Latent autoimmune diabetes of adulthood (LADA): An often misdiagnosed type of diabetes mellitus

Purpose: The purpose of this article is to raise awareness about a frequently misdiagnosed form of diabetes, latent autoimmune diabetes of adulthood (LADA), to describe its clinical and epidemiological characteristics, and to compare them to those of the more common and widely known types of diabetes, type 1 diabetes mellitus (DM) and type 2 DM.
Data sources: A review of the pertinent literature describing the features of LADA from 2000–2007 is summarized.
Conclusions: LADA is a rather common and often underrecognized form of diabetes whose clinical presentation falls somewhere between that of type 1 DM and type 2 DM. From a pathophysiological perspective, it is more closely related to type 1 DM, and some have even used the term type 1.5 diabetes to refer to it; however, it is most often misdiagnosed and treated as type 2 DM.
Implications for practice: Nurse practitioners (NPs) should always consider alternate diagnoses when patients with newly or previously identified adult-onset diabetes mellitus do not fit the traditional stereotype of type 2 DM (i.e., overweight with signs of insulin resistance and a significant family history of diabetes). Statistically, strong consideration must be given to the diagnosis of LADA, especially in those who are of normal weight, show little evidence of insulin resistance, and have hardly any family history of diabetes. Knowing the patient's exact diabetes type can give the NP a much greater understanding of the natural history of the patient's disease, the changes that may occur as the patient ages, and how to optimally manage their diabetes to minimize complications. Likewise, when a patient is correctly diagnosed, they can be empowered to manage their diabetes with the appropriate therapies.     

The Role of Adiponectin as a Compensatory Mediator for the Primary Secretory Defect in Latent Autoimmune Diabetes in Adults

Background

Increased adiposity in patients with newly diagnosed type 2 diabetes mellitus (DM), as well as in patients who do not have DM, affects the regulation of insulin sensitivity and the metabolic effects of adiponectin.

Objective

The goal of this study was to investigate the relationship between plasma adiponectin levels and obesity in patients developing DM mainly due to an early decline in β-cell function.

Methods

We studied 29 patients with latent autoimmune diabetes in adults (LADA), 38 patients with type 1 DM, and 55 healthy volunteers.

Results

Plasma adiponectin levels, adjusted for body mass index (BMI), were higher in patients with type 1 DM than in controls (P < 0.001) and similar to those in patients with LADA (P = 0.464). Plasma adiponectin levels were higher in LADA patients compared with controls (P < 0.001). In LADA patients, plasma adiponectin levels, adjusted for BMI, correlated significantly with insulin resistance (β coefficient, –6.453 [2.772]; P = 0.028). Interestingly, this relationship in LADA patients was significant in more overweight patients (β coefficient, –7.142 [3.249]; P = 0.048) but not in leaner patients (P = 0.571), a finding that was not confirmed through the results in the controls (P = 0.520 and P = 0.992, respectively).

Conclusions

In patients with LADA, increases in plasma adiponectin levels, after adjustment for BMI, could act as a mediator for improvement in insulin sensitivity and thus compensate for the primary secretory defect. This effect seems more profound in more overweight subjects than in leaner subjects.     

A clinical screening tool identifies autoimmune diabetes in adults

OBJECTIVE: Latent autoimmune diabetes in adults (LADA) is defined as adult-onset diabetes with circulating islet antibodies but not requiring insulin therapy initially. Diagnosing LADA has treatment implications because of the high risk of progression to insulin dependency. Currently, there are no recommendations for islet antibody testing in adult-onset diabetes. In this study, we aimed to develop a clinical screening tool to identify adults at high risk of LADA who require islet antibody testing. RESEARCH DESIGN AND METHODS: Subjects with LADA (n = 102, GAD antibody [GADA]+) and type 2 diabetes (n = 111, GADA-) (aged 30-75 years) were interviewed retrospectively. The clinical features documented were age of onset, acute symptoms of hyperglycemia, BMI, and personal and family history of autoimmune disease. Any clinical feature that was significantly more frequent in LADA was designated as a distinguishing clinical feature. In each subject, a "LADA clinical risk score," based on the total number of distinguishing features, was calculated. A prospective study of adults with newly diagnosed diabetes (n = 130) was used to determine whether the LADA clinical risk score could identify LADA. RESULTS: In the retrospective study, five clinical features were more frequent in LADA compared with type 2 diabetes at diagnosis: 1) age of onset <50 years (P < 0.0001), 2) acute symptoms (P < 0.0001), 3) BMI <25 kg/m2 (P = 0.0004), 4) personal history of autoimmune disease (P = 0.011), and 5) family history of autoimmune disease (P = 0.024). In the prospective study, the presence of at least two of these distinguishing clinical features (LADA clinical risk score > or =2) had a 90% sensitivity and 71% specificity for identifying LADA and a negative predictive value for a LADA clinical risk score < or =1 of 99%. CONCLUSIONS: At least two distinguishing clinical features are found in a majority of patients with LADA at diagnosis and can be used to identify adults with diabetes at higher risk for LADA.     

