Type 2 Diabetes Mellitus Research Articles

The cellular and molecular mechanisms mediating the protective effects of sodium-glucose linked transporter 2 inhibitors against metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a common, highly heterogeneous condition that affects about a quarter of the world's population, with no approved drug therapy. Current evidence from preclinical research and a number of small clinical trials indicates that SGLT2 inhibitors could also be effective for MAFLD. MAFLD is associated with a higher risk of chronic liver disease and multiple extrahepatic events, especially cardiovascular disease (CVD) and chronic kidney disease (CKD). MAFLD is considered a more appropriate terminology than NAFLD because it captures the complex bidirectional interplay between fatty liver and metabolic dysfunctions associated with disease progression, such as obesity and type 2 diabetes mellitus (T2DM). SGLT2 inhibitors are antidiabetic drugs that block glucose reabsorption in the kidney proximal tubule. In this article, we reviewed current clinical evidence supporting the potential use of SGLT2 inhibitors as a drug therapy for MAFLD and discussed the possible cellular and molecular mechanisms involved. We also reviewed the clinical benefits of SGLT2 inhibitors against MAFLD-related comorbidities, especially CVD, CKD and cardiovascular-kidney-metabolic syndrome (CKM). The broad beneficial effects of SGLT2 inhibitors support their use, likely in combination with other drugs, as a therapy for MAFLD.

Effect of smoking behaviour and related blood DNA methylation on visceral adipose tissues.

Recent studies have found that tobacco smoking is associated with fat distribution, yet limited research has focused on its relationship with visceral adipose tissues (VATs). Furthermore, the cellular and molecular mechanisms underlying the interactions among smoking, epigenetic modifications, and VATs remain unknown. We performed univariable Mendelian randomization (MR) analysis to elucidate the causal relationship between smoking behaviours and VATs, including epicardial and pericardial adipose tissue (EPAT), liver fat (LF), and pancreas fat (PF). This approach could minimize the impact of confounders and reverse causality through utilizing genetic variants to proxy the smoking behaviours. Mediation MR analysis were conducted to detect potential mediators. Additionally, summary-data-based MR (SMR) and colocalization analysis were performed to explore the association between smoking-related DNA methylation and VATs. We identified a convincing association between smoking initiation and increased EPAT (beta: 0.15, 95% CI: 0.06, 0.23, p = 7.01 × 10-4) and LF area (beta: 0.15, 95% CI = 0.05, 0.24, p = 2.85 × 10-3), respectively. Further mediation analysis suggested type 2 diabetes mellitus (T2DM) as a potential mediator within these co-relationships. When further exploring the associations between the smoking related DNA methylation and VATs, we identified that WT1 methylation at cg05222924 was significantly linked to a lower EPAT area (beta: -0.12, 95% CI: -0.16, -0.06, PFDR = 2.24 × 10-3), while GPX1 methylation at cg18642234 facilitated the deposition of EPAT (beta: 0.15, 95% CI: 0.10, 0.20, PFDR = 1.66 × 10-4). Our study uncovered a significant causal effect between smoking and VATs, with T2DM identified as a potential mediator. Further investigation into DNA methylation yielded novel insights into the pathogenic role of smoking on EPAT.

Impact of allulose on blood glucose in type 2 diabetes: A meta-analysis of clinical trials

ObjectiveThis meta-analysis aims to evaluate the impact of allulose on blood glucose levels in patients with type 2 diabetes mellitus (T2DM). Primary outcomes include postprandial blood glucose, while secondary outcomes are time in range (TIR), time above range (TAR), fasting plasma glucose (FPG), and insulin area under the curve (AUC). MethodsA systematic search was conducted across PubMed/MEDLINE, Web of Science, Scopus, and Cochrane Library until May 20, 2024. Randomized controlled trials assessing the effect of allulose on glycemic parameters in T2DM patients were included. Data were synthesized using a random-effects meta-analysis model, and the quality of studies was assessed using the Cochrane Risk of Bias tool. ResultsSix studies involving 126 participants were included. Allulose significantly reduced glucose AUC (SMD: −0.6662, 95 % CI [-1.1360, −0.1964], p = 0.0054) with moderate heterogeneity (I2 = 58.3 %). Insulin AUC showed a non-significant reduction (SMD: −0.3648, 95 % CI [-0.7783, 0.0488], p = 0.0839). FPG demonstrated a non-significant reduction (MD: −5.8925, 95 % CI [-20.4892, 8.7043], p = 0.4288), while TAR significantly decreased (MD: −8.8204, 95 % CI [-14.4101, −3.2307], p = 0.0020). No significant changes were observed in TIR (MD: 7.1211, 95 % CI [-1.6028, 15.8450], p = 0.1096). ConclusionAllulose demonstrated a significant reduction in postprandial glucose levels and TAR, supporting its role as a dietary intervention for glycemic control in T2DM patients. The findings are robust, though further research is needed to confirm its long-term effects on insulin sensitivity and metabolic health.

