胰岛素强化治疗老年隐匿性自身免疫性糖尿病的疗效及对胰岛β细胞功能的影响

目的观察胰岛素强化方法治疗老年隐匿性自身免疫性糖尿病(LADA)的疗效及其对胰岛β细胞功能的影响。方法对2006年6月至2013年6月住院的45例中青年(25⁶0岁)LADA患者、50例氨酸脱羧酶抗体(GADA)阳性老年(≥60岁)LADA患者及49例GADA阴性的老年2型糖尿病(T2DM)患者进行临床对照研究,比较其糖化血红蛋白(HbA1c)、体质量指数(BMI)、并发症、治疗前及治疗1年后空腹C肽与餐后2 h C肽水平。结果老年与中青年LADA患者治疗前空腹部C肽水平及餐后2 h C肽水平等无统计学差异,经胰岛素强化治疗后空腹C肽及餐后2 h C肽水平有统计学差异(P<0.05);老年LADA患者与T2DM患者相比,老年LADA患者HbA1c较高且并发症明显增多(均P<0.05),治疗前餐后2 h C肽无统计学差异(P>0.05),治疗后空腹C肽及餐后2 h C肽水平有显著差异(P<0.01)。结论胰岛素强化治疗可保护残余胰岛β细胞,对老年LADA具有较好的疗效。     

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。     

老年2型糖尿病C肽变化的初探

对111例2型糖尿病(DM)患者进行空腹及餐后2hC肽水平测定,按不同年龄及病程分组进行比较.结果≥70岁组餐后2hC肽/空腹C肽比值明显低于＜70岁组,P＜0.05.单一空腹C肽和餐后2hC肽水平,均可见≥10年组明显低于＜10年组,P＜0.05.餐后2hC肽/空腹C肽比值未见明显统计学差异.结论70岁以上老年2型DM患者餐后胰岛素分泌高峰有明显的减低,病程10年以上者β细胞功能显示进一步降低.     

血清三抗体及C肽检测对成人迟发型糖尿病诊断的意义

目的探讨谷氨酸脱羧酶抗体（GADA）、胰岛素自身抗体（IAA）、胰岛细胞抗体（ICA）和血清C肽检测对诊断成年迟发型糖尿病（LADA）的意义。方法对初诊为糖尿病的N0例患者进行血清GADA、IAA、ICA以及空腹和餐后C肽检测，并对抗体阳性及阴性患者的C肽水平进行比较。结果三抗体检测为阳性者58例，GADA阳性者21例（36．2％），ICA阳性者14例（24．1％），IAA阳性者6例（10．3％），双抗体阳性者15例（25．9％），三抗体阳性者2例，（3．4％）。抗体阳性患者的空腹和餐后C肽明显低于抗体阴性患者，双抗体和三抗体阳性患者的空腹和餐后C肽低于单抗体阳性患者，差异有统计学意义（P〈0．05）。结论三抗体检测有助于在初诊糖尿病患者中筛选LADA，对其早期诊断具有重要意义。     

C肽变化与糖尿病周围神经病变的关系

目的探讨C肽变化与糖尿病周围神经病变（DPN）的关系。方法检测120例2型糖尿病（T2DM）患者的空腹血糖、餐后2h血糖、糖化血红蛋白、空腹C肽（FC—P）、餐后2hC肽（2hC—P）、尿微量白蛋白及神经传导速度（NCN）。根据患者有无DPN分为DPN组及非DPN组,按病程分为〈5a组、5-10a组、〉10a组,比较各组C肽水平。结果DPN组2hC—P明显低于非DPN组,且不同病程组两两比较均有统计学差异（P均〈0．05）。与正常者比较,DPN组运动、感觉纤维异常者的NCV及2hC—P均明显降低（P〈0．05或〈0．01）。结论2hC—P水平与T2DM患者的DPN密切相关。     

