Relationship between serum Dickkopf-1 and albuminuria in patients with type 2 diabetes

BACKGROUND Diabetic kidney disease is a microvascular complication of diabetes with complex pathogenesis. Wingless signaling-mediated renal fibrosis is associated with diabetic kidney disease. Dickkopf-1, a negative regulator of Wingless, has been proven to participate in renal fibrosis, glucose metabolism, and inflammation. However, whether serum Dickkopf-1 levels are associated with diabetic kidney disease remains unclear.AIM To assess the relationship between serum Dickkopf-1 levels and albuminuria in individuals with type 2 diabetes.METHODS Seventy-three type 2 diabetes patients and 24 healthy individuals were enrolled in this case-control study. Diabetic individuals were separated into normal albuminuria, microalbuminuria, and macroalbuminuria groups based on their urinary albumin/creatinine ratios(UACRs). Clinical characteristics and metabolic indices were recorded. Serum Dickkopf-1 levels were determined by enzymelinked immunosorbent assay.RESULTS No significant difference in serum Dickkopf-1 levels was found between healthy individuals and the normal albuminuria group. However, the levels in the microalbuminuria group were significantly lower than those in the normal albuminuria group(P = 0.017), and those in the macroalbuminuria group were the lowest. Bivariate analysis revealed that serum Dickkopf-1 levels were positively correlated with hemoglobin A1 c level(r = 0.368, P 0.01) and estimated glomerular filtration rate(r = 0.339, P 0.01), but negatively correlated with diabetes duration(r =-0.231, P = 0.050), systolic blood pressure(r =-0.369, P = 0.001), serum creatinine level(r =-0.325, P 0.01), and UACR(r =-0.459, P 0.01). Multiple and logistic regression showed that serum Dickkopf-1 levels were independently associated with UACR(odds ratio = 0.627, P = 0.021).CONCLUSION Serum Dickkopf-1 levels are negatively associated with UACR. Lower serum Dickkopf-1 levels could be a critical risk factor for albuminuria in diabetes.     

Elevated levels of plasma von Willebrand factor and the risk of macro- and microvascular disease in type 2 diabetic patients with microalbuminuria.

BACKGROUND: The purpose of this study was to examine the concept suggesting that microalbuminuria in combination with high levels of plasma von Willebrand factor is a stronger predictor for cardiovascular disease and microvascular complications than microalbuminuria alone in type 2 diabetic patients. METHODS: One hundred and sixty patients with type 2 diabetes mellitus and persistent microalbuminuria were followed for an average of 3.8 (SD 0.3) years. 70% of the patients were treated with angiotensin converting enzyme (ACE)-inhibitors. Patients in this subanalysis were divided into two groups according to baseline plasma von Willebrand factor levels below or above the median. The main outcome was cardiovascular disease (cardiovascular mortality, non-fatal stroke, non-fatal myocardial infarction, coronary artery bypass graft and revascularization or amputation of legs), progression to diabetic nephropathy or progression in diabetic retinopathy. RESULTS: At baseline the two groups were comparable for HbA(1c), fasting levels of s-total-cholesterol, s-HDL-cholesterol and s-triglycerides, systolic and diastolic blood pressure, gender, known diabetes duration, smoking habits, previous cardiovascular disease and antihypertensive therapy as well as retinopathy. Odds ratio for cardiovascular disease was 1.11 (95% CI 0.45-2.73, P=0.82) (multiple logistic regression), odds ratio for progression to nephropathy was 1.08 (0.41-2.85, P=0.87) and odds ratio for progression in retinopathy was 0.96 (0.46-2.00, P=0.92), all with plasma von Willebrand factor levels above the median. CONCLUSIONS: Our results do not support the suggestion that the combination of high plasma levels of von Willebrand factor and microalbuminuria is a stronger predictor for cardiovascular disease, progression to diabetic nephropathy or progression in diabetic retinopathy than microalbuminuria alone in patients with type 2 diabetes and persistent microalbuminuria.     

