糖尿病微血管病变对骨密度及骨代谢指标的影响

目的 探讨糖尿病微血管病变对骨密度(bone mineral density,BMD)及骨代谢指标的影响,为预防骨质疏松症(osteoporosis,OP)提供科学依据.方法 选取2018年12月-2019年12月北京大学深圳医院内分泌科收治的年龄≥50岁的2型糖尿病(type 2 diabetes mellitus,...     

2型糖尿病微血管病变与骨密度的相关性研究

目的 探讨2型糖尿病（type 2 diabetes mellitus, T2DM）患者微血管病变（micro vascular disease, MVD）与骨密度（bone mineral density, BMD）的相关性。方法 横断面研究广西医科大学第一附属医院收治的317例T2DM住院患者（男性均≥50岁，女性均已绝经）相关资料，按是否合并糖尿病微血管病变将患者分为MVD组(178例)、无MVD组(139例)。运用多因素Logistic 回归分析评估微血管病变与骨密度的相关性。结果 T2DM合并MVD者的骨质疏松症患病率较无MVD者更高（43% vs 23%，P＝0.007）。在调整了糖尿病病程、性别、年龄、体质量指数（body mass index, BMI)、高血压、骨钙素、甲状旁腺素后，多因素回归显示女性、年龄≥65岁、合并高血压是T2DM合并骨质疏松症的独立危险因素，而BMI是独立保护因素。进一步分层分析显示在调整混杂因素后，男性T2DM患者合并微血管病变是骨质疏松症的独立危险因素，而在女性患者中无相关关系。结论 男性T2DM患者合并微血管病变是骨质疏松症的独立危险因素。     

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。     

2型糖尿病患者微血管病变与骨密度相关性研究

目的探讨2型糖尿病患者微血管病变与骨密度的相关性。方法本横断面研究共纳入2 170例2型糖尿病患者(包括1 188名绝经后女性和982名50岁男性)。根据24 h尿蛋白水平对这些受试者进行分组:一组(30 mg)、二组(30～299mg)和三组(300 mg)。通过双能X射线吸收测定法评估其腰椎、髋部和股骨颈的骨密度。视网膜病的眼底照相和24 h尿蛋白作为2型糖尿病中微血管病的标志物。比较受试者的特征和骨密度。多变量分析用于研究骨密度与微血管病之间的关联。结果第三组在两种性别中具有最低的骨密度水平。在调整年龄、体重指数、高血压、高脂血症、糖尿病状态、肝功能、肾功能、性激素和25(OH)维生素D后,多变量分析显示,微血管病变与女性骨密度呈负相关(腰椎:r=-0. 522,P0. 001;髋关节:r=-0. 301,P=0. 010;股骨颈:r=-0. 314,P=0. 009),男性未发现相关性。结论绝经后女性2型糖尿病患者的微血管病变与骨密度之间呈负相关。     

2型糖尿病视网膜病变与骨生化标志物的相关性分析

目的对2型糖尿病(type 2 diabetes mellitus,T2DM)绝经后女性骨代谢生化标志物与视网膜病变程度之间的关系进行探讨,并分析其相关因素。方法回顾性分析178例绝经后2型糖尿病女性患者视网膜病变程度与骨代谢生化标志物的相关性并探讨其可能机制。结果视网膜病变程度与年龄、体质指数(body mass index,BMI)、甲状旁腺素(parathyroid hormone,PTH)、骨钙素N端中分子片段(N-MID osteocalcin,N-MIDoc)、血钙(Ca)、血磷(P)、钙磷乘积(Ca×P)、糖化血红蛋白(hemoglobin A1C,HbA1C)无明显相关性;随着视网膜病变程度的进展,病程、I型胶原交联C-末端Beta特殊序列(β-carboxyl terminal peptide,β-CTX)、总I型原胶原N端前肽(total type I procollagen N-terminal propeptide,T-PINP)成上升趋势,C肽、25-羟基维生素D(25-hydroxy vitamin D,VitD-T)、右前臂骨密度(bone mineral density,BMD)、T值成逐渐下降趋势,且组间差异有统计学意义(P0.05)。Spearman相关分析示病程与右前臂BMD及T值呈负相关,C肽与ViTD-T呈正相关,HbA1C与PTH、N-MIDoc、T-PINP呈负相关。结论 2型糖尿病绝经后女性患者骨代谢生化标志物与视网膜病变程度呈明显相关趋势,表明糖尿病骨病很可能是糖尿病微血管病变的另一种表现形式。     