老年2型糖尿病C肽变化的初探

对111例2型糖尿病（DM）患进行空腹及餐后2hC肽水平测定，按不同年龄及病程分组进行比较。结果：≥70岁组餐后2hC肽／空腹C肽比值明显低于＜70岁组，P＜0．05。单一空腹C肽和餐后2hC肽水平，均可见≥10年组明显低于＜10年组，P＜0．05。餐后2hC肽／空腹C肽比值未见明显统计学差异。结论：70岁以上老年2型DM患餐后胰岛素分泌高峰有明显的减低，病程10年以上β细胞功能显示进一步降低。     

老年2型糖尿病标准脂餐后胰岛素及C肽的分析

对30例老年2型糖尿病患者及10例健康老年人空腹及标准脂肪餐后2h，4h，6h，8h胰岛素及C肽水平进行同步测定并加以分析。结果各时点胰岛素，老年糖尿病组高于对照组，空腹，餐后6h及8h统计学上有显著差异（P〈0．05）：老年糖尿病组各时点C肽水平低于对照组，有显著差异（P〈0．05）。结论老年2型糖尿病患者标准脂肪餐后胰岛素及C肽分泌试验出现分离现象，即出现高胰岛素低C肽现象，为今后2型糖尿病患者使用C肽治疗奠定理论基础。     

二甲双胍治疗老年2型糖尿病患者中加用阿卡波糖的临床观察

30例老年T2DM患者口服最大耐受剂量二甲双胍至少2个月,加用阿卡波糖100mg,治疗3个月。观察治疗前后空腹血糖（FBG）、餐后血糖（PBG）、糖化血红蛋白（HbA1c）、总胆固醇（TC）、甘油三酯（TG）、体重指数（BMI）及空腹C肽（FCP）、餐后2hC肽（PCP）的差异。结果治疗前后比较,FBG、PBG、HbA1c及TG下降（P均〈0.05）,PCP较治疗前上升（P〈0.05）。结论阿卡波糖可有效地降低老年T2DM患者的血糖,改善血脂水平和胰岛β细胞功能,且发生低血糖的风险低。     

中老年LADA与2型糖尿病的临床比较

目的探讨中老年成年人迟发性自身免疫性糖尿病(LADA)的临床特征,找出临床筛查线索.方法对住院的60例谷氨酸脱羧酶抗体(GADA)阳性中老年LADA患者和同期住院的120例GADA阴性的中老年2型糖尿病(T2DM)患者的临床资料进行比较.结果中老年LADA患者较中老年T2DM患者有较短的从发病到需住院治疗的病程,较高的磺豚类降糖药继发失效(SUF)患者比例,较短的SUF时间,较低的体重指数(BMI),较低的代谢综合征(MS)患者比例,较低的空腹、餐后1h和2h血清C肽水平,P＜0.05.而两组在有典型三多一少症状、糖尿病家族史、并发其他自身免疫疾病的患者比例及平均HbA1c等均无统计学差异,P＞0.05.结论对住院的初诊为T2DM的中老年患者,容易SUF、低BMI、非MS、低C肽水平是筛查LADA的临床线索,确诊LADA则需测定胰岛自身抗体.     

在2型糖尿病治疗中甘精胰岛素联合瑞格列奈的应用安全性分析

目的 对比研究甘精胰岛素联合瑞格列奈治疗2型糖尿病的临床效果及安全性。方法 回顾性分析2021年10月—2022年9月于山东省邹平市人民医院进行治疗的90例2型糖尿病患者为研究对象,依据治疗措施的不同平均分为对照组（45例）与观察组（45例）,对照组应用甘精胰岛素展开治疗,观察组应用甘精胰岛素+瑞格列奈联合治疗,对比分析两组临床效果、不良反应发生率、血糖（FBG、2 hPG与HbA1c）、空腹C肽以及餐后2 h C肽。结果 治疗前,两组FBG、2 hPG、HbA1c、空腹C肽以及餐后2 h C肽比较,差异无统计学意义（P>0.05）。治疗后,相较于对照组,观察组的FBG、2 hPG、HbA1c较低,空腹C肽以及餐后2 h C肽较高,差异有统计学意义（P<0.05）。观察组临床效果高于对照组,不良反应发生率低于对照组,差异有统计学意义（P<0.05）。结论 以甘精胰岛素+阿卡波糖联合治疗2型糖尿病患者可显著提升临床效果,降低不良反应发生率,降低血糖指标,提升空腹C肽以及餐后2 h C肽水平。     

