Factors in a Co-Culture System of Endothelial Cells and Monocytes

by Fransis Ghandour, Sameer Kassem, Elina Simanovich and Michal A. Rahat

Biomedicines 2024, 12(4), 706; https://doi.org/10.3390/biomedicines12040706 - 22 Mar 2024

Cited by 2 | Viewed by 1303

Abstract

Vascular complications in Type 2 diabetes mellitus (T2DM) patients increase morbidity and mortality. In T2DM, angiogenesis is impaired and can be enhanced or reduced in different tissues (“angiogenic paradox”). The present study aimed to delineate differences between macrovascular and microvascular endothelial cells that [...] Read more.

Vascular complications in Type 2 diabetes mellitus (T2DM) patients increase morbidity and mortality. In T2DM, angiogenesis is impaired and can be enhanced or reduced in different tissues (“angiogenic paradox”). The present study aimed to delineate differences between macrovascular and microvascular endothelial cells that might explain this paradox. In a monoculture system of human macrovascular (EaHy926) or microvascular (HMEC-1) endothelial cell lines and a monocytic cell line (U937), high glucose concentrations (25 mmole/L) increased the secretion of the pro-angiogenic factors CD147/EMMPRIN, VEGF, and MMP-9 from both endothelial cells, but not from monocytes. Co-cultures of EaHy926/HMEC-1 with U937 enhanced EMMPRIN and MMP-9 secretion, even in low glucose concentrations (5.5 mmole/L), while in high glucose HMEC-1 co-cultures enhanced all three factors. EMMPRIN mediated these effects, as the addition of anti-EMMPRIN antibody decreased VEGF and MMP-9 secretion, and inhibited the angiogenic potential assessed through the wound assay. Thus, the minor differences between the macrovascular and microvascular endothelial cells cannot explain the angiogenic paradox. Metformin, a widely used drug for the treatment of T2DM, inhibited EMMPRIN, VEGF, and MMP-9 secretion in high glucose concentration, and the AMPK inhibitor dorsomorphin enhanced it. Thus, AMPK regulates EMMPRIN, a key factor in diabetic angiogenesis, suggesting that targeting EMMPRIN may help in the treatment of diabetic vascular complications. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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19 pages, 8052 KiB

Open AccessArticle

Protective Effect of Topiramate against Diabetic Retinopathy and Computational Approach Recognizing the Role of NLRP3/IL-1β/TNF-α Signaling

by Hala M. F. Mohammad, Mohamed Ahmed Eladl, Asmaa K. K. Abdelmaogood, Rabie E. Elshaer, Walaa Ghanam, Abdelhakeem Elaskary, Mohamed A. K. Saleh, Amira H. Eltrawy, Sahar K. Ali, Suzan M. M. Moursi, Shymaa E. Bilasy, Sawsan A. Zaitone, Wafa Ali Alzlaiq and Hayam Atteya

Biomedicines 2023, 11(12), 3202; https://doi.org/10.3390/biomedicines11123202 - 1 Dec 2023

Cited by 2 | Viewed by 1527

Abstract

The possible impact of topiramate against diabetic retinopathy (DREN) and its molecular mechanisms in relation to the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has not been studied before. Thus, in the present study, we aimed to utilize a computational approach [...] Read more.

The possible impact of topiramate against diabetic retinopathy (DREN) and its molecular mechanisms in relation to the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has not been studied before. Thus, in the present study, we aimed to utilize a computational approach to investigate the possible protective effect of topiramate on experimental DREN and explore its impact on NLRP3/interlukin-1β signaling and brain-derived neurotrophic factor (BDNF) expression. Male albino mice were distributed to four experimental groups and assigned the following categorizations: (i) saline, (ii) diabetic, (iii) diabetic + topiramate 10 mg/kg and (iv) diabetic + topiramate 30 mg/kg. We observed shrinkage of total retinal thickness and elevation in retinal glutamate, malondialdehyde, NLRP3 and interlukin-1β but decreased glutathione (GSH) levels in the diabetic mice. Additionally, retinal ultra-structures in the diabetic group showed abnormalities and vacuolations in the pigmented epithelium, the photoreceptor segment, the outer nuclear layer, the inner nuclear layer and the ganglion cell layer (GCL). Mice treated with topiramate 10 or 30 mg/kg showed downregulation in retinal malondialdehyde, NLRP3 and interlukin-1β levels; improvements in the retinal pathologies; enhanced immunostaining for BDNF and improved ultra-structures in different retinal layers. Overall, the current results suggest topiramate as a neuroprotective agent for DREN, and future studies are warranted to further elucidate the mechanism of its protective action. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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10 pages, 260 KiB

Open AccessArticle

Neuropsychological Aspects of Children’s Somatic Disorders in Chronic Diseases: Diabetes and Short Stature in the Developmental Period

by Maia Stanisławska-Kubiak, Katarzyna Wiecheć, Katarzyna Anna Majewska, Grażyna Teusz, Ewa Mojs and Andrzej Kędzia

Biomedicines 2023, 11(11), 3089; https://doi.org/10.3390/biomedicines11113089 - 17 Nov 2023

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Abstract

Intellectual functioning studies carried out amongst children indicate that chronic diseases like type 1 diabetes and growth hormone deficiency (GHD), may, but do not necessarily, result in intellectual loss. Cognitive functions may decline as a child becomes older, as a disease persists over [...] Read more.

