latent autoimmune diabetes

潜伏性自身免疫性糖尿病
  • 文章类型: Multicenter Study
    目的:本研究调查了1型糖尿病(T1D)和隐匿性自身免疫性糖尿病(LAD)患者胰岛素瘤相关2自身抗体(IA-2A)和锌转运体8自身抗体(ZnT8A)的分布以及自身抗体与临床特征和HLA-DR-DQ基因的相关性。
    方法:这项横断面研究招募了来自中国46家医院的17,536名糖尿病患者。共有189例T1D患者和58例IA-2A阳性的LAD患者,126例T1D患者和86例LAD患者的ZnT8A阳性,并选择231例2型糖尿病(T2D)患者进行胰岛自身抗体评估,临床表型,HLA-DR-DQ基因频率。
    结果:IA-2A在T1D和LAD患者中呈双峰分布。低IA-2A滴度LAD患者的空腹C肽(FCP)较低(p<0.01),较低的餐后C肽(PCP)(p<0.001),与T2D患者相比,血红蛋白A1c(HbA1c)水平更高(p<0.05)。IA-2A滴度高的LAD患者比IA-2A滴度低的LAD患者年轻(p<0.05)。低IA-2A滴度T1D患者FCP较低(p<0.01),PCP降低(p<0.01),HbA1c水平高于高IA-2A滴度LAD患者(p<0.05)。HLA-DR-DQ遗传分析表明,IA-2A阳性患者的易感HLA单倍型频率高于T2D患者(p<0.001)。具有高ZnT8A滴度LAD的患者具有较低的FCP(p=0.045),下PCP(p=0.023),与低ZnT8A滴度LAD患者相比,更高的HbA1c水平(p=0.009)和更高的总易感单倍型频率(p<0.001)。
    结论:IA-2A在T1D和LAD患者中呈双峰分布,IA-2A的存在可以证明LAD的部分临床特征。ZnT8A滴度对LAD患者胰岛功能有一定的预测价值。
    This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies\' association with clinical characteristics and HLA-DR-DQ genes.
    This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency.
    IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD.
    IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.
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  • 文章类型: Journal Article
    目的:描述儿童和青少年患有青少年隐匿性自身免疫性糖尿病(LADY),并评估将个体分类为LADY的心血管(CV)危险因素的效用。
    方法:分析了来自25,520名前瞻性糖尿病随访登记处糖尿病患者Verlaufsdokumentation(DPV)的个体(诊断年龄<18岁)的数据。LADY定义为糖尿病诊断后≥1种胰岛自身抗体(iAb+)阳性且无胰岛素间期≥6个月。将LADYs与立即需要胰岛素的iAb+个体进行比较(“免疫证实”1型糖尿病,T1DM),iAbs-/Ins-个体(“经典”T2DM)和临床定义为T2DM的个体(iAbs未测量)。
    结果:LADYs(n=299)的临床特征介于T1DM(n=24,932)和T2DM(iAb-/Ins-,n=152)或疑似T2DM(iAB未测量,n=137)。然而,根据他们的临床诊断对LADYs进行分层显示出两个不同的群体,与T1DM或T2DM非常相似。特别是,CV风险概况,精确的动脉高血压和血脂异常的患病率,与分类为T1DM的LADYs相比,临床分类为T2DM的LADYs明显更高,与“经典”T2DM没有区别。
    结论:就CV风险而言,将患有糖尿病的儿童和青少年分类为LADYs没有额外的益处.相反,临床诊断似乎可以更好地将个体分配到适当的风险组,以增加CV风险.
    To characterize children and adolescents with latent autoimmune diabetes of the young (LADY), and to assess the utility of classifying individuals as LADYs regarding their cardiovascular (CV) risk factors.
    Data from 25,520 individuals (age at diagnosis <18 years) of the Prospective Diabetes Follow-up Registry Diabetes-Patienten Verlaufsdokumentation (DPV) were analyzed. LADY was defined as positivity of ≥one islet autoantibody (iAb+) and an insulin-free interval of ≥6 months upon diabetes diagnosis. LADYs were compared to iAb+ individuals immediately requiring insulin (\"immunologically confirmed\" type 1 diabetes, T1DM), iAb-/Ins- individuals (\"classical\" T2DM) and to those clinically defined as T2DM (iAbs not measured).
