Insulin Resistance In Type Research Articles

Decreased mitochondrial creatine kinase 2 impairs skeletal muscle mitochondrial function independently of insulin in type 2 diabetes.

Increased plasma creatine concentrations are associated with the risk of type 2 diabetes, but whether this alteration is associated with or causal for impairments in metabolism remains unexplored. Because skeletal muscle is the main disposal site of both creatine and glucose, we investigated the role of intramuscular creatine metabolism in the pathophysiology of insulin resistance in type 2 diabetes. In men with type 2 diabetes, plasma creatine concentrations were increased, and intramuscular phosphocreatine content was reduced. These alterations were coupled to reduced expression of sarcomeric mitochondrial creatine kinase 2 (CKMT2). In C57BL/6 mice fed a high-fat diet, neither supplementation with creatine for 2 weeks nor treatment with the creatine analog β-GPA for 1 week induced changes in glucose tolerance, suggesting that increased circulating creatine was associated with insulin resistance rather than causing it. In C2C12 myotubes, silencing Ckmt2 using small interfering RNA reduced mitochondrial respiration, membrane potential, and glucose oxidation. Electroporation-mediated overexpression of Ckmt2 in skeletal muscle of high-fat diet-fed male mice increased mitochondrial respiration, independent of creatine availability. Given that overexpression of Ckmt2 improved mitochondrial function, we explored whether exercise regulates CKMT2 expression. Analysis of public data revealed that CKMT2 content was up-regulated by exercise training in both humans and mice. We reveal a previously underappreciated role of CKMT2 in mitochondrial homeostasis beyond its function for creatine phosphorylation, independent of insulin action. Collectively, our data provide functional evidence for how CKMT2 mediates mitochondrial dysfunction associated with type 2 diabetes.

A-064 Improved Insulin production in Advanced glycation end-products (AGEs)-induced RIN-m5F pancreatic β-cells by using a Flavonoid-Rich Medicinal Plant, Kaempferia parviflora treatment

Abstract Background Advanced glycation end-products (AGEs) are glycated proteins that react with reducing sugar which causes the damages of function and cellular signaling of insulin production in insulinoma cells. AGEs also contribute to hyperglycemia-induced insulin resistance in type 2 diabetes. AGEs gradually form during the chronic high blood glucose condition, which is a major risk factor and harmful to β-cells function and survival, and could alter the insulin signaling and downregulate the insulin-responsive transcription factors including PDX-1, Glut-2, GCK, and Pre-INS. Kaempferia parviflora, also known as black ginger and flavonoid-rich medicinal plant, has beneficial properties for type 2 diabetes patients as a counteracts the detrimental effects of AGEs and improves the insulin production in pancreatic β-cells. Thus, we hypothesize that treated β-cells with K. parviflora, which is the most effective flavonoid-containing plant might protect against the damage of AGEs-induced insulin impairment, and these effects are also responsible for improved insulin synthesis and the essential transcription factors in pancreatic β-cells. Methods Rat pancreatic β-cell line RIN-m5F (ATCC CRL-2058) were maintained and cultured in RPMI 1640 medium containing 10% (v/v) FBS, 1% penicillin-streptomycin at 37◦C in a humidified atmosphere containing 5% CO2. RIN-m5F cells were pre-treated with the K. parviflora at concentrations 0, 25, and 50 µg/ml for 48 hours, and afterward, exposure to 250 µg/ml AGEs treatment. To quantify the bioactive compound of K. parviflora, total phenolic and flavonoid content assays were performed and the transcriptional changes of insulin-related genes (PDX-1, Glut-2, GCK, and Pre-INS) were determined by using real-time qRT-PCR. Results K. parviflora has shown a high phenolic content and flavonoid content was 50.43 ± 1.74, 26.66 ± 1.18 mg GAE/g Dry weight of sample, respectively. For the transcriptional changes of insulin-related genes, the levels of gene expression in the regulators of insulin secreting pathway (PDX-1, Glut-2, GCK, and Pre-INS) were significantly downregulated after exposure to AGEs-treated, while the pre-treatment of K. parviflora was showed statistically difference. PDX-1, Glut-2, GCK, and Pre-INS expressions were significantly upregulated after pre-treated with 50 µg/ml K. parviflora. However, under the AGEs-treated alone condition, the transcriptional levels were significantly decreased as compared to the control (untreated). Taken together, these results suggest K. parviflora could be a potential natural medicine to ameliorate the damage of insulin production in AGEs-induced β-cell damage and highlight promising alternatives for therapeutic avenue against diabetes. Conclusions Treated RIN-m5F pancreatic β-cells with K. parviflora, a flavonoid-rich medicinal plant, could upregulate the insulin-responsive transcription factors and improve the insulin production in damaging AGEs-induced pancreatic β-cells. Our findings provide a novel strategy related metabolic disease and insights into the regulation of insulin synthesis by using K. parviflora treatment as a therapeutic agent against type 2 diabetes.

