Effects of different doses of metformin on bone mineral density and bone metabolism in elderly male patients with type 2 diabetes mellitus

BACKGROUND Diabetes is a chronic disease,which may cause various complications.Patients with diabetes are at high risk of bone and joint disorders,such as osteoporosis and bone fractures.In addition,it became widely accepted that diabetes has an important impact on bone metabolism.Metformin is a commonly used and effective first-line treatment for type 2 diabetes.Some glucose-lowering agents have been found to have an effect on bone metabolism.The present study explored if different doses of metformin have an effect on bone mineral density(BMD)and bone metabolism in type 2 diabetes.AIM To investigate the effects of different doses of metformin on BMD and bone metabolism in elderly male patients with type 2 diabetes mellitus.METHODS A total of 120 elderly male outpatients with type 2 diabetes mellitus who were admitted to our hospital were included in the study from July 2018 to June 2019.They were randomly assigned to an experimental group and a control group with 60 patients in each group.Patients in the experimental group were given high dose metformin four times a day 0.5 g each time for 12 wk.Patients in the control group were given low dose metformin orally twice a day 0.5 g each time for 12 wk.The changes in bone mineral density and bone metabolism before and after treatment and the efficacy rate of the treatment were compared between the two groups.RESULTS There was no significant difference in the efficacy rate between the two groups(P>0.05).Before the treatment,there was no significant difference in BMD and bone metabolism between the two groups(P>0.05).However,after the treatment,BMD and bone metabolism were improved in the two groups.Moreover,BMD and 25-hydroxyvitamin D were significantly higher in the experimental group than in the control group,and N-terminal/midregion andβ-isomerized Cterminal telopeptides were significantly lower in the experimental group than in the control group(all P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).CONCLUSION Both high and low dose metformin can effectively control the blood glucose levels in elderly male patients with type 2 diabetes mellitus.However,the benefits of high dose metformin in improving BMD and bone metabolism level was more obvious in patients with type 2 diabetes mellitus.

Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2 diabetes mellitus

BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.

Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma

BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.

Subclinical impairment of left ventricular myocardium function in type 2 diabetes mellitus patients with or without hypertension

BACKGROUND Cardiovascular disease has been the leading cause of morbidity and mortality for type 2 diabetes mellitus(T2DM)patients over the last decade.AIM To determine whether layer-specific global longitudinal strain(GLS)combined with peak strain dispersion(PSD)can be used to assess left ventricle(LV)myocardium systolic dysfunction in T2DM patients or without hypertension(HP).METHODS We enrolled 97 T2DM patients,70 T2DM+HP patients and 101 healthy subjects.Layer-specific GLS and PSD were calculated by EchoPAC software in apical three-,four-and two-chamber views.GLS of the epimyocardial,middle-layer and endomyocardial(GLSepi,GLSmid,and GLSendo)were measured and recorded.Receiver operating characteristic analysis was performed to detect LV myocardium systolic dysfunction in T2DM patients.RESULTS There were significant differences in GLSepi,GLSmid,GLSendo,and PSD between healthy subjects,T2DM patients and T2DM patients with HP(P<0.001).Trend tests yielded the ranking of healthy subjects>T2DM patients>T2DM with HP patients in the absolute values of GLSepi,GLSmid and GLSendo(P<0.001),while PSD was ranked healthy subjects<T2DM<T2DM with HP(P<0.001).Layer-specific GLS and PSD had high diagnostic efficiency for detecting LV myocardium systolic dysfunction in T2DM patients,however,the area under the curve(AUC)for layer-specific GLS and PSD combined was significantly higher than the AUCs for the individual indices(P<0.05).CONCLUSION Layer-specific GLS and PSD were associated with LV myocardium systolic dysfunction in T2DM patients,T2DM patients with HP.T2DM patients with HP have more severe LV myocardium systolic dysfunction than T2DM patients without HP and normal control patients.The combination of layer-specific GLS and PSD may provide additional prognostic information for T2DM patients with or without HP.

