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     

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 2 4例 ,分别于第 0、6、12、3 0、3 6、42和 48个月进行随访 ,测定空腹C肽 (FCP)和 10 0 g馒头餐后 2hC肽 ( 2hCP)及糖代谢指标。采用放免法测定GAD Ab和C肽。结果　LADA组的FCP于第 3 0、3 6、42、48个月明显下降 ,而C肽较入组时下降 5 0 %以上者所占百分比则均于第 12个月时明显增加 (P <0 .0 5 ) ,2型DM组的胰岛功能在随访期间则无显著性变化。LADA入组时的GAD Ab滴度与随访结束时FCP下降的差值 (ΔFCP)呈正相关 (rs=0 .5 0 ,P =0 .0 5 ) ,而体重指数 (rs=-0 .64 ,P <0 .0 1)、发病年龄 (rs=-0 .5 7,P <0 .0 5 )与ΔFCP呈负相关 ,空腹血糖 (rs=0 .64 ,P <0 .0 1)与ΔFCP呈正相关。经多元逐步回归分析 ,GAD Ab、性别、发病年龄和病程为LADA患者胰岛 β细胞功能的影响因子。 结论　LADA患者胰岛 β细胞功能较 2型DM下降更快 ,GAD Ab滴度是预测胰岛功能减退速度的重要因素 ,而且发病年龄轻、男性和病程较长对LADA患者的胰岛 β细胞功能的减退亦有一定预测作用。     

两种成人隐匿性自身免疫糖尿病亚型的谷氨酸脱羧酶抗体界值的探讨

目的　探讨判别两种成人隐匿性自身免疫糖尿病(LADA)亚型的最佳谷氨酸脱羧酶抗体(GAD-Ab)界值及其诊断价值。　方法　绘制LADA患者GAD-Ab指数的频数分布图,进行曲线拟合。比较130例经典1型糖尿病、145例2型糖尿病和145例LADA患者的临床特点,利用受试者运筹特征(ROC)曲线比较不同GAD-Ab滴度对LADA患者中反映 LADA 1 型特征的胰岛素缺乏和反映LADA 2型特征的代谢综合征(MS)的诊断价值,确定诊断两种 LADA亚型的最佳 GAD-Ab界值。用放射配体法测定 GAD-Ab。　结果　(1) GAD-Ab 频数在 LADA患者中呈双峰分布模式。(2)以GAD Ab指数0.3为切点所区分的两组LADA患者具有差异的临床特征最多。(3)ROC曲线显示GAD Ab指数0.3是区分两种LADA亚型的最佳界值,其对胰岛素缺乏和MS诊断的敏感性和特异性分别为54 5%和92 1%,ROC曲线下面积为 0.79(与 0.5 相比,P<0.01)。　结论　GAD Ab指数0 3是区分LADA-1型和LADA-2型的最佳界值。     

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。     

磺脲类降糖药继发失效患者中成人隐匿性自身免疫糖尿病的患病率调查

目的　探讨磺脲类降糖药继发失效 (SF)患者中成人隐匿性自身免疫糖尿病 (LADA)的患病率及其临床特点。　方法　在SF组 (n =2 38)中筛查谷氨酸脱羧酶抗体 (GAD Ab)和胰岛细胞抗体 (ICA) ,并将之与非继发失效 (NSF)组 (n =110 )中的阳性率比较。　结果　SF组中GAD Ab阳性的LADA的患病率为 13.9%( 33 2 38) ,NSF组为 10 .0 %( 11 110 ) ,两组差异无显著意义 (P >0 .0 5 )。LADA患者体重指数低于GAD Ab阴性者 (P <0 .0 1) ,发病年龄、血压、甘油三酯、C肽值均降低 (P <0 .0 5 )。联合检测GAD Ab和ICA ,SF组中LADA的患病率可达 2 2 .7%( 5 4 2 38) ,NSF中为 18.1%( 2 0 110 ) ,SF组与NSF组LADA患病率高于单独以GAD Ab检测 (P <0 .0 1)。　结论　SF的糖尿病患者中LADA的患病率较高。联合检测GAD Ab和ICA可提高LADA诊断的敏感性。     

