Organophosphate pesticides and new-onset diabetes mellitus:From molecular mechanisms to a possible therapeutic perspective

Organophosphate is a commonly used pesticide in the agricultural sector.The main action of organophosphate focuses on acetylcholinesterase inhibition,and it therefore contributes to acute cholinergic crisis,intermediate syndrome and delayed neurotoxicity.From sporadic case series to epidemiologic studies,organophosphate has been linked to hyperglycemia and the occurrence of newonset diabetes mellitus.Organophosphate-mediated direct damage to pancreatic beta cells,insulin resistance related to systemic inflammation and excessive hepatic gluconeogenesis and polymorphisms of the enzyme governing organophosphate elimination are all possible contributors to the development of newonset diabetes mellitus.To date,a preventive strategy for organophosphatemediated new-onset diabetes mellitus is still lacking.However,lowering reactive oxygen species levels may be a practical method to reduce the risk of developing hyperglycemia.

Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation

AbstractAIM： To investigate the impact of minimum tacrolimus（TAC） on new-onset diabetes mellitus （NODM） afterliver transplantation （LT）.METHODS： We retrospectively analyzed the data of973 liver transplant recipients between March 1999and September 2014 in West China Hospital LiverTransplantation Center. Following the exclusion ofineligible recipients, 528 recipients with a TAC-dominantregimen were included in our study. We calculatedand determined the mean trough concentration ofTAC （cTAC） in the year of diabetes diagnosis in NODMrecipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value forpredicting NODM 6 mo after LT was identified usinga receptor operating characteristic curve. TAC-relatedcomplications after LT was evaluated by χ^2 test, andthe overall and allograft survival was evaluated usingthe Kaplan-Meier method. Risk factors for NODM afterLT were examined by univariate and multivariate Cox regression.RESULTS： Of the 528 transplant recipients, 131（24.8%） developed NODM after 6 mo after LT, andthe cumulative incidence of NODM progressivelyincreased. The mean cTAC of NODM group recipientswas significantly higher than that of recipients in thenon-NODM group （7.66 ± 3.41 ng/mL vs 4.47 ± 2.22ng/mL, P 〈 0.05）. Furthermore, NODM group recipientshad lower 1-, 5-, 10-year overall survival rates （86.7%,71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P 〈0.05） and allograft survival rates （92.8%, 84.6%, and75.7% vs 96.1%, 91%, and 86.1%, P 〈 0.05） thanthe others. The best cutoff of mean cTAC for predictingNODM was 5.89 ng/mL after 6 mo after LT. Multivariateanalysis showed that old age at the time of LT （〉 50years）, hypertension pre-LT, and high mean cTAC （≥5.89 ng/mL） after 6 mo after LT were independent riskfactors for developing NODM. Concurrently, recipientswith a low cTAC （〈 5.89 ng/mL） were less likely tobecome obese （21.3% vs 30.2%, P 〈 0.05） or todevelop dyslipidemia （27.5% vs 44.8%, P 〈0.05）,chronic kidney dysfunction （14.6% vs 22.7%, P 〈 0.05）,and moderate to severe infection （24.7% vs 33.1%, P〈 0.05） after LT than recipients in the high mean cTACgroup. However, the two groups showed no significantdifference in the incidence of acute and chronicrejection, hypertension, cardiovascular events and newonsetmalignancy.CONCLUSION： A minimal TAC regimen can decreasethe risk of long-term NODM after LT. Maintaining a cTACvalue below 5.89 ng/mL after LT is safe and beneficial.

Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation

BACKGROUND:New-onset diabetes after transplantation(NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation(LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients.METHODS:A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom Mass ARRAY. Modified clinical models in predicting NODAT were established and evaluated.RESULTS:The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients(56% vs 39%, P=0.014). Dominant model(GG vs GT+TT, P=0.030) and recessive model(GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age(OR=1.048, P=0.004), BMI(OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT(OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT(AUROC=0.743, P<0.001).CONCLUSION:ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.

