Pathophysiology Of Type 2 Diabetes Mellitus Research Articles

Liver and cardiovascular disease outcomes in metabolic syndrome and diabetic populations: Bi-directional opportunities to multiply preventive strategies

The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.

GLP-1 receptor agonists: A review of glycemic benefits and beyond.

Type 2 diabetes mellitus (T2DM) is a chronic medical condition affecting millions of individuals worldwide. The burden of disease is significant, as demonstrated by high morbidity and mortality and billions of healthcare dollars spent. The pathophysiology of T2DM is complex, with eight primary deficits. In recent years, an increased focus has been placed on incretin hormones, such as glucagon-like peptide-1 (GLP-1) for its glucose-lowering benefits. Several FDA-approved short-acting and long-acting GLP-1 receptor agonists (GLP-1 RAs) are available in the United States for the treatment of T2DM. These are liraglutide, exenatide, dulaglutide, and semaglutide, all administered via subcutaneous injection. Semaglutide is also available in an oral formulation. A newer dual glucose-dependent insulinotropic peptide (GIP) and GLP-1 RA, tirzepatide, is available as a subcutaneous injectable. In addition to improving glycemic control, GLP-1 RAs have been shown to lower total body weight, BP, and cholesterol as well as to improve renal function and beta-cell proliferation. These agents should be considered in every patient with T2DM due to their substantial clinical benefits and potential to help reduce disease burden.

The Effects of Diet Intervention on the Gut Microbiota in Type 2 Diabetes Mellitus: A Systematic Review.

The GI tract hosts a dynamic community known as the gut microbiota, which encompasses thriving bacteria that actively contribute to the physiological functions of the human body. The intricacies of its composition are profoundly influenced by dietary preferences, where the quality, quantity, and frequency of food consumption play a pivotal role in either fostering or impeding specific bacterial strains. Type 2 diabetes mellitus (T2DM) is a prevalent and deleterious condition that originates from excessive hyperglycemia. Do lifestyle interventions targeting dietary adjustments, nutritional supplements, physical activity, and weight management programs exhibit a significant relationship in altering the composition of the gut microbiome and managing T2DM? This paper aims to evaluate the effects of lifestyle interventions on patients with T2DM and the implications of these changes on disease outcomes and progression. Lifestyle interventions can significantly impact the management of T2DM, especially those targeting dietary adjustments, nutritional supplements, physical activity, and weight management programs. The adoption of a high-fiber diet and increased fruit consumption have shown positive impacts on both insulin sensitivity and the composition of the gut microbiota. Additionally, promising outcomes emerge from supplementing with Omega-3 fatty acids, Vitamin K2 (MK-7), and transglucosidase, which influence insulin levels, glycemic control, and gut microbiota composition. Personalized diet interventions and the transformative effects of the Mediterranean diet present positive outcomes in metabolic control. The intensity of exercise plays a pivotal role in shaping the composition of the gut microbiota, with moderate-intensity continuous exercise displaying positive effects on anti-inflammatory microbes. Chronic exercise showcases favorable impacts on glycemic control and systemic inflammation. Emphasizing the intricate relationship between dietary habits, gut microbiota, and the risk of T2DM underscores the potential of the gut microbiota as a universal biomarker for assessing diabetes risk. Nutritional supplements and exercise interventions provide potential avenues for the management of T2DM, emphasizing the necessity for tailored strategies. Further research is encouraged to delve into the long-term effects and intricate interplay between lifestyle factors and the gut microbiome, enhancing our understanding of T2DM pathophysiology for targeted therapeutic approaches.

