Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma

BACKGROUND Islet amyloid deposition and reducedβ-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects.To date,the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma(PDAC)have not been specifically addressed.AIM To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences(proximal vs distal residual pancreas)are associated with islet amyloid deposition.METHODS We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients,including 14 patients with normal glucose tolerance(NGT),16 patients with prediabetes and 15 new-onset diabetes(NOD)patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020.Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans.Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows:(1)Hematoxylin and eosin for general histological appearance;(2)hematoxylin and insulin for the determination of fractionalβ-cell area(immunohistochemistry);and(3)quadruple insulin,glucagon,thioflavin T and DAPI staining for the determination ofβ-cell area,α-cell area and amyloid deposits.RESULTS Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition,fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions,especially in the prediabetes and NOD groups.Consistent with this finding,the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group(37.35±12.16 cm^(3) vs 69.79±18.17 cm^(3),P<0.001).As expected,islets that stained positive for amyloid(islet amyloid density)were found in the majority of PDAC cases.The proportion of amyloid/islet area(severity of amyloid deposition)was significantly higher in both prediabetes and NOD patients than in NGT patients(P=0.002;P<0.0001,respectively).We further examined the regional differences in islet amyloid deposits.Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups(3.98%±3.39%vs 0.50%±0.72%,P=0.01;12.03%vs 1.51%,P=0.001,respectively).CONCLUSION In conclusion,these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation,which may be associated with the pathogenesis of NOD secondary to PDAC.

Association of TCF7L2 and GCG Gene Variants with Insulin Secretion,Insulin Resistance,and Obesity in New-onset Diabetes

This cohort study was designed to evaluate the association of transcription factor 7-like 2 （TCF7L2） and proglucagon gene （GCG） variants with disordered glucose metabolism and the incidence of type 2 diabetes mellitus （T2DM） in a rural adult Chinese population. A total of 7,751 non-T2DM participants 〉18 years old genotyped at baseline were recruited. The same questionnaire interview and physical and blood biochemical examinations were performed at both baseline and follow-up. During a median 6 years of follow-up, T2DM developed in 227 participants. After adjustment for potential contributory factors, nominally significant associations were seen between 3T genotype and the recessive model of TCFTI.2 rs7903146 and increased risk of T2DM [hazard ratio （HR）=4.068, 95% confidence interval （CI）： 1.270-13.026; HR=4.051, 95% CI： 1.268-12.946, respectively]. The TT genotype of rs7903146 was also significantly associated with higher fasting plasma insulin level and the homeostasis model assessment of insulin resistance in case of new-onset diabetes. In addition, the TCF7L2 rs290487 TT genotype was associated with abdominal obesity and the GCG rs12104705 CC genotype was associated with both general obesity and abdominal obesity in case of new-onset diabetes.

New-onset diabetes secondary to acute pancreatitis:An update

Diabetes is a condition of persistent hyperglycemia caused by the endocrine disorder of the pancreas.Therefore,all pancreatic diseases have the risk of diabetes.In particular,increasing attention has been paid recently to new-onset diabetes secondary to acute pancreatitis(AP).The complications of secondary diabetes have caused a lot of trouble for patients and have garnered increasing attention.At present,the pathophysiological mechanism of new-onset diabetes caused by AP is not clear.This review summarizes the current understanding of new-onset diabetes secondary to AP.

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.

New-onset diabetes after kidney transplantation:Incidence and associated factors

AIM To determine the incidence and associated factors of new-onset diabetes after transplantation(NODAT) in a Portuguese central hospital. METHODS This single-center retrospective study involved consecutive adult nondiabetic transplant recipients, who had undergone kidney transplantation between January 2012 and March 2016. NODAT was diagnosed according to the criteria of the American Diabetes Association. Data were collected from an institutional database of the Nephrology and Kidney Transplantation Department(Santa Maria Hospital, Lisbon, Portugal) and augmented with data of laboratorial parameters collected from the corresponding patient electronic medical records. Exclusion criteria were preexisting diabetes mellitus, missing information and follow-up period of less than 12 mo. Data on demographic and clinical characteristics as well as anthropometric and laboratorial parameters were also collected. Patients were divided into two groups: With and without NODAT-for statistical comparison.RESULTS A total of 156 patients received kidney transplantduring the study period, 125 of who were included in our analysis. NODAT was identified in 27.2% of the patients(n = 34; 53% female; mean age: 49.5 ± 10.8 years; median follow-up: 36.4 ± 2.5 mo). The incidence in the first year was 24.8%. The median time to diagnosis was 3.68 ± 5.7 mo after transplantation, and 76.5% of the patients developed NODAT in the first 3 mo. In the group that did not develop NODAT(n = 91), 47% were female, with mean age of 46.4 ± 13.5 years and median follow-up of 35.5 ± 1.6 mo. In the NODAT group, the pretransplant fasting plasma glucose(FPG) levels were significantly higher [101(96.1-105.7) mg/d L vs 92(91.4-95.8) mg/d L, P = 0.007] and pretransplant impaired fasting glucose(IFG) was significantly more frequent(51.5% vs 27.7%, P = 0.01). Higher pretransplant FPG levels and pretransplant IFG were found to be predictive risk factors for NODAT development [odds ratio(OR): 1.059, P = 0.003; OR: 2.772, P = 0.017, respectively]. CONCLUSION NODAT incidence was high in our renal transplant recipients, particularly in the first 3 mo posttransplant, and higher pretransplant FPG level and IFG were risk factors.