Calcium channel blocker monotherapy versus combination with reninangiotensin system inhibitors on the development of new-onset diabetes mellitus in hypertensive Korean patients

Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. Methods A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). Results After propensity score-matched (PSM) analysis, two propensity- matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. Conclusions The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.

Recent advances in new-onset diabetes mellitus after kidney transplantation

A common challenge in managing kidney transplant recipients(KTR)is posttransplant diabetes mellitus(PTDM)or diabetes mellitus(DM)newly diagnosed after transplantation,in addition to known pre-existing DM.PTDM is an important risk factor for post-transplant cardiovascular(CV)disease,which adversely affects patient survival and quality of life.CV disease in KTR may manifest as ischemic heart disease,heart failure,and/or left ventricular hypertrophy.Available therapies for PTDM include most agents currently used to treat type 2 diabetes.More recently,the use of sodium glucose co-transporter 2 inhibitors(SGLT2i),glucagon-like peptide-1 receptor agonists(GLP-1 RA),and dipeptidyl peptidase 4 inhibitors(DPP4i)has cautiously extended to KTR with PTDM,even though KTR are typically excluded from large general population clinical trials.Initial evidence from observational studies seems to indicate that SGLT2i,GLP-1 RA,and DPP4i may be safe and effective for glycemic control in KTR,but their benefit in reducing CV events in this otherwise high-risk population remains unproven.These newer drugs must still be used with care due to the increased propensity of KTR for intravascular volume depletion and acute kidney injury due to diarrhea and their single-kidney status,pre-existing burden of peripheral vascular disease,urinary tract infections due to immunosuppression and a surgically altered urinary tract,erythrocytosis from calcineurin inhibitors,and reduced kidney function from acute or chronic rejection.

Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors

BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies.However,improvement is needed to support its clinical utility.AIM To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.METHODS Ninety-seven new-onset T2DM patients(<12 mo)differing in BMI[normal weight(NW),n=33,BMI=22.23±1.60;overweight,n=42,BMI=25.9±1.07;obesity(OB),n=22,BMI=31.23±2.31]from the First People’s Hospital of Yunnan Province,Kunming,China,were studied.One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.RESULTS Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM patients.Arginine,histidine,leucine,methionine,and lysine were greater in male patients than in female patients.Moreover,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with HDL.CONCLUSION Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development.The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals.This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

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.

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.

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.

Prevalence of Anemia in Patients with Diabetes Mellitus:A Systematic Review and Meta-Analysis

Objective Anemia is a common public health concern in patients with type 2 diabetes worldwide.This study aimed to identify the prevalence of anemia among patients with diabetes.Methods Electronic databases,including PubMed,Scopus,Web of Sciences,and Google Scholar,were searched systematically for studies published between 2010 and 2021.After removing duplicates and inappropriate reports,the remaining manuscripts were reviewed and appraised using theNewcastleOttawa Scale(NOS)tool.A random-effects model was used to calculate the pooled estimates of the extracted data using Stata version 17.Heterogeneity of the studies was assessed using the Q statistic.Results A total of 51 articles containing information on 26,485 patients with diabetes were included in this study.The articles were mainly from Asia(58.82%)and Africa(35.29%).The overall prevalence of anemia was 35.45%(95%CI:30.30–40.76),with no evidence of heterogeneity by sex.Among the two continents with the highest number of studies,the prevalence of anemia in patients with diabetes was significantly higher in Asia[40.02;95%CI:32.72–47.54]compared to Africa[28.46;95%CI:21.90–35.50](P for heterogeneity=0.029).Moreover,there has been an increasing trend in the prevalence of anemia in patients with diabetes over time,from[15.28;95%CI:9.83–22.21]in 2012 to[40.70;95%CI:10.21–75.93]in 2022.Conclusion Globally,approximately 4 in 10 patients with diabetes suffer from anemia.Therefore,routine anemia screening and control programs every 3 months might be useful in improving the quality of life of these patients.

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.

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 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.

