High-Affinity ZnT8 Autoantibodies by Electrochemiluminescence Assay Improve the Risk Prediction for Type 1 Diabetes

2020 ◽  
Author(s):  
Xiaofan Jia ◽  
Ling He ◽  
Dongmei Miao ◽  
Kathleen Waugh ◽  
Cristy Geno Rasmussen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Risk Prediction ◽  
High Affinity ◽  
Znt8 Autoantibodies

159-LB: High-Affinity ZnT8 Autoantibodies by Electrochemiluminescence Assay Improve the Risk Prediction for Type 1 Diabetes

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 159-LB
Author(s):  
XIAOFAN JIA ◽  
LING HE ◽  
DONGMEI MIAO ◽  
KATHLEEN WAUGH ◽  
CRISTY GENO RASMUSSEN ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Risk Prediction ◽  
High Affinity ◽  
Znt8 Autoantibodies

scholarly journals High-affinity ZnT8 autoantibodies by electrochemiluminescence assay improve risk prediction for type 1 diabetes

2021 ◽  
Author(s):  
Xiaofan Jia ◽  
Ling He ◽  
Dongmei Miao ◽  
Kathleen Waugh ◽  
Cristy Geno Rasmussen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Binding Assay ◽  
Islet Autoantibody ◽  
Newly Diagnosed ◽  
High Affinity ◽  
Diabetic Children ◽  
Risk Of Progression ◽  
High Prediction ◽  
Znt8 Autoantibodies

Abstract Background The risk of progression to type 1 diabetes (T1D) in subjects positive only for ZnT8 autoantibody (ZnT8A) is currently not known. Methods We developed an electrochemiluminescence (ECL) assay to detect high-affinity ZnT8A and validated it in three populations: 302 patients newly diagnosed with T1D, 135 non-diabetic children positive for ZnT8A by standard radio-binding assay (RBA) among 23400 children screened by the Autoimmunity Screening for Kids (ASK), and 123 non-diabetic children multiple autoantibody positive or single ZnT8A positive by RBA participating in the Diabetes Autoimmunity Study in the Young (DAISY). Results In 302 patients with T1D at diagnosis, the positivity for ZnT8A was 62% in both RBA and ECL. Among ASK 135 participants positive for RBA-ZnT8A, 64 were detected ZnT8A as the only islet autoantibody. Of these 64, only 9 were confirmed by ECL-ZnT8A, found to be of high affinity with increased T1D risk. Overall positive predictive value of ECL-ZnT8A for T1D risk was 87.1%, significantly higher than that of RBA-ZnT8A (53.5%, P<0.0001). In DAISY, 11/2547 children who had no positivity previously detected for other islet autoantibodies were identified as single ZnT8A by RBA; of these, three were confirmed positive by ECL-ZnT8A and all three progressed to clinical T1D. Conclusions Large proportion of ZnT8A by RBA are single ZnT8A with low T1D risk while ZnT8A by ECL were of high-affinity and high prediction for T1D development.

scholarly journals The role of coronary artery calcification testing in incident coronary artery disease risk prediction in type 1 diabetes

Diabetologia ◽  
2018 ◽  
Vol 62 (2) ◽  
pp. 259-268 ◽  
Author(s):  
Jingchuan Guo ◽  
Sebhat A. Erqou ◽  
Rachel G. Miller ◽  
Daniel Edmundowicz ◽  
Trevor J. Orchard ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Type 1 Diabetes ◽  
Coronary Artery ◽  
Risk Prediction ◽  
Coronary Artery Calcification ◽  
Disease Risk ◽  
Coronary Artery Disease Risk ◽  
Artery Disease

Association of high-affinity autoantibodies with type 1 diabetes high-risk HLA haplotypes

2021 ◽  
Author(s):  
Taylor M Triolo ◽  
Laura Pyle ◽  
Hali Broncucia ◽  
Taylor Armstrong ◽  
Liping Yu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Islet Autoimmunity ◽  
Initial Visit ◽  
Prevention Study ◽  
High Affinity ◽  
Z Scores ◽  
Hla Haplotypes ◽  
Hla Dr3

