Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

Correlation of periodontal inflamed surface area with glycated hemoglobin,interleukin-6 and lipoprotein(a)in type 2 diabetes with retinopathy

BACKGROUND The two-way relationship between periodontitis and type 2 diabetes mellitus(T2DM)is well established.Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis,accentuating diabetic complications.An inflammatory link exists between diabetic retinopathy(DR)and periodontitis,but the studies regarding this association and the role of lipoprotein(a)[Lp(a)]and interleukin-6(IL-6)in these conditions are scarce in the literature.AIM To determine the correlation of periodontal inflamed surface area(PISA)with glycated Hb(HbA1c),serum IL-6 and Lp(a)in T2DM subjects with retinopathy.METHODS This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR.All subjects were assessed for periodontal parameters[bleeding on probing(BOP),probing pocket depth,clinical attachment loss(CAL),oral hygiene index-simplified,plaque index(PI)and PISA],and systemic parameters[HbA1c,fasting plasma glucose and postprandial plasma glucose,fasting lipid profile,serum IL-6 and serum Lp(a)].RESULTS The proportion of periodontitis in T2DM with and without DR was 47.5%and 27.5%respectively.Severity of periodontitis,CAL,PISA,IL-6 and Lp(a)were higher in T2DM with DR group compared to T2DM without DR group.Significant difference was observed in the mean percentage of sites with BOP between T2DM with DR(69%)and T2DM without DR(41%),but there was no significant difference in PI(P>0.05).HbA1c was positively correlated with CAL(r=0.351,P=0.001),and PISA(r=0.393,P≤0.001)in study subjects.A positive correlation was found between PISA and IL-6(r=0.651,P<0.0001);PISA and Lp(a)(r=0.59,P<0.001);CAL and IL-6(r=0.527,P<0.0001)and CAL and Lp(a)(r=0.631,P<0.001)among study subjects.CONCLUSION Despite both groups having poor glycemic control and comparable plaque scores,the periodontal parameters were higher in DR as compared to T2DM without DR.Since a bidirectional link exists between periodontitis and DM,the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.

Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus

BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.

Prevalence and risk factors of diabetes mellitus among elderly patients in the Lugu community

BACKGROUND Age is a significant risk factor of diabetes mellitus(DM).With the develop of population aging,the incidence of DM remains increasing.Understanding the epidemiology of DM among elderly individuals in a certain area contributes to the DM interventions for the local elderly individuals with high risk of DM.AIM To explore the prevalence of DM among elderly individuals in the Lugu community and analyze the related risk factors to provide a valid scientific basis for the health management of elderly individuals.METHODS A total of 4816 elderly people who came to the community for physical examination were retrospectively analyzed.The prevalence of DM among the elderly was calculated.The individuals were divided into a DM group and a non-DM group according to the diagnosis of DM to compare the differences in diastolic blood pressure(DBP)and systolic blood pressure(SBP),fasting blood glucose,body mass index(BMI),waist-to-hip ratio(WHR)and incidence of hypertension(HT),coronary heart disease(CHD),and chronic kidney disease(CKD).RESULTS DM was diagnosed in 32.70%of the 4816 elderly people.The BMI of the DM group(25.16±3.35)was greater than that of the non-DM group(24.61±3.78).The WHR was 0.90±0.04 in the non-DM group and 0.90±0.03 in the DM group,with no significant difference.The left SBP and SBP in the DM group were 137.9 mmHg±11.92 mmHg and 69.95 mmHg±7.75 mmHg,respectively,while they were 126.6 mmHg±12.44 mmHg and 71.15 mmHg±12.55 mmHg,respectively,in the non-DM group.These findings indicate higher SBP and lower DBP in DM patients than in those without DM.In the DM group,1274 patients were diagnosed with HT,accounting for 80.89%.Among the 3241 non-DM patients,1743(53.78%)were hypertensive and 1498(46.22%)were nonhypertensive.The DM group had more cases of HT than did the non-DM group.There were more patients with CHD or CKD in the DM group than in the non-DM group.There were more patients who drank alcohol more frequently(≥3 times)in the DM group than in the non-DM group.CONCLUSION Older adults in the Lugu community are at a greater risk of DM.In elderly individuals,DM is closely related to high BMI and HT,CHD,and CKD.Physical examinations should be actively carried out for elderly people to determine their BMI,SBP,DBP,and other signs,and sufficient attention should be given to abnormalities in the above signs before further diagnosis.

