2011年 · 第124卷第22期

In 2008,an Expert Committee was convened to redefine the diagnosis of diabetes mellitus (in non-pregnant individuals) using glycated hemoglobin (HbAlc).The Committee Members were appointed from the American Diabetes Association (ADA),the European Association for the Study of Diabetes (EASD) and the International Diabetes Federation (IDF).The recommendations1 were published in the July issue of Diabetes Care with an accompanying editorial2 and were presented at the 2009 ADA 69th Scientific Sessions.In 2010,the ADA stated in its Standards of Medical Care in Diabetes 2010 that "HbAlc,fasting plasma glucose or the 2-hour 75 g oral glucose tolerance test (OGTT) are appropriate for testing diabetes and assessing the risk of future diabetes," andthat"a confirmed HbA1c≥6.5％ is diagnosic for diabetes."

Abstract：Background Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties.The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function in newly diagnosed type 2 diabetic patients in an 8-year prospective study.Methods In the prospective study,we enrolled 133 newly diagnosed type 2 diabetic patients without subclinical atherosclerosis and gave them intensive therapy; the mean treatment period was 8 years.Intensive treatment was a stepwise implementation of behavior modification and pharmacological therapy targeting hyperglycaemia,hypertension,dyslipidaemia and obesity.We measured baseline circulating adiponectin with an enzyme-linked immunosorbent assay,endothelium-dependent and -independent vasodilation by high-resolution vascular ultrasound.At year 8,102 patients were reexamined for endothelium-dependent and -independent vasodilation.Results Sex-adjusted adiponectin level was positively correlated with endothelium-independent vasodilation both at baseline (r＝0.150,P＝0.043) and at year 8 (r＝0.339,P＝0.001),whereas no association was found between adiponectin and endothelium-dependent vasodilation.In a stepwise multivariate linear regression model,adiponectin was an independent predictor for impaired endothelium-independent vasodilation at year 8 (P＝0.001).Conclusions Plasma adiponectin concentration was associated with endothelium-independent vasodilation and hypoadiponectinemia predicted the impairment of endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients under multifactorial intervention.These data support the causative link of impairment of endothelium-independent vasodilation with hypoadiponectinemia。

Abstract：Background Fulminant type 1 diabetes (F1D) is a complex disease.Microarray analysis was used to identify gene expression changes and obtain understanding of the underlying mechanisms.Methods Microarray analysis was performed on peripheral blood mononuclear cells from six F1D patients and six matched healthy subjects.Real-time polymerase chain reaction was used to verify the differentially expressed genes.NK cell activity was detected by methyl thiazoleterazolium assay.Results Microarray analysis identified 759 genes differing in expression between F1D patients and controls at a false discovery rate of 0.05.Expression of TLR9,ELF4 and IL1RAP were verified and consistent with changes in microarray results.NK cell activity was decreased in F1D.With use of a knowledge base,differentially expressed genes could be placed within different pathways with predicted functions including interleukin-1,and tumor necrosis factor-α signaling.Conclusions These results identify several genes indicating possible mechanisms in F1D.NK cell dysfunction resulting from changes in expression of TLR9,ELF4 and IL1RAP,and pathways of interleukin-1 and tumor necrosis factor-α signaling might be involved in F1D through inducing β-cell dysfunction。

Abstract：Background Adaptor proteins containing PH domain,PTB domain,and leucine zipper motif 1 and 2 (APPL1/2) play a key role in cell proliferation in many tissues.APPL1 or APPL2 as an adaptor for adiponectin receptors mediates the signaling pathway of adiponectin which acts as an anti-atherosclerotic adipokine.This study aimed to investigate whether genetic variations in the APPL 1/2 genes affect the risk of coronary artery disease (CAD) in Chinese patients with type 2 diabetes mellitus (T2DM).Methods Seven haplotype-tagging single nucleotide polymorphisms (tag-SNPs) were selected from CHB HapMap database (Phase Ⅱ) and total 203 CAD-positive cases and 106 CAD-negative controls with T2DM were genotyped for the 7 tag-SNPs by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.Results The minor allele G of rs4640525 at APPL1 locus was protective from CAD in patients with T2DM,with the carriers of genotype CC at higher risk of CAD compared with non-carriers (OR＝2.830,95％ CI 1.285-6.230,P＝0.010;OR'＝4.992,95％ CI＝1.758-14.173,P'＝0.003,after adjustment for the other known CAD risk factors); the homozygotes of AA at rs11112412 in APPL2.gene had higher risk of CAD compared with those of GG (adjusted OR:＝5.697,95％ CI 1.006-32.257,P'＝0.049).Conclusion Genetic variation(s) in APPL1/2 may be associated with CAD risk in T2DM in Chinese population。