Abstract Objective ECL assays are high-affinity autoantibody (Ab) tests that are more specific than Abs detected by traditional radiobinding assays (RBA) for risk screening and prediction of progression to type 1 diabetes. We sought to characterize the association of high-risk HLA haplotypes and genotypes with electrochemiluminescence (ECL) positivity and levels in relatives of individuals with type 1 diabetes. Methods We analyzed 602 participants from the TrialNet Pathway to Prevention Study who were positive for at least one RBA diabetes related Ab (GADA or IAA) and for whom ECL and HLA data were available. ECL and RBA Ab levels were converted to SD units away from mean (Z-scores) for analyses. Results Mean age at initial visit was 19.4+13.7 years; 344 (57.1%) were female and 104 (17.3%) carried the high-risk HLA- DR3/4*0302 genotype. At initial visit 424/602 (70.4%) participants were positive for either ECL-GADA or ECL-IAA, and 178/602 (29.6%) were ECL negative. ECL and RBA-GADA positivity were associated with both HLA-DR3 and DR4 haplotypes (all p<0.05), while ECL and RBA-GADA z-score titers were higher in participants with HLA-DR3 haplotypes only (both p<0.001). ECL-IAA (but not RBA-IAA) positivity was associated with the HLA-DR4 haplotype (p<0.05). Conclusions ECL-GADA positivity is associated with the HLA-DR3 and HLA-DR4 haplotypes and levels are associated with the HLA-DR3 haplotype. ECL-IAA positivity is associated with HLA-DR4 haplotype. These studies further contribute to the understanding of genetic risk and islet autoimmunity endotypes in type 1 diabetes.

scholarly journals Antigenicity and Epitope Specificity of ZnT8 Autoantibodies in Type 1 Diabetes

2012 ◽  
Vol 77 (1) ◽  
pp. 21-29 ◽  
Author(s):  
H. Skärstrand ◽  
Å. Lernmark ◽  
F. Vaziri-Sani
Keyword(s):  
Type 1 Diabetes ◽  
Epitope Specificity ◽  
Znt8 Autoantibodies

scholarly journals Genetic Risk Score Enhances Coronary Artery Disease Risk Prediction in Individuals With Type 1 Diabetes

Diabetes Care ◽  
2022 ◽  
Author(s):  
Raija Lithovius ◽  
Anni A. Antikainen ◽  
Stefan Mutter ◽  
Erkka Valo ◽  
Carol Forsblom ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Type 1 Diabetes ◽  
Coronary Artery ◽  
Total Cholesterol ◽  
Risk Prediction ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Clinical Score ◽  
Artery Disease

OBJECTIVE Individuals with type 1 diabetes are at a high lifetime risk of coronary artery disease (CAD), calling for early interventions. This study explores the use of a genetic risk score (GRS) for CAD risk prediction, compares it to established clinical markers, and investigates its performance according to the age and pharmacological treatment. RESEARCH DESIGN AND METHODS This study in 3,295 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study (467 incident CAD, 14.8 years follow-up) used three risk scores: a GRS, a validated clinical score, and their combined score. Hazard ratios (HR) were calculated with Cox regression, and model performances were compared with the Harrell C-index (C-index). RESULTS A HR of 6.7 for CAD was observed between the highest and the lowest 5th percentile of the GRS (P = 1.8 × 10−6). The performance of GRS (C-index = 0.562) was similar to HbA1c (C-index = 0.563, P = 0.96 for difference), HDL (C-index = 0.571, P = 0.6), and total cholesterol (C-index = 0.594, P = 0.1). The GRS was not correlated with the clinical score (r = −0.013, P = 0.5). The combined score outperformed the clinical score (C-index = 0.813 vs. C-index = 0.820, P = 0.003). The GRS performed better in individuals below the median age (38.6 years) compared with those above (C-index = 0.637 vs. C-index = 0.546). CONCLUSIONS A GRS identified individuals at high risk of CAD and worked better in younger individuals. GRS was also an independent risk factor for CAD, with a predictive power comparable to that of HbA1c and HDL and total cholesterol, and when incorporated into a clinical model, modestly improved the predictions. The GRS promises early risk stratification in clinical practice by enhancing the prediction of CAD.