Sera Levels of microRNA-124 in Newly Diagnosed Patients with Type 2 Diabetes Mellitus in Iraqi Population

Recently, circulating microRNAs (miRNAs) have emerged as potential new biomarkers for diagnosing and prognosis a wide range of disorders. The study aimed to compare the sera levels of miRNA21 and miRNA124 among newly diagnosed patients e with type 2 diabetes mellitus (T2DM) patients with their levels in apparently healthy subjects using blood samples. The time frame for this case-control research is August 2022 through March 2023, and it took place at Al-Sadr Teaching Hospital/Madina in Masin. One hundred patients with a recent di recently patients with T2DM (50 females) and 100 control participants appeared to be healthy but were really between the ages of 5 and 70. We took 2 ml of blood from each patient and healthy person, placed it in an EDTA tube with 1 ml of Trizole as a preservative, and put the tubes in the freezer at -20 degrees Celsius until we were ready to analyze the samples. Recent studies prove the relationship between miR-124 and inflammatory processes and insulin resistance; our emphasis suggests the role miR-124 in insulin resistance in T2DM. Studies have explored the potential of miR-124 as a diagnostic biomarker for T2DM. Altered expression levels of these miRNAs have been detected in sera of newly T2DM-diagnosed patients, which promises to be a non-invasive technique for the disease. Regarding therapeutic scope, miR-124 may be used as a target for insulin sensitivity. Modulating this miRNA may have a potential therapeutic impact in managing T2DM. It is important to note that significant progress has been made in understanding the involvement of miR-124 in T2DM. New studies may provide additional knowledge on its mechanism to decrease insulin receptor resistance and beta cell function, hence, the pathophysiology of T2DM.

Comparative Efficacy and Safety of Tirzepatide in Asians and Non-Asians with Type2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Tirzepatide is a novel hypoglycemic agent for type2 diabetes mellitus (T2DM). However, the pathophysiology of T2DM in Asians is different from that in non-Asians, and there is no evidence to explain the differences in the efficacy and safety of tirzepatide between different races. A literature search was conducted in China National Knowledge Infrastructure (CNKI), PubMed, Cochrane Library, Clinical Trials.gov, and Embase databases for clinical studies of tirzepatide for T2DM. The data extraction process was done independently by two authors. All analyses were performed using STATA 14.0 software and Review Manager 5.3 software. A total of 2118 patients with T2DM from 6 studies were involved, with doses of tirzepatide ranging from 5 to 15mg administered subcutaneously once weekly. The results showed that compared with control/placebo, tirzepatide was more effective in decreasing fasting blood glucose (FBG) in non-Asians than in Asians, and 10mg rather than 15mg was the optimal dose to decrease FBG. Similarly, non-Asians were more effective than Asians in improving glycated hemoglobin (HbA1c). Asians were significantly more effective than non-Asians in reducing body weight and ≥ 5% weight loss. In terms of adverse events, the incidence of gastrointestinal adverse events was higher in Asians than in non-Asians at the same dose, while the incidence of metabolic and nutrition disorders was higher in non-Asians than in Asians. Tirzepatide is a novel agent for the treatment of diabetes and has different efficacy in Asians and non-Asians. Asians were more likely to experience weight loss and gastrointestinal adverse events, whereas non-Asians were more likely to have better glycemic control and more metabolic and nutritional disorders. PROSPERO registration no. CRD42023489588.

Label-free analysis of the β-hydroxybutyricacid drug on mitochondrial redox states repairment in type 2 diabetic mice by resonance raman scattering

BackgroundMitochondrial redox imbalance underlies the pathophysiology of type2 diabetes mellitus (T2DM), and is closely related to tissue damage and dysfunction. Studies have shown the beneficial effects of dietary strategies that elevate β-hydroxybutyrate (BHB) levels in alleviating T2DM. Nevertheless, the role of BHB has not been clearly elucidated. MethodsWe performed a spectral study to visualize the preventive effects of BHB on blood and multiorgan mitochondrial redox imbalance in T2DM mice via using label-free resonance Raman spectroscopy (RRS), and further explored the impact of BHB therapy on the pathology of T2DM mice by histological and biochemical analyses. FindingsOur data revealed that RRS-based mitochondrial redox states assay enabled clear and reliable identification of the improvement of mitochondrial redox imbalance by BHB, evidenced by the reduction of Raman peak intensity at 750 cm−1, 1128 cm−1 and 1585 cm−1 in blood, tissue as well as purified mitochondria of db/db mice and the increase of tissue mitochondrial succinic dehydrogenase (SDH) staining after BHB treatment. Exogenous supplementation of BHB was also found to attenuate T2DM pathology related to mitochondrial redox states, involving organ injury, blood glucose control, insulin resistance and systemic inflammation. InterpretationOur findings provide strong evidence for BHB as a potential therapeutic strategy targeting mitochondria for T2DM.

