scholarly journals Stratification of Type 1 Diabetes Risk on the Basis of Islet Autoantibody Characteristics

Diabetes ◽  
2004 ◽  
Vol 53 (2) ◽  
pp. 384-392 ◽  
Author(s):  
P. Achenbach ◽  
K. Warncke ◽  
J. Reiter ◽  
H. E. Naserke ◽  
A. J.K. Williams ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Risk ◽  
Islet Autoantibody

scholarly journals Type 1 diabetes risk assessment: improvement by follow-up measurements in young islet autoantibody-positive relatives

Diabetologia ◽  
2006 ◽  
Vol 49 (12) ◽  
pp. 2969-2976 ◽  
Author(s):  
P. Achenbach ◽  
K. Warncke ◽  
J. Reiter ◽  
A. J. K. Williams ◽  
A. G. Ziegler ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Type 1 Diabetes ◽  
Diabetes Risk ◽  
Islet Autoantibody

scholarly journals Islet Autoantibody Type-Specific Titer Thresholds Improve Stratification of Risk of Progression to Type 1 Diabetes in Children

2021 ◽  
Author(s):  
Kenney Ng ◽  
Harry Stavropoulos ◽  
Vibha Anand ◽  
Riitta Veijola ◽  
Jorma Toppari ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Familial Risk ◽  
Multivariable Analysis ◽  
Diabetes Risk ◽  
Islet Autoimmunity ◽  
Acid Decarboxylase ◽  
Islet Autoantibody ◽  
Surveillance Strategy ◽  
Risk Of Progression

OBJECTIVE: To utilize islet autoantibody titers to improve the estimation of future type 1 diabetes risk in children. <p>RESEARCH DESIGN AND METHODS: Prospective cohort studies in Finland, Germany, Sweden and the US followed 24,662 children at increased genetic or familial risk to develop islet autoimmunity and diabetes. For 1,604 children with confirmed positivity, titers of autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated antigen-2 (IA-2A) were harmonized for diabetes risk analyses.</p> <p>RESULTS: Survival analysis from time of confirmed positivity revealed markedly different 5-year diabetes risks associated with IAA (n=909), GADA (n=1076) or IA-2A (n=714), when stratified by quartiles of titer, ranging from 19% (GADA 1<sup>st</sup> quartile) to 60% (IA-2A 4<sup>th</sup> quartile). The minimum titer associated with a maximum difference in 5-year risk differed for each autoantibody, corresponding to the 58.6<sup>th</sup>, 52.4<sup>th</sup> and 10.2<sup>nd</sup> percentile of children specifically positive for each of IAA, GADA and IA-2A, respectively. Using these autoantibody type-specific titer thresholds in the 1,481 children with all autoantibodies tested, the 5-year risk conferred by single (n=954) and multiple (n=527) autoantibodies could be stratified from 6% to 75% (p<0.0001). The thresholds effectively identified children with 50% or higher 5-year risk when considering age-specific autoantibody screening (57-65% positive predictive value and 56-74% sensitivity for ages 1-5 years). Multivariable analysis confirmed the significance of associations between the three autoantibody titers and diabetes risk, informing a childhood risk surveillance strategy.</p> <p>CONCLUSIONS: This study defined islet autoantibody type-specific titer thresholds that significantly improved type 1 diabetes risk stratification in children.</p>

scholarly journals Islet Autoantibody Type-Specific Titer Thresholds Improve Stratification of Risk of Progression to Type 1 Diabetes in Children

2021 ◽  
Author(s):  
Kenney Ng ◽  
Harry Stavropoulos ◽  
Vibha Anand ◽  
Riitta Veijola ◽  
Jorma Toppari ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Familial Risk ◽  
Multivariable Analysis ◽  
Diabetes Risk ◽  
Islet Autoimmunity ◽  
Acid Decarboxylase ◽  
Islet Autoantibody ◽  
Surveillance Strategy ◽  
Risk Of Progression

OBJECTIVE: To utilize islet autoantibody titers to improve the estimation of future type 1 diabetes risk in children. <p>RESEARCH DESIGN AND METHODS: Prospective cohort studies in Finland, Germany, Sweden and the US followed 24,662 children at increased genetic or familial risk to develop islet autoimmunity and diabetes. For 1,604 children with confirmed positivity, titers of autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated antigen-2 (IA-2A) were harmonized for diabetes risk analyses.</p> <p>RESULTS: Survival analysis from time of confirmed positivity revealed markedly different 5-year diabetes risks associated with IAA (n=909), GADA (n=1076) or IA-2A (n=714), when stratified by quartiles of titer, ranging from 19% (GADA 1<sup>st</sup> quartile) to 60% (IA-2A 4<sup>th</sup> quartile). The minimum titer associated with a maximum difference in 5-year risk differed for each autoantibody, corresponding to the 58.6<sup>th</sup>, 52.4<sup>th</sup> and 10.2<sup>nd</sup> percentile of children specifically positive for each of IAA, GADA and IA-2A, respectively. Using these autoantibody type-specific titer thresholds in the 1,481 children with all autoantibodies tested, the 5-year risk conferred by single (n=954) and multiple (n=527) autoantibodies could be stratified from 6% to 75% (p<0.0001). The thresholds effectively identified children with 50% or higher 5-year risk when considering age-specific autoantibody screening (57-65% positive predictive value and 56-74% sensitivity for ages 1-5 years). Multivariable analysis confirmed the significance of associations between the three autoantibody titers and diabetes risk, informing a childhood risk surveillance strategy.</p> <p>CONCLUSIONS: This study defined islet autoantibody type-specific titer thresholds that significantly improved type 1 diabetes risk stratification in children.</p>