糖尿病合并骨质疏松与糖尿病微血管并发症的相关性研究

糖尿病(diabetes mellitus,DM)合并骨质疏松(osteoporosis,OP)和糖尿病微血管病变均是糖尿病的慢性并发症,由于发病的隐匿性,常常不被重视。随着人口老龄化程度的增加及医疗诊断水平的提高,糖尿病合并骨质疏松和DM微血管并发症的发病率及检出率呈现逐年上升趋势,近年来相关的研究也开始被广泛开展。糖尿病微血管病变及骨血流量减少可能导致骨量丢失和骨脆性增加,且微血管并发症的出现是DM患者骨量减少的临界因素。因此积极探讨DM合并骨质疏松与DM其他慢性微血管并发症之间的相关性,有助于早期对DM患者的不良结局进行综合性防范,改善患者预后。本文就糖尿病肾病(diabetic nephropathy,DN)、糖尿病视网膜病变(diabetic retinopathy,DR)、糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)以及糖尿病足(diabetic foot,DF)与糖尿病合并骨质疏松症(diabetic osteoporosis,DOP)的相关性研究作一综述。     

糖尿病肾病机制的研究进展

2型糖尿病（type2diabetes，T2D）是最常见的内分泌代谢病，而糖尿病肾病（diabeticnephropa—thy，DN）是糖尿病患者最主要的微血管病变之一。     

2型糖尿病患者骨密度及骨代谢指标与糖尿病视网膜病变相关性的研究

目的探究2型糖尿病(type 2 diabetes mellitus,T2DM)患者骨密度(bone mineral density,BMD)、骨代谢指标及骨量异常情况与糖尿病视网膜病变(diabetic retinopathy,DR)的关系,为T2DM患者骨健康提供科学依据。方法入选2018年12月至2019年12月北京大学深圳医院内分泌科收治的T2DM患者,根据是否合并DR分为无DR组和DR组,比较2组间的性别、年龄、糖尿病病程、BMI、吸烟/饮酒史、BMD、骨代谢指标及骨量异常患病情况。结果总纳入T2DM患者616例,无DR组452例,DR组164例。与无DR组相比,DR组糖尿病病程较长,腰椎L1～L4、股骨及股骨颈BMD、T值、Z值均偏低,血Ca、24 h尿Ca、25(OH) D3偏低及血P、β-CTX偏高。T2DM合并视网膜病变骨量异常患病率偏高(59.8%vs 50.2%,OR=1.48; 95%CI:0.99～2.22)。结论 T2DM患者合并视网膜病变时骨形成及骨吸收指标表达均升高,骨转换率加速,PTH升高,破骨细胞活性增强,BMD下降,骨量异常患病率偏高。     

阿仑磷酸钠对糖尿病骨质疏松症患者骨代谢的影响

目的探究阿仑磷酸钠对糖尿病骨质疏松症（DOP）患者骨代谢的影响。 方法前瞻性收集2017年12月至2018年12月秦皇岛军工医院收治的108例DOP患者，随机分为对照组（54例）和阿仑磷酸钠组（54例），所有患者均给予常规对症及降糖治疗，阿仑磷酸钠组在此基础上给予阿仑膦酸钠片。治疗2个月后，观察并比较两组患者的骨代谢指标、骨密度（BMD）、血生化指标和临床疗效。 结果治疗后，对照组的血清骨代谢指标骨特异型碱性磷酸酶（BAP）、骨钙素（BGP）、人抗酒石酸酸性磷酸酶5b（TRAP-5b）水平分别为（7.52±3.20）μg/L、（6.24±2.22）U/L、（3.30±1.13）ng/ml，阿仑磷酸钠组分别为（9.41±3.32）μg/L、（7.73±2.34）U/L、（2.45±1.18）ng/ml；治疗后，两组BAP和BGP水平较治疗前升高（t=4.670，t=6.120，P<0.05），组间比较，阿仑磷酸钠组高于对照组，差异有统计学意义（t=3.010，t=3.390，P<0.01）；两组TRAP-5b（t=4.780，t=5.620，P<0.05）水平较治疗前下降，组间比较，阿仑磷酸钠组低于对照组，差异有统计学意义（t=3.820，P<0.01）。治疗后，对照组的腰椎和股骨颈的BMD分别为（0.82±0.06）g/cm²、（0.74±0.05）g/cm²，阿仑磷酸钠组分别为（0.91±0.04）g/cm²、（0.83±0.08）g/cm²，两组腰椎和股骨颈BMD（t=3.840，t=3.760，P<0.05）水平较治疗前均升高，组间比较，阿仑磷酸钠组高于对照组（t分别=9.170和7.010，P<0.05）。治疗后，对照组空腹血糖（FBG）、餐后2 h血糖（2 hBG）、糖化血红蛋白（HbA1c）水平分别为（7.06±0.29）mmol/L、（8.02±3.17）mmol/L、（6.21±0.46）%，对照组FBG、2 hBG、HbA1c水平分别为（8.12±0.33）mmol/L、（9.98±0.54）mmol/L、（7.56±0.67）%，两组比较，阿仑磷酸钠组低于对照组，差异有统计学意义（t=17.730，4.480，12.210，P<0.01）。阿仑磷酸钠组总有效率（90.74%）高于对照组（79.63%，P<0.05）。 结论阿仑磷酸钠治疗DOP患者疗效显著，可有效改善其骨代谢，促进BMD水平增加，值得临床加以推广与应用。     

