Maturity-onset diabetes of the young type 9 or latent autoimmune diabetes in adults:A case report and review of literature

BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic genetic disease often clinically misdiagnosed as type 1 or type 2 diabetes.MODY type 9(MODY9)is a rare subtype caused by mutations in the PAX4 gene.Currently,there are limited reports on PAX4-MODY,and its clinical characteristics and treatments are still unclear.In this report,we described a Chinese patient with high autoimmune antibodies,hyperglycemia and a site mutation in the PAX4 gene.CASE SUMMARY A 42-year-old obese woman suffered diabetes ketoacidosis after consuming substantial amounts of beverages.She had never had diabetes before,and no one in her family had it.However,her autoantibody tested positive,and she managed her blood glucose within the normal range for 6 mo through lifestyle interventions.Later,her blood glucose gradually increased.Next-generation sequencing and Sanger sequencing were performed on her family.The results revealed that she and her mother had a heterozygous mutation in the PAX4 gene(c.314G>A,p.R105H),but her daughter did not.The patient is currently taking liraglutide(1.8 mg/d),and her blood glucose levels are under control.Previous cases were retrieved from PubMed to investigate the relationship between PAX4 gene mutations and diabetes.CONCLUSION We reported the first case of a PAX4 gene heterozygous mutation site(c.314G>A,p.R105H),which does not appear pathogenic to MODY9 but may facilitate the progression of latent autoimmune diabetes in adults.

WJD 5^(th) Anniversary Special Issues(3): Type 1 diabetes Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

Ever since its first appearance among the multiple forms of diabetes,latent autoimmune diabetes in adults(LADA),has been the focus of endless discussions concerning mainly its existence as a special type of diabetes.In this mini-review,through browsing important peer-reviewed publications,(original articles and reviews),we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity.A unique combination of immunological,clinical and metabolic characteristics has been identified in this group of patients,namely persistent islet cell antibodies,high frequency of thyroid and gastric autoimmunity,DR3 and DR4 human leukocyte antigen haplotypes,progressive loss of beta cells,adult disease onset,normal weight,defective glycaemic control,and without tendency to ketoacidosis.Although anthropomorphic measurements are useful as a first line screening,the detection of C-peptide levels and the presence of glutamic acid decarboxylase(GAD)autoantibodies is undoubtedly the sine qua non condi-tion for a confirmatory LADA diagnosis.In point of fact,GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied.Nevertheless,the lack of diagnostic criteria and guidelines still puzzle the physicians,who struggle between early diagnosis and correct timing for insulin treatment.

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.

Latent autoimmune diabetes in adults:A distinct but heterogeneous clinical entity

Latent autoimmune diabetes in adults(LADA) accounts for 2-12 of all cases of diabetes.Patients are typically diagnosed after 35 years of age and are often misdiagnosed as type Ⅱ Diabetes Mellitus(DM).Glycemic control is initially achieved with sulfonylureas but patients eventually become insulin dependent more rapidly than with type Ⅱ DM patients.Although they have a type Ⅱ DM phenotype,patients have circulating beta(β) cell autoantibodies,a hallmark of type Ⅰ DM.Alternative terms that have been used to describe this condition include type 1.5 diabetes,latent type Ⅰ diabetes,slowly progressive Insulin Dependent Diabetes Mellitus,or youth onset diabetes of maturity.With regards to its autoimmune basis and rapid requirement for insulin,it has been suggested that LADA is a slowly progressive form of type Ⅰ DM.However,recent work has revealed genetic and immunological differences between LADA and type Ⅰ DM.The heterogeneity of LADA has also led to the proposal of criteria for its diagnosis by the Immunology of Diabetes Society.Although many workers have advocated a clinically oriented approach for screening of LADA,there are no universally accepted criteria for autoantibody testing in adult onset diabetes.Following recent advances in immunomodulatory therapies in type Ⅰ DM,the same strategy is being explored in LADA.This review deals with the contribution of the genetic,immunological and metabolic components involved in the pathophysiology of LADA and recent approaches in screening of this distinct but heterogeneous clinical entity.

