Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

New Advances in Type 2 Diabetes and Its Complications

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (20 December 2024) | Viewed by 28275

Share This Special Issue

Special Issue Editor

Dr. Anca Pantea Stoian

E-Mail Website
Guest Editor

Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
Interests: diabetes; nutrition; metabolic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I have the honour and privilege of being a Guest Editor for the new Special Issue "New Advances in Type 2 Diabetes and Its Complications".

Type 2 diabetes is one of the most common chronic diseases in modern society. Nevertheless, unfortunately, there are still insufficient research data on the pathogenesis of type 2 diabetes and its complications.

This Special Issue aims to bring forward exciting papers based on the new pathological mechanisms and therapeutic discoveries related to type 2 diabetes and its complications. Therefore, we encourage you to submit original research and review articles regarding recent advances in diabetes pathophysiology and new therapeutic molecules, as well as those related to cardiovascular disease, stroke, neuropathy, retinopathy, chronic kidney disease or non-alcoholic fatty liver disease in patients with type 2 diabetes.

Thank you in advance for your interest.

Dr. Anca Pantea Stoian
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 type 2
diabetes complications
pathophysiology of type 2 diabetes
new diabetes treatment
cardiovascular disease
stroke
peripheral artery disease
chronic kidney disease
retinopathy
neuropathy
non-alcoholic fatty liver disease in diabetes

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

24 pages, 1019 KiB

Open AccessArticle

Adiponectin and TNF-Alpha Differentially Mediate the Association Between Cystatin C and Oxidized LDL in Type 2 Diabetes Mellitus Patients

by Ahmed Bakillah, Ayman Farouk Soliman, Maram Al Subaiee, Khamis Khamees Obeid, Arwa Al Hussaini, Shahinaz Faisal Bashir, Mohammad Al Arab, Abeer Al Otaibi, Sindiyan Al Shaikh Mubarak and Ali Ahmed Al Qarni

Int. J. Mol. Sci. 2025, 26(7), 3001; https://doi.org/10.3390/ijms26073001 - 25 Mar 2025

Viewed by 305

Abstract

In individuals with type 2 diabetes mellitus (T2DM), elevated levels of both plasma and urinary cystatin C (Cys-C) contribute to increased oxidation, which in turn accelerates the oxidation of low-density lipoprotein (LDL). This process may worsen the development of atherosclerosis and cardiovascular disease by promoting endothelial dysfunction and inflammation. Despite its potential significance, the relationship between Cys-C and oxidized LDL (ox-LDL) in T2DM remains poorly understood. This study investigated the relationship between plasma and urinary Cys-C and ox-LDL levels in T2DM patients. The cohort included 57 patients with T2DM (mean age 61.14 ± 9.99 years; HbA1c 8.66 ± 1.60% and BMI 35.15 ± 6.65 kg/m²). Notably, 95% of the patients had hypertension, 82% had dyslipidemia, 59% had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m², 14% had coronary artery disease (CAD), and 5% had a history of stroke. Plasma and urinary Cys-C and ox-LDL levels were measured using ELISA. Adipokine and cytokine levels were measured using the multiplex^® MAP Human Adipokine Magnetic Bead Panels. Spearman’s correlation analysis revealed a significant positive correlation of plasma and urinary Cys-C with ox-LDL (r = 0.569, p = 0.0001 and r = 0.485, p = 0.0001, respectively). Multivariable regression analysis indicated that both plasma and urinary Cys-C were independently associated with ox-LDL, after adjusting for confounding factors (β = 0.057, p = 0.0001 and β = 0.486, p = 0.003, respectively). Stepwise linear regression identified TNFα and adiponectin as the strongest predictors of the relationship between urinary Cys-C and ox-LDL (β = 0.382, p = 0.0001; r² = 0.64), while adiponectin alone was the best predictor of the plasma Cys-C and ox-LDL association (β = 0.051, p = 0.005; r² = 0.46). Furthermore, adiponectin partly mediated the relationship between plasma Cys-C and ox-LDL, explaining 18% of the variance in this association. In contrast, TNFα partly mediated the relationship between urinary Cys-C and ox-LDL, accounting for 28% of the variance. This study emphasizes the complex interaction between Cys-C and ox-LDL in T2DM. It highlights the need for additional research involving larger patient cohorts to improve our understanding of the therapeutic potential of plasma and urinary Cys-C in conjunction with ox-LDL for managing complications associated with T2DM. Full article