    Clinical characteristics of LADYs (n = 299) fell in between those with T1DM (n = 24,932) and T2DM (iAb-/Ins-, n = 152) or suspected T2DM (iAB not measured, n = 137). Stratifying LADYs according to their clinical diagnosis however revealed two distinct populations, highly resembling either T1DM or T2DM. Particularly, CV risk profile, precisely prevalence rates of arterial hypertension and dyslipidemia, was significantly higher in LADYs clinically classified as T2DM compared to LADYs classified as T1DM, and did not differ from those with \"classical\" T2DM.
    In terms of CV risk, classifying children and adolescents with diabetes as LADYs provides no additional benefit. Instead, clinical diagnosis seems to better assign individuals to appropriate risk groups for increased CV risk profiles.
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  • 文章类型: Case Reports
    Charcot神经关节病是与神经病相关的进行性关节病。在糖尿病患者中,Charcot神经关节病主要影响足部。在目前的情况下,我们在1例成人隐匿性自身免疫性糖尿病患者中,罕见出现Charcot膝关节和足部神经关节病.病人,他们可能由于不适当的体育锻炼而患上了这种疾病,采用全膝关节置换术治疗。
    Charcot neuroarthropathy is a progressive arthropathy associated with neuropathy. In patients with diabetes, Charcot neuroarthropathy mostly affects the foot. In the present case, we encountered a rare presentation of Charcot neuroarthropathy of the knee and foot in a patient with latent autoimmune diabetes in adults. The patient, who may have developed the disease as a result of inappropriate physical exercise, was treated with total knee arthroplasty.
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  • 文章类型: Journal Article
    LADA是一种常见的糖尿病形式,被描述为1型和2型糖尿病之间的混合物。了解基因和环境因素在LADA发展中的相互作用是未来预防疾病的核心。这篇综述旨在综合与LADA风险相关的生活方式因素的文献,并讨论它们与遗传易感性的潜在相互作用。
    目前对LADA环境风险因素的了解主要基于斯堪的纳维亚人口的观测数据。越来越多的证据表明,生活方式因素促进2型糖尿病,如肥胖,镇静,低出生体重和吸烟,与LADA的风险有关。孟德尔随机化研究的数据支持LADA与肥胖之间的联系,低出生体重和吸烟是因果关系。有限的证据表明,包括食用红肉在内的饮食因素,咖啡和甜味饮料可能会增加风险,而酒精和omega-3脂肪酸的消费可能会降低风险。几个生活方式因素,包括吸烟和肥胖,似乎与自身免疫相关的人类白细胞抗原基因相互作用,在暴露于这两种因素的人群中,对疾病风险的影响要大得多。
    现有研究表明,改变生活方式有可能预防LADA,特别是对于患有疾病的高风险个体,如具有遗传易感性的个体。然而,对LADA风险因素的研究有限,确认是有保证的,许多因素仍有待探索,并且有必要进行干预研究来评估因果关系。
    LADA is a common form of diabetes described as a mix between type 1 and type 2 diabetes. Understanding of how genes and environmental factors interact in the development of LADA is central for future efforts to prevent the disease. This review aims to synthesize the literature on lifestyle factors linked to LADA risk and discuss their potential interaction with genetic susceptibility.
    Current knowledge on environmental risk factors for LADA is primarily based on observational data from Scandinavian populations. Increasing evidence suggest that lifestyle factors promoting type 2 diabetes such as obesity, sedentariness, low birth weight and smoking, is implicated in the risk of LADA. Data from mendelian randomization studies support that the link between LADA and obesity, low birth weight and smoking is causal. Limited evidence indicates that dietary factors including consumption of red meat, coffee and sweetened beverages may increase the risk while consumption of alcohol and omega-3 fatty acids may reduce the risk. Several lifestyle factors, including smoking and obesity, seem to interact with human leukocyte antigen genes associated with autoimmunity, conferring much stronger effects on disease risk among those exposed to both factors.
