Biomedicines

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15 pages, 486 KiB

Open AccessArticle

Material Technologies for Improved Diabetic Foot Ulcer (DFU) Treatment: A Questionnaire Study of Healthcare Professionals’ Needs

by Marian Gabriela Vargas Guerrero, Lieve Vonken, Erwin Peters, Jimmy Lucchesi and Jacobus J. C. Arts

Biomedicines 2024, 12(11), 2483; https://doi.org/10.3390/biomedicines12112483 - 29 Oct 2024

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Abstract

Background/Objectives: Diabetic foot ulcers (DFUs) are a common and severe complication of diabetic patients, with significant global prevalence and associated health burdens, including high recurrence rates, lower-limb amputations, and substantial associated economic costs. This study aimed to understand the user needs of healthcare [...] Read more.

Background/Objectives: Diabetic foot ulcers (DFUs) are a common and severe complication of diabetic patients, with significant global prevalence and associated health burdens, including high recurrence rates, lower-limb amputations, and substantial associated economic costs. This study aimed to understand the user needs of healthcare professionals treating diabetic foot ulcers for newly developed material technologies. Methods: An open-ended questionnaire was used to identify user needs, identify the limitations of current treatments, and determine the specific requirements for ideal treatment. This information was used to develop a list of key considerations for creating innovative material technologies to improve diabetic wound treatment results. Results: Most respondents indicated that they followed published treatment guidelines for DFUs but noted that treatment often required a case-specific approach. Antibiotics and surgical debridement were commonly used for infection control. The participants showed a strong preference for wound dressings with lasting antibacterial properties. Respondents identified ideal properties for new products, including ease of use, enhanced antibacterial properties, affordability, and targeted biological activity. The respondents also highlighted the importance of a holistic approach to DFU management, integrating product development with comprehensive care strategies and patient education. Conclusions: This study highlights the complexity of DFU care, emphasizing that no single product can address all treatment needs. Future materials could focus on combination therapies and specific use cases. Additionally, understanding global variations in treatment practices and educating users on the proper application of newly developed material technologies is crucial for improving the management of DFUs and patient outcomes. Full article

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

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12 pages, 798 KiB

Open AccessArticle

Diabetes Control Status and Severity of Depression: Insights from NHANES 2005–2020

by Raedeh Basiri, Yatisha Rajanala, Megan Kassem, Lawrence J. Cheskin, Cara L. Frankenfeld and Maryam S. Farvid

Biomedicines 2024, 12(10), 2276; https://doi.org/10.3390/biomedicines12102276 - 8 Oct 2024

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Abstract

Background/Objectives: Examining the risk of depression among patients with diabetes is crucial for understanding the mental health burden of this chronic condition. This study examined the likelihood of depression severity among participants in the National Health And Nutrition Examination Survey (NHANES) from 2005 [...] Read more.

Background/Objectives: Examining the risk of depression among patients with diabetes is crucial for understanding the mental health burden of this chronic condition. This study examined the likelihood of depression severity among participants in the National Health And Nutrition Examination Survey (NHANES) from 2005 to 2020, based on glycemic control status. Methods: Depression severity was categorized into three levels using the Patient Health Questionnaire-9 (PHQ-9), and glycemic control status was categorized into five groups based on prior diabetes diagnoses and hemoglobin A1c (HbA1c) levels. Using multinomial logistic regression models, the odds ratio (OR) and 95% confidence intervals (95%CIs) of various severities of depression by glycemic control status were calculated after comprehensive adjustments. Results: Out of 76,496 NHANES participants from 2005 to 2020, 37,037 individuals who met our inclusion criteria were analyzed. The likelihood of depression in individuals with prediabetes was not significantly different from those with normoglycemia. In contrast, participants with diabetes had a higher likelihood of having depression versus individuals with normoglycemia even when they kept their HbA1c within the normal range (lower than 5.7%). Among individuals with diabetes, those with HbA1c < 5.7% had a higher likelihood of mild depression (OR: 1.54, 95%CI: 1.02–2.34), while having HbA1c ≥ 10.0% was significantly associated with a greater likelihood of moderate to severe depression (OR: 1.53, 95%CI: 1.07–2.19) compared to those with HbA1c levels of 5.7–10.0%. Conclusions: Our findings highlight the need for a holistic approach to diabetes care that includes mental health considerations, especially for those who are at the extremes of the HbA1c spectrum. Full article

