2型糖尿病患者晨尿微量白蛋白／肌酐与24h尿微量白蛋白相关性分析

目的：研究2型糖尿病（T2DM）患者晨尿微量白蛋白（MALB）/肌酐（Cr）影响因素及用晨尿MALB/Cr评估尿蛋白排泄的可行性。方法：收集179例T2DM患者晨尿和24h尿,测定晨尿MALB、Cr、24h尿MALB及其他各项生化指标,并按肌酐清除率（Ccr）分为25.66-49mL/min、50-79mL/min、≥80mL/min3组,进行各项生化指标与晨尿MALB/Cr的相关性分析。结果：晨尿MALB/Cr与年龄、体质指数（BMI）、DM病程、24h尿MALB、24h尿蛋白（24h尿TP）、收缩压（SBP）、舒张压（DBP）、糖尿病视网膜病变（DR）呈正相关。DM病程、SBP、DR是T2DM患者晨尿MALB/Cr的影响因素。Ccr≥25.66mL/min时,各组晨尿MALB/Cr与24h尿MALB呈正相关。结论：晨尿MALB/Cr可代替24h尿MALB,用于观察尿蛋白排泄情况并对2型糖尿病肾病进行检测和评估,此测定适用于尿量Ccr≥25.66mL/min的不同Ccr的T2DM患者。

2型糖尿病合并不稳定性心绞痛患者尿微量白蛋白、血浆内皮素与冠脉病变程度的关系研究

目的探讨2型糖尿病合并不稳定性心绞痛患者尿微量白蛋白(MA)和血浆内皮素(ET)与冠脉病变程度的关系。方法通过将笔者医院2009年1月～2011年1月住院治疗的85例不稳定性心绞痛患者依据冠脉病变支数和Gensini积分进行分组,并分析MA和ET与冠脉病变支数及Gensini积分相关性。结果①多支病变组(≥2支)共有69例患者,占81.2%,单支病变组16例患者,占18.8%;严重病变组(即Gensini积分﹥20分)共有53例患者,占62.4%,非严重病变组(即Gensini积分0～20分)32例患者,占37.6%;②单支病变组的ET水平(72.32±7.34pg/ml vs 81.47±5.65pg/ml,P<0.05)和MA水平(23.46±1.15mg/L vs 35.21±4.23mg/L,P<0.01)均低于多支病变组,非严重病变组的ET水平和MA水平均低于严重病变组(P<0.01和P<0.05);③2型糖尿病合并不稳定性心绞痛患者ET水平和MA水平与Gensini积分具有显著相关性(r=0.75,P<0.05和r=0.63,P<0.05)。结论 2型糖尿病合并不稳定性心绞痛患者的尿微量白蛋白和血浆内皮素与冠脉病变程度有显著性的正相关,随着冠脉病变程度的加重,其尿微量白蛋白和血浆内皮素的水平升高。

六味地黄丸联合地特胰岛素对2型糖尿病合并冠心病病人的血糖控制及心血管事件的影响

目的分析六味地黄丸联合地特胰岛素对2型糖尿病合并冠心病病人的血糖控制及心血管事件的影响。方法选择2013年3月—2014年4月我院收治的120例2型糖尿病合并冠心病病人,按照随机数表法将病人分为观察组(60例)和对照组(60例)。对所有病人均给予氯吡格雷、β-受体阻滞剂、他汀类、肠溶阿司匹林以及冠脉介入术等的常规治疗,观察组在此基础上给予六味地黄丸联合地特胰岛素治疗。对照组在此基础上给予病人地特胰岛素治疗。对所有病人治疗疗效进行评定,比较治疗前后空腹血糖、餐后2h血糖,心血管不良事件(死亡、心肌梗死、急性冠脉综合征、不稳定型心绞痛、靶血管重建、冠脉搭桥术)情况。结果观察组病人心电图疗效总有效率(96.67%)显著高于对照组(76.67%),差异具有统计学意义(P<0.05)。治疗后4周、8周,观察组空腹血糖、餐后2h血糖水平均低于对照组血糖水平,两组差异具有统计学意义(P<0.05)。治疗后,观察组急性冠脉综合征、不稳定型心绞痛、靶血管重建发生率均低于对照组(P<0.05)。观察组与对照组心血管不良事件总发生率分别为13.33%与86.67%(P<0.01)。结论六味地黄丸联合地特胰岛素对2型糖尿病合并冠心病病人的血糖控制良好,且能够降低心血管事件的发生率。

Role of Sclerostin in the Bone Loss of Postmenopausal Chinese Women with Type 2 Diabetes

Objective To evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes me｜litus. Methods The postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion.