Genotype-based precision nutrition strategies for the prediction and clinical management of type 2 diabetes mellitus.

Globally, type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders. T2DM physiopathology is influenced by complex interrelationships between genetic, metabolic and lifestyle factors (including diet), which differ between populations and geographic regions. In fact, excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM, whereas habitual intakes of plant-based healthy diets usually exert a protective effect. Moreover, genomic studies have allowed the characterization of sequence DNA variants across the human genome, some of which may affect gene expression and protein functions relevant for glucose homeostasis. This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression, some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions. Also, novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations. Furthermore, progresses in other omics areas (epigenomics, metagenomics, proteomics, and metabolomics) are improving current understanding of genetic insights in T2DM clinical outcomes. Although more investigation is still needed, the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening, prevention, diagnosis, management, and prognosis of T2DM through precision nutrition.

Association between type 2 diabetes mellitus and body composition based on MRI fat fraction mapping.

To explore the association between type 2 diabetes mellitus (T2DM) and body composition based on magnetic resonance fat fraction (FF) mapping. A total of 341 subjects, who underwent abdominal MRI examination with FF mapping were enrolled in this study, including 68 T2DM patients and 273 non-T2DM patients. The FFs and areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and abdominal muscle (AM) were measured at the level of the L1-L2 vertebral. The FF of bone marrow adipose tissue (BMAT) was determined by the averaged FF values measured at the level of T12 and L1 vertebral, respectively. The whole hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured based on 3D semi-automatic segmentation on the FF mapping. All data were analyzed by GraphPad Prism and MedCalc. VAT area, VAT FF, HFF, PFF of T2DM group were higher than those of non-T2DM group after adjusting for age and sex (P < 0.05). However, there was no differences in SAT area, SAT FF, BMAT FF, AM area and AM FF between the two groups (P > 0.05). VAT area and PFF were independent risk factors of T2DM (all P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) for VAT area and PFF in differentiating between T2DM and non-T2DM were 0.685 and 0.787, respectively, and the AUC of PFF was higher than VAT area (P < 0.05). Additionally, in seemingly healthy individuals, the SAT area, VAT area, and AM area were found to be significantly associated with being overweight and/or obese (BMI ≥ 25) (all P < 0.05). In this study, it was found that there were significant associations between T2DM and VAT area, VAT FF, HFF and PFF. In addition, VAT area and PFF were the independent risk factors of T2DM. Especially, PFF showed a high diagnostic performance in discrimination between T2DM and non-T2DM. These findings may highlight the crucial role of PFF in the pathophysiology of T2DM, and it might be served as a potential imaging biomarker of the prevention and treatment of T2DM. Additionally, in individuals without diabetes, focusing on SAT area, VAT area and AM area may help identify potential health risks and provide a basis for targeted weight management and prevention measures.

Exploring the Effects of Cyanidin-3-O-Glucoside on Type 2 Diabetes Mellitus: Insights into Gut Microbiome Modulation and Potential Antidiabetic Benefits.

Berries and their functional components have been put forward as an alternative to pharmacological treatments of type 2 diabetes mellitus (T2DM), and more attention has been paid to the gut microbiome in the pathophysiology of T2DM. Thus, we tried to examine the metabolic impact of red bayberry-derived cyanidin-3-O-glucoside (C3G) and investigate whether the antidiabetic effects of C3G were associated with the gut microbiome. As a result, C3G administration was found to reduce blood glucose levels of diabetic db/db mice, accompanied by increased levels of glucagon-like peptide (GLP-1) and insulin. Moreover, 16S rRNA analysis showed that the dominant microbiota modulated by C3G were pivotal in the glucose metabolism. Furthermore, the modulation of C3G on metabolic activities of gut bacteria leads to an increase in intestinal levels of key metabolites, particularly short-chain fatty acids. This contribution helps in promoting the secretion of GLP-1, which in turn increases insulin release with the purpose of reducing blood glucose levels. Overall, these findings may offer new thoughts concerning C3G against metabolic disorders in T2DM.