cNPAS2 inducedβcell dysfunction by regulating KANK1 expression in type 2 diabetes

BACKGROUND Diabetes mellitus type 2(T2DM)is formed by defective insulin secretion with the addition of peripheral tissue resistance of insulin action.It has been affecting over 400 million people all over the world.AIM To explore the pathogenesis of T2DM and to develop and implement new prevention and treatment strategies for T2DM.METHODS Receiver operating characteristic(ROC)curve analysis was used to conduct diagnostic markers.The expression level of genes was determined by reverse transcription-PCR as well as Western blot.Cell proliferation assays were performed by cell counting kit-8(CCK-8)tests.At last,T2DM mice underwent Roux-en-Y gastric bypass surgery.RESULTS We found that NPAS2 was significantly up-regulated in isletβcell apoptosis of T2DM.The ROC curve revealed that NPAS2 was capable of accurately diagnosing T2DM.NPAS2 overexpression did increase the level of KANK1.In addition,the CCK-8 test revealed knocking down NPAS2 and KANK1 increased the proliferation of MIN6 cells.At last,we found that gastric bypass may treat type 2 diabetes by down-regulating NPAS2 and KANK1.CONCLUSION This study demonstrated that NPAS2 inducedβcell dysfunction by regulating KANK1 expression in type 2 diabetes,and it may be an underlying therapy target of T2DM.

Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes

BACKGROUND Myosteatosis,rather than low muscle mass,is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus(T2DM).Myosteatosis may lead to a series of metabolic dysfunctions,such as insulin resistance,systematic inflammation,and oxidative stress,and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis.AIM To investigate the association between myosteatosis and coronary artery calcification(CAC)in patients with T2DM.METHODS Patients with T2DM,who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography(CT)scans,were included.The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level.The CAC score was determined from thoracic CT images using the Agatston scoring method.Myosteatosis was diagnosed according to Martin’s criteria.Severe CAC(SCAC)was defined when the CAC score exceeded 300.Logistic regression and decision tree analyses were performed.RESULTS A total of 652 patients with T2DM were enrolled.Among them,167(25.6%)patients had SCAC.Logistic regression analysis demonstrated that myosteatosis,age,duration of diabetes,cigarette smoking,and alcohol consumption were independent risk factors of SCAC.Myosteatosis was significantly associated with an increased risk of SCAC(OR=2.381,P=0.003).The association between myosteatosis and SCAC was significant in the younger patients(OR=2.672,95%CI:1.477-4.834,P=0.002),but not the older patients(OR=1.456,95%CI:0.863-2.455,P=0.188),and was more prominent in the population with lower risks of atherosclerosis.The decision tree analyses prioritized older age as the primary variable for SCAC.In older patients,cigarette smoking was the main contributing factor for SCAC,while in younger patients,it was myosteatosis.CONCLUSION Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM,especially in the population with younger ages and fewer traditional risk factors.

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.

Roles of fibroblast growth factors in the treatment of diabetes

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations

BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across different populations.AIM To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM.METHODS We searched PubMed,Embase,Web of Science,Cochrane Library,Medline,Baidu Academic,China National Knowledge Infrastructure,China Biomedical Literature Database,and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12,2022.Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature.RESULTS Twelve case–control studies(including 11273 cases and 11654 controls)met our inclusion criteria.In the full population,allelic model[odds ratio(OR):1.19;95%confidence interval(95%CI):1.09–1.29;P<0.0001],recessive model(OR:1.20;95%CI:1.11–1.29;P<0.0001),dominant model(OR:1.27.95%CI:1.14–1.42;P<0.0001),and codominant model(OR:1.36;95%CI:1.15–1.60;P=0.0003)(OR:1.22;95%CI:1.10–1.36;P=0.0002)indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM.In stratified analysis,this association was confirmed in Asian populations:allelic model(OR:1.25;95%CI:1.13–1.37;P<0.0001),recessive model(OR:1.29;95%CI:1.11–1.49;P=0.0007),dominant model(OR:1.35;95%CI:1.20–1.52;P<0.0001),codominant model(OR:1.49;95%CI:1.22–1.81;P<0.0001)(OR:1.26;95%CI:1.16–1.36;P<0.0001).In non-Asian populations,this association was not significant:Allelic model(OR:1.06,95%CI:0.98–1.14;P=0.12),recessive model(OR:1.04;95%CI:0.75–1.42;P=0.83),dominant model(OR:1.06;95%CI:0.98–1.15;P=0.15),codominant model(OR:1.08;95%CI:0.82–1.42;P=0.60.OR:1.15;95%CI:0.95–1.39;P=0.14).CONCLUSION KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population.Carriers of the C allele had a higher risk of T2DM.This association was not significant in non-Asian populations.

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.

Serum tumor markers expression(CA199,CA242,and CEA)and its clinical implications in type 2 diabetes mellitus

BACKGROUND Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus(T2DM)is associated with the levels of serum tumor markers of the digestive tract,such as cancer antigen(CA)199.Therefore,tumor markers in T2DM are important.AIM To evaluate the expression of serum tumor markers[CA199,CA242,and carcinoembryonic antigen(CEA)]and the clinical implications of the expression in T2DM.METHODS For this observational study conducted at Hefei BOE Hospital,China,we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020.Levels of fasting blood glucose(FBG),tumor markers(CA199,CEA,and CA242),glycosylated hemoglobin(HbA1c),etc.were measured and group index levels were compared.Moreover,FBG and HbA1c levels were correlated with tumor marker levels.Tumor markers were tested for diagnostic accuracy in patients with>9%HbA1c using the receiver operating curve(ROC)curve.RESULTS The T2DM group had high serum FBG,HbA1c,CA199,and CEA levels(P<0.05).A comparative analysis of the two groups based on HbA1c levels(Group A:HbA1c≤9%;Group B:HbA1c>9%)revealed significant differences in CEA and CA199 levels(P<0.05).The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809,respectively.CA199,CEA,and CA242 levels positively correlated with HbA1c(r=0.308,0.426,and 0.551,respectively)and FBG levels(r=0.236,0.231,and 0.298,respectively).CONCLUSION As compared to controls,serum CEA and CA199 levels were higher in patients with T2DM.HbA1c and FBG levels correlated with CA199,CEA,and CA242 levels.Patients with poorly controlled blood sugar must be screened for tumor markers.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus:A real-world experience

BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACR),and adverse effects were recorded retrospectively.RESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.Median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(P<0.001 for all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(P<0.001)respectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACR 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and urinary infection-20(8.8%)&17(7.5%)with dapagliflozin;9(5.6%)&5(3.13%)with canagliflozin;and 4(5%)&4(5%)with empagliflozin.Diabetic ketoacidosis was observed in 4(1.8%)with dapagliflozin and 1(0.63%)with canagliflozin.CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c,body weight,and better than those reported in RCTs,with low side effect profiles.A review of large-scale real-world data is needed to inform better clinical practice decision making.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.

Agmatine ameliorates diabetes type 2-induced nephropathy in rats

Objective:To assess the nephroprotective potential of agmatine in a rat model of streptozotocin-induced diabetic nephropathy.Methods:A single dose of streptozotocin(40 mg/kg)coupled with a fructose diet induced diabetes in Wistar rats.Agmatine(40 and 80 mg/kg)was administered to rats for 12 weeks.The body weight and fasting blood glucose were measured weekly.Insulin level,urine output,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C were also determined at the end of the experiment.Furthermore,superoxide dismutase,glutathione,interleukin-1β,interleukin-6,and tumor necrosis factor-alpha were evaluated in kidney tissue.Histopathological study was also performed using hematoxylin and eosin staining.Results:Agmatine at both doses significantly increased final body weight,and lowered fasting blood glucose,urine output,insulin,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C levels compared with the diabetic group(P<0.05).Inflammatory markers and antioxidant effect were significantly improved in agmatine-treated rats.Moreover,the histopathological changes in renal structure were ameliorated by agmatine treatment.Conclusions:Agmatine alleviates diabetic nephropathy by improving renal functions and reducing inflammation and oxidative stress.The molecular mechanisms of its nephroprotective actions need to be investigated in future study.

