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En la Diabetes tipo 1 (DM1) la pérdida de células ß pancreáticas es consecuencia de un proceso de autoinmunidad que cursa con la presencia de autoanticuerpos anti-islotes pancreáticos (AAPs). Estos AAPs son marcadores útiles para la clasificación de la enfermedad. En un centro pediátrico de tercer nivel se analizó la frecuencia de presentación de GADA, IA-2A, ZnT8A e IAA en un grupo con reciente debut entre enero 2018 y agosto 2021 (n= 90). Además, se investigó la frecuencia de presentación y relación de los AAPs con la edad, sexo y tiempo de evolución en pacientes en seguimiento (n= 240). En el grupo de debut se obtuvo positividad de GADA, IA-2A, ZnT8A y IAA en 77,8; 60; 62 y 47,8% de los pacientes respectivamente, un 4% no presentó AAPs. El 95,6% de los pacientes presentaron al menos un AAPs positivo. La frecuencia de IAA en el grupo en debut fue mayor en menores de 5 años. En el grupo en seguimiento el 75,2% resultaron GADA positivo (85,7% en mujeres y 62,8% en varones) p<0,05. IA-2A y ZnT8A fueron positivos en 45 y 51.7% respectivamente. El 91% presentaron al menos un AAP positivo. En este grupo se evidenció una menor positividad en función del tiempo de evolución. Se pudo determinar la frecuencia de presentación de los AAPs en un grupo en debut y la relación con la edad, sexo y tiempo de evolución en pacientes en seguimiento. La determinación de APPs facilita la correcta clasificación y elección de la terapia adecuada (AU)
In type 1 diabetes (DM1) the loss of pancreatic ß-cells is a consequence of an autoimmune process that results in the presence of pancreatic anti-islet autoantibodies (PAAs). PAAs are useful markers for the classification of the disease. The frequency of presentation of GADA, IA-2A, ZnT8A, and IAA in a group with recent debut seen between January 2018 and August 2021 (n= 90) was analyzed in a tertiary pediatric center. In addition, we investigated the frequency of presentation and association of PAAs with age, sex, and time of evolution in patients in follow-up (n= 240). In the debut group, GADA, IA2A, ZnT8A, and IAA positivity was found in 77.8, 60, 62, and 47.8% of patients, respectively; no PAAs were observed in 4% of the patients. Overall, 95.6% presented at least one positive PAA. The frequency of IAA in the debut group was higher in children younger than 5 years. In the follow-up group, 75.2% were GADA positive (85.7% of females and 62.8% of males) p<0.05. IA-2A and ZnT8A were positive in 45 and 51.7% respectively. Ninety-one percent presented with at least one positive PAA. In this group, a lower positivity was evidenced as a function of the time of evolution. The frequency of presentation of PAAs in a debut group and the relationship with age, sex, and time of evolution in patients in follow-up was demonstrated. The assessment of PAAs facilitates the correct classification and choice of adequate therapy (AU)
Subject(s)
Humans , Infant , Child, Preschool , Child , Adolescent , Autoantibodies , Diabetes Mellitus, Type 1/classification , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/blood , Insulin-Secreting Cells , Autoimmune Diseases , Cross-Sectional Studies , Retrospective Studies , Glutamate DecarboxylaseABSTRACT
Objective:To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification.Methods:Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC).Results:A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m 2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95% CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions:There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.
ABSTRACT
Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease mediated by T cells. Untreated T1DM deteriorate rapidly. Early prediction and diagnosis lead to early treatment and prognosis of patients. Immune system plays an important role in the destruction of β cells in T1DM patients, and the emergence of immunological markers has facilitated the diagnosis and prediction of T1DM. Based on the results of various cohort studies and clinical studies in recent years, this review comprehensively discusses the application of immunological markers in the prediction and diagnosis of T1DM from two aspects: humoral immune markers and cellular immune markers.
