2009年 · 第122卷第21期

Diabetes has spread across the world at a rapid speed since the 21st century's coming,and it is expected to increase to 300 million in 2025 and become a major burden on society.Chinese people are susceptible to diabetes.Diabetes prevention and treatment is becoming increasingly grim in China along with the increase of obesity resulting from increased degree of aging,improvement of living standards and unhealthy lifestyle。

Abstract：Background Vaspin is a newly-identified adipocytokine related to obesity and insulin sensitivity.However,its pathophysiologic role in humans remains largely unknown.The aim of our study was to investigate the relationship between serum vaspin level and glucose metabolism or obesity in Chinese adults.Methods A total of 123 subjects,including 84 subjects with normal glucose tolerance(NGT)and 39 subjects with diabetes,were enrolled in this study.Anthropometric parameters,abdominal fat areas,plasma glucose concentration,serum insulin,lipids,and vaspin level were measured in each participant.Results Serum vaspin concentration was significantly higher in diabetic patients than that in NGT subjects(592 (438-695)pg/ml vs 380(294-517)pg/ml,P=0.020)in women.In all participants,age,fasting plasma glucose concentration(FPG),2-hour post-load plasma glucose(PG2h),hemoglobin Alc(HbAlc)and high-density lipoprotein cholesterol(HDL-c)significantly increased from the lower tertile to the higher tertile of vaspin.Univariate linear regression analyses revealed that vaspin level was only positively correlated with age(β=0.340,P=0.002)in NGT subjects.And vaspin was positively associated with FPG(β=0.365,P=0.023),PG2h(β=0.526,P=0.001),HbA1c(13=0.388,P=0.016),and HDL-c(β=0.353,P=0.027),while negatively with homeostasis model assessment of beta cell function(HOMA-β)(β=-0.361,P=0.024)in diabetic patients.In stepwise multivariate regression analyses,age was independently associated with circulating vaspin in NGT subjects,whereas PG2h was an independent predictor of vaspin in diabetic patients.In addition,there was no significant difference of serum vaspin level between men and women.And no significant correlations between vaspin and body fat indexes were detected.Conclusions Serum vaspin level is higher in diabetic patients than that in NGT subjects in women.Age predicts serum vaspin level in NGT subjects,while PG2h is independently associated with vaspin in diabetic patients。

Abstract：Background Not only the obese,but also the non-obese adults have the high prevalence of metabolic syndrome in the upper normal weight.The aim of this study was to assess the prevalence rates of metabolic syndrome and its individual components in non-obese adult Taiwanese(body mass index(BMI)≤26.9 kg/m2).Methods A cross-sectional study was conducted from January 2006 to December 2007.One thousand six hundred and fifty-nine subjects(aged 47.5+12.4 years),60.8% of which were men,were enrolled.The prevalence and odds ratios of metabolic syndrome,defined by the American Heart Association/National Heart,Lung and Blood Institute(2005),were analyzed in the BMI category according to 2.0 unit increments,in individuals seeking a health examination.Results The higher the BMI categories,the more prevalent the metabolic syndrome was in women and in men(P＜0.001).Compared with those women with a BMI≤20.9 kg/m2,the odds ratios for metabolic syndrome in women were 1.3(95% CI:0.5-3.2)with BMI 21.0-22.9 kg/m2,3.0(1.3-7.1)with BMI 23.0-24.9 kg/m2,and 8.6(3.6-20.8)for women with BMI 25.0-26.9 kg/m2,after controlling for age,smoking status,alcohol consumption,betel nut chewing,blood routine,biochemical data,hepatitis B virus surface antigen and anti-hepatitis C virus.The corresponding odds ratios in men were 1.6(0.6-4.2),3.7(1.6-8.8),and 9.9(4.2-23.2).Conclusions Individuals in the upper normal weight and slightly overweight BMI range have relatively high prevalence and increased risk of having metabolic syndrome.Therefore,physicians should screen metabolic syndrome in not only obese but also non-obese individuals for the prevention of cardiovascular disease。

