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.

The association of coagulation function with progressive proteinuria in type 2 diabetic patients was retrospectively analyzed.With increasing microalbuminuria,fibrinogen level was increased significantly.Fibrinogen was an independent risk factor of microalbuminuria. In patients as the early-stage diabetic nephropathy (DN)progressed to clinical-stage DN,the baseline level of fibrinogen was also increased [ ( 3.5 ± 0.9 vs 3.0 ± 0.6 ) g/L,P＜0.05 ].Fibrinogen may serve as a useful predictor of progressive proteinuria in type 2 diabetes.

Blood lipid level and its associations with insulin resistance were studied in patients with impaired glucose tolerance (IGT).Two hundred and twenty first degree relatives of type 2 diabetes mellitus were grouped into normal glucose tolerance (NGT) and IGT groups according to results of oral glucose tolerance test.Compared with the NGT group,the IGT patients had higher serum levels of total triglyceride (TG),total cholesterol (TC),low density lipoprotein-C (LDL-C) but a lower serum level of high density lipoprotein-C (HDL-C).Homeostasis model of assessment for insulin resistance index (HOMA-IR) and area under curve of insulin (AUCI) also increased.A positive relationship was found between TG and HOMA-IR (or AUCI),but a negative relationship existed between HDL-C and HOMA-IR.In conclusion,abnormal blood lipid metabolism is present in IGT patients and it has a close correlation with insulin resistance.

Objective To evaluate the functions of pancreatic islet α-cells and β-cells in different disease courses of type 2 diabetes mellitus.Methods Two hundred and eighty three patients with type 2 diabetes mellitus were divided into 4 groups according to their disease courses:group A (course of disease ≤1 years),group B (1 years ＜ course ≤ 5 years),group C (5 years ＜ course ≤ 10 years) and group D (course ＞ 10 years).Oral glucose tolerance test (OGTT),insulin releasing test and glucagon releasing test were performed to observe the differences of glucagon,glucagon/insulin,ratio of insulin increment/glucose increment 30 min after glucose-load (△I30/△G30),area under curve (AUC) of insulin in receiver operational characteristic (ROC) curve of insulin (AUCI) and glucagon among 4 groups and the correlation analysis was performed between glucagon and other indicators.Results (1) Glucagon,glucagon/insulin and AUC of glucagon increased significantly with the prolonged course of disease (P ＜0.05),0、30、60、120、180 min of group A were (71 ± 20)、(106 ± 36)、(143 ± 54)、(133 ± 68) 和 (87 ± 55) ng/L respectively,glucagon increased significantly with the prolonged course of disease,0、30、60、120、180 min of group D (80 ±19)、(125 ± 36)、(167 ± 47)、(178 ± 64)、(129 ± 65) ng/L respectively.(2) There were no significant differences in homeostasis nodel assessment for insulin resistance index (HOMA-IR) and insulin sensitive index (ISI) among 4 groups (P ＞0.05); compared to group A,HOMA of β-cell function (HOMA-β),△I30/△G30,AUCI in groups B,C and D were significantly lower (F =3.75,3.77 and 3.07 respectively,all P ＜ 0.05).(3) Multiple stepwise regression analysis showed that glucagon was positively correlated with FPG and AUC of glucose (AUCG) (t =6.23 and 3.41,all P ＜ 0.05),and negatively correlated with AUCI/AUCG (t =-2.13,P ＜ 0.05).Conclusions In order to reach the blood glucose control target,in the early stage of diabetes attentions should be given to regulation of glucagon while protect the β-cell function.

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.

[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.

In subclinical diabetic nephropathy with glomerular hyperfiltration,the renal size parameters are increased significantly,and this change sets in as early as before the appearance of microalbuminuria.The average kidney length discriminator value for glomerular hyperfiltration by receiver operating characteristic (ROC) curve analysis is 10.53 cm,with the best sensitivity,higher specificity and total coincidence rate,and can be a clinical indicator for screening early diabetic nephropathy with glomerular hyperfiltration.

0.05).Conclusion Tripterygium wilfordii,combined with routine treatment,appeared to decrease 24-hour proteinuria in a certain extent and did not adversely affect liver function,renal function and the blood routine test in most patients with diabetic nephropathy.