氟中毒大鼠骨形态计量学分析及硒的影响

目的　观察硒对氟中毒大鼠骨形态计量病理变化的影响。方法　２组 Ｗ ｉｓｔａｒ 大鼠饮１．５８、２．６３ｍ ｍ ｏｌ／ Ｌ 高氟水造成水型氟中毒,同时加饲２．０ｍ ｇ／ｋｇ 硒饲料。在８、１４月时测其尿、血硒（ Ｓｅ）,尿、血、骨氟（ Ｆ）含量和骨形态计量学参数骨小梁相对体积（ Ｔ Ｂ Ｖ）、骨小梁类骨质表面（ Ｓｏｓ）、骨小 梁吸收表面（ Ｓｒ）、四环素双标记间平均距离（ Ｄ Ｄ Ｌ）、矿化沉积速率（ Ｍ Ｉ Ａ Ｒ）、平均类骨质宽度（ Ｍ Ｏ Ｓ Ｗ ）、矿化延迟时间（ Ｍ Ｌ Ｔ）。结果　氟中毒大鼠尿、血、骨氟升高。骨形态学参数 Ｔ Ｂ Ｖ、 Ｓｏｓ 增加, Ｓｒ 减少;骨动力学参数 Ｄ Ｄ Ｌ、 Ｍ Ｉ Ａ Ｒ 增加, Ｍ Ｏ Ｓ Ｗ 、 Ｍ Ｌ Ｔ 延长。氟中毒大鼠服硒后尿氟排泄升高,血、骨氟减少,骨形态计量学参数程度不同的恢复。结论　氟中毒大鼠骨建平衡紊乱,氟刺激骨增生和导致骨矿化障碍。投硒影响氟中毒大鼠骨形态计量学参数,使骨量减少,同时对骨矿化障碍产生抑制作用。     

2型糖尿病脓系胰岛素分泌功能的研究

目的 探讨胰岛素抵抗（ＩＲ）和胰岛细胞功能障碍在２型糖尿病（ＤＭ）发病中的作用，方法２ＤＭ家系中，对部分成员进行口服葡萄糖耐量试验（ＯＧＴＴ）〈按ＷＨＯ标准将家系成员ＤＭ一级亲属正常组（１０６例，糖耐量低减组（ＩＧＴ）组（３９例），新诊断ＤＭ组（６３例）和原诊断ＤＭ组（８３例，病程１年以上）〉计算各组成员的胰岛素敏感性指数（ＩＳＩ）以及有遍初期分泌功能的指数，民无ＤＭ家族史的健康人（５３例）相比较     

血管紧张素Ⅱ对实验性糖尿病大鼠心肌病变的影响及卡托普利？…

目的 对实验性糖尿病大鼠（ＳＴＺ－Ｗｉｓｔａｒ大鼠）心肌组织血管紧张素Ⅱ（Ａｇ－Ⅱ）含量及Ａｇ－Ⅱ受体亚型１（ＡＴ１受体）基因ｍＲＮＡ表达和卡托普利（血管紧张素转换酶抑制剂，ＡＣＥＩ）应用对心脏病变可能的保护作用进行了观察。方法 应用分子生物学和放射免疫的方法。结果 未经胰岛素治疗的糖尿病大鼠（ＤＭ组）在４个月病程时，心重／体重（ＨＷ／ＢＷ）比值增加，心脏组织中Ａｇ－Ⅱ含量ＤＭ组高于正常对照组（Ｎ     

