期刊
DIABETOLOGIA
卷 61, 期 9, 页码 2043-2053出版社
SPRINGER
DOI: 10.1007/s00125-018-4660-9
关键词
Diabetes in childhood; Genetics of type 1 diabetes; Prediction and prevention of type 1 diabetes; Weight regulation and obesity
资金
- NIH through the National Institute of Diabetes and Digestive and Kidney Diseases
- NIH through the National Institute of Allergy and Infectious Diseases
- NIH through the Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085466, U01 DK085499, U01 DK085504]
- JDRF
- [U01 DK085509]
- [U01 DK103180]
- [U01 DK103153]
- [U01 DK085476]
- [U01 DK103266]
- [U01 DK103282]
- [U01 DK106984]
- [U01 DK106994]
- [U01 DK107013]
- [U01 DK107014]
- [UC4 DK106993]
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 [NNW], 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 (re=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.
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