    Available studies suggest that lifestyle modification has the potential for prevention of LADA, particularly for individuals with high risk of disease such as those with genetic susceptibility. Research into risk factors of LADA is however limited, confirmations are warranted, many factors remain to be explored, and there is a need for intervention studies to assess causality.
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  • 文章类型: Case Reports
    1型糖尿病是一种慢性疾病,其特征是由于胰岛素缺乏引起的代谢异常和高血糖。由于胰腺β细胞的自身免疫破坏,胰岛素产生迅速下降。1型糖尿病的部分缓解(蜜月期)在新诊断的1型糖尿病的儿童和年轻人中很常见。存在β细胞功能的暂时恢复,使得很少或不需要外源性胰岛素。在需要静脉内胰岛素和随后的皮下胰岛素治疗的紧急入院后不久停止胰岛素治疗可能对患者和医疗保健提供者都是可怕的。在此期间,受影响的患者需要教育和支持。本报告描述了一名28岁男子的病例,该男子向急诊科就诊,具有1型糖尿病和糖尿病酮症酸中毒的特征。他接受了静脉输液和静脉胰岛素治疗,并采用皮下胰岛素方案出院。尽管对几种类型的胰岛细胞自身抗体检测呈阳性,患者能够在诊断后3个月内停止胰岛素治疗.患者保持自我启动的低碳水化合物饮食,有规律的减重锻炼,和正常的葡萄糖水平,而不需要胰岛素治疗。1型糖尿病的蜜月期,隐匿性自身免疫性糖尿病,和酮症倾向的2型糖尿病被讨论为重要的鉴别诊断。
    Type 1 diabetes is a chronic disease characterized by abnormal metabolism and hyperglycemia due to insulin deficiency. There is a rapid decline in insulin production due to autoimmune destruction of the pancreatic beta cells. Partial remission (honeymoon phase) of type 1 diabetes is common in children and young adults with newly diagnosed type 1 diabetes. There is temporary restoration of beta cell function such that little or no exogenous insulin is required. Stopping insulin therapy soon after an emergency admission requiring intravenous insulin and subsequent subcutaneous insulin therapy can be frightening for both patient and healthcare provider. Affected patients require education and support during this period. This report describes a case of a 28-year-old man who presented to the emergency department with features of type 1 diabetes and diabetic ketoacidosis. He was treated with intravenous fluids and intravenous insulin and discharged on a subcutaneous insulin regimen. Despite testing positive for several types of islet cell autoantibodies, the patient was able to stop insulin therapy within three months of diagnosis. The patient maintained a self-initiated low-carbohydrate diet, regular weight-reducing exercise, and normal glucose levels without the need for insulin therapy. The honeymoon phase of type 1 diabetes, latent autoimmune diabetes, and ketosis-prone type 2 diabetes are discussed as important differential diagnoses.
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  • 文章类型: Case Reports
    成人隐匿性自身免疫性糖尿病(LADA)是一种始于成年期(通常在35岁之后)的自身免疫性糖尿病;其主要特征是存在与糖尿病相关的自身抗体(最常见的是抗谷氨酸脱羧酶的自身抗体),导致朗格汉斯岛的逐渐破坏。这是一种异质性疾病,具有1型糖尿病和2型糖尿病常见的临床和实验室表现。我们报道了一个71岁的男性,两年前被诊断患有2型糖尿病,口服抗糖尿病治疗控制不佳,并在第三年恶化。他在两个二级亲属(侄子)中有2型糖尿病家族史。在体格检查中未发现病理结果。他的体重指数为23kg/m2,糖化血红蛋白为10.6%。实验室检查显示低基础C肽(<0.1ng/mL)和谷氨酸脱羧酶抗体阳性,LADA的诊断得到了证实。这个案例突出了意识到这种疾病的重要性,尤其是在先前诊断为2型糖尿病的患者中,这些患者仍然不受饮食和口服降糖药的控制。LADA经常与2型糖尿病混淆,因此,管理往往不足。早期诊断和治疗对于延缓疾病进展至关重要。
    Latent autoimmune diabetes of adults (LADA) is a type of autoimmune diabetes that begins in adulthood (usually after the age of 35 years); its main feature is the presence of diabetes-associated autoantibodies (most often autoantibody against glutamic acid decarboxylase), which leads to progressive destruction of the islets of Langerhans. This is a heterogeneous condition that presents with clinical and laboratory manifestations common to type 1 diabetes and type 2 diabetes. We report a case of a 71-year-old man diagnosed with type 2 diabetes two years ago, poorly controlled with oral antidiabetic therapy, and worsening in the third year. He had a positive family history of type 2 diabetes in two second-degree relatives (nephews). No pathologic findings at the physical examination were found. His body mass index was 23 kg/m2 and glycated hemoglobin was 10.6%. Laboratory workup revealed low basal C-peptide (<0.1 ng/mL) and positive glutamic acid decarboxylase antibodies, and the LADA diagnosis was confirmed. This case highlights the importance of being aware of this disease, especially in patients previously diagnosed with type 2 diabetes who remain uncontrolled with diet and oral hypoglycemic agents. LADA is often confused with type 2 diabetes, and therefore, the management is frequently inadequate. An early diagnosis and treatment are crucial to delaying disease progression.