甲状腺功能亢进患者骨代谢变化的研究

目的　进一步探讨甲状腺功能对骨代谢的影响。方法　本文对４４ 例甲状腺功能亢进症（ 甲亢） 患者及４７ 例健康志愿者采用酶联免疫法（ Ｅ Ｌ Ｉ Ｓ Ａ） 测定了尿脱氧吡啶啉（ Ｄ Ｐ Ｄ） ，放射免疫法（ Ｒ Ｉ Ａ） 测定 Ｆ Ｔ３ 、 Ｆ Ｔ４ ，双能 Ｘ 线吸收骨密度仪测定腰椎（ Ｌ２４ ） 、股骨颈（ Ｎｅｃｋ） 、 Ｗａｒｄ’ｓ 三角（ Ｗａｒｄ’ｓ） 、大转子（ Ｔｒｏｃｈ） 部位的骨密度（ Ｂ Ｍ Ｄ） ，以及骨代谢相关指标。结果　尿 Ｄ Ｐ Ｄ 水平为相应年龄对照组的６ 倍（ Ｐ＜ ０ ．００１） ，血清碱性磷酸酶（ Ａ Ｌ Ｐ） 活性为对照组２ 倍（ Ｐ＜ ０ ．００１） ，腰椎及股骨上端 Ｂ Ｍ Ｄ 与对照组同部位比较有不同程度降低，其骨量丢失发生率达５０ ％ 以上，且严重程度及发生率尚随年龄而增加。相关分析还表明，尿 Ｄ Ｐ Ｄ与 Ｆ Ｔ３ 、 Ｆ Ｔ４ 、 Ａ Ｌ Ｐ 之间呈正相关，与骨密度无相关性。结论　甲状腺激素可能直接参与加速骨转换过程，并以增加骨吸收过程为显著，由此导致骨量丢失。     

己烯雌酚对去卵巢大鼠密质骨影响的定量研究

将２７只３月龄ＳＤ雌大白鼠随机分为基础对照组（Ａ）、年龄对照组（Ｂ）、去卵巢组（Ｃ）和去卵巢加己烯雌酚（ＤＥＳ）治疗组（Ｄ）。Ｂ组和Ｃ组用生理盐水５ｍｌ·ｋｇ－１／ｄ．ｉｇ，Ｄ组用浓度为４．５ｍｇ／Ｌ的己烯雌酚按５ｍｌ·ｋｇ－１／ｄ．ｉｇ，每周６次。１２周后，对各组大鼠胫骨中段不脱钙骨片进行骨计量学分析。去卵巢大鼠由于骨吸收大于骨形成，密质骨变薄，骨髓腔扩大，出现高转换型骨质疏松，己烯雌酚能明显抑制去卵巢后的骨高转换，保持密质骨厚度，维持骨量的正常。     

小剂量胰岛素,葡萄糖持续静脉滴注法测定高血压病胰岛素敏感性

目的探讨以小剂量胰岛素、葡萄糖持续静脉滴注法测定高血压病患者的胰岛素敏感性及培哚普利对其的影响。方法３６例高血压患者，依糖耐量试验，将其分为单纯高血压组（ＨＴ）与高血压合并糖尿病或糖耐量异常组（ＨＴ＋ＤＭ或ＩＧＴ），以小剂量胰岛素、葡萄糖持续静滴法测定两组胰岛素敏感性差异。患者经服用长效ＡＣＥＩ培哚普利４～８ｍｇ，一日１次，４周后９例完成再次小剂量胰岛素、葡萄糖持续静滴试验，以研究ＡＣＥＩ对胰岛素敏感性的影响。胰岛素敏感性指数（ＩＳＩ）以每血清胰岛素浓度葡萄糖清除率表示。结果ＨＴ＋ＤＭ或ＩＧＴ组胰岛素敏感性指数明显低于ＨＴ组：ＨＴ组ＩＳＩ为１９．６４±１０．８９，ＨＴ＋ＤＭ或ＩＧＴ组：７．７９±４．８９（Ｐ＜０．０１）。服用培哚普利前后ＩＳＩ具统计学显著性差异：治疗前：１４．７２±８．１９；治疗后：１５．３２±８．１８（Ｐ＜０．０１）。结论单纯高血压病患者胰岛素敏感性与高血压合并ＤＭ或ＩＧＴ者具有差异；服用４周培哚普利对胰岛素敏感性有正性作用，进而可能对高血压病患者的心血管系统的重构有逆转作用。然而，尚需对本课题作长期的大样本临床观察。     