The Diagnosis and Management of Atypical Types of Diabetes

In addition to type 1 and type 2 diabetes, there are other types of diabetes that can present diagnostic challenges for nurse practitioners. This article reviews the more unusual types of diabetes, including latent autoimmune diabetes in adults, maturity-onset diabetes of the young, and type 3c diabetes. To promote optimal patient outcomes, nurse practitioners should be aware of evidence-based management principles for less common types of diabetes.     

羧基肽酶-H抗体阳性成人隐匿性自身免疫糖尿病患者的TNF-α、IL-12，IL-18、IFN-γ水平观察

目的观察羧基肽酶-H抗体（CPH—Ab）阳性成人隐匿性自身免疫糖尿病（LADA）患者的肿瘤坏死因子α（TNF—α）、白介素-12（IL-12）、白介素-18（IL-18）、干扰素-γ（IFN-γ）的水平。方法时13例LADA患者、20例2型糖尿病（T2DM）患者及加例健康对照者，采用双抗夹心酶联免疫吸附法（ELISA）检测TNF—α、IL—12、IL—18、IFN-γ的含量。结果LADA组各项指标水平与T2DM组和对照组相比均有升高（均P〈0．05）；T2DM组TNF—α、IFN-γ水平较对照组升高（P〈0．05）；T2DM组IL—12、IL—18水平与对照组比较无明显差异（P〉0.05）。结论LADA患者体内活跃着细胞介导的细胞免疫反应，LADA诊断采取直接检测针对胰岛细胞自身抗原的细胞免疫反应要优于检测针对同一抗原的自身抗体水平。     

Crucial points at diagnosis. Type 2 diabetes or slow type 1 diabetes

Two major types of diabetes have been recognized since the late 1930s. However, in recent times there have been major changes in classification and understanding of these types, including improved knowledge of maturity-onset diabetes in the young, with the identification of mutations relating to impaired insulin secretion and the recognition of slow-onset type 1 diabetes in adults now designated as latent autoimmune diabetes in adults (LADA). A major problem area in diabetes classification concerns cases of slowly progressive forms of type 1 and type 2 diabetes, particularly in adults aged 25-50 years. This is a more contemporary problem because cases of type 2 diabetes are presenting at an increasingly younger age. In the landmark U.K. Prospective Diabetes Study of type 2 diabetes, islet cell antibodies (ICAs) and antibodies to glutamic acid decarboxylase (anti-GAD) were measured at diagnosis in 3,672 patients. The overall proportion with ICAs was 6%, and anti-GADs was 10%. These subjects clearly had type 1 diabetes or LADA by both phenotypic and genotypic features. The presence of auto antibodies correlated particularly with a younger age and phenotypic features consistent with type 1 diabetes (e.g., early age at diagnosis, lower BMI, and reduced beta-cell function). Overall, of patients requiring insulin by 6 years, 38% were anti-GAD+ at baseline compared with 5.3% of those not on insulin at 6 years. Antibodies to GAD indicate an underlying autoimmune process and have a high positive predictive value for type 1 diabetes and future insulin dependency in adults.     

Section I. Oral Symptoms and Signs of Nutritional Deficiency

PREVIEW

A number of patients with poor glycemic control receive the diagnosis of type 2 diabetes despite the fact that they do not exhibit some of the traditional characteristics of the disease, such as obesity. A more accurate diagnosis for many of these patients is latent autoimmune diabetes of adulthood (LADA). In this article, Dr Nabhan and coauthors describe features that LADA has in common with type 1 and type 2 diabetes, as well as those that distinguish LADA from these more widely recognized forms of diabetes. The authors also describe the pathogenesis of the disease, potential complications, and treatment options.     

