胰岛素样生长因子1对2型糖尿病合并骨质疏松中骨钙素表达的影响

随着流行病学的调查研究发现,2型糖尿病患者与健康人群相比,其罹患骨折事件的发生率明显增高,所以骨质疏松及骨折等并发症需引起2型糖尿病患者的足够重视。在分子机制层面的研究显示,2型糖尿病合并骨质疏松的发生可能与胰岛素样生长因子1、葡萄糖毒性、硬骨素、骨钙素及氧化应激等多种代谢途径的改变有关。胰岛素样生长因子1是骨形成的调节因子,在调节成骨细胞和破骨细胞介导的骨骼重建过程中起着重要的作用。骨钙素是由成骨细胞产生的一种非胶原蛋白,能够反映成骨细胞的活性,常作为骨形成和骨转换的特异性指标。有研究显示,胰岛素样生长因子1以浓度依赖方式刺激骨钙素的合成增加,本文试就胰岛素样生长因子1对2型糖尿病合并骨质疏松中骨钙素表达的影响做一综述,探讨在2型糖尿病合并骨质疏松患者中胰岛素样生长因子1与骨钙素之间的相关性,以期对2型糖尿病合并骨质疏松患者能够进行早期诊断及治疗,预防骨折事件的发生,提高患者生活质量。     

老年糖尿病患者骨密度的变化及其相关因素研究

目的探讨老年2型糖尿病患者骨密度的影响因素。方法选取2010年3月-2012年3月来我院内分泌科就诊的2型糖尿病患者72例及同期健康老人60例，通过对两组骨代谢指标、骨密度的测定，对比两组骨代谢指标、骨密度的变化情况，同时对其骨代谢指标与骨密度间的相关性进行分析。结果老年2型糖尿病患者的骨代谢异常，BGP呈下降趋势，PTH、DPD、血磷浓度均有所上升（P〈0．05）；同时与对照组相比，糖尿病患者的骨密度降低（P〈0．05）；且骨密度与BGP水平呈正相关，与PTH、DPD呈负相关。结论老年2型糖尿病患者骨密度出现下降现象，骨质疏松的发生增多，这些都与其骨代谢指标的改变有关。     

降糖药对糖尿病患者骨代谢的影响

糖尿病（diabetes mellitus，DM）是一组常见的以血浆葡萄糖水平增高为特征的代谢内分泌疾病，无论是1型还是2型糖都可存在不同程度的骨量改变。影响糖尿病骨量的原因有很多，如遗传、环境因素、生活方式、年龄、绝经、药物等。其中降糖药除发挥降糖及心血管保护等有益作用外，还影响着骨的代谢。     

多学科综合治疗肥胖症合并2型糖尿病

2型糖尿病常合并肥胖症、高血压、高血脂等代谢综合征症候群。对于此类难以控制的2型糖尿病合并肥胖症的诊断和治疗，内科常用非手术如控制饮食、运动、药物方式治疗；外科则可采用手术方式，改善2型糖尿病及其代谢综合征症候群，达到“治愈”糖尿病和高脂血症的目的。中南大学湘雅三医院对1例肥胖症合并2型糖尿病患者采用多学科协作综合治疗模式，取得了较好疗效。     

2 型糖尿病性骨质疏松的鼠类模型的研究进展

2型糖尿病性骨质疏松(Type 2 Diabetic Osteoporosis,T2DOP)的病因复杂,对治疗带来困难,因此,建立符合人类2型糖尿病发病特点、骨代谢和骨结构的动物模型在T2DOP发病机制及其防治研究中的意义重大。由于鼠类的骨结构特点与人类相似,而且容易繁殖,目前国内外T2DOP动物模型研究也大多数在鼠类的研究。国内采用诱发性鼠类模型观察到其骨代谢和骨结构异常报道居多,国内外观察自发性2型糖尿病鼠类模型和转基因/基因敲除2型糖尿病鼠类模型的骨代谢和骨结构也存在异常,但是尚无一种既能在其骨骼成熟后发展为2型糖尿病,又能协同多基因和环境因素的2型糖尿病鼠类模型。故本文对研究的T2DOP鼠类模型的构建、骨代谢特征及其骨结构做一综述,为建立更为完善的2型糖尿病模型,进一步推动2型糖尿病性骨质疏松的机制研究和药物研发。     