Relationship between lipoprotein （a） and micro/macro complications in type 2 diabetes mellitus： a forgotten target

Objectives Increased lipoprotein （a） serum concentration seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein （a） and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association. Methods This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data （insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro and macrovascular complications were collected. Results Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein （a） was 22.2± 17.3 mg/dL （22.1± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females）. Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein （a）. Similarly, the patients with hyperlipoprotein （a） （≥30 mg/dL） presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein （a） is positively correlated with coronary heart disease and diabetic nephropathy （P 〈 0.01 and P 〈 0.005, respectively）. Conclusions The elevation of plasma levels of lipoprotein （a） are associ- ated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein （a） may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.

Yi-Qi-Zeng-Min-Tang,a Chinese medicine,ameliorates insulin resistance in type 2 diabetic rats

AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabetes model group,low-dose,medium-doseand high-dose YQZMT groups,and rosiglitazone group.Age-matched NPD-fed rats served as controls.YQZMT or rosiglitazone were administered for 8 wk.Intraperitoneal glucose and insulin tolerance tests were performed before and after the treatment to measure the glucose tolerance and insulin sensitivity.Serum levels of biochemical parameters,adipocytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),as well as free fatty acids(FFAs),were also analyzed.RESULTS:There was significant elevation of insulin resistance and serum levels of fasting glucose(12.82 ± 1.08 mmol/L vs 3.60 ± 0.31 mmol/L,P < 0.01),insulin(7197.36 ± 253.89 pg/mL vs 4820.49 ± 326.89 pg/mL,P < 0.01),total cholesterol(TC)(8.40 ± 0.49 mmol/L vs 2.14 ± 0.06 mmol/L,P < 0.01),triglyceride(2.24 ± 0.12 mmol/L vs 0.78 ± 0.05 mmol/L,P < 0.01),low-density lipoprotein cholesterol(LDL-c)(7.84 ± 0.51 mmol/L vs 0.72 ± 0.04 mmol/L,P < 0.01) and decrease in high-density lipoprotein cholesterol(HDL-c)(0.57 ± 0.03 mmol/L vs 1.27 ± 0.03 mmol/L,P < 0.01) in the low-dose STZ and high-fat diet induced type 2 diabetic group when compared with the control group.Administration of YQZMT induced dose-and timedependent changes in insulin resistance,glucose and lipid profile,and reduced levels of FFA,TNF-α and IL-6 in the type 2 diabetic rats.After the treatment,compared with the diabetic group,the insulin resistance was ameliorated in the high-dose YQZMT(2.82 g/100 g per day) group,with a significant reduction in serum glucose(12.16 ± 1.00 mmol/L vs 17.65 ± 2.22 mmol/L,P < 0.01),homeostasis model assessment of basal insulin resistance(22.68 ± 2.37 vs 38.79 ± 9.02,P < 0.05),triglyceride(0.87 ± 0.15 mmol/L vs 1.99 ± 0.26 mmol/L,P < 0.01),TC(3.31 ± 0.52 mmol/L vs 6.50 ± 1.04 mmol/L,P < 0.01) and LDL-c(2.47 ± 0.50 mmol/L vs 6.00 ± 1.07 mmol/L,P < 0.01),and a signif icant increase in HDL-c(0.84 ± 0.08 mmol/L vs 0.50 ± 0.03 mmol/L,P < 0.01).But the body weight was not changed signif icantly.CONCLUSION:YQZMT,which ameliorates insulin resistance and does not cause increase in body weight,may be a suitable therapeutic adjunct for the treatment of type 2 diabetes.

Research on saponin active compounds of Tuchao Baibiandouren for the treatment of type-2 diabetes based on UHPLC-Q-Exactive Orbitrap MS and network pharmacology