谷氨酸脱羧酶抗体水平对两种成人隐匿性自身免疫糖尿病亚型的识别

目的　探讨不同谷氨酸脱羧酶 (GAD65)抗体水平的成人隐匿性自身免疫糖尿病(LADA)患者的临床特点 ,了解LADA患者中是否存在两种不同的亚型。方法　对 750例临床初诊为2型糖尿病 (T2DM)患者及其志愿参加进一步研究的 2 95例患者用放免法进行GAD65抗体 (GADA)测定 ,绘制GADA指数的频数分布图 ,进行各组间临床特点的比较。结果　 (1 )GADA在初诊 2型糖尿病中的阳性率为 9 7% ,高抗体水平者 (GADA指数≥ 0 5)占 2 8%。 (2 )LADA患者中抗体滴度较低(GADA指数 0 0 5～ <0 5)者在胰岛功能 (空腹C肽 50 0pmol/L比 50 4pmol/L ,P >0 0 5)、高血压比例(48 7%比 42 5 % ,P >0 0 5)及体重指数 (2 3 2kg/m2 比 2 2 3kg/m2 ,P >0 0 5)等方面与 2型糖尿病相似 ,即为LADA 2型 ;抗体滴度较高者 (GADA指数≥ 0 5)具有起病年龄小、胰岛功能差、更多使用胰岛素治疗 (P <0 0 1 )等特点 ,临床表现更类似经典的 1型糖尿病 ,即为LADA 1型。结论　LADA患者具有异质性 ,存在LADA 1和LADA 2两种亚型 ,LADA 1型的临床特点更类似于经典的 1型糖尿病     

The clinical characteristics of latent autoimmune diabetes in adults and its relation with chronic complications in metabolically poor controlled Turkish patients with Type 2 diabetes mellitus

It has been reported that some patients with Type 2 diabetes mellitus (DM) have latent autoimmune diabetes in adults (LADA) and may show different clinical characteristics than those with Type 2 DM. We aimed to determine the ratio and clinical features of LADA in patients with diagnosed initially as Type 2 DM. We measured glutamic acid decarboxylase antibodies (GADA) in 54 patients, diagnosed clinically with Type 2 DM. Of 54 patients, 17 (31%) were GADA positive. GADA-positive patients had significantly earlier diabetes onset age (P<.001), lower BMI (P<.05), and lower serum C-peptide value (P<.001) than did those who were GADA negative. A higher proportion of the GADA-positive patients were receiving insulin therapy (P<.01). With respect to the duration of DM, familial history of DM, and the levels of blood pressures, fasting plasma glucose, and HbA1c, there was no difference between the two groups. Nephropathy and retinopathy were more frequent in GADA-positive than in GADA-negative patients. The prevalence of neuropathy was comparable between the two groups. GADA was negatively associated with BMI, C-peptide levels, and diabetes-onset age, but positively related to retinopathy, nephropathy, and insulin treatment. This study indicated that the important portion of the patients who were initially diagnosed as Type 2 DM may have LADA. In Type 2 diabetic patients who have lower BMI and diagnosis of diabetes in relatively younger age, the possibility of LADA should be taken into consideration. The higher prevalence of nephropathy and retinopathy in GADA-positive patients also suggests the importance of early diagnosis and strict metabolic control in these patients.     

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.     

Insulin and glucagon secretion in patients with slowly progressing autoimmune diabetes (LADA)

To metabolically characterize patients with slowly progressing autoimmune diabetes (LADA) of short duration we measured insulin, C peptide, and glucagon responses to glucose and arginine at three blood glucose levels (fasting and 14 and 28 mmol/L) in 11 patients with LADA, 11 patients with type 2 diabetes, and 14 healthy control subjects matched for age and body mass index. The acute insulin response to arginine was impaired in LADA vs. type 2 diabetes at all glucose levels, with the greatest impairment in the maximally stimulated insulin concentrations (P<0.04). In contrast, beta-cell sensitivity to glucose was unaltered in LADA and type 2 diabetes. The glucagon concentrations were elevated in both LADA and type 2 diabetic patients compared with healthy control subjects (P<0.02), but did not differ between the diabetic groups. In conclusion, patients with LADA share insulin resistance with type 2 diabetic patients, but display a more severe defect in maximally stimulated beta-cell capacity than patients with type 2 diabetes.     