Balancing Relief and Pain: Effects of COX-2 Inhibitor Valdecoxib

Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, was initially acclaimed for its gastrointestinal safety and effectiveness in managing chronic inflammatory conditions and pain. It reduced gastrointestinal complications compared to other anti-inflammatory drugs, benefiting patients with complex medication regimens. The injectable form, parecoxib, was seen as promising for acute post-surgery pain management. However, clinical trials in high-risk cardiovascular patients, particularly those undergoing coronary artery bypass grafting, revealed increased risks when using higher doses of parecoxib. These findings led to the re-evaluation of valdecoxib’s safety profile and its subsequent market withdrawal due to cardiovascular concerns and reports of serious skin reactions. Despite its withdrawal, valdecoxib has garnered interest for repurposing in other conditions. Its pharmacodynamic and pharmacokinetic properties suggest potential in qualifying palmitate-induced insulin resistance in type 2 diabetes and inhibiting matrix metalloproteinases for wound healing. Its efficacy against SARS-CoV-2 highlights drug repurposing strategies for health crises like COVID-19. Valdecoxib's established success in arthritis, dysmenorrhea, and postoperative pain, along with its potential in treating glaucoma, underscores the value of repurposing existing drugs for new therapeutic purposes. In conclusion, valdecoxib exemplifies the balance between drug safety, clinical utility, and innovative repurposing. The aim of this study is to fully harness drug potential in medical science through a concerted effort made by the scientific community, regulatory bodies, and industry stakeholders to navigate the technological and regulatory hurdles.

The Role of Nitric Oxide, Lipocalin-2, and Proinflammatory Cytokines on Proteinuria and Insulin Resistance in Type 2 Diabetes Mellitus Subgroups.

Nitric oxide (NO) is a bioactive signaling molecule that mediates various physiological and biological processes. Type 2 diabetes mellitus (T2DM) can be categorized into several subgroups according to fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels. Few studies have closely examined the effect of NO and lipocalin-2 on albuminuria and insulin resistance in T2DM subgroups. This study investigated the role of NO, lipocalin-2, and proinflammatory cytokines on the development of proteinuria and insulin resistance in patients with T2DM subgroups. A total of 256 subjects, including 191 patients with T2DM and 65 non-diabetic healthy individuals, were evaluated. NO metabolites (NOx), lipocalin-2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured. Patients with T2DM were classified into three subgroups: patients with FPG-defined diabetes (PG-DM), those with HbA1c-defined diabetes (HA-DM), and those who met the criteria for both FPG and HbA1c (PG/HA-DM). The albumin-to-creatinine ratio (ACR) and the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated. NOx, lipocalin-2, and TNF-α levels were significantly higher in patients with T2DM than in healthy individuals. Patients with PG/HA-DM had significantly higher NOx levels than those with PG-DM or HA-DM. Of the patients with high NOx levels, patients with lipocalin-2 elevation exhibited higher ACR and HOMA-IR than those without lipocalin-2 elevation. NOx was positively correlated with lipocalin-2, ACR, HOMA-IR, and TNF-α but not with HOMA-B and IL-6. The upper quartile of NOx levels led to a 1.2-fold increase in the risk of albuminuria (odds ratio: 1.215; 95% CI: 1.012-2.418; p < 0.001). NO plays a crucial role in proteinuria and insulin resistance by collaborating with lipocalin-2 and TNF-α, showing significantly higher levels in patients with PG/HA-DM than in those with PG-DM or HA-DM.

Altered Subcortical Brain Volume and Cortical Thickness Related to Insulin Resistance in Type 2 Diabetes Mellitus.