Latent Autoimmune Diabetes in Adults Complicated by Persistent Isolated Glucosuria in the Absence of Hyperglycemia

Latent autoimmune diabetes in adults (LADA) is an autoimmune diabetes of adult-onset with the presence of diabetes associated autoantibodies. Familial renal glucosuria (FRG) is an inherited renal tubular disorder that causes persistent isolated glucosuria in the absence of hyperglycemia. We report a novel case of LADA and certain FRG. A 44-year-old man was admitted to our hospital for uncontrolled diabetes. Before admission, he had never suffered from diabetic coma and showed an improvement in HbA1c only with diet therapy. His HbA1c was 11.9% (107 mmol/mol), and anti-glutamic acid decarboxylase antibody was 13.0 U/mL. A glucagon stimulation test showed the decrease of insulin secretion: plasma C-peptide (CPR) 0 min, 0.69 ng/mL;CPR 6 min, 0.90 ng/mL. Analysis of genomic DNA revealed a novel heterozygous mutation in the SGLT2 coding gene, SLC5A2 (c.875G >A, p.Cys292Tyr), which was assessed as probably damaging with a score of 0.998 (sensitivity: 0.27;specificity: 0.99) by an in silico analysis. Therefore, he was diagnosed with LADA and certain FRG. He has not shown any symptoms and his HbA1c improved to 6.4% (46 mmol/mol) three months after the introduction of insulin therapy. Our case clearly implies the clinical effectiveness of SGLT2 inhibition in patients with LADA.

Newly diagnosed diabetes mellitus patients presenting with proliferative diabetic retinopathy as an initial sign

AIM: To investigate the clinical features of newly diagnosed diabetes mellitus(NDM) patients showing proliferative diabetic retinopathy(PDR) as an initial sign. ·METHODS: As a retrospective case series,the medical records of a total of four hundred and thirty-two patients who underwent a vitrectomy due to PDR were reviewed to find the subjects. Of 432 patients,six cases of NDM patients showing PDR as an initial sign were included and analyzed with their systemic and ocular features. Main outcome measures: the systemic features and ocular features [preoperative and postoperative best corrected visual acuity(BCVA),intraoperative findings]. ·RESULTS: The mean onset age of visual symptoms was 36.3 years old. The mean serum insulin and C-peptide titer was below the normal range. The mean fasting plasma glucose was 178mg/dL and the mean postprandial 2h plasma glucose was 306mg/dL. The mean HbA1c at diagnosis was 11.02%. In all cases,an acute progressive fibrovascular proliferation was observed. Intraoperative retinal tears were found in three cases of six. The mean preoperative BCVA was +0.67 ± 0.58 logMAR and the mean BCVA at postoperative 6 months was +0.20±0.30 logMAR. ·CONCLUSION: All patients were considered to have latent autoimmune diabetes in adults(LADA). A rapid deterioration of kidney function as well as poor diabetic control status at diagnosis was observed in all six cases. The ocular features of the patients showed acute progressive fibrovascular proliferation and relatively favorable postoperative visual acuity.

