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 mell...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.展开更多
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 recentl...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.展开更多
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,intermedia...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.展开更多
Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells(DC)for the induction of peripheral toler- ance may be highly rel...Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells(DC)for the induction of peripheral toler- ance may be highly relevant.We examined the properties of DC associated with immune suppression in NOD mice by insulin injection subcutaneously and their ability to suppress diabetes transfer by diabeto- genic effector cells in secondary NOD-SCID recipients.Our data showed that the surface expressions of MHCⅡand CD86 on NOD-derived DC were increased after insulin treatment compared with those on PBS controlled mice.The dendritic cells with a mature phenotype and increased MLR stimulation adop- tively transferred immune tolerogenic effects on secondary NOD-SCID mice,which were associated with significantly greater IL-10,TGF-beta production and CD4^+ CD25^+ T differentiation from splenocytes compared with NOD-SCID control recipients.Moreover,treatment with DC remarkably decreased the incidence of diabetes in secondary recipients.These results suggest that a subtype of DC generated by insulin subcutaneous treated NOD mice confers potential protection against diabetes through polarizing the immune response towards a Th2 regulatory pathway.展开更多
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 reci...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.展开更多
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 nond...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.展开更多
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 amin...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.展开更多
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 s...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.展开更多
目的观察NOD小鼠人源化后,CD4^+和CD8^+调节性T细胞(regulatory T cells,Tregs)频率和功能的变化,揭示Tregs在人源化NOD小鼠1型糖尿病中的作用及免疫学机制可能的变化。方法流式细胞术分别分析12周龄未发病的人源化NOD小鼠和NOD小鼠脾...目的观察NOD小鼠人源化后,CD4^+和CD8^+调节性T细胞(regulatory T cells,Tregs)频率和功能的变化,揭示Tregs在人源化NOD小鼠1型糖尿病中的作用及免疫学机制可能的变化。方法流式细胞术分别分析12周龄未发病的人源化NOD小鼠和NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T和CD4^+CD25^+Foxp3^+T细胞的频率,并采用3H-Td R掺入法检测脾CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能。结果人源化NOD小鼠和NOD小鼠的脾淋巴细胞和胰腺淋巴结细胞中CD4^+CD25^+Foxp3^+T细胞频率无显著性差异(P>0.05),而人源化NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T细胞等CD8^+Tregs亚群的频率较NOD小鼠都显著降低,但NOD小鼠人源化后,CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能并没有显著性差异;同时与人源化NOD小鼠相比,NOD小鼠的胰腺淋巴结细胞中CD8^+T细胞频率更低。结论人源化NOD小鼠脾脏和胰腺淋巴结中CD8^+Tregs亚群频率的降低,引起其胰腺淋巴结中CD8^+T细胞频率的升高,导致胰岛β细胞破坏更严重,可能是引起人源化NOD小鼠自发1型糖尿病较NOD小鼠明显提前且加重的因素之一。展开更多
基金supported by the National Natural Science Foundation of China(Nos.81373074 and 81402752)Science and Technology Development Foundation of Shenzhen(No.JCYJ20140418091413562)+1 种基金Natural Science Foundation of Shenzhen University(No.201404)High-level Personnel Special Support Project of Zhengzhou University(No.ZDGD13001)
文摘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.
文摘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.
基金Chang Gung Memorial Hospital,Linkou,Taiwan,No.CORPG3K0191 and No.CMRPG3J1051-3.
文摘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.
基金This study was supported by the National Natural Science Foundation of China(No.30200343).
文摘Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells(DC)for the induction of peripheral toler- ance may be highly relevant.We examined the properties of DC associated with immune suppression in NOD mice by insulin injection subcutaneously and their ability to suppress diabetes transfer by diabeto- genic effector cells in secondary NOD-SCID recipients.Our data showed that the surface expressions of MHCⅡand CD86 on NOD-derived DC were increased after insulin treatment compared with those on PBS controlled mice.The dendritic cells with a mature phenotype and increased MLR stimulation adop- tively transferred immune tolerogenic effects on secondary NOD-SCID mice,which were associated with significantly greater IL-10,TGF-beta production and CD4^+ CD25^+ T differentiation from splenocytes compared with NOD-SCID control recipients.Moreover,treatment with DC remarkably decreased the incidence of diabetes in secondary recipients.These results suggest that a subtype of DC generated by insulin subcutaneous treated NOD mice confers potential protection against diabetes through polarizing the immune response towards a Th2 regulatory pathway.
基金Supported by Key Technology Support Program of Sichuan ProvinceNo.2013SZ0023
文摘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.
文摘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.
基金Supported by the Open Project Grant for Clinical Medical Center of Yunnan Province,No.2019LCZXKF-NM03Medical Leader Training Grant,No.L-201624and Yunnan Province Ten Thousand Talents:“Medical Expert”grant,No.YNWR-MY-2019-020.
文摘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.
基金supported by a grant from China National Key Clinical Specialty Construction Project (No.2022YW030009).
文摘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.
文摘目的观察NOD小鼠人源化后,CD4^+和CD8^+调节性T细胞(regulatory T cells,Tregs)频率和功能的变化,揭示Tregs在人源化NOD小鼠1型糖尿病中的作用及免疫学机制可能的变化。方法流式细胞术分别分析12周龄未发病的人源化NOD小鼠和NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T和CD4^+CD25^+Foxp3^+T细胞的频率,并采用3H-Td R掺入法检测脾CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能。结果人源化NOD小鼠和NOD小鼠的脾淋巴细胞和胰腺淋巴结细胞中CD4^+CD25^+Foxp3^+T细胞频率无显著性差异(P>0.05),而人源化NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T细胞等CD8^+Tregs亚群的频率较NOD小鼠都显著降低,但NOD小鼠人源化后,CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能并没有显著性差异;同时与人源化NOD小鼠相比,NOD小鼠的胰腺淋巴结细胞中CD8^+T细胞频率更低。结论人源化NOD小鼠脾脏和胰腺淋巴结中CD8^+Tregs亚群频率的降低,引起其胰腺淋巴结中CD8^+T细胞频率的升高,导致胰岛β细胞破坏更严重,可能是引起人源化NOD小鼠自发1型糖尿病较NOD小鼠明显提前且加重的因素之一。