The objective of this study is to examine the alterations in subcortical brain volume and cortical thickness among individuals diagnosed with Type 2 diabetes mellitus (T2DM) through the application of morphometry techniques and, additionally, to investigate the potential association between these modifications and insulin resistance (IR). The present cross-sectional study comprised a total of 121 participants (n=48 with healthy controls [HCs] and n=73 with T2DM) who were recruited and underwent a battery of cognitive testing and structural magnetic resonance imaging (MRI). FreeSurfer was used to process the MRI data. Analysis of covariance compared discrepancies in cortical thickness and subcortical brain volume between T2DM and HCs, adjusting for the potential confounding effects of gender, age, education, and body mass index (BMI). Exploratory partial correlations investigated links between IR and brain structure in T2DM participants. Compared with HCs, individuals with T2DM demonstrated a cortical thickness decrease in the right caudal middle frontal gyrus, right pars opercularis, left precentral gyrus, and bilateral superior frontal gyrus. Furthermore, this study for T2DM found that the severity of IR was inversely related to the volume of the left putamen and left hippocampus, as well as the thickness of the left pars orbitalis, left pericalcarine, right entorhinal area, and right rostral anterior cingulate gyrus. The evidence for structural brain changes in T2DM was observed, and alterations in cortical thickness were concentrated in the frontal lobes. Correlations between IR and frontal cortical thinning may serve as a potential neuroimaging marker of T2DM and lead to various diabetes-related brain complications.

Increased carbohydrate intake does not alter insulin resistance in type 2 diabetic patients

Increased carbohydrate intake does not alter insulin resistance in type 2 diabetic patients

Targeting insulin resistance: myricetin and isorhamnetin from Hardwickia binata, and luteolin from Hedysarum alpinum enhance glucose uptake and AMPK signaling in HepG2 cells

This study examined five plants (Xylopia aethiopica, Agave sisalana, Hardwickia binata, Hedysarum alpinum, and Toxicodendron vernicifluum) for their potential to address insulin resistance in type 2 diabetes. In-vitro assays showed that H. binata leaves and H. alpinum flowers inhibited α-glucosidase and α-amylase while enhancing glucose uptake in normal and insulin-resistant HepG2 cells. Phytochemical screening and SPE purification identified the key constituents responsible for the effects. The chromatographic and spectral analysis confirmed flavonoids in H. binata (myricetin, isorhamnetin, quercetin, kaempferol, and catechin) and H. alpinum (luteolin, quercetin, kaempferol, and apigenin). Myricetin, isorhamnetin, and luteolin significantly increased glucose uptake, enhanced hexokinase and pyruvate kinase activities, and promoted IRec and IRS-1 phosphorylation, modulating insulin signalling. They activated AMPK and Akt, with molecular docking confirming strong AMPK binding. These findings suggest that H. binata, H. alpinum, and their flavonoids are promising candidates for managing insulin resistance and type 2 diabetes, warranting further research.

Evaluation of serum irisin level and severity of erectile dysfunction in diabetic males: a cross sectional prospective study

BackgroundIrisin is an exercise-induced myokine that alleviates endothelial dysfunction and reduces insulin resistance in type 2 diabetes mellitus (T2DM). The current study aimed to assess the serum level of irisin in T2DM men with erectile dysfunction (ED) compared to T2DM patients with normal erectile function and healthy controls, as well as investigate the association between serum irisin level and the severity of ED in T2DM patients.Patients and methodsA cross-sectional study was conducted on 90 males, divided into three groups: 32 T2DM patients with ED, 24 T2DM patients without ED, and 34 healthy controls. Socio-demographic characteristics and scores of the validated Arabic version of the international Index of Erectile Function-5 (ArIIEF-5), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were obtained. Furthermore, routine laboratory tests employed for diabetes monitoring and serum levels of total testosterone and irisin were assessed within these groups.ResultsT2DM men with ED had significantly lower serum levels of irisin and testosterone, as well as a lower ArIIEF-5 score, but their GAD-7 and PHQ-9 scores were significantly higher than those without ED or controls (p < 0.001). Among T2DM men, serum irisin levels positively associated with ArIIEF-5 scores and serum testosterone (r = 0.413, p = 0.002; r = 0.936, p < 0.001, respectively) but negatively associated with glycosylated hemoglobin levels (r = -0.377, p = 0.004). Multivariate regression analysis to predict ED in T2DM patients found that GAD-7 score was the only most significant predictor for ED (ꞵ = − 1.176, standard error = 0.062, p < 0.001).ConclusionThe current study had demonstrated that irisin positively correlated with the ArIIEF-5 and serum testosterone but negatively correlated with HbA1c in T2DM men. Nevertheless, further validation of these findings is necessary through cohort studies.