糖尿病合并血管病变血浆内皮素测定的临床分析

采用族免法对６８例住院的非胰岛素依赖型糖尿病患者（ＮＩＤＤＭ）及２０例无心脑血管病变的健康人进行血浆内皮素测定，结果表明，ＤＭ患者血浆内皮素水平（ＥＴ）较正常对照组高，ＤＭ组中有并发症者ＥＴ水平较无并发症者高，两组比较，均存在着显著性差异（Ｐ〈０．０５），对于血糖控制不理想者，ＥＴ水平与病程密切相关，并随病程增加而升高。     

Ⅱ型糖尿病一级亲属糖尿病筛查

调查Ⅱ型糖尿病家系２２个,其一级系属１１６人,已诊为Ⅱ型糖尿病５４人,余行７５ｇ葡萄糖耐量及胰岛素释放试验,结果新发现糖尿病４人,糖耐量异常１６人。将新诊糖尿病例为ＤＭ组（ｎ＝１６）,新诊糖耐量异常为ＩＧＴ组（ｎ＝１６）,糖耐量正常列为ＮＧＴ组（ｎ＝３１）。经统计分析发现ＤＭ与ＩＧＴ存在明显高胰岛素血症,胰岛素敏感性（ＩＳＩ）明显低于正常组。     

糖尿病和高血压患者血液动力学的改变与胰岛素,血脂及血液…

对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）、高血压（ＨＴ）及ＮＩＤＤＭ合并ＨＴ三组患者的血液动力学、胰岛素、血脂和血液流变学的改变进行了测定。结果：（１）三患者组周围总阻（ＴＰＲ）、甘油三酯（ＴＧ）和胰岛素面积（Ｉｎｓ）显著增高，ＨＴ和ＮＩＤＤＭ合并ＨＴ组左室收缩期峰值室壁应力（ＰＳＳ）显示增高；（２）三患者组ＰＳＳ，ＴＰＲ和ＴＧ与各自ＩｎｓＳ分别呈显著正相关；（３）各患者组全血粘度（ｎｂ）升高，ＴＰＲ     

糖尿病和高血压患者血液动力学的改变与胰岛素、血脂及血液流变学的关系

对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）、高血压（ＨＴ）及ＮＩＤＤＭ合并ＨＴ三组患者的血液动力学、胰岛素、血脂和血液流变学的改变进行了测定。结果：（１）三患者组周围总阻（ＴＰＲ）、甘油三酯（ＴＧ）和胰岛素面积（ＩｎｓＳ）显著增高，ＨＴ和ＮＩＤＤＭ合并ＨＴ组左室收缩期峰值室壁应力（ＰＳＳ）显著增高；（２）三患者组ＰＳＳ，ＴＰＲ和ＴＧ与各自ＩｎｓＳ分别呈显著正相关；（３）各患者组全血粘度（ηｂ）升高，ＴＰＲ与ηｂ呈显著正相关。     