酒精性慢性胰腺炎继发糖尿病的临床特点分析

目的：探讨酒精性慢性胰腺炎继发的糖尿病与成年隐匿性自身免疫糖尿病（ LADA）及2型糖尿病（T2DM）患者的临床资料、代谢指标及生化检查的差异。方法对2005~2014年于本院内分泌和消化科住院治疗的符合WHO糖尿病诊断标准的酒精性慢性胰腺炎继发的糖尿病患者24例,LADA患者30例及T2DM患者40例的病史,临床资料进行回顾性分析和比较。结果酒精性慢性胰腺炎继发糖尿病患者的体重指数（BMI）与LADA患者的差异无显著性,明显低于T2DM患者。酒精性慢性胰腺炎继发糖尿病的空腹C肽值要高于LADA组患者,低于T2DM患者,总胆固醇（ CHO）和低密度脂蛋白胆固醇（ LDL-C）水平低于LADA及T2DM患者,外周血管病变的发生低于T2DM患者。结论长期大量饮酒患者出现糖尿病,应注意鉴别有无酒精性慢性胰腺炎继发的糖尿病,该类患者体型偏瘦,CHO及LDL-C低于LADA及T2DM患者,易出现低血糖,但是无酮症倾向。     

The role of C-peptide levels in screening for latent autoimmune diabetes in adults

Early detection of latent autoimmune diabetes in adults (LADA) is important in that the earlier insulin therapy is initiated, the greater the preservation of pancreatic beta cells. This study assessed whether a random C-peptide level is an effective screening test for LADA. Random C-peptide levels were measured in 39 subjects with LADA and 39 subjects with type 2 diabetes who were matched for age, race, gender, and duration of diabetes. LADA was definitively diagnosed by the presence of antiglutamic acid decarboxylase antibodies. The mean C-peptide level in the LADA group was 1.0 +/- 0.2 ng/mL and 5.1 +/- 0.4 ng/mL in the group with type 2 diabetes. Only 1 LADA subject had a C-peptide level above the normal range, and all subjects with type 2 diabetes had a C-peptide level within or above the normal range. LADA can be ruled out in adult-onset diabetes by the presence of elevated C-peptide. The more expensive testing for anti-GAD antibodies to definitively diagnose LADA should be reserved for patients who on screening have a low or normal random C-peptide level.     

Similar genetic features and different islet cell autoantibody pattern of latent autoimmune diabetes in adults (LADA) compared with adult-onset type 1 diabetes with rapid progression

OBJECTIVE: To compare the clinical parameters, C-peptide levels, pattern of islet cell-specific autoantibodies, and prevalence of predisposing genotypes in subjects with latent autoimmune diabetes in adults (LADA) and those with adult-onset type 1 diabetes with rapid progression. RESEARCH DESIGN AND METHODS: We evaluated the clinical parameters, C-peptide levels, and islet cell-specific autoantibodies in 54 LADA, 57 adult-onset type 1 diabetic, and 190 type 2 diabetic patients. Islet cell autoantibodies were also compared between subgroups of newly diagnosed patients with LADA and those with newly diagnosed adult-onset and childhood-onset type 1 diabetes. The genetic study was performed in subjects with LADA and those with adult-onset type 1 diabetes in comparison with a control population. RESULTS: There were no differences in the clinical parameters between LADA and adult-onset type 1 diabetes. Patients with LADA had lower BMI (P < 0.0001), waist-to-hip ratio (0.0029), total cholesterol (P = 0.001), and triglycerides (P = 0.001); higher HDL cholesterol levels (P < 0.0001); and lower prevalence of hypertension (P = 0.0028) compared with patients with type 2 diabetes. C-peptide levels were similar at onset (P = 0.403) but decreased less rapidly in LADA than in adult-onset type 1 diabetes (P = 0.0253). Single-autoantibody positivity was more often seen in LADA than in type 1 diabetes (P = 0.0001). The prevalence of predisposing HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 genotypes and the DR4-DQB1*0302 haplotype were increased in both LADA and adult-onset type 1 diabetic subjects compared with the control population. There were no differences in the frequencies of these risk alleles and haplotypes between the two patient groups. CONCLUSIONS: Subjects with LADA had clinical characteristics similar to those with adult-onset type 1 diabetes with rapid progression. C-peptide levels did not differ at onset but decreased less rapidly in LADA. Patients with LADA rather had single islet cell-specific autoantibody positivity. The prevalence of HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 risk alleles and the DR4-DQB1*0302 high-risk haplotype did not differ in the two forms of autoimmune diabetes.     

