scholarly journals Clinical phenotype and β-cell autoimmunity in Italian patients with adult-onset diabetes

2006 ◽  
Vol 154 (3) ◽  
pp. 441-447 ◽  
Author(s):  
S Genovese ◽  
E Bazzigaluppi ◽  
D Gonçalves ◽  
A Ciucci ◽  
M G Cavallo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glutamic Acid Decarboxylase ◽  
Clinical Phenotype ◽  
Acid Decarboxylase ◽  
Adult Onset ◽  
Β Cell ◽  
Onset Diabetes ◽  
Adult Onset Diabetes ◽  
Glutamic Acid Decarboxylase 65

Objective: To characterize the phenotype of a large population of Italian patients with adult onset (≥40 years) diabetes who were attending outpatient clinics and who were screened for glutamic acid decarboxylase 65 autoantibodies (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and IA-2β/phogrin (IA-2βA). Design and methods: This was a cross-sectional study comprising a total of 881 patients, aged ≤ 70 years, diagnosed with type 2 diabetes after the age of 40 years, and consecutively recruited in five clinics located in different geographic areas of Italy (Milan, Florence, Rome, Naples and Catania). Their mean disease duration was 8.1 (6.9; s.d.) years. GADA, IA-2A and IA-2βA were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2β. Anthropometric and clinical data were collected and compared amongst patients with or without autoantibodies. Results: Sixty-three (7.1%) patients had one or more autoantibodies, 58 (6.6%) had GADA, 22 (2.5%) had IA-2A, six (0.7%) had IA-2βA and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2βA, in the absence of GADA, were found in only five patients. Autoantibody-positive patients were more often female (63.5 vs 36.5%; P < 0.009), had higher glycated haemoglobin (Hb A1c) (P < 0.001), lower body mass index (BMI; P < 0.0005) and waist/hip ratio (WHR; P < 0.01); female gender being the main contributor to BMI and WHR. We did not observe any differences in age at diagnosis or duration of disease with respect to the presence or absence of islet autoantibodies. The proportion of patients on insulin therapy was higher in patients with two or more antibodies, compared with those with one antibody only, and no antibodies (P for trend < 0.001), and among patients with GADA, in those with higher antibody titre (73.9% in those with > 10 units vs 42.0% in those with ≤ 10 units; P < 0.007). Conclusions: Patients with adult onset diabetes characterized by autoimmunity to β-cells showed a clinical phenotype with anthropometric features that differed from those classically observed in patients with type 2 diabetes. The number and titre of autoantibodies, which reflect the severity of autoimmunity and β-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings.

scholarly journals Improving clinical utility of GAD65 autoantibodies by electrochemiluminescence assay and clinical phenotype when identifying autoimmune adult-onset diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Yong Gu ◽  
Xiaofan Jia ◽  
Tanwi Vartak ◽  
Dongmei Miao ◽  
Fran Dong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Clinical Utility ◽  
Insulin Treatment ◽  
Clinical Phenotype ◽  
Adult Onset ◽  
Onset Diabetes ◽  
Adult Onset Diabetes

Abstract Aims/hypothesis It is important to differentiate the two major phenotypes of adult-onset diabetes, autoimmune type 1 diabetes and non-autoimmune type 2 diabetes, especially as type 1 diabetes presents in adulthood. Serum GAD65 autoantibodies (GADA) are the most sensitive biomarker for adult-onset autoimmune type 1 diabetes, but the clinical value of GADA by current standard radiobinding assays (RBA) remains questionable. The present study focused on the clinical utility of GADA differentiated by a new electrochemiluminescence (ECL) assay in patients with adult-onset diabetes. Methods Two cohorts were analysed including 771 diabetic participants, 30–70 years old, from the Action LADA study (n = 6156), and 2063 diabetic participants, 20–45 years old, from the Diabetes in Young Adults (DiYA) study. Clinical characteristics of participants, including requirement of early insulin treatment, BMI and development of multiple islet autoantibodies, were analysed according to the status of RBA-GADA and ECL-GADA, respectively, and compared between these two assays. Results GADA was the most prevalent and predominant autoantibody, >90% in both cohorts. GADA positivity by either RBA or ECL assay significantly discriminated clinical type 1 from type 2 diabetes. However, in both cohorts, participants with ECL-GADA positivity were more likely to require early insulin treatment, have multiple islet autoantibodies, and be less overweight (for all p < 0.0001). However, clinical phenotype, age at diagnosis and BMI independently improved positive predictive value (PPV) for the requirement of insulin treatment, even augmenting ECL-GADA. Participants with GADA detectable by RBA, but not confirmed by ECL, had a phenotype more similar to type 2 diabetes. These RBA-GADA positive individuals had lower affinity GADA compared with participants in which GADA was confirmed by ECL assay. Conclusions/interpretation Detection of GADA by ECL assay, given technical advantages over RBA-GADA, identified adult-onset diabetes patients at higher risk of requiring early insulin treatment, as did clinical phenotype, together allowing for more accurate clinical diagnosis and management. Graphical abstract

scholarly journals A convenient diagnostic tool for discriminating adult-onset glutamic acid decarboxylase antibody-positive autoimmune diabetes from type 2 diabetes: a retrospective study

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8610
Author(s):  
Hon-Ke Sia ◽  
Shih-Te Tu ◽  
Pei-Yung Liao ◽  
Kuan-Han Lin ◽  
Chew-Teng Kor ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glutamic Acid Decarboxylase ◽  
Autoimmune Diabetes ◽  
Age At Onset ◽  
Acid Decarboxylase ◽  
Adult Onset ◽  
Discriminant Functions ◽  
Glutamic Acid Decarboxylase Antibody ◽  
Linear Discriminant

Background The glutamic acid decarboxylase antibody (GADA) test, commonly used to diagnose autoimmune diabetes, is not cost-effective in areas of low prevalence. The aim of this study was to develop a convenient tool to discriminate adult-onset GADA-positive autoimmune diabetes from type 2 diabetes (T2DM) in patients with newly diagnosed diabetes. Methods This retrospective cross-sectional study, conducted at Changhua Christian Hospital in Taiwan, collected electronic medical record data from January 2009 to December 2018. Patients were divided into a case group (GADA+, n = 152) and a reference group (T2DM, n = 358). Variables that differed significantly between the groups were subjected to receiver operator characteristic analysis to establish cutoff values. Discriminant function analysis was then employed to discriminate the two groups. Results At the onset of diabetes, the GADA+ group was younger, with lower body mass index (BMI), higher hemoglobin A1c (HbA1c), higher high-density lipoprotein cholesterol (HDL-C), and lower total cholesterol and triglycerides (TG). Five major factors were identified to form the linear discriminant functions: BMI, age at onset, TG, HDL-C, and HbA1c. BMI < 23 kg/m2 was the most important factor, followed by TG < 98 mg/dL, HDL-C ≥ 46 mg/dL, age at onset < 30 years, and HbA1c ≥ 8.6%. The overall accuracy of the linear discriminant functions was 87.1%, with 84.2% sensitivity and 88.3% specificity. Conclusions Routine tests in diabetes care were used to establish a convenient, low-cost tool that may assist in the early identification of adult-onset GAD+ autoimmune diabetes in clinical practice.

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