新诊断2型糖尿病患者谷氨酸脱羧酶抗体、胰岛细胞抗体和胰岛素自身抗体联合筛查成人隐匿性自身免疫性糖尿病的意义

目的 研究新诊断T2DM患者中LADA的检出率,并分析其临床特征. 方法 测定152例病程＜1年,且非酮症起病的新诊断T2DM患者GADA、ICA、IAA、血压、身高、体重及BMI,同时检测血脂、FPG、胰岛素、C-P、HbA1c、促甲状腺激素（TSH）、甲状腺球蛋白抗体（TG-Ab）和甲状腺过氧化物酶抗体（TPOAb）水平.观察LADA患者与T2DM患者临床特征与生化特征的差异. 结果 新诊断T2DM患者中LADA的检出率为7.89％;与自身抗体阴性组相比,自身抗体阳性组BMI、TC降低,胰岛素及C-P水平较低,嗜中性粒细胞计数TSH异常检出率与TPO阳性率增高（P＜0.05）. 结论 新诊断T2DM患者中存在一定比例的LADA患者;对于BMI较低、胰岛功能较差的新诊断T2DM患者应尽早测定GADA、ICA和IAA.LADA患者可能具有更高的免疫炎症因子表达及更低的TC水平.     

LADA患者胰岛β细胞功能的前瞻性研究

目的 探讨成人隐匿性自身免疫糖尿病(LADA)患者胰岛功能变化的特点及其影响因素。方法 2型糖尿病(DM)中谷氨酸脱羧酶抗体(GAD-Ab)阳性的LADA患者16例和GAD-Ab阴性的2型DM患者24例，分别于第0、6、12、30、36、42和48个月进行随访，测定空腹C肽(FCP)和100g馒头餐后2hC肽(2hCP)及糖代谢指标。采用放免     

胰岛自身抗体与β细胞功能关系的研究

目的分析胰岛自身抗体与β细胞功能关系,探讨胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体(GADA)在类似2型糖尿病的成人隐匿性自身免疫糖尿病(LADA)中的诊断价值,指导临床糖尿病分型诊断和治疗。方法初诊2型糖尿病病人70例,正常糖耐量者70例,测定ICA、GADA及胰岛素释放,计算胰岛素分泌指数(HOMA-IS)、胰岛素抵抗指数(HOMA-IR)及ICA、GADA阳性率。初诊2型糖尿病自身抗体阳性组与阴性组进行年龄、体重指数(BMI)、腰臀比值(WHR)、糖化血红蛋白(HbA1c)、空腹和餐后2h胰岛素(FINS、餐后2hINS2h)、HOMA-IS及HOMA-IR等临床特征比较。结果初诊2型糖尿病组ICA阳性率为11.4%,正常糖耐量组为0.0%(P<0.01);GADA阳性率在糖尿病组为18.6%,正常糖耐量组为4.3%(P<0.01)。空腹及餐后2h胰岛素在抗体阳性组明显低于阴性组(P<0.001);HOMA-IS指数及HOMA-IR指数在抗体阴性组、抗体单阳性组及双阳性组依次降低。结论临床诊断为2型DM病人中可能有LADA病人,抗体阳性者胰岛功能明显低于抗体阴性者,提示其胰岛功能有明显损伤,而抗体阴性组胰岛素抵抗明显,提示胰岛自身抗体结合胰岛β细胞功能对LADA病人早期诊断有帮助。     

2型糖尿病患者胰岛细胞抗体检测及临床意义探讨

我们采用 ABC检测法 ,测定了一组临床已诊断为 2型糖尿病患者胰岛细胞抗体 (ICA) ,并对有关因素作了比较 ,报告如下。一、材料与方法1.研究对象 :根据 WHO(1985 )标准诊断为 2型糖尿病的患者 2 46例 ,男 12 6例 ,女 12 0例 ,平均年龄 49.5± 10 .2 (30～76 )岁。2 .主要试剂 :兔胰腺冰冻切片 (北京协和医院 )。ABC试剂盒 (VECTASTATN) ,工作浓度 1∶ 10 0。C肽试剂盒 (北京原子能公司 )。3.检测方法 :自行设计建立的免疫组化 ABC法定性检测患者血中 ICA。4.统计学处理 :ICA阳性率以百分率表示 ,其他数据以 x±s表示 ,显著性…     