Latent Autoimmune Diabetes of Adults (LADA) Is Likely to Represent a Mixed Population of Autoimmune (Type 1) and Nonautoimmune (Type 2) Diabetes

Latent autoimmune diabetes of adults (LADA) is typically defined as a new diabetes diagnosis after 35 years of age, presenting with clinical features of type 2 diabetes, in whom a type 1 diabetes–associated islet autoantibody is detected. Identifying autoimmune diabetes is important since the prognosis and optimal therapy differ. However, the existing LADA definition identifies a group with clinical and genetic features intermediate between typical type 1 and type 2 diabetes. It is unclear whether this is due to 1) true autoimmune diabetes with a milder phenotype at older onset ages that initially appears similar to type 2 diabetes but later requires insulin, 2) a disease syndrome where the pathophysiologies of type 1 and type 2 diabetes are both present in each patient, or 3) a heterogeneous group resulting from difficulties in classification. Herein, we suggest that difficulties in classification are a major component resulting from defining LADA using a diagnostic test—islet autoantibody measurement—with imperfect specificity applied in low-prevalence populations. This yields a heterogeneous group of true positives (autoimmune type 1 diabetes) and false positives (nonautoimmune type 2 diabetes). For clinicians, this means that islet autoantibody testing should not be undertaken in patients who do not have clinical features suggestive of autoimmune diabetes: in an adult without clinical features of type 1 diabetes, it is likely that a single positive antibody will represent a false-positive result. This is in contrast to patients with features suggestive of type 1 diabetes, where false-positive results will be rare. For researchers, this means that current definitions of LADA are not appropriate for the study of autoimmune diabetes in later life. Approaches that increase test specificity, or prior likelihood of autoimmune diabetes, are needed to avoid inclusion of participants who have nonautoimmune (type 2) diabetes. Improved classification will allow improved assignment of prognosis and therapy as well as an improved cohort in which to analyze and better understand the detailed pathophysiological components acting at onset and during disease progression in late-onset autoimmune diabetes.     

LADA患者外周血Th17细胞相关因子表达水平及临床意义

目的检测成人隐匿性糖尿病（LADA）患者外周血Th17细胞因子的表达水平,探讨其参与LADA的发病机制的作用。方法收集LADA组30例,2型糖尿病（T2DM）组35例,健康对照组30例,采用酶联免疫吸附（ELISA）法检测 Th17细胞相关因子IL-17、IL-6、IL-23的表达水平及Treg细胞相关因子IL-2、IL-10的表达水平,并采用Pearson直线相关分析其与LADA患者各项代谢参数的相关性。结果与健康对照组比较,LADA组与T2DM 组 Th17细胞相关因子IL-17,IL-6,IL-23含量均升高（P＜0．05）,且T2DM 组较LADA组升高更为显著（P＜0．05）;LADA组与T2DM组Treg细胞相关因子IL-2,IL-10含量均下降（P＜0．05）,且T2DM 组下降更为显著（P＜0．05）;Th17／Treg细胞相关因子与LADA患者各项代谢参数相关性分析显示：IL-17、IL-23与空腹血糖均呈明显正相关,与空腹C肽呈负相关,IL-10与空腹C肽呈正相关,而IL-6、IL-2则与各项参数无明显相关性。结论 LADA患者体内存在Th17细胞因子的高表达,其表达的炎症性因子可能参与了LADA发病机制。     

Latent Autoimmune Diabetes in Adults

Latent autoimmune diabetes in adults (LADA) is a genetically linked, autoimmune form of type 1 diabetes mellitus that is commonly seen after age 30 in patients who often have a normal body mass index without overt signs of metabolic syndrome. They have positive circulating antibodies reflecting the autoimmune nature of beta cell destruction, and they frequently are poorly controlled on oral anti-diabetic agents. Because they are older when first symptomatic, they are often diagnosed with type 2 diabetes. However, it is important to recognize patients with LADA because they often progress quickly to insulin dependence. The characteristics of LADA, pathogenesis, diagnostic work-up, complications, and evidence-based management of the disease will be reviewed. Implications for practice will be included.     