Low-intensity pulsed ultrasound ameliorates insulin resistance in type 2 diabetes mice via promoting glucagon-like peptide-1 release

Abstract Glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal L-cells. It regulates glucose levels by boosting insulin secretion, inhibiting glucagon release, and preventing β-cell death. GLP-1 is increasingly used in managing type 2 diabetes mellitus (T2DM). This study assessed the effectiveness of low-intensity pulsed ultrasound (LIPUS), a non-pharmacological intervention, in enhancing insulin resistance in diabetic mice by stimulating GLP-1 release. T2DM was induced in C57BL/6J mice through a high-fat diet and streptozotocin injection. Mice were divided into Control, T2D-sham and T2D-LIPUS groups. The T2D-LIPUS group received LIPUS treatment with a frequency of 1MHz, intensity of 120mW/cm2, and duty cycle of 20%for 20 minutes/day, 5 days/week for 4 weeks. Glucose tolerance and insulin resistance were measured through tests. Pancreatic histology and GLP-1 expression in serum were evaluated. Results showed that T2DM increased insulin resistance, but LIPUS treatment alleviated it. GLP-1 levels significantly increased in the T2D-LIPUS group compared to the T2D-sham group, approaching the control group’s level. LIPUS also reduced apoptosis of islet β cells. These findings suggest that LIPUS stimulation of the intestine can enhance islet β-cell activity through GLP-1 regulation of the gut-pancreas axis, mitigating insulin resistance in T2DM.

Relationship between indices of insulin resistance and incident type 2 diabetes mellitus in Chinese adults.

Insulin resistance (IR) is a pivotal pathogenesis characteristic of type 2 diabetes mellitus (T2DM). The current study aimed to explore the association between triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c), triglyceride-glucose (TyG), and triglyceride glucose-body mass index (TyG-BMI), and T2DM incidence. A total of 116,855 Chinese adults aged over 20 without diabetes were included. Multivariate Cox regression analysis and restricted cubic spine were utilized to investigate the association between IR indicators and T2DM. The T2DM risk across different quartiles of IR parameters was compared using Kaplan-Meier curves. The receiver operating characteristic analysis was used to investigate the predictive potential of each IR indicator for future T2DM. A total of 2685 participants developed T2DM during a median follow-up of 2.98 years. The adjusted hazard ratios (HR) of incident T2DM were 1.177, 2.766, and 1.1018 for TG/HDL-c, TyG, and TyG-BMI, respectively. There were significant increasing trends of T2DM across the quartiles of TG/HDL-c, TyG, and TyG-BMI. The HRs of new-onset T2DM in the highest quartiles versus the lowest quartile of TG/HDL-c, TyG, and TyG-BMI were 3.298, 8.402, and 8.468. RCS revealed the nonlinear relationship between IR and T2DM risk. The correlations between IR and T2DM were more pronounced in subjects aged <40. TyG-BMI had the highest predictive value for incident T2DM (AUC = 0.774), with a cut-off value of 213.289. TG/HDL-c, TyG, and TyG-BMI index were all significantly positively associated with higher risk for future T2DM. Baseline TyG-BMI level had high predictive value for the identification of T2DM.