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  • 文章类型: Journal Article
    Type 1 and type 2 diabetes mellitus incur an increased risk of fracture, with a generally higher risk among individuals with type 1 diabetes. The fracture risk among individuals with latent autoimmune diabetes of adulthood (LADA) is not known. The present cohort study aimed to estimate the risk of hip and forearm fracture among individuals with LADA, alongside type 1 and type 2 diabetes, using data from the second survey of the Trøndelag Health Study (HUNT2) in 1995-97. All inhabitants aged 20 years or older (N = 92,936) were invited to attend, of whom 65,234 (70%) participated. A total of 1972 (3%) reported to have diabetes; 1399 were found to have type 2 diabetes, 144 to have LADA, and 138 to have type 1 diabetes. All participants were followed prospectively with respect to hip- and forearm fractures by linkage to the local fracture registry. During a median follow-up of 16.2 years, 2695 persons with hip fractures and 3533 persons with forearm fractures were identified. There was an increased risk of hip fracture in women with type 2 diabetes (HR = 1.51, 95% CI 1.24-1.85) and LADA (HR = 2.15, 95% CI 1.25-3.72), whereas women with type 1 diabetes did not have a significantly increased risk (HR = 2.13, 95% CI 0.89-5.14). Among men, only LADA was associated with an increased risk of hip fracture (HR = 2.69, 95% CI 1.34-5.41). There was no statistically significant association between any of the diabetes types and forearm fracture. In women with type 2 diabetes, the highest risks of hip fracture were observed among those with highest HbA1c level at baseline, longest time since diagnosis, and most visual and movement impairment. We found that individuals with LADA had an increased risk of hip fracture similar to that previously reported for individuals with type 1 diabetes, and no increased risk of forearm fracture.
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  • 文章类型: Case Reports
    低血糖表现出相对典型的症状。然而,当它像胰岛素自身免疫综合征一样自发发生时,很难在实验室进行预定的生化检查。该研究介绍了一名31岁的白人女性,其反复的低血糖症状是进一步诊断的原因。最终结果显示胰岛素自身抗体和谷氨酸脱羧酶自身抗体的阳性测试。因此,不仅证实了低血糖的潜在原因,而且证实了成人隐匿性自身免疫性糖尿病典型的主动自身免疫过程.结论自身免疫性低血糖可能是与成人糖尿病和糖尿病前期相关的自身免疫过程的一部分。
    Hypoglycemia presents relatively typical symptoms. However, when it occurs spontaneously - like in insulin autoimmune syndrome - it is difficult to perform scheduled biochemical tests at the laboratory. The study presents the case of a 31-year-old Caucasian female whose recurrent hypoglycemia symptoms were the reason for further diagnostics. The final results revealed a positive test for insulin autoantibody and glutamic acid decarboxylase autoantibody. Therefore, not only the potential causes of hypoglycemia but also an active autoimmune process typical for latent autoimmune diabetes in adults were confirmed. It was concluded that autoimmune hypoglycemia can be a part of the autoimmune process associated with diabetes and pre-diabetes in adults.