Abstract：Background Glycemic control prevents onset and progression of diabetes-related long-term complications.The objective of this study was to demonstrate that twice daily insulin lispro low mix 25 is noninferior to twice daily human insulin mix 30/70 in achieving glycemic control as measured by hemoglobin A1c(HbA1c),from baseline to endpoint,in patients with type 1 or 2 diabetes.Methods In this phase Ⅳ,crossover,open-label,multicenter study,117 Chinese patients with diabetes were randomly assigned to one of two treatment sequence groups.One group received 12-week treatment with twice daily human insulin mix 30/70 followed by 12-week treatment with twice daily insulin lispro low mix 25,while the other group received the reverse treatment sequence.HbA1c,baseline-to-endpoint change in HbA1c,proportion of patients achieving target HbA1c≤7% and≤6.5%,fasting blood glucose,and daily insulin doses were measured for each period.Safety and tolerability were also assessed.Results A statistically significant reduction(P≤0.0001)of HbA1c was achieved after each treatment(human insulin mix 30/70:mean HbA1c=7.91%(95% CI:7.67%,8.15%);insulin lispro low mix 25:mean HbA1c=7.96%(95% CI:7.72%,8.20%)).The 95% CI(-0.20,0.10)of the difference between the two treatments satisfied the prespecified noninferiority margin of 0.3%(lower limit of 95% CI＞-0.3%).No statistically significant differences between treatments were observed for any of the secondary efficacy measures.The incidence of treatment-emergent adverse events and hypoglycemia between the two treatments and treatment sequence groups was similar.Three serious adverse events were reported(human insulin mix 30/70 group:2 patients(1.7%,hypoglycemic coma and cardiac failure);insulin lispro low mix 25 group:1 patient(0.9%,stroke)).All serious adverse events were resolved and no patients died during the study.Conclusion The results support noninferiority of twice daily insulin lispro low mix 25 versus twice daily human insulin mix 30/70 in HbAlc control in Chinese patients with type 1 or 2 diabetes。

Abstract：Background As one of most widely-used biguanides,metformin can induce the lactic acidosis in patients with renal failure though its incidence is very low.However,lactic acidemia induced by mefformin was reported in patients without renal dysfunction.It is unclear that whether lactatemia exists in diabetic patients with normal renal function in Chinese or not and its influencing factors.This study aimed to clarify the influencing factors of lactic acid,and identify a practiced clinical marker to predict the hyperlactacidemia in diabetics with normal renal function.Methods The clinical data and venous blood samples of 1024 type 2 diabetic patients treated with(n=426)or without metformin(n=599)were collected.The lactic acid was assayed by enzyme-electrode method.The biochemical indexes included creatinine(Cr)and hepatase were measured with enzymatic procedures.The lactic acid concentrations of different Cr subgroups were compared,and the correlation and receiver operating characteristic curve analysis were used.Results The mean lactic acid level and the proportion of hyperlactatemia of metformin group were significantly higher than that of non-metformin group(P＜0.01),but no lactic acidosis was found in all patients.The correlation and multiple stepwise regression analysis indicated that the correlative factors of lactic acid in turn were Cr,metformin,alanine transferase(ALT),body mass index(BMI),Urine albumin(Ualb),and blood urea nitrogen(BUN)in total patients;and Cr,ALT,BMI and BUN in non-metformin treated patients;Cr and ALT in metformin-group.The lactate concentration increased with the increment of Cr levels,and reached its peak at Cr 111-130 μmol/L,and the optimal cutoff of Cr in predicting hyperlactacidemia was 96.5 μmol/L.Conclusions Metformin can increase the incidence of lactatemia in type 2 diabetic patients without renal dysfunction.Cr,ALT,and BMI are independent associated factors of blood lactic acid levels.There is low proportion of lactatemia in type 2 diabetics without metformin therapy,the optimal cutoff of Cr to predict lactatemia in these patients is 96.5 μmol/L。

Abstract：Background Early intensive insulin therapies in newly diagnosed type 2 diabetic patients may improve β-cell function and yield prolonged glycemic remissions.This study was performed to evaluate the relationship between the glycemic remission and β-cell function and assess the variables predictive of long-term near-normoglycemic remission.Methods Eighty-four newly diagnosed type 2 diabetic patients were treated with 2-week continuous subcutaneous insulin infusion(CSII)and followed up longitudinally.Intravenous glucose tolerance tests(IVGTTs)were performed,and blood glucose,hemoglobin A1c(HbA1c)and insulin were measured at baseline,after CSII and at 2-year visit.The patients who maintained glycemic control for two years were defined as the remission group and those who relapsed before the 2-year visit were the non-remission group.Results The duration to be diagnosed of the patients(from the time that patients began to have diabetic symptoms until diagnosis)in the remission group was shorter than that in the non-remission group(1.00 month vs 4.38 months,P=0.040).The increase of the acute insulin response(AIR)was maintained after 2 years in the remission group model showed that a shorter duration to be diagnosed positively affected the duration of near-nomoglycemic remission with an odds ratio(OR)1.019,P=0.038,while fasting plasma glucose(FPG)and post-breakfast plasma glucose(PPG)after CSII were the risk factors(OR 1.397,P=0.024 and OR 1.187,P=0.035,respectively).Conclusion The near-normoglycemic remission is closely associated with long-term maintenance of β-cell function and occurs more commonly in patients with shorter duration to be diagnosed and better glycemic control during CSII。