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

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9 pages, 233 KiB

Open AccessArticle

Neonatal Outcomes in Patients with Gestational Diabetes Mellitus Treated with Metformin: A Retrospective Study in Saudi Arabia

by Khaled H. Aburisheh, Mazen M. Barhoush, Abdulaziz N. Alahmari, Ziyad A. Altasan and Muffarah H. Alharthi

Biomedicines 2024, 12(9), 2040; https://doi.org/10.3390/biomedicines12092040 - 7 Sep 2024

Viewed by 956

Abstract

Background: Gestational diabetes mellitus (GDM) is a common endocrine disease that can occur during pregnancy, increasing the risk of fetal morbidity and mortality. Metformin is a commonly used therapeutic approach for managing GDM. However, there is controversy regarding the effects of metformin on [...] Read more.

Background: Gestational diabetes mellitus (GDM) is a common endocrine disease that can occur during pregnancy, increasing the risk of fetal morbidity and mortality. Metformin is a commonly used therapeutic approach for managing GDM. However, there is controversy regarding the effects of metformin on fetal outcomes during pregnancy. This study aimed to evaluate the safety of metformin in relation to neonatal complications, compared to treatment with insulin and/or specialized diets. Method: This was a retrospective study that included pregnant women who were diagnosed with GDM and treated with specialized diets, metformin, or insulin. Data were collected from patients’ electronic medical records and analyzed to evaluate the risk of neonatal outcomes in the metformin group compared to the others. Results: The study included 234 women with GDM. There was no difference between the metformin and insulin groups in terms of the rates of neonatal outcomes, while neonatal hypoglycemia, neonatal hyperbilirubinemia, large for gestational age, and respiratory distress were higher in the metformin group when compared to the diet group. Metformin slightly increased the risk of a lower APGAR score compared to diet alone. Conclusions: Metformin was found to be a safe therapy for the fetus when used to manage GDM, compared to insulin therapy. More randomized studies are needed to confirm these findings in the Saudi population. Full article

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

11 pages, 1703 KiB

Open AccessArticle

Study of the Effects of Deuterium-Depleted Water on the Expression of GLUT4 and Insulin Resistance in the Muscle Cell Line C2C12

by Masumi Kondo, Kaichiro Sawada, Yosuke Matsuda, Makiko Abe, Noriyuki Sanechika, Yumi Takanashi, Yoshitaka Mori, Moritsugu Kimura and Masao Toyoda

Biomedicines 2024, 12(8), 1771; https://doi.org/10.3390/biomedicines12081771 - 6 Aug 2024

Viewed by 1237

Abstract

Deuterium-depleted water (DDW) is used in the treatment of many diseases, including cancer and diabetes. To detect the effect of DDW on gene expression and activation of the insulin-responsive transporter GLUT4 as a mechanism for improving the pathology of diabetes, we investigated the [...] Read more.

Deuterium-depleted water (DDW) is used in the treatment of many diseases, including cancer and diabetes. To detect the effect of DDW on gene expression and activation of the insulin-responsive transporter GLUT4 as a mechanism for improving the pathology of diabetes, we investigated the GLUT4 expression and glucose uptake at various concentrations of DDW using the myoblast cell line C2C12 differentiated into myotubes. GLUT4 gene expression significantly increased under deuterium depletion, reaching a maximum value at a deuterium concentration of approximately 50 ppm, which was approximately nine times that of natural water with a deuterium concentration of 150 ppm. GLUT4 protein also showed an increase at similar DDW concentrations. The membrane translocation of GLUT4 by insulin stimulation reached a maximum value at a deuterium concentration of approximately 50–75 ppm, which was approximately 2.2 times that in natural water. Accordingly, glucose uptake also increased by up to 2.2 times at a deuterium concentration of approximately 50 ppm. Drug-induced insulin resistance was attenuated, and the glucose uptake was four times higher in the presence of 10 ng/mL TNF-α and three times higher in the presence of 1 μg/mL resistin at a deuterium concentration of approximately 50 ppm relative to natural water. These results suggest that DDW promotes GLUT4 expression and insulin-stimulated activation in muscle cells and reduces insulin resistance, making it an effective treatment for diabetes. Full article