Exploring the interplay between DHCR7, vitamin D deficiency, and type 2 diabetes mellitus (T2DM): a systematic review.

Type 2 diabetes mellitus (T2DM) is a growing global health concern. The pathogenesis of T2DM is multifactorial and intricate, involving a complex interplay of genetic predisposition, environmental factors, and molecular interactions. Vitamin D (circulating 25-hydroxyvitamin D concentration) regulates factors crucial for T2DM, including insulin secretion, sensitivity, and inflammation. Thus, vitamin D deficiency has been linked to poor health outcomes in T2DM patients. The cholesterol-synthesizing enzyme 7-dehydrocholesterol reductase (DHCR7) represents a critical regulatory switch between cholesterol and vitamin D3 synthesis. Recent findings suggest that the enzyme DHCR7 may indicate T2DM glycolipid metabolic disorder and is associated with deficient circulating vitamin D (circulating 25-hydroxyvitamin D concentration) status. In this PRISMA-guided systematic review, articles were sourced from two databases, namely, PubMed and Cochrane Library, to evaluate the impact of vitamin D deficiency in patients with T2DM and to explore the emerging role of DHCR7 in T2DM pathogenesis. Our findings strongly indicate a positive correlation between deficient vitamin D status and poor health outcomes in T2DM patients. Finally, this systematic review presents a novel perspective on T2DM development, focusing on the interplay between T2DM-associated hyperglycemia, expression of DHCR7, and abrogation of vitamin D synthesis.

Influenza Vaccination Coverage and Influencing Factors in Type 2 Diabetes in Mainland China: A Systematic Review and Meta-Analysis

Background: Influenza has many harmful effects on people with type 2 diabetes mellitus (T2DM), such as hyperglycemia and increasing incidence of cardiovascular and cerebrovascular diseases. Epidemiological evidence shows that influenza vaccinations can effectively prevent deterioration in T2DM patients. At present, there is a lack of nationwide studies on the vaccination status of influenza vaccines for patients with certain chronic diseases. This study aimed to evaluate the influenza vaccination status of T2DM patients in mainland China and the factors affecting their influenza vaccination. Methods: Data were sourced from PubMed, Embase, Web of Science, the China Biology Medicine Disc (CBMdisc), the China National Knowledge Infrastructure (CNKI), and the Wanfang Database. The keywords used in the literature search included “diabetes”, “diabetes mellitus”, “DM”, “diabetic”, “T2DM”, “influenza vaccine”, “flu vaccine”, “China”, and “Chinese”. A total of 249 articles were retrieved through the searches; 7 articles met the inclusion criteria. The fixed-effects model was used when heterogeneity was low and a random-effects model was used when the heterogeneity was high. Results: The influenza vaccination coverage rate was 1.46% in diabetic patients and 9.99% in elderly diabetic patients. The influenza vaccination rate of type 2 diabetes patients with a high education level is higher than that of patients with a low education level. (OR: 1.462 [1.123, 1.903]). Meanwhile, gender (OR: 1.076, 95%CI: 0.893–1.295), marriage (OR: 1.283; 95%CI: 0.931–1.766), and occupation (OR: 1.049; 95% CI: 4.422–2.606) have no significant impact on influenza vaccination in patients with type 2 diabetes. Conclusions: This study found that the coverage of influenza vaccination in patients with T2DM in Chinese mainland was low, and there were few relevant research articles. In China’s mainland areas, education background is an important factor affecting the influenza vaccination of T2DM patients. China should continue to improve the influenza vaccination rate of patients with type 2 diabetes.

Ligandrol Ameliorates High-Fat Diet- and Streptozotocin-Induced Type 2 Diabetes Mellitus and Prevents Pancreatic Islets Degeneration.