Evaluation of left ventricular systolic function in type 2 diabetes mellitus patients with and without peripheral vascular disease

BACKGROUND Peripheral vascular disease(PVD)is a common complication of type 2 diabetes mellitus(T2DM).Patients with T2DM have twice the risk of PVD as nondiabetic patients.AIM To evaluate left ventricular(LV)systolic function by layer-specific global longitudinal strain(GLS)and peak strain dispersion(PSD)in T2DM patients with and without PVD.METHODS Sixty-five T2DM patients without PVD,57 T2DM patients with PVD and 63 normal controls were enrolled in the study.Layer-specific GLS[GLS of the epimyocardium(GLSepi),GLS of the middle myocardium(GLSmid)and GLS of the endocardium(GLSendo)]and PSD were calculated.Receiver operating characteristic(ROC)analysis was performed to calculate the sensitivity and specificity of LV systolic dysfunction in T2DM patients with PVD.We calculated Pearson’s correlation coefficients between biochemical data,echocardiographic characteristics,and layer-specific GLS and PSD.RESULTS There were significant differences in GLSepi,GLSmid and GLSendo between normal controls,T2DM patients without PVD and T2DM patients with PVD(P<0.001).Trend tests revealed a ranking of normal controls>T2DM patients without PVD>T2DM patients with PVD in the absolute value of GLS(P<0.001).PSD differed significantly between the three groups,and the trend ranking was as follows:normal controls<T2DM patients without PVD<T2DM patients with PVD(P<0.001).ROC analysis revealed that the combination of layer-specific GLS and PSD had high diagnostic efficiency for detecting LV systolic dysfunction in T2DM patients with PVD.Lowdensity lipoprotein cholesterol was positively correlated with GLSepi,GLSmid and PSD(P<0.05),while LV ejection fraction was negatively correlated with GLSepi,GLSmid and GLSendo in T2DM patients with PVD(P<0.01).CONCLUSION PVD may aggravate the deterioration of LV systolic dysfunction in T2DM patients.Layer-specific GLS and PSD can be used to detect LV systolic dysfunction accurately and conveniently in T2DM patients with or without PVD.

The Effect of Tuberculosis Infection on Pancreatic Beta-Cell Function in Patients with Type 2 Diabetes Mellitus

Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.

Investigation of 25-Hydroxy Vitamin D Status and Related Factors in Hospitalised Patients with Type 2 Diabetes Mellitus

Objective: To investigate the distribution of 25-hydroxy Vitamin D level status in type 2 diabetes mellitus inpatients, as well as the differences in general conditions and clinical indicators in patients with different Vitamin D status. Methods: Retrospective analysis of 250 admitted type 2 diabetes inpatients admitted to the endocrinology department of qinghai provincial hospital of traditional chinese medicine from september 2022 to december 2023, collated and analysed the general data and laboratory indicators of the patient cases, and applied spss26.0 to process and analyse the data and explore the differences in the general conditions and commonly used clinical nutritional indicators of type 2 diabetes in patients with different 25-hydroxyVitamin D levels. The differences between the different 25-hydroxy Vitamin D levels in type 2 diabetes mellitus patients. Results: 1) A total of 250 inpatients with type 2 diabetes mellitus were included in this study, of which 56 cases (22.4%) were patients with 25 hydroxyvitamin D deficiency [25(OH)D P P P P > 0.05). 3) The distribution of some laboratory indexes among the three groups of patients was differentiated, with the average level of glycated haemoglobin in the lack group being significantly higher than that of the remaining two groups, the average level of albumin being significantly lower than that of the remaining two groups, and the average level of haemoglobin being significantly lower than that of the good group (P P > 0.05). Conclusion: The 25(OH)D level of type 2 diabetes mellitus inpatients is not optimistic. In clinical diagnosis and treatment, we should pay attention to the changes in 25 hydroxyvitamin D levels and other nutritional indexes of patients with type 2 diabetes mellitus, and focus on the control of blood glucose levels and timely supplementation of vitamins, proteins, and lipids, in order to improve the patients’ physical status, reduce the incidence of complications, and improve the clinical efficacy and the patients’ quality of life.

