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Molecular Diagnosis and Treatments of Diabetes Mellitus: 2nd Edition

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

Deadline for manuscript submissions: 20 April 2026 | Viewed by 1776

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Dr. Mihail Virgil Boldeanu

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Department of Immunology, University of Medicine and Pharmacy, 200349 Craiova, Romania
Interests: pancreatic disorders; polymorphism; genotype; VEGFR-2; vitamin C; ascorbic acid; diabetes mellitus; periodontal disease; antigens; monoclonal antibody; NLRP3; citokines; pro-angiogenic factors; chronic periodontitis; case-control; matrix metalloproteinase; periodontal pa-rameters
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Dear Colleagues,

In recent years, several studies conducted among different populations, as well as on mice, have revealed new knowledge about the role of neurotransmission and inflammation in type 2 diabetes mellitus (T2DM) that is not currently included in protocols.

Thus, a more solid functional link between these neurotransmitters and markers of inflammation must be established. To better understand and describe this complex association, further large-scale studies among different patient groups are needed.

Epidemiological studies have established an association between inflammatory molecular biomarkers and the occurrence of T2DM and its complications. Because fat cells, macrophages, and other immune cells in the expanding adipose tissue interact with each other, it seems that adipose tissue is a major source of these molecular biomarkers. The identification of key molecular triggers of inflammation in T2DM is still poorly understood. The inflammatory response probably plays a part in the development of T2DM by making insulin less effective. This is made worse when hyperglycemia is present, which makes diabetes complications worse over time. Targeting inflammatory molecular pathways could be a component of strategies to prevent and control diabetes and its associated complications.

Serotonin, released by intestinal enterochromaffin cells, appears to regulate energy homeostasis through peripheral mechanisms. Serotonergic effects on energy balance lead to secondary effects on glucose homeostasis, based on a well-established link between obesity and insulin resistance.

This Special Issue invites research papers that highlight the involved DM molecular markers and pathways and outline perspectives for personalized DM diagnosis and treatment. Systemizing reviews on these topics are also welcome.

Dr. Mihail Virgil Boldeanu
Guest Editor

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Keywords

metabolic disorders
diabetes mellitus
inflammation
neurotransmitter
inflammatory biomarkers
molecular target
molecular diagnostics
therapeutics
insulin resistance

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Molecular Diagnosis and Treatments of Diabetes Mellitus in International Journal of Molecular Sciences (10 articles)

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Research

26 pages, 967 KB

Open AccessArticle

Neurotransmitter Levels (Dopamine, Epinephrine, Norepinephrine, Serotonin) and Associations with Lipid Profiles in Patients with Prediabetes or Newly Diagnosed Type 2 Diabetes Mellitus

by Roxana Viorela Ahrițculesei, Lidia Boldeanu, Mohamed-Zakaria Assani, Adina Mitrea, Cosmin Vasile Obleaga, Ionela Mihaela Vladu, Diana Clenciu, Mihail Virgil Boldeanu and Cristin Constantin Vere

Int. J. Mol. Sci. 2025, 26(20), 10068; https://doi.org/10.3390/ijms262010068 - 16 Oct 2025

