Setting Ranges in Potential Biomarkers for Type 2 Diabetes Mellitus Patients Early Detection By Sex-An Approach with Machine Learning Algorithms.

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic diseases in the world and poses a significant public health challenge. Early detection and management of this metabolic disorder is crucial to prevent complications and improve outcomes. This paper aims to find core differences in male and female markers to detect T2DM by their clinic and anthropometric features, seeking out ranges in potential biomarkers identified to provide useful information as a pre-diagnostic tool whie excluding glucose-related biomarkers using machine learning (ML) models. We used a dataset containing clinical and anthropometric variables from patients diagnosed with T2DM and patients without TD2M as control. We applied feature selection with three different techniques to identify relevant biomarker models: an improved recursive feature elimination (RFE) evaluating each set from all the features to one feature with the Akaike information criterion (AIC) to find optimal outputs; Least Absolute Shrinkage and Selection Operator (LASSO) with glmnet; and Genetic Algorithms (GA) with GALGO and forward selection (FS) applied to GALGO output. We then used these for comparison with the AIC to measure the performance of each technique and collect the optimal set of global features. Then, an implementation and comparison of five different ML models was carried out to identify the most accurate and interpretable one, considering the following models: logistic regression (LR), artificial neural network (ANN), support vector machine (SVM), k-nearest neighbors (KNN), and nearest centroid (Nearcent). The models were then combined in an ensemble to provide a more robust approximation. The results showed that potential biomarkers such as systolic blood pressure (SBP) and triglycerides are together significantly associated with T2DM. This approach also identified triglycerides, cholesterol, and diastolic blood pressure as biomarkers with differences between male and female actors that have not been previously reported in the literature. The most accurate ML model was selection with RFE and random forest (RF) as the estimator improved with the AIC, which achieved an accuracy of 0.8820. In conclusion, this study demonstrates the potential of ML models in identifying potential biomarkers for early detection of T2DM, excluding glucose-related biomarkers as well as differences between male and female anthropometric and clinic profiles. These findings may help to improve early detection and management of the T2DM by accounting for differences between male and female subjects in terms of anthropometric and clinic profiles, potentially reducing healthcare costs and improving personalized patient attention. Further research is needed to validate these potential biomarkers ranges in other populations and clinical settings.

Branched-Chain and Aromatic Amino Acids, Type 2 Diabetes, and Cardiometabolic Risk Factors among Puerto Rican Adults.

(1) Background: Branched-chain and aromatic amino acids (BCAAs/AAAs) have been considered as markers of type 2 diabetes (T2D); however, studies on associations between these metabolites and T2D and cardiometabolic traits in Hispanic populations are limited. The aim of this study was to examine the associations between baseline BCAAs (isoleucine, leucine, valine)/AAAs (phenylalanine, tyrosine) and prevalent and incident T2D, as well as baseline and longitudinal (2 year) changes in cardiometabolic traits (measures of glycemia, dyslipidemia, inflammation, and obesity) in two large cohorts of adults of Puerto Rican descent. (2) Methods: We included participants of the Boston Puerto Rican Health Study (BPRHS, n = 670) and San Juan Overweight Adult Longitudinal study (SOALS, n = 999) with available baseline metabolite and covariate data. T2D diagnosis was defined based on American Diabetes Association criteria. Multivariable logistic (for baseline T2D), Poisson (for incident T2D), and linear (for cardiometabolic traits) regression models were used; cohort-specific results were combined in the meta-analysis and adjusted for multiple comparisons. (3) Results: Higher baseline BCAAs were associated with higher odds of prevalent T2D (OR1SD BCAA score = 1.46, 95% CI: 1.34-1.59, p < 0.0001) and higher risk of incident T2D (IRR1SD BCAA score = 1.24, 95% CI: 1.13-1.37, p < 0.0001). In multivariable longitudinal analysis, higher leucine and valine concentrations were associated with 2-year increase in insulin (beta 1SD leucine = 0.37 mcU/mL, 95% CI: 0.11-0.63, p < 0.05; beta 1SD valine = 0.43 mcU/mL, 95% CI: 0.17-0.68, p < 0.01). Tyrosine was a significant predictor of incident T2D (IRR = 1.31, 95% CI: 1.09-1.58, p < 0.05), as well as 2 year increases in HOMA-IR (beta 1SD tyrosine = 0.13, 95% CI: 0.04-0.22, p < 0.05) and insulin concentrations (beta 1SD tyrosine = 0.37 mcU/mL, 95% CI: 0.12-0.61, p < 0.05). (4) Conclusions: Our results confirmed the associations between BCAAs and prevalent and incident T2D, as well as concurrent measures of glycemia, dyslipidemia, and obesity, previously reported in predominantly White and Asian populations. Baseline leucine, valine, and tyrosine were predictors of 2 year increases in insulin, whereas tyrosine was a significant predictor of deteriorating insulin resistance over time. Our study suggests that BCAAs and tyrosine could serve as early markers of future glycemic changes in Puerto Ricans.

