Heart rate variability(HRV)analysis and its circadian rhythm(CR)were determined in 58patients with type 2 diabetes mellitus with lower extremity neuropathy(diabetic neuropathy group), 59 patients with type 2 diabetes mellitus without lower extremity neuropathy(diabetes group), and 50 healthy controls according to 24-hour Holter recording. Frequency domain parameters of HRV were significantly decreased in both diabetes groups. Frequency domain parameter of HRV in healthy controls,and daytime/nighttime difference were statistically significant. CR of HRV was changed in diabetes group and disappeared in diabetic neuropathy group. Impaired and seriously impaired autonomic nervous function developed in type 2 diabetes mellitus without and with lower extremity neuropathy respectively.

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.

Background and purpose: Protein kinase P1k3 could increase the transcriptional activity of p53. However, the effect of P1k3 on the transcriptional activity of p73 is still unknown. Our study was to investigate the effect of P1k3 on the transcriptional activity of p73. Methods: Luciferase reporter assay, RT-PCR and colony formation assay were adopted to study the effect of P1k3 and kinase-deficient P1k3 (K52R) on the transcriptional activity of p73 in p53-deficient human lung carcinoma H1299 cells. Results: Luciferase reporter assay showed that p73 increased the luciferase activities induced by p21~(WAF1) and Bax promoters (P<0.05). After co-transfection with p73 and P1k3, the luciferase activities induced by p21~(WAF1) and Bax promotors were significantly decreased in a dose-dependent manner as compared with the group that transfected p73 only (P<0.05). However, kinase-deficient Plk3 (K52R) had no significant effect on the luciferase activities induced by p21~(WAF1) and Bax promoters (P>0.05). RT-PCR showed that p73 increased the mRNA expressions of p21~(WAF1) and BAX (P<0.05). P1k3 decreased the expressions of p21~(WAF1) and Bax induced by p73 (P<0.05). Kinase-deficient P1k3 (K52R) had no significant effect on the expressions of p21~(WAF1) and Bax induced by p73 (P>0.05). Colony formation assay revealed that p73 decreased the colony formation of H1299 cells (P<0.05). P1k3 decreased the inhibitory effect of p73 on the colony formation of H1299 cells (P<0.05). Kinase-deficient P1k3 (K52R) had no significant effect on the inhibitory effect of p73 on the colony formation of H1299 cells (P>0.05).Conclusion: P1k3 can inhibit the transcriptional activity of p73, where as kinase-deficient P1k3 has no effect on the transcriptional activity of p73.

OBJECTIVE: To establish a quantitative preliminary evaluation of introduced drugs. METHODS: A quantitative form was designed for new drugs’ preliminary evaluation, which included many factors, such as qualification of pharmaceutical factory or company, category of drugs in medical insurance, the result of the biding drugs, comparison with other drugs of the same category, PK and PD data,special use and clinical demand. Each factor was given a definite score .If the total scores of a given drug amounted to the expected figure, this drug could pass the preliminary evaluation and enter the next step, and if not, the drug may be eliminated. RESULTS&CONCLUSION: The purpose of evaluating the new drugs scientifically and objectively can be basically achieved through quantitative method, which can lessen the blindness in introduction of new drugs.

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.

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.

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.

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.

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.

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.