绝经后2型糖尿病患者血脂与骨代谢的关系

目的探讨绝经后2型糖尿病患者血脂与骨代谢的相关性。方法将300例绝经后2型糖尿病患者按T值分成骨质疏松组和非骨质疏松组;检测两组患者血清总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及骨代谢指标,分析血脂各成分与骨代谢之间的关系。结果 (1)绝经后2型糖尿病患者的HDL-C与OT、TrACP、uNTX/Cr存在正相关(r1=0.134,P1=0.020;r2=0.181,P2=0.002;r3=0.126,P3=0.030),与BALP无相关性;TC与TrACP呈负相关(r=-0.153,P=0.038),与OT、BALP、uNTX/Cr无相关性;TG、LDL-C与OT、BALP、TrACP、uNTX/Cr均无相关性。(2)在校正年龄、绝经年限和BMI影响因素后,HDL-C与TrACP、uNTX/Cr仍存在正相关(r1=0.160,P1=0.010;r2=0.125,P2=0.045),而HDL-C与OT、TC与TrACP间的相关性失去统计学意义。结论绝经后2型糖尿病患者的HDL-C与TrACP、uNTX/Cr存在正相关,与OT、BALP无相关性;而TC、TG、LDL-C与OT、BALP、TrACP、uNTX/Cr无明显相关性。     

2型糖尿病患者骨质疏松发生率及骨代谢生化指标测定分析

目的 探讨2型糖尿病患者合并骨质疏松的发生率及骨代谢生化指标变化.方法 ①对142例2型糖尿病患者进行桡骨定量骨超声测定及骨钙素、尿1型胶原C端肽及血钙、磷、碱性磷酸酶等骨代谢生化指标检测,分别计算男、女2型糖尿病患者骨质疏松发生率并与非糖尿病对照人群进行比较;②分析糖尿病患者骨超声测定值(骨超声波波速,SOS,m/s)与其年龄、病程、代谢控制程度及体重指数等之间的关系;③根据骨超声测定结果将2型糖尿病患者分为合并骨质疏松组、骨量减少组与未合并骨质疏松组,比较组三间的骨代谢生化指标变化,并与健康对照组做比较.结果 ①糖尿病患者骨质疏松发生率明显高于非糖尿病人群,②糖尿病患者骨超声值与其年龄、病程、尿CTX及体重指数呈负相关,与骨钙素、糖化血红蛋白及空腹血糖未发现相关性;③糖尿病患者中合并骨质疏松组尿CTX测定明显高于骨量减少组及骨量正常组(P<0.05),血PTH在骨质疏松组明显高于骨量正常组,血钙、磷、碱性磷酸酶及血清骨钙素测定组间相比无显著性差异(P>0.05);总体糖尿病患者与非糖尿病对照人群相比血清骨钙素测定明显降低(P<0.05),尿CTX明显升高(P<0.05).结论 2型糖尿病患者较易患骨质疏松,其骨代谢改变特点是:骨形成下降、骨吸收增加,糖尿病骨代谢异常的发生与众多因素有关,在治疗糖尿病的同时,应注意骨质疏松的预防和治疗.     