Abstract：Background Dyslipidaemia is a potential independent risk factor for cerebrovascular disease in patients with diabetes.The aim of this study was to investigate dyslipidaemia,treatment and control of dyslipidaemia among diabetic patients with ischemic stroke in a Chinese hospital.Methods A total of 1046 type 2 diabetic patients were assigned to diabetes with(n=522)and diabetes without stroke groups.The two groups were matched by gender,age and diabetes duration.Lipid and lipoprotein profile were measured.Serum level and control of lipids were assessed and classified according to Amedcan Diabetes Association(ADA)guidelines and an intensified low density lipoprotein-cholesterol(LDL-C)target recommended in Chinese dyslipidaemia control criteria.Results Diabetic patients suffering stroke displayed not only poorly-controlled lipid and lipoprotein profiles,including the significantly lower proportion of patients achieving intensified LDL-C target of＜2.07 mmol/L(80 mg/dl),and high density lipoprotein-cholesterol(HDL-C)target(14.4% vs 21.0%,P=0.005;45.8% vs 51.9%,P=0.048 respectively),but also less adherence to therapy prescribed for dyslipidaemia(30.8% vs 41.0%,P=0.001),when compared with diabetic patients without stroke.For the diabetic women with stroke,situation of dyslipidaemia was worse,with significantly lower serum level of HDL-C and apoA1,higher LDL-C level and higher ratio of apoB/apoA1 when compared with diabetic counterparts without stroke.Conclusions Many diabetic patients with ischernic stroke remain uncontrolled for dyslipidaemia.Intensified LDL-C and overall lipid lowering clinical goals are potential precautions taken against ischemic stroke among diabetic patients in China。

Abstract：Background Diabetic nephropathy is a common complication of diabetes mellitus.This study aimed to explore whether mesenchymal stem cells(MSCs)transplantation could attenuate diabetic nephropathy in experimental diabetic rats.Methods Sprague-Dawley rats received a single intraperitoneal injection of streptozotocin(STZ)(60 mg/kg).Diabetic rats were randomized to four groups:diabetes control group(DC),ciclosporin A group(CsA),MSC group,and MSC+CsA group(MSCA).Bone marrow mesenchymal stern cells were cultured,identified and labeled by 5-bromo-2'-deoxyuridine(BrdU)in vitro.Then they were transplanted to diabetic rats via introcardiac infusion.Ciclosporin A was administered daily at 5 mg/kg.At 1,2,4,8 weeks after transplantation,random blood glucose,urine albumin/creatinine ratio(AIb/Cr),endogenous creatinine clearance rate and renal mass index were tested.Renal morphology and labeled cells were examined.Results Cultured MSCs expressed mesenchymal cell phenotype,and could be multidifferentiated to osteogenic and adipogenic cells.Labeled MSCs could be detected in the kidney of nephropathic rats,mainly in renal interstitium,but they did not propagate after engrafting in kidney.Over the course of the experiment,MSCA group showed a significant decrease in blood glucose compared with MSC group,CsA group and DC group(P＜0.05,respectively).The AIb/Cr in MSCA group and MSC group were significantly lower than CsA group and DC group(P＜0.05).And the AIb/Cr in MSCA group showed a significant decrease compared with MSC group(0.74 vs 0.84,P＜0.05).There was a significant difference in renal mass index between the MSCA group and DC group(5.66 vs 6.37,P＜0.05).No significant difference was found in creatinine clearance rate among 4 groups(P＞0.05).Treatment with MSC+CsA significantly ameliorated the morphology of diabetic kidney.Conclusion MSC could mildly ameliorate diabetic nephropathy by decreasing blood glucose,AIb/Cr ratio and renal mass index。