糖尿病性骨质疏松的辨证施治

目的:探讨辨证施治糖尿病性骨质疏松的效果。方法:糖尿病性骨质疏松患者144例根据中医证型分为肝肾亏虚证60例、阴阳两虚证40例、气滞血瘀证44例,肝肾亏虚证给予滋肾降糖丸治疗,阴阳两虚证给予糖骨康胶囊治疗,气滞血瘀证给予归丸加味胶囊治疗,均治疗观察3个月,观察或比较两组疗效。结果:治疗3个月后肝肾亏虚证、阴阳两虚证、气滞血瘀证的总有效率分别为96.7%、95.0%和97.7%,3证型间无显著差异(P0.05);上述3证型的治疗3个月空腹血糖分别为(5.38±1.49)mmol/L、(5.42±1.22)mmol/L、(4.39±1.74)mmol/L,糖化血红蛋白分别为(6.10±0.58)%、(6.08±1.11)%、(6.13±1.42)%,都较治疗前呈显著下降的趋势(P0.05);腰椎正位1～4椎体骨密度都显著高于治疗前(P0.05);血清白细胞介素-17分别为(5.20±1.48)pg/nL、(4.99±2.19)pg/nL、(5.09±2.81)pg/nL,都显著低于治疗前(P0.05),但证型间对比无显著差异(P0.05)。结论:辨证施治糖尿病性骨质疏松,能抑制炎症因子的释放,促进骨密度的恢复,降低血糖与糖化血红蛋白值,从而提高治疗疗效。     

Treatment of Osteoporosis and Osteopenia in Long-term Renal Transplant Patients with Alendronate

Bone mineral density (BMD) and biochemical markers of bone-turnover were evaluated in a 2-year study in 58 long-term renal transplant recipients with good renal function. In the first year of study, data were collected and patients with osteoporosis and parameters of high bone turnover were classified as being at high risk for on-going bone loss (Group A; n = 29). Patients with lesser degrees of bone loss or without biochemical parameters of high bone turnover were followed longitudinally (Group B; n = 29). Group A patients were then placed on alendronate 10mg/day and both groups were followed for an additional year. Changes in regional BMD and bone-turnover markers between the first and second year within each group were analyzed using paired tests. BMD in Group A, which had declined at the lumbar spine (- 1.6 +/- 0.5%) and total femur (-1.5 +/- 0.4%) during the first year of the study, increased on alendronate therapy at both the lumbar spine (+3.4 +/- 0.6%, p = 0.001) and total femur (+1.6 +/- 0.6%, p <0.001). These patients also experienced a significant decline in levels of serum alkaline phosphatase, osteocalcin, urinary levels of deoxypyridinoline and pyridinoline. In contrast, neither BMD nor biochemical markers changed significantly over 2 years in Group B. The current results demonstrate that renal transplant patients with osteoporosis and biochemical parameters of high bone turnover are at continued risk for bone loss. Therapy with a bisphosphonate can reverse this bone loss and even increase bone mass in these patients. Whether patients with lesser degrees of bone loss and/or patients without parameters of high bone turnover can also benefit from bisphosphonate therapy deserves further study.     

绝经后骨质疏松性腰椎骨折骨代谢指标的变化

目的了解雌二醇和白细胞介素-6等骨代谢指标在骨质疏松症发病中的作用。方法选择女性腰椎骨折患者120例,绝经后有骨质疏松者60例(OP组),绝经后无骨质疏松者30例(NOP组),另外选择绝经前妇女30例为对照组。对120名妇女雌二醇、骨密度、白细胞介素-6、血清总碱性磷酸酶、骨钙素、尿羟脯氨酸肌酐比值、尿钙肌酐比值等指标进行了测定。结果绝经后妇女骨形成指标骨钙素及碱性磷酸酶明显高于对照组妇女,其中碱性磷酸酶在OP组和NOP组间有差异,而骨钙素在OP组和NOP组间无差异;绝经后妇女骨吸收指标尿羟脯氨酸肌酐比值及尿钙肌酐比值明显高于对照组妇女,OP组又明显高于NOP组;绝经后妇女的血清雌二醇的含量明显低于对照组(绝经前妇女),OP组又明显低于NOP组;绝经后妇女血清白细胞介素-6的含量明显高于对照组妇女,而OP组又明显高于NOP组。结论雌二醇、白细胞介素-6等骨代谢指标与骨质疏松关系密切。这充分说明雌激素水平的下降,IL-6分泌增多,导致骨吸收加速。     