Association of stiff-person syndrome with autoimmune endocrine diseases

BACKGROUND Stiff-person syndrome(SPS)and its subtype,stiff limb syndrome(SLS),are rare neurological disorders characterized by progressive muscular rigidity and spasms.Glutamic acid decarboxylase(GAD)is the enzyme that catalyzes the production ofγ-aminobutyric acid(GABA),a major inhibitory neurotransmitter of the central nervous system.SPS is an autoimmune disease triggered by antiglutamic acid decarboxylase antibody(anti-GAD Ab).Clinically,anti-GAD Ab is associated with SPS,type 1 diabetes mellitus(T1DM),and other autoimmune diseases.AIM To investigate the link of autoimmune endocrine disorders with anti-GAD Ab in SPS subjects.METHODS This retrospective study was approved by the Institutional Review Board of Chang Gung Memorial Hospital,Taiwan.We collected the patients with SPS from January 2001 to June 2018.By reviewing 14 patients from medical records,we analyzed the clinical findings with coexisting autoimmune diseases,particularly diabetes mellitus and thyroid disease,which are associated with anti-GAD antibody titers or other immunological test results(anti-thyroid peroxidase and anti-nuclear antibodies).We also evaluated malignancies,major complications,and reported treatment to improve symptoms.Anti-GAD antibodies were measured using radioimmunoassay and enzyme-linked immunosorbent assay(ELISA).The cut-off values of these tests are<1 U/mL and<5 U/mL,respectively.RESULTS The median age of all patients was 39.3(range,28.0-54.0)years with a median follow-up period of 6.0(2.7-13.3)years.Five(35.7%)patients were female;twelve(85.7%)were diagnosed with classic SPS and two(14.3%)with SLS.The median age of onset of symptoms was 35.0(26.0-56.0)years with a median follow-up duration of 9.0(2.1-14.9)years in the classic SPS group;the SLS group had a median age of onset of 46.7 years and a shorter follow-up duration of 4.3 years.Among nine classic SPS patients who underwent the anti-GAD Ab test,three were anti-GAD Ab seropositive and each of these three patients also had T1DM,latent autoimmune diabetes in adults,and autoimmune thyroid disease,respectively.In contrast,other rare autoimmune diseases co-existed in six anti-GAD Ab seronegative SPS patients.None of the SLS patients had additional autoimmune diseases.CONCLUSION While typical clinical symptoms are crucial for the diagnosis of SPS,the presence of anti-GAD autoantibody may consolidate the diagnosis and predict the association with other autoimmune diseases.

Latent autoimmune diabetes in adults： evidences for diabetes spectrum？

In 1936, Himworth first investigated insulin resistance and non-insulin resistance in diabetes. Then the terminology ＂type 1 diabetes （T1D）＂ and ＂type 2 diabetes （T2D）＂ were first used in 1951. In 1999, the World Health Organization （WHO） announced the classification of diabetes： as we all known, T1D and T2D.1 This classification is widely accepted and used. However, in clinical practice, it is quite often to find some patients cannot be simply diagnosed as T1D or T2D.

Diagnostic role of antibodies to glutamic acid decarboxylase in latent autoimmune diabetes mellitus in adults

Objective To investigate the diagnostic role of antibodies to glutamic acid decarboxylase (GAD 65 Ab) in latent autoimmune diabetes of adults (LADA) and the frequency of GAD Ab in Chinese patients initially diagnosed as non insulin dependent diabetes mellitus (NIDDM) Methods Forty five control subjects and 195 consecutive inpatients initially classified as NIDDM with ≥35 years of age at onset and nonketotic history for >6 months after diagnosis, were recruited In vitro transcripted and translated recombinant human 35 S GAD 65 was used in radioligand assay of GAD Ab Results The overall prevalence of GAD 65 Ab was 14 8% (29/195) in NIDDM patients and 2 2% (1/45) in control subjects, respectively Of the 29 GAD 65 Ab positive patients, 17 (58 6%) were insulin deficient while 12 (41 4%) were non insulin deficient The prevalence of GAD 65 Ab in NIDDM group with age of <40 years at diabetes onset, ketotic history, body mass index (BMI) <21 kg/m 2, were significantly higher than that of corresponding control diabetic subgroups (2 5, 4 1 and 3 2 times, respectively) The sex, duration, symptoms of polyphagia, polydipsia, polyuria and weight loss at onset of the disease were not related to the prevalence of GAD 65 Ab positivity Conclusions In China, patients initially diagnosed as NIDDM may in many cases suffer from LADA Testing by GAD 65 Ab may be of assistance to identifying LADA at the earliest stage of disease