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Objective To investigate the clinical value in changes of serum glutamic acid decarboxylase antibody (GAD-Ab) ,islet cell antibodies(ICA) ,insulin autoantibodies (IAA) and high-sensitivity C-reactive protein (hs-CRP) and renal function in elderly type 2 diabetic patients .Methods 122 cases of endocrine inpatient in our hospital had been diagnosed with type 2 diabetes were chosen from January 2012 to December 2012 .They were divided into islet autoimmunity antibody positive group (n=21) and islet autoimmunity antibody negative group (n=101) according to the antibody test results ,Fasting C-peptide(FCP) ,2-hour postprandial C-peptide(2 h CP) ,glycosylated hemoglobin(HbA1c) ,high-sensitivity-CRP(hs-CRP) and renal function[urea (UREA) ,creatinine (Cr) ,microalbuminuria(urinary mALB) ,urinary β2-microglobulin (urinary β2-MG)]were detected .Test results were statistically analyzed and compared .Results At least one Islet autoimmune antibodies were found in 21 cases of 122 elderly patients with type 2 diabetes .The positive rate was 17 .21% .GAD-Ab was detected positive in 14 cases(11 .47% ) ,ICA was detected positive in 10 ca-ses(8 .19% ) ,IAA was detected positive in 1 case(0 .82% ) ,Two antibodies were detected positive together in 4 patients(3 .27% ) , Three antibodies were not detected positive together .The levels of hs-CRP ,UREA and Cr in Islet autoantibodies positive group were higher then in islet autoimmunity antibody negative group ,the difference was statistically significant (P0 .05) . Conclusion Chronic inflammation and the appearance of islet autoantibodies are closely related to the damage of islet cell function . It has a higher value in monitoring complications and efficacy through understanding islet autoantibodies ,inflammation and changes in renal function in elderly type 2 diabetes .
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Diabetes affects today an estimated 366 million people world-wide, including 20 million to 40 million of patients with type 1 diabetes (T1D). While T1D accounts for 5% to 20% of those with diabetes, it is associated with higher morbidity, mortality and health care cost than the more prevalent type 2 diabetes. Patients with T1D require exogenous insulin for survival and should be identified as soon as possible after diagnosis to avoid high morbidity due to a delay in insulin treatment. It is also important to present to the patient correct prognosis that differs by the type of diabetes. From the research point of view, correct classification should help to identify the etiologies and to develop specific prevention for T1D. This review summarizes evidence that may be helpful in diagnosing T1D in various ethnic groups. Challenges in interpretation of results commonly used to determine the type of diabetes are highlighted.
Subject(s)
Humans , C-Peptide , Diabetes Mellitus, Type 1 , Ethnicity , Health Care Costs , Insulin , Insulin Resistance , PrognosisABSTRACT
Oral glucose tolerance test(OGTT)was performed in 419 first-degree relatives(FDRs)of type 1 diabetes mellitus. GADA, IA-2A, and IAA were determined by radioligand assay, and the positive rates were 7.16%, 1.43%, and 1.26%, respectively. Intravenous glucose tolerance test(IVGTT)and nateglinide-OGTT were performed in 39 controls, 11 first-degree relatives with positive autoantibody(Ab+group), 14 ones with negative autoantibody(Ab-group)during 5-7 days.The first-phase insulin release(FPIR), area under insulin release during 0-10 min [AUC0-10] of IVGTT and the value of(ΔI30/ΔG30)of nateglinide-OGTT in Ab+group were lower than those of control and(2.75±0.37 vs 3.61±1.05)mU/mmol, all P＜0.05]. The 1st min insulin release in Ab+group was lower than that of Ab-group [(3.80±0.30 vs 4.52±0.70)mU/L, P＜0.05]. The HOMA-IR was higher in Ab-group than that in control group(2.92±1.04 vs 1.96±1.22, P＜0.05). The results suggest that the positivity rates of autoantibodies in FDRs of type 1 diabetes mellitus are very close to those of Caucasian. There exist insulin secretion defects in FDRs with positive autoantibody while insulin resistance in FDRs with negative autoantibody.
