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

Abstract

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.

Figure 1:

Flow-diagram of islet autoimmunity progression and type 1 diabetes development in TrialNet PTP participants. (*T1D: Type 1 Diabetes Mellitus, PTP: Pathway to Prevention)

Figure 2:

Cumulative incidence of multiple autoantibody positivity in Hispanics vs NHWs TrialNet PTP participants with single confirmed autoantibody positivity at screening (p=0.01). Curves are adjusted for autoantibody type, age, sex, DPTRS, and HLA DR3-DQ2/DR4-DQ8 status. We used the following lines for each group: the solid line for NHWs, and the dashed line for Hispanics. (*PTP: Pathway to Prevention, NHWs: Non-Hispanic Whites, Ab+: autoantibody positive)

Figure 3:

Cumulative incidence of type 1 diabetes mellitus in TrialNet PTP participants <12 years old with multiple positive autoantibodies, by ethnicity (i.e. Hispanic vs NHW) and BMI groups. Curves are adjusted for sex, number of autoantibodies, DPTRS, and HLA DR3-DQ2/DR4-DQ8 status. We used the following lines for each group: the solid line for lean NHWs, the dashed line for overweight/obese NHWs, the dotted line for lean Hispanics, and the dash-dotted line for overweight/obese Hispanics. (*PTP: Pathway to Prevention, NHWs: Non-Hispanic Whites, Ab+: autoantibody positive)

Figure 4:

Cumulative incidence of type 1 diabetes mellitus in TrialNet PTP participants <12 years old in all at-risk cohort (i.e., both single confirmed and multiple autoantibody positive cohort), by ethnicity (i.e. Hispanic vs NHW) and BMI groups. Curves are adjusted for sex, number of autoantibodies, DPTRS, and HLA DR3-DQ2/DR4-DQ8 status. We used the following lines for each group: the solid line for lean NHWs, the dashed line for overweight/obese NHWs, the dotted line for lean Hispanics, and the dash-dotted line for overweight/obese Hispanics. (*PTP: Pathway to Prevention, NHWs: Non-Hispanic Whites, Ab+: autoantibody positive)