Monoamines' role in islet cell function and type 2 diabetes risk.

The two monoamines serotonin and melatonin have recently been highlighted as potent regulators of islet hormone secretion and overall glucose homeostasis in the body. In fact, dysregulated signaling of both amines are implicated in β-cell dysfunction and development of type 2 diabetes mellitus (T2DM). Serotonin is a key player in β-cell physiology and plays a role in expansion of β-cell mass. Melatonin regulates circadian rhythm and nutrient metabolism and reduces insulin release in human and rodent islets in vitro. Herein, we focus on the role of serotonin and melatonin in islet physiology and the pathophysiology of T2DM. This includes effects on hormone secretion, receptor expression, genetic variants influencing β-cell function, melatonin treatment, and compounds that alter serotonin availability and signaling.

Integrative bioinformatics analysis of biomarkers and pathways for exploring the mechanisms and molecular targets associated with pyroptosis in type 2 diabetes mellitus.

Research has shown that pyroptosis contributes greatly to the progression of diabetes and its complications. However, the exact relationship between this particular cell death process and the pathology of type 2 diabetes mellitus (T2DM) remains unclear. In this study, we used bioinformatic tools to identify the pyroptosis-related genes (PRGs) associated with T2DM and to analyze their roles in the disease pathology. Two microarray datasets, GSE7014 and GSE25724, were obtained from the GEO database and assessed for differentially expressed genes (DEGs). The T2DM-associated DEGs that overlapped with differentially expressed PRGs were noted as T2DM-PRGs. Subsequently, 25 T2DM-PRGs were validated and subjected to functional enrichment analysis through Gene Ontology annotation analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene set enrichment analysis (GSEA). The diagnostic and predictive value of the T2DM-PRGs was evaluated using receiver operating characteristic curves (ROC). Additionally, a single-sample GSEA algorithm was applied to study immune infiltration in T2DM and assess immune infiltration levels. We identified 25 T2DM-PRGs that were significantly enriched in the nuclear factor-kappa B signaling and prostate cancer pathways. The top five differentially expressed prognostic T2DM-PRGs targeted by miRNAs were PTEN, BRD4, HSP90AB1, VIM, and PKN2. The top five differentially expressed T2DM-PRGs associated with transcription factors were HSP90AB1, VIM, PLCG1, SCAF11, and PTEN. The genes PLCG1, PTEN, TP63, CHI3L1, SDHB, DPP8, BCL2, SERPINB1, ACE2, DRD2, DDX58, and BTK showed excellent diagnostic performance. The immune infiltration analysis revealed notable differences in immune cells between T2DM and normal tissues in both datasets. These findings suggest that T2DM-PRGs play a crucial role in the development and progression of T2DM and could be used as potential diagnostic biomarkers and therapeutic targets. Investigating the mechanisms and biomarkers associated with pyroptosis may offer valuable insights into the pathophysiology of T2DM and lead to novel therapeutic approaches to treat the disease.