Objective To explore the pharmacological mechanism of active saponin compounds of Tuchao Baibiandouren(Lablab Semen Album fried with earth,TCBBDR)in treating type 2 diabetes(T2DM)using UHPLC-Q-Exactive Orbitrap MS and network pharmacology.Methods UHPLC-Q-Exactive Orbitrap MS was used for a qualitative analysis of saponin compounds in TCBBDR.PharmMapper and CTD were used to screen drug active compounds and disease targets,and an active compound-target network was constructed via Cytoscape 3.8.0.Molecular docking was applied with the drug active compounds and key targets using AutoDock Vina 1.1.2,and a trajectory for the molecular dynamics simulation was completed by GROMACS 2019-3.Results Sixteen saponin compounds were identified from TCBBDR,along with 292 saponin compoud targets and 792 T2DM targets.Through Venn analysis of target saponin constituents and T2DM related targets,a total of 91 intersection targets were screened out in the treatment of T2DM with saponin.The mean values of degree,betweenness centrality and closeness centrality were taken as the thresholds to screen out 22 key genes,among which 4 key proteins namely MAPK1,IGF1 EGFR,PIK3R1 were selected in the top 10 key genes.On this basis,the saponin active constituent-target-signaling pathway network was established.The Gene Ontology(GO)enrichment analysis showed that the related biological modules included activity of steroid hormone receptor,steroid binding,and insulin receptor binding,etc.;the related signaling pathways were EGFR,PI3K-Akt and MAPK,etc.;regulating signaling pathways like MAPK could induce the proliferation,inhibition and apoptosis of pancreaticβcells,increase the quantity of pancreaticβcells,improve the functions of pancreaticβcells and stimulate the insulin secretion.Docking experiment analysis showed that all selected saponin compounds could enter the active sites of targets and form 3–14 hydrogen bonds with residues of the active sites.Moreover,van der Waals forces were present between chemical compounds and active sites.By combining the docking binding energy,we determined that the chemical compounds showed strong binding energy to the targets.Conclusion TCBBDR exerts therapeutic effects on diabetes through multi-compound and multi-target collaboration.Specifically,saponin components mediate pathways including inflammatory reaction and signal transduction to treat T2DM by regulating several key proteins that interact with EGFR and a series of signaling pathways related to disease development.

Analysis on blood glucose excursions in well-controlled patients with type 2 diabetes mellitus

Objective:To probe glycemic excursions in type 2 diabetic patients whose hemoglobin A1c(HbA1c) was kept ≤6.0%.Methods:Totally 36 cases with type 2 diabetes(T2DM) with HbA1c≤6.0% and 30 cases with normal glucose tolerance(NGT) from December 2005 to December 2007 in our department were subjected prospectively.Continuous glucose monitoring system(CGMS) was employed to record their continuous blood glucose level for 3 d.The blood glucose profiles including the mean blood glucose(MBG),standard differentiation(SD),mean amplitude of glycemic excursions(MAGE) and absolute means of daily differences(MODD) were analyzed.Results:T2DM group had obviously postprandial hyperglycemia,in about 2 h after meal,especially after breakfast.Fifty-two hypoglycemic episodes occurred during the monitoring period in T2DM groups,of which 73.1%(38 episodes) were absence of symptomatic hypoglycemia with the lowest value of blood glucose only 2.0 mmol/L.And 20 episodes took place during the day hours,while 32 episodes observed during the night hours.Compared with NGT groups,SD,MAGE and MODD were all significantly higher in T2DM groups.MBG was significantly correlated with HbA1c in T2DM groups,but SD,MAGE,NGE and MODD were all independent of HbA1c.MAGE was independent of MODD.Conclusion:The amplitude of glycemic excursions is higher in normol-controlled T2DM groups than the NGT groups.Thus ideally glycemic control is not only to make HbA1c reach standard,but also to lessen glycemic excursions and reduce hypoglycemia episodes.

Vague relationship between alcohol consumption and metabolic syndrome in nonobese people

Fatty liver, including non-alcoholic fatty liver disease, is closely associated with metabolic syndrome (MS). Thus, the presence of fatty liver without MS in some conditions may be clinically important. Many studies have shown that compared with no or occasional alcohol intake, moderate alcohol consumption is associated with lower prevalence rates of hypertension and type 2 diabetes, and lower levels of circulating C-reactive protein, a valuable marker for MS and insulin resistance. Considering these findings, light to moderate alcohol consumption has theoretical benefits on fatty liver and MS. Fatty liver, including non-alcoholic fatty liver disease, may be more clinically important than MS, particularly in non-obese individuals, because fatty liver can develop before MS in several conditions, such as regular alcohol consumers. Furthermore, most of the currently used MS criteria are unable to detect "true MS" because of variations in multiple factors such as age, height, medications, and complications.