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality rate.We aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and CAP.METHODS:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April 2020.Patients were allocated to the DM or non-DM group and paired with propensity score matching.Baseline characteristics and clinical outcomes up to 90 days were evaluated.The primary outcome was the 10-day mortality.Receiver operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical analysis.RESULTS:Among 152 enrolled patients,60 pairs were successfully matched.There was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml vs.median 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747.The cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,respectively.Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with DM.CONCLUSION:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.

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.

A novel clinical model for risk prediction and stratification of new-onset diabetes mellitus after distal pancreatectomy

Background:The incidence of new-onset diabetes mellitus(NODM)after distal pancreatectomy(DP)remains high.Few studies have focused on NODM in patients with pancreatic benign or low-grade malignant lesions(PBLML).This study aimed to develop and validate an effective clinical model for risk prediction and stratification of NODM after DP in patients with PBLML.Methods:A follow-up survey was conducted to investigate NODM in patients without preoperative DM who underwent DP.Four hundred and forty-eight patients from Peking Union Medical College Hospital(PUMCH)and 178 from Guangdong Provincial People’s Hospital(GDPH)met the inclusion criteria.They constituted the training cohort and the validation cohort,respectively.Univariate and multivariate Cox regression,as well as least absolute shrinkage and selection operator(LASSO)analyses,were used to identify the independent risk factors.The nomogram was constructed and verified.Concordance index(C-index),receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA)were applied to assess its predictive performance and clinical utility.Accordingly,the optimal cut-off point was determined by maximally selected rank statistics method,and the cumulative risk curves for the high-and low-risk populations were plotted to evaluate the discrimination ability of the nomogram.Results:The median follow-up duration was 42.8 months in the PUMCH cohort and 42.9 months in the GDPH cohort.The postoperative cumulative 5-year incidences of DM were 29.1%and 22.1%,respectively.Age,body mass index(BMI),length of pancreatic resection,intraoperative blood loss,and concomitant splenectomy were significant risk factors.The nomogram demonstrated significant predictive utility for post-pancreatectomy DM.The C-indexes of the nomogram were 0.739 and 0.719 in the training and validation cohorts,respectively.ROC curves demonstrated the predictive accuracy of the nomogram,and the calibration curves revealed that prediction results were in general agreement with the actual results.The considerable clinical applicability of the nomogram was certified by DCA.The optimal cut-off point for Background:The incidence of new-onset diabetes mellitus(NODM)after distal pancreatectomy(DP)remains high.Few studies have focused on NODM in patients with pancreatic benign or low-grade malignant lesions(PBLML).This study aimed to develop and validate an effective clinical model for risk prediction and stratification of NODM after DP in patients with PBLML.Methods:A follow-up survey was conducted to investigate NODM in patients without preoperative DM who underwent DP.Four hundred and forty-eight patients from Peking Union Medical College Hospital(PUMCH)and 178 from Guangdong Provincial People’s Hospital(GDPH)met the inclusion criteria.They constituted the training cohort and the validation cohort,respectively.Univariate and multivariate Cox regression,as well as least absolute shrinkage and selection operator(LASSO)analyses,were used to identify the independent risk factors.The nomogram was constructed and verified.Concordance index(C-index),receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA)were applied to assess its predictive performance and clinical utility.Accordingly,the optimal cut-off point was determined by maximally selected rank statistics method,and the cumulative risk curves for the high-and low-risk populations were plotted to evaluate the discrimination ability of the nomogram.Results:The median follow-up duration was 42.8 months in the PUMCH cohort and 42.9 months in the GDPH cohort.The postoperative cumulative 5-year incidences of DM were 29.1%and 22.1%,respectively.Age,body mass index(BMI),length of pancreatic resection,intraoperative blood loss,and concomitant splenectomy were significant risk factors.The nomogram demonstrated significant predictive utility for post-pancreatectomy DM.The C-indexes of the nomogram were 0.739 and 0.719 in the training and validation cohorts,respectively.ROC curves demonstrated the predictive accuracy of the nomogram,and the calibration curves revealed that prediction results were in general agreement with the actual results.The considerable clinical applicability of the nomogram was certified by DCA.The optimal cut-off point for risk prediction value was 2.88, and the cumulative risk curves of each cohort showed significant differences between the high- and low-risk groups. Conclusions: The nomogram could predict and identify the NODM risk population, and provide guidance to physicians in monitoring and controlling blood glucose levels in PBLML patients after DP.