Viewed by 131

Abstract

Neurotransmitters play a pivotal role not only in central nervous system signaling but also in the regulation of systemic energy metabolism, insulin sensitivity, and cardiovascular function. The contribution of neuroendocrine dysregulation to the development of type 2 diabetes mellitus (T2DM) is increasingly being recognized; however, the interplay between neurotransmitter levels and lipid/insulin resistance profiles in T2DM and prediabetes (PreDM) remains poorly characterized. We evaluated serum dopamine (DA), norepinephrine (NE), epinephrine (EPI), and serotonin (ST) in 110 individuals with PreDM (n = 40) or newly diagnosed T2DM (n = 70). Extended metabolic profiling included HbA1c, lipid panels, and insulin resistance indices (triglyceride-to-glucose index (TyG), TyG-derived indices). Neurotransmitter levels were compared across body mass index (BMI) categories, gender, and glycosylated hemoglobin A1c (HbA1c) quartiles. We applied multivariable linear regression (MLR) adjusted for body mass index (BMI), age, sex, lipids, penalized logistic regression (predicting T2DM status), and exploratory Spearman correlations with False Discovery Rate (FDR) correction. All four neurotransmitters were significantly higher in T2DM versus PreDM (p < 0.001). In T2DM patients, DA and NE levels increased across HbA1c quartiles, and NE levels were significantly higher in quartile 3 compared to quartile 2 (p = 0.045). In multivariable models, T2DM status was the only consistent predictor of neurotransmitter elevations. Logistic regression identified ST (OR = 8.70) and NE (OR = 3.76) as key discriminators of T2DM status, in addition to HbA1c. Exploratory correlation analyses in T2DM showed trends between EPI and insulin resistance indices (TyG adjusted for waist circumference (TyG-WC), TyG adjusted for waist-to-height ratio (TyG-WHtR)) and between DA and low-density lipoprotein cholesterol (LDL-C), although these did not survive to FDR correction. Neurotransmitter levels are elevated in T2DM and correlate with glycemic and metabolic profiles, suggesting early neuroendocrine involvement in the pathogenesis of diabetes. Serotonin and norepinephrine may serve as adjunctive biomarkers for disease stratification, meriting further prospective and mechanistic investigation. Full article

(This article belongs to the Special Issue Molecular Diagnosis and Treatments of Diabetes Mellitus: 2nd Edition)

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21 pages, 1551 KB

Open AccessArticle

Relationship Between Insulin Resistance Indicators and Type 2 Diabetes Mellitus in Romania

by Adela-Gabriela Ştefan, Diana Clenciu, Ionela-Mihaela Vladu, Adina Mitrea, Diana-Cristina Protasiewicz-Timofticiuc, Maria-Magdalena Roşu, Theodora-Claudia Gheonea, Beatrice-Elena Vladu, Ion-Cristian Efrem, Delia-Viola Reurean Pintilei, Eugen Moţa and Maria Moţa

Int. J. Mol. Sci. 2025, 26(20), 9888; https://doi.org/10.3390/ijms26209888 - 11 Oct 2025

Viewed by 237

Abstract

Diabetes mellitus (DM) is a complex chronic disease, with a prevalence that has reached alarming proportions in recent decades. In this study, we aimed to analyze the association of type 2 diabetes mellitus (T2DM) with certain insulin resistance (IR) indicators, according to the gender of the participants enrolled in the PREDATORR study. Biomarkers such as the triglyceride–glucose (TyG) index and its derivates, triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-c), and metabolic score for insulin resistance (METS-IR), as well as recent indicators, like cholesterol, HDL, the glucose (CHG) index and its derivates, CHG–body mass index (CHG-BMI), and CHG–waist circumference (CHG-WC), as well as its newly proposed derivates, such as CHG–waist-to-height ratio (CHG-WHtR), CHG–neck circumference (CHG-NC), and CHG–neck-to-height ratio (NHtRs were analyzed in 2080 subjects, divided into two groups, according to gender). Univariate and multivariate logistic regression was used to identify the relationships between IR indicators and T2DM. Regardless of gender, all the analyzed indicators presented statistically significantly higher values in T2DM (+) compared to T2DM (−). For both studied groups, CHG–WHtR had the largest AUROC curve: in males, the AUROC curve was 0.809, the cut-off value being 3.22, with a 70.7% sensitivity and 75.3% specificity; in females, the AUROC curve was 0.840, the cut-off value was 3.20, with a 79.3% sensitivity and 75.5% specificity, respectively. Regardless of gender, the age-adjusted model for multivariate logistic regression analysis demonstrated that TyG and CHG were predictive factors for T2DM. Full article

(This article belongs to the Special Issue Molecular Diagnosis and Treatments of Diabetes Mellitus: 2nd Edition)

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13 pages, 239 KB

Open AccessArticle

Improvement in Glucometric Outcomes After Control-IQ Initiation in Pediatric and Adolescent Type 1 Diabetes Patients: The Impact of Basal Time in Range

by Ana Gómez-Perea, Alfonso Lendínez-Jurado, Silvia Gallego-Gutiérrez, Fuensanta Guerrero-Del-Cueto, Ana García-Ruiz, Cristina López-De La Torre, Fernando Cardona-Díaz and Isabel Leiva-Gea