Androgen therapy has been shown to alleviate type 2 diabetes mellitus (T2DM) but is also associated with severe side effects such as prostate cancer. The present study aims to identify the best hit selective androgen receptor (AR) modulator by in silico studies and then investigates its antidiabetic effects in high-fat diet- and streptozotocin (STZ)-induced T2DM male rat model. Molecular docking and molecular dynamics (MD) studies were carried out using Maestro 13.1 and Desmond (2023-2024). Cytotoxicity and insulin secretion were measured in MIN6 cell lines. T2DM was induced using high-fat diet (HFD) for 4 weeks, followed by single STZ (40 mg/kg, intraperitoneally). OneTouch Ultra glucometer was used to measure fasting blood glucose. Gene expression was determined using reverse transcription polymerase chain reaction. Histopathology was carried out using hematoxylin and eosin stain. Through molecular docking, we identify ligandrol as a potential hit. Ligandrol showed a good binding affinity (-10.74 kcal/mol). MD showed that ligandrol is stable during the 100 ns simulation. Ligandrol increases insulin secretion in a dose-dependent manner in vitro in 2 h. Ligandrol (0.3 and 1 mg/kg, orally) significantly decreased the body weight and fasting blood glucose levels compared with the HFD and STZ group. Gene expression showed that ligandrol significantly increased the AR-targeted gene, neurogenic differentiation 1, compared with the HFD and STZ group. Histopathological staining studies showed that ligandrol prevents pancreatic islet degeneration compared with the HFD and STZ group. Our findings suggest that ligandrol's protective effect on pancreatic islets leading to its antidiabetic effect occurs through the activation of AR.

Association between hydroxychloroquine use and risk of diabetes mellitus in systemic lupus erythematosus and rheumatoid arthritis: a UK Biobank-based study

Context/ObjectivesHydroxychoroquine has hypoglycemic effects and may reduce the risk of diabetes mellitus (DM). We determined the association between hydroxychoroquine use and the incidence of DM in a population-based cohort of pations with Rheumatic diseaseMethodsA prospective cohort study among 502392 Potentially eligible participants in the context of UK Biobank, recruitment to the database began between 2006 and 2010. Patients diagnosed with diabetes and fasting glucose greater than or equal to 7 mmol/L at baseline (n=619) were excluded and patients diagnosed with either RA or SLE at baseline (n=6793) were followed up until 2022. Diagnosis was recorded using the International Classification of Diseases, tenth edition (ICD-10) code. The mean follow-up was 13.78 years and the primary outcome was newly recorded type 2 diabetes mellitus (T2DM), with the time of onset of diabetes as the follow-up endpoint date.ResultsDuring a median follow-up period of 13.78 (12.93, 14.49) years, diabetes developed in 537 participants, with an incidence of 7.9%. New diabetes cases not taking hydroxychloroquine and taking hydroxychloroquine was 504 (8.03%) and 33 (6.36%), respectively. In univariate models, the hazard ratio for diabetes was 0.89 (95% confidence interval, 0.81-0.98, P=0.014) for hydroxychloroquine users compared with those not taking hydroxychloroquine. After adjusting for age, sex, race, education level, and BMI the hazard ratio for incident diabetes among hydroxychloroquine users was 0.88 (95% confidence interval, 0.80-0.97, P=0.008). In complete multivariate model hazard ratio for hydroxychloroquine was 0.87 (95% confidence interval, 0.79- 0.96, P=0.005).ConclusionHydroxychloroquine was associated with decreased risk of DM among rheumatoid arthritis patients, our data taken together with correlational studies, warrant further investigation of the potential preventive effect of hydroxychloroquine against T2DM.

Effect of Glycated Haemoglobin (HBA1c) on Cardiorespiratory Fitness (CRF) in a Population with Type 2 Diabetes Mellitus (T2DM): A Cross-Sectional Study