Abstract：Background Autologous peripheral stem cell transplantation was first reported in 2007 to treat type 1 diabetes mellitus (DM) and achieved encouraging effect,but whether similar outcome can be achieved in type 2 DM is not well demonstrated.The objective of this study was to determine the effect of combination of autologous bone marrow stem cell transplantation (BMT) and hyperbaric oxygen treatment on type 2 DM.Methods The study involved 31 patients with type 2 DM (aged 33 to 62 years) from January 2009 to January 2011 in the Central Hospital of Wuhan,China.Clinical variables (body mass index,duration of DM,insulin requirement,oral hypoglycemic drugs,time free from insulin,time free from oral drugs) and laboratory variables (hemoglobin A1c (HbA1c)),mononuclear cells infused,and C-peptide in four time points) were assessed.Purified bone marrow stem cells were infused into major pancreatic arteries.Follow-up was performed at the 30,90,180,360,540 and 720 days (mean 321 days) after BMT.Results Mean HbA1c values showed a significant reduction during follow-up in all patients after BMT.It decreased by more than 1.5％ (from 8.7％ to 7.1％) as quickly as at 30 days after BMT.Afterwards mean HbA1c fluctuated between plus or minus 0.5％ until 24 months rather than declined continuously.At 90 days after the combined therapy C-peptide increased significantly compared with baseline (P ＜0.0001).But in other time points C-peptide was similar with baseline data (P＞0.3).All patients had insulin and/or oral hypoglycemic drugs reduced to different levels.The dose of insulin of 7 patients (7/26,27％) reduced for a period of time after BMT.Conclusions Combined therapy of intrapancreatic BMT and hyperbaric oxygen treatment can improve glucose control and reduce the dose of insulin and/or oral hypoglycemic drugs in type 2 DM patients,but it only improve pancreatic β-cell function transiently.Further randomized controlled clinical trials involved more patients will be required to confirm these findings and the mechanism needs to be illustrated deeply。

Abstract：Background Recently,some studies had shown that elevated serum uric acid (SUA) itself may increase the risk for development of renal disease in patients with diabetes.This study aimed to explore whether SUA was a predictor of microalbuminuria and impaired renal function in type 2 diabetes in Chinese patients.Methods This cross-sectional study included 2108 type 2 diabetic patients.Kidney function was estimated using the simplified modification of diet in renal disease (MDRD) equation to obtain estimated glomerular filtration rate.The urine samples were obtained for measuring the albumin-to-creatinine ratio (ACR).Results According to the ACR level,these patients were divided into two groups,normal ACR (NA) and non-normal ACR (non-NA).Both SUA and creatinine were significantly higher in the non-NA group than those in the NA group ((318.89+107.52) vs.(283.44±88.64) μmol/L,and (95.08±53.24) vs.(79.63±18.20) μmol/L,respectively).Logistic regression analysis showed that diabetic duration,systolic blood pressure,creatinine and SUA were the independent predictors of albuminuria.Furthermore,to identify the factors associated with renal function,these patients were divided into two groups according to the MDRD level (MDRD＜90 or MDRD＞90).Both SUA and creatinine were significantly higher in the lower MDRD group than those in the higher MDRD group ((301.90±96.46) vs.(264.07+84.74) μmol/L,and (89.10±31.00) vs.(66.37±11.15) μ mol/L,respectively).Logistic regression analysis showed that only age and SUA were the independent predictors of MDRD.Conclusion High-normal SUA was associated with albuminuria and impaired glomerular filtration rate in Chinese type 2 diabetic patients。