Virtual and in Vitro Screening Employing a Repurposing Approach Reveal 13-cis-Retinoic Acid is a PTP1B Inhibitor.

Current treatments for type 2 diabetes (T2D) mainly rely on exercise, dietary control, and anti-diabetic drugs to enhance insulin secretion and improve insulin sensitivity. However, there is a need for more therapeutic options, as approved drugs targeting different pharmacological objectives are still unavailable. One potential target that has attracted attention is the protein tyrosine phosphatase 1B (PTP1B), which negatively regulates the insulin signaling pathway. In this work, a comprehensive computational screening was carried out using cheminformatics and molecular docking on PTP1B, employing a rigorous repurposing approach. The screening involved approved drugs and compounds under research as anti-diabetics that bind to targets such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and α-glucosidase. Several computational hits were then meticulously tested in vitro against PTP1B, with 13-cis-retinoic acid (3a) showing an IC50 of 0.044 mM and competitive inhibition. Molecular dynamics studies further confirmed that 3a can bind to the catalytic binding site of PTP1B. Finally, 3a is the first time it has been reported as an inhibitor of PTP1B, making it a potentially valuable candidate for further studies in D2T treatment.

Identification of differentially expressed genes, pathways, and immune infiltration in diabetes.

This study aimed to perform exhaustive bioinformatic analysis by using GSE29221 micro-array maps obtained from healthy controls and Type 2 Diabetes (T2DM) patients. Raw data are downloaded from the Gene Expression Omnibus database and processed by the limma package in R software to identify Differentially Expressed Genes (DEGs). Gene ontology functional analysis and Kyoto Gene Encyclopedia and Genome Pathway analysis are performed to determine the biological functions and pathways of DEGs. A protein interaction network is constructed using the STRING database and Cytoscape software to identify key genes. Finally, immune infiltration analysis is performed using the Cibersort method. This study has implications for understanding the underlying molecular mechanism of T2DM and provides potential targets for further research.

Antidiabetic drugs in Parkinson's disease.

This review explores the intricate connections between type 2 diabetes (T2D) and Parkinson's disease (PD), both prevalent chronic conditions that primarily affect the aging population. These diseases share common early biochemical pathways that contribute to tissue damage. This manuscript also systematically compiles potential shared cellular mechanisms between T2D and PD and discusses the literature on the utilization of antidiabetic drugs as potential therapeutic options for PD. This review encompasses studies investigating the experimental and clinical efficacy of antidiabetic drugs in the treatment of Parkinson's disease, along with the proposed mechanisms of action. The exploration of the benefits of antidiabetic drugs in PD presents a promising avenue for the treatment of this neurodegenerative disorder.

Association of BMI and WC for insulin resistance and type 2 diabetes among Brazilian adolescents.