Background and Objective: The aim of this study was to evaluate cardiorespiratory fitness (CRF) measures, maximal oxygen consumption (VO2 max), and minute ventilation/carbon dioxide production (VE/VCO2 slope and others) among the T2DM population based on glycated haemoglobin (HBA1c). Material and Methods: The present study comprised a cross-sectional design, with two groups, based on HbA1c values (≤7 and ≥7.1). Laboratory samples were taken to evaluate glycated haemoglobin and fasting blood glucose (FBS). Cardiopulmonary exercise testing was performed to calculate various fitness-related parameters. Data analysis: An independent t-test was used to analyse the outcomes in the two groups. p < 0.05 was considered significant. Linear regression was used to examine the influence of predictor variables on dependent variables. Results: A total of 70 patients agreed to participate in the study, with 19 females and 51 males. The mean (standard deviation) BMI (body mass index) of all participants was 29.7(5.2), the mean (SD) weight was 84.4 (18.9) kg, and the mean height was 167.4 (23) cm. The average age of the individuals was 52 ± 8 years. The independent t-test revealed a significant difference between the two groups in terms of CRF measures. Conclusions: The current research identified the presence of poor glycaemic control and cardiorespiratory fitness measures among the Brazilian population with T2DM. HBA1c, duration of diabetes, age, and BMI can be employed to predict the ventilatory threshold (VT) and VO2 max.

Oat polar lipids and sunflower lecithin similarly improve cardiometabolic risk markers and appetite controlling hormone responses after breakfast and a subsequent lunch. A randomized crossover study in healthy adults

IntroductionThe alarming global increase in lifestyle-related disorders such as obesity and type 2 diabetes mellitus (T2DM) has increased during the last several decades. Poor dietary choices significantly contribute to this increase and prevention measures are urgently needed. Dietary intake of bioactive compounds found in foods are linked to a decrease likelihood of these disorders. For this purpose, a randomized crossover meal study was performed to compare the postprandial metabolic effects of lecithin and oat polar lipids in healthy subjects.Materials and methodsEighteen young healthy subjects ingested test meals enriched with lecithin, oat polar lipids (PLs) or rapeseed oil. There were four test meals (i) 15 g oat polar lipids: OPL, (ii) 18 g sunflower lecithin (of which 15 g were polar lipids): LPL, (iii) 18 g rapeseed oil: RSO, and (iv) reference white wheat bread: WWB. Lipid-enriched test meals contained equivalent amounts of total fat (18 g), and all breakfast meals contained 50 g available carbohydrates. The meals were served as breakfast followed by a standardised lunch (white wheat bread and meat balls) after 3.5 h. Test variables were measured at fasting and repeatedly during 5.5 h after ingestion of the breakfast.ResultsOur study demonstrated that both LPL and OPL had beneficial effects on postprandial glucose and insulin responses, and appetite regulating gut hormones, as compared to RSO and WWB. Significant increase in GLP-1, GIP, and PYY concentrations were seen after consuming breakfast meals with LPL and OPL, and ghrelin concentration was reduced compared to meals with RSO and WWB (p < 0.05). Furthermore, triglycerides (TG) concentration was significantly reduced after OPL compared to RSO (p < 0.05). Our data show that there were no significant variations in glycaemic and insulin responses, TG, and gut hormone concentrations between LPL and OPL during breakfast (0–210 min) or over the whole study period (0–330 min).ConclusionOur study revealed that the consumption of both lecithin and oat PLs included in breakfast meal may similarly enhance postprandial glucose tolerance, reduce TG, and enhance the secretion of incretins and appetite regulating hormones in healthy young adults.Clinical trial registrationClinicalTrials.gov, identifier NCT05139355.

Dietary inflammatory index as a predictor of prediabetes in women with previous gestational diabetes mellitus

IntroductionGestational diabetes mellitus (GDM) is associated with an increased risk of developing type 2 diabetes mellitus (T2DM). The inflammatory potential of diet is crucial in GDM development. This study compares dietary inflammatory indices (DII) in females with and without a history of GDM and constructs a predictive model for prediabetes risk.MethodsCross-sectional data from NHANES cycles (2011–2014) were analyzed using the DII. Independent t tests, chi-square test, and Mann-Whitney U test examined DII scores in relation to GDM history. Multivariate logistic regression assessed DII’s association with prediabetes in females with GDM history. Restricted cubic spline (RCS) and LASSO regression modeled non-linear relationships and predicted prediabetes risk.Results971 female participants were included. Those with GDM history had lower DII scores (1.62 (0.58, 2.93) vs. 2.05 (0.91, 2.93)). Higher DII scores in females with GDM were linked to prediabetes, remaining significant after adjusting for confounders. RCS analysis found no non-linear correlation (non-linear p = 0.617). The prediabetes model for GDM history had strong predictive performance (AUC = 88.6%, 95% CI: 79.9-97.4%).ConclusionFemales with GDM history show lower DII levels, potentially reflecting improved diet and health awareness. Higher DII scores correlate with increased prediabetes risk in this group, emphasizing diet’s role in diabetes risk. Further studies are needed to confirm these findings.

