Increasing plasma glucose before the development of type 1 diabetes-the TRIGR study

被引:7
作者
Ludvigsson, Johnny [1 ,2 ]
Cuthbertson, David [3 ]
Becker, Dorothy J. [4 ]
Kordonouri, Olga [5 ]
Aschemeier, Barbel [5 ]
Pacaud, Daniele [6 ]
Clarson, Cheril [7 ,8 ]
Krischer, Jeffrey P. [3 ]
Knip, Mikael [9 ,10 ,11 ,12 ,13 ]
机构
[1] Linkoping Univ, Crown Princess Victoria Childrens Hosp, Dept Biomed & Clin Sci, Linkoping, Sweden
[2] Linkoping Univ, Div Pediat, Linkoping, Sweden
[3] Univ S Florida, Hlth Informat Inst, Tampa, FL 33620 USA
[4] UPMC, Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA USA
[5] Kinder & Jugendkrankenhaus Auf Bult, Diabet Ctr Children & Adolescents, Hannover, Germany
[6] Alberta Childrens Prov Gen Hosp, Dept Pediat, Calgary, AB, Canada
[7] Univ Western Ontario, Dept Paediat, London, ON, Canada
[8] Lawson Hlth Res Inst, London, ON, Canada
[9] Univ Helsinki, Childrens Hosp, Pediat Res Ctr, Helsinki, Finland
[10] Helsinki Univ Hosp, Helsinki, Finland
[11] Univ Helsinki, Fac Med, Res Program Clin & Mol Metab, Helsinki, Finland
[12] Tampere Univ Hosp, Tampere Ctr Child Hlth Res, Tampere, Finland
[13] Folkhalsan Res Ctr, Helsinki, Finland
基金
芬兰科学院; 加拿大健康研究院;
关键词
accelerator hypothesis; autoantibodies; HbA1c; plasma glucose; type; 1; diabetes; beta-cell stress; HYDROLYZED INFANT FORMULA; PSYCHOLOGICAL STRESS; CELL AUTOIMMUNITY; WEIGHT-GAIN; C-PEPTIDE; CHILDREN; INSULIN; RISK; PREDICTION; DIAGNOSIS;
D O I
10.1111/pedi.13251
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: The beta-cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children. Research Design and Methods: A cohort of children (N = 2159) with an affected first-degree relative and increased HLA risk were recruited 2002-2007 and followed until 2017. To study the relationship between plasma glucose/HbA1c and the development of autoantibodies or clinical disease Kaplan-Meir curves were developed. Mixed models were constructed for plasma glucose and HbA1c separately. Results: A family history of type 2 diabetes was related to an increase in plasma glucose (p < 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p < 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p < 0.003 resp < 0.001) and the development of diabetes (p < 0.002 resp < 0.001. Participants without autoantibodies had lower HbA1c (mean 5.18%, STD 0.24; mean 33.08 mmol/mol, STD 2.85) than those who progressed to clinical disease (5.31%, 0.42; 34.46 mmol/mol, 4.68; p < 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p < 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p < 0.003). Conclusions: A pronounced increase in plasma glucose and HbA1c precedes development of clinical diabetes, while the association between plasma glucose or HbA1c and development of autoantibodies is complex. Increased insulin demand may contribute to development of type 1 diabetes.
引用
收藏
页码:974 / 981
页数:8
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