EFEKTIVITAS SEDUHAN DAUN ASAM JAWA TERHADAP KADAR HOMA-IR DAN HOMA-β PADA PASIEN DIABETES MELLITUS TIPE 2

This study assessed the impact of tamarind leaf tea on HOMA-IR and HOMA-β levels in patients with Type 2 Diabetes Mellitus (DM). Thirty-two patients aged 20-50 years from Sungai Ambawang District Health Center, who were not using any DM medication, participated. They were divided into control (KN) and treatment (KP) groups, with KP receiving a tamarind leaf tea infusion for 7 days. HOMA-IR and HOMA-β levels were calculated using standardized formulas based on fasting insulin and glucose levels. The Wilcoxon signed-rank test revealed a significant decrease in HOMA-IR levels in the KP group (p&lt;0.05), while no significant change was observed in the KN group. Although no significant difference in HOMA-β levels was found between the two groups, the KP group showed a notable increase by 4. These findings suggest that a 7-day tamarind leaf tea infusion effectively reduced HOMA-IR levels in patients with type 2 DM, although it did not significantly affect HOMA-β levels. This study highlights the potential of tamarind leaf tea as a complementary approach for managing insulin resistance in Type 2 DM patients. Further research is needed to explore the long-term effects and mechanisms of action for improving β-cell function. The conclusion of this study is that steeping tamarind leaves for seven days can reduce HOMA-I levels and slightly increase HOMA-β levels in patients with type 2 Diabetes Mellitus.

Oxytocin does not acutely improve glucose tolerance in men with type 2 diabetes.

To assess oxytocin's acute glucoregulatory impact in men with type 2 diabetes in the context of our previous findings that oxytocin improves β-cell responsivity in healthy men. In a double-blind, crossover comparison, intranasal oxytocin (24 IU) and placebo, respectively, were administered to 25 fasted men with non-insulin-treated type 2 diabetes (age ± standard error of the mean, 63.40 ± 1.36 years; body mass index, 27.77 ± 0.66 kg/m2; HbA1c, 6.86% ± 0.08%; Homeostatic Model Assessment of Insulin Resistance (HOMA-IR, 3.44 ± 0.39) 60 minutes before an oral glucose tolerance test (oGTT). Key outcomes were compared with previous results in men with normal weight or obesity. Oxytocin compared with placebo increased plasma oxytocin concentrations and reduced the heart rate, but did not alter glucose metabolism in the 3 hours after oGTT onset (area under the curve, glucose, 2240 ± 80.5 vs. 2190 ± 69.5 mmol/L × min; insulin, 45 663 ± 4538 vs. 44 343 ± 4269 pmol/L × min; C-peptide, 235 ± 5.1 vs. 231 ± 15.9 nmol/L × min). This outcome contrasts with the oxytocin-induced attenuation of early postprandial glucose excursions in normal-weight individuals, but is in line with the absence of respective effects in men with obesity. We conclude that insulin resistance in type 2 diabetes is associated with decreased sensitivity to the acute glucoregulatory effect of oxytocin in male individuals.

Formononetin attenuates hepatic injury in diabetic mice by regulating macrophage polarization through the PTP1B/STAT6 axis

BackgroundFormononetin (FNT) is an isoflavone known for its anti-inflammatory properties and has been shown to reduce insulin resistance in Type 2 Diabetes Mellitus (T2DM). However, its effects and the underlying mechanisms in diabetic liver injury remain largely unexplored. MethodsWe established a T2DM-induced liver injury mouse model by feeding high-fat diet, followed by injecting streptozotocin. The mice were then treated with FNT and the liver function in these mice was assessed. Macrophage markers in FNT-treated T2DM mice or human THP-1 cells were evaluated using flow cytometry, RT-qPCR, and Western blotting. The expression of PTP1B and STAT6 in mouse liver tissues and THP-1 cells was analyzed. Molecular docking predicted the interaction between PTP1B and STAT6, which was validated via co-immunoprecipitation (Co-IP) and phos-tag analysis. Microscale thermophoresis (MST) assessed the binding affinity of FNT to PTP1B. ResultsFNT treatment significantly ameliorated blood glucose levels, hepatocyte apoptosis, inflammatory response, and liver dysfunction in T2DM mice. Moreover, FNT facilitated M2 macrophage polarization in both T2DM mice and high glucose (HG)-induced THP-1-derived macrophages. The PTP1B/STAT6 axis, deregulated in T2DM mice, was normalized by FNT treatment, which counteracted the T2DM-induced upregulation of PTP1B and downregulation of phosphorylated STAT6. Molecular docking and subsequent analyses revealed that PTP1B binds to and dephosphorylates STAT6 at the S325A site. In contrast, FNT strongly binds to PTP1B and influences its expression at the K116A site, promoting M2 polarization of THP-1 cells via downregulation of PTP1B. ConclusionFormononetin mitigates diabetic hepatic injury by fostering M2 macrophage polarization via the PTP1B/STAT6 axis.