2型糖尿病患者性激素水平与骨密度的相关研究

目的：探讨2型糖尿病患者的骨密度变化与性激素水平的关系。方法：运用DEXA测定70例2型糖尿病患者的骨密度（BMD）,以放免方法测定血清性激素水平,和88例正常人做对照。结果：男性患者腰椎BMD和女性患者髋部BMD分别低于同龄对照,雌二醇和孕酮水平分别与第2,3腰椎BMD相关,空腹血糖与Troch部位BMD相关,Wards三角BMD与年龄和血尿酸水平相关。结论：2型糖尿病患者腰椎骨密度下降主要与性激素水平相关,而髋部BMD主要受糖尿病的影响。     

Bladder dysfunction in type 2 diabetic patients

AIMS: To reevaluate urodynamic findings of bladder dysfunction (BD) in type 2 diabetic patients with patient characteristics and concommittant chronic complications. METHODS: Patients (M/F:27/27) with lower urinary tract symptoms (LUTS) underwent a detailed urodynamic investigation. Urodynamic findings were classified as diabetic cystopathy [DC, characterized by impaired bladder sensation, increased post-void residual urine (PVR) and increased bladder capacity and decreased bladder contractility], detrusor overactivity, bladder outlet obstruction (BOO), urge and stress urinary incontinence or BD in which one of the alterations was included. Glycated hemoglobin (HbA1C), diabetic retinopathy, nephropathy, sensorimotor, and autonomic neuropathies were evaluated. RESULTS: BD was present in 74.07% of men (DC, 50%; BOO, 25%; detrusor overactivity, 25%) and in 59.26% of diabetic women (DC, 43.75%; detrusor overactivity, 31%; urge incontinence, 12.5%; stress urinary incontinence 12.5%). In men, age, duration of diabetes and HbA1C threshold values predicting BD were >64 years, >9 year, >7.9%, while in women, they were >56 years, >8 years, >7%, respectively. Prolongation of QTc, abnormal esophageal transit and gastric emptying times, diabetic retinopathy, and microalbuminuria were associated with an increased risk of PVR >or= 100 ml. CONCLUSIONS: DC was the most frequent finding in patients. Ageing, duration of diabetes, worse metabolic control, PVR 100 ml, cardiac, esophageal and gastric parasympathetic autonomic neuropathies, retinopathy, and microalbuminuria provided a means to predict BD in patients in order to investigate by urodynamics. The establishment of DC in at least 8-9 years after the diagnosis of type 2 DM was an important parameter to inform our diabetic patients.     

25-(OH)VD与2型糖尿病患者的糖尿病肾病相关性研究

目的 探讨25-(OH)VD与2型糖尿病患者的糖尿病肾病相关性。方法 收集937例未接受维生素D补充治疗的2型糖尿病患者,测定各临床指标以分析糖尿病肾病的相关因素。结果 与正常尿微量白蛋白组患者相比,微量或大量尿白蛋白组患者的25-(OH)VD 水平较低且具有显著统计学差异。相关性分析显示,用性别和BMI作为校正指数,年龄、糖尿病病程、高血压病程、收缩压、糖化血红蛋白、肌酐、尿素氮与尿微量白蛋白呈正相关,而25-(OH)VD 水平与尿微量白蛋白呈负相关。结论 25-(OH)VD 水平与2型糖尿病患者的尿微量白蛋白呈显著负相关。     

Effect of glycemic control on microalbuminuria development among type 2 diabetes with high-normal albuminuria