OBJECTIVE: To investigate how body mass index (BMI) and waist circumference (WC) may be associated with insulin resistance and type 2 diabetes (T2DM) in Brazilian adolescents. METHODS: Cross-sectional study using data from the Brazilian Study of Cardiovascular Risks in Adolescents (ERICA) including adolescents aged 12-17 years. The relationship between adiposity and T2DM was investigated using ordinal logistic regression models. To study the association between adiposity categories and the occurrence of insulin resistance, linear regression models were used. RESULTS: The prevalence of T2DM for the same BMI category did not increase with the presence of high WC. Regarding insulin resistance, for the same BMI categories, having a high WC resulted in a higher prevalence of insulin resistance (HOMA-IR). The only groups significantly associated with prediabetes and T2DM were those with obesity by BMI with elevated WC (POR 1.68, 95 % CI 1.45; 1.94) and obesity with normal WC (POR 1.58, 95 % CI 1.01; 2.46). Similar findings were observed concerning insulin resistance, where the increased WC had its greatest effect when associated with obesity by BMI (ß Coefficient 2.20, 95 % CI 1.89; 2.50). CONCLUSION: The combination of BMI and WC is better for assessing adolescents at risk of developing T2DM.

Factors associated with vitamin D deficiency in health care workers exposed to SARS-CoV-2: a cross-sectional study.

Introduction: Globally, up to 76.6% of the population may be affected by vitamin D (VD) deficiency, which has been linked to increased morbidity and mortality from COVID-19. This underscores the importance of further research into VD supplementation, particularly for health care workers, who are at higher risk due to indoor work environments and dietary challenges associated with shift schedules. Objective: This study aimed to identify factors associated with VD deficiency in Mexican health care workers exposed to SARS-CoV-2. Materials and methods: We conducted a cross-sectional study from June 2020 to January 2021 among frontline health care workers treating hospitalized COVID-19 patients. Blood samples were collected to measure 25-hydroxy VD levels via radioimmunoassay. We also assessed previous COVID-19 infection and comorbidities that could influence VD levels. Results: The study included 468 health care workers. The median serum VD concentration was 16.6 ng/mL. VD deficiency was found in 69.4% (n = 325) of participants, while only 5.1% (n = 24) had normal levels. Those with type 2 diabetes (13.3 ng/mL vs. 17.1 ng/mL) or obesity (15.7 ng/mL vs. 17.1 ng/mL) had significantly lower VD levels than their counterparts (p < 0.001 and p = 0.049, respectively). No significant differences were found among participants with high blood pressure. Multivariate analysis revealed that type 2 diabetes was independently associated with VD deficiency. Conclusion: There is a high prevalence of VD deficiency among health care workers, which is potentially linked to both personal health factors and occupational conditions.

Electronic Glycemic Management System Improved Glycemic Control and Reduced Complications in Patients With Diabetes Undergoing Coronary Artery Bypass Surgery: A Randomized Controlled Trial.

BACKGROUND: In-hospital hyperglycemia poses significant risks for patients with diabetes mellitus undergoing coronary artery bypass graft (CABG) surgery. Electronic glycemic management systems (eGMSs) like InsulinAPP offer promise in standardizing and improving glycemic control (GC) in these settings. This study evaluated the efficacy of the InsulinAPP protocol in optimizing GC and reducing adverse outcomes post-CABG. METHODS: This prospective, randomized, open-label study was conducted with 100 adult type 2 diabetes mellitus (T2DM) patients post-CABG surgery, who were randomized into two groups: conventional care (gCONV) and eGMS protocol (gAPP). The gAPP used InsulinAPP for insulin therapy management, whereas the gCONV received standard clinical care. The primary outcome was a composite of hospital-acquired infections, renal function deterioration, and symptomatic atrial arrhythmia. Secondary outcomes included GC, hypoglycemia incidence, hospital stay length, and costs. RESULTS: The gAPP achieved lower mean glucose levels (167.2 ± 42.5 mg/dL vs 188.7 ± 54.4 mg/dL; P = .040) and fewer patients-day with BG above 180 mg/dL (51.3% vs 74.8%, P = .011). The gAPP received an insulin regimen that included more prandial bolus and correction insulin (either bolus-correction or basal-bolus regimens) than the gCONV (90.3% vs 16.7%). The primary composite outcome occurred in 16% of gAPP patients compared with 58% in gCONV (P < .010). Hypoglycemia incidence was lower in the gAPP (4% vs 16%, P = .046). The gAPP protocol also resulted in shorter hospital stays and reduced costs. CONCLUSIONS: The InsulinAPP protocol effectively optimizes GC and reduces adverse outcomes in T2DM patients' post-CABG surgery, offering a cost-effective solution for inpatient diabetes management.