中老年糖尿病患者胰岛自身抗体检测的意义

目的探讨谷氨酸脱羧酶抗体（GAD—Ab）和SOX13抗体（SOX13-Ab）在／〉50岁糖尿病患者中的分布规律及其与胰岛功能的关系。方法检测211例≥50岁糖尿病患者GAD—Ab和SOX13-Ab,分析两种抗体在不同病程、体质指数（BMI）及空腹C肽（FCP）组的阳性率,比较抗体阳性与阴性患者的临床特征。结果①单独GAD—Ab与单独SOX13-Ab阳性率（9．0％与9．9％）之间无显著差异,但均显著高于抗体双阳性者（0．9％,P〈0．05）;②SOX13-Ab单一阳性组病程显著低于抗体阴性组,而GAD—Ab单一阳性组病程显著高于抗体阴性组（P均〈0．05）;③不同病程（〈5、≥5年）范围内,GAD—Ab单一阳性组FCP、2hPCP显著低于抗体阴性组（P〈0．05）,而SOX13-Ab单一阳性组FCP、2hPCP与抗体阴性组无显著差异。结论中老年糖尿病患者GAD—Ab与SOX13-Ab分布的重叠性低,联合检测有助于分型诊断;这两种抗体对中老年糖尿病患者胰岛功能的影响程度不同,此可能部分解释了中老年糖尿病患者胰岛功能的异质性。     

老年糖尿病患者胰岛细胞自身免疫现象

目的：了解老年糖尿病患者胰岛细胞抗体（ICA）及谷氨酸脱羧酶抗体（GADA）的检出情况及其胰岛β-细胞功能状况。方法：87例新发的老年糖尿病患者为实验组,100例新发非老年糖尿病病人为对照组。2组均行ICA、GADA检测、口服葡萄糖耐量实验及C－肽释放实验。结果：实验组中有14．9％呈ICA和（或）GADA阳性,对照组中有16％呈上述抗体阳性,2组阳性率无明显差异（P＞0．05）。与其他组相比,抗体阳性的老年糖尿病患者服糖前后各点血清C－肽浓度均较低（P＜0．01）。结论老年糖尿病中亦有一定数量的1型糖尿病患者,其发生率与非老年组相同,但这类患者胰岛细胞储备能力减退更为明显。     

维生素D对LADA患者胰岛β细胞功能的影响

为探讨维生素D对成人隐匿性自身免疫性糖尿病(LADA)患者胰岛β细胞功能的影响,本研究对临床初诊为2型糖尿病(DM)的患者进行谷氨酸脱羧酶抗体(GAD Ab)检测,筛选出GAD Ab阳性的LADA患者。纳入病程≤5年和空腹C肽≥0.2nmol/L的LADA患者62例,首先对患者的GAD Ab滴度和空腹C肽水平进     

继发性磺脲类药物失效的2型糖尿病患者胰岛自身免疫抗体检测的意义

我们通过对继发性磺脲类药物失效的2型糖尿病患者胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体(GADA)阳性率测定及其与胰岛β细胞功能的关系研究,探讨ICA和GADA对胰岛功能的预测价值和成人隐匿性自身免疫糖尿病(LADA)[1]的早期诊断干预,以期对继发性磺脲类药物失效的机制进行探讨。对象与方法1.对象:所有研究对象均选自2002年4月~2005年4月间在本院就诊的糖尿患者。纳入标准为:(1)符合1999年WHO糖尿病诊断标准;(2)起病年龄>15岁<40岁;(3)起病半年内无酮症或酮症酸中毒发生;(4)所有患者均应用磺脲类药物有效时间1年以上。对照组为使用饮食…     

不同胰岛素联合治疗对2型糖尿病患者胰岛细胞功能的影响

目的探讨不同胰岛素联合治疗对2型糖尿病患者胰岛细胞功能的影响。方法选择50例2型糖尿病患者,根据用药方式不同分为观察组和对照组各25例。对照组予以门冬胰岛素联合甘精胰岛素治疗,观察组采用门冬胰岛素联合地特胰岛素治疗,疗程均为3个月。比较两组治疗前后空腹胰岛素、餐后2 h胰岛素、C肽、糖化血红蛋白(Hb A1c)及果糖胺等水平变化情况。结果两组患者治疗前空腹、餐后2 h的C肽及胰岛素指标比较差异均无统计学意义(P0.05),治疗后空腹胰岛素及C肽水平均显著上升(P0.05),观察组餐后2 h胰岛素水平与治疗前相比明显升高,也显著高于对照组,差异均有统计学意义(P0.05)。与治疗前相比,治疗后两组患者Hb A1c、果糖胺水平均显著下降,差异均有统计学意义(P0.05)。结论 2型糖尿病患者采用门冬胰岛素联合地特胰岛素治疗可明显改善患者的胰岛素细胞功能,与门冬胰岛素联合甘精胰岛素治疗相比治疗效果更佳,应用价值更高。     

胰岛自身抗体对Ⅰ型糖尿病诊断效率的研究

目的 探讨免疫指标谷氨酸脱羧酶抗体（ＧＡＤ６５－Ａｂ）与胰岛细胞抗体（ＩＣＡ）对Ⅰ型糖尿病的诊断价值。方法 Ⅰ型糖尿病１０４例,正常对照１０２例,用放射配体分析法检测ＧＡＤ６５－Ａｂ,ＥＬＩＳＡ法检测ＩＣＡ;用受试者运筹特性（ＲＯＣ）曲线及曲线下面积比较二者的诊断效率。结果 （１）ＧＡＤ６５－Ａｂ最佳界值０．３０,ＩＣＡ最佳界值０．４５。ＧＡＤ６５－Ａｂ、ＩＣＡ、ＲＯＣ曲线下面积分别为０．８３５、     

2型糖尿病胰岛细胞胰岛素抵抗的机制

胰岛素抵抗是2型糖尿病(T2DM)主要病理生理机制之一.肝脏、肌肉和脂肪组织存在胰岛素抵抗.近年来研究显示,胰岛α细胞与β细胞也存在胰岛素抵抗.高糖、高游离脂肪酸(FFA)、氧化应激、炎性反应均可导致胰岛素抵抗:高糖作用可下调胰岛α、β细胞磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(PKB)途径;高FFA抑制胰岛素受体底物(IRS)及PI3K活性;氧化应激使胰岛α、β细胞的IRS表达下降;炎性因子可干扰IRS/PI3K信号通路.     

初诊2型糖尿病患者血清总骨钙素水平对胰岛β细胞功能的影响

目的 分析初诊2型糖尿病患者不同总骨钙素水平组间的胰岛素抵抗指标及胰岛β细胞分泌功能指标差异及其相关性,探讨总骨钙素与胰岛功能的关系。方法 选取2016年12月至2018年10月于北京大学国际医院内分泌科门诊及住院的初诊2型糖尿病患者216例,根据患者总骨钙素水平分为4组,比较不同血清总骨钙素水平组间胰岛素抵抗指标及胰岛β细胞分泌功能之间的差异及上述指标间的相关性。结果 4组间甲状旁腺素水平比较差异有统计学意义（P<0.05）,低骨钙素水平组甲状旁腺素水平较低（F=3.55,P<0.05）。女性患者,骨钙素水平与稳态模型评估β指数（homeostasis model assessment β,HOMA-β）及葡萄糖处置指数（disposition index 0,DI0）水平呈显著正相关（r=0.41,P<0.05;r=0.45,P<0.05）。60岁以上男性患者,骨钙素水平与HOMA-β及DI0水平呈显著正相关（r=0.34,P<0.05;r=0.32,P<0.05）。多元线性回归分析结果显示,女性及60岁以上男性2型糖尿病患者低骨钙素水平与胰岛β细胞分泌功能降低独立相关（P<0.05）。结论 对于初诊女性及60岁以上男性2型糖尿病患者,低骨钙素水平可能与胰岛β细胞分泌功能降低独立相关,这为2型糖尿病的发病机制及治疗提供了新的研究方向。     

Target antigen of islet cell antibody in Japanese insulin-dependent diabetes mellitus

The target antigens of islet cell antibody (ICA) have not been clarified. We tried to modify the antigen in human pancreatic tissues and characterize the ICA with immunohistochemical methods. Human pancreatic tissues were treated with periodate (A), borohydride (B), neuraminidase (C), methanol (D), chloroform-methanol (E), or protease (F) to modify the antigens, and stained by an immunofluorescent method using ICA-positive sera from five Japanese insulin-dependent diabetes mellitus (IDDM) patients. In all sera the fluorescence of islets disappeared or waned after A, C, D, and E, and did not change after F. The disappearance or loss of fluorescence induced by A was recovered after B. It is, therefore, suggested that one of the antigens of ICA in Japanese IDDM patients is the sialic acid residue of glycolipid.     

Anti-single-stranded DNA antibody in the sera of patients with type 2 diabetes mellitus

Anti-single-stranded(ss)DNA antibodies were searched for by enzyme-linked immunosorbent assay (ELISA) in the serum of 202 outpatients with non-insulin-dependent diabetes mellitus and 135 healthy subjects to investigate their prevalence in the serum of patients with type 2 diabetes and their relationship with the presence of vascular complications. Of the 202 patients 128 had vascular complications. Anti-ssDNA antibodies were observed to be significantly more frequent in the serum of patients with vascular complications (33.6%) and in particular in patients with overt nephropathy (50%) than in patients without complications (6.7%) or controls (6.7%). Anti-ssDNA antibodies have been previously described in patients with type 1 diabetes before clinical evidence of vascular disease, and their cross-reactivity with a variety of anionic biological molecules or cells, i.e. platelets and endothelial cells, assessed. It seems not unreasonable that these autoantibodies detected in patients with type 2 diabetes could be of importance in the pathogenesis or progression of angiopathy. Received: 19 March 1996 / Accepted in revised form: 9 October 1996     

