Corresponding author:PAN Cong-qing,E-mail:cq.pan@163.com Objective The prevalence of diabetic foot was 2.3% for out-patients and 8.6% (208/2428) for in-patients with amputation rate of 17.3% in our hospital from May 1997 to Dec 2000, more often seen on right than left extremity and in patients over 50 years old than in the younger.

Objective To investigate the relationship between fasting plasma glucose (FPG) and islet α-cell and β-cell function in patients with type 2 diabetes mellitus (T2DM).Methods Four hundred and thirty-seven patients with T2DM were divided into 3 groups according to the level of FPG:F1 group:FPG ≤ 6 mmol/L (73 cases),F2 group:6 mmol/L ＜ FPG ≤ 7 mmol/L (103 cases),and F3 group:FPG ＞ 7mmol/L (261 cases),and 30 cases of healthy people were selected as control group.Oral glucose tolerance test,insulin releasing test and glucagon releasing test were performed to observe the differences of glucagon,glucagon/ insulin,the ratio of 30 min insulin and blood glucose value after glucose load (△ I30/△ G30),and the area under curve of insulin (AUC1) among the 4 groups and the correlation analysis was performed between glucagon and other indicators.Results Glycosylated hemoglobin (HbA1c),plasma glucose 120 at min after glucose load in F1,F2 and F3 group were significantly higher than those in control group,and there were statistical differences (P ＜0.05).In F1,F2,F3 group,with the increase of the HbA1c,the course of disease and plasma glucose at 120 min after glucose load showed increasing trend.The triglyceride in F2 group and F3 group was significantly higher than that in F1 group and control group,and low density lipoprotein cholesterol in F3 group was significantly higher than that in F1 group,F2 group and control group,and there were statistical differences (P ＜ 0.05).The glucagon at 60,120 min after glucose load in F1 group,30,60,120 min after glucose load in F2 group,and 30,60,120,180 min after glucose load in F3 group was significantly higher than that in control group,and there were statistical differences (P ＜ 0.05).The glucagon at 60,120,180 min after glucose load in F2 group,at fasting and 30,60,120,180 rain after glucose load in F3 group was significantly higher than that in F1 group,and there were statistical differences (P ＜ 0.05).The glucagon at fasting and 30,60,120,180 min after glucose load in F3 group was significantly higher than that in F2 group,and there were statistical differences (P ＜ 0.05).The area under curve of glucagon in control group was 9.5 ±0.3,in F1 group was 9.7 ± 0.2,in F2 group was 9.9 ± 0.2,in F3 group was 10.2 ± 0.3,and there were statistical differences among the 4 groups (P ＜ 0.05).The glucagon/insulin at fasting and 30,60 min after glucose load in F1 groups,fasting and 30,60,120 min after glucose load in F2 group,fasting and 30,60,120 min after glucose load in F3 group was significantly higher than that in control group,and there were statistical differences (P＜ 0.05).The glucagon/insulin at fasting and 60,120 min after glucose load in F2 group,fasting and 30,60,120,180 min after glucose load in F3 group was significantly higher than that in F1 group,and there were statistical differences (P ＜ 0.05).The glucagon/insulin 30,60,120,180 min after glucose load in F3 group was significantly higher than that in F2 group,and there were statistical differences (P＜ 0.05).The homeostasis model of assessment for insulin resistance index (HOMA-IR) in F2 group and F3 group was significantly higher than that in control group and F1 group,in F3 group was significantly higher than that in F2 group,and there were statistical differences (P＜ 0.05).The insulin sensitivity index (ISI) in F2 group and F3 group was significantly lower than that in control group and F1 group,in F3 group was significantly lower than that in F2 group,and there were statistical differences (P ＜ 0.05).The homeostasis model of assessment for islet β-cell function index (HOMA-β) and △I30/△G30 in F1,F2,F3 group were significantly lower than those in control group,and there were statistical differences (P ＜ 0.05).The AUC1 in F2 group was significantly lower than that in control group,and AUC1 in F3 group was significantly lower than that in control group,F1 group and F2 group,there were statistical differences (P ＜0.05).The results of Pearson correlation analysis showed there was negative correlation between glucagon and △I30/△G30,HOMA-β,body mass index,ISI,AUC1 (r =-0.229,-0.153,-0.151,-0.146,-0.136,P＜0.01 or ＜0.05),and there was positive correlation between glucagon and FPG,area under curve of glucose (AUCG),HbA1c,course of disease and HOMA-IR (r =0.545,0.476,0.273,0.193,0.189,P ＜ 0.01).The results of multiplestepwise regression analysis showed there was positive correlation between glucagon and FPG,AUCG,HbA1c,course of disease (P ＜0.01 or ＜0.05),and there was negative correlation between glucagon and △I30/△ G30 (P ＜ 0.05).Conclusions Islet β-cell function is decreased with the increasing of FPG,while islet α-cell function is increased,especially in those with higher levels of FPG.Regulation of glucagon should be concerned to make the blood glucose target easier to reach,at the same time of protecting β-cell function.