绝经后2型糖尿病患者骨质疏松影响因素及骨转换特点

目的 探讨绝经后2型糖尿病(T2DM)人群骨质疏松影响因素及骨转换特点及其防治策略.方法 150例绝经后T2DM住院患者测定骨密度(BMD)后分为骨量正常(NP)、骨量减低(DP)和骨质疏松(OP)组.登记年龄(Age),绝经年限(LOP),糖尿病病程(YSM),计算体重指数(BMI),测定空腹血糖(FPG)、餐后2 h血糖(PPG),空腹胰岛素(FIns)、餐后2 h胰岛素(2 h Ins),血Ⅰ型胶原C端肽(CTX-Ⅰ)、抗酒石酸酸性磷酸酶5b(TRACP5b)、骨特异性碱性磷酸酶(BALP)、雌激素(E2).结果 ①绝经后T2DM人群OP发病率54%;②绝经后T2DM并发OP患者与骨量减少和骨量正常组比较绝经年限、糖尿病病程及血糖水平明显增高,胰岛素和E2水平明显降低(P<0.05);③OP组患者与骨量减少和骨量正常组比较CTX-Ⅰ、TRACP5b、BALP等骨转换指标明显升高(P<0.05);④CTX-Ⅰ与腰椎2～4、股骨颈BMD呈明显负相关(P<0.05),与大转子、粗隆间BMD无明显相关性;TRACP5b、BALP与腰椎2～4、股骨颈、大转子、粗隆间BMD呈明显负相关(P<0.05).结论 LOP、血糖、YSM、FIns和E2水平可影响绝经后T2DM患者骨量;该人群骨重建特点为高转换型,骨吸收标记物TRACP5b可作为早期预测绝经后T2DM骨量减少及OP的敏感指标.     

糖尿病对骨量的影响及其相关因素的分析

为评估糖尿病对骨量的影响及各种相关因素对骨丢失的意义，本文对３００例糖尿病患者和１８００例正常人的前臂进行了骨密度测定。根据骨密度结果的不同，在骨量正常和降低组间进行了有关因素的比较，对可能影响骨量的各种因素进行了逐步回归分析。结果为：糖尿病人骨量减少的发生率为５８％。Ⅰ型和Ⅱ型糖尿病骨量减少的发生率和程度无显著性差异。骨量减少的发生率与病程长短无关。血碱性磷酸酶和尿羟脯氨酸在骨密度降低组显著增高，可作为观察骨量减少较为敏感的两项生化指标。多因素逐步回归分析结果所分析的指标对骨量无显著影响。由于病程对骨量减少无明显影响，我们认为骨量减少有可能是糖尿病基础病变的一部分。胰岛素缺乏所导致的骨形成不足和骨重建负平衡可能为骨量减少的原因。若给予足量的胰岛素治疗对预防和减轻骨量减少是有效的。     

老年2型糖尿病发生骨质疏松的临床多因素分析

目的 探讨老年2型糖尿病(T2DM)患者发生骨质疏松的影响因素. 方法 根据患者的骨密度值将患者分为骨量正常(NOP)组、低骨量(LBMD)组、骨质疏松(OP)组,对比3组在年龄、糖尿病病程、体质量指数(BMI)、胱抑素C(Cys C)、经皮氧分压检查(TcPO2)、糖化血红蛋白(HbA1c)、尿C肽(U-CP)等指标之间的差异,并进行相关性分析. 结果 (1)与NOP组相比,LBMD及OP组年龄、病程显著性升高,U-CP显著性下降;(2)OP组BMI、Cys C显著低于NOP组;(3)OP组年龄显著高于LBMD组,而BMI显著低于LBMD组(P＜0.05或P＜0.01).老年T2DM患者的BMD与年龄、病程呈负相关,与BMI、U-CP呈正相关.逐步多元回归分析显示U-CP是BMD的正性预测因子. 结论 老年T2DM患者并发骨质疏松与多因素有关,包括高龄、低体质量、病程长、胰岛功能差等.     