Inter-organ crosstalk during development and progression of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by tissue-specific insulin resistance and pancreatic β-cell dysfunction, which result from the interplay of local abnormalities within different tissues and systemic dysregulation of tissue crosstalk. The main local mechanisms comprise metabolic (lipid) signalling, altered mitochondrial metabolism with oxidative stress, endoplasmic reticulum stress and local inflammation. While the role of endocrine dysregulation in T2DM pathogenesis is well established, other forms of inter-organ crosstalk deserve closer investigation to better understand the multifactorial transition from normoglycaemia to hyperglycaemia. This narrative Review addresses the impact of certain tissue-specific messenger systems, such as metabolites, peptides and proteins and microRNAs, their secretion patterns and possible alternative transport mechanisms, such as extracellular vesicles (exosomes). The focus is on the effects of these messengers on distant organs during the development of T2DM and progression to its complications. Starting from the adipose tissue as a major organ relevant to T2DM pathophysiology, the discussion is expanded to other key tissues, such as skeletal muscle, liver, the endocrine pancreas and the intestine. Subsequently, this Review also sheds light on the potential of multimarker panels derived from these biomarkers and related multi-omics for the prediction of risk and progression of T2DM, novel diabetes mellitus subtypes and/or endotypes and T2DM-related complications.

Alzheimer's Disease in Diabetic Patients: A Lipidomic Prospect.

Diabetes Mellitus (DM) and Alzheimer's disease (AD) have been two of the most common chronic diseases affecting people worldwide. Type 2 DM (T2DM) is a metabolic disease depicted by insulin resistance, dyslipidemia, and chronic hyperglycemia while AD is a neurodegenerative disease marked by Amyloid β (Aβ) accumulation, neurofibrillary tangles aggregation, and tau phosphorylation. Various clinical, epidemiological, and lipidomics studies have linked those diseases claiming shared pathological pathways raising the assumption that diabetic patients are at an increased risk of developing AD later in their lives. Insulin resistance is the tipping point beyond where advanced glycation end (AGE) products and free radicals are produced leading to oxidative stress and lipid peroxidation. Additionally, different types of lipids are playing a crucial role in the development and the relationship between those diseases. Lipidomics, an analysis of lipid structure, formation, and interactions, evidently exhibits these lipid changes and their direct and indirect effect on Aβ synthesis, insulin resistance, oxidative stress, and neuroinflammation. In this review, we have discussed the pathophysiology of T2DM and AD, the interconnecting pathological pathways they share, and the lipidomics where different lipids such as cholesterol, phospholipids, sphingolipids, and sulfolipids contribute to the underlying features of both diseases. Understanding their role can be beneficial for diagnostic purposes or introducing new drugs to counter AD.

Decreased plasma myonectin levels in female patients with type 2 diabetes mellitus and its correlation with lipid and glycemic parameters.

Myonectin is a novel myokine which has significant implications on diabetes. This study aimed to investigate plasma myonectin levels in patients with type 2 diabetes mellitus (T2DM), and their correlation with body composition, lipid and glycemic parameters. The study participants included 40 diabetic and 33 non-diabetic healthy adult Saudi females matched for their BMI and age. Body composition was assessed by bioelectrical impedance analysis. Fasting blood samples were used to investigate plasma myonectin levels by ELISA, along with lipid and glycemic parameters. We found that plasma myonectin levels were significantly decreased in diabetic patients (40.90±4.13 ng/ml, p<0.05) compared to non-diabetic participants (59.58±4.41). Diabetic patients with poor glycemic parameters had significantly decreased myonectin levels (35.18±4.03 ng/ml p<0.05) compared to non-diabetic healthy subjects. There was no significant difference in myonectin levels between diabetic patients with good glycemic control (55.76±8.09 ng/ml p>0.05) and non-diabetic healthy participants. Pearson correlation analysis indicated a significant negative correlation with fasting blood sugar (R=-0.366, p=0.001), HbA1c (R=-0.406, p<0.0001), triglycerides (R=-0.264, p=0.024), insulin (R=-0.278, p=0.017), and HOMA-IR (R=-0.409, p<0.0001). Our findings highlight an important aspect of myonectin in the pathophysiology of T2DM. They also show that myonectin has the potential to be a useful biomarker and therapeutic target in T2DM.

A Comprehensive Review on Prospects of Polymeric Nanoparticles for Treatment of Diabetes Mellitus: Receptors-Ligands, In vitro & In vivo Studies.