Intellectual functioning studies carried out amongst children indicate that chronic diseases like type 1 diabetes and growth hormone deficiency (GHD), may, but do not necessarily, result in intellectual loss. Cognitive functions may decline as a child becomes older, as a disease persists over time and/or due to non-compliance with treatment recommendations or high stress levels. This study aimed to assess the cognitive functioning of children and youths with T1D and GHD-related short stature compared to healthy children. Methods: The study was carried out on 88 children with type 1 diabetes, 38 children suffering from short stature caused by (GHD), as well as a control group comprising 40 healthy children. Weschler’s tests were applied to measure intellectual and cognitive functions. Results: The results suggest that for children suffering from type 1 diabetes and short stature, their chronic childhood diseases per se do not impair cognitive development. It was observed that the higher the age of chronically ill children and the longer the disease persists, the lower their scores in individual cognitive subtests. For healthy children, age is correlated with the acquisition of particular skills and higher scores in specific subtests. Conclusions: On the basis of qualitative analysis of the cognitive functions subject to the study and close clinical observation of chronically ill children, we have been able to conclude that chronic diseases may alter cognitive functioning. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

12 pages, 2115 KiB

Open AccessArticle

Analysis of Methylglyoxal Concentration in a Group of Patients with Newly Diagnosed Prediabetes

by Edyta Sutkowska, Izabela Fecka, Dominik Marciniak, Katarzyna Bednarska, Magdalena Sutkowska and Katarzyna Hap

Biomedicines 2023, 11(11), 2968; https://doi.org/10.3390/biomedicines11112968 - 3 Nov 2023

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Abstract

Background: The abnormal serum concentration of methylglyoxal (MGO) has been presented as an indicator of chronic complications in diabetes (DM). Because such complications are also found in pre-DM, we decided to assess the concentration of this compound in individuals with pre-DM, without cardio-vascular [...] Read more.

Background: The abnormal serum concentration of methylglyoxal (MGO) has been presented as an indicator of chronic complications in diabetes (DM). Because such complications are also found in pre-DM, we decided to assess the concentration of this compound in individuals with pre-DM, without cardio-vascular diseases. Methods: Frozen samples from individuals newly diagnosed with pre-DM (N = 31) and healthy subjects (N = 11) were prepared and MGO concentration was determined using UHPLC-ESI-QqTOF-MS. Results: Statistical significance was established when the groups were compared for body weight, BMI, fasting glucose level, fatty liver and use of statins but not for the other descriptive parameters. The positive linear correlation showed that the higher HbA1c, the higher MGO concentration (p = 0.01). The values of MGO were within the normal range in both groups (mean value for pre-DM: 135.44 nM (±SD = 32.67) and for the control group: 143.25 nM (±SD = 17.93); p = 0.46 (±95% CI)), with no statistical significance between the groups. Conclusions: We did not confirm the elevated MGO levels in the group of patients with pre-DM. The available data suggests a possible effect of statin intake on MGO levels. This thesis requires confirmation on a larger number of patients with an assessment of MGO levels before and after the introduction of statins. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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10 pages, 603 KiB

Open AccessArticle

Clinical Outcomes of Diabetic Ketoacidosis in Type 2 Diabetes Patients with and without SGLT2 Inhibitor Treatment: A Retrospective Study

by Afif Nakhleh, Areen Othman, Amin Masri, Moshe Zloczower, Sagit Zolotov and Naim Shehadeh

Biomedicines 2023, 11(10), 2689; https://doi.org/10.3390/biomedicines11102689 - 1 Oct 2023

Cited by 2 | Viewed by 1353

Abstract

Aim: This study aimed to compare the clinical course and outcomes of DKA in T2DM patients who received treatment with SGLT2 inhibitors versus those who did not. Methods: A retrospective analysis was conducted on T2DM patients who were admitted to the Rambam Health [...] Read more.

Aim: This study aimed to compare the clinical course and outcomes of DKA in T2DM patients who received treatment with SGLT2 inhibitors versus those who did not. Methods: A retrospective analysis was conducted on T2DM patients who were admitted to the Rambam Health Care Campus with DKA between 7/2015 and 9/2020. Demographic, clinical, and laboratory data were obtained from electronic medical records. Outpatient mortality was monitored until 12/2022. Results: Of 71 T2DM patients admitted with DKA, 16 (22.5%) were on SGLT2 inhibitor treatment upon admission. SGLT2 inhibitor users had a higher BMI and were less likely to be treated with insulin. During hospitalization, the rates of acute kidney injury, concomitant infections, and inpatient mortality among SGLT2 inhibitor users were comparable to non-users. The median follow-up period was 35.1 months for the SGLT2 inhibitor users and 36.7 months for non-users. The long-term mortality from any cause was lower among the SGLT2 inhibitor users (12.5% vs. 52.7%, p = 0.004). In Cox regression analysis, SGLT2 inhibitor use was associated with a lower risk of long-term mortality from any cause (HR = 0.19, p = 0.04). Conclusion: T2DM patients with DKA who received SGLT2 inhibitors had lower long-term mortality from any cause compared to those who did not receive SGLT2 inhibitors. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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13 pages, 1383 KiB