2型糖尿病患者骨质疏松发生率及骨代谢生化指标测定分析

目的 探讨2型糖尿病患者合并骨质疏松的发生率及骨代谢生化指标变化.方法 ①对142例2型糖尿病患者进行桡骨定量骨超声测定及骨钙素、尿1型胶原C端肽及血钙、磷、碱性磷酸酶等骨代谢生化指标检测,分别计算男、女2型糖尿病患者骨质疏松发生率并与非糖尿病对照人群进行比较;②分析糖尿病患者骨超声测定值(骨超声波波速,SOS,m/s)与其年龄、病程、代谢控制程度及体重指数等之间的关系;③根据骨超声测定结果将2型糖尿病患者分为合并骨质疏松组、骨量减少组与未合并骨质疏松组,比较组三间的骨代谢生化指标变化,并与健康对照组做比较.结果 ①糖尿病患者骨质疏松发生率明显高于非糖尿病人群,②糖尿病患者骨超声值与其年龄、病程、尿CTX及体重指数呈负相关,与骨钙素、糖化血红蛋白及空腹血糖未发现相关性;③糖尿病患者中合并骨质疏松组尿CTX测定明显高于骨量减少组及骨量正常组(P<0.05),血PTH在骨质疏松组明显高于骨量正常组,血钙、磷、碱性磷酸酶及血清骨钙素测定组间相比无显著性差异(P>0.05);总体糖尿病患者与非糖尿病对照人群相比血清骨钙素测定明显降低(P<0.05),尿CTX明显升高(P<0.05).结论 2型糖尿病患者较易患骨质疏松,其骨代谢改变特点是:骨形成下降、骨吸收增加,糖尿病骨代谢异常的发生与众多因素有关,在治疗糖尿病的同时,应注意骨质疏松的预防和治疗.     

高胆固醇对骨代谢影响的研究进展

近年来,以高脂血症为代表的脂代谢异常疾病及骨代谢疾病发病率日益增高,且脂代谢异常会引发骨代谢异常。高脂血症是引发骨质疏松等骨代谢疾病的危险因素之一,对骨代谢通常起负调控作用。胆固醇又是血脂的主要成分,因此对骨代谢调节有重要影响,这种影响在分子水平上涉及多种胆固醇与成骨/破骨细胞的关系及对骨髓间充质干细胞选择性分化的调控。胆固醇与骨代谢之间的相互调节机制复杂多样,至今仍未完全阐明。因此,该文主要综述胆固醇对成骨/破骨细胞的影响及探讨其对骨代谢影响的通路机制,以明确两者间相关性的靶点,为骨代谢疾病的防治提供新的方向。     

90例2型糖尿病合并慢性并发症的骨代谢的变化

目的 探讨2型糖尿病合并慢性并发症骨代谢的改变和机制。方法 测定90例2型糖尿病合并慢性并发症及70例2型糖尿病无并发症患与年龄，体重指数相匹配100例健康对照组的骨密度，血清骨钙素（BGP），钙（Ga)，尿羟脯氨酸（HOP），空腹及餐后2h的血糖，糖化血红蛋白（HbAlc)等进行比较。结果 2型糖尿病合并慢性并发症组BMD明显下降，FBG，PBG，尿HOP均高于2型糖尿病无慢性并发症组，BMD与糖尿病的病程，FBG，PBG，尿HOP呈显的负相关。结论 2型糖尿病合并慢性并发症组，糖尿病病程长，血糖高，BMD下降，比2型糖尿病无慢性并发症患更易患骨质疏松，骨吸收大于骨形成，骨矿含量明显下降。     

Epidemiology of fractures in type 2 diabetes

Type 2 diabetes affects an increasing proportion of older adults, the population that is also at elevated risk of fracture. Type 2 diabetes itself increases the risk of fracture, particularly in African–American and Latino populations. In Western countries, overweight and obesity, associated with reduced fracture risk, are highly prevalent in diabetic patients. Studies in East Asian countries that have a lower prevalence of obesity with diabetes may help to disentangle the effects of diabetes and obesity on the skeleton. Type 2 diabetes is also associated with higher bone density, and as a result standard tools for fracture prediction tend to underestimate fracture risk in this population, an important challenge for risk assessment in the clinical setting. Contributing factors to the increased fracture risk in type 2 diabetes include more frequent falls and deficits in diabetic bone, not captured by dual X-ray absorptiometry (DXA), that are as yet not clearly understood. Recent epidemiological studies indicate that poor glycemic control contributes to increased fracture risk although intensive lowering of A1C is not effective in preventing fracture.This article is part of a Special Issue entitled “Bone and diabetes”.     