Insulin resistance in nonobese type 2 diabetic Goto Kakizaki rats is associated with a proinflammatory T lymphocyte profile.

Goto-Kakizaki (GK) rats develop a well-defined insulin resistance (IR) and type 2 diabetes mellitus (T2DM) without presenting obesity. The lymphocyte profile in nonobese diabetic conditions is not yet characterized. Therefore, GK rats were chosen to explore T lymphocyte (TL) dynamics at various stages (21, 60, and 120 days) compared to Wistar rats. GK rats exhibit progressive disruption of glucose regulation, with early glucose intolerance at 21 days and reduced insulin sensitivity at 60 days, confirming IR. Glucose transporter 1 (GLUT1) expression was consistently elevated in GK rats, suggesting heightened TL activation. T-regulatory lymphocyte markers diminished at 21 days. However, GK rats showed increased Th1 markers and reduced Gata-3 expression (crucial for Th2 cell differentiation) at 120 days. These findings underscore an early breakdown of anti-inflammatory mechanisms in GK rats, indicating a proinflammatory TL profile that may worsen chronic inflammation in T2DM.

Efficiency of periodontal treatment to improve type 2 diabetes mellitus outcomes: A systematic review and meta-analysis of economic evaluations.

BACKGROUND: To assess the efficiency of periodontal treatment (PT) in improving diabetes-related outcomes in adults with type 2 diabetes mellitus (T2DM) and periodontitis, providing an updated and comprehensive synthesis from economic evaluations (EE). METHODS: Seven databases and one register were independently searched by two reviewers for articles published up to 8 May 2024. Studies that assessed the efficiency of PT versus no treatment or other dental treatments were included. Risk of bias was assessed using the Cochrane RoB 2, ROBINS-I and ECOBIAS tools for the first stage of EE and the CHEERS checklist and NICE quality appraisal tool for overall EE. Qualitative and quantitative syntheses of the articles were conducted and assessed using the GRADE approach. RESULTS: Eleven studies were included. PT reduces total healthcare costs, including inpatient and outpatient, diabetes-related costs and other drug costs (low to moderate certainty). A total incremental net benefit of USD 12 348 (2022 currency, 95% CI 12 195-12 500) was estimated from three high-quality model-based cost-utility analyses (high certainty). DISCUSSION: The inclusion of PT in the comprehensive treatment of patients with T2DM and periodontitis is cost-effective. Future research is required to ensure the transferability of these findings and inform decision makers from different countries. REGISTRATION: PROSPERO CRD42023443146.

Pancreatic beta cell function and insulin resistance profiles in first-degree relatives of patients with prediabetes and type 2 diabetes.

AIMS: To evaluate insulin secretion and insulin resistance profiles in individuals with family history of prediabetes and type 2 diabetes. METHODS: This was a cross-sectional study to evaluate clinical and metabolic profiles between individuals with type 2 diabetes, prediabetes and their relatives. There were 911 subjects divided into five groups: (i) normoglycemic (NG), (ii) type 2 diabetes, (iii) prediabetes, (iv) first-degree relatives of patients with type 2 diabetes (famT2D), and (v) first-degree relatives of patients with prediabetes (famPD); anthropometrical, biochemical and nutritional evaluation, as well as insulin resistance and pancreatic beta cell function measurement was performed by oral glucose tolerance to compare between groups. RESULTS: The most prevalent type 2 diabetes risk factors were dyslipidemia (81%), family history of type 2 diabetes (76%), central obesity (73%), male sex (63%), and sedentary lifestyle (60%), and most of them were progressively associated to prediabetes and type 2 diabetes groups. Insulin sensitivity was lower in famT2D groups in comparison to NG group (p < 0.0001). FamPD and famT2D had a 10% lower pancreatic beta cell function (DI) than the NG group (NG group 2.78 ± 1.0, famPD 2.5 ± 0.85, famT2D 2.4 ± 0.75, p˂0.001). CONCLUSIONS: FamPD and famT2D patients had lower pancreatic beta cell function than NG patients, highlighting that defects in insulin secretion and insulin sensitivity appear long time before the development of hyperglycemia in patients genetically predisposed.