(This article belongs to the Special Issue New Advances in Type 2 Diabetes and Its Complications)

► Show Figures

Figure 1

21 pages, 680 KiB

Open AccessArticle

Plasma Atrial Natriuretic Peptide Predicts Oxidized Low-Density Lipoprotein Levels in Type 2 Diabetes Mellitus Patients Independent of Circulating Adipokine and Cytokine

by Ahmed Bakillah, Maram Al Subaiee, Ayman Farouk Soliman, Khamis Khamees Obeid, Shahinaz Faisal Bashir, Arwa Al Hussaini, Mohammad Al Arab, Abeer Al Otaibi, Sindiyan Al Shaikh Mubarak and Ali Ahmed Al Qarni

Int. J. Mol. Sci. 2025, 26(5), 1859; https://doi.org/10.3390/ijms26051859 - 21 Feb 2025

Viewed by 549

Abstract

Atrial natriuretic peptide (ANP) and oxidized low-density lipoprotein (ox-LDL) play essential roles in the development and progression of vascular complications associated with type 2 diabetes mellitus (T2DM), and both are independently linked to cardiovascular diseases (CVD). However, the relationship between ANP and ox-LDL in patients with T2DM remains unclear as previous studies have primarily focused on circulating levels in various diseases. This study investigated the relationship between ANP and ox-LDL levels in obese individuals with T2DM. The cohort included 57 patients with T2DM (mean age 61.14 ± 9.99 years; HbA1c 8.66 ± 1.60%; BMI 35.15 ± 6.65 kg/m²). Notably, 95% of the patients had hypertension, 82% had dyslipidemia, 59% had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m², 14% had coronary artery disease (CAD), and 5% had a history of stroke. Plasma concentrations of ANP and ox-LDL were measured using ELISA. Adipokines and cytokines levels were measured using the multiplex^® MAP Human Adipokine Magnetic Beads Spearman’s correlation analysis which revealed a negative correlation between ANP and ox-LDL (r = −0.446, p = 0.001) as well as with the ox-LDL/apoB ratio (r = −0.423, p = 0.001) and ox-LDL/LDLc ratio (r = −0.307, p = 0.038). Multivariable regression analysis indicated that ANP was independently associated with ox-LDL (β = −115.736, p = 0.005). Stepwise linear regression further identified TNFα, leptin, and adiponectin as the strongest predictors influencing the relationship between ANP and ox-LDL levels (β = −64.664, p = 0.0311, and r² = 0.546 for the model). However, these factors did not significantly mediate this association. This study emphasizes the need for further exploration of the complex interaction between ANP and ox-LDL in larger patient populations. This could provide valuable insights into potential therapeutic approaches for managing vascular complications in obese individuals with T2DM. Full article

(This article belongs to the Special Issue New Advances in Type 2 Diabetes and Its Complications)

► Show Figures

Figure 1

20 pages, 5339 KiB

Open AccessArticle

The Interplay Between High Cumulative Doses of Radioactive Iodine and Type 2 Diabetes Mellitus: A Complex Cardiovascular Challenge

by Adina Elena Stanciu, Madalina Lucica Bolovan, Adina Zamfir-Chiru-Anton, Catalina Voiosu, Pradeep Kumar Dabla, Marcel Marian Stanciu, Nafija Serdarevic and Mirela Gherghe

Int. J. Mol. Sci. 2025, 26(1), 37; https://doi.org/10.3390/ijms26010037 - 24 Dec 2024

