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.

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.

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 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

羧基肽酶-H自身抗体对LADA的诊断价值(英文)

目的 :探讨羧基肽酶H(carboxypeptidaseH ,CPH)自身抗体检测对成人隐匿性自身免疫性糖尿病 (LA DA)的诊断价值。方法 :选择 1型糖尿病患者 15 4例 ,2型糖尿病患者 10 4例 ,健康对照 14 4例。重组人CPH在体外翻译时用3 5S 甲硫氨酸标记 ,采用免疫沉淀法检测血清CPH抗体滴度。谷氨酸脱羧酶抗体 (GAD Ab)、酪氨酸磷酸酶细胞内段抗体 (IA2ic Ab)和胰岛素自身抗体 (IAA)均采用放射免疫分析法检测。结果 :CPH抗体频率在 1型糖尿病患者 (5 / 15 4 ,3.2 % ) ,2型糖尿病患者 (6 / 10 4 ,5 .7% )和健康对照 (3/ 14 4 ,2 .1% )间差异无显著性 (P >0 .0 5 )。 2型糖尿病患者GAD Ab ,IA2ic Ab和IAA频率分别为 15 .4 % (16 / 10 4 ) ,2 .9% (3/ 10 4 )和 2 .3% (1/ 4 3) ,且IA2ic Ab或IAA阳性者均为GAD Ab阳性 ,但CPH抗体阳性者无一例GAD Ab ,IA2ic Ab和IAA阳性。结论 :CPH抗体对LADA有辅助诊断价值 ,与GAD Ab联合检测可提高LADA诊断的敏感性。

老年LADA的临床特点分析

目的探讨老年起病(≥60岁)成人隐匿性自身免疫糖尿病(LADA)的临床特点.方法采用回顾性分析方法,对2000年～2003年中南大学湘雅二医院内分泌科住院的846例临床初诊为2型糖尿病(T2DM)患者进行谷氨酸脱羧酶抗体(GAD-Ab)检测,分别比较老年LADA(GAD-Ab阳性)与老年T2DM(GAD-Ab阴性),老年LADA与中青年LADA(15～59岁)的C肽、体重指数(BMI)、HBA1c等.GAD-Ab采用放射配体法,C肽测定采用放射免疫法.结果老年LADA占老年初诊2型糖尿病的8.8%(18/204),中青年LADA占中青年初诊2型糖尿病患者的9.3%(60/642),差异无显著性(P＞0.05);老年LADA与老年T2DM比较,C肽、体重指数(BMI)、HBA1c等无统计学差异(P＞0.05);老年LADA与中青年LADA比较,C肽水平较高、BMI较大(P＜0.05).结论老年LADA占老年初诊2型糖尿病的8.8%,其临床特点与老年T2DM相似,需测定GAD-Ab以利早期分型.

GADAb、ICA和IAA联合检测与LADA早期诊断

目的 联合检测GADAb、ICA和IAA。早期诊断成人隐匿性自身免疫性糖尿病 (LADA ) ,以保护胰岛 β细胞功能。方法 初次临床诊断的 2型糖尿病 (2 -DM ) 13 0例 ,正常对照组 5 0例分别用酶免法测定谷氨酸脱羧酶抗体(GADA)、胰岛细胞抗体 (ICA) ,用放免法测定胰岛素自身抗体 (IAA)、空腹及餐后 2小时胰岛素、C -P ,另予每例测身高和体重 ,计算BMI。结果 DM组抗体总阳性率高于对照组 ;与肥胖及超重组 (BMI >2 3kg/m2 )相比 ,非肥胖组 (BMI≤2 3kg/m2 )抗体阳性率明显增高 ,抗体阳性组胰岛素和C肽水平低于阴性组。结论 临床初步诊断的 2 -DM者胰岛 β细胞自身抗体的检测 ,有助于LADA的早期诊断和其 β细胞功能的保护。

LADA一级亲属GAD-Ab、IA-2Ab与CPH-Ab联合检测的价值

采用放射配体法检测128例LADA一级亲属的GAD-Ab、IA-2Ab和CPH-Ab,发现GAD-Ab和IA-2Ab的检出率与欧美高加索人及我国T1DM一级亲属接近,三种抗体联合检测可提高对LADA一级亲属筛查的敏感性。