Family out-of-pocket expenditure for type 2 diabetes mellitus care and percentage of family income.

BACKGROUND: Type 2 diabetes has economic implications involving family income and out-of-pocket spending. OBJECTIVE: Determine family out-of-pocket expenditure for type 2 diabetes mellitus care and percentage of family income. MATERIAL AND METHODS: Study of family out-of-pocket spending in families with patients with type 2 diabetes treated at primary care level. Out-of-pocket expenses included expenses for transportation, food-drinks, and external medications. Family income corresponded to the total economic income contributed by family members. The percentage of out-of-pocket spending in relation to family income was identified with the relationship between these two variables. Statistical analysis included averages and percentages. RESULTS: The annual family out-of-pocket expenditure on transportation was $2,621.24, the family out-of-pocket expenditure on food and beverages was $1,075.67, and the family out-of-pocket expenditure on external medications was $722.08. The total annual family out-of-pocket expense was $4,418.89 and corresponds to 4.73% of family income. CONCLUSION: The family out-of-pocket expense in the family with a patient with diabetes mellitus 2 was $4,418.89 and represents 4.73% of the family income.

ANTECEDENTES: La diabetes tipo 2 tiene implicaciones económicas en el ingreso familiar y el gasto de bolsillo. OBJETIVO: Determinar el gasto de bolsillo familiar en la atención de la diabetes mellitus tipo 2 y el porcentaje que representa en el ingreso familiar. MATERIAL Y MÉTODOS: Estudio de gasto de bolsillo de las familias con pacientes con diabetes tipo 2 atendidos en el primer nivel de atención. El gasto de bolsillo familiar incluyó gasto en traslado, alimentos-bebidas y medicamentos externos. El ingreso familiar correspondió al total de ingresos económicos aportados por los miembros de la familia. El porcentaje del gasto de bolsillo con relación al ingreso familiar se identificó con la relación entre estas dos variables. El análisis estadístico incluyó promedios y porcentajes. RESULTADOS: El gasto de bolsillo familiar anual en transporte fue de $2621.24, en alimentos y bebidas fue de $1075.67 y en medicamentos externos fue de $722.08. El gasto familiar de bolsillo total anual fue de $4418.89 y correspondió a 4.73 % del ingreso familiar. CONCLUSIÓN: El gasto de bolsillo en las familias con un paciente con diabetes mellitus tipo 2 fue de $4418.89 y representó 4.73 % del ingreso familiar.

Metabolic features of neutrophilic differentiation of HL-60 cells in hyperglycemic environments.

INTRODUCTION: Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study. RESEARCH DESIGN AND METHODS: We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression. We then used HL-60 cells differentiated towards neutrophil-like cells in standard media and investigated the effect of doubling glucose concentration on differentiation metabolism. We measured the oxygen consumption rate (OCR), and the enzymatic activity of carnitine palmitoyl transferase 1 (CPT1) and citrate synthase during neutrophil-like differentiation. We compared the surface phenotype, functions, and OCR of neutrophil-like cells differentiated under both glucose concentrations. RESULTS: Donor neutrophils showed significant instability of CD11b and OCR after phorbol 12-myristate 13-acetate stimulation at 3 hours post-enrichment. During HL-60 neutrophil-like cell differentiation, there was a significant increase in surface CD15 and CD11b expression together with the loss of mitochondrial mass. Differentiated neutrophil-like cells also exhibited higher CD11b expression and were significantly more phagocytic. In higher glucose media, we measured a decrease in citrate synthase and CPT1 activities during neutrophil-like differentiation. CONCLUSIONS: HL-60 neutrophil-like differentiation recapitulated known molecular and metabolic features of human neutrophil differentiation. Increased glucose concentrations correlated with features described in hyperglycemic donor neutrophils including increased CD11b and phagocytosis. We used this model to describe metabolic features of neutrophil-like cell differentiation in hyperglycemia and show for the first time the downregulation of CPT1 and citrate synthase activity, independently of mitochondrial mass.