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.

Usefulness of CA 19–9 for pancreatic cancer screening in patients with new-onset diabetes

Background： Generally, carbohydrate antigen 19–9 （CA 19–9） is not useful for screening pancreatic cancerin the asymptomatic general population. This study aimed to evaluate the utility of CA 19–9 level as a screening indicator of pancreatic cancer in asymptomatic patients with new-onset diabetes.

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.

New-onset diabetes mellitus after kidney transplantation:Current status and future directions

A diagnosis of new-onset diabetes after transplantation(NODAT) carries with it a threat to the renal allograft,as well as the same short-and long-term implications of type 2 diabetes seen in the general population.NODAT usually occurs early after transplantation,and is usually diagnosed according to general population guidelines.Non-modifiable risk factors for NODAT include advancing age,African American,Hispanic,or South Asian ethnicity,genetic background,a positive family history for diabetes mellitus,polycystic kidney disease,and previously diagnosed glucose intolerance.Modifiable risk factors for NODAT include obesity and the metabolic syndrome,hepatitis C virus and cytomegalovirus infection,corticosteroids,calcineurin inhibitor drugs(especially tacrolimus),and sirolimus.NODAT affects graft and patient survival,and increases the incidence of post-transplant cardiovascular disease.The incidence and impact of NODAT can be minimized through pre-and post-transplant screening to identify patients at higher risk,including by oral glucose tolerance tests,as well as multi-disciplinary care,lifestyle modification,and the use of modified immunosuppressive regimens coupled with glucose-lowering therapies including oral hypoglycemic agents and insulin.Since NODAT is a major cause of post-transplant morbidity and mortality,measures to reduce its incidence and impact have the potential to greatly improve overall transplant success.

New-onset diabetes in COVID-19 and clinical outcomes: A systematic review and meta-analysis

BACKGROUND Diabetes mellitus(DM)is associated with adverse clinical outcomes and high mortality in patients with coronavirus disease 2019(COVID-19).The relationship between diabetes and COVID-19 is known to be bidirectional.AIM To analyze the rate of new-onset diabetes in COVID-19 patients and compare the clinical outcomes of new-onset diabetes,pre-existing diabetes,hyperglycemic,and non-diabetes among COVID-19 patients.METHODS We used the Meta-analysis of Observational Studies in Epidemiology statement for the present meta-analysis.Online databases were searched for all peerreviewed articles published until November 6,2020.Articles were screened using Covidence and data extracted.Further analysis was done using comprehensive meta-analysis.Among the 128 studies detected after thorough database searching,seven were included in the quantitative analysis.The proportion was reported with 95%confidence interval(CI)and heterogeneity was assessed using I2.RESULTS Analysis showed that 19.70%(CI:10.93-32.91)of COVID-19 patients had associated DM,and 25.23%(CI:19.07-32.58)had associated hyperglycemia.The overall mortality rate was 15.36%(CI:12.57-18.68)of all COVID-19 cases,irrespective of their DM status.The mortality rate was 9.26%among non-diabetic patients,10.59%among patients with COVID-19 associated hyperglycemia,16.03%among known DM patients,and 24.96%among COVID-19 associated DM patients.The overall occurrence of adverse events was 20.52%(CI:14.21-28.70)among COVID-19 patients in the included studies,15.29%among non-diabetic patients,20.41%among patients with COVID-19 associated hyperglycemia,20.69%among known DM patients,and 45.85%among new-onset DM.Metaregression showed an increasing rate of mortality among new hyperglycemic patients,known diabetics,and new-onset DM patients in comparison to those without diabetes.CONCLUSION A significantly higher rate of new onset DM and hyperglycemia was observed.Higher mortality rates and adverse events were seen in patients with new-onset DM and hyperglycemia than in the non-diabetic population.

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.

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.

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.

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.

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.