Diabetes Mellitus: Does it Affect Bone?

Both diabetes and fractures affect a large proportion of older adults. Recent cohort studies indicate that diabetes itself is associated with increased risk of fracture of the hip, proximal humerus, and foot. Observational studies and animal models suggest that decreased bone strength in diabetes may contribute to fracture risk but this remains a controversial issue. Type 1 diabetes is associated with modest reductions in bone mineral density (BMD) but type 2 diabetes is often characterized by elevated BMD. This paradox of higher BMD but increased fracture risk in type 2 diabetes may be explained by a combination of more frequent falls and poorer bone quality. Diabetes can impact bone through multiple pathways, some with contradictory effects, including obesity, changes in insulin levels, higher concentrations of advanced glycation end products in collagen, hypercalciuria associated with glycosuria, reduced renal function, lower insulin-like growth factor-I, microangiopathy, and inflammation. A better understanding of how diabetes metabolism and treatments affect bone would improve fracture prevention efforts in older diabetic adults.     

Diabetes and bone loss at the hip in older black and white adults.

Type 2 diabetes may be associated with elevated fracture risk, but the impact on bone loss is unknown. Analysis of 4-year change in hip BMD data from a cohort of white and black well-functioning men and women 70-79 years of age found that white women with diabetes had more rapid bone loss at the femoral neck than those with normal glucose metabolism. INTRODUCTION: Type 2 diabetes may be associated with elevated fracture risk in older adults. Although type 2 diabetes is not associated with lower BMD, older diabetic adults have a higher prevalence of other risk factors for fracture, including more frequent falls, functional limitations, and diabetic complications. With this burden of risk factors, loss of BMD could place older adults with diabetes at higher risk of sustaining a fracture. MATERIALS AND METHODS: To determine if bone loss is increased with type 2 diabetes, we analyzed data from the Health, Aging, and Body Composition Study of white and black well-functioning men and women 70-79 years of age. Hip BMD was measured at baseline and 4 years later in 480 (23%) participants with diabetes, 439 with impaired glucose metabolism, and 1172 with normal glucose homeostasis (NG). RESULTS: Those with diabetes had higher baseline hip BMD and weight, but among white women, had more weight loss over 4 years. White women with diabetes lost more femoral neck and total hip BMD than those with NG in age-adjusted models. After multivariable adjustment, diabetes was associated with greater loss of femoral neck BMD (-0.32%/year; 95% CI: -0.61, -0.02) but not total hip BMD. In men and black women, change in hip BMD was similar for participants with diabetes and NG. CONCLUSIONS: Despite having higher baseline BMD, diabetic white women, but not men or black women, had more rapid bone loss at the femoral neck than those with NG. This increased bone loss may contribute to the higher fracture risk observed in older diabetic women.     

Association of diabetic retinopathy and renal function in patients with types 1 and 2 diabetes mellitus