Analysis of the Application Effect of Family Collaborative Care Model on Elderly Patients with Type 2 Diabetes Mellitus and the Situation of Self-Care Ability

Objective: To study the application effect of the family collaborative care model on elderly patients with type 2 diabetes mellitus and its influence on self-care ability. Methods: The elderly type 2 diabetes mellitus patients (400 cases) treated in our hospital between March 2020 and July 2023 were divided into two groups by randomized grouping method;the control group received the conventional nursing program, while the observation group received the family collaborative nursing model. Blood glucose level, self-care ability, and quality of life were compared between the groups. Results: The blood glucose level of the observation group was lower than that of the control group (P < 0.05). The self- care ability and quality of life scores of the observation group were higher than those of the control group (P < 0.05). Conclusion: The family collaborative care model for elderly patients with type 2 diabetes mellitus can promote their self- care ability, improve the effect of glycemic control, and improve their quality of life, and is suitable for further promotion and application.

Analysis of the Effect of Integrated Extended Care Model in Improving the Quality of Life of Elderly Patients with Type 2 Diabetes Mellitus

Objective: To analyze the impact of an integrated extended care model on improving the quality of life of elderly patients with Type 2 Diabetes Mellitus (T2DM). Methods: A total of 176 patients admitted to the hospital from March 2015 to February 2018 were selected and randomly assigned to an observation group and a control group, with 88 patients each. The control group implemented conventional nursing interventions, and the observation group carried out an integrated extended-care model. The level of glycemic control, quality of life, and daily medication adherence between both groups were compared. Results: The observation group showed significant improvement in the level of glycemic control, and their fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin levels were significantly lower as compared with those in the study group (P < 0.05). The quality of life of the patients in the observation group was higher than that of the control group (P < 0.05). The observation group had a higher compliance score (95.48 ± 7.45) than the control group (81.31 ± 8.72) (t = 8.909, P < 0.05). Conclusion: The integrated extended care model allows patients to receive comprehensive and individualized nursing services after discharge, which improves the effect of drug therapy and the quality of life of patients.

Association of plasma vitamin A level with type 2 diabetes mellitus:a community aging population-based cross-sectional study

Recent studies indicated that vitamin A(VA)might be involved in the pathology of type 2 diabetes mellitus(T2DM).This cross-sectional study was conducted to explore the association between circulating VA level and T2DM.A total of 1818 subjects aged 50 years old and above were recruited from the community.Binomial logistic regression and restricted cubic spline(RCS)were applied to analyze the association of plasma VA level with the risk of T2DM.Serum VA and lipid-adjusted VA levels of T2DM patients were significantly higher than that of non-T2DM subjects(P<0.05).The ratios of plasma VA/total cholesterol(TC),VA/high-density lipoprotein cholesterol(HDL-c)and VA/low-density lipoprotein cholesterol(LDL-c)were positively associated with the risk of T2DM in the aging population(P<0.05).Compared with the Q1 level,subjects with Q2 to Q3 levels of plasma VA/triglyceride(TG)have decreased risk of T2DM(odds ratio(OR)Q2=0.68,P_(Q2)=0.021;ORQ3=0.59,P_(Q3)<0.01).Our results indicated that the imbalance of circulating lipids and VA might affect the relationship between VA and T2DM.The middle and aging subjects with higher ratios of plasma VA/TC,VA/HDL-c,and VA/LDL-c displayed increased risk for T2DM,but the moderate ratio of VA/TG might protect against risk of T2DM.

The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity:A Meta-Analysis

Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and obesity.Therefore,we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1(GLP-1)receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity.Methods PubMed,Web of Science,Embase,the Cochrane Central Register of Controlled Trials,and Clinicaltrial.gov were systematically searched from inception to July 2023.Randomized controlled trials(RCTs)of GLP-1 receptor-based agonists(GLP-1RA,GLP-1 based dual and triple receptor agonist)with reports of asthma events were included.Outcomes were computed as risk ratios(RR)using a fixedeffects model.Results Overall,39 RCTs with a total of 85,755 participants were included.Compared to non-GLP-1 receptor-based agonist users,a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments,although the difference was not statistically significant[RR=0.91,95%confidence interval(CI):0.68 to 1.24].Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users(RR=0.65,95%CI:0.43 to 0.99,P=0.043).We also performed sensitivity analyses for participant characteristics,study design,drug structure,duration of action,and drug subtypes.However,no significant associations were observed.Conclusion Compared with non-users,a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments.Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment

BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.