联合3种抗体检测诊断成人隐匿性自身免疫性糖尿病的意义

目的探讨联合胰岛素自身抗体(IAA)、谷氨酸脱羧酶抗体(GADA)、抗胰岛素细胞抗体(ICA)检测诊断成人隐匿性自身免疫性糖尿病(LADA)的应用价值。方法选取2017年11月—2018年11月该院收治的420例初诊2型糖尿病患者为研究对象,根据其最终的临床确诊结果分为392例2型糖尿病患者和28例隐匿性自身免疫性糖尿病患者。所有患者均进行胰岛自身抗体及生化指标检测,包括IAA、GADA、ICA和空腹血糖(FBG)、餐后2 h血糖(2 hFBG)、空腹C肽、餐后2 hC肽与糖化血红蛋白(HbA1c)。结果 420例初诊2型糖尿病患者,确诊为LADA患者28例,检出率为6.67%。LADA患者的IAA、GADA、ICA阳性率及IAA+GADA+ICA阳性率,均显著高于2型糖尿病患者,比较差异有统计学意义(P0.05)。与2型糖尿病患者相比,LADA患者的FBG、2 hFBG和HbAlc值,均明显更高,比较差异有统计学意义(P0.05);且其空腹C肽和餐后2 hC肽,明显更低,比较差异有统计学意义(P0.05)。结论联合3种胰岛自身抗体检测与生化指标水平检测能够显著提高LADA的诊断准确率,为临床治疗提供可靠指标,可将该诊断方式进行临床推广应用。     

胰岛素自身抗体对成人隐匿性自身免疫糖尿病的诊断价值

目的 探讨胰岛素自身抗体(IAA)对成人隐匿性自身免疫糖尿病(LADA)的诊断价值.方法 选取2003年10月至2007年3月连续在中南大学湘雅二医院就诊的1003例初诊2型糖尿病、110例1型糖尿病患者,并选取同期米院体格检杏的317名健康对照者,采用微量平板放射免疫法和放射配体法检测IAA及谷氨酸脱羧酶抗体(GADA)和蛋门酪氨酸磷酸酶抗体(IA-2A)水平,了解IAA阳性率及与其他抗体重叠情况.对4例IAA单独阳性的LADA患者进行了4年随访,观察其临床特征变化.采用卡方榆验比较初诊2型糖尿病组、健康对照组和初诊1型糖尿病组IAA阳性率,采用t检验比较IAA阳性组和阴性匹配组空腹胰岛素(FINS)水平下降速率.结果 (1)初诊2型糖尿病患者IAA阳性率3.39%(34/1003)高于健康埘照组0.95%(3/317)(X2=5.3,P<0.05),但低于1型糖尿病组21.82%(24/110)(x2=68.2,P<0.01).(2)初诊2型糖尿病患者三种抗体联合检测阳性率为10.47%(105/1003),高于GADA 6.58%(66/1003)、IA-2A 2.79%(28/1003)、IAA3.39%(34/1003)单个抗体检测(x2值分别为9.2、37.8和46.2,P值均<0.05).IAA联合检测可提高LADA阳性检出率2.39%.(3)在4年随访期间,IAA阳性者逐年转阴,4例中的2例患者合并GADA阳性;IAA阳性组FINS水平下降速率较阴性匹配组呈增高趋势(分别为15.37%和5.29%;t=1.7,P=0.059).结论 IAA对初诊2型糖尿病患者筛查LADA有一定价值;联合检测IAA、GADA、IA-2A能提高LADA诊断效率.     