AIMS: It takes years for microvascular complications in diabetes mellitus such as diabetic retinopathy (RP) and nephropathy (NP) to develop. Since retinal and renal vessels are exposed to the diabetic milieu, it is often assumed that progression of diabetic RP and NP occurs at the same time. However, smaller studies have demonstrated that this may not always be the case. The present study was undertaken to correlate diabetic retinopathy with parameters of renal function in a large ambulatory collective of patients with Types 1 and 2 diabetes. METHODS: The study design was cross-sectional. Ambulatory patients from a large university out-patient clinic were studied (323 patients with Type 1, 906 patients with Type 2 diabetes). RP status was obtained through retinal photography by an experienced ophthalmologist and was grouped into no RP, RP Stages 1-3, or blind. Retinal pathology was correlated with clinical parameters of renal function (proteinuria, estimated glomerular filtration rate according to the MDRD formula, presence of urinary sediment abnormalities, hypertension). RESULTS: No patient showed urinary sediment abnormalities (e.g. presence of hematuria or acanthocytes) or increased urinary excretion of immunoglobulin light chains suggesting the absence of other nondiabetic renal diseases. The majority of Type 1 diabetes patients with macroalbuminuria (> or = 200 mg/l) had some signs of RP independent of the presence of hypertension. There was a correlation between RP and microalbuminuria (r = 0.164, p < 0.01). In contrast, up to 47.5% of the hypertensive patients with Type 2 diabetes and overt proteinuria had no signs of RP. There was also discordance of microalbuminuria and RP in patients with Type 2 diabetes. Stratification according to K/DOQI States 2-5 (MDRD formula) showed that the majority of patients with Type 1 diabetes in States 3-5 had signs of RP, albeit the absolute number of patients in these K/DOQI stages was very small. In contrast, up to 40% of dialysis-dependent Type 2 diabetics (K/DOQI State 5) showed no evidence of RP. CONCLUSIONS: This study revealed that many patients with Type 2 diabetes and renal abnormalities (proteinuria and/or renal insufficiency) showed, in contrast to Type 1 diabetics, no signs of RP. Our study was, however, limited by the lack of renal biopsies. Although urinary sediment analysis was normal in these patients, other causes for renal insufficiency (e.g. vascular nephropathy), especially in Type 2 diabetics, cannot be excluded. Nevertheless, we believe that absence of RP in patients with Type 2 diabetes does not imply that renal abnormalities including diabetic nephropathy, are also absent. It is recommended that these patients undergo renal biopsy.     

通过Micro-CT评价瘦素受体缺乏的2型糖尿病小鼠四肢骨的骨代谢变化

目的探讨瘦素受体(leptin receptor,Lepr)缺乏的2型糖尿病小鼠的骨骼表型,为2型糖尿病((T2DM)合并骨质疏松(OP)的防治提供一个新的靶点。方法获取20只14周龄雄性db/db小鼠(瘦素受体缺乏小鼠)和野生型小鼠(C57BL小鼠)的胫骨(各10只),通过Micro-CT检测比较两者骨小梁相对体积(BV/TV)、骨表面积组织体积比值(BS/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)、骨结构模型指数(SMI)、骨皮质厚度(Ct.Th)、骨皮质面积(Ct.Ar)等骨微结构参数的差异。结果与野生型小鼠相比,14周龄的db/db小鼠的胫骨骨小梁相对体积(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)明显减小,小梁骨间距(Tb.Sp)相应增加,皮质骨厚度(Ct.Th)、横截面积(Ct.Ar)减小,两者比较差异均有显著统计学意义(P0.05);其结构模式指数(structure model index,SMI)较野生型明显减小,两者比较差异均有统计学意义(P0.05)。结论 2型糖尿病可能是通过瘦素受体参与的信号通路影响了骨量变化,为利用该模型进行DOP病因及治疗方法研究提供了新的方向。且在缺乏瘦素信号传导的情况下,骨质量和强度的降低验证了瘦素在体内起着合成代谢骨因子的作用。     