Viewed by 956

Abstract

Starting from the metabolic profile of type 2 diabetes mellitus (T2DM), we hypothesized that the mechanisms of ¹³¹I-induced cardiotoxicity differ between patients diagnosed with differentiated thyroid cancer (DTC) with/without T2DM, with metformin potentially acting as a cardioprotective agent by mitigating inflammation in patients with T2DM. To address this hypothesis, we quantified, using ELISA, the serum concentration of several key biomarkers that reflect cardiac injury (NT-proBNP, NT-proANP, ST2/IL-33R, and cTn I) in 74 female patients with DTC/−T2DM and 25 with DTC/+T2DM treated with metformin. All patients received a cumulative oral dose of ¹³¹I exceeding 150 mCi (5.55 GBq) over approximately 53 months. Our results showed the following: (i) In DTC/−T2DM patients, high-cumulative ¹³¹I doses promote a pro-inflammatory state that accelerates the development of cardiotoxicity. Monitoring NT-proBNP, ST2/IL-33R, and cTn I in these patients may help identify those at risk of developing cardiac complications. (ii) In patients with DTC/+T2DM, high-cumulative ¹³¹I doses lead to the release of NT-proANP (r = 0.63), which signals that the atria are under significant stress. (iii) In patients with DTC/+T2DM, metformin suppresses inflammation, leading to a dose-dependent reduction in cTn I (r = −0.59). Monitoring cTn I and NT-proANP, and considering the use of metformin as part of the therapeutic strategy, could help manage cardiotoxicity in T2DM patients undergoing ¹³¹I therapy. Full article

(This article belongs to the Special Issue New Advances in Type 2 Diabetes and Its Complications)

► Show Figures

Figure 1

16 pages, 2846 KiB

Open AccessArticle

Dioxin-Induced PAI-1 Expression: A Novel Pathway to Pancreatic β-Cell Failure in Type 2 Diabetes

by Suyeol Im, Sora Kang, Woo Jung Son, Minuk Son, Seung Jun Oh, Hye Ji Yoon and Youngmi Kim Pak

Int. J. Mol. Sci. 2024, 25(22), 11974; https://doi.org/10.3390/ijms252211974 - 7 Nov 2024

Viewed by 1339

Abstract

Exposure to environment-polluting chemicals (EPCs), which are ligands of the aryl hydrocarbon receptor (AhR), is associated with the development of type 2 diabetes (T2D). This study explores the mechanisms by which AhR ligands contribute to β-cell failure in T2D. Incubation of RINm5F rat pancreatic β-cells with low-dose 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent AhR ligand, inhibited glucose-stimulated insulin secretion (GSIS). A single injection of TCDD in wild type mice reduced the size of Langerhans islets, but not in AhR liver knock-out mice (AhR-LKO). RNA-seq database analysis identified Serpine1, encoding for plasminogen activator inhibitor type-1 (PAI-1) as a TCDD-mediated secretory protein that is synthesized in an AhR-dependent manner in the liver. Elevated PAI-1 levels were shown to induce Caspase-3/7-dependent apoptosis in RINm5F cells, suggesting a novel pathway through which EPCs exacerbate T2D. These findings support the hypothesis that chronic exposure to AhR ligands may directly inhibit GSIS in pancreatic β-cells and indirectly induce β-cell apoptosis through increased PAI-1. This study provides new insights into the EPC-PAI-1 axis as a missing link between pancreatic β-cell failure and the progression of T2D and offers a potential target for therapeutic intervention. Full article

(This article belongs to the Special Issue New Advances in Type 2 Diabetes and Its Complications)

► Show Figures

Figure 1

Review

Jump to: Research

24 pages, 841 KiB

Open AccessReview

Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications

by Ewelina Młynarska, Witold Czarnik, Natasza Dzieża, Weronika Jędraszak, Gabriela Majchrowicz, Filip Prusinowski, Magdalena Stabrawa, Jacek Rysz and Beata Franczyk

