Pathogenesis Of Type 2 Diabetes Mellitus Research Articles

Matriptase as a potential biomarker and therapeutic target in newly diagnosed type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that affects the processing of carbohydrates, proteins, and lipids. In T2DM, metabolic dysregulation occurs through various pathways caused by increased levels of many adipokines and inflammatory chemokines. Impaired insulin-glucose metabolism occurs in tissues. The proteolytic enzyme matriptase is thought to be closely related to glucose metabolism due to its glycolization sites. Our study aimed to evaluate the correlation between matriptase, a proteolytic enzyme, and metabolic parameters in individuals recently diagnosed with T2DM. We also sought to investigate the potential involvement of matriptase in the development of diabetes. We measured all participants' metabolic laboratory parameters, including basic biochemical tests, hemograms, high-sensitivity C-reactive protein (hsCRP), and matriptase levels. Our results showed a significant increase in circulating matriptase levels in individuals with T2DM compared to the control group. Furthermore, individuals with metabolic syndrome had significantly higher matriptase levels than those without in the T2DM and control groups. We also observed that T2DM patients had elevated levels of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), hsCRP, and matriptase, which displayed a positive correlation. Our study is the first to report elevated levels of matriptase in individuals with newly diagnosed T2DM and/or metabolic syndrome. Additionally, we found a significant positive correlation between matriptase levels and metabolic and inflammatory parameters, indicating a potential role for matriptase in the pathogenesis of T2DM and glucose metabolism. Further research on matriptase could lead to its recognition as a novel target for investigation.

Quantification of ectopic fat storage in the liver and pancreas using six-point Dixon MRI and its association with insulin sensitivity and β-cell function in patients with central obesity.

To assess the association of ectopic fat deposition in the liver and pancreas quantified by Dixon magnetic resonance imaging (MRI) with insulin sensitivity and β-cell function in patients with central obesity. A cross-sectional study of 143 patients with central obesity with normal glucose tolerance (NGT), prediabetes (PreD), and untreated type 2 diabetes mellitus (T2DM) was conducted between December 2019 and March 2022. All participants underwent routine medical history taking, anthropometric measurements, and laboratory tests, including a standard glucose tolerance test to quantify insulin sensitivity and β-cell function. The fat content in the liver and pancreas was measured with MRI using the six-point Dixon technique. Patients with T2DM and PreD had a higher liver fat fraction (LFF) than those with NGT, while those with T2DM had a higher pancreatic fat fraction (PFF) than those with PreD and NGT. LFF was positively correlated with homeostatic model assessment of insulin resistance (HOMA-IR), while PFF was negatively correlated with homeostatic model assessment of insulin secretion (HOMA-β). Furthermore, using a structured equation model, we found LFF and PFF to be positively associated with glycosylated hemoglobin via HOMA-IR and HOMA-β, respectively. In patients with central obesity, the effects of LFF and PFF on glucose metabolism. were associated with HOMA-IR and HOMA-β, respectively. Ectopic fat storage in the liver and pancreas quantified by MR Dixon imaging potentially plays a notable role in the onset ofT2DM. We highlight the potential role of ectopic fat deposition in the liver and pancreas in the development of type 2 diabetes in patients with central obesity, providing valuable insights into the pathogenesis of the disease and potential targets for intervention. • Ectopic fat deposition in the liver and pancreas is associated with T2DM. • T2DM and prediabetes patients had higher liver and pancreatic fat fractions than normal individuals. • The results provide valuable insights into pathogenesis of T2DM and potential targets for intervention.

A comparative study of the gut microbiome in Indian children with type 1 diabetes and healthy controls.