This study was aimed at revealing the factors and the interrelationships between factors on microalbuminuria development among type 2 diabetes (T2D) patients. Between 2004 and 2011, 461 T2D patients with a baseline urine albumin-to-creatinine ratio (UACR) of <30?mg/g, and an estimated glomerular filtration rate (eGFR) of >60?mL/min were evaluated retrospectively. Sixty-eight (14.8%) subjects had developed microalbuminuria in a mean follow-up of 6.82 years. Statistical analysis had revealed that the higher baseline UACR (10?mg/g; sensitivity, 80.9%, specificity, 63.6%; AUC?=?0.774) and glycohemoglobin level (HbA1c) (8%; sensitivity, 72.1%, specificity, 61.6%; AUC?=?0.698) were the two independent microalbuminuria risk factors. When considering the risk of microalbuminuria, the data were normalized with respect to subjects with low-normal UACR (<10?mg/g) and HbA1c??8%, high-normal UACR/HbA1c?8% were 2.59 (p?=?0.107), 6.15 (p?=?0.001), and 16.96 (p?10%) showed a progressively increase of the hazard risk in baseline high-normal UACR group. But the same correlation was not shown in the low-normal UACR group. This study identified the relationships of high-normal albuminuria and glycemic control on microalbuminuria development among T2D patients. Glycemic control is especially beneficial for T2D patients with baseline high-normal UACR in preventing microalbuminuria development.     

2型糖尿病骨密度变化及相关因素初探

目的：观察2型糖尿病骨密度变化及影响因素。方法：对59例男性60例女性2型糖尿病患及148例健康用双能X射线吸收法行L2-4、Wards区、股骨颈、大转子骨密度测量,并测定糖尿病患空腹、餐后血糖,空腹、餐后胰岛素,空腹C肽、24小时尿白蛋白等。结果：①男性糖尿病患L4骨密度较健康显降低,其余部位无显差别。女性糖尿病患L2-4、Wards、股骨颈、大转子均较健康显降低。②多元分析显示：男女性糖尿病患骨密度改变与C肽正相关、与尿白蛋白负相关,男性糖尿病患骨密度改变与病程负相关,女性糖尿病患骨密度改变还与绝经年龄负相关。结论：糖尿病患存在骨密度降低,女性患更为显。2型糖尿病患胰岛功能减退及尿白蛋白增加对骨密度降低有一定作用。     

老年男性2型糖尿病患者骨密度变化的分析

目的:探讨老年男性2型糖尿病患者骨密度的变化情况.方法:应用双能X线骨密度测定法测定52例老年男性2型糖尿病患者腰椎和股骨颈的骨密度,同时检测身高,体重,血钙、磷、碱性磷酸酶,24 h尿钙,计算体质指数,并与46例同龄正常健康老年男性进行比较.结果:老年男性2型糖尿病患者骨质疏松症的患病率为11.5%,正常对照组骨质疏松的患病率为3.8%.两组间体质指数,血钙、磷及碱性磷酸酶无明显差异,但糖尿病组24 h尿钙高于正常对照组,差异具有显著性(P＜0.01).结论:老年男性2型糖尿病患者的骨质疏松患病率较正常男性明显增高,是2型糖尿病的常见并发症.     

中老年2型糖尿病周围神经病变患者骨代谢指标变化研究

目的探讨中老年2型糖尿病合并周围神经病变与骨代谢指标β-CTX、PINP之间的相关性。方法选取遵义医科大学附属医院内分泌科2017年10月至2018年8月的2型糖尿病患者189例,基于患者有无合并周围神经病变进行分组,将患者划分为合并病变组(DPN组)和未合并病变组(NDPN组),两组分别为97例和92例。测定各组FPG、HbA1c、C肽、FIns、HOMA-IR、TG、TC、LDL-C、HDL-C、Ca、P、BMD(L2-L4、Neck、Troch、Ward’s三角)、β-CTX、PINP水平。结果与NDPN组比较,DPN组FPG、HbA1c、FIns、HOMA-IR、TG均高于NDPN组,而P、HDL-C、腰椎L2-L4、股骨颈Neck、Troch处BMD、β-CTX、PINP低于NDPN组(P<0.05);Pearson相关性分析显示,β-CTX与FPG呈负相关(r=0.484,P<0.05);PINP与HDLC、P呈正相关(r分别为0.242、0.309,P<0.05),与HbA1c、HOMA-IR、股骨颈Neck呈负相关(r分别为-0.173、-1.460、-0.237,P<0.05)。结论DPN患者血清β-CTX、PINP水平降低,骨转换指标异常,可能具有更高的骨折风险。     