Int. J. Mol. Sci. 2025, 26(3), 1094; https://doi.org/10.3390/ijms26031094 - 27 Jan 2025

Cited by 4 | Viewed by 8132

Abstract

Type 2 diabetes mellitus (T2DM), a prevalent chronic disease affecting over 400 million people globally, is driven by genetic and environmental factors. The pathogenesis involves insulin resistance and β-cell dysfunction, mediated by mechanisms such as the dedifferentiation of β-cells, mitochondrial dysfunction, and oxidative stress. Treatment should be based on non-pharmacological therapy. Strategies such as increased physical activity, dietary modifications, cognitive-behavioral therapy are important in maintaining normal glycemia. Advanced therapies, including SGLT2 inhibitors and GLP-1 receptor agonists, complement these treatments and offer solid glycemic control, weight control, and reduced cardiovascular risk. Complications of T2DM, such as diabetic kidney disease, retinopathy, and neuropathy, underscore the need for early diagnosis and comprehensive management to improve patient outcomes and quality of life. Full article

(This article belongs to the Special Issue New Advances in Type 2 Diabetes and Its Complications)

► Show Figures

Figure 1

18 pages, 2619 KiB

Open AccessReview

Pathophysiological Relationship between Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease: Novel Therapeutic Approaches

by Shifat-E Ferdous and Jessica M. Ferrell

Int. J. Mol. Sci. 2024, 25(16), 8731; https://doi.org/10.3390/ijms25168731 - 10 Aug 2024

Cited by 3 | Viewed by 3688

Abstract

Type 2 diabetes mellitus (T2DM), often featuring hyperglycemia or insulin resistance, is a global health concern that is increasing in prevalence in the United States and worldwide. A common complication is metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of metabolic syndrome that is also rapidly increasing in prevalence. The majority of patients with T2DM will experience MASLD, and likewise, individuals with MASLD are at an increased risk for developing T2DM. These two disorders may act synergistically, in part due to increased lipotoxicity and inflammation within the liver, among other causes. However, the pathophysiological mechanisms by which this occurs are unclear, as is how the improvement of one disorder can ameliorate the other. This review aims to discuss the pathogenic interactions between T2D and MASLD, and will highlight novel therapeutic targets and ongoing clinical trials for the treatment of these diseases. Full article

(This article belongs to the Special Issue New Advances in Type 2 Diabetes and Its Complications)

► Show Figures

Figure 1

15 pages, 521 KiB

Open AccessReview

Skin Autofluorescence as a Potential Adjunctive Marker for Cardiovascular Risk Assessment in Type 2 Diabetes: A Systematic Review

by Delia Reurean-Pintilei, Anca Pantea Stoian, Claudia-Gabriela Potcovaru, Teodor Salmen, Delia Cinteză, Roxana-Adriana Stoica, Sandra Lazăr and Bogdan Timar

Int. J. Mol. Sci. 2024, 25(7), 3889; https://doi.org/10.3390/ijms25073889 - 31 Mar 2024

Cited by 7 | Viewed by 2315

Abstract

Diabetes mellitus (DM), due to its long-term hyperglycemia, leads to the accumulation of advanced glycation end-products (AGEs), especially in the vessel walls. Skin autofluorescence (SAF) is a non-invasive tool that measures AGEs. DM patients have a rich dietary source in AGEs, associated with high oxidative stress and long-term inflammation. AGEs represent a cardiovascular (CV) risk factor, and they are linked with CV events. Our objective was to assess whether SAF predicts future CV events (CVE) by examining its association with other CV risk factors in patients with type 2 DM (T2DM). Additionally, we assessed the strengths and limitations of SAF as a predictive tool for CVE. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, we conducted a systematic review with CRD42024507397 protocol, focused on AGEs, T2DM, SAF, and CV risk. We identified seven studies from 2014 to 2024 that predominantly used the AGE Reader Diagnostic Optic tool. The collective number of patients involved is 8934, with an average age of 63. So, SAF is a valuable, non-invasive marker for evaluating CV risk in T2DM patients. It stands out as a CV risk factor associated independently with CVE. SAF levels are influenced by prolonged hyperglycemia, lifestyle, aging, and other chronic diseases such as depression, and it can be used as a predictive tool for CVE. Full article