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。     

罗格列酮对低滴度谷氨酸脱羧酶抗体的LADA患者胰岛β细胞功能的影响

目的　探讨罗格列酮对谷氨酸脱羧酶抗体 (GAD Ab)低滴度的成人隐匿性自身免疫糖尿病(LADA)患者胰岛 β细胞功能的影响。 方法　将病程≤ 5年、空腹C肽 (FCP)≥ 0 .3nmol/L且GAD Ab滴度介于 0 .0 5～ 0 .3 0之间的 3 4例LADA患者随机分为磺脲类组 (SUR组 ,n =16)和罗格列酮组 (RSG组 ,n= 18)。每 6个月随访一次 ,采血检测空腹血糖、C肽、HbA1c、75g葡萄糖负荷后 2h血糖和C肽以评价胰岛功能变化。采用放射免疫法检测GAD Ab和C肽。结果　 (1)随访至 6个月时 ,SUR组患者的HOMA IS较治疗前下降 ;而RSG组患者的HOMA IS无变化 ,其HOMA IR及FCP水平较前降低。 (2 )随访至 12个月时 ,SUR组患者的HOMA IS水平较基线继续呈显著性下降 (97.2vs 10 7.3mU/mmol ,P <0 .0 5 ) ;而RSG组患者的HOMA IS水平无显著性变化。 (3 )随访至 18个月时 ,RSG组糖负荷后 2hC肽 (4 .3 2vs 1.99nmol/L ,P <0 .0 5 )及ΔCP水平 (3 .47vs 1.3 3nmol/L ,P <0 .0 5 )均高于SUR组。结论　与磺脲类药物相比 ,罗格列酮能更好地保护GAD Ab低滴度LADA患者的胰岛 β细胞功能。     

成人隐匿性自身免疫糖尿病颈动脉内膜中膜厚度与谷氨酸脱羧酶抗体滴度的关系

目的探讨成人隐匿性自身免疫糖尿病(LADA)患者颈动脉内膜中膜厚度(C-IMT)与谷氨酸脱羧酶抗体(GADA)滴度的关系。方法选取2015年9月至2019年4月参与中南大学湘雅二医院国家代谢性疾病临床医学研究中心LADA临床试验研究的160名患者基线资料。以GADA滴度为界值分为高滴度LADA-1型(GADA滴度≥0.3)和低滴度LADA-2型(0.05≤GADA滴度0.3)。收集其颈动脉内膜中膜厚度资料及其他临床资料进行横断面分析。结果 LADA-2型患者年龄、高血压比例、代谢综合征比例、体质量、体质指数、腰围、臀围、收缩压、舒张压、空腹C肽、HOMA-IR、甘油三酯水平明显高于LADA-1型患者(P0.05),而胰岛素使用比例明显低于LADA-1型患者(P0.01)。与LADA-1型患者比较,LADA-2型患者C-IMT增厚者明显增多(P0.01),且C-IMT增厚更为显著(P0.001),在校正代谢综合征相关因素后差异仍显著。多元线性回归分析显示,C-IMT与饮酒史呈正相关(P0.01),与GADA滴度呈负相关(P0.01)。根据HOMA-IR将患者分为低HOMA-IR组(HOMA-IR≤2.0)和高HOMA-IR组(HOMA-IR2.0),LADA-1型高HOMA-IR组较低HOMA-IR组C-IMT显著升高(P0.01),而LADA-2型患者高、低HOMA-IR组无差异。结论 GADA低滴度的LADA患者较高滴度患者有更高的动脉粥样硬化风险,该风险与胰岛素抵抗相关。GADA滴度为LADA患者C-IMT增厚的独立影响因素。     

成人隐匿性自身免疫糖尿病与甲状腺自身免疫的关系

目的探讨成人隐匿性自身免疫糖尿病(LADA)与甲状腺自身免疫的关系.方法对90例LADA患者、104例1型糖尿病(T1DM)患者、100例2型糖尿病(T2DM)患者和100例健康对照进行甲状腺过氧化物酶抗体(TPO-Ab)、甲状腺球蛋白抗体(TG-Ab)检测.糖尿病患者还进行谷氨酸脱羧酶抗体(GAD-Ab)检测.TPO-Ab、TG-Ab采用放免法检测,GAD-Ab采用放射配体法检测.结果(1) LADA患者TPO-Ab的检出率为16.7%(15/90)高于T2DM患者(7.0%, 7/100; P<0.05).LADA患者中任一甲状腺自身抗体(TPO-Ab或 TG-Ab阳性)的检出率与T1DM差异无显著性(18.9%,17/90比25.0%,26/104,P>0.05),且均高于正常对照的8.0%(8/100, P<0.05).(2)携高滴度GAD-Ab(GAD-Ab指数≥0.5)的LADA患者中任一甲状腺自身抗体的检出率为50.0%(9/18),高于低滴度GAD-Ab 的LADA患者(12.5%, 8/64; P<0.05).(3) 甲状腺自身抗体阳性的LADA患者甲状腺功能异常率高于抗体阴性者(47.1 %, 8/17比17.1%, 6/34, P<0.05).结论 (1)LADA患者, 尤其是携高滴度GAD-Ab的 LADA患者,与经典的T1DM相似,易合并甲状腺自身免疫紊乱.(2)LADA患者甲状腺自身抗体的存在预示甲状腺功能异常的风险增高.(3)LADA可作为自身免疫多内分泌腺病综合征(APS)的一个重要组成成分,且常以APS-Ⅲ型存在.     