Investigating the causal association between obesity and risk of hepatocellular carcinoma and underlying mechanisms

Obesity is a global health concern and independent risk factor for cancers including hepatocellular carcinoma (HCC). However, evidence on the causal links between obesity and HCC is limited and inconclusive. This study aimed to investigate the causal relationship between obesity-related traits and HCC risk and explore underlying mechanisms using bioinformatics approaches. Two-sample Mendelian randomization analysis was conducted leveraging publicly available genome-wide association study summary data on obesity traits (body mass index, body fat percentage, waist circumference, waist-to-hip ratio, visceral adipose tissue volume) and HCC. Associations of obesity with primary mechanisms (insulin resistance, adipokines, inflammation) and their effects on HCC were examined. Differentially expressed genes in obesity and HCC were identified and functional enrichment analyses were performed. Correlations with tumor microenvironment (TME) and immunotherapy markers were analyzed. Genetically predicted higher body mass index and body fat percentage showed significant causal relationships with increased HCC risk. Overall obesity also demonstrated causal links with insulin resistance, circulating leptin levels, C-reactive protein levels and risk of severe insulin resistant type 2 diabetes. Four differentially expressed genes (ESR1, GCDH, FAHD2A, DCXR) were common in obesity and HCC. Enrichment analyses indicated their roles in processes like RNA capping, viral transcription, IL-17 signaling and endocrine resistance. They exhibited negative correlations with immune cell infiltration and immunotherapy markers in HCC. Overall obesity likely has a causal effect on HCC risk in Europeans, possibly via influencing primary mechanisms. The identified differentially expressed genes may be implicated in obesity-induced hepatocarcinogenesis through regulating cell cycle, inflammation and immune evasion. Further research on precise mechanisms is warranted.

Study of the Relationship between Platelet Distribution Width, Red Blood Cell Distribution Width and Insulin Resistance in Type 2 Diabetic Patients with Non-Alcoholic Fatty Liver Disease

Abstract Background Insulin resistance is identified as an impaired biological response to insulin stimulation of target tissues, primarily the liver, muscle, and adipose tissue. The metabolic consequences of insulin resistance can result in hyperglycaemia, hypertension, dyslipidaemia, visceral adiposity, hyperuricemia, elevated inflammatory markers, endothelial dysfunction, and a prothrombotic state. Progression of insulin resistance can lead to metabolic syndrome, non- alcoholic fatty liver disease, and type 2 diabetes mellitus. Aim of the Work We aimed by our study to assess the relationship of platelet distribution width and red blood cell distribution width with insulin resistance in patients with type 2 diabetes with and without non-alcoholic fatty liver disease (NAFLD) and to check if platelet distribution width or red blood cell distribution width could be easy predictors of insulin resistance. Patients and Methods The present study is a Case Control Study was conducted in Ain Shams University Hospital. This study includes 80 subjects with matched age and sex. Results The present study results confirmed that low RDW was associated with increased risk of developing diabetes mellitus. Their study found that RDW is negatively correlated with waist and FG, insulin and TG concentrations. We also found that the group with the lowest quartile of RDW had the highest glucose, insulin and HOMA levels. Moreover, our results were found that there is a significant negative correlation of RDW with poor glycemic control. Our results also found that decreased levels of red blood cell distribution widths (RDW) were all associated with increased fasting insulin. Our study was documented a negative correlation between HbA1c and the platelet index PDW. Conclusion In our study, we found a relation between insulin resistance and red blood cell distribution width. RDW (fl) could be used to discriminate between patients with type II diabetes and controls.