Case Report: Endovascular approach with kissing stent technique in aortoiliac occlusive disease (Leriche syndrome) patient

Background Aortoiliac occlusive disease (AIOD) or Leriche syndrome, is a form of peripheral arterial disease involving the infrarenal aorta and iliac arteries. The presentation of AIOD ranges from asymptomatic cases to limb-threatening emergencies. Advances and innovations in endovascular devices have replaced traditional surgical interventions for the management of AIOD. Here we report a case of a 52-year-old man presenting with AIOD managed by endovascular approach using kissing stent technique. Case presentation A 52-year-old man, with history of chronic coronary artery disease, diabetes mellitus type 2, long-standing hypertension, and a significant history of smoking, was admitted to our hospital with symptoms of long-standing bilateral claudication which recently progressed to rest pain. A history of AIOD was previously established. AIOD (TASC II Type D) diagnosis was made by lower extremity duplex ultrasound and CT angiography. The patient underwent urgent percutaneous transluminal angioplasty with kissing stent technique. The patient was discharged 4 days after the procedure without any significant complaints, received best medical therapy. Conclusion Endovascular interventions present excellent alternatives to surgical techniques in the treatment of complex AIOD. Herein we presented an endovascular treatment of AIOD utilizing the kissing stent technique which showed satisfactory outcomes.

Interleukin 37 Role in Diabetic Iraqi Patients: A comparison between patients treated with and without Insulin

Background: Diabetes Mellitus (DM) is defined as a metabolic disorder that is characterized by some clinical features, such as chronic hyperglycemia accompanied by impairment of carbohydrates metabolism, proteins, and lipids. However, relative or absolute insulin deficiency is associated with the high blood glucose levels, which is attributed to the β-cells dysfunction, insulin resistance or could be both. The anti-inflammatory cytokine interleukin-37 (IL-37) negatively regulates inflammation, therefore, reduces inflammation and alters metabolic pathways. It acts by suppressing inflammatory cytokines and chemokines, activation of IL-37 inhibits inflammation and obstructs the infiltration of pro-inflammatory cells, primarily neutrophils and eosinophils. Aim of Study: The estimation of IL 37 and other biochemical parameters in patients with Diabetes mellitus and study its role in the pathogenicity of the disease. Materials and methods: A case-control study design was adopted to study the relationship between Interleukin 37 and insulin treatment in Nasiriyah in the Diabetes and Endocrinology Specialized Center between December 2023 and January 2024. It was conducted on patients with Diabetes Mellitus type 2 (60 patients) divided into two groups (30 patients treated with Insulin injection) and (30 patient treated with oral tab only). On the other hand, 30 people were taken as a control group without Diabetes Mellitus.Result: Patients with diabetes mellitus have been noticed to have higher levels of IL-37 in comparison to the healthy control groups. In general, patients with diabetes mellitus have higher levels of IL-37 compared to three groups, G1, G2, and healthy control groups. Conclusion We demonstrated that serum levels concentration of IL 1b and IL 37 significantly increased in our patients also FBS, HbA1c, Insulin Resistance, HOMO IR, TG, cholesterol, and decrease C- peptide as compared to healthy individuals.

Vitamin D Deficiency in Patients with Type 2 Diabetes Mellitus with and without Pulmonary Tuberculosis