Anticardiolipin and anti-beta2 glycoprotein I antibody concentrations in patients with type 2 diabetes mellitus

Anticardiolipin and anti-beta2 glycoprotein I antibodies are associated with an increased tendency to thrombosis by various mechanisms. This study aimed to evaluate the association between micro and macrovascular complications of diabetes and anticardiolipin and anti-beta2 glycoprotein I antibodies. Forty-six patients with type 2 diabetes mellitus (T2DM) were studied. Twenty-one patients had coronary artery disease as a macrovascular complication. Twenty-five age and sex matched healthy subjects formed a control group. Anticardiolipin IgM, IgG, anti-beta2 glycoprotein IgM and IgG antibody levels were studied in both patient and control groups. Diabetic patients with ischaemic heart disease had significantly higher titres of anticardiolipin IgG antibody than patients without ischaemic heart disease (P < 0.001). However, none of these patients had an anticardiolipin IgG antibody level higher than 20 GPL, which is accepted as a clinically significant value, so this association may not be clinically important. There was no association with the microvascular complications. There was also no significant association between anti-beta2 glycoprotein I antibodies in type 2 diabetic patients and micro and macrovascular complications. Anticardiolipin and anti-beta2 glycoprotein I antibodies do not have a major role in the pathogenesis of diabetic complications in type 2 diabetic patients. Prospective studies of large populations are needed to explore this association further.     

Hypercoagulability in patients with type 2 diabetes mellitus detected by a thrombin generation assay

Diabetes is a risk factor for the development of atherothrombosis and venous thromboembolism (VTE). We investigated whether plasma from patients with type 2 diabetes has an imbalance of pro- versus anti-coagulation resulting in hypercoagulability despite normal conventional coagulation tests. We analyzed blood samples from 60 patients with type 2 diabetes and 60 gender- and age-matched healthy subjects (controls) for the levels of pro- and anti-coagulant factors, for thrombin generation and for the numbers of cell-derived circulating microparticles bearing such pro-coagulant triggers as tissue factor and negatively charged phospholipids. The levels of pro- or anti-coagulants as measured with conventional coagulation tests or single factor measurements were similar to those of the control population. In contrast, the median (range) of the height of the thrombin peak (taken as an index of thrombin generation) was higher in patients [205 nM (126–352)] than controls [151 nM (41−289)], P < 0.001. The median numbers of circulating microparticles were higher for patients [5,041/μl (1,821–13,132)] than for controls [1,753/μl (554–13,308)], P < 0.001 and their values were correlated with the height of the thrombin peak (ρ = 0.66, P < 0.001). In conclusion, plasma from patients with type 2 diabetes possesses an imbalance of pro- versus anti-coagulation resulting in hypercoagulability that can be detected by thrombin generation tests, but not by the measurement of the single pro- or anti-coagulant factors. This hypercoagulability is associated with increased numbers of circulating microparticles bearing endogenous pro-coagulant triggers. These findings might explain the relatively high risk of atherothrombosis and VTE described in these patients.     

成人糖尿病患者血清GADA和ICA检测的临床意义

目的　研究血清胰岛细胞抗体 (ICA)、谷氨酸脱羧酶抗体 (GADA)检测对 1型糖尿病 (DM)早期诊断的意义 ,以及抗体阳性患者胰岛 β细胞功能。方法　采用 EL ISA法检测 ICA、GADA;放射免疫法检测血清空腹和餐后 C肽。结果　 16 3例 2型 DM患者中 ,ICA及 GADA阳性共 32例为 1型 DM,其中 ICA阳性 18例 ,GADA阳性 2 5例 ,GADA阳性率 (15 .3% )高于 ICA(11.0 % )。抗体阳性患者的空腹和餐后 C肽 [(0 .6 3± 0 .31)和 (1.76± 0 .82 ) pmol/ L]明显低于抗体阴性患者 [(0 .91± 0 .81)和 (3.18± 1.92 ) pm ol/ L]。GADA阳性患者的空腹和餐后 C肽 [(0 .2 9± 0 .18)和 (0 .74± 0 .4 3) pm ol/ L ]明显低于 ICA阴性患者 [(0 .4 8± 0 .32 )和 (1.11± 0 .4 5 )pmol/ L ]。结论　 ICA、GADA检测对 1型 DM的早期诊断有重要意义。