Objective To investigate the association of single nucleotide polymorphism (SNP) rs13333226 in uromodulin (UMOD) gene with diabetic kidney diseases (DKD) in Han population in Tianjin,China.Methods A total of 210 type 2 diabetes (T2DM),90 normal controls (NC) and 280 DKD patients were recruited.According to the level of estimated glomerular filtration rate (eGFR),the DKD subjects were further subdivided into three groups:GFR≥90 ml/min group (n=105),60 ml/mim≤GFR ＜ 90 ml/min group (n=84) and GFR ＜ 60 ml/min group (n=91).Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for UMOD rs13333226C genotyping.Results The frequencies of AA,GA,GG genotype were 27.8％,58.9％,13.3％ in NC group and 41.0％,48.6％,10.5％ in T2DM group and 54.3％,36.1％,9.6％ in DKD group.The frequency of G allele was 42.8％ in NC group,34.8％ in T2DM group and 27.7％ in DKD group.The genotype distribution of UMOD was statistically significant between NC group and DKD group,and between T2DM group and DKD group (P ＜ 0.05).G allele of UMOD was an independent protective gene polymorphism of DKD in Logistic regression (B=-0.248,Wald=8.012,P=0.021,OR=0.780,95％ CI 0.612-0.968).Conclusion The G allele of UMOD gene may be an independent protective factor of DKD in Han population in Tianjin,China.

T-cell exhaustion is characterized by the stepwise and progressive loss of T cell functions under conditions of antigen-persistence, which occurs following chronic infections and tumor outgrowth. Exhausted T cells present functional defects, express multiple inhibitory receptors and show reprogrammed transcriptional regulation. As T cell exhaustion is correlated to its dysfunction to control infections and tumors, exploring new strategies to target exhausted T cell may reverse this dysfunctional state and reinvigorate immune response. This study takes CD8+ T cell as an example, which acts as an important subset involved in exhaustion state, discuss current understanding of the properties of exhausted T cell and the mechanisms that promote and maintain this state, and reveal new therapeutic targets for chronic infection and cancer.

According to the analysis of 9 237 hospitalized type 2 diabetic patients, the prevalence of diabetic retinopathy ( DR )was 32.9％ , with the prevalence of mild, moderate, and serious non-proliferative DR and proliferative DR being 10. 1％, 18. 3％, 3.2％, and 1.3％ respectively. The prevalence of diabetic macular edema ( DME ) was 3.56％ in type 2 diabetics and i 0. 8％ in patients with DR. Diabetes duration and proteinuria were the common risk factors of DR and DME.