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

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23 pages, 4133 KiB

Open AccessArticle

An Assessment of Semaglutide Safety Based on Real World Data: From Popularity to Spontaneous Reporting in EudraVigilance Database

by Anca Butuca, Carmen Maximiliana Dobrea, Anca Maria Arseniu, Adina Frum, Adriana Aurelia Chis, Luca Liviu Rus, Steliana Ghibu, Anca Maria Juncan, Andrei Catalin Muntean, Antonina Evelina Lazăr, Felicia Gabriela Gligor, Claudiu Morgovan and Andreea Loredana Vonica-Tincu

Biomedicines 2024, 12(5), 1124; https://doi.org/10.3390/biomedicines12051124 - 18 May 2024

Viewed by 2297

Abstract

Some glucagon-like peptide-1 receptor agonists (GLP-1 RAs), first used in the treatment of type 2 diabetes mellitus (T2DM), have been approved for the treatment of obesity in patients with or without T2DM (liraglutide—LIR, semaglutide—SEM, and tirzepatide—TIR). Social media had an important influence on [...] Read more.

Some glucagon-like peptide-1 receptor agonists (GLP-1 RAs), first used in the treatment of type 2 diabetes mellitus (T2DM), have been approved for the treatment of obesity in patients with or without T2DM (liraglutide—LIR, semaglutide—SEM, and tirzepatide—TIR). Social media had an important influence on the off-label use of GLP-1 RAs for obesity, especially for SEM. We analyzed the Google queries related to SEM to assess people’s interest in this drug. We also investigated the occurrence of adverse drug reactions (ADRs) by searching the EudraVigilance database (EV) for Individual Case Safety Reports (ICSRs) that reported SEM as the suspected drug and performed a descriptive and a disproportionality analysis. The data obtained for SEM were compared to other GLP-1 RAs. SEM had the highest proportions of searches on Google associated with the term “weight loss” and presented the lowest number of severe ADRs, but it also had the highest number of ICSRs reported in EV. Even though no unexpected safety issues have been reported for it until now, SEM has a hi3gh tendency for overdose reports. The most frequent off-label use was reported for SEM and TIR. In order to lower the risks of ADRs, the off-label use should be reduced and carefully monitored. Full article

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

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13 pages, 661 KiB

Open AccessArticle

Depressive Symptoms Associated with Peripheral Artery Disease and Predicting Mortality in Type 2 Diabetes

by Yu-Hsuan Li, Yu-Cheng Cheng, Hsiu-Chen Liu, Junyi Wu and I-Te Lee

Biomedicines 2024, 12(1), 29; https://doi.org/10.3390/biomedicines12010029 - 21 Dec 2023

Cited by 1 | Viewed by 1078

Abstract

This retrospective cohort study aimed to assess the mortality risk in patients with type 2 diabetes mellitus (DM) by screening for depressive symptoms and peripheral artery disease (PAD). We enrolled patients aged ≥60 years who had undergone assessments of both the ankle–brachial index [...] Read more.

This retrospective cohort study aimed to assess the mortality risk in patients with type 2 diabetes mellitus (DM) by screening for depressive symptoms and peripheral artery disease (PAD). We enrolled patients aged ≥60 years who had undergone assessments of both the ankle–brachial index (ABI) and the five-item Geriatric Depression Scale (GDS-5). PAD and depression were defined as ABI ≤ 0.90 and GDS-5 ≥ 1, respectively. The primary endpoint was total mortality. In 1673 enrolled patients, the prevalence of PAD was higher in those with depression than in those without depression (8.9% vs. 5.7%, p = 0.021). After a median follow-up of 56.6 months (interquartile range: 47.0–62.3 months), a total of 168 (10.0%) deaths occurred. The patients in the depression and PAD subgroup had the highest hazard ratio of mortality, followed by the PAD without depression subgroup and the depression without PAD subgroup (2.209, 95%CI: 1.158–4.217; 1.958, 95%CI: 1.060–3.618; and 1.576, 95%CI: 1.131–2.196; respectively) in comparison to the patients without depression and PAD after adjustment for associated factors. In conclusion, a combination of depression and PAD predicted the highest mortality risk. Screening for depression and PAD is recommended in patients aged ≥60 years with type 2 DM. Full article

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

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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

by 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

Cited by 9 | Viewed by 1686

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 [...] Read more.