Background: Vitamin D has a role in the body's calcium balance and immunodeficiency effects, and stimulates dendric cells, monocytes, T cells, macrophages in pathogenic microbes’ elimination. The variation occurrence as polymorphism on VDR might cause problem in production, transportation, and activity of vitamin D. The gap between the occurrence findings in previous studies shows that there are indication factors of VDR levels that probably associate with the T2DM range in comorbid with pulmonary tuberculosis. To determine vitamin D levels and factors associated with vitamin D deficiency in Type 2 Diabetes Mellitus (T2DM) patients with and without pulmonary Tuberculosis (TB). Method: The design of this study was cross-sectional. T2DM subjects with pulmonary TB were 45 people, and 43 people without pulmonary TB were 43 people. Sampling was done by consecutive sampling from October to December 2017. We collected data through interviews and examination of plasma vitamin D (25-OH) levels by ELISA. Data analysis using the Mann-Whitney test, and chi-square test with a confidence level of 95%. Result: There were 88 T2DM patients who met the inclusion criteria, consisting of 43 T2DM patients without pulmonary TB and 45 T2DM patients with pulmonary TB as the study subjects. There were differences in the distribution of T2DM subjects based on sex and BMI measurements. The mean plasma vitamin D levels in T2DM with pulmonary TB and T2DM without pulmonary TB were 20.08 ng/ml (SD ± 0.83 ng/ml) and 20.29 ng/ml (SD ± 0.81 ng/ml), respectively, we found no significant result in statistic (p = 0.287). Vitamin D deficiency was not associated with the incidence of pulmonary TB in T2DM, whereas female sex, age> 50 years, BMI ? 25.0 kg /m2, and duration of T2DM> 5 years were associated with vitamin D deficiency (p <0.05). This research has contributed in novel findings of the correlation between sex and BMI associated in duration of T2DM impacted the Vitamin D insufficiently. Conclusion: Sex, age, BMI, and duration of T2DM had a significant correlation with vitamin D deficiency in T2DM patients with and without pulmonary TB.

Alterations in subgingival microbiome and advanced glycation end-products levels in periodontitis with and without type 1 diabetes mellitus: a cross-sectional study.

Existing studies predominantly focused on the relationship between periodontitis and type 2 diabetes mellitus (T2DM), with limited data on the association between periodontitis and type 1 diabetes mellitus (T1DM). This study aimed to examine the impact of T1DM and periodontitis on the subgingival microbiome and levels of advanced glycation end-products (AGEs). Samples were collected from four groups: T1DM, periodontitis (P), T1DM with periodontitis (DP), and periodontally and systemically healthy controls (Control). Subgingival microbiome composition and AGE levels were assessed using 16S rRNA gene sequencing and enzyme-linked immunosorbent assay (ELISA), respectively. Correlations between clinical indexes, microbiome composition, and AGEs were analyzed using Spearman correlation coefficient. Alpha and beta diversity analyses revealed significant differences in bacterial diversity between the DP group and other groups. Linear discriminant analysis effect size (LEfSe) analysis identified specific bacteria influencing each group: Acinetobacter, Leptotrichia, Raoultibacter, and Veillonella in the Control group; Tannerella, Porphyromonas, Filifactor, and Treponema in the P group; and Lactobacillales in T1DM individuals. Prevotella and Selenomonas were notably influential in the DP group. PICRUSt2 analysis showed pathways alterations were concentrated in cell motility, translation, cell growth and death and metabolism in the DP and P groups. Spearman correlation analysis indicated a positive correlation between AGEs and periodontitis or diabetes-related parameters and AGEs were positively correlated with Haemophilus and Arachnia. The findings suggested that the composition and function of the subgingival microbiome in the P group with or without T1DM were significantly different. Additionally, AGEs were involved in the development of periodontitis even in absence of hyperglycemia.

Exploring the Molecular Mechanisms underlying SADI-S Improves Glucose Metabolism in Type 2 Diabetic Rats through Liver Transcriptomics and Proteomics Analysis.

Metabolic surgery could improve or even reverse type 2 diabetes mellitus (T2DM). Single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is one of the most effective metabolic surgeries for T2DM. However, the molecular mechanisms behind the SADI-S-induced T2DM improvement are not fully understood.Here,T2DM rats received SADI-S and were sacrificed after 8 weeks; the controls received sham surgery; Liver tissues were collected for transcriptomics and proteomics analysis to identify differentially expressed genes (DEGs) and proteins (DEPs). Parallel reaction monitoring (PRM) was performed to validate the accuracy of the proteomics results.SADI-S significantly improved glucose metabolism in T2DM rats.A total of 120 genes/proteins(e.g., phosphoenolpyruvate carboxykinase (Pck1) and pyruvate kinase (Pklr)) exhibited consistent expression trends at both mRNA and protein levels. Among the upregulated genes/proteins involved in glucose metabolic pathways, enrichment was observed in pathways such as the pyruvate metabolic pathway, insulin signaling pathway, glycolysis/gluconeogenesis biological processes, glucagon signaling pathway, and AMPK signaling pathway. Downregulated genes/proteins were enriched in the pyruvate metabolic pathway. The above-mentioned signaling pathways are implicated in glucose metabolism, suggesting a potential mechanism for SADI-S-mediated alleviation of T2DM. The PRM validation results indicated that all selected proteins showed consistent trends between PRM and proteomics data. This consistency suggests the reliability of the proteomics results.