Insulin autoantibody could help to screen latent autoimmune diabetes in adults in phenotypic type 2 diabetes mellitus in Chinese

Latent autoimmune diabetes in adults (LADA) is characterized by a relatively mild diabetes onset, autoantibody positivity, and eventual requirement for insulin therapy. Glutamic acid decarboxylase autoantibodies (GADA) or cytoplasmic islet cell autoantibodies (ICA) play a key role in distinguishing LADA from type 2 diabetes mellitus (T2DM) in clinical practice. The aim of our research was to determine whether insulin autoantibody (IAA) has some additional value in diagnosing LADA. We analyzed IAA, GADA, and IA-2A (antibodies to insulinoma-associated antigen-2) in 1,003 newly diagnosed phenotypic T2DM patients, 110 type 1 diabetes mellitus (T1DM) patients, and 317 normal controls to survey the prevalence of IAA in phenotypic T2DM patients and the overlapping positivity of IAA with other autoantibodies. Sera were drawn within 7?days from the start of insulin therapy. Results showed that 3.39% of the newly diagnosed phenotypic T2DM, 0.95% of normal control (χ²?=?5.3, P?<?0.05), and 21.82% of T1DM (χ²?=?68.2, P?<?0.001) were positive for IAA at diagnosis. The combination frequency of three antibodies was 10.47%, which was higher than any single antibody testing. Combination testing of IAA with GADA and IA-2A could improve LADA diagnose rate by 2.39% than that of GADA and IA-2A. IAA-positive subjects had diabetes family history more common compared to its matched group (67.6% vs. 14.7%, P?=?0.000). Postprandial C-peptide in IAA-positive group tended to be lower, but the difference was not statistically significant (P?=?0.084). We concluded that IAA can be used to screen LADA in phenotypic T2DM in the Chinese population.     

High titre of antiglutamic acid decarboxylase autoantibody is a strong predictor of the development of thyroid autoimmunity in patients with type 1 diabetes and latent autoimmune diabetes in adults

Objective Type 1 diabetes mellitus (T1DM) is frequently associated with autoimmune thyroid diseases (AITD), but little is known about the risk of AITD in latent autoimmune diabetes in adults (LADA). We evaluated the genetic and immunological factors involved in the development of thyroid autoimmunity in patients with LADA and T1DM. Patients and measurements One hundred and ninety T1DM and 135 LADA patients were recruited in the study. Thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), glutamic acid decarboxylase antibody (GADA) and thyroid function were measured. The cytotoxic‐lymphocyte‐associated antigen‐4 (CTLA‐4) +49A/G and CT60 polymorphisms and the human leucocyte antigen (HLA)‐DQA1‐DQB1 genotype were determined. Results The prevalence of thyroid antibodies (TGAb and/or TPOAb) and thyroid dysfunction was 27·4% and 9·5% in patients with T1DM, and 21·5% and 11·1% in patients with LADA. Thyroid‐antibody‐positive T1DM patients had higher frequencies of GADA and HLA‐DQA1*03‐DQB1*0401 haplotypes than thyroid‐antibody negatives (P < 0·05). Thyroid‐antibody‐positive LADA patients had higher GADA titre, lower C‐peptide levels and higher frequencies of HLA‐DQA1*03‐DQB1*0401 haplotypes (P < 0·05). The CTLA‐4 +49A/G and CT60 polymorphism was associated with T1DM complicated with thyroid autoimmunity (OR = 2·33 and 2·54). Logistic regression revealed that only high‐titre GADA was associated with development of thyroid autoimmunity in patients with T1DM and LADA (OR = 3·50 and 3·10, respectively), and the presence of thyroid antibody predicted high risk for thyroid dysfunction in patients with T1DM and LADA (OR = 9·25 and 10·70, respectively). Conclusion Regular screening of thyroid antibody and function are recommended, especially in patients with T1DM and LADA with high GADA titre.     