成人隐匿性自身免疫性糖尿病的生物学标志物研究进展

成人隐匿性自身免疫性糖尿病(LADA)是一种成年起病的自身免疫性糖尿病,大部分LADA患者在发病初期易被误诊为1型或2型糖尿病。对LADA患者进行非标准化的管理不利于保护其残余胰岛β细胞功能,而且会增加早期并发症的发生风险和病死率。文章从基因、转录、蛋白质、代谢组学、炎症等方面综述可能预测LADA的生物学标志物,旨在为早期识别并诊断LADA,以及延缓LADA患者胰岛β细胞功能衰竭提供参考。

25羟维生素D3及T淋巴细胞亚群变化与成人隐匿性自身免疫性糖尿病患者胰岛功能的关系

目的:观察不同滴度谷氨酸脱羧酶抗体(GADA)成人隐匿性自身免疫性糖尿病(LADA)患者25羟维生素D3[25(OH)D3]水平及T淋巴细胞亚群的变化,探讨其与胰岛β细胞功能的关系。方法:在成人糖尿病(DM)患者中筛查获得GADA阳性患者,根据GADA滴度水平分为低滴度组和高滴度组,对照组为普通2型糖尿病(T2DM)患者。检测空腹血糖(FBG)、血脂、肝肾功能,糖化血红蛋白(HbA1c)、空腹血清C肽(FCP)、25(OH)D3和T淋巴细胞亚群(CD3^(+)、CD4^(+)和CD8^(+))。计算胰岛素抵抗指数[Homa-IR(CP)]和胰岛功能指数[Homa-islet(CP)]。结果:与T2DM组比较,高滴度组体重指数(BMI)、25(OH)D3水平、FCP、餐后2 h C肽(2 hCP)、Homa-IR(CP)和Homa-islet(CP)均降低,差异有统计学意义(P<0.05),同时合并有较低的总胆固醇(TC)、三酰甘油(TG)、尿酸(UA)水平,差异有统计学意义(P<0.05);低滴度组也表现出BMI、25(OH)D3水平、FCP、2 hCP、Homa-IR(CP)和Homa-islet(CP)降低,伴低TC水平,差异有统计学意义(P<0.05)。高滴度组CD4^(+)/CD8^(+)T比值高于低滴度组,差异有统计学意义(P<0.05),LADA患者CD4^(+)/CD8^(+)比值与GADA滴度呈正相关(r=0.37,P<0.01),25(OH)D3水平与Homa-islet(CP)呈正相关(r=0.32,P=0.02)。结论:低25(OH)D3水平及T淋巴细胞亚群比例失衡与胰岛β细胞功能损伤有关并参与LADA病程的进展。

成人隐匿性自身免疫性糖尿病早期血浆SERPING1的变化及意义

目的：检测成人隐匿性自身免疫性糖尿病（LADA）患者早期血浆中C1酯酶抑制物（SERPING1）的水平，探讨其临床意义。方法检测LADA组患者SERPING1水平，并与1型糖尿病（T1DM）组、2型糖尿病（T2DM）组和正常对照组进行比较。对SERPING1与年龄、病程、糖化血红蛋白（HbA1c）、空腹血糖（FPG）、餐后2 h血糖（2 hPG）、空腹C肽（FCP）、餐后2 hC肽（2hCP）进行相关性分析和多元逐步回归分析。采用受试者工作特征曲线（ROC曲线）分析SERPING1早期预测LADA的效果。结果 LADA组血浆SERPING1水平（325.00±177;72.70）明显高于T2DM组（296.45±177;71.20）和正常对照组（292.04±177;58.46），差异有统计学意义；SERPING1与FCP呈负相关（rs=-0.680），与HbA1c、FPG、2 hPG呈正相关（rs分别为0.550、0.547、0.476，P＜0.05），与年龄、病程、2 hCP等其他指标无明显相关性。FCP可进入回归方程（P＜0.05），是血浆SERPING1的主要影响因素。ROC曲线下面积（AUC）为0.613（P＜0.05），95%CI为0.514~0.712。SERPING1早期预测LADA的最佳临界值为289.71 mg/L，灵敏度69%，特异度48%。结论 SERPING1结合其他指标可能成为早期预测LADA的有效指标，帮助临床早期鉴别LADA与T2DM。