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Objective To investigate the clinical characteristics of islet auto-antibodies and ?-cell function in patients with ketosis-prone diabetes(KPD). Methods A total of 78 patients with KPD were divided into four categorical groups based on the presence or absence of auto-antibodies (A+ or A-) and of ?-cell functional reserve(?+ ?-):A+?+(group 1,n=13),A-?-(group 2,n=18),A-?+(group 3,n=28),A+?-(group 4,n=19).Islet auto-antibodies,including glutamic acid decarboxylase antibody(GAD-Ab),islet cell antibody(ICA)and insulin autoantibody(IAA) were measured. The clinical characteristics,biochemical parameters and serum peptide were compared among four groups. Results Compared with group 1,2 and 4,group 3 showed the oldest age at onset,and higher levels of BMI,hypertension,serum triglyceride,cholesterol,fasting and postprandial C-peptide. Patients in group 2 had the youngest age at onset,the lowest level of serum C peptide. The phenotypes of patients in group 1 and group 4 were intermediate between group 2 and group 3. Conclusions About 39.7% of patients with KPD have positive islet auto-antibodies. Patients with KPD show significantly different levels of ?-cell function,clinical characteristics and biochemical parameters,which may need different therapeutic strategies.
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Objective To evaluate the association of islet autoantibodies [ glutamic acid decarboxylase antibody(GADA),protein tyrosine phosphatase antibody(IA-2A)and insulin autoantibodies(IAA)1 with HLA- DQ genotypes in the first-degree relatives of autoimmune type 1 diabetes mellitus.Methods This was a cross- sectional and case-control study.Three hundred and fifty-one first-degree relatives with normal glucose tolerance of patients with type 1 diabetes mellitus and 376 healthy controls were recruited and measured for GADA,IA-2A and IAA by radioligand assay,and 156 first-degree relatives of patients with autoimmune type 1 diabetes mellitus and 278 controls were typed for genetic polymorphisms of HLA-DQ with PCR sequencing-based typing method.Results (1)DQA1*03,DQBI*0303,*0401 alleles and DQA1 * 03-DQBI * 0303,DQA1 * 05-DQBI * 0201,DQA1 * 03-DQBI * 0401 haplotypes were significantly increased in the first-degree relatives of autoimmune type 1 diabetes mellitus(P
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Objective To optimize the radioligand assays for glutamic acid decarboxylase antibody (GAD-Ab), tyrosine phosphatase antibody (IA-2A) and insulin autoantibody (IAA) and to facilitate their application in clinical practice. Methods The radioligand assays established in our laboratory were optimized in several aspects, including the mode and time of antigen-antibody incubation, pH value of TBST buffer, times of washing, and type of centrifuge. The sensitivity and specificity of the optimized assays were calculated by the Diabetes Antibody Standardization Program (DASP, 2003). And the results were compared to those measured with domestic radioimmune assay kits. Results The optimal condition for radiligand assay were as followed: incubating the antigens of GAD-Ab and IA-2A with serum by rotating slowly for 24 hours and IAA for 72 hours respectively; washing the precipitation complex of GAD-Ab and IA-2A with TBST buffer (pH value 7 2～7 4) 4 times and IAA 5 times respectively; and applying the horizontal type of centrifuge. The results from DASP demonstrated that sensitivity and specificity of the optimized assays were 82% and 98% respectively for GAD-Ab, and 64% and 100% for IA-2A. The proportion of consistency between our results for 82 IAA gradient index of optimized assay and those measured with domestic radioimmune kits was 89%. The extensive analysis showed that the consistency reached 100% for those with IAA index less than 0 04 or more than 1 00, and the inconsistency was for the bordline positive ones (index 0 04～1 0). Conclusion The optimized radioligand assays for islet autoantibodies are high sensitivity and specificity, and are applicable in clinical practice.