Variable number of tandem repeats of the insulin gene determines susceptibility to latent autoimmune diabetes in adults.

BACKGROUND: The different clinical presentations of latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus may be the result of susceptibility genes in determining the mode of onset. We analyzed the 5' polymorphisms of the insulin mini-satellite region (INS), a variable number of tandem repeats (VNTR) [repeat units; RU]. We evaluated the association of the different INS-VNTR alleles in patient susceptibility to LADA autoimmune diabetes. To our knowledge, this constitutes the first study of this kind performed in a Caucasian population. METHODS: From an group of 160 Argentinean patients previously characterized as having LADA, we selected 44 patients who presented with humoral autoimmunity for genotyping and compared them to 88 patients with type 1 diabetes and 138 healthy individuals. The INS-VNTR allele classes were determined by Southern blotting (class I: 21-44RU; class III: 138-159RU). Subjects with class I alleles were further studied using PCR amplification to determine the exact length of the alleles (short 1S: 22-37RU; medium 1M: 38-41RU; large 1L: 42-43RU). Allelic and genotype frequencies were estimated by chi(2) tests for independence with 2 x 2 contingency tables and the relative risks (RR) were determined using GraphPad InStat software. RESULTS: We observed differential associations among the class I alleles when comparing patients with LADA (80.6%) and type 1 diabetes (81.3%) with the controls (70%; p < 0.005). This increase was largely due to the high frequency of the 1S/S genotype (63.6% LADA vs 37% controls, with a p-value of 0.0019 [p1]; 53.4% type 1 diabetes vs 37% controls, with a p-value of 0.0149 [p2]). Remarkably, all LADA patients genotyped as class I homozygous had the shorter (S) class I allele (100%). Differences in the overall 1S distribution were observed: in LADA the 94.4% of the alleles were equal to or smaller than 35RU, while in patients with type 1 diabetes it was 78.3% and in controls 74.1%. Moreover, the relative risks associated with the 1S/S genotype for patients with LADA showed a substantial increase with respect to those with type 1 diabetes (52%) when we compare them to the controls (1S/S LADA/control, 2.282 [RR1] vs type 1 diabetes/control, 1.497 [RR2]). CONCLUSION: The presence of the 1S allele could be considered a risk factor in LADA patients, as previously reported for type 1 diabetes. The class I INS-VNTR allele in LADA increases genetic susceptibility to disease development.     