Type 1 diabetes mellitus (T1DM) occurs in genetically susceptible individuals due to certain environmental triggers causing destruction of insulin secreting beta cells. One of the environmental triggers studied recently in the pathogenesis and progression of T1DM is the role of gut microbiome. (1) To compare the gut microbiome profile of T1DM children with healthy age, gender, and body mass index (BMI) matched controls. (2) To assess the relationship of abundance of genera with glycemic control in children with T1DM. Cross-sectional, case-control study. Sixty-eight children with T1DM and 61 age-, gender-, and BMI-matched healthy controls were enrolled. QIAamp Fast DNA Stool Mini kit protocol and reagents were used for DNA isolation and Miseq sequencing platform for targeted gene sequencing. Alpha and beta diversity analysis showed no significant differences in the abundance of microbes between the groups. At phylum level, Firmicutes was the dominant phylum followed by Actinobacteria and Bacteroidota in both groups. Analysis of microbiome at the genera level showed that percentage abundance for Parasutterella was higher in children with T1DM as compared to the healthy group (p < .05). A linear regression analysis showed that increase in abundance of Haemophilus (adjusted R2 = -1.481 p < .007) was associated with a significant decrease in glycated hemoglobin (HbA1c) concentrations (p < .05). Our comparative study of gut microbiome profile showed significant differences in the taxonomial composition between Indian children with T1DM and healthy controls. Short chain fatty acid producers may play an important role in glycemic control.

Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes Mellitus.

The high prevalence of type 2 diabetes mellitus (T2DM), and the lack of effective therapy, determine the need for new treatment options. The present study is focused on the NO-donors drug class as effective antidiabetic agents. Since numerous biological systems are involved in the pathogenesis and progression of T2DM, the most promising approach to the development of effective drugs for the treatment of T2DM is the search for pharmacologically active compounds that are selective for a number of therapeutic targets for T2DM and its complications: oxidative stress, non-enzymatic protein glycation, polyol pathway. The nitrosyl iron complex with thiosulfate ligands was studied in this work. Binuclear iron nitrosyl complexes are synthetic analogues of [2Fe-2S] centers in the regulatory protein natural reservoirs of NO. Due to their ability to release NO without additional activation under physiological conditions, these compounds are of considerable interest for the development of potential drugs. The present study explores the effects of tetranitrosyl iron complex with thiosulfate ligands (TNIC-ThS) on T2DM and its complications regarding therapeutic targets in vitro, as well as its ability to bind liposomal membrane, inhibit lipid peroxidation (LPO), and non-enzymatic glycation of bovine serum albumin (BSA), as well as aldose reductase, the enzyme that catalyzes the reduction in glucose to sorbitol in the polyol pathway. Using the fluorescent probe method, it has been shown that TNIC-ThS molecules interact with both hydrophilic and hydrophobic regions of model membranes. TNIC-ThS inhibits lipid peroxidation, exhibiting antiradical activity due to releasing NO (IC50 = 21.5 ± 3.7 µM). TNIC-ThS was found to show non-competitive inhibition of aldose reductase with Ki value of 5.25 × 10-4 M. In addition, TNIC-ThS was shown to be an effective inhibitor of the process of non-enzymatic protein glycation in vitro (IC50 = 47.4 ± 7.6 µM). Thus, TNIC-ThS may be considered to contribute significantly to the treatment of T2DM and diabetic complications.

Signaling pathways and intervention for therapy of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) represents one of the fastest growing epidemic metabolic disorders worldwide and is a strong contributor for a broad range of comorbidities, including vascular, visual, neurological, kidney, and liver diseases. Moreover, recent data suggest a mutual interplay between T2DM and Corona Virus Disease 2019 (COVID-19). T2DM is characterized by insulin resistance (IR) and pancreatic β cell dysfunction. Pioneering discoveries throughout the past few decades have established notable links between signaling pathways and T2DM pathogenesis and therapy. Importantly, a number of signaling pathways substantially control the advancement of core pathological changes in T2DM, including IR and β cell dysfunction, as well as additional pathogenic disturbances. Accordingly, an improved understanding of these signaling pathways sheds light on tractable targets and strategies for developing and repurposing critical therapies to treat T2DM and its complications. In this review, we provide a brief overview of the history of T2DM and signaling pathways, and offer a systematic update on the role and mechanism of key signaling pathways underlying the onset, development, and progression of T2DM. In this content, we also summarize current therapeutic drugs/agents associated with signaling pathways for the treatment of T2DM and its complications, and discuss some implications and directions to the future of this field.