对氧磷酯酶基因多态性与糖尿病肾病的关系

目的探讨对氧磷酯酶2(PON2)基因A148G多态性与糖尿病肾病的关系.方法(1)用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法探查PON2基因A148G多态性在正常对照组、单纯2型糖尿病组、糖尿病肾病组中的基因频率分布;(2)放射免疫法检测血清免疫反应性胰岛素(IRI)、C肽(C-P)水平.结果(1)糖尿病肾病组GG基因型和G等位基因频率明显高于单纯2型糖尿病组(X2=4.26 P＜0.05,X2=4.89P＜0.05)和正常对照组(X2=4.79 P＜0.05,X2=5.49P＜0.01);(2)基因型为GG的糖尿病患者空腹血糖浓度高于基因型为GA和AA的糖尿病患者的空腹血糖浓度(F=3.90 P＜0.05,F=4.23 P＜0.05);(3)Logistic回归分析表明GG基因型是糖尿病肾病的独立变异危险因素(P＜0.05).结论PON2基因多态性与糖尿病肾病的发生有关.     

Effect of aerobic and anaerobic exercises on glycemic control in type 1 diabetic youths

AIM:To evaluate the long-term effect of aerobic and/or anaerobic exercise on glycemic control in youths with type 1 diabetes.METHODS:Literature review was performed in spring and summer 2014 using Pub Med/MEDLINE,Google Scholar,Scopus,and Science Direct with the following terms:aerobic,anaerobic,high-intensity,resistance,exercise/training,combined with glycemic/metabolic control,glycated haemoglobin A1c(Hb A1c) and type 1diabetes.Only peer-reviewed articles in English were included published in the last 15 years.It was selected from 1999 to 2014.Glycemic control was measured with Hb A1 c.Studies with an intervention lasting at least 12 wk were included if the Hb A1 c was measured before and after the intervention.RESULTS:A total of nine articles were found,and they were published between the years of 2002-2011.The sample size was 401 diabetic youths(166 males and 235 females) with an age range of 10-19 years except one study,in which the age range was 13-30 years.Study participants were from Australia,Tunisia,Lithuania,Taiwan,Turkey,Brazilia,Belgium,Egypt and France.Four studies were aerobic-based,four were combined aerobic and anaerobic programs,and one compared aerobic exercise to anaerobic one.Available studies had insufficient evidence that any type of exercise or combined training would clearly improve the glycemic control in type 1 diabetic youth.Only three(two aerobic-based and one combined) studies could provide a significant positive change in glycemic control.CONCLUSION:The regular physical exercise has several other valuable physiological and health benefits that justify the inclusion of exercise in pediatric diabetes treatment and care.     

走出自设的心理困境

英语老师已经连续两个星期没有在课堂上提问小琴了,这让小琴非常忧虑,她觉得一定是英语老师对自己有意见了。更让小琴担心的是,此种状况如果持续下去的话,她的英语学习就会受到很大的影响,她找到我,特别想改变英语老师不提问她的现状。"小琴,你从感觉到英语老师对你有意见到现在多长时间了?""一个星期吧。"小琴回答。     

肾功能正常的男性2型糖尿病并发白蛋白尿患者骨密度变化

目的分析男性2型糖尿病(T2DM)并发白蛋白尿但肾功能正常患者的骨密度(BMD)变化。方法本研究为回顾性分析,纳入202例肾功能正常的男性T2DM患者和99例男性健康对照者(A组)。T2DM患者根据尿白蛋白与肌酐比值(UACR)分为正常白蛋白尿组(B组)、微量白蛋白尿组(C组)及大量白蛋白尿组(D组)。采用双能X线吸收法(DXA)测量所有受试者腰椎及髋部BMD值。结果 B组、C组腰椎BMD较A组升高(P0.05);D组腰椎BMD较A有升高趋势,较B组、C组间有降低趋势,但差异均无统计学意义(P0.05)。大转子区(Troch)、转子间区(Inter)、髋部总体区(Total Hip)BMD在B组、C组较A组升高(P0.05),在D组较A、B、C组间均有升高趋势,但差异无统计学意义(P0.05)。股骨颈区(Neck)、Ward三角区(Ward)BMD在4组间差异无统计学意义(P0.05)。L1-4BMD和Total Hip BMD在C较B组有升高趋势,但差异无统计学意义(P0.05)。结论男性T2DM患者BMD较健康人群升高,并发微量白蛋白尿时BMD可能继续升高,出现大量白蛋白尿后腰椎BMD有回降趋势,而髋部BMD有进一步升高趋势。     