联合检测GAD-Ab和ICA对LADA的临床异质性特点研究

目的 探讨中国人群成人隐匿性自身免疫性糖尿病 (LADA)的临床异质性特点。方法 对 82 0例 2型糖尿病患者检测谷氨酸脱羧酶抗体 (GAD -Ab) ,并对其中自愿参加进一步研究的 311例患者 ,根据GAD -Ab、胰岛细胞抗体 (ICA)阳性结果分组 ,比较各组间临床特点。结果 (1)GAD -Ab在 2型糖尿病中的阳性率为 11.3% ;(2 )GAD -Ab阳性组与GAD -Ab阴性组相比 ,起病年龄、体质量指数 (BMI)、空腹C肽、餐后 2hC肽低 ,发生酮症的机会多 ,而高血压、高血脂发生率低 ;(3)LADA患者中LADA - 1与LADA - 2相比较 ,具有胰岛功能更差 ,体质量较低 ,更需胰岛素治疗而高血压、高血脂发生率低等特点 ,临床表现更似经典的 1型糖尿病。结论 中国人群LA DA临床表现存在着异质性改变 ,可通过对GAD -Ab和ICA的联合检测来判断。

LADA与2型糖尿病患者临床特点的比较

目的:探讨成人隐匿性自身免疫性糖尿病(LADA)患者与2型糖尿病(T2DM)患者临床特点的差异。方法:对社区筛检出的46例LADA患者和同期筛检出的452例T2DM患者进行问卷调查、体格检查和实验室检查,并采用t检验分析两组均数的差异,采用χ2检验分析两组构成比的差异。结果:LADA患者中仅注射胰岛素的比例高于T2DM患者,差别有统计学意义;LA-DA患者的平均收缩压和极低密度脂蛋白胆固醇水平均低于T2DM患者,差别有统计学意义。结论:LADA与T2DM患者血压、血脂水平和注射胰岛素比例存在差异。

D6S2420与1型糖尿病和LADA的相关性研究

目的 了解 1型糖尿病 (IDDM)的易感位点 IDDM5与中国人群 IDDM和成人迟发型 IDDM(L ADA)的关系。方法 应用 PCR- PAGE结合产物直接测序的技术 ,在 10 5例无亲缘关系的成都地区正常汉族人 ,48例 1型糖尿病患者以及 2 2例成人迟发型 1型糖尿病 L ADA患者中 ,对 1型糖尿病易感位点 IDDM5的连锁标记 D6 S2 42 0的多态性进行分析。结果 D6 S2 42 0位点的等位基因 A4的频率在 1型糖尿病组中显著高于正常对照组 ,为 2 6 .0 4% vs12 .86 %、P<0 .0 385 ;在 L ADA组中 ,各等位基因的频率分布与正常对照组相比无显著性差异 ,P值均 >0 .0 5。结论 1型糖尿病的易感位点 IDDM5与中国人群的 1型糖尿病相关 ,但与 L ADA不相关 ;1型糖尿病与 L ADA发病的遗传因素可能存在差异。