NF-κB/NLRP3 inflammasome axis and risk of Parkinson's disease in Type 2 diabetes mellitus: A narrative review and new perspective.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Genetic predisposition and immune dysfunction are involved in the pathogenesis of PD. Notably, peripheral inflammatory disorders and neuroinflammation are associated with PD neuropathology. Type 2 diabetes mellitus (T2DM) is associated with inflammatory disorders due to hyperglycaemia-induced oxidative stress and the release of pro-inflammatory cytokines. Particularly, insulin resistance (IR) in T2DM promotes the degeneration of dopaminergic neurons in the substantia nigra (SN). Thus, T2DM-induced inflammatory disorders predispose to the development and progression of PD, and their targeting may reduce PD risk in T2DM. Therefore, this narrative review aims to find the potential link between T2DM and PD by investigating the role of inflammatory signalling pathways, mainly the nuclear factor kappa B (NF-κB) and the nod-like receptor pyrin 3 (NLRP3) inflammasome. NF-κB is implicated in the pathogenesis of T2DM, and activation of NF-κB with induction of neuronal apoptosis was also confirmed in PD patients. Systemic activation of NLRP3 inflammasome promotes the accumulation of α-synuclein and degeneration of dopaminergic neurons in the SN. Increasing α-synuclein in PD patients enhances NLRP3 inflammasome activation and the release of interleukin (IL)-1β followed by the development of systemic inflammation and neuroinflammation. In conclusion, activation of the NF-κB/NLRP3 inflammasome axis in T2DM patients could be the causal pathway in the development of PD. The inflammatory mechanisms triggered by activated NLRP3 inflammasome lead to pancreatic β-cell dysfunction and the development of T2DM. Therefore, attenuation of inflammatory changes by inhibiting the NF-κB/NLRP3 inflammasome axis in the early T2DM may reduce future PD risk.

Mechanism of immune attack in the progression of obesity-related type 2 diabetes

Obesity and overweight are widespread issues in adults, children, and adolescents globally, and have caused a noticeable rise in obesity-related complications such as type 2 diabetes mellitus (T2DM). Chronic low-grade inflammation is an important promotor of the pathogenesis of obesity-related T2DM. This proinflammatory activation occurs in multiple organs and tissues. Immune cell-mediated systemic attack is considered to contribute strongly to impaired insulin secretion, insulin resistance, and other metabolic disorders. This review focused on highlighting recent advances and underlying mechanisms of immune cell infiltration and inflammatory responses in the gut, islet, and insulin-targeting organs (adipose tissue, liver, skeletal muscle) in obesity-related T2DM. There is current evidence that both the innate and adaptive immune systems contribute to the development of obesity and T2DM.

Novel Insight into the Effect of Probiotics in the Regulation of the Most Important Pathways Involved in the Pathogenesis of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is considered one of the most common disorders worldwide. Although several treatment modalities have been developed, the existing interventions have not yielded the desired results. Therefore, researchers have focused on finding treatment choices with low toxicity and few adverse effects that could control T2DM efficiently. Various types of research on the role of gut microbiota in developing T2DM and its related complications have led to the growing interest in probiotic supplementation. Several properties make these organisms unique in terms of human health, including their low cost, high reliability, and good safety profile. Emerging evidence has demonstrated that three of the most important signaling pathways, including nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and nuclear factor erythroid 2-related factor 2 (Nrf2), which involved in the pathogenesis of T2DM, play key functions in the effects of probiotics on this disease. Hence, we will focus on the clinical applications of probiotics in the management of T2DM. Then, we will also discuss the roles of the involvement of various probiotics in the regulation of the most important signaling pathways (NF-κB, PI3K/Akt, and Nrf2) involved in the pathogenesis of T2DM.

Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance. The incidence of T2DM is increasing globally, and a growing body of evidence suggests that gut microbiota dysbiosis may contribute to the development of this disease. Gut microbiota-derived metabolites, including bile acids, lipopolysaccharide, trimethylamine-N-oxide, tryptophan and indole derivatives, and short-chain fatty acids, have been shown to be involved in the pathogenesis of T2DM, playing a key role in the host-microbe crosstalk. This review aims to summarize the molecular links between gut microbiota-derived metabolites and the pathogenesis of T2DM. Additionally, we review the potential therapy and treatments for T2DM using probiotics, prebiotics, fecal microbiota transplantation and other methods to modulate gut microbiota and its metabolites. Clinical trials investigating the role of gut microbiota and its metabolites have been critically discussed. This review highlights that targeting the gut microbiota and its metabolites could be a potential therapeutic strategy for the prevention and treatment of T2DM.

Role of obesity related inflammation in pathogenesis of peripheral artery disease in patients of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) has emerged as one of the greatest global health challenges of twenty-first century. Visceral obesity is one of the most important determinant of insulin resistance (IR) as well as T2DM complications. Therefore this review focuses on the molecular mechanism of obesity induced inflammation, signaling pathways contributing to diabetes, as well as role of lifestyle interventionsand medical therapies in the prevention and management of T2DM. Articles were searched on digital data base PubMed, Cochrane Library, and Web of Science. The key words used for search included Type 2 diabetes mellitus, obesity, insulin resistance, vascular inflammation and peripheral arterial disease. Visceral obesity is associated with chronic low grade inflammation and activation of immune systems which are involved in pathogenesis of obesity related IR and T2DM. Metabolic dysregulation of adipose tissue leads to local hypoxia, misfolded/unfolded protein response and increased circulating free fatty acids, which in turn initiate inflammatory signaling cascades in the population of infiltrating cells. Mechanism that relates the role of adipocytokines with insulin sensitivity and glucose homeostasis might throw a light on the development of therapeutic interventions and subsequently might result in the reduction of vascular complications.

U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population.

To clarify the expression of N6-methyladenosine (m6 A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population. The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6 A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6 A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23-7.47]) in model 4. Seven significantly altered m6 A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6 A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

Association of Interleukin-32α with Interleukin-35 and Transforming Growth Factor-β Produced by the Peripheral Blood Mononuclear Cells from Patients with Type 2 Diabetes Mellitus

Background and Objective: Cytokine production was shown to be changed in Type 2 diabetes mellitus (T2DM). Nonetheless, the relationship of pro-inflammatory interleukin (IL)-32α with anti-inflammatory IL-35 and transforming growth factor (TGF)-β is unclear in T2DM. The present study aimed to evaluate the IL-32α, IL-35, and TGF-β levels produced by peripheral blood mononuclear cells (PBMCs) in patients compared to healthy controls (HCs). Correlations between the IL-32α and IL-35 and TGF-β, as well as between those cytokines and paraclinical parameters [(fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c), GFR, albumin, and creatinine)] were assessed. Materials and Methods: Blood samples were taken from 38 patients and 38 HCs. The PBMCs from each donor were isolated with the ficoll method and cultured with in vitro stimulator for four days. The production of IL-32α, IL-35, and TGF-β in culture supernatants was determined with ELISA. Paraclinical parameters were evaluated by standard laboratory methods. Results: High levels of IL-32α and low levels of IL-35 were found in patients compared to in HCs (P=0.006; P&lt;0.001). A negative correlation between IL-32α and IL-35 was detected in patients (P&lt;0.001). IL-32α was positively correlated with FPG and HbA1c (P=0.002, P=0.005), whereas IL-35 was negatively correlated with them in patients (both P&lt;0.001). No correlations were detected between the cytokines and BMI, GFR, albumin, and creatinine, as well as between the TGF-β levels. Conclusion: Increased IL-32α but diminished IL-35 production are linked with each other and with the glucose metabolism parameters in T2DM. It seems that IL-32α and IL-35 have a potential role in T2DM pathogenesis.