绝经后女性2型糖尿病患者血糖控制与骨密度关系的观察

目的 探讨2型糖尿病绝经后女性患者血糖水平与骨密度的关系.方法 选择规律治疗1年以上的2型糖尿病绝经后女性患者30例,其中15例为血糖控制较好组[GGC组:平均年龄(61.2±1.1)岁],另外15例为血糖控制较差组[PGC组:平均年龄(63.4±0.9)岁].另设正常对照组15例[NC组:平均年龄(61.8±1.5)岁].分别测定3组成员股骨颈及L1～4水平的BMD、空腹及餐后血糖、糖化血红蛋白、空腹IGF-1、空腹C-肽、血钙、血磷、血镁、全段甲状旁腺素、碱性磷酸酶、谷氨酰转肽酶以及超敏C反应蛋白.结果 3组在iPTH和IGF-1水平上差异无显著性.糖尿病组与非糖尿病患者比较,股骨颈BMD值无统计学差异.结论 2型糖尿病绝经后女性骨密度水平与IGF-1、体重等指标相关,骨吸收增加与高血糖无明显相关.     

2型糖尿病合并骨质疏松症患者类胰岛素生长因子-1与骨转换关系研究

目的 了解2型糖尿病合并骨质疏松患者其类胰岛素生长因子－1（IGF－1）的变化与骨转换之关系。方法 分别测定2型糖尿病合并骨质疏松组（A组）、2型糖尿病未合并骨质疏松组（B组）、绝经后骨质疏松组（C组）和对照组（D组）的血清IGF－1、总碱性磷酯酶（总AKP）、骨特异碱性磷酸酶（骨AKP）、骨钙素（BGP）、尿吡啶啉（PYD）、尿脱氧吡啶啉（DPD），全段甲状旁腺素（IPTH），并进行组间比较和聚类相关分析。结果 A、C组病例其尿PYD和DPD值明显高于B、D组；而IGF－1水平则A、C组明显低于B和D组。聚类相关性分析表明在2型糖尿病合并骨质疏松组骨密度值与IGF－1关系最为密切，而在绝经后骨质疏松组则主要为绝经时间和骨吸收指标（PYD和DPD）。结论 骨形成减少是2型糖尿病合并骨质疏松的原因之一，而IGF-1的减少可能与2型糖尿病的骨形成减少有关。     

2型糖尿病肾病患者p22phox基因多态性的研究

目的研究NADPH氧化酶p22phox亚基基因多态性与中国上海汉族人群2型糖尿病肾病（DN）相关性。方法应用限制性片断长度多态性（RFLP）-PCR方法对105例健康对照组和194例2型糖尿病（DM）患者（其中71例DN）进行p22phox亚基C242T、A640G基因型检测。同时检测其身高、体重、血压、血脂、空腹血糖及胰岛素、HbAlc的水平。结果DN组CT＋TT基因型频率明显高于2型DM和对照组（26．76％比17．07％、3．81％，P=0．0002）；DN组T等位基因频率明显高于2型DM和对照组（22．54％比13．42％、2．86％，P=0．0001）；3组间AA基因型频率与A等位基因频率差异无统计学意义。多元回归分析显示，T242等位基因、收缩压、空腹血糖、HbAlc、β细胞功能指数（Homa-IS）是DN的危险因素。结论p22phox亚基T242等位基因变异可能是中国上海地区汉族人群DN的易感基因：而p22phox亚基A640G基因多态性与上述人群DN无相关性。T242等位基因、收缩压、空腹血糖、HbAlc、Homa-IS是DN的危险因素。     