Effects of Helicobacter pylori Infection on Insulin Resistance in Type 2 Mellitus Diabetics and Non-Diabetics Subjects at Brazzaville University Hospital

Introduction: H.pylori infection is the most common bacterial infection worldwide and is associated with gastrointestinal diseases and extra-gastrointestinal pathologies such as diabetes mellitus and insulin resistance. Objective: To evaluate insulin resistance in diabetics and non-diabetics infected with H. pylori. Methods: We conducted a descriptive cross-sectional study. 90 patients were selected and divided into two groups, 44 patients with T2DM and 46 non-diabetic patients. All information concerning the age and sex of subjects was collected from medical records. Insulin levels were determined by ELISA, blood glucose and HbA1C levels by Cobas c 311, and the HOMA-IR index was calculated. Results: The mean age of T2DM patients was 51 ± 11 years, and that of NDT patients 40±15 years. Women (68) predominated over men (22), with a sex ratio of 0.32. The mean values for T2DM patients were: glycemia 12.6±2.3 mmol/l, HbA1C 10.37±2.9%, HOMA-IR 2.69±1.35 (p&lt;0.001), Insulinemia 8.71±3.14 μU/ml (p= 0.801). Univariate logistic regression analysis showed: Glycemia OR 2.29 [95% IC 1.80-4.5], HbA1C OR 3.08 [95% IC 0.87-1.02], Insulin OR 1.02 [95% IC 1.0-0.16] and HOMA-IR OR 4.4 [95% IC 0.55-0.95]. Means for NDT infections were: blood glucose 9.7±1.0 mmol/l, insulin 9.7±1.64 μU/ml, HOMA-IR 1.45±0.42, HbA1C 8.6±0.9%. Univariate logistic regression analysis showed: Blood glucose OR1.1 [95% IC1.01-2.14], HbA1C OR 1.35 [95% IC 0.08-1.34], Insulin OR 0.51 [95% IC 0.12-1.08], HOMA-IR OR 2.4 [95% IC 0.32-1.45]. Conclusion: Our study showed a statistical significant difference between H.pylori infection and Insulin resistance, also confirms the link of both.Abbreviations: T2DM: Type two diabetes of mellitus, NDT: No-Diabetics, OR: Odd ratio.

Comparative Determination of Mitochondrial Biomarkers and Their Relationship With Insulin Resistance in Type 2 Diabetic Patients: An Observational Cross-Sectional Study.

Data suggest malfunctioning mitochondria reduce oxidation and adenosine triphosphate (ATP) production, disrupting insulin signalling. Cytochrome c(CC), acylcarnitine (AC) and citrate synthase (CS) are essential components of the mitochondria machinery and can be used as reliable biomarkers of mitochondrial dysfunction. This study aimed to determine whether mitochondrial biomarkers (AC, CS and CC) are altered in individuals with type 2 diabetes mellitus (T2DM) and to examine the association between these biomarkers and insulin resistance. A cross-sectional observational study that recruited 170 participants (88 with T2DM and 82 without DM) was conducted. Blood samples were collected from the recruits and analysed for levels of fasting glucose (FBG), AC, CS, CC, insulin, total cholesterol, triglycerides (TG), glycated haemoglobin (HbA1c) and magnesium. Blood pressure (BP) and anthropometric characteristics of participants were also taken. Appropriate formulas were used to determine %body fat, body mass index (BMI), waist-to-hip ratio (WHR), the homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-β). Patients with T2DM had higher levels of CC, %body fat, FBG, TG, HbA1c, BMI and HOMA-IR than controls (p < 0.05, respectively). Results showed a significant relationship between circulating CC levels versus HOMA-β (r = -0.40, p = 0.001), CS (r = -0.70, p = 0.001) and AC (r = -0.72, p = 0.001) levels in patients with T2DM. The adjusted odds increased in the T2DM patients for VLDL (OR = 6.66, p = 0.002), HbA1c (OR = 6.50, p = 0.001), FPG (OR = 3.17, p = 0.001), TG (OR = 2.36, p = 0.010), being female (OR = 2.09, p = 0.020) and CC (OR = 1.14, p = 0.016). Overall, alterations in mitochondrial biomarkers, measured by AC, CC and CS, were observed in people with T2DM and showed a direct relationship with insulin resistance. These findings are potentially significant in Africa, although additional confirmation from a larger cohort is necessary.