儿童1型糖尿病合并自身免疫性甲状腺疾病12例临床分析

目的 分析儿童1型糖尿病(T1DM)合并自身免疫甲状腺疾病(AITD)对T1DM治疗的影响。方法 1993～2002年在我院诊治的T1DM患儿合并甲状腺疾病者12例。对患儿的病史、家族史、体格检查及内分泌相关检查的结果进行分析。抗体检查：GAD-Ab、IAA、ICA、TG-Ab、TPO-Ab、TRAb和肾上腺皮质细胞浆抗体(ACC)。采用t检验将T1DM合并Graves病(GD)与合并桥本甲状腺炎(HT)者进行糖化血红蛋白(HbA1c)和胰岛素用量的分组比较；采用秩和检验对病程进行比较。结果 该组儿童患GD和HT者，分别为4例和8例。T1DM和AITD发病间隔为0～10年；GD的临床表现可不突出。有内分泌家族史者占25％。GD控制前患儿的HbA1c分别为10％、12％和14％，1例结束GD疗程者的HbA1c为7．8％。合并HT者的糖尿病代谢控制相对较好，HbA1c为7．2％～10％，1例新诊断T1DM合并HT且尚未治疗HT的患儿，HbA1c为6．3％。经t检验显示两组患儿的HbA1c差异有显著意义(P=0．011)，而病程和胰岛素用量差异无显著意义。结论该组患儿女性多于男性；HT患儿较GD患儿为多；有较强的内分泌疾病家族史。AITD影响糖尿病控制。T1DM患儿宜定期进行甲状腺自身抗体和甲状腺功能检查。     

Bone mass in obese,goldthioglucose-treated,hyperglycaemic mice

Summary In contrast to insulin-dependent diabetics, bone mass in obese non-insulin dependent diabetics seems to be greater than in normal subjects. Hyperglycaemic, obese goldthioglucose mice were studied as a model for this last type of diabetes. A significantly greater cortical bone mass (cortical surface: 1.32mm² vs 1.15mm² for controls, p<0.01) with enhanced bone apposition was found together with a significantly greater trabecular bone mass (trabecular surface 0.17 mm² vs 0.13 mm², p = 0.05) increasing bone solidity. The pathogenesis is unclear but hyperinsulinism and overnutrition may be contributory factors.     

Thiazolidinedione-induced skeletal fragility – mechanisms and implications

Recent evidence suggests that the risk of several types of fracture is increased in type 2 diabetes mellitus (T2DM). Thiazolidinediones (TZDs) are now widely used in the management of T2DM, and their use may increase in other diseases characterized by insulin resistance. The PPAR-γ, the molecular target of the TZDs currently in clinical use, is expressed in skeletal tissue. Evidence from preclinical studies has demonstrated that activation of PPAR-γ (i) inhibits bone formation by diverting mesenchymal stem cells from the osteogenic to the adipocytic lineage and (ii) may increase bone resorption by stimulating the development of osteoclasts. There is also potential for indirect adverse skeletal effects of PPAR-γ activation by modulation of circulating levels of hormones and cytokines known to influence bone metabolism. Recent studies in humans have demonstrated that TZDs decrease markers of bone formation decrease bone mass, and increase fracture rates, at least in women. The implication of these findings is that fracture risk should be considered in patients with T2DM for whom TZD therapy is being considered, and appropriate therapy instigated to prevent fractures in individuals ascertained to be at high risk.     

Calcium and phosphorus metabolism in insulin dependent and non-insulin dependent diabetics, well-controlled and poorly-controlled

We studied phosphorus and calcium metabolism in 50 adult insulin dependent and non insulin dependent diabetics arranged in 4 groups according to therapy and control of diabetes. We observed: a low level of blood magnesium in all diabetics a lower level of P T H, more pronounced with poorly controlled diabetes. a decrease of 1-25 (OH) 2 D levels without modification of the 25 (OH) D levels in badly controlled diabetics. This decrease may be related to the low level of PTH with a 1 alpha hydroxylation defect. These results are in favor of the hypothesis of a primary bone problem leading to the pre-senile and subclinical osteoporosis observed in diabetics. Hyperglycaemia rather than insulinopenia may be involved. Rigorous diabetes control significantly decreases all the observed differences, except the low magnesium level.     