胰岛自身抗体定量检测在糖尿病分型诊断中的应用价值

目的探讨抗酪氨酸磷酸酶抗体(IA2)、抗胰岛细胞抗体(ICA)、抗胰岛素抗体(IAA)和抗谷氨酸脱羧酶抗体(GADA)及生化指标在糖尿病分型诊断中的应用价值。方法选取2019年9月至2021年6月广州中医药大学第一附属医院收治的195例糖尿病患者作为研究对象。研究对象中2型糖尿病(T2DM)患者150例(T2DM组)、成人隐匿性自身免疫性糖尿病(LADA)患者45例(LADA组),另同时选取体检健康者50例作为对照组。各组分别进行4种胰岛自身抗体、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、糖化血清蛋白(GA)、果糖胺(FRA)、空腹胰岛素、空腹C肽、甘油三酯(TG)、总胆固醇(CHOL)检测并对其结果进行比较分析。结果LADA组的ICA、IAA、GADA阳性率均高于对照组和T2DM组,差异有统计学意义(P<0.05)。LADA组GADA、ICA+GADA、ICA+IAA+GADA阳性率均高于T2DM组,差异有统计学意义(P<0.05)。LADA组的ICA、GADA水平均高于对照组和T2DM组,差异有统计学意义(P<0.05)。LADA组HbA1c、GA、FRA、FBG水平均高于T2DM组,空腹胰岛素、空腹C肽、TG水平均低于T2DM组,差异有统计学意义(P<0.05)。LADA组患者的GADA水平与HbA1c、GA、FRA、FBG呈正相关(P<0.05),与空腹胰岛素、空腹C肽呈负相关(P<0.05);而LADA组患者的ICA、IAA水平与各生化指标均无相关性(P>0.05)。结论胰岛自身抗体联合生化指标的定量检测对糖尿病初期LADA的鉴别诊断和胰岛β细胞功能预判具有重要价值,对LADA的早期诊断和早期治疗有一定的指导意义。

1例胰岛素泵导管致皮肤软组织感染伴过敏性皮炎的成人隐匿性自身免疫糖尿病患者的护理经验

总结1例胰岛素泵导管致皮肤软组织感染伴过敏性皮炎的成人隐匿性自身免疫糖尿病患者的皮肤及伤口护理经验。护理要点包括:针对伤口护理,前期给予以清创、引流、全身及局部抗感染,后期应用负压伤口疗法,促进伤口愈合;实施腹针联合激光疗法治疗过敏性皮炎的护理经验;根据病情全方位血糖管理,指导患者胰岛素泵规范化自我管理,监测盐酸克林霉素、左氧氟沙星、克林霉素等消炎药物的不良反应,预防并发症;加强心理护理和健康教育。患者经治疗护理16d后好转出院,糖尿病足伤口门诊及微信随访,出院3d后伤口愈合良好,血糖控制稳定。