Representaciones sociales sobre diabetes tipo 2 en pacientes del área Metropolitana de Buenos Aires, Argentina

Introducción: Las características y complejidad de la diabetes mellitus tipo 2 motivan la necesidad de un abordaje multi e interdisciplinario. El estudio persigue caracterizar las representaciones sociales de la diabetes mellitus tipo 2 que posee un grupo de pacientes adultos, residentes en Área Metropolitana de Buenos Aires, Argentina Método: Estudio cuantitativo, descriptivo, corte transversal. Se aplicó cuestionario sociodemográfico elaborado ad hoc y técnica de palabras asociadas. Participaron 90 pacientes adultos, reclutados principalmente del servicio de diabetológica del Hospital de Clínicas "José de San Martin" dependiente de la Universidad de Buenos Aires. Resultados: El núcleo de la representación social estuvo integrado por palabras referidas al impacto y malestar emocional que causa esta patología; la identidad de la enfermedad y la necesidad de cuidado de la salud. La periferia contuvo los siguientes temas, de mayor a menor importancia: obesidad, complicaciones de la diabetes, plan alimentario, tratamiento médico y medicación. En menor medida, se mencionaron elementos como actividad física y sedentarismo. De manera tangencial, surgieron los elementos de desinformación y sexualidad. Discusión: La representación social de la diabetes mellitus tipo 2 en pacientes se caracteriza por reflejar, en su núcleo, el temor, impacto y malestar que causa esta enfermedad. La reproducción del discurso médico mediante los temas referidos a factores de riesgo, complicaciones y tratamiento, conforman el sistema periférico de la representación. Elementos importantes tales como actividad física, sedentarismo, desinformación y sexualidad, son poco mencionados. Se destaca la importancia de la salud mental, como una problemática central a abordar en este tipo de patologías. También se sugiere implementación de educación terapéutica.

Introduction: Characteristics and complexity of type 2 diabetes generates the need for a multi and interdisciplinary approach. The aim of the study is to characterize social representations of type 2 diabetes in a group of adult patients, living in the Metropolitan Area of Buenos Aires, Argentina. Method: Descriptive and cross-sectional design. An ad-hoc sociodemographic questionnaire and the associated words technique were applied. 90 adult patients participated, recruited mainly from a diabetes service of a public hospital. Results: The core of the social representation was made up of words referring to the impact and emotional discomfort caused by this pathology, the identity of the disease and the need for health care. The periphery contained the following topics, from most to least important: obesity, diabetes complications, eating plan, medical treatment, and medication. Elements such as physical activity and sedentary lifestyle were mentioned to a lesser extent. Also, misinformation and sexuality were mentioned tangentially. Discussion: Social representation of type 2 diabetes in patients is characterized by reflecting at its core, the fear, impact and discomfort that this disease causes. The reproduction of medical discourse, through topics related to risk factors, complications and treatment, make up the peripheral system of representation. Important elements such as physical activity, sedentary lifestyle, misinformation and sexuality are rarely mentioned. The importance of mental health is highlighted as a central problem to be addressed in this type of pathology. Also, it's suggested the implementation of therapeutic education.

Assessing the impact of concurrent high-fructose and high-saturated fat diets on pediatric metabolic syndrome: A review.