(This article belongs to the Special Issue New Advances in Type 2 Diabetes and Its Complications)

► Show Figures

Figure 1

19 pages, 2676 KiB

Open AccessReview

Natural Inhibitors of Mammalian α-Amylases as Promising Drugs for the Treatment of Metabolic Diseases

by Aleksandr P. Kalinovskii, Oksana V. Sintsova, Irina N. Gladkikh and Elena V. Leychenko

Int. J. Mol. Sci. 2023, 24(22), 16514; https://doi.org/10.3390/ijms242216514 - 20 Nov 2023

Cited by 16 | Viewed by 4959

Abstract

α-Amylase is a generally acknowledged molecular target of a distinct class of antidiabetic drugs named α-glucosidase inhibitors. This class of medications is scarce and rather underutilized, and treatment with current commercial drugs is accompanied by unpleasant adverse effects. However, mammalian α-amylase inhibitors are abundant in nature and form an extensive pool of high-affinity ligands that are available for drug discovery. Individual compounds and natural extracts and preparations are promising therapeutic agents for conditions associated with impaired starch metabolism, e.g., diabetes mellitus, obesity, and other metabolic disorders. This review focuses on the structural diversity and action mechanisms of active natural products with inhibitory activity toward mammalian α-amylases, and emphasizes proteinaceous inhibitors as more effective compounds with significant potential for clinical use. Full article

(This article belongs to the Special Issue New Advances in Type 2 Diabetes and Its Complications)

► Show Figures

Figure 1

16 pages, 1736 KiB

Open AccessReview

A Critical View over the Newest Antidiabetic Molecules in Light of Efficacy—A Systematic Review and Meta-Analysis

by Teodor Salmen, Liviu-Ionut Serbanoiu, Ioana-Cristina Bica, Cristian Serafinceanu, Emir Muzurović, Andrej Janez, Stefan Busnatu, Maciej Banach, Ali Abbas Rizvi, Manfredi Rizzo and Anca Pantea Stoian

Int. J. Mol. Sci. 2023, 24(11), 9760; https://doi.org/10.3390/ijms24119760 - 5 Jun 2023

Cited by 13 | Viewed by 4615

Abstract

The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy. The novel antidiabetic drugs can improve this global therapeutic and health problem in patients with diabetes mellitus (DM). We aimed to establish the efficacy (A1c hemoglobin reduction) and safety of the newest antidiabetic drugs (considered so due to their novelty in medical practice use), specifically DPP-4i, SGLT-2i, GLP-1 Ra, and tirzepatide. The present meta-analysis followed the protocol registered at Prospero with the CRD42022330442 registration number. The reduction in HbA1c in the DPP4-i class for tenegliptin was 95% CI −0.54 [−1.1, 0.01], p = 0.06; in the SGLT2-iclass for ipragliflozin 95% CI −0.2 [−0.87, 0.47], p = 0.55; and for tofogliflozin 95% CI 3.13 [−12.02, 18.28], p = 0.69, while for tirzepatide it was 0.15, 95% CI [−0.50, 0.80] (p = 0.65). The guidelines for treatment in type 2 DM are provided from cardiovascular outcome trials that report mainly major adverse cardiovascular events and data about efficacy. The newest antidiabetic non-insulinic drugs are reported to be efficient in lowering HbA1c, but this effect depends between classes, molecules, or patients’ age. The newest antidiabetic drugs are proven to be efficient molecules in terms of HbA1c decrease, weight reduction, and safety, but more studies are needed in order to characterize exactly their efficacy and safety profiles. Full article

(This article belongs to the Special Issue New Advances in Type 2 Diabetes and Its Complications)

► Show Figures

Journal Menu

Journal Browser

New Advances in Type 2 Diabetes and Its Complications

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI