Gestational diabetes mellitus combined with fulminant type 1 diabetes mellitus, four cases of double diabetes: A case report

BACKGROUND Fulminant type 1 diabetes mellitus(FT1DM)that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM(PF),always without history of abnormal glucose metabolism.Here,we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus(GDM).CASE SUMMARY The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected,and the patients and their infants were followed up.All patients were diagnosed with GDM during the second trimester and were treated.The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM.Two patients had an insulin allergy,and two had symptoms of upper respiratory tract infection before onset.One patient developed ketoacidosis,and three developed ketosis.Two patients had cesarean section deliveries,and two had vaginal deliveries.The growth and development of the infants were normal.C-peptide levels were lower than those at onset,suggesting progressive impairment of islet function.The frequencies of the DRB109:01,DQB103:03,DQA103:02,DPA101:03,DPA102:02,DPB105:01,DRB401:03,G 01:01,and G 01:04 human leukocyte antigen(HLA)-G alleles were high in the present study.CONCLUSION In comparison with pregnancy-associated FT1DM(PF),patients with GDM combined with FT1DM had an older age of onset,higher body mass index,slower onset,fewer prodromal symptoms,and less acidosis.The pathogenesis may be due to various factors affecting the already fragileβ-cells of GDM patients with genetically susceptible class II HLA genotypes.We speculate that GDM combined with FT1DM during pregnancy,referred to as“double diabetes,”is a subtype of PF with its own unique characteristics that should be investigated further.

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.

Circulating glycated albumin levels and gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is characterized by glucose intolerance that is first diagnosed during pregnancy,making it the most common complication associated with this period.Early detection and targeted treatment of GDM can minimize foetal exposure to maternal hyperglycaemia and subsequently reduce the associated adverse pregnancy outcomes.Previous studies have inconsistently suggested that the level of glycated albumin(GA)might predict GDM.AIM To review and synthesize existing evidence to evaluate the relationship between GA levels and the development of GDM.METHODS We sought to compare GA levels between GDM and control groups in this metaanalysis by systematically searching the Web of Science,PubMed,Cochrane Library,and Embase databases for articles published up to June 2023.The analysis utilized the weighted mean difference(WMD)as the primary metric.The data were meticulously extracted,and the quality of the included studies was assessed.Additionally,we conducted a subgroup analysis based on study region and sample size.We assessed heterogeneity using I2 statistics and evaluated publication bias through funnel plots.Additionally,trim-and-fill analysis was employed to detect and address any potential publication bias.RESULTS The meta-analysis included a total of 11 studies involving 5477 participants,comprising 1900 patients with GDM and 3577 control individuals.The synthesized results revealed a notable correlation between elevated GA levels and increased susceptibility to GDM.The calculated WMD was 0.42,with a 95%confidence interval(95%CI)ranging from 0.11 to 0.74,yielding a P value less than 0.001.Concerning specific GA levels,the mean GA level in the GDM group was 12.6,while for the control group,it was lower,at 11.6.This discrepancy underscores the potential of GA as a biomarker for assessing GDM risk.Moreover,we explored the levels of glycated haemoglobin(HbA1c)in both cohorts.The WMD for HbA1c was 0.19,with a 95%CI ranging from 0.15 to 0.22 and a P value less than 0.001.This observation suggested that both GA and HbA1c levels were elevated in individuals in the GDM group compared to those in the control group.CONCLUSION Our meta-analysis revealed a substantial correlation between elevated GA levels and increased GDM risk.Furthermore,our findings revealed elevated levels of HbA1c in GDM patients,emphasizing the significance of monitoring both GA and HbA1c levels for early GDM detection and effective management.

Correlation between type 2 diabetes mellitus remission and intrapancreatic fat deposition

BACKGROUND Intrapancreatic fat deposition(IPFD)exerts a significant negative impact on patients with type 2 diabetes mellitus(T2DM),accelerates disease deterioration,and may lead to impairedβ-cell quality and function.AIM To investigate the correlation between T2DM remission and IPFD.METHODS We enrolled 80 abdominally obese patients with T2DM admitted to our institution from January 2019 to October 2023,including 40 patients with weight lossinduced T2DM remission(research group)and 40 patients with short-term intensive insulin therapy-induced T2DM remission(control group).We comparatively analyzed improvements in IPFD[differential computed tomography(CT)values of the spleen and pancreas and average CT value of the pancreas];levels of fasting blood glucose(FBG),2-h postprandial blood glucose(2hPBG),and insulin;and homeostasis model assessment of insulin resistance(HOMA-IR)scores.Correlation analysis was performed to explore the association between T2DM remission and IPFD.RESULTS After treatment,the differential CT values of the spleen and pancreas,FBG,2hPBG,and HOMA-IR in the research group were significantly lower than those before treatment and in the control group,and the average CT value of the pancreas and insulin levels were significantly higher.Correlation analysis revealed that the greater the T2DM remission,the lower the amount of IPFD.

Gestational diabetes mellitus may predispose to metabolic dysfunction-associated steatotic liver disease

The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease(MASLD).Insulin resistance,subclinical inflammation,dyslipidemia,obesity,and hypertension are all factors in this reciprocal interaction that contribute to the development of MASLD,which includes hepatocellular carci-noma,advanced fibrosis/cirrhosis,and non-alcoholic steatohepatitis(NASH).A new risk factor for MASLD/NASH that affects the course of the disease independently throughout life is gestational diabetes mellitus(GDM).Women with a history of GDM had a higher chance of developing NASH,according to a recent study that used a large-scale database.Although the precise etiology is yet unknown,temporary disruption of pancreatic beta cell activity during pregnancy may set off systemic inflammation,affecting distant organs including the liver.Early screening and management strategies are crucial in mitigating MASLD progression and preventing adverse cardiovascular events in affected individuals.

Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.

Remission of type 2 diabetes mellitus:Emerging concepts and proposed diagnostic criteria

The remission of type 2 diabetes mellitus(T2DM)is a topic that has been widely discussed recently,and it gives new hope for people with T2DM.Achievement of normal blood glucose levels or levels below the diagnostic threshold for T2DM without pharmacotherapy among people with T2DM after metabolic surgery and carbohydrate or calorie-restricted diet paved the way for more enthusiastic research in this area.There is a lot of confusion regarding the appropriate terminology and definition of remission of T2DM.In this short review,we briefly analyzed the emerging concepts and proposed criteria for diagnosing remission of T2DM,which will be helpful for healthcare providers and people with T2DM.

Honeymoon phase in type 1 diabetes mellitus: A window of opportunity for diabetes reversal?

The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.

Cellular and molecular overview of gestational diabetes mellitus:Is it predictable and preventable?

BACKGROUND In contrast to overt diabetes mellitus(DM),gestational DM(GDM)is defined as impaired glucose tolerance induced by pregnancy,which may arise from exaggerated physiologic changes in glucose metabolism.GDM prevalence is reported to be as high as 20%among pregnancies depending on the screening method,gestational age,and the population studied.Maternal and fetal effects of uncontrolled GDM include stillbirth,macrosomia,neonatal diabetes,birth trauma,and subsequent postpartum hemorrhage.Therefore,it is essential to find the potential target population and associated predictive and preventive measures for future intensive peripartum care.AIM To review studies that explored the cellular and molecular mechanisms of GDM as well as predictive measures and prevention strategies.METHODS The search was performed in the Medline and PubMed databases using the terms“gestational diabetes mellitus,”“overt diabetes mellitus,”and“insulin resistance.”In the literature,only full-text articles were considered for inclusion(237 articles).Furthermore,articles published before 1997 and duplicate articles were excluded.After a final review by two experts,all studies(1997-2023)included in the review met the search terms and search strategy(identification from the database,screening of the studies,selection of potential articles,and final inclusion).RESULTS Finally,a total of 79 articles were collected for review.Reported risk factors for GDM included maternal obesity or overweight,pre-existing DM,and polycystic ovary syndrome.The pathophysiology of GDM involves genetic variants responsible for insulin secretion and glycemic control,pancreaticβcell depletion or dysfunction,aggravated insulin resistance due to failure in the plasma membrane translocation of glucose transporter 4,and the effects of chronic,low-grade inflammation.Currently,many antepartum measurements including adipokines(leptin),body mass ratio(waist circumference and waist-to-hip ratio),and biomarkers(microRNA in extracellular vesicles)have been studied and confirmed to be useful markers for predicting GDM.For preventing GDM,physical activity and dietary approaches are effective interventions to control body weight,improve glycemic control,and reduce insulin resistance.CONCLUSION This review explored the possible factors that influence GDM and the underlying molecular and cellular mechanisms of GDM and provided predictive measures and prevention strategies based on results of clinical studies.

Successful lifestyle modifications may underlie umbilical cordmesenchymal stromal cell effects in type 2 diabetes mellitus

Type 2 diabetes mellitus(T2DM)is a lifelong condition and a grave threat to human health.Innovative efforts to relieve its detrimental effects are acutely needed.The sine qua non in T2DM management is consistent adherence to a prudent lifestyle and nutrition,combined with aerobic and resistance exercise regimens,together repeatedly shown to lead to complete reversal and even longterm remission.Non-adherence to the above lifestyle adjustments condemns any treatment effort and ultimately the patient to a grim fate.It is thus imperative that every study evaluating the effects of innovative interventions in T2DM objectively compares the novel treatment modality to lifestyle modifications,preferably through double-blind controlled randomization,before claiming efficacy.

Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

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.

Icariin accelerates bone regeneration by inducing osteogenesisangiogenesis coupling in rats with type 1 diabetes mellitus

BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

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.

Predictive value of bilirubin and serum γ-glutamyltranspeptidase levels in type-2 diabetes mellitus patients with acute coronary syndrome

BACKGROUND Cardiovascular disease is a major complication of diabetes mellitus(DM).Type-2 DM(T2DM)is associated with an increased risk of cardiovascular events and mortality,while serum biomarkers may facilitate the prediction of these outcomes.Early differential diagnosis of T2DM complicated with acute coronary syndrome(ACS)plays an important role in controlling disease progression and improving safety.AIM To investigate the correlation of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)with major adverse cardiovascular events(MACEs)in T2DM patients with ACS.METHODS The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively.According to different conditions,they were divided into the T2DM complicated with ACS group(T2DM+ACS,n=96),simple T2DM group(T2DM,n=85),and simple ACS group(ACS,n=90).The clinical data and laboratory indices were compared among the three groups,and the correlations of serum total bilirubin(TBIL)levels and serumγ-GGT levels with other indices were discussed.T2DM+ACS patients received a 90-day follow-up after discharge and were divided into event(n=15)and nonevent(n=81)groups according to the occurrence of MACEs;Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients.RESULTS The T2DM+ACS group showed higherγ-GGT,total cholesterol,low-density lipoprotein cholesterol(LDL-C)and glycosylated hemoglobin(HbA1c)and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups(P<0.05).Based on univariate analysis,the event and nonevent groups were significantly different in age(t=3.3612,P=0.0011),TBIL level(t=3.0742,P=0.0028),γ-GGT level(t=2.6887,P=0.0085),LDL-C level(t=2.0816,P=0.0401),HbA1c level(t=2.7862,P=0.0065)and left ventricular ejection fraction(LEVF)levels(t=3.2047,P=0.0018).Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs,and age andγ-GGT level were risk factors(P<0.05).CONCLUSION Serum TBIL levels are decreased andγ-GGT levels are increased in T2DM+ACS patients,and the two indices are significantly negatively correlated.TBIL andγ-GGT are independent influencing factors for MACEs in such patients.

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.

Serum proteins differentially expressed in gestational diabetes mellitus assessed using isobaric tag for relative and absolute quantitation proteomics

BACKGROUND As a well-known fact to the public,gestational diabetes mellitus(GDM)could bring serious risks for both pregnant women and infants.During this important investigation into the linkage between GDM patients and their altered expression in the serum,proteomics techniques were deployed to detect the differentially expressed proteins(DEPs)of in the serum of GDM patients to further explore its pathogenesis,and find out possible biomarkers to forecast GDM occurrence.METHODS Subjects were divided into GDM and normal control groups according to the IADPSG diagnostic criteria.Serum samples were randomly selected from four cases in each group at 24-28 wk of gestation,and the blood samples were identified by applying iTRAQ technology combined with liquid chromatography-tandem mass spectrometry.Key proteins and signaling pathways associated with GDM were identified by bioinformatics analysis,and the expression of key proteins in serum from 12 wk to 16 wk of gestation was further verified using enzyme-linked immunosorbent assay (ELISA).RESULTS Forty-seven proteins were significantly differentially expressed by analyzing the serum samples between the GDMgravidas as well as the healthy ones. Among them, 31 proteins were found to be upregulated notably and the rest16 proteins were downregulated remarkably. Bioinformatic data report revealed abnormal expression of proteinsassociated with lipid metabolism, coagulation cascade activation, complement system and inflammatory responsein the GDM group. ELISA results showed that the contents of RBP4, as well as ANGPTL8, increased in the serumof GDM gravidas compared with the healthy ones, and this change was found to initiate from 12 wk to 16 wk ofgestation.CONCLUSION GDM symptoms may involve abnormalities in lipid metabolism, coagulation cascade activation, complementsystem and inflammatory response. RBP4 and ANGPTL8 are expected to be early predictors of GDM.