Metabolic syndrome and autoimmune diabetes: action LADA 3

OBJECTIVE—The purpose of this study was to estimate whether prevalence of metabolic syndrome in adult European diabetic patients is associated with type of diabetes.RESEARCH DESIGN AND METHODS—A consecutive series of patients attending hospital-based diabetes clinics were assessed for the frequency of metabolic syndrome and compared with population-based control subjects as part of the Action LADA study. In total, 2,011 subjects (aged 30–70 years) were studied, including 1,247 patients with recent-onset type 2 diabetes without glutamic acid decarboxylase autoantibodies (GADAs), 117 non–insulin-requiring patients with GADAs who had not received insulin therapy for at least 6 months after diagnosis (designated latent autoimmune diabetes of adults [LADA]), 288 type 1 diabetic patients, and 359 normal subjects.RESULTS—Frequency of metabolic syndrome was significantly different in patients with type 1 diabetes (31.9%) and LADA (41.9%) (P = 0.015) and in both conditions was less frequent than in type 2 diabetic patients (88.8%) (P < 0.0001 for each). Eliminating glucose as a variable, the prevalence of metabolic syndrome was similar in patients with autoimmune diabetes (type 1 diabetes and/or LADA) (17.3%) and control subjects (23.7%) but remained more common in type 2 diabetic patients (47.8%) (P = 0.001 for all groups). In both type 1 diabetic patients and those with LADA, individual components of metabolic syndrome were similar but less common than in type 2 diabetic patients (P < 0.0001 for each).CONCLUSIONS—The prevalence of metabolic syndrome is significantly higher in type 2 diabetic patients than in patients with LADA or adults with type 1 diabetes. Excluding glucose as a variable, metabolic syndrome is not more prevalent in patients with autoimmune diabetes than in control subjects. Metabolic syndrome is not a characteristic of autoimmune diabetes.Type 1 diabetes is an autoimmune disease in which insulin deficiency results from immune-mediated destruction of insulin-secreting islet cells. The majority of patients with type 1 diabetes have autoantibodies in their peripheral blood, and these autoantibodies can predict the disease. Autoimmune diabetes, as characterized by these autoantibodies, such as glutamic acid decarboxylase autoantibodies (GADAs), is the most prevalent form of diabetes in children and also occurs in a proportion of patients who initially present with adult-onset non–insulin-requiring diabetes, also called latent adult-onset autoimmune diabetes (LADA) (1).Because glucose disposal and blood glucose are determined by both insulin secretion and insulin action, it follows that insulin sensitivity could be important in the pathogenesis of autoimmune diabetes. Insulin sensitivity has not been studied in detail in autoimmune diabetes, although studies suggest that its loss may occur in established disease as well as in the pre-diabetic phase (2–5). Loss of insulin sensitivity is difficult to assess epidemiologically but is reflected in the cluster of metabolically related cardiovascular risk factors that together comprise the metabolic syndrome and include altered glucose levels, central obesity, dyslipidemia, and hypertension. Several groups, including the International Diabetes Federation (IDF) and the National Cholesterol Education Program (NCEP), with Adult Treatment Panel III (6), have proposed their own definitions for the metabolic syndrome.LADA is clearly distinct from type 2 diabetes, in that LADA is associated with histocompatability (HLA) genes, diabetes-associated autoantibodies, reduced insulin secretion, no need for insulin therapy initially after diagnosis, and less prevalence of metabolic syndrome (7–9). The key question is whether LADA is distinct from type 1 diabetes (1,10,11), that is, whether LADA is one end of a rainbow of pathophysiological variations encompassing autoimmune diabetes with a frequency of metabolic syndrome similar to that of childhood-onset type 1 diabetes or whether LADA is a distinct form of autoimmune diabetes that resembles type 2 diabetes, showing evidence of insulin resistance with a high frequency of metabolic syndrome (1). Therefore, the aim of this study was to test whether individuals with type 2 diabetes and autoimmune diabetes (incorporating type 1 diabetes and LADA) have a higher frequency of metabolic syndrome than normal subjects, and our hypothesis was that they would.     

胰岛自身抗体联合生化指标检测在成人隐匿性糖尿病诊断中的临床意义

目的 通过对血清谷氨酸脱羧酶抗体(GAD)、胰岛细胞抗体(ICA)、血糖、糖化血红蛋白(HbAlc)的联合检测,探讨临床诊断为2型糖尿病(T2DM)患者中发现成人隐匿性自身免疫性糖尿病(LADA)的意义和诊断价值.方法 测定349例T2DM患者的血清GAD、ICA、C肽、血糖及HbAlc,检测出其中的LADA患者,并与T2DM患者的各项指标进行比较分析.结果 349例T2DM患者中共确诊为LADA患者27例(7.74％).LADA患者空腹C肽及餐后2hC肽分别为(0.31±0.21)、(0.90±0.22)μg/L,较T2DM患者的空腹C肽(1.23±0.85)μg/L和餐后2hC肽(3.45±2.96)μg/L明显降低,差异有统计学意义(P＜0.05).LADA患者空腹血糖及HbAlc分别为(12.15±25.01 )mmol/L、(10.12±2.78)％,较T2DM患者的(9.45±13.07)mmol/L、(8.04±2.95)％明显升高,差异有统计学意义(P＜0.05).结论 各项指标联合胰岛β细胞自身抗体检测可提高LADA患者的检出率,有助于LADA的早期诊断.     

