Ethnic differences in progression of islet autoimmunity and type 1 diabetes in relatives at risk

Diabetologia. 2018 Sep;61(9):2043-2053. doi: 10.1007/s00125-018-4660-9. Epub 2018 Jun 21.


Aims/hypothesis: We hypothesised that progression of islet autoimmunity and type 1 diabetes mellitus differs among races/ethnicities in at-risk individuals.

Methods: In this study, we analysed the data from the Type 1 Diabetes TrialNet Pathway to Prevention Study. We studied 4873 non-diabetic, autoantibody-positive relatives of individuals with type 1 diabetes followed prospectively (11% Hispanic, 80.9% non-Hispanic white [NHW], 2.9% non-Hispanic black [NHB] and 5.2% non-Hispanic other [NHO]). Primary outcomes were time from single autoantibody positivity confirmation to multiple autoantibody positivity, and time from multiple autoantibody positivity to type 1 diabetes mellitus diagnosis.

Results: Conversion from single to multiple autoantibody positivity was less common in Hispanic individuals than in NHW individuals (HR 0.66 [95% CI 0.46, 0.96], p = 0.028) adjusting for autoantibody type, age, sex, Diabetes Prevention Trial Type 1 Risk Score and HLA-DR3-DQ2/DR4-DQ8 genotype. In participants who screened positive for multiple autoantibodies (n = 2834), time to type 1 diabetes did not differ by race/ethnicity overall (p = 0.91). In children who were <12 years old when multiple autoantibody positivity was determined, being overweight/obese had differential effects by ethnicity: type 1 diabetes risk was increased by 36% in NHW children (HR 1.36 [95% CI 1.04, 1.77], p = 0.024) and was nearly quadrupled in Hispanic children (HR 3.8 [95% CI 1.6, 9.1], p = 0.0026). We did not observe this interaction in participants who were ≥12 years old at determination of autoantibody positivity, although this group size was limited. No significant differential risks were observed between individuals of NHB and NHW ethnicity.

Conclusions/interpretation: The risk and rate of progression of islet autoimmunity were lower in Hispanic compared with NHW at-risk individuals, while significant differences in the development of type 1 diabetes were limited to children <12 years old and were modified by BMI.

Keywords: Diabetes in childhood; Genetics of type 1 diabetes; Prediction and prevention of type 1 diabetes; Weight regulation and obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anthropometry
  • Autoantibodies / immunology*
  • Autoimmunity / genetics
  • Autoimmunity / physiology*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / ethnology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Obesity / immunology
  • Young Adult


  • Autoantibodies