UGRP1与成人隐匿性自身免疫性糖尿病的相关性

目的探讨子宫球蛋白相关蛋白1(UGRP1)与成人隐匿性自身免疫性糖尿病(LADA)的相关性。方法选取124例受试者,其中LADA患者45例为LADA组,2型糖尿病(T2DM)患者41例为T2DM组,无糖尿病的健康人38例为对照组,分别比较3组间一般资料、糖尿病相关指标、血清UGRP1水平。采用Spearman相关性分析血清UGRP1与糖尿病相关指标的关系。采用二元Logistic回归分析UGRP1是否为LADA发病的独立危险因素。采用ROC曲线分析探讨UGRP1在LADA中的诊断价值。结果3组间体质量指数(BMI)、收缩压(SBP)、舒张压(DBP)、空腹血糖(FBG)及餐后2 h血糖(2hPBG)、C肽(FCP)及餐后2 h C肽(2hCP)、糖基化血红蛋白(HbA1c)、糖尿病抗体(GADAb、IA-2、ZnT8)指标比较,差异有统计学意义(P<0.05)。LADA组血清UGRP1水平高于对照组及T2DM组,差异有统计学意义(P<0.05)。Spearman相关性分析结果显示,糖尿病患者血清UGRP1水平与FCP、2hCP、GADAb、阳性糖尿病抗体数目相关。二元Logistic回归分析显示血清UGRP1水平为LADA发病的独立危险因素。ROC曲线分析结果提示UGRP1可作为诊断LADA较好的辅助指标。结论UGRP1可能与LADA的发病相关。

成人隐匿性自身免疫糖尿病的研究进展

成人隐匿性自身免疫糖尿病是一种进展缓慢的器官特异性自身免疫疾病,由免疫系统攻击自身胰岛B细胞所致。该疾病早期有1型糖尿病的自身抗体谱,可不依赖胰岛素治疗,故极易被误诊为2型糖尿病,后期发展为胰岛素依赖。目前临床对该病的诊疗仅提出专家共识,尚无权威性指南。该文从其流行病学、发病机制、临床特征、诊断标准及治疗等方面进行综述,以期为该病的临床诊疗提供理论依据。

谷氨酸脱羧酶抗体诊断成人隐匿性自身免疫性糖尿病探讨

采用放射配体法检测谷氨酸脱羧酶（GAD65）抗体，对195例≥35岁非酮症Ⅱ型糖尿病起病半年以上者和45例正常对照者的观察表明：本组Ⅱ型糖尿病者GAD65抗体阳性率为14．8％，高于正常对照者的2.2％；发病年龄＜40岁、有酮症史、体重指数（BMI）＜21kg／m2、空腹血清C肽＜0．3nmol／L和（或）胰升糖素刺激后6分钟血清C肽＜0．6nmol／L者，GAD65抗体阳性率均高于相应对照组（前者分别为后者的25、4.1、3.2和5.8倍）；而患者性别、病程和发病时多饮、多尿、多食及消瘦症状的多寡与GAD65抗体无显著性关联。结果提示：①我国成人隐匿性自身免疫性糖尿病（LADA）占Ⅱ型糖尿病的比例较高；②Ⅱ型糖尿病起病患者发病年龄轻、有酮症史、低体重和胰岛素缺乏为LADA诊断的重要线索；③GAD抗体检测对早期诊断LADA有实用价值。

3种自身抗体联合生化指标检测在2型糖尿病患者的临床意义

目的探讨2型糖尿病患者中血清谷氨酸脱羧酶抗体(GADA)、抗胰岛素抗体(IAA)、抗胰岛细胞抗体(ICA)和生化指标检测的临床意义及成人隐匿性自身免疫性糖尿病(LADA)比例。方法对107例2型糖尿病患者和50例健康对照者进行3种自身抗体、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、糖化清蛋白(GA)、空腹胰岛素(INS)、空腹C肽进行检测,结合临床诊断出其中的LADA患者,对上述检测指标进行比较分析。结果GADA、IAA、ICA在2型糖尿病患者检测的阳性率分别为15.88%、17.75%、3.73%;联合检测阳性率为28.03%,高于健康对照组和单一抗体患者。自身抗体阳性组和阴性组比较,HbA1c、GA、空腹C肽水平比较,差异有统计学意义(P<0.05)。107例2型糖尿病患者中确诊11例LADA患者,LADA患者HbA1c、GA水平高于非LADA 2型糖尿病患者,C肽水平低于非LADA 2型糖尿病患者,差异均有统计学意义(P<0.05)。结论在2型糖尿病患者中检测胰岛自身抗体对检出其中的LADA有重要指导价值,联合生化指标连续监测有利于对疾病鉴别诊断,从而尽快采取措施保护胰岛β细胞功能,减少进一步损伤。