Characteristics of the Gut Microbiota and Metabolism in Patients With Latent Autoimmune Diabetes in Adults: A Case-Control Study

OBJECTIVEType 1 and type 2 diabetes are associated with gut dysbiosis. However, the relationship between the gut microbiota and latent autoimmune diabetes in adults (LADA), sharing clinical and metabolic features with classic type 1 and type 2 diabetes, remains unclear. Here, we used a multiomics approach to identify the characteristics of the gut microbiota and metabolic profiles in patients with LADA.RESEARCH DESIGN AND METHODSThis age- and sex-matched case-control study included 30 patients with LADA, 29 patients with classic type 1 diabetes, 31 patients with type 2 diabetes, and 29 healthy individuals. The gut microbiota profiles were identified through the 16S rRNA gene, and fecal and serum metabolites were measured through untargeted liquid chromatography-mass spectrometry.RESULTSPatients with LADA had a significantly different structure and composition of the gut microbiota and their metabolites as well as a severe deficiency of short-chain fatty acid–producing bacteria. The gut microbiota structure of the patients with LADA was more similar to that of patients with type 1 diabetes who were positive for GAD antibody. We identified seven serum metabolite modules and eight fecal metabolite modules that differed between the LADA group and the other groups.CONCLUSIONSThe characteristic gut microbiota and related metabolites of patients with LADA are associated with autoantibodies, glucose metabolism, islet function, and inflammatory factors, which may contribute to the pathogenesis of LADA. Future longitudinal studies should explore whether modulating the gut microbiota and related metabolites can alter the natural course of autoimmune diabetes in the quest for new therapeutics.     

成人隐匿性自身免疫糖尿病与2型糖尿病的血管并发症比较

目的 探讨成人隐匿性自身免疫糖尿病(LADA)与2型糖尿病(T2DM)血管并发症(包括微血管病变及相关大血管疾病)的差异.方法 比较203例LADA患者与年龄、性别、糖尿病病程及糖尿病家族史匹配的T2DM患者24 h尿白蛋白、眼底检查或荧光造影、心电图、肌电图、血压、血脂、体质指数、空腹血糖、餐后2h血糖、糖化血红蛋白、C肽等方面的差异.结果 ①微血管病变:LADA患者较T2DM患者糖尿病肾病的患病率高(39.9%vs.28.6%,P＜0.05),而2组间视网膜病变和周围神经病变的患病率差异无统计学意义(P＞0.05).②大血管病变:LADA患者较T2DM患者高血压、代谢综合征的患病率低(38.9%vs.55.7%,P＜0.01;33.0%vs.45.3%,P＜0.01),2组间冠心病及脑梗死的患病率差异无统计学意义(均P＞0.05).结论LADA患者与T2DM患者血管并发症存在差异:LADA患者糖尿病肾病患病率较高,而高血压和代谢综合征的患病率较低.     

Chronic complications in patients with slowly progressing autoimmune type 1 diabetes (LADA).

OBJECTIVE: To study the prevalence of chronic diabetic complications in patients with the slowly progressing autoimmune form of type 1 diabetes, also referred to as latent autoimmune diabetes in adults (LADA). RESEARCH DESIGN AND METHODS: We evaluated factors associated with chronic diabetic complications in 59 patients with GAD antibodies (GADAs) and age at onset of diabetes >35 years and in 59 GADA-negative type 2 diabetic patients. The prevalence of chronic complications was further compared with the prevalence in 111 type 1 diabetic patients. RESULTS: The LADA patients had lower BMI (P = 0.04), waist-to-hip ratio (P = 0.02 for men and P = 0.03 for women), and fasting C-peptide concentrations (P<0.001) higher HDL2 concentrations (P = 0.04), and less hypertension (58 vs. 75%, P = 0.05) than the type 2 diabetic patients. These differences were even more marked in patients with short disease duration. The prevalence of retinopathy (51 vs. 56%), neuropathy (29 vs. 27%), and microalbuminuria (27 vs. 29%) did not differ between the groups. The type 1 diabetic patients had lower prevalence of neuropathy (13%, P = 0.02) and higher prevalence of retinopathy (76%, P = 0.002) compared with the other groups. Neither the prevalence of coronary heart disease (CHD) (56 vs. 58%) nor cardiovascular mortality (7.4 vs. 12.4%, P = 0.2) significantly differed between the LADA and type 2 diabetic patients. In a multiple logistic regression analysis, glycemic control was associated with CHD (P = 0.02) in the LADA group but not in the type 2 diabetic group. CONCLUSIONS: Glycemic control is a stronger risk factor for cardiovascular disease in LADA patients than in patients with type 2 diabetes. This could be related to the lower prevalence of the metabolic syndrome seen in the former.