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  • 文章类型: Journal Article
    探讨自身抗体(锌转运蛋白8自身抗体(ZnT8A),胰岛素抗体(IAAs),谷氨酸脱羧酶自身抗体(GAD65),阳性自身抗体的类型和阳性自身抗体的数量与LADA(成人隐匿性自身免疫性糖尿病)患者的血糖和血脂状况的关系,并将其与2型糖尿病(T2DM)患者的代谢状况进行比较。
    在德黑兰招募了263名T2DM患者进行这项横断面研究,伊朗。患者的数据包括完整的病史,GAD65,ZnT8A,IAA和常规代谢实验室检查。使用ELISA试剂盒进行自身抗体的测定。使用单变量和多变量回归分析评估糖尿病患者自身抗体与血糖和血脂之间的关联。
    我们的研究表明,在263名T2DM患者中,29例(11%)IAAs阳性,9(3.4%)对于ZnT8A,GAD65为12(4.6%)。六名(2.3%)的患者具有三重阳性抗体。阳性结果的患者更年轻,体重指数(BMI)较低,c-肽,甘油三酯,低密度脂蛋白(LDL),高密度脂蛋白(HDL),HbA1c和空腹血糖(FBG)水平。三重抗体阳性与C肽水平降低显着相关,甘油三酯,FBG,和HbA1c与三阴性抗体相比。
    对于任一自身抗体(GAD65、ZnT8和IAA)具有LADA阳性的患者呈现较差的血糖控制。这些自身抗体的测量可有助于区分这些患者并有助于早期控制血糖谱。
    To explores the prevalence of autoantibodies (zinc transporter 8 autoantibodies (ZnT8A), antibodies to insulin (IAAs), glutamic acid decarboxylase autoantibody (GAD65)), the relation of the type of positive autoantibody and the number of positive autoantibodies with the glycemic and lipid profile of the patients with LADA (Latent Autoimmune Diabetes in Adults) and compares it to the metabolic profile of patients presenting with type 2 diabetes (T2DM).
    263 patients with T2DM were recruited for this cross-sectional study in Tehran, Iran. Data from patients included complete medical history, GAD65, ZnT8A, IAA and routine metabolic laboratory workup. Assay for autoantibodies were conducted using ELISA kits. The association between autoantibodies and glycemic and lipid profile of patients with diabetes was assessed using univariate and multivariate regression analysis.
    Our study revealed that among 263 patients with T2DM, 29 (11%) cases were positive for IAAs, 9 (3.4%) for ZnT8A, and 12 (4.6%) for GAD65. Six (2.3%) of the patients had triple positive antibodies. Patients with positive results were younger, had lower body mass index (BMI), c-peptide, triglyceride, low-density lipoprotein (LDL), and higher high-density lipoprotein (HDL), HbA1c and fasting blood glucose (FBG) levels. Triple antibody positivity was significantly associated with lower levels of C-Peptide, Triglycerides, FBG, and HbA1c compared to triple negative antibodies.
    Patients with LADA positive for either of the autoantibodies (GAD65, ZnT8 and IAA) presented with worse glycemic control. Measurement of these autoantibodies can assist in discrimination of these patients and help with earlier control of glycemic profile.
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  • 文章类型: Journal Article
    Latent autoimmune diabetes in adults (LADA) is characterized by the presence of islet autoantibodies and initial insulin independence, which can lead to misdiagnosis of type 2 diabetes (T2D). As such, understanding the genetic etiology of LADA could aid in more accurate diagnosis. However, there is ongoing debate regarding the exact definition of LADA, so understanding its impact in different populations when contrasted with type 1 diabetes (T1D) and T2D is one potential strategy to gain insight into its etiology. Unfortunately, the lack of consistent and thorough autoantibody screening around the world has hampered well-powered genetic studies of LADA. This review highlights recent genetic and epidemiological studies of LADA in diverse populations as well as the importance of autoantibody screening in facilitating future research.
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