The Prediction of Type 1 Diabetes by Multiple Autoantibody Levels and Their Incorporation Into an Autoantibody Risk Score in Relatives of Type 1 Diabetic Patients

被引:91
作者
Sosenko, Jay M. [1 ]
Skyler, Jay S. [1 ]
Palmer, Jerry P. [2 ]
Krischer, Jeffrey P. [3 ]
Yu, Liping [4 ]
Mahon, Jeffrey [5 ]
Beam, Craig A. [3 ]
Boulware, David C. [3 ]
Rafkin, Lisa [1 ]
Schatz, Desmond [6 ]
Eisenbarth, George [4 ]
机构
[1] Univ Miami, Div Endocrinol, Miami, FL 33152 USA
[2] Univ Washington, Div Endocrinol Metab & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA
[3] Univ S Florida, Div Informat & Biostat, Tampa, FL USA
[4] Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, HLA DNA Lab, Denver, CO 80262 USA
[5] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada
[6] Univ Florida, Div Endocrinol, Gainesville, FL USA
基金
美国国家卫生研究院;
关键词
ANTIBODY-POSITIVE RELATIVES; PREVENTION TRIAL-TYPE-1; 1ST-DEGREE RELATIVES; METABOLIC MARKERS; GLUCOSE-TOLERANCE; INSULIN-SECRETION; NATURAL-HISTORY; CHILDREN; MELLITUS; VALIDATION;
D O I
10.2337/dc13-0425
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity.RESULTS The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23-3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P 0.01 for all comparisons).CONCLUSIONS These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.
引用
收藏
页码:2615 / 2620
页数:6
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