The association between PPP1R3 gene polymorphisms and type 2 diabetes mellitus

Objective To detect the relationship between the polymorphism of the glycogen-targeting regulatory subunit of the skeletal muscle glycogen-associated protein phosphatase 1 (PPP1R3) gene and type 2 diabetes by case-control study. Methods We genotyped the PPP1R3 gene Asp905Tyr polymorphism and a common 3'-untranslated region AT (AU)-rich element (ARE) polymorphism in 101 type 2 diabetic patients and 101controls by oligonucleotide ligation assay (OLA) and polyacrylamide gel elecrophoresis, respectively. Results Subjects with Tyr/Tyr genotypes whose body mass index (BMI)<25 were used as the reference group. Those whose BMI25 with Asp905 had a 3.66-fold increase (95% CI: 1.48-9.06, P=0.005) in type 2 diabetes risk. No association was found between 3'UTR ARE polymorphism and type 2 diabetes mellitus (OR=1.15; 95% CI: 0.62-2.14, P=0.65). Conclusion A joint effect between the Asp905 and BMI increases the risk of type 2 diabetes, and Asp905Tyr and ARE polymorphism of PPP1R3 gene are not the major diabetogenic gene variants in Chinese population.

Efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus:a meta-analysis of randomized controlled trials

As a new oral hypoglycemic agent, saxagliptin belongs to the class of dipeptidyl peptidase-4 （DPP-4） inhibitors. However, it remains inconclusive whether saxagliptin is associated with increased risk of adverse events （AE） and efficacy as add-on treatment. Therefore, we performed an up-to-date meta-analysis to compare the efficacy and safety of saxagliptin with placebo and other oral hypoglycemic agents in adult patients with type 2 diabetes mellitus （T2DM）. Randomized clinical trials （RCTs） comparing saxagliptin with comparators were retrieved by selecting articles from Pubmed, Embase, Cochrane Library and Clinical Trials Registry Platform up to Oct. 2013. Weighted mean difference （WMD） was used to analyze the effect of hypoglycemic agents on HbAlc, weight and fasting plasma glucose （FPG）. While the patients who achieved HbAlc〈7.0% and had AE were analyzed as relative risks （RR）. A total of 18 articles from 16 RCTs and one clinic trial from the WHO International Clinical Trials Registry Platform met the included criterion. Clinically significant decrease from baseline HbAlc compared with placebo was certified for 2.5 mg/day saxagliptin （WMD = -0.45%, 95% CI, -0.48% to -0.42%） and 5 mg/d saxagliptin （WMD = -0.52%, 95% CI, -0.60% to -0.44%）. Saxagliptin as add-on therapy was superior to thiazolidinediones, up-titrated glyburide, up-titrated metformin or metformin monotherapy in achieving HbA1c〈7.0%. Treatment with saxagliptin had negligible effect on weight, and it was considered weight neutral. Saxagliptin treatment did not increase the risk of hypoglycemia （RR = 1.28, 95% CI 0.72 to 2.27, P = 0.40） and serious adverse experiences （RR = 1.25, 95% CI 0.94 to 1.66, P = 0.13）. No statistically significant differences were observed between saxagliptin and comparators in terms of the risk of infections. The present study showed that saxagliptin was effective in improving glycaemic control in T2DM with a low risk of hypoglycaemia and incidence of infections in either monotherapy or add-on treatment. This founding should be further certified by large-sample size and good-designed RCT.

Retrospective study of Traditional Chinese Medicine treatment of type 2 diabetes mellitus

OBJECTIVE: To provide clinical evidence in support of Dahuang Huanglian Xiexin decoction(DHXD) to treat type 2 diabetes mellitus(T2DM) and to introduce a new treatment option for clinicians.METHODS: Retrospective analysis was used to evaluate DHXD for the treatment of T2DM by analyzing clinical records of 183 cases. Patients with T2DM who met the inclusion criteria between January 1,2013 and January 1, 2014 were enrolled. The effects of the treatment were evaluated by the changes in fasting blood-glucose(FBG), postprandial blood sugar(PBG), hemoglobin A1c(Hb Alc), blood lipid profiles and body mass index(BMI) at 1, 2, 3 and 6 months. The changes in main symptoms were alsoevaluated. The dosage of Huanglian(Rhizoma Coptidis) and related factors were analyzed.RESULTS: There was a significant improvement in mean Hb A1C at 3 and 6 months after DHXD treatment compared with the baseline level(P < 0.01).There were also significant improvements in FBG,PBG, blood lipid series and BMI. DHXD also improved the main symptoms of stomach and intestine excessive heat syndrome in patients with obese T2DM. Huanglian(Rhizoma Coptidis) was the most frequently used in 678 clinical visits, the dosage of Huanglian(Rhizoma Coptidis) was related to age, BMI, DM duration, the level of blood glucose,and use of Western hypoglycemic drugs.CONCLUSION: This study suggests that DHXD could decrease blood glucose and improve T2DM symptoms and reduce body weight. The use of DHXD may indicate a new optional treatment for T2 DM.