High-saturated fat (HF) or high-fructose (HFr) consumption in children predispose them to metabolic syndrome (MetS). In rodent models of MetS, diets containing individually HF or HFr lead to a variable degree of MetS. Nevertheless, simultaneous intake of HF plus HFr have synergistic effects, worsening MetS outcomes. In children, the effects of HF or HFr intake usually have been addressed individually. Therefore, we have reviewed the outcomes of HF or HFr diets in children, and we compare them with the effects reported in rodents. In humans, HFr intake causes increased lipogenesis, hypertriglyceridemia, obesity and insulin resistance. On the other hand, HF diets promote low grade-inflammation, obesity, insulin resistance. Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents, there is little information about the combined effects of HF plus HFr intake in children. The aim of this review is to warn about this issue, as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population. We consider that this is an alarming issue that needs to be assessed, as the simultaneous intake of HF plus HFr is common on fast food menus.

Unveiling myocardial microstructure shifts: exploring the impact of diabetes in stable CAD patients through CMR T1 mapping.

BACKGROUND: This study investigates myocardial structural changes in stable coronary artery disease (CAD) patients with type 2 diabetes (T2D) using cardiac magnetic resonance (CMR) strain and T1 mapping. METHODS: A total of 155 stable CAD patients underwent CMR examination, including left ventricular (LV) morphology and function assessment, late gadolinium enhancement (LGE), and feature tracking (CMR-FT) for LV global longitudinal, circumferential, and radial strain. T1 mapping with extracellular volume (ECV) evaluation was also performed. RESULTS: Among the enrolled patients, 67 had T2D. Diabetic patients exhibited impaired LV strain and higher ECV compared to non-diabetics. Multivariate analysis identified T2D as an independent predictor of increased ECV and decreased strain. CONCLUSIONS: CMR-based strain and T1 mapping highlighted impaired myocardial contractility, elevated ECV, and potential interstitial fibrosis in diabetic patients with stable CAD. This suggests a significant impact of diabetes on myocardial health beyond CAD, emphasizing the importance of a comprehensive assessment in these individuals. TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN09454308.

Analysis of Circulating miRNA Expression Profiles in Type 2 Diabetes Patients with Diabetic Foot Complications.

Type 2 diabetes mellitus (T2DM) is associated with various complications, including diabetic foot, which can lead to significant morbidity and mortality. Non-healing foot ulcers in diabetic patients are a major risk factor for infections and amputations. Despite conventional treatments, which have limited efficacy, there is a need for more effective therapies. MicroRNAs (miRs) are small non-coding RNAs that play a role in gene expression and have been implicated in diabetic wound healing. miR expression was analyzed through RT-qPCR in 41 diabetic foot Mexican patients and 50 controls. Diabetic foot patients showed significant increases in plasma levels of miR-17-5p (p = 0.001), miR-191-5p (p = 0.001), let-7e-5p (p = 0.001), and miR-33a-5p (p = 0.005) when compared to controls. Elevated levels of miR-17, miR-191, and miR-121 correlated with higher glucose levels in patients with diabetic foot ulcers (r = 0.30, p = 0.004; r = 0.25, p = 0.01; and r = 0.21, p = 0.05, respectively). Levels of miR-17 showed the highest diagnostic potential (AUC 0.903, p = 0.0001). These findings underscore the possible role of these miRs in developing diabetes complications. Our study suggests that high miR-17, miR-191, and miR-121 expression is strongly associated with higher glucose levels and the development of diabetic foot ulcers.

Influence of prosthodontic rehabilitation and dietary advice on glycaemic control, nutritional status and oral health-related quality of life of older adults with type 2 diabetes.