Abstract：Background Cardiac failure is a leading cause of the mortality of diabetic patients.In part this is due to a specific cardiomyopathy,referred to as diabetic cardiomyopathy.Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease.This study aimed to test whether the antioxidant α-lipoic acid(α-LA)could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy.Methods A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin(STZ)45 mg/kg.Experimental animals were randomly assigned to 3 groups:normal control(NC),diabetes(DM)and DM treated with α-LA (α-LA).The latter group was administered with α-LA(100 mg/kg ip per day),the remainder received the same volume vehicle.At weeks 4,8,and 12 after the onset of diabetes,cardiac apoptosis was examined by TUNEL assay.Cardiomyopathy was evaluated by assessment of cardiac structure and function.Oxidative damage was evaluated by the content of malondialdehyde(MDA),reduced glutathione(GSH)and the activity of manganese superoxide diamutase (Mn-SOD)in the myocardial mitochondria.Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blottingResults At 4,8,and 12 weeks after the onset of diabetes,significant reductions in TUNEL-positive cells,caspase-9,-3 expression,and mitochondrial cytochrome c release were observed in the α-LA group compared to the DM group.In the DM group,the content of MDA in the myocardial mitochondria was significantly increased,and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD.They were significantly improved by α-LA treatment.HE staining displayed structural abnormalities in diabetic hearts,while α-LA reversed this structural derangement.The index of cardiac function(±dp/dtmax)in the diabetes group was aggravated progressively from 4 weeks to 12 weeks,but α-LA delayed deterioration of cardiac function(P＜0.05).Conclusions Our findings indicate that the antioxidant α-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy.The ability of α-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria。

Abstract：Background A 65-kD mdr1(multi-drug resistance protein 1,P-glycoprotein)-like protein has been suggested to be the regulatory protein to the chloride channel protein 3(CIC-3)mediating insulin granules acidification and release in mouse pancreatic beta cells.But the protein has not been deeply investigated.In this study,we identified existence of the 65-kda protein in rat islets and preliminarily explored its biological functions.Methods Total RNAs of rat kidneys served as positive controls,and pancreas,islets and INS-1 cells were extracted for reverse-transcript PCR(RT-PCR),respectively.The cDNAs were run with specific primers selected from the mRNA of abcblb encoding P-glycoprotein.All PCR products were visualized in agarose gel electrophoresis and sequenced.Homogenates of rat islets and INS-1 cells were applied to SDS-PAGE.P-glycoprotein was detected by a specific monoclonal antibody,C219.Biphasic insulin release was measured in static incubations of rat islets with radioimmunology assay.Results Compared with positive control,expression of the P-glycoprotein mRNA segments were detected in the islets,INS-1 cells and pancreas.Sequence analysis confirmed that the PCR products were matched with mRNA of P-glycoprotein.A 65-kda protein was recognized by the antibody in the islets homogenate but not in that of INS-1 cells in Western-blotting.Instead,the homogenate of INS-1 cells contained a 160-kda protein recognized by the antibody.Insulin secretion of rat islets were stimulated by high glucose(16.7mmol/L),and showed biphasic curve during 60-minute incubation.After co-incubation with cyclosporine A(CsA),specific inhibitor to P-glycoprotein,the second phase of insulin secretion was reduced significantly while the first phase was not influenced.Conclusions The 65-kda protein expressed in rat islets is most likely a mini-P-glycoprotein.It may play a key role regulating biphasic insulin release。

Abstract：Background Matrix metalloproteinase-1(MMP-1)plays an important role in atherosclerosis.This study was to examine expression of MMP-1 mRNA in peripheral blood mononuclear cells(PBMCs)of patients with systemic lupus erythematosus(SLE),and to explore its relationship with atherosclerosis in SLE.Methods Fluorescent quantitative reverse transcription polymerase chain reaction(RT-PCR)was used to examine the expression of MMP-1 mRNA in PBMCs in 80 SLE patients,including 39 prone to atherosclerosis(Group A)and 41 unprone to atherosclerosis(Group B).Meanwhile,30 patients who were free of cardiovascular diseases and 30 healthy individuals were selected as disease and normal control group(Groups C and D).The changes of MMP-1 gene expression were analyzed by differences of cycle threshold(△Ct),with the following formula:△Ct = Cttarget gene-Ctreference gene.Results The expression level of MMP-1 mRNA in Group A was significantly higher than that of group B(△Ct=8.64±2.43 vs △Ct=12.09±2.26,t=6.588,P＜0.01).The expression level of MMP-1 mRNA of SLE patients was significantly higher than that of Group C(△Ct=10.41±2.90 vs △Ct=12.29±2.51,t=-3.135,P＜0.01)and Group D(△Ct=10.41±2.90 vs △Ct=12.48±1.69,t=3.675,P＜0.01).Conclusions In comparison to disease and control group,expression of MMP-1 mRNA in PBMCs of SLE patients was significantly elevated,and significant difference of MMP-1 mRNA expression was also found between SLE patients prone and unprone to atherosclerosis,indicating that expression of MMP-1 mRNA may be correlated with the pathogenesis and activity of atherosclerosis in SLE。

