Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk

被引：15

作者：

Nucci, Anita M. ^{[1
]}

Virtanen, Suvi M. ^{[2
,3
,4
,5
,6
]}

Cuthbertson, David ^{[7
]}

Ludvigsson, Johnny ^{[8
,9
]}

Einberg, Ulle ^{[10
]}

Huot, Celine ^{[11
]}

Castano, Luis ^{[12
]}

Aschemeier, Baerbel ^{[13
]}

Becker, Dorothy J. ^{[14
,15
]}

Knip, Mikael ^{[16
,17
,18
,19
,20
]}

Krischer, Jeffrey P. ^{[7
]}

机构：

[1] Georgia State Univ, Dept Nutr, Atlanta, GA 30303 USA

[2] Finnish Inst Hlth & Welf, Welf & Hlth Promot Unit, Helsinki, Finland

[3] Tampere Univ, Fac Social Sci, Unit Hlth Sci, Tampere, Finland

[4] Tampere Univ, Ctr Child Hlth Res, Tampere, Finland

[5] Tampere Univ Hosp, Tampere, Finland

[6] Pirkanmaa Hosp Dist, Sci Ctr, Tampere, Finland

[7] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL 33620 USA

[8] Linkoping Univ, Crown Princess Victoria Childrens Hosp, Linkoping, Sweden

[9] Linkoping Univ, Dept Biomed & Clin Sci, Div Pediat, Linkoping, Sweden

[10] Tallinn Childrens Hosp, Tallinn, Estonia

[11] CHU Ste Justine, Montreal, PQ, Canada

[12] Univ Basque Country, Univ Hosp, Biocruces Bizkaia Res Inst, CIBERDEM,CIBERER,Endo ERN,Cruces, Bilbao, Bizkaia, Spain

[13] Childrens & Adolescents Hosp AUF DER BULT, Diabet Ctr Children & Adolescents, Hannover, Germany

[14] Univ Pittsburgh, Div Endocrinol, Pittsburgh, PA USA

[15] UPMC Childrens Hosp Pittsburgh, Pittsburgh, PA USA

[16] Univ Helsinki, Childrens Hosp, Pediat Res Ctr, Helsinki, Finland

[17] Helsinki Univ Hosp, Helsinki, Finland

[18] Univ Helsinki, Fac Med, Res Program Clin & Mol Metab, Helsinki, Finland

[19] Folkhalsan Res Ctr, Helsinki, Finland

[20] Tampere Univ Hosp, Dept Pediat, Tampere, Finland

来源：

DIABETOLOGIA | 2021年 / 64卷 / 04期

基金：

加拿大健康研究院; 美国国家卫生研究院; 芬兰科学院;

关键词：

Beta cell autoimmunity; Childhood growth; Genetic risk; Length; Type; 1; diabetes; Weight; INCREASED LINEAR GROWTH; BODY-MASS INDEX; WEIGHT-GAIN; ACCELERATOR HYPOTHESIS; INCREASING INCIDENCE; EXCESS BMI; CHILDHOOD; OVERWEIGHT; OBESITY; AGE;

D O I：

10.1007/s00125-020-05358-3

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims/hypothesis We aimed to evaluate the relationship between childhood growth measures and risk of developing islet autoimmunity (IA) and type 1 diabetes in children with an affected first-degree relative and increased HLA-conferred risk. We hypothesised that being overweight or obese during childhood is associated with a greater risk of IA and type 1 diabetes. Methods Participants in a randomised infant feeding trial (N = 2149) were measured at 12 month intervals for weight and length/height and followed for IA (at least one positive out of insulin autoantibodies, islet antigen-2 autoantibody, GAD autoantibody and zinc transporter 8 autoantibody) and development of type 1 diabetes from birth to 10-14 years. In this secondary analysis, Cox proportional hazard regression models were adjusted for birthweight and length z score, sex, HLA risk, maternal type 1 diabetes, mode of delivery and breastfeeding duration, and stratified by residence region (Australia, Canada, Northern Europe, Southern Europe, Central Europe and the USA). Longitudinal exposures were studied both by time-varying Cox proportional hazard regression and by joint modelling. Multiple testing was considered using family-wise error rate at 0.05. Results In the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) population, 305 (14.2%) developed IA and 172 (8%) developed type 1 diabetes. The proportions of children overweight (including obese) and obese only were 28% and 9% at 10 years, respectively. Annual growth measures were not associated with IA, but being overweight at 2-10 years of life was associated with a twofold increase in the development of type 1 diabetes (HR 2.39; 95% CI 1.46, 3.92; p < 0.001 in time-varying Cox regression), and similarly with joint modelling. Conclusions/interpretation In children at genetic risk of type 1 diabetes, being overweight at 2-10 years of age is associated with increased risk of progression from multiple IA to type 1 diabetes and with development of type 1 diabetes, but not with development of IA. Future studies should assess the impact of weight management strategies on these outcomes. Graphical abstract

引用

页码：826 / 835

页数：10

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