[Summary] To investigate the association between sleep disorder and ambulatory blood pressure rhythm in patients with type 2 diabetes. 418 patients with type 2 diabetes were divided into two groups according to Pittsburgh sleep quality index ( PSQI):patients without sleep disorder and patients with sleep disorder. Oral glucose tolerance test, insulin releasing test, and C-peptide releasing test were performed to investigate the differences in the β-cell function, the circadian rhythm of blood pressure, and blood pressure variation between the two groups after fasting and glucose-load. The correlation and regression analysis were performed between PSQI and other indicators. (1)The level of HbA1C , fasting plasma insulin, area under curve of insulin, fasting plasma C-peptide, area under curve of C-peptide, and homeostasis model assessment for insulin resistance ( HOMA-IR) were significantly higher in patients withsleepdisordercomparedtothoseinpatientswithoutsleepdisorder[(8.2±2.1)% vs(7.4±1.8)%,(13.42± 4.55vs11.86±4.52)mU/L,(8.51±0.54vs8.38±0.51)mU·L-1·min,(2.42±1.25vs1.79±0.73)ng/ml, (6.59±0.39vs6.49±0.43)μg·L-1·min,4.63±1.12vs3.86±0.97,allP<0.05]. Insulinsensitivityindex (ISI) was lower in patients with sleep disorder than that in patients without sleep disorder(-4. 26 ± 0. 78 vs-4. 05 ± 0.62,P<0.05). (2)Thelevelof24hmeansystolicanddiastolicbloodpressure,nocturalsystolicanddiastolicblood pressure, and systolic blood pressure during daytime and nighttime were significantly higher in patients with type 2 diabetes who were suffering from sleep disorder. The blood pressure variation was more marked in patients with sleep disorder. (3)Multiple stepwise regression analysis showed that PSQI score was positively related to area under curve of C-peptide, HOMA-IR, 24 h mean systolic blood pressure, and noctural systolic blood pressure (β=0. 242, 0. 293, 0. 352, 0. 413, all P<0. 05), and negatively related to ISI and decreasing ratio of noctural systolic blood pressure (β=-0. 124 and -0. 226, both P<0. 05). Sleep disorder may cause abnormal circadian rhythm of blood pressure through various mechanisms. Improving sleep disorder may help to ameliorate insulin resistance and restore normal circadian rhythm of blood pressure.

Through retrospective analysis of the clinical and laboratory data of 1 466 inpatients with type 2 diabetes mellitus(T2DM),we investigated the prevalence of chronic kidney disease (CKD) and analyzed the risk factors.The prevalence of CKD in hospitalized patients with T2DM was 52.25％.In the patients with CKD,protein urine was present in 93.47％ of the cases,27.93％ of them had glomerular filtration rate(eGFR) ≤60 ml · min-1 · 1.73 m-2,damage of renal tubular function was present in 24.28％,and abnormal renal imaging in 14.88％.Logistic regression showed that age,body mass index(BMI),duration of diabetes,systolic blood pressure,serum uric acid,low density lipoprotein-cholesterol (LDL-C),and smoking were independently associated with patients of T2 DM and CKD.The prevalence of CKD was increased with aging,diabetic course,BMI,and LDL-C.CKD is a common chronic complication in patients with T2DM,especially in patients with prolonged course,advanced age,and obesity.Much attention should be paid to early detection of CKD in patients with diabetes.In addition to detecting urinary protein and eGFR,renal tubular function and morphological examination should also be included.

Objective To investigate the clinical characteristics of diabetic retinopathy(DR)and diabetic nephropathy(DN)and their correlation. Methods All of 9237 hospitalized type 2 diabetes patients from January 2004 to June 2009 were collected. The prevalence and clinical of characteristics of DR and DN as well as their relationship were analyzed. Results The total prevalence of DR was 33.0%(3045/9237),and the prevalence of DR in the microalbuminuria, macroproteinuria and macroalbuminuria combined with renal dysfunction patients were 36.3%(588/1618),53.7%(1113/2074)and 70.7%(1206/1706)respectively.The prevalence of DN was 58.4%(5398/9237). Compared with that in the diabetes patients without DR, the levels of microalbumin and total protein in the urine were higher in the patients with moderate non-proliferative diabetic retinopathy(NPDR), serious NPDR and proliferative diabetic retinopathy(PDR), but the endogenous creatinine clearance rate was lower(P＜ 0.05). According to the non-conditional Logistic regression model,the risk factors of DR included diabetes duration,urinary protein,fibrinogen, C-reactive protein and peripheral neuropathy, and the risk factors of DN included diabetes duration, HbA1c, systolic blood pressure,urinary protein,low density lipoprotein and DR. Conclusions DR and DN are the chronic microvascular complications in the type 2 diabetes and have higher prevalence. There are good correlations between DR and DN.