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

by Tiantian Wu, Qiang Wang, Changsheng Pu and Keming Zhang

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

Viewed by 1105

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 [...] Read more.

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

by Aleksejs Fedulovs, Lilian Tzivian, Polina Zalizko, Santa Ivanova, Renāte Bumane, Jana Janeviča, Lelde Krūzmane, Eduards Krustins and Jelizaveta Sokolovska

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

Cited by 2 | Viewed by 1748

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 [...] Read more.

(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

by 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

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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 [...] Read more.

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

by Tao Liu, Xing-Xing Zhuang and Jia-Rong Gao

Biomedicines 2023, 11(9), 2454; https://doi.org/10.3390/biomedicines11092454 - 4 Sep 2023

Cited by 4 | Viewed by 2280

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) [...] Read more.

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

by Salvatore Greco, Vincenzo M. Monda, Giorgia Valpiani, Nicola Napoli, Carlo Crespini, Fabio Pieraccini, Anna Marra and Angelina Passaro

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

Viewed by 1524

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 [...] Read more.

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

Jump to: Research, Other

27 pages, 3213 KiB

Open AccessReview

Modern Challenges in Type 2 Diabetes: Balancing New Medications with Multifactorial Care

by Alfredo Caturano, Raffaele Galiero, Maria Rocco, Giuseppina Tagliaferri, Alessia Piacevole, Davide Nilo, Giovanni Di Lorenzo, Celestino Sardu, Erica Vetrano, Marcellino Monda, Raffaele Marfella, Luca Rinaldi and Ferdinando Carlo Sasso

Biomedicines 2024, 12(9), 2039; https://doi.org/10.3390/biomedicines12092039 - 7 Sep 2024

Cited by 1 | Viewed by 1759

Abstract

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by insulin resistance and progressive beta cell dysfunction, presenting substantial global health and economic challenges. This review explores recent advancements in diabetes management, emphasizing novel pharmacological therapies and their physiological mechanisms. [...] Read more.

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by insulin resistance and progressive beta cell dysfunction, presenting substantial global health and economic challenges. This review explores recent advancements in diabetes management, emphasizing novel pharmacological therapies and their physiological mechanisms. We highlight the transformative impact of Sodium-Glucose Cotransporter 2 inhibitor (SGLT2i) and Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA), which target specific physiological pathways to enhance glucose regulation and metabolic health. A key focus of this review is tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors. Tirzepatide illustrates how integrating innovative mechanisms with established physiological pathways can significantly improve glycemic control and support weight management. Additionally, we explore emerging treatments such as glimins and glucokinase activators (GKAs), which offer novel strategies for enhancing insulin secretion and reducing glucose production. We also address future perspectives in diabetes management, including the potential of retatrutide as a triple receptor agonist and evolving guidelines advocating for a comprehensive, multifactorial approach to care. This approach integrates pharmacological advancements with essential lifestyle modifications—such as dietary changes, physical activity, and smoking cessation—to optimize patient outcomes. By focusing on the physiological mechanisms of these new therapies, this review underscores their role in enhancing T2DM management and highlights the importance of personalized care plans to address the complexities of the disease. This holistic perspective aims to improve patient quality of life and long-term health outcomes. Full article

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

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13 pages, 756 KiB

Open AccessReview

Stress and the CRH System, Norepinephrine, Depression, and Type 2 Diabetes

by Michele Perrelli, Pruthvi Goparaju, Teodor T. Postolache, Laura del Bosque-Plata and Claudia Gragnoli

Biomedicines 2024, 12(6), 1187; https://doi.org/10.3390/biomedicines12061187 - 27 May 2024

Cited by 3 | Viewed by 1775

Abstract

Major depressive disorder (MDD) increases the risk of type 2 diabetes (T2D) by 60% in untreated patients, and hypercortisolism is common in MDD as well as in some patients with T2D. Patients with MDD, despite hypercortisolism, show inappropriately normal levels of corticotropin-releasing hormone [...] Read more.