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.

Prevalence and Risk Factors of Stroke in Inpatients with Type 2 Diabetes Mellitus in China

Objective The prevalence and the cluster characteristics of risk factors of stroke were assessed in a Chinese diabetic population.Methods Clinical data of 30693 inpatients who were diagnosed with type 2 diabetes mellitus(T2DM)and admitted between 2013 and 2018 were retrospectively analyzed.The age-standardized prevalence of stroke was estimated using the 2010 Chinese population census data,and risk factors were analyzed by multiple imputation and regression.Results The crude and standardized prevalence rates of stroke in patients with T2DM were 34.4%and 21.5%,respectively,and 85.2%of the stroke patients had ischemic stroke.Nearly half of the patients who experienced stroke had clusters of more than 4 risk factors.Compared with no-risk-factor clustering,the risk of stroke significantly increased 3-4 times in the presence of more than 4 risk-factor clusters(P<0.001).Hypertension was the most common major risk factor for ischemic stroke[odds ratio(OR),2.34;95%confidence interval(CI),2.18-2.50]and hemorrhagic stroke(OR,3.68;95%CI 2.95-4.59;P<0.001).Moreover,a 1-standard-deviation increase in fasting blood glucose(FBG)was significantly negatively correlated with ischemic stroke risk,and the same change in FBG was significantly associated with an 8%increased risk of hemorrhagic stroke.Conclusion The prevalence of stroke in patients with T2DM is rather high,and the clustering of risk factors is associated with the development of stroke in T2DM patients.Risk factors differ in different stroke subtypes.Identifying risk factors for a specific high-risk group is necessary.

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.

Effects of axylitol-casein complex on insulin resistance and gut microbiota composition in high-fat-diet+streptozotocin-induced type 2 diabetes mellitus mice

This study investigated the effects of a xylitol-casein non-covalent complex(XC)on parameters related to type 2 diabetes mellitus(T2DM),in addition to related changes in gut microbiome composition and functions.High-fat-diet(HFD)+streptozotocin(STZ)-induced T2DM mice were treated with xylitol(XY),casein(CN),and XC,after which fecal samples were collected for gut microbiota composition and diversity analyses based on 16S rRNA high-throughput sequencing and multivariate statistics.XC decreased body weight and improved glucose tolerance,insulin sensitivity,pancreas impairment,blood lipid levels,and liver function in T2DM mice compared to XY-and CN-treated mice.Furthermore,XC modulated theα-diversity,β-diversity and gut microbiota composition.Based on Spearman’s correlation analysis,the relative abundances of Alistipes,Bacteroides,and Faecalibaculum were positively correlated and those of Akkermansia,Lactobacillus,Bifidobacterium,and Turicibacter were negatively correlated with the phenotypes related to the improvement of T2DM.In conclusion,we found that XC alleviated insulin resistance by restoring the gut microbiota of T2DM mice.Our results provide strong evidence for the beneficial effects of XC on T2DM and motivation for further investigation in animal models and,eventually,human trials.

Reconsidering the role of depression and common psychiatric disorders as partners in the type 2 diabetes epidemic

Common psychiatric disorders(CPDs)and depression contribute significantly to the global epidemic of type 2 diabetes(T2D).We postulated a possible pathophysiological mechanism that through Bridge-Symptoms present in depression and CPDs,promotes the establishment of emotional eating,activation of the reward system,onset of overweight and obesity and,ultimately the increased risk of developing T2D.The plausibility of the proposed pathophysiological mechanism is supported by the mechanism of action of drugs such as naltrexonebupropion currently approved for the treatment of both obesity/overweight with T2D and as separate active pharmaceutical ingredients in drug addiction,but also from initial evidence that is emerging regarding glucagon-like peptide 1 receptor agonists that appear to be effective in the treatment of drug addiction.We hope that our hypothesis may be useful in interpreting the higher prevalence of CPDs and depression in patients with T2D compared with the general population and may help refine the integrated psychiatric-diabetic therapy approach to improve the treatment and or remission of T2D.