不同阶段2型糖尿病诱发骨质疏松症的致病机制研究进展

大量临床研究表明,2型糖尿病(type 2 diabetes mellitus,T2DM)患者的骨折风险明显增加。因此,T2DM诱发的骨质疏松症(osteoporosis,OP)被认为是最严重的糖尿病并发症之一。骨脆性增加是糖尿病性骨质疏松症(diabetic osteoporosis,DOP)的典型特征,其发病机制是多因素引起的,包括肥胖、高胰岛素血症、高血糖(hyperglycemia,HG)、晚期糖基化终产物(advanced glycation end products,AGEs)积聚和氧化产物积累以及微血管病变的存在等。这些因素在T2DM不同时期是相互平衡或相互促进的,而肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、白细胞介素-1(interleukin 1,IL-1)、白细胞介素-6(interleukin 6,IL-6)等炎症因子的异常活化打破了骨形成和骨吸收的代谢平衡,导致骨脆性增加。骨强度和骨折风险的变化取决于疾病进展的阶段。因此,糖尿病骨病的病理生理变化可以通过分别考虑糖尿病早期和晚期骨骼相关因素来广泛讨论,其中早期阶段以胰岛素抵抗和高胰岛素血症为特征,这些因素会导致糖尿病发病和初始阶段的骨密度(bone mineral density,BMD)增加。而晚期阶段的特征是β细胞衰竭,AGEs和氧化产物的堆积,加速衰老和血管并发症的发展。为此,本文希望对T2DM的不同阶段与骨代谢的关系进行综述,以便更好的认识T2DM的进展加速骨脆性风险的病理过程和致病机制,为治疗T2DM和T2DM诱发的OP、降低T2DM患者骨折发生的风险发挥积极的作用。     

Differential Bone Metabolism Between Postmenopausal Women With Osteoarthritis and Osteoporosis

A comparative study of bone metabolism between postmenopausal women with osteoarthritis and osteoporosis showed that differential levels of bone remodeling markers, leptin, free leptin index, and osteoprotegerin might partly contribute to the proposed inverse relationship in bone mass between postmenopausal women with osteoarthritis and osteoporosis. Introduction : Osteoarthritis (OA) and osteoporosis (OP) are two common disorders affecting the quality of life in the elderly. The association between OA and OP has always been debated. The objective of this study was to compare bone metabolism between postmenopausal women with OA and OP. Materials and Methods : A total of 120 postmenopausal women with OA and OP (n = 60, respectively) were included in this comparative study. Anthropometric parameters and BMD at the spine and the proximal femur were measured. Serum leptin, soluble leptin receptor (sLR), osteoprotegerin (OPG), and bone remodeling markers, including bone‐specific alkaline phosphatase (BALP), osteocalcin (OC), deoxypyridinoline cross‐links (DPD), and cross‐linked N‐telopeptides of type I collagen (NTX), were quantified with commercial ELISA or EIA kits. Free leptin index (FLI) was also calculated by the ratio between serum leptin and sLR levels. Results : Postmenopausal women with OA had higher body weight, body mass index, fat mass, and percentage of fat than those suffered from OP. Compared with the patients in OP group, the patients in OA group had significantly higher BMD values at all sites measured. Higher serum leptin and FLI and lower OPG levels were shown in the OA group (leptin: 31.22 ± 6.4 versus 26.50 ± 9.27 ng/ml, p < 0.001; FLI: 3.20 ± 1.02 versus 2.50 ± 0.95, p < 0.05; OPG: 4.75 ± 1.97 versus 6.96 ± 2.75 pM, p < 0.001), whereas lower serum OC and higher urine DPD were noted in the OP group (OC: 16.45 ± 8.45 versus 13.06 ± 6.25 ng/ml, p < 0.05; DPD: 10.83 ± 7.12 versus 15.29 ± 6.65 nM BCE/mM Cr, p < 0.001). Serum OPG levels negatively correlated with BMD at all sites assessed. However, no correlation was found between leptin and BMD. Only in the OA group di positive correlations exist between FLI and Z‐score at the femoral neck and Ward's triangle region. After stepwise regression analysis, it was found that differential factors were able to predict the variance of BMD at different sites to a certain extent. Conclusions : Our study suggests that there are significant differences in bone metabolism between postmenopausal women with OA and OP and provides evidence for the inverse relationship between OA and OP. Differential levels of bone remodeling markers, leptin, FLI, and OPG may partly contribute to the proposed inverse relationship. Roles of leptin and its soluble receptor in bone metabolism regulation should be explored further.     