Major depressive disorder (MDD) increases the risk of type 2 diabetes (T2D) by 60% in untreated patients, and hypercortisolism is common in MDD as well as in some patients with T2D. Patients with MDD, despite hypercortisolism, show inappropriately normal levels of corticotropin-releasing hormone (CRH) and plasma adrenocorticotropin (ACTH) in the cerebrospinal fluid, which might implicate impaired negative feedback. Also, a positive feedback loop of the CRH–norepinephrine (NE)–CRH system may be involved in the hypercortisolism of MDD and T2D. Dysfunctional CRH receptor 1 (CRHR1) and CRH receptor 2 (CRHR2), both of which are involved in glucose regulation, may explain hypercortisolism in MDD and T2D, at least in a subgroup of patients. CRHR1 increases glucose-stimulated insulin secretion. Dysfunctional CRHR1 variants can cause hypercortisolism, leading to serotonin dysfunction and depression, which can contribute to hyperglycemia, insulin resistance, and increased visceral fat, all of which are characteristics of T2D. CRHR2 is implicated in glucose homeostasis through the regulation of insulin secretion and gastrointestinal functions, and it stimulates insulin sensitivity at the muscular level. A few studies show a correlation of the CRHR2 gene with depressive disorders. Based on our own research, we have found a linkage and association (i.e., linkage disequilibrium [LD]) of the genes CRHR1 and CRHR2 with MDD and T2D in families with T2D. The correlation of CRHR1 and CRHR2 with MDD appears stronger than that with T2D, and per our hypothesis, MDD may precede the onset of T2D. According to the findings of our analysis, CRHR1 and CRHR2 variants could modify the response to prolonged chronic stress and contribute to high levels of cortisol, increasing the risk of developing MDD, T2D, and the comorbidity MDD-T2D. We report here the potential links of the CRH system, NE, and their roles in MDD and T2D. Full article

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

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Open AccessReview

Role of Oxidative Stress in Tuberculosis Meningitis Infection in Diabetics

by Inesa Navasardyan, Stephanie Yeganyan, Helena Nguyen, Payal Vaghashia, Selvakumar Subbian and Vishwanath Venketaraman

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

Cited by 1 | Viewed by 1895

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, [...] Read more.

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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16 pages, 2537 KiB

Open AccessSystematic Review

Comparative Efficacy and Safety of Weekly GLP-1/GIP Agonists vs. Weekly Insulin in Type 2 Diabetes: A Network Meta-Analysis of Randomized Controlled Trials

by Hazem Ayesh, Sajida Suhail, Suhail Ayesh and Kevin Niswender

Biomedicines 2024, 12(9), 1943; https://doi.org/10.3390/biomedicines12091943 - 23 Aug 2024

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Abstract

Background: Diabetes mellitus (DM) significantly impacts global health due to its complications and the economic burden it places on healthcare systems. The rise of novel once-weekly diabetes medications with different mechanisms of action necessitates an evaluation of their relative efficacy and safety. Objectives: [...] Read more.

Background: Diabetes mellitus (DM) significantly impacts global health due to its complications and the economic burden it places on healthcare systems. The rise of novel once-weekly diabetes medications with different mechanisms of action necessitates an evaluation of their relative efficacy and safety. Objectives: This study compares the efficacy and tolerability of once-weekly insulin analogs (icodec and BIF) with once-weekly GLP-1/GIP agonists (semaglutide, exenatide, tirzepatide, dulaglutide) in managing type 2 diabetes mellitus (T2DM). Methods: We conducted a network meta-analysis (NMA) using data from randomized controlled trials (RCTs) that compared these treatments with a baseline of daily basal insulin. Primary outcomes included changes in HbA1c, body weight, and tolerability. Results: The analysis integrated data from 25 RCTs, involving 18,257 patients. Tirzepatide significantly outperformed other treatments in reducing HbA1c and promoting weight loss. Weekly insulins, compared to GLP-1/GIP agonists, showed a more tolerable profile and were beneficial for certain patient demographics emphasizing weight stability. Conclusion: Our findings suggest that while once-weekly GLP-1/GIP agonists provide superior glycemic control and weight management, weekly insulins offer viable options for patients prioritizing fewer side effects and weight stability. This comprehensive comparison aids in refining personalized treatment strategies for T2DM management. Full article

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

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