A Prospective Study on the Prevalence of MASLD in Patients With Type 2 Diabetes and Hyperferritinaemia.

Elevated levels of serum ferritin, a marker of hepatic iron overload and inflammation, may be associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatic fibrosis. To determine the prevalence of MASLD and significant hepatic fibrosis among patients with type 2 diabetes mellitus (T2DM) and hyperferritinaemia. This is a cross-sectional analysis of a prospective cohort of 523 adults (64% female) aged 50-80 with T2DM and without a diagnosis of haemochromatosis. MASLD and significant fibrosis were defined as magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% and magnetic resonance elastography (MRE) ≥ 3.0 kPa, respectively. Hyperferritinaemia was defined as serum ferritin ≥ 200 ng/mL in females or ≥ 300 ng/mL in males. The primary objective was to determine the prevalence of MASLD and significant fibrosis in hyperferritinaemia. The mean age and body mass index were 64.1 (±8.1) years and 31.5 (±5.9) kg/m2, respectively. The overall prevalence of hyperferritinaemia was 20.5% (n = 107). The prevalence of MASLD (78.5% vs. 62.1%, p = 0.001) and significant fibrosis (35.5% vs. 22.1%, p = 0.002) were higher in participants with hyperferritinaemia than those without. Hyperferritinaemia remained an independent predictor of MASLD (OR 2.01; 95% CI 1.19-3.39; p = 0.009) and significant fibrosis (OR 2.33; CI 1.43-3.77; p = 0.001), even after adjustment for age, sex, obesity and insulin use. Approximately 80% of people with hyperferritinaemia and T2DM have MASLD, and more than a third have significant hepatic fibrosis. Hyperferritinaemia may be a useful biomarker for MASLD and significant fibrosis in people with T2DM.

Association between blood heavy metals and diabetic kidney disease among type 2 diabetic patients: a cross-sectional study.

Studies on the correlation of exposure to metals with diabetic kidney disease (DKD) is scarce, especially concerning the impact of mixed metals on DKD. This study aimed to explore the association of blood heavy metals with DKD risk among type 2 diabetes mellitus (T2DM) patients. This cross-sectional study enrolled patients with T2DM in NHANES 2011-2020. ICP‒MS was applied to detect five metals, namely, Pb, Cd, Hg, Se and Mn, in blood. At the same time, the impacts of exposure to single and mixed metals on DKD were assessed using multivariable logistic regression, WQS, and BKMR models. The relationship was examined based on age, sex, BMI, hypertension, smoking status and PIR. Totally 2362 participants were enrolled for final analysis. Among them, 634 (26.84%) patients undergoing T2DM had DKD. Logistic regression indicated that, Pb (Q4: OR [95% CI]: 1.557 [1.175, 2.064]) was related to DKD when all covariates were adjusted. The WQS analysis, which was set in a positive directional mode, suggested that Pb was correlated positively with a higher incidence of DKD. In BKMR analysis, linear dose‒response curves were generated for Pb when fixing the other metals in the 50th percentile. In addition, exposure to mixed metals was significantly positively related to DKD. Subgroup analysis during logistic regression demonstrated that Pb was significantly and positively related to DKD in females, over 50 years, those with over 25kg/m2, no hypertension, no smoking status and under PIR. Serum albumin (ALB) did not regulate the indirect impact of blood Pb on DKD risk. The results showed that the increased mixed metal concentration may lead to an increased DKD risk among patients with T2DM. Blood Pb is positively related to the DKD risk in diabetic patients, especially, in females, over 50 years, those with over 25kg/m2, no hypertension, no smoking status and under PIR in T2DM patients. According to our observations, Pb absorption at least slightly influences DKD occurrence and progression. More studies are needed to validate the results in this work and illustrate the relevant biological mechanism.