成人隐匿性自身免疫糖尿病患者胰岛素抵抗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)患者胰岛素抵抗的情况及其与谷氨酸脱羧酶抗体(GAD-Ab)滴度的关系。方法在临床初诊为"2型糖尿病"的患者中,筛选出GAD-Ab阳性的LADA患者141例,测量其身高和体质量,抽血检测血脂、空腹血糖和空腹C肽水平。根据GAD-Ab滴度0.3为截点将LADA患者分为高滴度组(LADA-1亚型)和低滴度组(LADA-2亚型)。利用HOMA2软件计算胰岛素抵抗和胰岛功能水平。用放射配体法和放射免疫法检测GAD-Ab和C肽水平。结果与低滴度者相比,高滴度的LADA-1型患者的起病年龄较轻、体质量指数较低、糖化血红蛋白水平较高,空腹和餐后C肽的水平较差,同时合并有较低的甘油三酯水平。根据HOMA2软件计算的胰岛素抵抗指数(HOMA2-IR)显示,高GAD-Ab滴度的LADA-1型的HOMA2-IR的水平显著性低于低滴度的LADA-2型患者(1.6±1.1 vs 2.1±1.1,P=0.001)。患者的HOMA2-IR指数与GAD-Ab滴度呈负相关。结论 LADA患者的胰岛素抵抗水平与谷氨酸脱羧酶抗体滴度相关,低抗体滴度者的胰岛素抵抗较为严重。

成人隐匿性自身免疫性糖尿病患者胰岛β细胞功能的6年前瞻性研究

目的 探讨谷氨酸脱羧酶抗体 (GAD Ab)阳性的成人隐匿性自身免疫性糖尿病(LADA)患者胰岛 β细胞功能变化的特点及其影响因素。 方法 GAD Ab阳性的LADA患者 4 5例(LADA 1组 16例 ,LADA2组 2 9例 ) ,年龄 2 8～ 6 8岁 ;GAD Ab阴性的 2型糖尿病 (T2DM )患者 4 5例(T2DM 1组 16例 ,T2DM 2组 2 9例 ) ,年龄 2 6～ 6 8岁。每半年随访一次 ,LADA 1组和T2DM 1组随访至第 6年 ,LADA 2组和T2DM 2组随访至第 1 5年。测定空腹C肽 (FC P)和 10 0g馒头餐后 2hC肽 (2hC P)及糖代谢控制指标。采用放射配体法测定GAD Ab ,放免法测定C P。 结果 LADA1组的FC P较入组时下降 5 0 %以上 ,随访第 1 5年时为 2 5 % ,随访第 2 5年平均水平呈显著性下降[(396± 189) pmol/L对 (5 73± 2 89) pmol/L ,P <0 0 5 ]直至第 6年 ,而T2DM 1组的FC P在随访期间则无显著变化 (P >0 0 5 ) ;LADA患者平均每年FC P下降 15 8% (4 0 %～ 91 0 % ) ,而T2DM平均为 5 2 % (- 3 5 %～ 35 5 % ,P =0 0 0 0 )。LADA患者的FC P与GAD Ab滴度呈负相关 (r =-0 4 83,P =0 0 0 0 ) ;FC P平均每年下降百分数的相关因素为GAD Ab滴度、体质指数 (BMI)和发病年龄 (r分别为 0 4 0 8、- 0 30 1和 - 0 5 2 3,P <0 0 5 )。 结论 LADA患者胰岛 ?