Abstract：Background Diabetic retinopathy (DR) has emerged as a leading cause of visual impairment and blindness in the working-aged population worldwide.This study aimed to assess frequency and associated factors of progression of DR in subjects with known diabetes in a population-based setting.Methods The Beijing Eye Study is a population based study performed in Greater Beijing in 2001 and 2006.The present investigation included all subjects with known diabetes mellitus in 2001,who participated in the follow-up examination in 2006.Fundus photographs were assessed.Results The study included 170 subjects; 51 (30％) subjects showed signs of DR in 2001 and were re-examined in 2006,36 (21.2％) subjects (18 subjects with DR present at baseline,18 subjects with newly diagnosed DR in 2006)showed a progression of DR during follow-up.Progression of DR was associated with rural region (odds ratio (OR):5.43,P＝0.001) and self-reported arterial hypertension (OR:3.85,P＝0.023).In the non-progressive subgroup,presence of DR was associated with different levels of education (＜middle school,middle school,college or higher,OR:0.30,P＝0.023),treatment modes of diabetes mellitus (OR:10.24,P＝0.003) and cataract surgery (OR:9.14,P＝0.007).Conclusions In a population-based setting in Greater Beijing,progression of DR occurred in 35％ of subjects with pre-existing DR and overall in 21％ of subjects with known diabetes within a 5-year period.Progression of DR was significantly associated with rural region and self-reported arterial hypertension.In the stable subjects,presence of DR was significantly associated with poor educational level,insulin treatment of diabetes and cataract surgery。

Abstract：Background The accurate and comprehensive assessment of glycemic control in patients with diabetes is important for optimizing glycemic management and for formulating personalized diabetic treatment schemes.This study aimed to analyze the correlation between 1,5-anhydroglucitol (1,5-AG) and glycemic excursions in type 2 diabetic patients.Methods Seventy-one outpatients with type 2 diabetes mellitus were randomly recruited from Chinese People's Liberation Army General Hospital.Using a continuous glucose monitoring system (CGMS),these patients' blood glucose levels were monitored for three consecutive days to obtain mean blood glucose (MBG) data.Intraday glycemic excursions were evaluated using the mean amplitude of glycemic excursions (MAGE),the largest amplitude of glycemic excursions (LAGE),standard deviation of blood glucose (SDBG) and the M-value.Interday glycemic excursion was assessed by absolute mean of daily difference (MODD).Postprandial glycemic fluctuations were evaluated using postprandial glucose excursions (PPGE) and postprandial incremental area under the curve (iAUC).Fasting venous blood samples were collected to measure serum 1,5-AG,whole-blood hemoglobin A1c (HbA1c) and serum glycated albumin (GA).Clinical markers of glycemia and parameters of glycemic excursions from CGMS were analyzed using the Pearson correlation coefficient and multivariate stepwise regression.Results Pearson correlation analysis revealed that 1,5-AG was significantly correlated with MAGE,SDBG,M-value,LAGE,PPGE and iAUC (r values were -0.509,-0.430,-0.530,-0.462,-0.416 and -0.435,respectively,P ＜0.01),especially in moderately and well-controlled patients,based on defined HbA1c levels.Multivariate stepwise regression analysis revealed a negative correlation between 1,5-AG and the above parameters,but not HbA1c and GA.Finally,HbA1c and GA were positively correlated with MBG and fasting blood glucose (FBG).Conclusions 1,5-AG was much better than HbA1c and GA as a marker of glycemic excursions in type 2 diabetic patients.Based on these results 1,5-AG is the best metric for assessing postprandial glucose levels in moderately and well-controlled patients,while HbA1c and GA were superior to 1,5-AG for monitoring MBG and FBG。

Abstract：Background Insulin resistance is an underlying feature of both type 2 diabetes and metabolic syndrome.Currently,it is unclear whether nuclear factor (NF)-κB inducing kinase (NIK) plays a role in the development of insulin resistance.The present in vivo study investigated the roles of NIK and IKB kinase α (IKKα) in obesity-induced insulin resistance using animal models.Methods NIK expression was evaluated by Westem blotting in male Lepob mice and C57BL/6J mice fed a high-fat diet (HFD) (45％ fat).After metformin and sulfasalazine treatment,NIK expression was investigated during the improvement of insulin resistance.Results NIK was increased by about 1-fold in the renal tissues of Lepob mice and C57BL/6J mice fed a HFD for 12 weeks.After 1 and 3 weeks of high-fat feeding,we observed an almost 50％ decrease in NIK and IKKα expression in the liver and renal tissues of C57BL/6J mice.NIK expression was significantly lower in the liver and renal tissues of HFD-fed mice that were treated with insulin sensitizers,metformin and sulfasalazine.However,IKKα expression was increased after metformin treatment in both tissues.Conclusion These results suggest a possible role of NIK in the liver and renal tissues of insulin-resistant mice。