Immunization profiles and progression of islet autoimmunity in children at type 1 diabetes risk

2012 ◽  
Vol 7 (S 01) ◽  
Author(s):  
R Chmiel ◽  
S Krause ◽  
A Knopff ◽  
C Matzke ◽  
D Höfelmann ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Risk ◽  
Islet Autoimmunity

243-OR: Integrating Genetic Risk Score and Islet Autoantibody Characteristics in the Predictive Model for Type 1 Diabetes in the TrialNet Study

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 243-OR
Author(s):  
LAURIC A. FERRAT ◽  
ANDREA STECK ◽  
HEMANG M. PARIKH ◽  
LU YOU ◽  
SUNA ONENGUT-GUMUSCU ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Predictive Model ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Islet Autoantibody

scholarly journals An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood

2021 ◽  
Author(s):  
Ezio Bonifacio ◽  
Andreas Weiß ◽  
Christiane Winkler ◽  
Markus Hippich ◽  
Marian J. Rewers ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Confidence Interval ◽  
Islet Autoantibodies ◽  
Islet Autoimmunity ◽  
Islet Autoantibody ◽  
Age Related ◽  
At Risk Children ◽  
Exponential Decline ◽  
Design And Methods

<b>Objective</b>. Islet autoimmunity develops prior to clinical type 1 diabetes and includes multiple and single autoantibody phenotypes. The objective was to determine age-related risks of islet autoantibodies that reflect etiology and improve screening for pre-symptomatic type 1 diabetes. <p><b>Research Design and Methods</b>. The Environmental Determinants of Diabetes in the Young study prospectively followed 8,556 genetically at-risk children at 3–6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. The age-related change in the risk of developing islet autoantibodies was determined using landmark and regression models. </p> <p><b>Results</b>. The 5-year risk of developing multiple islet autoantibodies was 4.3% (95% confidence interval, 3.8–4.7) at 7.5 months of age and declined to 1.1% (95% confidence interval, 0.8–1.3) at a landmark age of 6.25 years (<i>P</i><0.0001). Risk decline was slight or absent in single insulin- and GAD-autoantibody phenotypes. The influence of sex, <i>HLA</i> and other susceptibility genes on risk subsided with increasing age and was abrogated by age six years. Highest sensitivity and positive predictive value of multiple islet autoantibody phenotypes for type 1 diabetes was achieved by autoantibody screening at 2 years and again at 5–7 years of age. </p> <p><b>Conclusions</b>. The risk of developing islet autoimmunity declines exponentially with age and the influence of major genetic factors on this risk is limited to the first few years of life. </p>

scholarly journals Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study

2018 ◽  
Vol 56 (9) ◽  
pp. 602-605 ◽  
Author(s):  
Andreas Beyerlein ◽  
Ezio Bonifacio ◽  
Kendra Vehik ◽  
Markus Hippich ◽  
Christiane Winkler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Factors ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Islet Autoimmunity ◽  
Islet Autoantibody ◽  
Clinical Type

BackgroundProgression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown.MethodsIn 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determinants of Diabetes in the Young) study, we investigated whether a genetic risk score that had previously been shown to predict islet autoimmunity is also associated with disease progression.ResultsIslet autoantibody-positive children with a genetic risk score in the lowest quartile had a slower progression from single to multiple autoantibodies (p=0.018), from single autoantibodies to diabetes (p=0.004), and by trend from multiple islet autoantibodies to diabetes (p=0.06). In a Cox proportional hazards analysis, faster progression was associated with an increased genetic risk score independently of HLA genotype (HR for progression from multiple autoantibodies to type 1 diabetes, 1.27, 95% CI 1.02 to 1.58 per unit increase), an earlier age of islet autoantibody development (HR, 0.68, 95% CI 0.58 to 0.81 per year increase in age) and female sex (HR, 1.94, 95% CI 1.28 to 2.93).ConclusionsGenetic risk scores may be used to identify islet autoantibody-positive children with high-risk HLA genotypes who have a slow rate of progression to subsequent stages of autoimmunity and type 1 diabetes.

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