Increased expression of serum IL-18 and IL-18R in newly diagnosed type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a heterogeneous metabolic disorder in which genetic, sedentary lifestyle, obesity, and environmental factors come together to produce insulin resistance in target tissues, leading to hyperglycemia. Evidence reveals that inflammation may play an essential role in the pathogenesis of T2DM. Interleukin-18 (IL-18), a proinflammatory cytokine, plays a crucial role in the acute and chronic inflammatory process. The association of IL-18 levels with IL-18R expression in T2DM has not been investigated so far. The aim of this study was to compare the peripheral changes in serum IL-18 levels and its receptor (IL18R) expression in newly diagnosed T2DM and healthy controls. A total of 35 newly diagnosed type 2 diabetic cases and 35 non-diabetic controls were enrolled after obtaining informed consent. Venous whole blood was taken under aseptic conditions. Biochemical parameters were estimated in an auto-analyzer. Serum IL-18 levels were calculated using ELISA, whereas IL-18R expression was determined via RT-PCR. GAPDH was used as an internal control. When compared to non-diabetic controls, the serum IL-18 levels were significantly higher in T2DM patients (P=0.010) along with a significant upregulation of IL18R (P=0.0018). Serum IL-18 levels in T2DM and non-diabetic controls were 669.5 (445) and 498.3 (404.9) pg/mL respectively, and IL-18R showed a fold change of 10.33. Both serum IL-18 and its receptor IL-18R is significantly higher in newly diagnosed T2DM patients.

Shared peripheral blood biomarkers for Alzheimer’s disease, major depressive disorder, and type 2 diabetes and cognitive risk factor analysis

BackgroundAlzheimer's disease (AD), type 2 diabetes mellitus (T2DM), and Major Depressive Disorder (MDD) have a higher incidence rate in modern society. Although increasing evidence supports close associations between the three, the mechanisms underlying their interrelationships remain elucidated. ObjectiveThe primary purpose is to explore the shared pathogenesis and the potential peripheral blood biomarkers for AD, MDD, and T2DM. MethodsWe downloaded the microarray data of AD, MDD, and T2DM from the Gene Expression Omnibus database and constructed co-expression networks by Weighted Gene Co-Expression Network Analysis to identify differentially expressed genes. We took the intersection of differentially expressed genes to obtain co-DEGs. Then, we performed GO and KEGG enrichment analysis on the common genes in the AD, MDD, and T2DM-related modules. Next, we utilized the STRING database to find the hub genes in the protein-protein interaction network. ROC curves were constructed for co-DEGs to obtain the most diagnostic valuable genes and to make drug predictions against the target genes. Finally, we conducted a present condition survey to verify the correlation between T2DM, MDD and AD. ResultsOur findings indicated 127 diff co-DEGs, 19 upregulated co-DEGs, and 25 down-regulated co-DEGs. Functional enrichment analysis showed co-DEGs were mainly enriched in signaling pathways such as metabolic diseases and some neurodegeneration. Protein-protein interaction network construction identified hub genes in AD, MDD and T2DM shared genes. We identified seven hub genes of co-DEGs, namely, SMC4, CDC27, HNF1A, RHOD, CUX1, PDLIM5, and TTR. The current survey results suggest a correlation between T2DM, MDD and dementia. Moreover, logistic regression analysis showed that T2DM and depression increased the risk of dementia. ConclusionOur work identified common pathogenesis of AD, T2DM, and MDD. These shared pathways might provide novel ideas for further mechanistic studies and hub genes that may serve as novel therapeutic targets for diagnosing and treating.