Abstract：Background A five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A(SAA)levels and the incidence of atherosclerosis(AS)in patients with short-duration type 2 diabetes mellitus(T2DM)without maoroangiopathy,and whether intensive multifactorial intervention could prevent or at least postpone the occurence of macroangiopathy.Methods Among 150 patients with short-duration T2DM,75 were assigned to receive conventional outpatient treatment (conventional group)and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia,hypertension,dyslipidemia and received aspirin simultaneously(intensive group).Results Plasma SAA levels were higher in diabetic patients than those in healthy control subjects,and decreased obviously after intensive multifactorial intervention.The levels of SAA were positively correlated with body mass index(BMI),waist hip ratio(WHR),triglyceride(TG),high sensitive C-reactive protein(hs-CRP)and common carotid intima-media thickness(CC-IMT).The standard-reaching rates of glycemia,blood pressure and lipidemia were significantly higher in intensive group than those of conventional group.The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group.Conclusions Intensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM.SAA might be one of the risk factors of T2DM combined with AS。

Abstract：Background The immunologic response to allergens mediated by T lymphocytes is an incipient key element in the pathogenesis of asthma,and Th1/Th2 balance is regarded as the core of asthma pathogenesis.Notch is a single-pass transmembrane receptor protein that regulates differentiation,proliferation and apoptosis in a broad range of cells.It is considered that the Notch signal pathway works in every stage of T cell development and differentiation.Whether the pathway of asthma pathogenesis is related to Notch1 remains unknown.This study is aimed to investigate whether the pathway of asthma pathogenesis is related to Notch1 by examining the effect of knockdown of the Notch1 gene by small interfering RNA on T cell differentiation.Methods An OVA-induced asthma mouse model was established.The expression of Notch1 in the tissue and T cells of the lung from asthmatic mice was detected by RT-PCR and Western blotting.The expression of Notch1 and cytokine interleukin(IL)-4 and interferon(IFN)-γ in activated lung T cells was detected by RT-PCR and enzyme-linked immunosorbent assay after blocking Notch1 by small interfering RNA.Results The mRNA and protein expression of Notch1 increased significantly both in the lung tissue and lung T cells of asthmatic mice(both P＜0.05).IL-4 decreased and IFN-γ increased significantly in active lung T cells after Notch1 was blocked by Notch1-specific small interfering RNA(IL-4:(2.51±0.51)pg/ml vs 0.64±0.27)pg/ml protein;IFN-γ:(21.72±4.24)pg/ml vs(39.79±4.09)pg/ml protein,P＜0.05).Conclusion This study demonstrated that the Notch1 signal might play a role in the pathogenesis of asthma by its involvement in Th1/Th2 differentiation。

Diabetes mellitus known as its macro-and microangiopathy has caused thousands of mortality per year.Recent researches showed that hyperglycemia,advanced glycation end products(AGEs)and some other factors acted on the process of atherogenesis.AGEs can combine with receptors of AGEs(RAGEs),which exist on the vascular endothelium,smooth muscle cells,macrophage,lymphocyte and so on。

Primary gallbladder carcinoma is the most common malignant tumor of the biliary system.There is a reduced likelihood for radical cure of primary gallbladder carcinomas because of the insidious onset.1 Spiral computed tomography(SCT)scanning is an important means for diagnosing lesions involving the gallbladder。

Tethered spinal cord syndrome(TCS)is a condition of overstretching or compression of the caudal part of the spinal cord caused by various spinal lesions,such as a tight filum terminale or an intraspinal lipoma.1-9 Though it is a well-recognized cause of neurological deterioration in childhood,its symptomatic onset in adulthood is uncommon.10-23 Eleven cases of TCS are presented here.In addition,their related clinical features,surgical procedures and outcomes are investigated。

Extracorporeal membrane oxygenation(ECMO)can play an important role by providing short-term circulatory support to enable myocardial recovery in patients with life-threatening heart failure.Currently,over 4000 children who received ECMO for cardiac support have been reported to the Extracorporeal Life Support Registry,with the majority of patients placed on ECMO following cardiac surgery。

Usually the vertebral artery(VA)arises from the first part of the subclavian artery and enters the transverse foramen of the C-6 vertebra(first segment)and then ascends through the transverse foramen from C-6 to the atlas(second segment)。

Adenomatoid tumors(ATs)are benign neoplasms that most commonly occur in the genital tracts of both male and females。