Early intensive insulin therapy attenuates the p38 pathway in the renal cortex and indices of nephropathy in diabetic rats

In this rodent study, we compared the effects of early versus late intensive insulin therapy on diabetic nephropathy and potential causal mechanisms. Diabetes was induced in rats by high-fat diet and low-dose streptozotocin. Intensive insulin therapy was initiated in the early intensive insulin therapy groups as soon as diabetes was confirmed and lasted for 8 (8wEI group) and 16 weeks (16wEI group). In the late insulin therapy group (LI group), intensive insulin treatment was initiated 8 weeks later and lasted for 8 weeks. Age-matched diabetic rats (8wDM group and 16wDM group) and non-diabetic rats (8wNC group and 16wNC group) served as controls. Histological analysis, real-time PCR, and western blot were performed in renal cortex specimens. Glomerular hypertrophy and mesangial matrix expansion were prominent in the 16wDM and LI groups while the EI groups remained normal and similar to the 16wNC group. Western blots revealed that p38 MAPK activities in the EI groups decreased significantly, whereas the level in the LI group was markedly higher than the 16wEI group, and not different from the DM groups. Activities of MKK3/6, CREB and MKP-1 proteins as well as CREB and MKP-1 mRNA showed a similar pattern. Therefore, we concluded that early intensive insulin treatment and attainment of good glycemic control counteracted some renal molecular pathways associated with epigenetic metabolic memory to minimize risk of diabetic nephropathy. However, late insulin therapy did not abrogate the increased renal cortical p38 MAPK pathway activation in diabetic rats and led to glomerular hypertrophy and extracellular matrix expansion.     

胰岛素抵抗对2型糖尿病及单纯胰岛素抵抗老龄大鼠的肾损伤和骨密度的影响

目的观察胰岛素抵抗（IR）对2型糖尿病（T2DM）及单纯IR老龄大鼠的肾损伤和骨密度（BMD）的影响.方法18月龄Wistar大鼠30只,分为正常对照组、IR组、DM组,用正常血糖胰岛素钳夹技术（euglycemic insulin clamptechnique,EICT）测定各组大鼠IR,用葡萄糖输注速率（Glucoseinfusion rate,GIR）表示IR情况,放免法测定各组大鼠24 h尿白蛋白,双能X线骨密度测量仪（DEXA）测定各组大鼠腰椎、股骨BMD.结果DM组和IR组GIR低于N组（P＜0.01）.与对照组比较,DM组24h尿白蛋白升高（P=0.008）,IR组有升高趋势（P＞0.05）;DM组24 h尿白蛋白显著高于IR组（P=0.017 5）.IR组腰椎、股骨BMD低于正常对照组,高于DM组（P＜0.05）.IR组和DM组GIR与24 h尿白蛋白呈负相关,与腰椎、股骨BMD呈正相关.结论IR在T2DM及单纯IR时均可致肾脏损伤和骨密度降低.     

Bone, sweet bone--osteoporotic fractures in diabetes mellitus

Diabetes mellitus adversely affects the skeleton and is associated with an increased risk of osteoporosis and fragility fractures. The mechanisms underlying low bone strength are not fully understood but could include impaired accrual of peak bone mass and diabetic complications, such as nephropathy. Type 1 diabetes mellitus (T1DM) affects the skeleton more severely than type 2 diabetes mellitus (T2DM), probably because of the lack of the bone anabolic actions of insulin and other pancreatic hormones. Bone mass can remain high in patients with T2DM, but it does not protect against fractures, as bone quality is impaired. The class of oral antidiabetic drugs known as glitazones can promote bone loss and osteoporotic fractures in postmenopausal women and, therefore, should be avoided if osteoporosis is diagnosed. A physically active, healthy lifestyle and prevention of diabetic complications, along with calcium and vitamin D repletion, represent the mainstay of therapy for osteoporosis in patients with T1DM or T2DM. Assessment of BMD and other risk factors as part of the diagnostic procedure can help design tailored treatment plans. All osteoporosis drugs seem to be effective in patients with diabetes mellitus. Increased awareness of osteoporosis is needed in view of the growing and aging population of patients with diabetes mellitus.