Inverse relationship between platelet Akt activity and hippocampal atrophy:A pilot case-control study in patients with diabetes mellitus

BACKGROUND Akt plays diverse roles in humans.It is involved in the pathogenesis of type 2 diabetes mellitus(T2DM),which is caused by insulin resistance.Akt also plays a vital role in human platelet activation.Furthermore,the hippocampus is closely associated with memory and learning,and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without dementia.AIM To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients.METHODS Platelet-rich plasma(PRP)was prepared from the venous blood of patients with T2DM or age-matched controls.The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt,p38 mitogen-activated protein(MAP)kinase and glyceraldehyde 3-phosphate dehydrogenase(GAPDH).Phosphorylation levels were quantified by densitometric analysis.Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer’s disease on magnetic resonance imaging,which proposes the Z-score as a parameter that reflects hippocampal volume.RESULTS The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects,whereas the levels of phosphorylated Akt corrected with GAPDH were not.However,this relationship was not observed in the control patients.CONCLUSION These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients.Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.

Gut-targeted therapies for type 2 diabetes mellitus: A review

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance.The global prevalence of T2DM has reached epidemic proportions,affecting approximately 463 million adults worldwide in 2019.Current treatments for T2DM include lifestyle modifications,oral antidiabetic agents,and insulin therapy.However,these therapies may carry side effects and fail to achieve optimal glycemic control in some patients.Therefore,there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of T2DM.The gut microbiota,which refers to the community of microorganisms that inhabit the human gut,has been shown to play a crucial role in the regulation of glucose metabolism and insulin sensitivity.Alterations in gut microbiota composition and diversity have been observed in T2DM patients,with a reduction in beneficial bacteria and an increase in pathogenic bacteria.This dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier function.Several gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in T2DM.One potential approach is the use of probio-tics,which are live microorganisms that confer health benefits to the host when administered in adequate amounts.Several randomized controlled trials have demonstrated that certain probiotics,such as Lactobacillus and Bifidobacterium species,can improve glycemic control and insulin sensitivity in T2DM patients.Mechanisms may include the production of short-chain fatty acids,the improvement of gut barrier function,and the reduction of inflammation.Another gut-targeted therapy is fecal microbiota transplantation(FMT),which involves the transfer of fecal material from a healthy donor to a recipient.FMT has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM.A recent randomized controlled trial showed that FMT from lean donors improved glucose metabolism and insulin sensitivity in T2DM patients with obesity.However,FMT carries potential risks,including transmission of infectious agents and alterations in the recipient's gut microbiota that may be undesirable.In addition to probiotics and FMT,other gut-targeted therapies are being investigated for the management of T2DM,such as prebiotics,synbiotics,and postbiotics.Prebiotics are dietary fibers that promote the growth of beneficial gut bacteria,while synbiotics combine probiotics and prebiotics.Postbiotics refer to the metabolic products of probiotics that may have beneficial effects on the host.The NIH SPARC program,or the Stimulating Peripheral Activity to Relieve Conditions,is a research initiative aimed at developing new therapies for a variety of health conditions,including T2DM.The SPARC program focuses on using electrical stimulation to activate peripheral nerves and organs,in order to regulate glucose levels in the body.The goal of this approach is to develop targeted,non-invasive therapies that can help patients better manage their diabetes.One promising area of research within the SPARC program is the use of electrical stimulation to activate the vagus nerve,which plays an important role in regulating glucose metabolism.Studies have shown that vagus nerve stimulation can improve insulin sensitivity and lower blood glucose levels in patients with T2DM.Gut-targeted therapies,such as probiotics and FMT,have shown potential for improving glycemic control and insulin sensitivity in T2DM patients.However,further research is needed to determine the optimal dose,duration,and safety of these therapies.