Objective To evaluate the inhibitory effect of statins on glucose-stimulated insulin secretion (GSIS) of pancreatic islet in rat and to explore its mechanisms. Methods According to the average volume, freshly isolated or 24-hour cultured pancreatic islets were randomly divided into control group( incubated with Kreb-Ringer bicarbonate buffer), the atorvastatin group( incubated with 100 μ mol/L atorvastatin), the fluvastatin group (incubated with 100 μ mol/L fluvastatin)and the pravastatin group (incubated with 100 μ mol/L pravastatin). Stimulated by 2. 8,5. 5,11.1,16. 7 mmol/L and 25.0 mmol/L glucose respectively, the effect of 100 μ mol/L statins on ATP content and GSIS was compared in the four groups. GSIS was performed by the 37℃ bath incubation method and ATP content was measured by chemiluminescence method. Results Incubated with 100 μ mol/L atorvastatin for 30 minutes, in the presence of 16. 7 mmol/L glucose, the ATP content [(9. 54 ± 1. 64) pmol/islet vs ( 12. 33 ± 1.89) pmol/islet] and GSIS (1.60 ± 0. 21 vs 2. 39 ± 0. 30) were significantly reduced in comparison with the control group (P＜0. 05). Cultured with 100 μmol/L fluvastatin for 24 hours, the ATP content [( 10. 24 ±2.01 )pmol/islet vs (12. 31 ±2. 16) pmol/islet] and GSIS (3. 12 ± 0. 32 vs 4. 17 ±0. 37 ) were all significantly decreased at the higher glucose concentration of 16. 7 mmol/L ( P ＜ 0. 05). Conclusion Atorvastatin and fluvastatin may inhibit GSIS by decreasing ATP content in pancreatic islet and the inhibitory effect is related to the strength of its lipophilicity.

Objective To compare efficacy of nateglinide or acarbose combined with metformin in patients with newly diagnosed type 2 diabetes.Methods Ninety-six patients with newly diagnosed type 2 diabetes in Metabolic Diseases Hospital of Tianjin Medical University,were randomly to receive nateglinide combined with metformin (group A,n =46) or acarbose combined with metformin (group B,n =42) for four months.Drug dose was adjusted every two weeks.Before and after treatment,oral glucose tolerance test and insulin release test were performed to observe changes of their glucose tolerance,homeostasis model assessment for insulin resistance (HOMA-IR) ,insulin secretion function of β-cells and glucose disposition index (DI) in the two groups.Results After four-month treatment,six patients restored to normal glucose tolerance and 13 patients returned to impaired glucose tolerance (IGT) in group A and 12 patients restored to IGT in group B.Their HOMA-IR was markedly improved compared with baseline in both groups,decreased to 7.1 ± 1.3 from 8.6 ± 1.2 in group A and to 6.9 ± 1.7 from 8.6 ± 1.7 in group B ( P ＜ 0.05 ).Compared with group B,early insulin secretion ( LN△I30/△G30 ) obviously improved in group A [( 1.9 ±0.8) vs.(1.6±0.6) mU/mmol] (P＜0.05) and DI also increased (1.05±0.25 vs.0.89±0.21,P＜0.05 ).Conclusions Nateglinide combined with metformin can obviously restore early insulin secretion and improve insulin resistance in patients with newly diagnosed type 2 diabetes,thus facilitate restoration of their glucose tolerance.