Type 2 diabetes and bone fragility in children and adults

Type 2 diabetes (T2D) is a global epidemic disease. The prevalence of T2D in adolescents and young adults is increasing alarmingly. The mechanisms leading to T2D in young people are similar to those in older patients. However, the severity of onset, reduced insulin sensitivity and defective insulin secretion can be different in subjects who develop the disease at a younger age. T2D is associated with different complications, including bone fragility with consequent susceptibility to fractures. The purpose of this systematic review was to describe T2D bone fragility together with all the possible involved pathways. Numerous studies have reported that patients with T2D show preserved, or even increased, bone mineral density compared with controls. This apparent paradox can be explained by the altered bone quality with increased cortical bone porosity and compr-omised mechanical properties. Furthermore, reduced bone turnover has been described in T2D with reduced markers of bone formation and resorption. These findings prompted different researchers to highlight the mechanisms leading to bone fragility, and numerous critical altered pathways have been identified and studied. In detail, we focused our attention on the role of microvascular disease, advanced glycation end products, the senescence pathway, the Wnt/β-catenin pathway, the osteoprotegerin/receptor-activator of nuclear factor kappa B ligand, osteonectin and fibroblast growth factor 23. The understanding of type 2 myeloid bone fragility is an important issue as it could suggest possible interventions for the prevention of poor bone quality in T2D and/or how to target these pathways when bone disease is clearly evident.     

2型糖尿病性骨质疏松症发病机制研究进展

2型糖尿病属于临床常见病,可引发骨骼、血管、神经等多系统并发症,骨质疏松症是其常见并发症之一。2型糖尿病性骨质疏松症患者主要表现为骨代谢异常、骨脆性增加,易发生骨折。当前关于2型糖尿病性骨质疏松症发病机制的研究众多,其中涉及高血糖状态、氧化应激、糖尿病慢性并发症、细胞因子及激素水平变化等多个方面。笔者就国内外关于2型糖尿病性骨质疏松症发病机制的最新研究进行综述,旨在为下一步研究及临床工作提供参考。     

骨转换标志物在糖尿病中的研究进展

随着糖尿病和骨质疏松症在我国的广泛流行,糖尿病性骨质疏松症已成为糖尿病患者致死、致残的重要原因,严重影响患者的生活质量,并给个人、社会带来沉重负担。1型糖尿病患者骨密度降低,骨折风险增加;2型糖尿病患者骨密度常增高或正常,但骨折风险也是增加的,这不能仅靠双能X线骨密度来解释。骨转换标志物具有灵敏度高、特异性强、稳定性好等优点,近年来在糖尿病中得到广泛研究,如骨碱性磷酸酶、1型原胶原N-端前肽、1型胶原交联C-末端肽、骨钙素、骨保护素、脱氧吡啶啉等。骨转换标志物反映骨吸收和骨形成的具体变化情况,反映骨强度,较骨密度更早的反映骨量变化,大量临床研究发现,它为临床早期发现和诊断糖尿病性骨质疏松症,评估糖尿病患者骨折风险提供了新思路。联合检测骨转换标志物和骨密度,更全面、合理的评估骨转换,及时发现高危人群,更有利于糖尿病性骨质疏松症患者的早期诊断及治疗,预防骨折的发生。本文将对骨转换标志物在糖尿病中的研究进展作一综述。     

Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

Type 2 diabetes(T2 D) is associated with systemic abnormal bone remodeling and bone loss. Meanwhile,abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis(OA).Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2 D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic(n = 70) and diabetes(n = 51) groups. Tibial plateaus were also collected from cadaver donors(n = 20) and used as controls.Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase(TRAP), osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International(OARSI) scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~+ osteoclasts and lower number of Osterix~+ osteoprogenitors and Osteocalcin~+ osteoblasts. T2 D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2 D-associated knee OA.     

定量CT对2型糖尿病性骨质疏松的诊断意义

2型糖尿病(type 2 diabetes mellitus, T2DM)通过多种因素影响骨微结构和骨密度,导致骨强度下降,骨折风险增加。定量CT(quantitative computed tomography, QCT)测定三维体积骨密度(volume bone mineral density, vBMD)优于双能X线吸收法(dual energy X-ray absorptiometry, DXA)测定的面积骨密度(area bone mineral density, aBMD)对T2DM患者骨折风险评估,还能发现松质骨的结构改变、皮质骨多孔性结构,对骨量细微改变具有高敏感性。将QCT与有限元分析法结合,通过骨密度、骨组织结构同时分析骨应力来评价骨强度,对T2DM患者骨折风险的预测更有价值。