Effect of Cryolipolysis on Insulin Resistance in Type 2 Diabetic Females with Abdominal Obesity

Effect of Cryolipolysis on Insulin Resistance in Type 2 Diabetic Females with Abdominal Obesity

Long term administration of thiamine disulfide improves FOXO1/PEPCK pathway in liver to reduce insulin resistance in type 1 diabetes rat model

ObjectiveThe main objective of this study was to find if thiamine disulfide (TD) lowers blood glucose level and improves insulin resistance (IR) in liver and muscle in rats with chronic type 1 diabetes (T1DM) using euglycemic-hyperinsulinemic clamp technique. MethodsA total of fifty male Wistar rats were assigned to five groups consisted of: non-diabetic control (NDC), diabetic control (DC), diabetic treated with thiamine disulfide (D-TD), diabetic treated with insulin (D-insulin), and diabetic treated with both TD and insulin (D-insulin+TD). Diabetes was induced by a 60 mg/kg dose of streptozotocin. Blood glucose levels, pyruvate tolerance test (PTT), intraperitoneal glucose tolerance test (IPGTT), levels of glycosylated hemoglobin (HbA1c), glucose infusion rate (GIR), liver and serum lipid profiles, liver glycogen stores, liver enzymes ([ALT], [AST]), and serum calcium and magnesium levels. were evaluated. Additionally, gene expression levels of phosphoenolpyruvate carboxykinase (Pepck), forkhead box O1 (Foxo1), and glucose transporter type 4 (Glut4) were assessed in liver and skeletal muscle tissues. ResultsBlood glucose level was reduced by TD treatment. In addition, TyG index, HOMA-IR, serum and liver lipid profiles, HbA1c levels, and expressions of Foxo1 and Pepck genes were decreased significantly (P<0.05) in all the treated groups. However, TD did not influence Glut4 gene expression, but GIR as a critical index of IR were 5.0±0.26, 0.29±0.002, 1.5±0.07, 0.9±0.1 and 1.3±0.1 mg.min−1Kg−1 in NDC, DC, D-TD, D-insulin and D-insulin+TD respectively. ConclusionsTD improved IR in the liver primarily by suppressing gluconeogenic pathways, implying the potential use of TD as a therapeutic agent in diabetes.

Metabolic Score for Insulin Resistance and New-Onset Type 2 Diabetes in a Middle-Aged and Older Adult Population: Nationwide Prospective Cohort Study and Implications for Primary Care.

The metabolic score for insulin resistance (METS-IR) has emerged as a noninsulin-based index for the approximation of insulin resistance (IR), yet longitudinal evidence supporting the utility of METS-IR in the primary prevention of type 2 diabetes mellitus (T2DM) remains limited. We aimed to investigate the longitudinal association between METS-IR, which combines fasting plasma glucose (FPG), lipid profiles, and anthropometrics that can be routinely obtained in resource-limited primary care settings, and the incidence of new-onset T2DM. We conducted a closed-cohort analysis of a nationwide, prospective cohort of 7583 Chinese middle-aged and older adults who were free of T2DM at baseline, sampled from 28 out of 31 provinces in China. We examined the characteristics of participants stratified by elevated blood pressure (BP) at baseline and new-onset T2DM at follow-up. We performed Cox proportional hazard regression analysis to explore associations of baseline METS-IR with incident T2DM in participants overall and in participants stratified by baseline BP. We also applied net reclassification improvement and integrated discrimination improvement to examine the incremental value of METS-IR. During a mean follow-up period of 6.3 years, T2DM occurred in 527 participants, among which two-thirds (332/527, 62.9%; 95% CI 58.7%-67.1%) had baseline FPG<110 mg/dL. A SD unit increase in baseline METS-IR was associated with the first incidence of T2DM (adjusted hazard ratio [aHR] 1.33, 95% CI 1.22-1.45; P<.001) in all participants. We obtained similar results in participants with normal baseline BP (aHR 1.41, 95% CI 1.22-1.62; P<.001) and elevated baseline BP (aHR 1.29, 95% CI 1.16-1.44; P<.001). The predictive capability for incident T2DM was improved by adding METS-IR to FPG. In study participants with new-onset T2DM whose baseline FPG was <126 mg/dL and <110 mg/dL, 62.9% (332/527; 95% CI 60%-65.9%) and 58.1% (193/332; 95% CI 54.3%-61.9%) of participants had baseline METS-IR above the cutoff values, respectively. METS-IR was significantly associated with new-onset T2DM, regardless of baseline BP level. Regular monitoring of METS-IR on top of routine blood glucose in clinical practice may add to the ability to enhance the early identification of primary care populations at risk for T2DM.