Abstract：Background Increased levels of plasma lipopolysaccharide (LPS) have been found in obesity and diabetes patients.This study was to investigate the effect of LPS on pancreatic beta-cell viability and the involvement of caspase 3 in NIT-1 cell line.Methods Mouse insulinoma NIT-1 cells were treated with LPS for the indicated time and dose.Cell viability was measured by cell counting kit-8 reagent.Toll-like receptor 4 (TLR4),caspase 3 and cleaved caspase 3 were detected by Western blotting.Insulin was determined by radioimmunoassay (RIA).Results LPS promoted NIT-1 cell proliferation at 1 μg/ml,peaked at 72 hours of incubation.A reduction in cleavage of caspase 3 was observed upon LPS treatment.Bay11-7082,a specific inhibitor of nuclear factor (NF)-κB,blunted LPS-induced inhibition of caspase 3 cleavage.Reduction in chronic insulin secretion was observed after treatment with LPS at 1 μg/ml for 48 and 72 hours,not for 24 hours.TLR4 protein was upregulated when NIT-1 cells were treated with LPS at 1 pg/ml for 24 hours.Conclusions LPS promotes early NIT-1 cell proliferation in association with NF-κB-mediated inhibition of caspase 3 cleavage.LPS exerts a time-dependent inhibitory effect on chronic insulin secretion from NIT-1 cells。

Abstract：Background Pancreatic beta-cell apoptosis induced by lipotoxicity,to a large extent,contributes to the progression of type 2 diabetes.To investigate the mechanism of free fatty acid induced apoptosis,we aimed to study the effects of palmitic acid (PA) on the apoptosis and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression in βTC3 cells as well as the possible role of nuclear factor-κB (NF-κB) in this process.Methods Hoechst 33258 was used to detect βTC3 cell apoptosis,which was induced by PA stimulation for 12 hours.PGC-1α expression was analyzed by reverse transcription polymerase chain reaction,IκB kinase β (IKKβ),IKBα,NF-κB-inducing kinase (NIK) and Rel-B expressions were analyzed by Western blotting.MG132 was employed to block the endogenous IκBα degradation before PA administration,and then its effect on PA-inducing cell apoptosis and PGC-1α mRNA expression was analyzed.Results Significant increased cell apoptosis was found at the concentration of 0.5 mmol/L and 1.0 mmol/L PA administration.PA (0.5 mmol/L) could extensively reduced the expression of PGC-1α mRNA.After exposing βTC3 cells to 0.5 mmol/L PA for different time periods (0,4,6,8,10 and 12 hours),IKKβ protein expression increased while IκBα,NIK and Rel-B protein expression declined in a time-dependent manner.Pretreatment with MG132 to inhibit the degradation of IκBα,partially prevented the down-regulation of PGC-1α mRNA expression after 12-hour PA treatment in accordance with the decrease of PA induced apoptosis.Conclusions NF-κB canonical pathway was activated in PA-mediated βTC3 cell apoptosis,whereas non-canonical pathway was inhibited.Reduced PGC-1α expression by PA in βTC3 cells could involve the activation of canonical NF-κB pathway,so as to deteriorate the PA induced apoptosis。

Abstract：Objective To review the effect of stem cells in erectile dysfunction as well as their application to the therapy of erectile dysfunction.Data sources The data used in the present article were mainly from PubMed with relevant English articles published from 1974 to 2011.The search terms were "stem cells" and "erectile dysfunction".Study selection Articles regarding the role of stem cells in erectile dysfunction and their application to the therapy of erectile dysfunction were selected.Results Stem cells hold great promise for regenerative medicine because of their ability to self-renew and to differentiate into various cell types.Meanwhile,in preclinical experiments,therapeutic gene-modified stem cells have been approved to offer a novel strategy for cell therapy and gene therapy of erectile dysfunction.Conclusion The transplantation of stem cells has the potential to provide cell types capable of restoring normal function after injury or degradation inerectile dysfunction.However,a series of problems,such as the safety of stem cells transplantation,their application in cell therapy and gene therapy of erectile dysfunction need further investigation。

Abstract：Objective To review the vasorelaxant effects of hydrogen sulfide (H2S) in arterial rings in the cardiovascular system under both physiological and pathophysiological conditions and the possible mechanisms involved.Data sources The data in this review were obtained from Medline and Pubmed sources from 1997 to 2011 using the search terms "hydrogen sulfide" and ""vascular relaxation".Study selection Articles describing the role of hydrogen sulfide in the regulation of vascular activity and its vasorelaxant effects were selected.Results H2S plays an important role in the regulation of cardiovascular tone.The vasomodulatory effects of H2S depend on factors including concentration,species and tissue type.The H2S donor,sodium hydrosulfide (NarS),causes vasorelaxation of rat isolated aortic rings in a dose-dependent manner.This effect was more pronounced than that observed in pulmonary arterial rings.The expression of KATP channel proteins and mRNA in the aortic rings was increased compared with pulmonary artery rings.H2S is involved in the pathogenesis of a variety of cardiovascular diseases.Downregulation of the endogenous H2S pathway is an important factor in the pathogenesis of cardiovascular diseases.The vasorelaxant effects of H2S have been shown to be mediated by activation of KATP channels in vascular smooth muscle cells and via the induction of acidification due to activation of the CI/HCO3 exchanger.It is speculated that the mechanisms underlying the vasoconstrictive function of H2S in the aortic rings involves decreased NO production and inhibition of cAMP accumulation.Conclusion H2S is an important endogenous gasotransmitter in the cardiovascular system and acts as a modulator of vascular tone in the homeostatic regulation of blood pressure。