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.     

The prevalence and characteristics of latent autoimmune diabetes in adults (LADA) and its relation with chronic complications in a clinical department of a university hospital in Korea

Few studies were performed to evaluate the prevalence of latent autoimmune diabetes in adults (LADA) and the difference of chronic complications between LADA, T1DM, and T2DM in Korean. The aim of this study is to establish the prevalence of LADA in a diabetic clinic of Soonchunhyang University hospital and to compare the phenotypic characteristics according to DM classification based on positivity of glutamic acid decarboxylase antibodies (GADA). Also, another important point concerns the occurrence of diabetes chronic microvascular complications in LADA. 323 patients who were checked GADA among diabetic patients admitted at Soonchunhyang University hospital were recruited. Twenty-eight patients (8.7%) were identified as positive for GADA. 11.5% (n = 37) were diagnosed with T1DM and 5.3% (n = 17) were diagnosed with LADA. GADA titer showed significant negative correlation with age of onset, total cholesterol (TC), triglyceride (TG), fasting C-peptide, stimulated C-peptide, BMI, and positive correlation with HbA1C and HDL-C. Compared with those that tested negative for GADA, patients with GADA positive had lower values of onset age, BMI, TC, TG, LDL-C, fasting, and stimulated C-peptide levels and higher values of HbA1C. A significant gradual increase of values was observed for the onset age, BMI, SBP, DBP, fasting, and stimulated C-peptide across the T1DM, LADA, and T2DM subgroups. Concerning the chronic complications there was no difference in prevalence of retinopathy, neuropathy and nephropathy between three groups. Of LADA patients, 12 patients were receiving insulin treatment and mean time to insulin initiation was about 37 months. In conclusion, because our study suggests LADA subgroups in Korea appear to have a faster decline in C-peptide levels, it is worth detecting the patients with LADA early and effort to preserve beta cell function. Furthermore, our results showed that the prevalence of microvascular complication was comparable between the subgroups.     

Clinical, biochemical, and immunological characteristics of newly diagnosed nonobese diabetic patients aged 18-45 years in China

BackgroundThe purpose was to characterize the clinical, biochemical, and immunological features of newly diagnosed adult-onset nonobese diabetic patients in China.MethodsNewly diagnosed diabetic patients aged 18–45 years with body mass index<23 kg/m² were included. Excluding one mitochondrial diabetes patient, there were 102 diabetic patients enrolled in this study. Clinical and biochemical data were collected and analyzed. Radioimmunoassay was used to detect islet autoantibodies.ResultsAmong the 102 study participants, 68.6% had type 1 diabetes (T1DM), 20.6% had type 2 diabetes (T2DM), and 10.8% had latent autoimmune diabetes in adults (LADA). About 92% of the T1DM patients presented hyperglycemic symptoms. The corresponding number in T2DM and LADA patients was 13% and 38%, respectively (P<.01). C-peptide in T2DM patients (1.4±0.7 ng/ml) was significantly higher than that in T1DM (0.4±0.3 ng/ml) and LADA (0.4±0.2 ng/ml) patients (P<.01). The prevalence of glutamic acid decarboxylase antibody (GADA) (64.3%) in T1DM patients was higher than that of insulin autoantibody (17.1%) (P<.05). GADA and islet cell antibody (ICA) combination was positive in 75.7% of T1DM patients.ConclusionT1DM patients accounted for majority of the study sample. In addition, the clinical symptoms of T1DM patients were more severe compared with T2DM patients. GADA is the most sensitive autoantibody marker for adult-onset T1DM and LADA. GADA and ICA are the best test combination for adult-onset autoimmune diabetes. Specific types of diabetes should be in mind when diabetes presents itself with special transmission mode or with other extrapancreatic manifestations.     