As per International Diabetes Federation Report 2022, worldwide diabetes mellitus (DM) caused 6.7M moralities and ~537M adults suffering from diabetes mellitus. It is a chronic condition due to β-cell destruction or insulin resistance that leads to insulin deficiency. This review discusses Type-1 DM and Type-2 DM pathophysiology in detail, with challenges in management and treatment. The toxicity issues of conventional drugs and insulin injections are complex to manage. Thus, there is a need for technological intervention. In recent years, nanotechnology has found a fruitful advancement of novel drug delivery systems that might potentially increase the efficacy of anti-diabetic drugs. Amongst nano-formulations, polymeric nanoparticles have been studied to enhance the bioavailability and efficacy of anti-diabetic drugs and insulin. In the present review, we summarized polymeric nanoparticles with different polymers utilized to deliver anti-diabetic drugs with in vitro and in vivo studies. Furthermore, this review also includes the role of receptors and ligands in diabetes mellitus and the utilization of receptor-ligand interaction to develop targeted nanoparticles. Additionally, we discussed the utility of nanoparticles for the delivery of phytoconstituents which aids in protecting the oxidative stress generated during diabetes mellitus.

The NLRP3 inflammasome rs35829419 C>A polymorphism is associated with type 2 diabetes mellitus in Saudi Arabia.

To investigate the frequency of NLRP3 gene rs35829419C>A single-nucleotide polymorphism (SNP) in a Saudi Arabian population from Jazan (Southwest Saudi Arabia) and test its potential association with type 2 diabetes mellitus (T2DM). This case-control study included 546 volunteers (271 patients with T2DM and 275 healthy controls) recruited from outpatient clinics at Jazan University Hospital and King Fahad Central Hospital in Jazan, Saudi Arabia, between December 2021 and July 2022. Genomic DNA was extracted from all samples and genotyped for the NLRP3 rs35829419C>A SNP using TaqMan technology. The association between the NLRP3 rs35829419 polymorphism and T2DM was examined using logistic regression analysis. Overall genotype distributions were 90.5% (CC), 9.3% (CA), and 0.2% (AA). The heterozygous CA genotype was more frequent in T2DM group (12.2%) compared to the control group (6.5%) and logistic regression analysis showed a statically significant association with T2DM risk under codominant (CA versus CC; odds ratio [OR]=1.99; 95% confidence interval [CI]= [1.11-3.61]; p=0.0270), and dominant (CA+AA versus CC; OR=2.05; CI=[1.16-3.75]; p=0.019) models of inheritance. This study revealed the frequency of NLRP3 rs35829419C>A polymorphism in our population and showed a direct correlation between having the minor allele for A and having a higher risk of developing T2DM. This study highlights the significance of NLRP3 rs35829419C>A polymorphism in the pathophysiology of T2DM.

Reduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus

Evidence from animal experiments has shown that the hypothalamic paraventricular nucleus (PVN) plays a key role in regulating body weight and blood glucose levels. However, it is unclear whether neuron populations in the human PVN are involved in the development of type 2 diabetes mellitus (T2DM). To address this, we investigated the neuronal and glial populations in the PVN of 26 T2DM patients and 20 matched controls. Our findings revealed a significant reduction in oxytocin (Oxt) neuron density in the PVN of T2DM patients compared to controls, while other neuronal populations remained unchanged. This suggests that Oxt neurons may play a specific role in the pathophysiology of T2DM. Interestingly, the reduction in Oxt neurons was accompanied by a decreased melanocortinergic input in to the PVN as reflected by a reduction in alpha-MSH immunoreactivity. We also analysed two glial cell populations, as they are important for maintaining a healthy neural microenvironment. We found that microglial density, phagocytic capacity, and their proximity to neurons were not altered in T2DM patients, indicating that the loss of Oxt neurons is independent of changes in microglial immunity. However, we did observe a reduction in the number of astrocytes, which are crucial for providing trophic support to local neurons. Moreover, a specific subpopulation of astrocytes characterized by aquaporin 4 expression was overrepresented in T2DM patients. Since this subset of astrocytes is linked to the glymphatic system, their overrepresentation might point to alterations in the hypothalamic waste clearance system in T2DM. Our study shows selective loss of Oxt neurons in the PVN of T2DM individuals in association with astrocytic reduction and gliovascular remodelling. Therefore, hypothalamic Oxt neurons may represent a potential target for T2DM treatment modalities.