Comparison of Plasma Exosome Proteomes Between Obese and Non-Obese Patients with Type 2 Diabetes Mellitus.

Obesity is considered a promoter of type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. This study aimed to identify plasma exosome differentially expressed proteins (DEPs) that are potentially involved in the development of obesity-related T2DM. Exosomes were isolated from the plasma of obese and non-obese T2DM patients (n = 10 for each group). A label-free quantitative mass spectrometry analysis was applied to identify plasma exosome DEPs in obese patients compared with non-obese patients, followed by bioinformatics analysis including GO annotation, KEGG analysis, subcellular localization prediction, transcription factor analysis, and protein-protein interaction (PPI) prediction. We identified 2 significantly upregulated proteins (C9 and PON1) and 5 significantly downregulated proteins (HPX, A1BG, CFHR1, ANG, and CALM) in obese patients compared with those in non-obese patients. KEGG analysis demonstrated that the insulin signaling pathway was one of the pathways that significantly correlated with the DEPs. The DEPs were primarily localized in the extracellular space (5 out of 7). HMG-box and NF-Y beta might regulate the transcription of the DEPs. C9, PON1, HPX, and CFHR1 were present in the PPI network. The plasma exosome DEPs are potentially responsible for the development of obesity-related T2DM possibly through the insulin signaling pathway and the interaction with other proteins. Our study may guide future research direction toward the pathogenesis of obesity-related T2DM.

Bariatric Surgery: Targeting pancreatic β cells to treat type II diabetes.

Pancreatic β-cell function impairment and insulin resistance are central to the development of obesity-related type 2 diabetes mellitus (T2DM). Bariatric surgery (BS) is a practical treatment approach to treat morbid obesity and achieve lasting T2DM remission. Traditionally, sustained postoperative glycemic control was considered a direct result of decreased nutrient intake and weight loss. However, mounting evidence in recent years implicated a weight-independent mechanism that involves pancreatic islet reconstruction and improved β-cell function. In this article, we summarize the role of β-cell in the pathogenesis of T2DM, review recent research progress focusing on the impact of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on pancreatic β-cell pathophysiology, and finally discuss therapeutics that have the potential to assist in the treatment effect of surgery and prevent T2D relapse.

The interactions between inflammation and insulin resistance: molecular mechanisms in insulin-producing and insulin-dependent tissues

In the modern world the prevalence of obesity and type 2 diabetes mellitus (T2DM) significantly increases. In this light the risks of obesity-associated complications also grow up. The crucial linkage between obesity and its metabolic and cardiovascular complications is inflammatory process. The mechanism of this linkage is similar in pancreas and insulin-dependent tissues both on cells, cell-to-cell communication and signaling pathway levels: the catalysts are different lipids (cholesterol, free fatty acids, triglycerides), which are able to activate Toll-like receptors of innate immunity and inflammation. Nextly, IKK- and JNK-dependent cascades activate the secretion of inflammatory cytokines TNFa, IL-1b, IL-6 and others, which act by paracrine and autocrine manner and support inflammation both in local and systemic levels. Thus, insulin-producing and insulin-dependent tissues, which are involved in T2DM pathogenesis, through the inflammatory process integrate in pathogenic and self-maintaining cycle, which leads to the suppression of insulin secretion, pancreatic β-cell failure and the development of insulin-dependent tissues insulin resistance.

Liraglutide on type 2 diabetes mellitus with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 16 RCTs.

Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM). Our aim is to investigate the effects of liraglutide on T2DM with NAFLD. Relevant articles published from the earliest publication to March 2022 were selected from several databases. The Cochrane Collaboration's RevMan software was used for the analysis. Sixteen studies are selected for this meta-analysis, which includes totally 634 patients in the treatment group and 630 patients in the control group. As a result, 14 studies show that fasting plasma glucose levels of the experimental group are lower than that of the control group; 15 studies show that glycosylated hemoglobin A1c levels of the experimental group are lower than that of the control group; 13 studies show that triglyceride levels of the experimental group are lower than that of the control group; twelve studies show that total cholesterol levels of the experimental group are lower than that of the control group; 10 studies show that alanine aminotransferase levels of the experimental group is lower than that of the control group; 10 studies show that no significant difference in changes in aspartate transaminase between 2 groups; 13 studies show that low density lipoprotein cholesterol levels of the experimental group is lower than that of the control group; 9 studies show that no significant difference in changes in high density lipoprotein cholesterol between 2 groups; 7 studies mentioned adverse effects and the difference is significant. Liraglutide is potentially curative for T2DM with NAFLD.

Firmicutes/Bacteroidetes Ratio of Gut Microbiota and Its Relationships with Clinical Parameters of Type 2 Diabetes Mellitus: A Systematic Review

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a global health problem with multifactorial etiopathogenesis. Recent studies show gut microbiota dysbiosis that plays a crucial role in pathogenesis and complications of T2DM. Firmicutes and Bacteroidetes phylum ratio (F/B ratio) is one of the markers for gut microbiota dysbiosis which remains to be investigated in recent decades. AIM: The present study summarized the correlation between B/F ratio with some clinical parameters of T2DM. METHODS: A systematic review of the literature for clinical studies was performed on PubMed, ProQuest, and Google Scholar. Studies were assessed for risk of bias using Newcastle–Ottawa scale. All observational cross-sectional, case–control, and cohort studies that studied F/B or B/F ratio in T2DM were included. Key evidence was analyzed and qualitatively synthesized. RESULT: Seven relevant studies were included. Five studies were high-quality and two studies were medium-quality. The F/B ratio of the gut microbiota varies in different types of T2DM and is associated with different clinical parameters. The F/B ratio decreased inT2DM and had significant negative correlation with OGTT blood glucose but had unsignificant correlation with fasting fasting blood glucose, postprandial blood glucose, and HbA1C. The F/B ratio might increase in T2DM and was positively correlated with lean tissue index and associated with the wider left atrial size. CONCLUSION: Current systematic review demonstrated that intestinal microbiota dysbiosis played a key role in the pathogenesis of T2DM. The gut microbiota F/B ratio was varied and was associated with various clinical parameters in T2DM.

Increased intestinal-fatty acid binding protein in obesity-associated type 2 diabetes mellitus.

Obesity is a traditional risk factor for type 2 diabetes mellitus (T2DM). However, recent studies reported that metabolically unhealthy obesity (MUO) exerts a higher risk of developing T2DM than metabolically healthy obesity (MHO) because of its higher state of insulin resistance. This may happen due to metabolic endotoxemia through gut dysbiosis and increased intestinal permeability. Our study aimed to know the association of intestinal permeability using intestinal fatty acid-binding protein (I-FABP) with obesity-related T2DM patients in Indonesia. This was a cross-sectional study that recruited 63 participants with obesity defined using body mass index (BMI) classification for the Asia-Pacific population (BMI ≥25 kg/m2). All participants were then grouped into T2DM and non-T2DM based on American Diabetes Association (ADA) diagnostic criteria. The I-FABP levels were measured using the enzyme-linked immunosorbent assay method. The I-FABP level of T2DM group was higher compared to non-T2DM group, namely 2.82 (1.23) ng/mL vs. 1.78 (0.81) ng/mL (p<0.001; mean difference 1.033 with 95% CI 0.51-1.55). This difference was not attenuated even after adjustment for age. The fitted regression model using linear regression was: i-FABP = 1.787+1.034*(DM) (R2 = 18.20%, standardized ß = 0.442, p<0.001). This study underscores the association of intestinal permeability with T2DM in people with obesity and supports the evidence of the potential role of intestinal permeability in the pathogenesis of obesity-related T2DM.