Ghalwash, M.* ; Dunne, J.L.* ; Lundgren, M.* ; Rewers, M.* ; Ziegler, A.-G. ; Anand, V.* ; Toppari, J.* ; Veijola, R.* ; Hagopian, W.*
     
 
    
        
Two-age islet-autoantibody screening for childhood type 1 diabetes: A prospective cohort study.
    
    
        
    
    
        
        Lancet Diabet. Endocrinol. 10, 589-596 (2022)
    
    
    
		
		
			
				BACKGROUND: Early prediction of childhood type 1 diabetes reduces ketoacidosis at diagnosis and provides opportunities for disease prevention. However, only highly efficient approaches are likely to succeed in public health settings. We sought to identify efficient strategies for initial islet autoantibody screening in children younger than 15 years. METHODS: We harmonised data from five prospective cohorts from Finland (DIPP), Germany (BABYDIAB), Sweden (DiPiS), and the USA (DAISY and DEW-IT) into the Type 1 Diabetes Intelligence (T1DI) cohort. 24 662 children at high risk of diabetes enrolled before age 2 years were included and followed up for islet autoantibodies and diabetes until age 15 years, or type 1 diabetes onset, whichever occurred first. Islet autoantibodies measured included those against glutamic acid decarboxylase, insulinoma antigen 2, and insulin. Main outcomes were sensitivity and positive predictive value (PPV) of detected islet autoantibodies, tested at one or two fixed ages, for diagnosis of clinical type 1 diabetes. FINDINGS: Of the 24 662 participants enrolled in the Type 1 Diabetes Intelligence cohort, 6722 total were followed up to age 15 years or until onset of type 1 diabetes. Type 1 diabetes developed by age 15 years in 672 children, but did not develop in 6050 children. Optimal screening ages for two measurements were 2 years and 6 years, yielding sensitivity of 82% (95% CI 79-86) and PPV of 79% (95% CI 75-80) for diabetes by age 15 years. Autoantibody positivity at the beginning of each test age was highly predictive of diagnosis in the subsequent 2-5·99 year or 6-15-year age intervals. Autoantibodies usually appeared before age 6 years even in children diagnosed with diabetes much later in childhood. INTERPRETATION: Our results show that initial screening for islet autoantibodies at two ages (2 years and 6 years) is sensitive and efficient for public health translation but might require adjustment by country on the basis of population-specific disease characteristics. FUNDING: Juvenile Diabetes Research Foundation.
			
			
				
			
		 
		
			
				
					
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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
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        Schlagwörter
        Genetic Risk; Children; Appearance; Ia-2
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2022
    
 
    
        Prepublished im Jahr 
        0
    
 
    
        HGF-Berichtsjahr
        2022
    
 
    
    
        ISSN (print) / ISBN
        2213-8587
    
 
    
        e-ISSN
        2213-8595
    
 
    
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	    Band: 10,  
	    Heft: 8,  
	    Seiten: 589-596 
	    Artikelnummer: ,  
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Elsevier
        
 
        
            Verlagsort
            Ste 800, 230 Park Ave, New York, Ny 10169 Usa
        
 
	
        
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        Begutachtungsstatus
        Peer reviewed
    
 
     
    
        POF Topic(s)
        30201 - Metabolic Health
    
 
    
        Forschungsfeld(er)
        Helmholtz Diabetes Center
    
 
    
        PSP-Element(e)
        G-502100-001
    
 
    
        Förderungen
        Juvenile Diabetes Research Foundation
    
 
    
        Copyright
        
    
 	
    
    
    
    
    
    
        Erfassungsdatum
        2022-10-27