The circadian rhythm: an influential soundtrack in the diabetes story.

Type 2 Diabetes Mellitus (T2DM) has been the main category of metabolic diseases in recent years due to changes in lifestyle and environmental conditions such as diet and physical activity. On the other hand, the circadian rhythm is one of the most significant biological pathways in humans and other mammals, which is affected by light, sleep, and human activity. However, this cycle is controlled via complicated cellular pathways with feedback loops. It is widely known that changes in the circadian rhythm can alter some metabolic pathways of body cells and could affect the treatment process, particularly for metabolic diseases like T2DM. The aim of this study is to explore the importance of the circadian rhythm in the occurrence of T2DM via reviewing the metabolic pathways involved, their relationship with the circadian rhythm from two perspectives, lifestyle and molecular pathways, and their effect on T2DM pathophysiology. These impacts have been demonstrated in a variety of studies and led to the development of approaches such as time-restricted feeding, chronotherapy (time-specific therapies), and circadian molecule stabilizers.

A Review of micro RNAs changes in T2DM in animals and humans.

Type 2 diabetes mellitus (T2DM) and its associated complications have become a crucial public health concern in the world. According to the literature, chronic inflammation and the progression of T2DM have a close relationship. Accumulated evidence suggests that inflammation enhances the insulin secretion lost by islets of Langerhans and the resistance of target tissues to insulin action, which are two critical features in T2DM development. Based on recently highlighted research that plasma concentration of inflammatory mediators such as tumor necrosis factor α and interleukin-6 are elevated in insulin-resistant and T2DM, and it raises novel question marks about the processes causing inflammation in both situations. Over the past few decades, microRNAs (miRNAs), a class of short, noncoding RNA molecules, have been discovered to be involved in the regulation of inflammation, insulin resistance, and T2DM pathology. These noncoding RNAs are specifically comprised of RNA-induced silencing complexes and regulate the expression of specific protein-coding genes through various mechanisms. There is extending evidence that describes the expression profile of a special class of miRNA molecules altered during T2DM development. These modifications can be observed as potential biomarkers for the diagnosis of T2DM and related diseases. In this review study, after reviewing the possible mechanisms involved in T2DM pathophysiology, we update recent information on the miRNA roles in T2DM, inflammation, and insulin resistance.

An evaluation of the effects of mixed heavy metals on prediabetes and type 2 diabetes: epidemiological and toxicogenomic analysis.

The link between mixed heavy metals (mercury, lead, and cadmium), prediabetes, and type 2 diabetes mellitus (T2DM), especially molecular mechanisms, is poorly understood. Thus, we aimed to identify the association between mixed heavy metals and T2DM and its components using a data set from the Korean National Health and Nutrition Examination Survey. We further analyzed the main molecular mechanisms implicated in T2DM development induced by mixed heavy metals using in-silico analysis. Our findings observed that serum mercury was associated with prediabetes, elevated glucose, and ln2-transformed glucose when using different statistical methods. "AGE-RAGE signaling pathway in diabetic complications", "non-alcoholic fatty liver disease", "metabolic Syndrome X", and three miRNAs (hsa-miR-98-5p, hsa-let-7a-5p, and hsa-miR-34a-5p) were listed as the most important molecular mechanisms related to T2DM development caused by mixed heavy metals. These miRNA sponge structures were created and examined, and they may be beneficial in the treatment of T2DM. The predicted cutoff values for three heavy metal levels linked to T2DM and its components were specifically identified. Our results imply that chronic exposure to heavy metals, particularly mercury, may contribute to the development of T2DM. To understand the changes in the pathophysiology of T2DM brought on by a combination of heavy metals, more research is required.