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.     

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.     

不同胰岛自身抗体阳性1型糖尿病临床特征分析

目的探讨单独或合并锌转运体8自身抗体(ZnT8A)、谷氨酸脱羧酶抗体(GADA)及蛋白酪氨酸磷酸酶抗体(IA-2A)阳性患者的1型糖尿病(T1DM)患者临床特征。方法采用放射配体检测法检测中南大学湘雅二医院1999—2009年收治的539例T1DM患者的ZnT8A、GADA及IA-2A,并将其分成三个亚组进行比较。结果(1)单一ZnT8A阳性组较抗体阴性组病程更长,胰岛素用量更大,收缩压更低,合并代谢综合征比例更少。单一ZnT8A阳性组较单一GADA阳性组BMI、WHR及空腹C肽值更高(P<0.05),而糖化血红蛋白水平更低(P<0.05);(2)多个抗体阳性组起病年龄显著低于抗体阴性组(P<0.05);1个抗体阳性患者的空腹C肽及餐后2 h C肽显著低于抗体阴性组(P<0.05);3个抗体阳性患者较1个抗体阳性患者的起病年龄更小(P<0.01),BMI更低(P<0.05),病程更短(P<0.05)。(3)合并任意两种抗体阳性中"GADA阳性与IA-2A阳性"组餐后C肽最低(P<0.01),空腹C肽也较低,但差异无统计学意义(P>0.05)。结论单独或合并ZnT8A,GADA及IA-2A的T1DM临床特征分析对临床具有重要的指导意义。     

Der latent autoimmune Diabetes im Erwachsenenalter (LADA): Eine Sonderform des Diabetes?

Latent autoimmune diabetes in adults (LADA) is often clinically diagnosed as a type 2 diabetes that leads however more quickly to insulin deficiency. Immunologically it is characterized by diabetes type 1-associated autoantibodies against glutamic decarboxylase (GADA) or islet cells (ICA). In Europe about 10% of type 2 diabetes patients are positive for GADA/ICA and classified therefore with LADA. This means in Germany about two times more patients with LADA exist than with type 1 diabetes. Several observations suggest interpreting LADA as a separate form of diabetes, linking both ends of the type 1 and type 2 spectrum. According the guidelines of the German Diabetes Association, LADA is allocated to type 1 diabetes, though it differs in that the insulin requirement is mostly not necessary at diagnosis, in contrast to type 1 diabetes. At the moment no evidence-based recommendations regarding therapy are available, since very few clinical studies address this point. The current therapeutic recommendation is optimization of blood glucose and concomitant risk factors, though many prefer insulin therapy due to the similarities with type 1 diabetes.     

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.     

成人迟发自身免疫性糖尿病与1、2型糖尿病临床表现的比较

目的：探讨成人迟发自身免疫性糖尿病（LADA）的临床特征，方法：评价谷氨酸脱羧酶抗体（GADA）、胰岛细胞抗体（ICA）阳性LADA患者各种急性和慢性并发症的患病率，并与速发型1和2型糖尿病（DM）相比较。结果：LADA患者的年龄，BMI，空腹及餐后C肽水平介于1和2型DM之间，LADA组29％患者有酮症，再次酮症的频率与1型相似，但至首次酮症的时间较长。视网膜病变患病率为19．5％，与1型DM相似；白内障患病率为48．8％，与2型DM相似；冠心病患病率与2型DM相似，高血压患病率介于1、2型DM之间。LADA组有微量白蛋白尿者较少，3组间显性肾病变。周围神经病变和高脂血症的患病率相似。结论：LADA的临床特征及急性和慢性并发症的患病率与1和2型DM有所不同。