Int. J. Mol. Sci. 2025, 26(19), 9638; https://doi.org/10.3390/ijms26199638 - 2 Oct 2025

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Abstract

The development of closed-loop systems represents an evolutionary advance in the management of patients with type 1 diabetes (T1D). This study aimed to analyze the impact of the Control-IQ advanced hybrid closed-loop (AHCL) system on glucometric outcomes in a pediatric and adolescent population with T1D, comparing results with baseline values and assessing the influence of baseline Time in Range (TIR) on glycemic control in children under 6 years old over a 12-month period. A 12-month prospective analysis was conducted in 26 patients with T1D (aged 2–15 years) initiating the Control-IQ system. Glucometric variables were assessed at baseline (before system implementation) and at 1, 3, 6, and 12 months post-implementation. A subgroup analysis was performed in patients under 6 years old (n = 13), to evaluate the relationship between basal TIR and glucometric outcomes during the follow-up. TIR increased significantly from 62.04% at baseline to 72.50% at one month (from 57.58% to 66.18% in patients under 6 years), with this improvement sustained throughout follow-up. Time in hyperglycemia 180–250 mg/dL (TAR1) also showed significant improvement (26.84% to 17.40% at one month; 28.66% to 20.09% in patients under 6 years), with significant reductions maintained at all timepoints. Stratification according to the proportion of patients meeting consensus targets revealed significant improvements in TIR and TAR2 at 1 and 12 months in the overall cohort, though not in the under-6 subgroup. Significant differences in TIR and coefficient of variation (CV) were observed based on baseline TIR categorization (<70% vs. ≥70%). Our study revealed a significant enhancement in TIR and time spent in hyperglycemia from the first month after the implementation of the closed-loop system, which was maintained at 12 months, in both the overall cohort and the subgroup under 6 years old. In this younger subgroup, baseline TIR predicted subsequent glycemic control, with higher baseline TIR associated with better long-term outcomes in both TIR and CV. Full article

(This article belongs to the Special Issue Molecular Diagnosis and Treatments of Diabetes Mellitus: 2nd Edition)

12 pages, 1831 KB

Open AccessArticle

Serum Vitamin D Levels as Predictors of Response to Intravitreal Anti-VEGF Therapy in Diabetic Macular Edema: A Clinical Correlation Study

by Nejla Dervis, Sanda Jurja, Tatiana Chisnoiu, Cristina Maria Mihai and Ana Maria Stoica

Int. J. Mol. Sci. 2025, 26(17), 8481; https://doi.org/10.3390/ijms26178481 - 1 Sep 2025

Viewed by 597

Abstract

Our study explored the role of serum 25-hydroxyvitamin D [25(OH)D] levels as an indicator of response to intravitreal anti–vascular endothelial growth factor (anti-VEGF) therapy in patients with diabetic macular edema (DME), highlighting functional and anatomical outcomes linked to systemic biomarker profiles. In a cohort of treatment-naive diabetic patients, vitamin D status was correlated with post-treatment changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA), illustrating layered therapeutic responses among deficient, insufficient, and sufficient vitamin D groups. Functional gains, measured as improvements in decimal BCVA, and anatomical improvements, defined by CMT reduction via spectral-domain optical coherence tomography (SD-OCT), were primarily detected in patients with sufficient vitamin D levels. Remarkably, patients with serum 25(OH)D ≥ 30 ng/mL revealed complete dual-response rates, while those in the deficient group manifested partial therapeutic efficacy, supporting the immunoangiogenic modulatory role of vitamin D. Statistical associations exposed a tight linear connection between baseline and final visual acuity and a pronounced inverse relationship between CMT and final vision, suggesting that vitamin D may play a role in treatment-mediated structural recovery. These results may imply that low vitamin D levels lead to subclinical endothelial dysfunction and impaired retinal barrier repair, possibly through dysregulated anti–vascular endothelial growth factor (anti-VEGF) signaling, chronic inflammation, and oxidative stress. Our findings underscore the need for and importance of further research of vitamin D status as an adjunctive biomarker in the clinical approach of personalized DME and validates the potential of circulating vitamin D evaluation in therapeutic classification and predictive eye care. Full article

(This article belongs to the Special Issue Molecular Diagnosis and Treatments of Diabetes Mellitus: 2nd Edition)

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