Transcutaneous auricular vagal nerve stimulation modulates blood glucose in ZDF rats via intestinal melatonin receptors and melatonin secretion

BackgroundMelatonin (MLT) and its receptor deficiency have been shown to be associated with type 2 diabetes mellitus (T2DM). Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive alternative intervention for patients suffering from hyperglycemia. Here, we aimed to investigate the role of taVNS on blood glucose modulation via intestinal melatonin receptors (MRs) and MLT secretion in hyperglycemia.MethodsAdult male Zucker diabetes fatty (ZDF) rats and Zucker lean (ZL) littermates were used. Forty ZDF rats were randomized into ZDF, taVNS, Px + taVNS and Lu + Px + taVNS groups (Px: pinealectomy, Lu: Luzindole). ZL rats served as a control group for comparison with ZDF rats without involvement in the taVNS intervention. Thirty min-taVNS interventions (2/15 Hz, 2 mA, 30 min/days) were administered once daily under anesthesia for 3 consecutive weeks in taVNS, Px + taVNS and Lu + Px + taVNS groups. Body weight and fasting blood glucose (FBG) were measured weekly in all rats, and real-time blood glucose was tested in the ZL and ZDF groups before, during and after the taVNS intervention. Plasma MLT concentration and the expression of MRs in the duodenum, jejunum and ileum were measured by the end of experiments.ResultsCompared with the ZL group, the level of FBG and body weight increased (all p < 0.01), plasma MLT secretion and the expression of MRs in duodenum, jejunum and ileum of ZDF rats decreased obviously (all p < 0.05), respectively. TaVNS can significantly reverse the hyperglycemia by regulating the non-pineal-derived MLT and MRs system in Px + taVNS group. Compared with the ZDF group, the expression of different intestinal MRs in the taVNS group was increased and more compactly arranged (both p < 0.05), the level of plasma MLT secretion was up-regulated (p < 0.01), and FBG and body weight were decreased (both p < 0.01). Meanwhile, after taVNS intervention in rats in the Px + taVNS group, we observed an increase in MLT secretion and the number of intestinal MRs compared with the taVNS group (all p > 0.05). In contrast, ZDF rats in which the pineal gland was excised by taVNS intervention and injected with the MRs antagonist Luzindole did not show these changes.ConclusionThe glucose reduction effect of taVNS may be related to regulating MLT levels and expressing intestinal MRs.

New Dosage Form of Insulin: Review Article

Many patients with advanced type 2 diabetes mellitus (T2DM) and all patients with T1DM require insulin to keep blood glucose levels in the target range. The most common route of insulin administration is subcutaneous insulin injections. There are many ways to deliver insulin subcutaneously, such as vials and syringes, insulin pens, and insulin pumps. Though subcutaneous insulin delivery is the standard route of insulin administration, it is associated with injection pain, needle phobia, lipodystrophy, noncompliance, and peripheral hyperinsulinemia. Therefore, the need exists to deliver insulin in a minimally invasive or noninvasive way and in the most physiological way. Inhaled insulin was the first approved noninvasive and alternative way to deliver glucose, but it has been withdrawn from the market. Researchers are exploring technologies to enable noninvasive insulin delivery. Some of the routes for insulin administration that are under investigation are oral, buccal, nasal, peritoneal, and transdermal. This article has focused on different possible routes of insulin administration, their advantages and limitations, and the possible scope of the new drug development.

Enzyme (α-Glucosidase, α-Amylase, PTP1B & VEGFR-2) Inhibition and Cytotoxicity of Fluorinated Benzenesulfonic Ester Derivatives of the 5-Substituted 2-Hydroxy-3-nitroacetophenones

The prevalence of small multi-target drugs containing a fluorinated aromatic moiety among approved drugs in the market is due to the unique properties of this halogen atom. With the aim to develop potent antidiabetic agents, a series of phenylsulfonic esters based on the conjugation of the 5-substituted 2-hydroxy-3-nitroacetophenones 1a–d with phenylsulfonyl chloride derivatives substituted with a fluorine atom or fluorine-containing (-CF3 or -OCF3) group were prepared. Their structures were characterized using a combination of spectroscopic techniques complemented with a single-crystal X-ray diffraction (XRD) analysis on a representative example. The compounds were, in turn, assayed for inhibitory effect against α-glucosidase, α-amylase, protein tyrosine phosphatase 1 B (PTP1B) and the vascular endothelial growth factor receptor-2 (VEGFR-2) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The antigrowth effect of selected compounds was evaluated on the human breast (MCF-7) and lung (A549) cancer cell lines. The compounds were also evaluated for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The results of an in vitro enzymatic study were augmented by molecular docking (in silico) analysis. Their ADME (absorption, distribution, metabolism and excretion) properties have been evaluated on the most active compounds against α-glucosidase and/or α-amylase to predict their drug likeness.