Vitamin D and selenium for type 2 diabetes mellitus with Hashimoto’s thyroiditis:Dosage and duration insights

This letter discusses the publication by Feng et al.Iodine,selenium,and vitamin D are closely associated with thyroid hormone production in humans;however,the efficacy of selenium and vitamin D supplementation for type 2 diabetes mellitus(T2DM)patients with Hashimoto’s thyroiditis(HT)remains controversial.In the retrospective study we discuss herein,the authors highlighted significant improvements in thyroid function,thyroid antibodies,blood glucose,and blood lipid in T2DM patients with HT following addition of vitamin D and selenium to their antidiabetic regimens,underscoring the value of these supplements.Our team is currently engaged in research exploring the relationship between micronutrients and HT,and we have obtained invaluable insights from the aforementioned study.Based on this research and current literature,we recommend a regimen of 4000 IU/day of vitamin D and 100-200μg/day of selenium for over three months to six months for patients with HT,particularly for those with concurrent T2DM.

Examining the association between delay discounting,delay aversion and physical activity in Chinese adults with type-2 diabetes mellitus

BACKGROUND The role of physical activity in diabetes is critical,influencing this disease's development,man-agement,and overall outcomes.In China,22.3%of adults do not meet the minimum level of physical activity recommended by the World Health Organization.Therefore,it is imperative to identify the factors that contributing to lack of physical activity must be identified.AIM To investigate the relationship among delay discounting,delay aversion,glycated hemoglobin(HbA1c),and various levels of physical activity in Chinese adults diagnosed with type 2 diabetes mellitus(T2DM).METHODS In 2023,400 adults with T2DM were recruited from the People's Hospital of Linxia Hui Autonomous Prefecture of Gansu Province.A face-to-face questionnaire was used to gather demographic data and details on physical activity,delay discounting,and delay aversion.In addition,HbA1c levels were measured in all 400 participants.The primary independent variables considered were delay discounting and delay aversion.The outcome variables included HbA1c levels and different intensity levels of physical activity,including walking,moderate physical activity,and vigorous physical activity.Multiple linear regression models were utilized to assess the relationship between delay discounting,delay aversion,and HbA1c levels,along with the intensity of different physical activity measured in met-hours per week.RESULTS After controlling for the sample characteristics,delay discounting was negatively associated with moderate physical activity(β=-2.386,95%CI:-4.370 to-0.401).Meanwhile,delay aversion was negatively associated with the level of moderate physical activity(β=-3.527,95%CI:-5.578 to-1.476)in the multiple linear regression model,with statistically significant differences.CONCLUSION Elevated delay discounting and increased delay aversion correlated with reduced levels of moderate physical activity.Result suggests that delay discounting and aversion may influence engagement in moderate physical activity.This study recommends that health administration and government consider delay discounting and delay aversion when formulating behavioral intervention strategies and treatment guidelines involving physical activity for patients with T2DM,which may increase participation in physical activity.This study contributes a novel perspective to the research on physical activity in adults with T2DM by examining the significance of future health considerations and the role of emotional responses to delays.

Functional analysis of the novel mitochondrial tRNA^(Trp)and tRNA^(Ser(AGY))variants associated with type 2 diabetes mellitus

BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA^(Trp)A5514G and tRNA^(Ser(AGY))C12237T variants,however,the effects of these mt-tRNA variants on T2DM progression are largely unknown.AIM To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic,molecular,and biochemical levels.METHODS Cytoplasmic hybrid(cybrid)cells carrying both m.A5514G and m.C12237T variants,and healthy control cells without these mitochondrial DNA(mtDNA)variants were generated using trans-mitochondrial technology.Mitochondrial features,including mt-tRNA steady-state level,levels of adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),reactive oxygen species(ROS),mtDNA copy number,nicotinamide adenine dinucleotide(NAD+)/NADH ratio,enzymatic activities of respiratory chain complexes(RCCs),8-hydroxy-deoxyguanine(8-OhdG),malondialdehyde(MDA),and superoxide dismutase(SOD)were examined in cell lines with and without these mt-tRNA variants.RESULTS Compared with control cells,the m.A5514G variant caused an approximately 35%reduction in the steady-state level of mt-tRNA^(Trp)(P<0.0001);however,the m.C12237T variant did not affect the mt-tRNA^(Ser(AGY))steady-state level(P=0.5849).Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells:ATP,MMP,NAD+/NADH ratio,enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells(P<0.05 for all measures).By contrast,the levels of ROS,8-OhdG and MDA were significantly increased(P<0.05 for all measures),but mtDNA copy number was not affected by m.A5514G and m.C12237T variants(P=0.5942).CONCLUSION The m.A5514G variant impaired mt-tRNA^(Trp)metabolism,which subsequently caused mitochondrial dysfunction.The m.C12237T variant did not alter the steady-state level of mt-tRNA^(Ser(AGY)),indicating that it may be a modifier of the m.A5514G variant.The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.

Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus:A pilot bioinformatics study

BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.

Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy

In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes

BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive dysfunction.Hyperglycemia is closely related to neurological abnormalities,while often disregarded in clinical practice.Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)levels.METHODS A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital.The participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical indicators.Meanwhile,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.RESULTS The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-1.188,P<0.01)were independent predictors of poor glycemic control.CONCLUSION The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control,which may be the basis for the changes in cognitive function in diabetic patients.

Mechanism of Gegen Qinlian Decoction in Treating Type 2 Diabetes Mellitus Complicated with NAFLD Based on Network Pharmacology

[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian Decoction.[Methods]TCMSP database was used to analyze the active components of Gegen Qinlian Decoction,and pubchem and Swiss ADME databases were also used to predict drug targets,extract T2DM complicated with NAFLD targets from OMIM and Genecards databases.Venny plot was drawn to obtain intersection targets,and finally Cytoscape was used to make core target maps and drug-target-disease network maps.Using DAVID and Metascape database to analyze the intersection targets,the gene ontology information of Go and KEGG was obtained.Microbial informatics technology was used to visualize GO,and Cytoscape was used to make drug-target-disease network map-enrichment pathway map.[Results]The network pharmacological analysis showed that Gegen Qinlian Decoction acted on the key targets of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,such as ALB and ALT1,through many components,and achieved the purpose of treating this disease.The chemical constituents of the drug include formononetin,5-hydroxyisomucronulatol-2,5-2-O-glucoside,cholesteryl laurate,isoliquiritigenin,etc.[Conclusions]This study provides a new idea and theoretical support for future drug research and clinical practice.

Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance

BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease featured by insulin resistance(IR)and decreased insulin secretion.Currently,vitamin D deficiency is found in most patients with T2DM,but the relationship between vitamin D and IR in T2DM patients requires further investigation.AIM To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM.METHODS Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed.Based on the diagnostic criteria of IR,the patients were divided into a resistance group(n=100)and a non-resistance group(n=62).Subsequently,patients in the resistance group were subdivided to a conventional group(n=44)or a joint group(n=56)according to the treatment regimens.Logistic regression was carried out to analyze the risk factors of IR in T2DM patients.The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment.RESULTS Notable differences were observed in age and body mass index(BMI)between the resistance group and the non-resistance group(both P<0.05).The resistance group exhibited a lower 25-hydroxyvitamin D_(3)(25(OH)D_(3))level,as well as notably higher levels of 2-h postprandial blood glucose(2hPG),fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)than the non-resistance group(all P<0.0001).Additionally,the resistance group demonstrated a higher triglyceride(TG)level but a lower high-density lipoprotein-cholesterol(HDL-C)level than the non-resistance group(all P<0.0001).The BMI,TG,HDL-C,25(OH)D_(3),2hPG,and HbA1c were found to be risk factors of IR.Moreover,the posttreatment changes in levels of 25(OH)D_(3),2hPG,FBG and HbA1c,as well as TG,total cholesterol,and HDL-C in the joint group were more significant than those in the conventional group(all P<0.05).CONCLUSION Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the noninsulin resistant group.Logistic regression analysis revealed that 25(OH)D_(3)is an independent risk factor influencing IR.Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.