羧基肽酶-H抗体与LADA患者胰岛β细胞功能关系的横断面研究

目的:探讨羧基肽酶-H自身抗体(CPH-Ab)与成人隐匿性自身免疫性糖尿病(LADA)患者胰岛β细胞功能的关系,以进一步明确其对LADA的诊断价值。方法:选择临床初诊2型糖尿病(T2DM)患者545例,采用放射配体法检测血清CPH-Ab和谷氨酸脱羧酶抗体(GAD-Ab)滴度,以筛出的CPH-Ab阳性患者为病例组,以GAD-Ab阳性患者和抗体阴性的T2DM患者为对照组,比较3组研究对象的胰岛β细胞功能(以空腹和餐后2hC肽值表示),分析CPH-Ab与成人隐匿性自身免疫性糖尿病(LADA)患者胰岛β细胞功能的关系。结果:CPH-Ab阳性患者的空腹C肽介于GAD-Ab阳性与两种抗体(GAD-Ab和CPH-Ab)均阴性的T2DM患者之间(P<0.05),以病程分层后三者的C肽值仍具有统计学意义(均P<0.05),而以BMI分层无明显差异(均P>0.05)。经以年龄、起病年龄、病程、性别等为协变量校正后,3组间的空腹C肽和餐后2hC肽值仍存在显著性差异(均P<0.001),其中CPH-Ab+组仅空腹C肽低于Ab-T2DM组(P<0.05),而GAD-Ab+组空腹和餐后2hC肽均低于Ab-T2DM组(P<0.05和P<0.01)。胰岛素缺乏患者在CPH-Ab+组、GAD-Ab+组和Ab-T2DM组的比例分别为27.6%(8/29),48.1%(8/52)和13.5%(54/400),三者间差异有统计学意义(P(0.001)。多元线性逐步回归分析提示,GAD-Ab,BMI和空腹血糖对T2DM患者的空腹C肽和餐后2hC肽均有影响(均P<0.05),而CPH-Ab与二者均无统计学相关(均P>0.05)。结论:CPH抗体对LADA患者胰岛β细胞功能的影响不如GAD-Ab显著,CPH-Ab对LADA患者胰岛功能衰减的作用需前瞻性研究。

佛山地区初诊2型糖尿病患者中LADA的患病率调查

目的调查佛山地区临床初诊2型糖尿病患者中成人隐匿性自身免疫性糖尿病(LADA)的患病率及其与2型糖尿病临床特点的差别。方法对526例临床初诊为2型糖尿病患者用化学发光法测定谷氨酸脱羧酶抗体(GAD-Ab)、酪氨酸磷酸酶蛋白抗体(ICA-Ab)及胰岛素自身抗体(IAA-Ab),计算LADA的患病率并分析其临床特点。结果 (1)临床初诊2型糖尿病患者中LADA患者检出率为5.9%(31/526),其中GAD-Ab、ICA-Ab及IAA-Ab的阳性检出率为5.2%、2.3%及0.9%。(2)病程1年内的初诊2型糖尿病患者其LADA检出率为11.3%,高于病程1年以上患者的4.6%(P<0.05)。(3)LADA检出率与患者的临床特征有关,无家族发病史、低体重、低C-肽水平及发病年龄小者有较高LADA发生风险。(4)43.6%的LADA患者伴有两种以上代谢异常,其患病率由高到低依次为:血脂异常、高血压、肥胖。在LADA患者中有16.1%的代谢综合征(MS)患病率。结论 (1)临床初诊为2型糖尿病患者中有5.9%为LADA,应及早进行糖尿病抗体检测及临床干预。(2)超过2/5的LADA患者有多种代谢异常,提示LADA患者应进行代谢方面检查以进行早期干预。

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。

LADA老年患者治疗中胰岛素强化方法对胰岛β细胞功能和临床疗效的影响

目的 对比老年2型糖尿病（DM）患者及老年成人隐匿性自身免疫性糖尿病（LADA）患者进行胰岛素强化方法 治疗的胰岛β细胞功能和治疗效果.方法选取2011年2月至2015年6月就诊的共44例2型DM患者作为DM组.选取同期的46例LADA患者作为LADA组.采用胰岛素强化治疗,对比两组患者治疗前后胰岛β细胞功能,治疗前后空腹及餐后1h和2h的C肽、胰岛素、糖化血红蛋白（HbA1c）、血糖水平.结果 DM组患者治疗前后HOMA-IS显著高于LADA组患者,且差异均有统计学意义（P〈0.05）,两组患者治疗后HOMA-IS水平明显高于各组治疗前,且差异具有统计学意义（P〈0.05）.DM组患者治疗前后的空腹、餐后1h和餐后2hC肽和胰岛素水平均明显高于LADA组患者,且差异均有统计学意义（P〈0.05）,两组患者治疗后空腹、餐后1h和餐后2hC肽和胰岛素水平均明显高于治疗前,且差异均有统计学意义（P〈0.05）.两组患者治疗前后HbA1c、空腹血糖和2h血糖水平对比均无明显差异（P〉0.05）,两组患者治疗后HbA1c、空腹血糖和2h血糖水平均明显低于治疗前,且差异均有统计学意义（P〈0.05）.结论 应用胰岛素强化方法治疗老年LADA患者在临床疗效方面明显优于2型DM患者.