Open AccessArticle

Impacts of the DPP-4 Inhibitor Saxagliptin and SGLT-2 Inhibitor Dapagliflozin on the Gonads of Diabetic Mice

by Ali A. Alshamrani, Mohammed A. Al-Hamamah, Norah A. Albekairi, Mohamed S. M. Attia, Sheikh F. Ahmad, Mohammed A. Assiri, Mushtaq A. Ansari, Ahmed Nadeem, Saleh A. Bakheet, Wael A. Alanazi and Sabry M. Attia

Biomedicines 2023, 11(10), 2674; https://doi.org/10.3390/biomedicines11102674 - 29 Sep 2023

Cited by 3 | Viewed by 1275

Abstract

Diabetes mellitus is a metabolic disease that can cause systemic problems, including testicular dysfunction. Several diabetes medications have demonstrated potential adverse effects on the male reproductive system; however, the effects of saxagliptin and dapagliflozin have not been sufficiently examined. This investigation studied the [...] Read more.

Diabetes mellitus is a metabolic disease that can cause systemic problems, including testicular dysfunction. Several diabetes medications have demonstrated potential adverse effects on the male reproductive system; however, the effects of saxagliptin and dapagliflozin have not been sufficiently examined. This investigation studied the impacts of saxagliptin and dapagliflozin treatments on the gonads in a male mouse model of diabetes. Testicular disturbances were assessed by sperm DNA damage, diakinesis-metaphase I chromosome examination, and spermiogram analysis. Our results showed more sperm DNA damage, more spermatocyte chromosome aberrations, lower sperm motility/count, and more sperm morphological anomalies in diabetic mice than in the control mice. Dapagliflozin significantly restored all examined measures to the control values in diabetic mice, unlike saxagliptin, which exacerbated the reduction in sperm count and motility. Both drugs significantly restored the gonadal redox imbalances in diabetic mice by decreasing reactive oxygen species accumulation and increasing glutathione levels. In conclusion, our study presents preliminary evidence for the safety and efficacy of dapagliflozin in alleviating testicular abnormalities induced by diabetes, making it a promising candidate drug for patients with diabetes in their reproductive age. As saxagliptin may have negative effects on fertility, its prescription should be avoided in young male diabetic patients. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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Review

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21 pages, 1529 KiB

Open AccessReview

Genetic and Epigenetic Aspects of Type 1 Diabetes Mellitus: Modern View on the Problem

by Ildar Minniakhmetov, Bulat Yalaev, Rita Khusainova, Ekaterina Bondarenko, Galina Melnichenko, Ivan Dedov and Natalia Mokrysheva

Biomedicines 2024, 12(2), 399; https://doi.org/10.3390/biomedicines12020399 - 8 Feb 2024

Cited by 3 | Viewed by 3301

Abstract

Omics technologies accumulated an enormous amount of data that advanced knowledge about the molecular pathogenesis of type 1 diabetes mellitus and identified a number of fundamental problems focused on the transition to personalized diabetology in the future. Among them, the most significant are [...] Read more.

Omics technologies accumulated an enormous amount of data that advanced knowledge about the molecular pathogenesis of type 1 diabetes mellitus and identified a number of fundamental problems focused on the transition to personalized diabetology in the future. Among them, the most significant are the following: (1) clinical and genetic heterogeneity of type 1 diabetes mellitus; (2) the prognostic significance of DNA markers beyond the HLA genes; (3) assessment of the contribution of a large number of DNA markers to the polygenic risk of disease progress; (4) the existence of ethnic population differences in the distribution of frequencies of risk alleles and genotypes; (5) the infancy of epigenetic research into type 1 diabetes mellitus. Disclosure of these issues is one of the priorities of fundamental diabetology and practical healthcare. The purpose of this review is the systemization of the results of modern molecular genetic, transcriptomic, and epigenetic investigations of type 1 diabetes mellitus in general, as well as its individual forms. The paper summarizes data on the role of risk HLA haplotypes and a number of other candidate genes and loci, identified through genome-wide association studies, in the development of this disease and in alterations in T cell signaling. In addition, this review assesses the contribution of differential DNA methylation and the role of microRNAs in the formation of the molecular pathogenesis of type 1 diabetes mellitus, as well as discusses the most currently central trends in the context of early diagnosis of type 1 diabetes mellitus. Full article

(This article belongs to the Special Issue Diabetes and Complications of Diabetes: Pathophysiology, Mechanisms, and Therapies)

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