P2487Echocardiography and NT-ProBNP both provide independent and improved prediction of prognosis in a type 1 diabetes population without heart disease and with preserved ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Roerth ◽  
P G Jorgensen ◽  
H U Andersen ◽  
J P Goetze ◽  
P Rossing ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Heart Disease ◽  
Ejection Fraction ◽  
Risk Prediction ◽  
Cardiovascular Events ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Risk Engine

Abstract Background Cardiovascular disease is the most common comorbidity in type 1 diabetes (T1D). Current guidelines, however, do not include routine echocardiography or cardiac biomarkers in T1D. Objectives To investigate if echocardiography and NT-proBNP provide incremental prognostic information in individuals with T1D without heart disease and with preserved left ventricular ejection fraction (LVEF). Methods A prospective cohort of individuals with T1D without heart disease and with preserved LVEF (≥45%) from the outpatient clinic were included. Follow-up was performed through Danish national registers. The association between E/e', a marker of diastolic function, from echocardiography and NT-proBNP with major adverse cardiovascular events (MACE) was tested. MACE was defined as death from all-causes, acute coronary syndromes, cardiac revascularization, incident heart failure, or stroke. Additionally, the incremental prognostic value when adding E/e' and NT-proBNP to the clinical Steno T1D Risk Engine score (including age, sex, duration of diabetes, systolic blood pressure, LDL, HbA1c, presence of albuminuria (micro-or macroalbuminuria), eGFR, smoking status, and physical activity [low, medium, high]), was examined. Follow-up was 100% complete. Results Of 964 individuals (mean (SD)) age 49.7 (14.5) years, 51% men, HbA1c 66 (14) mmol/mol, BMI 25.6 (4.0) kg/m2, and diabetes duration 26.1 (14.5) years), 121 (12.6%) experienced MACE during 7.5 years of follow-up. In the full multivariable model, E/e' significantly and independently predicted MACE: (HR (95%)) E/'e <8 (n=639) vs. 8–12 (n=248): 2.00 (1.23; 3.25), p=0.005, E/'e <8 vs E/e'≥12 (n=77): 3.36 (1.8; 6.1), p<0.001. Also, NT-proBNP significantly predicted outcome: NT-proBNP <150 pg/ml (n=435) vs. 150–450 pg/ml (n=386): 1.52 (0.9; 2.5), p=0.11, NT-proBNP <150 pg/ml vs NT-proBNP >450 pg/ml (n=143): 2.78 (1.6; 4.9), p<0.001. Adding both (log)E/e' and (log)NT-proBNP to the Steno T1D Risk Engine score significantly and incrementally improved risk prediction: Harrell's C-index: Steno T1D Risk Engine (AUC 0.783 (0.747; 0.818)) vs. Steno T1D Risk Engine + (log)E/e' (AUC 0.805 (0.773; 0.837)): p<0.001 and Steno T1D Risk Engine + (log)E/e' + (log) NT-proBNP (AUC 0.816 (0.783; 0.848)): p=0.002. The risk of MACE by groups of E/e' and NT-proBNP is shown in the figure. Figure 1 Conclusion In individuals with T1D without heart disease and with preserved LVEF, E/e' and NT-proBNP significantly improved risk prediction of cardiovascular events beyond clinical risk factors alone. Echocardiography and NT-proBNP could have a role in clinical care.

scholarly journals Mature high-affinity immune responses to (pro)insulin anticipate the autoimmune cascade that leads to type 1 diabetes

2004 ◽  
Vol 114 (4) ◽  
pp. 589-597 ◽  
Author(s):  
Peter Achenbach ◽  
Kerstin Koczwara ◽  
Annette Knopff ◽  
Heike Naserke ◽  
Anette-G. Ziegler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
High Affinity
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