新诊断男性2型糖尿病患者骨密度临床分析

目的研究新诊断男性2型糖尿病患者(T2DM)骨密度改变情况及危险因素。方法应用双能X射线吸收法测定了200例新诊断男性T2DM和200例男性对照组的L2-4、Wards区、股骨颈、大转子骨密度。并记录年龄、体重指数、血糖、胰岛素及糖化血红蛋白(HbAlc)等临床指标进行比较。结果男性T2DM的血糖、糖化血红蛋白显著高于对照组(P<0.001),而BMD较对照组显著降低(P<0.05)。T2DM的骨质疏松检出率明显高于对照者(P<0.05)。线性回归分析显示HbA1c为BMD独立危险因素(P=0.003,OR=2.15,95%可信区间:2.89～3.52)。结论 T2DM的骨密度降低明显,骨质疏松发生率高,加强控制糖尿病。     

2型糖尿病患者微血管病变与骨密度的相关性

目的分析2型糖尿病(type 2 diabetes mellitus,T2DM)并发微量白蛋白尿、视网膜病变患者的骨密度变化。方法选择49例T2DM无微量白蛋白尿、无视网膜病变患者(A组)、52例T2DM伴微量白蛋白尿或视网膜病变两者之一患者(B组)、43例T2DM同时合并微量白蛋白尿和视网膜病变患者(C组),60例来我院体检的健康对照组(N组)。采用双能X线骨密度仪对4组受试者测定腰椎2~4、左侧股骨颈及Ward三角区的骨密度,分析组间骨密度差异。结果 C组腰椎、股骨颈、Ward三角区骨密度均低于B组、A组及N组,差异均有统计学意义(P0.05)。B组腰椎骨密度低于A组及N组,但差异无统计学意义,股骨颈及Ward三角区骨密度低于A组及N组,差异有统计学意义(P0.05)。A组腰椎骨密度与N组差异无统计学意义,但股骨颈及Ward三角区骨密度高于N组,差异有统计学意义(P0.05)。T2DM患者骨密度与年龄、糖尿病病史、空腹血糖、糖化血红蛋白、尿微量白蛋白/肌酐比值呈负相关(P0.05),与体重指数、空腹胰岛素水平呈正相关(P0.05)。结论T2DM无微量白蛋白尿、无视网膜病变时骨密度呈增高趋势,但发展到微量白蛋白尿和视网膜病变时骨密度明显降低,尤其是股骨近端可出现较快的骨量流失。     

Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus: A review

Cardiovascular disease is the predominant cause of death in type 2 diabetes mellitus (T2DM). Evidence suggests a strong association between duration and degree of hyperglycemia and vascular disease. However, large trials failed to show cardiovascular benefit after intensive glycemic control, especially in patients with longer diabetes duration. Atherosclerosis is a chronic and progressive disease, with a long asymptomatic phase. Subclinical atherosclerosis, which is impaired in T2DM, includes impaired vasodilation, increased coronary artery calcification (CAC), carotid intima media thickness, arterial stiffness, and reduced arterial elasticity. Each of these alterations is represented by a marker of subclinical atherosclerosis, offering a cost-effective alternative compared to classic cardiac imaging. Their additional use on top of traditional risk assessment strengthens the predictive risk for developing coronary artery disease (CAD). We, herein, review the existing literature on the effect of glycemic control on each of these markers separately. Effective glycemic control, especially in earlier stages of the disease, attenuates progression of structural markers like intima-media thickness and CAC. Functional markers are improved after use of newer anti-diabetic agents, such as incretin-based treatments or sodium-glucose co-transporter-2 inhibitors, especially in T2DM patients with shorter disease duration. Larger prospective trials are needed to enhance causal inferences of glycemic control on clinical endpoints of CAD.