Abstract：Background Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion.The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly.We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma.Methods Six patients with spontaneous remission of acromegaly or gigantism were enrolled.The clinical characteristics,endocrinological evaluation and imageological characteristics were retrospectively analyzed.Results In these cases,the initial clinical presences were diabetes mellitus or hypogonadism.No abrupt headache,vomiting,visual function impairment,or conscious disturbance had ever been complained of.The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher,but nadir GH levels were all still ＞1 μg/L in 75 g oral glucose tolerance test.Magnetic resonance imaging detected enlarged sella,partial empty sella and compressed pituitary.The transsphenoidal surgery was performed in 2 cases,and the other patients were conservatively managed.All the patients were in clinical remission.Conclusions When the clinical presences,endocrine evaluation,biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly,the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed.To these patients,conservative therapy may be appropriate。

Abstract：Abdominal obesity (AO) has become a major health problem to most of the Asian communities.The severity and consequences of AO are higher among females.It has virtually become an epidemic in most South Asian countries and the health care systems in this region are likely to be challenged by one of the biggest health issues in the near future.Yet,the recognition of the magnitude of the problem by health authorities is poor.The purpose of this paper is to motivate health care professionals,planners and policy makers towards better control of the epidemic of AO while highlighting the paucity of evidence on clinical management of AO from the South Asian region。

Abstract：Endolymphatic sac papillary tumor (ELST) is an extremely rare and aggressive tumor characterized by hearing loss and temporal bone destruction.A case with clinical,imaging,pathologic and treatment data is reported and relevant literature is reviewed.A 25-year-old woman,with ELST underwent craniotomy for tumor subtotal resection,and the diagnosis was confirmed by pathologic examination.Postoperative radiotherapy consisted of 50.4 Gy/28 f was given accordingly.The patient is currently alive with no signs of tumor recurrence locally and no radiation side-effects observed after one year follow-up.Complete resection is impossible in most cases,local resection,adjuvant radiotherapy may provide favored local control.A long-term follow-up is highly advocated in consideration of its slow development course。

Abstract：A 78-year-old man presented with an eight-hour history of chest distress.Electrocardiograph and serum cardiac enzymes were suggestive of acute inferior myocardial infarction with right ventricular infarction.The patient,who underwent emergency percutaneous coronary intervention,suffered from thrombocytopenia presenting with cerebral infarction and myocadial reinfarction during haparin exposure.The laboratory test for heparin-induced thrombocytopenia (HIT) specific antibodies (heparin-platelet factor,PF4) was positive.The case was diagnosed as arteries thrombosis due to heparin-induced thrombocytopenia; the patient died after cessation of heparin。

Abstract：The present case is a patient with advanced non-small cell lung cancer (NSCLC) who developed leukoencephalopathy following radiotherapy and gefitinib treatments.There are rarely reports of such incidences because the median survival period of advanced NSCLC is only ten months.The features of leukoencephalopathy in this case were atypical for radiation leukoencephalopathy,so it was suspected that the leukoencephalopathy was associated with gefitinib。

Abstract：Uveitis was a rare adverse event of vaccination.We met two cases of acute uveitis with exudative retinal detachment following vaccination of H1N1 influenza.Case 1 was a 10-year-old boy who was admitted for bilateral blurred vision at 10 days after vaccination of H1N1 influenza.Vitreous opacity was obvious in both eyes.Broad exudative retinal detachment was observed in the right eye.Case 2 was a 47-year-old female who suffered from an acute high fever at 2 days after the vaccination of H1 N1 influenza.Later,she encountered bilateral headache and decreasing vision.In both eyes,mutton fat keratic precipitates,positive Tyndall phenomenon,congestion of optic disc and exudative retinal detachment were observed。