Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease

Abstract

Objective: The Environmental Determinants of Diabetes in the Young (TEDDY) study is designed to identify environmental exposures triggering islet autoimmunity and type 1 diabetes (T1D) in genetically high-risk children. We describe the first 100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at an early stage of disease, (ii) a high proportion are diagnosed by an oral glucose tolerance test (OGTT), and (iii) risk for early T1D is related to country, population, human leukocyte antigen (HLA)-genotypes and immunological markers.

Methods: Autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2) and insulin (IAA) were analyzed from 3 months of age in children with genetic risk. Symptoms and laboratory values at diagnosis were obtained and reviewed for ADA criteria.

Results: The first 100 children to develop T1D, 33 first-degree relatives (FDRs), with a median age 2.3 yr (0.69-6.27), were diagnosed between September 2005 and November 2011. Although young, 36% had no symptoms and ketoacidosis was rare (8%). An OGTT diagnosed 9/30 (30%) children above 3 yr of age but only 4/70 (5.7%) below the age of 3 yr. FDRs had higher cumulative incidence than children from the general population (p < 0.0001). Appearance of all three autoantibodies at seroconversion was associated with the most rapid development of T1D (HR = 4.52, p = 0.014), followed by the combination of GADA and IAA (HR = 2.82, p < 0.0001).

Conclusions: Close follow-up of children with genetic risk enables early detection of T1D. Risk factors for rapid development of diabetes in this young population were FDR status and initial positivity for GADA, IA-2, and IAA or a combination of GADA and IAA.

Keywords: TEDDY study; autoantibodies; diagnosis; follow-up studies; type 1 diabetes.

Figure 1

Panel A) Cumulative incidence of T1D in the general population by country, Panel B) Cumulative incidence of T1D in the first degree relatives by country, Panel C) Cumulative incidence of T1D by FDR status and Panel D) Survival analysis of first autoantibody measured and proportion of children diagnosed with type 1 diabetes over time

Figure 1

Panel A) Cumulative incidence of T1D in the general population by country, Panel B) Cumulative incidence of T1D in the first degree relatives by country, Panel C) Cumulative incidence of T1D by FDR status and Panel D) Survival analysis of first autoantibody measured and proportion of children diagnosed with type 1 diabetes over time

Figure 1

Panel A) Cumulative incidence of T1D in the general population by country, Panel B) Cumulative incidence of T1D in the first degree relatives by country, Panel C) Cumulative incidence of T1D by FDR status and Panel D) Survival analysis of first autoantibody measured and proportion of children diagnosed with type 1 diabetes over time

Figure 1

Panel A) Cumulative incidence of T1D in the general population by country, Panel B) Cumulative incidence of T1D in the first degree relatives by country, Panel C) Cumulative incidence of T1D by FDR status and Panel D) Survival analysis of first autoantibody measured and proportion of children diagnosed with type 1 diabetes over time

Figure 2

a) The first positive autoantibody (n) measured in the TEDDY study in the 100 children that later developed T1D; b) Confirmed autoantibodies at diagnosis of T1D; c) Persistent confirmed autoantibodies at diagnosis of T1D (17 subjects were not persistent). 6/100 subjects developing T1D did not have positive autoantibodies before diagnosis.

Figure 2

a) The first positive autoantibody (n) measured in the TEDDY study in the 100 children that later developed T1D; b) Confirmed autoantibodies at diagnosis of T1D; c) Persistent confirmed autoantibodies at diagnosis of T1D (17 subjects were not persistent). 6/100 subjects developing T1D did not have positive autoantibodies before diagnosis.