Six-year follow-up of pancreatic β cell function in adults with latent autoimmune diabetes

AIM: To investigate the characteristics of the progression of islet β cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to explore the prognostic factors for β cell function. METHODS: Forty-five LADA patients with GAD-Ab positivity screened from phenotypic type 2 diabetic (T2DM) patients and 45 T2DM patients without GAD-Ab matched as controls were followed-up every 6 mo. Sixteen patients in LADA1 and T2DM1 groups respectively have been followed-up for 6 years, while 29 patients in LADA2 and T2DM2 groups respectively for only 1.5 years. GAD-Ab was determined by radioligand assay, and C-peptides (CP) by radioimmune assay. RESULTS: The percentage of patients whose fasting CP(FCP) decreased more than 50% compared with the baseline reached to 25.0% at 1.5th year in LADA1 group, and FCP level decreased (395.8&#177;713 vs 572.8&#177;72.3 pmol/L, P&lt;0.05) at 2.5th year and continuously went down to the end of follow-up. No significant changes of the above parameters were found in T2DM1 group. The average decreased percentages of FCP per year in LADA and T2DM patients were 15.8% (4.0-91.0%) and 5.2% (-3.5 to 35.5%, P=0.000) respectively. The index of GAD-Ab was negatively correlated with the FCP in LADA patients (rs = -0.483, P = 0.000). The decreased percentage of FCP per year in LADA patients were correlated with GAD-Ab index, body mass index (BMI) and age at onset (rs = 0.408, -0.301 and -0.523 respectively, P&lt;0.05). Moreover, GAD-Ab was the only risk factor for predicting 13 cell failure in LADA patients (B = 1.455, EXP (B) = 4,283, P = 0.023). CONCLUSION: The decreasing rate of islet 13 cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet 13 cell function, and age at onset and BMI could also act as the predictors.     

Six-year follow-up of pancreatic β cell function in adults with latent autoimmune diabetes

AIM: To investigate the characteristics of the progression of islet β cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to explore the prognostic factors for β cell function. METHODS: Forty-five LADA patients with GAD-Ab positivity screened from phenotypic type 2 diabetic (T2DM) patients and 45 T2DM patients without GAD-Ab matched as controls were followed-up every 6 mo. Sixteen patients in LADA1 and T2DM1 groups respectively have been followed-up for 6 years, while 29 patients in LADA2 and T2DM2 groups respectively for only 1.5 years. GAD-Ab was determined by radioligand assay, and C-peptides (CP) by radioimmune assay.RESULTS: The percentage of patients whose fasting CP(FCP) decreased more than 50% compared with thebaseline reached to 25.0% at 1.5th year in LADA1 group, and FCP level decreased (395.8±71.5 vs 572.8±72.3 pmol/L, P＜0.05) at 2.5th year and continuously went down to the end of follow-up. No significant changes of the above parameters were found in T2DM1 group. The average decreased percentages of FCP per year in LADA and T2DM patients were 15.8% (4.0-91.0%) and 5.2% (-3.5 to 35.5%, P= 0.000) respectively. The index of GAD-Ab was negatively correlated with the FCP in LADA patients (rs= -0.483, P = 0.000). The decreased percentage of FCP per year in LADA patients were correlated with GAD-Ab index, body mass index (BMI) and age at onset (rs = 0.408, -0.301 and -0.523 respectively, P＜0.05). Moreover, GAD-Ab wasthe only risk factor for predicting βcell failure in LADA patients (B = 1.455, EXP (B) = 4.283, P = 0.023). CONCLUSION: The decreasing rate of islet β cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet β cell function, and age at onset and BMI could also act as the predictors.     

Diabetes-related antibodies in adult diabetic patients

Islet autoimmunity is made evident by the appearance of islet-cell antibodies directed against insulin (IAA), glutamic acid decarboxylase (GADA), protein tyrosine phosphatase IA-2 (IA-2Ab) and other autoantigens. IAA and IA-2Ab are predominantly detected in childhood type 1 diabetes mellitus (T1DM), while frequency of GADA is not affected by age. In adult-onset T1DM patients, GADA is the immune marker of higher diagnostic sensitivity. In adult diabetic patients not requiring insulin treatment for at least 6 months after diagnosis, GADA identifies the so-called latent autoimmune diabetes in adults (LADA). In over 80% of cases, LADA patients develop insulin dependency within a few years after the diagnosis and have an increased risk for the development of other organ-specific autoimmune diseases. High GADA titers identify a subgroup of LADA patients with low body mass index (BMI), low C-peptide levels and increased frequency of T1DM-related HLA class II haplotypes. GADA assay should be offered to every diabetic patient, and in cases of positivity screening for other autoimmune diseases should be carried out.