在仅通过饮食和运动控制血糖的绝经后2型糖尿病患者中血脂、骨代谢与骨密度的相关性研究

目的 分析在仅通过饮食和运动控制血糖的绝经后2型糖尿病患者中血脂、骨代谢与骨密度的相关性。方法 纳入2018年1月至2020年1月在宁夏回族自治区人民医院内分泌科治疗的105例2型糖尿病患者,年龄45～70 岁。记录受试者的糖尿病病程、身高、体重、体质量指数(body mass index,BMI),检测血脂(TC、TG、HDL、LDL)、糖化血红蛋白(HbA1c)。采用双能X线骨密度仪测定受试者腰椎( L1～4 )、股骨颈(Neck)、大转子(Troch)和Ward 三角(Ward’s)的骨密度(bone mineral density,BMD),并进行统计学分析。结果 随年龄增高,骨密度呈下降趋势,年龄、病程、糖化血红蛋白、TG、LDL、PTH、OC、TPINP、β-CTX与各部位的骨密度呈负相关;BMI、25(OH)D与各部位的骨密度呈正相关;多元逐步回归分析显示糖化血红蛋白、TG、LDL、TPINP与骨密度存在负相关,25(OH)D与骨密度正相关。 结论 绝经后2型糖尿病患者应注意补充维生素D制剂、良好控制血糖,全面检查血脂、骨代谢,尽早对骨质疏松相关危险因素进行管控。     

Renal Microvascular Injury in Chronic Aristolochic Acid Nephropathy and Protective Effects of Cozaar

Background: To investigate the renal microvascular injury in chronic aristolochic acid nephropathy (AAN) and the protective effects of Cozaar. Methods: Male Sprague-Dawley rats were randomized into three groups. Rats in the model group received Caulis Aristolochiae manshuriensis (CAM) decoction by gavage (10 mL/kg/day); those in the Cozaar group were gavaged with CAM and Cozaar (33.3 mg/kg/day); and those in the control group only received an equal daily volume of saline solution by gavage. Kidney tissues were observed under a light and electron microscope. CD34, caspase-3, and bone morphogenetic protein-7 (BMP-7) were determined by immunohistochemistry, and expressions of angiopoietin (Ang) 1 and 2, Tie-2, BMP-7, and vascular endothelial growth factor (VEGF) mRNA were monitored via real-time polymerase chain reaction (PCR). Results: (1) The kidney tissue injury in the chronic AAN model group was apparent, compared to the normal structure in the normal control group, and the Cozaar group showed relieved injury. (2) The expression of caspase-3 in the model group was elevated, while expressions of BMP-7 and CD34 were decreased (p < 0.05). Cozaar lessened caspase-3 expression (p < 0.05) and promoted BMP-7 and CD34 expressions (p < 0.05). (3) Real-time PCR demonstrated a downregulation of Ang-1, Tie-2, BMP-7, and VEGF mRNA (p < 0.05) and an upregulation of Ang-2 mRNA (p < 0.01) in the renocortex, while Cozaar upregulated the expression of Ang-1, Tie-2, BMP-7, and VEGF mRNA (p < 0.05). Conclusion: Renal microvascular injury was observed in chronic AAN, which was hypothetically correlated with a lack in the expressions of Ang-1, BMP-7, Tie-2, and VEGF and an excess in caspase-3 and Ang-2. Cozaar can significantly ameliorate the renal microvascular injury and protect renal function.     

肠道菌群在骨质疏松症发病机制中的研究

骨质疏松症是一种慢性全身性代谢性骨病，由于骨吸收与骨形成的失衡造成骨量减少及骨密度的降低，与此同时骨组织微结构的破坏导致骨折风险升高，影响患者的生活质量甚至威胁生命安全。对于骨质疏松症的发病机制，目前认为与激素、内分泌、免疫、肠道菌群等因素有关。近年来微生物-肠-骨轴成为了骨代谢领域的研究热点。本文将从肠道粘膜屏障、骨免疫学、肠道菌群代谢产物等方面对肠道菌群在骨质疏松症中的发病机制进行综述。