OBJECTIVES: This prospective clinical study aimed to determine the influence of oral prosthodontic rehabilitation with partial removable dentures and simplified dietary advice on glycaemic control, nutritional status and oral health-related quality of life (OHRQoL) of older adults with type 2 diabetes. BACKGROUND: Individuals with tooth loss who did not wear complete or partial dentures are more likely to be at nutritional risk, suggesting that using dental prostheses would benefit the re-establishment of an adequate nutritional status and potentially improve quality of life. Nutritional therapy is essential for diabetes prevention, treatment and management, favouring glycaemic control. The literature provides little evidence on the contribution of partial removable dentures to improving diabetes control, nutritional profile and satisfaction in older adults, especially those with type 2 diabetes. MATERIALS AND METHODS: Older individuals diagnosed with type 2 diabetes mellitus, aged 60 years or older and needing oral rehabilitation with partial removable dentures were eligible for this prospective study. The primary outcome measure was glycaemic control, measured by glycated haemoglobin (HbA1c) levels. The Oral Health Impact Profile (OHIP-14) questionnaire and the Mini Nutritional Assessment short-form (MNA-SF) represented secondary outcome measures. These measures were assessed at baseline and 12 months of follow-up after prosthesis delivery, combined with simple dietary advice in pamphlet form. The data were analysed using the Wilcoxon matched-pairs test. RESULTS: Forty-four patients who met the inclusion criteria and required treatment with removable partial dentures were selected for this study, which was carried out for a year. During this period, seven participants declined to participate because they moved to another city. Hence, a final sample of 37 participants (16 men and 21 women, average age of 65.8 years, ranging from 60 to 83 years) were included in the study. No laboratory parameter (HbA1c levels) changed significantly during the investigation. The number of older adults at risk of malnutrition was significantly lower at 12 months than at baseline. Furthermore, nutritional status significantly improved 12 months after prosthodontic treatment combined with dietary advice, and the effect sizes were large. OHRQoL significantly improved after prosthodontic therapy combined with dietary advice. CONCLUSIONS: Prosthodontic treatment with partial dentures associated with simple dietary advice did not influence glycaemic control but improved the nutritional status and OHRQoL of older adults with type 2 diabetes.

Congenital anomalies in pregnancies with overt and pregestational type 2 diabetes: a gray portrayal from a cohort in Brazil.

OBJECTIVE: To describe the frequency and types of congenital anomalies and associated risk factors in Brazilian women with type 2 diabetes. METHODS: In this retrospective cohort study between 2005 and 2021, we included all pregnant participants with type 2 diabetes from the two major public hospitals in southern Brazil. We collected data from the electronic hospital records. Congenital anomalies were classified by the 10th revised International Classification of Diseases, Q chapter, enhanced by the EUROCAT registry classification, and categorized by type and gravity. We used multiple Poisson regression with robust estimates to estimate risks. RESULTS: Among 648 participants, we excluded 19, and 62 were lost to follow-up; therefore, we included 567 participants. Overt diabetes arose in 191 participants (33.7%, 95% CI 30.0% - 38.0%). Less than 20% of the participants supplemented folate. Congenital anomalies occurred in 78 neonates (13.8%, CI 11.0 - 16.9%), 73 babies (93.6%) presented major anomalies, and 20 (10.5%) cases occurred in participants with overt diabetes. Cardiac anomalies were the most frequent (43 isolated and 12 combined). Pre-eclampsia was associated with an increased risk in the analyses including all women (adjusted RR 1.87 (95% CI 1.23-2.85), p = 0.003), but not in analyses including only women with an HbA1c measured up to the 14th gestational age. HbA1c, either measured at any time in pregnancy (adjusted RR 1.21 (95% CI 1.10-1.33), p < 0.001) or up to the first 14 weeks (adjusted RR 1.22, 95% CI 1.10-1.35, p < 0.001) was the only sustained risk factor. Risk factors such as maternal age, obesity, diabetes diagnosis, or use of antidiabetic medications were not associated with congenital anomalies. CONCLUSION: We found a high frequency of congenital anomalies associated with poor maternal glycemic control and revealed an almost universal lack of preconception care. An urgent call to action is mandatory for the reversal of this gray scenario.

Dysregulated microRNAs in type 2 diabetes and breast cancer: Potential associated molecular mechanisms.

Type 2 diabetes (T2D) is a multifaceted and heterogeneous syndrome associated with complications such as hypertension, coronary artery disease, and notably, breast cancer (BC). The connection between T2D and BC is established through processes that involve insulin resistance, inflammation and other factors. Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC, especially through microRNAs (miRNAs), remain elusive. miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes. However, the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated. This review aims to identify dysregulated miRNAs in both T2D and BC, exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.