Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes

被引:28
|
作者
Triolo, Taylor M. [1 ]
Fouts, Alexandra [1 ]
Pyle, Laura [2 ]
Yu, Liping [1 ,15 ]
Gottlieb, Peter A. [1 ]
Steck, Andrea K. [1 ]
Greenbaum, C. J. [3 ]
Atkinson, M. [4 ]
Baidal, D. [5 ]
Battaglia, M. [6 ,61 ]
Becker, D. [7 ]
Bingley, P. [8 ]
Bosi, E. [9 ,61 ]
Buckner, J. [3 ]
Clements, M. [10 ]
Colman, P. [11 ]
DiMeglio, L. [12 ,59 ]
Gitelman, S. [13 ]
Goland, R. [14 ]
Gottlieb, P. [15 ]
Herold, K. [16 ]
Knip, M. [17 ]
Krischer, J. [18 ]
Lernmark, A. [19 ,51 ,62 ]
Moore, W. [10 ]
Moran, A. [20 ]
Muir, A. [21 ]
Palmer, J. [22 ]
Peakman, M. [23 ]
Philipson, L. [24 ]
Raskin, P. [25 ]
Redondo, M. [26 ,58 ]
Rodriguez, H. [18 ]
Russell, W. [27 ]
Spain, L. [28 ]
Schatz, D. A. [4 ]
Sosenko, J. [5 ]
Wentworth, J. [11 ]
Wherrett, D. [29 ]
Wilson, D. [30 ]
Winter, W. [4 ]
Ziegler, A. [31 ]
Anderson, M. [13 ]
Antinozzi, P. [32 ]
Benoist, C. [33 ]
Blum, J. [12 ,59 ]
Bourcier, K. [15 ]
Chase, P. [15 ]
Clare-Salzler, M. [4 ]
Clynes, R. [14 ]
机构
[1] Univ Colorado, Sch Med, Barbara Davis Ctr Diabet, Aurora, CO 80045 USA
[2] Univ Colorado, Dept Pediat, Anschutz Med Campus, Aurora, CO USA
[3] Benaroya Res Inst, Seattle, WA USA
[4] Univ Florida, Gainesville, FL 32611 USA
[5] Univ Miami, Coral Gables, FL 33124 USA
[6] San Raffaele Diabet Res Inst, Milan, Italy
[7] Univ Pittsburgh, Pittsburgh, PA 15260 USA
[8] Univ Bristol, Bristol, Avon, England
[9] San Raffaele Univ, Milan, Italy
[10] Childrens Mercy Hosp, Kansas City, MO 64108 USA
[11] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia
[12] Indiana Univ, Bloomington, IN 47405 USA
[13] Univ Calif San Francisco, San Francisco, CA 94143 USA
[14] Columbia Univ, New York, NY 10027 USA
[15] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Boulder, CO 80309 USA
[16] Yale Univ, New Haven, CT 06520 USA
[17] Univ Helsinki, Helsinki, Finland
[18] Univ S Florida, Tampa, FL USA
[19] Skane Univ, Scania, Sweden
[20] Univ Minnesota, Minneapolis, MN 55455 USA
[21] Emory Univ, Atlanta, GA 30322 USA
[22] Univ Washington, Seattle, WA 98195 USA
[23] Kings Coll London, London, England
[24] Univ Chicago, Chicago, IL 60637 USA
[25] Univ Texas Southwestern, Dallas, TX USA
[26] Baylor Univ, Waco, TX 76798 USA
[27] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA
[28] NIDDK, Bethesda, MD USA
[29] Univ Toronto, Toronto, ON, Canada
[30] Stanford Univ, Stanford, CA 94305 USA
[31] Tech Univ Munich, Munich, Germany
[32] Wake Forest Univ, Winston Salem, NC 27109 USA
[33] Joslin Diabet Ctr, Boston, MA 02215 USA
[34] NICHHD, Bethesda, MD 20892 USA
[35] Juvenile Diabet Res Fdn, New York, NY USA
[36] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA
[37] St Vincents Inst Med Res, Fitzroy, Vic, Australia
[38] Univ Western Ontario, London, ON, Canada
[39] Univ Turku, Turku, Finland
[40] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA
[41] Leiden Univ, Med Ctr, Leiden, Netherlands
[42] George Washington Univ, Washington, DC 20052 USA
[43] Georgetown Univ, Washington, DC 20057 USA
[44] Univ Penn, Philadelphia, PA 19104 USA
[45] Cleveland Clin, Cleveland, OH 44106 USA
[46] Case Western Reserve, Cleveland, OH USA
[47] Medtronic, Dublin, Ireland
[48] Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA
[49] Univ Calif Los Angeles, Los Angeles, CA 90024 USA
[50] Cornell Univ, Ithaca, NY 14853 USA
基金
美国国家卫生研究院;
关键词
CELL AUTOIMMUNITY; AUTOANTIBODIES; CONCORDANCE; PROGRESSION; AGE; DIAGNOSIS; MELLITUS; IDDM;
D O I
10.2337/dc18-0288
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVEThere are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings.RESEARCH DESIGN AND METHODSSubjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years.RESULTSAt screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody-positive, 13% for single autoantibody-positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody-positive, 12% for single autoantibody-positive, and 0.5% for initially autoantibody-negative subjects.CONCLUSIONSRisk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody-positive identical twins and multiple autoantibody-positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.
引用
收藏
页码:192 / 199
页数:8
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