Simplifying prediction of disease progression in pre-symptomatic type 1 diabetes using a single blood sample

被引：17

作者：

Bediaga, Naiara G. ^{[1
,2
]}

Li-Wai-Suen, Connie S. N. ^{[2
,3
]}

Haller, Michael J. ^{[4
]}

Gitelman, Stephen E. ^{[5
,6
]}

Evans-Molina, Carmella ^{[7
]}

Gottlieb, Peter A. ^{[8
]}

Hippich, Markus ^{[9
]}

Ziegler, Anette-Gabriele ^{[9
,10
]}

Lernmark, Ake ^{[11
]}

DiMeglio, Linda A. ^{[7
,12
]}

Wherrett, Diane K. ^{[13
]}

Colman, Peter G. ^{[14
]}

Harrison, Leonard C. ^{[1
,2
]}

Wentworth, John M. ^{[1
,2
,14
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Dept Populat Hlth & Immun, Parkville, Vic, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia

[3] Walter & Eliza Hall Inst Med Res, Dept Bioinformat, Parkville, Vic, Australia

[4] Univ Florida, Diabet Inst, Gainesville, FL USA

[5] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA

[6] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA USA

[7] Indiana Univ Sch Med, Ctr Diabet & Metab Dis, Indianapolis, IN 46202 USA

[8] Univ Colorado, Sch Med, Barbara Davis Ctr, Aurora, CO USA

[9] Helmholtz Zentrum Munchen, Inst Diabet Res, German Res Ctr Environm Hlth, Munich, Germany

[10] Tech Univ Munich, Forschergrp Diabet, Klinikum Rechts Isar, Munich, Germany

[11] Lund Univ CRC, Skane Univ Hosp, Dept Clin Sci, Malmo, Sweden

[12] Indiana Univ Sch Med, Div Pediat Endocrinol, Dept Pediat, Indianapolis, IN 46202 USA

[13] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Endocrinol, Toronto, ON, Canada

[14] Royal Melbourne Hosp, Dept Diabet & Endocrinol, Parkville, Vic, Australia

来源：

DIABETOLOGIA | 2021年 / 64卷 / 11期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

Disease progression; OGTT; Prediction; Prevention; Risk stratification; Type; 1; diabetes; 1 RISK SCORE; ISLET AUTOANTIBODIES; KETOACIDOSIS; POPULATION; RELATIVES; CHILDREN; TEDDY;

D O I：

10.1007/s00125-021-05523-2

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims/hypothesis Accurate prediction of disease progression in individuals with pre-symptomatic type 1 diabetes has potential to prevent ketoacidosis and accelerate development of disease-modifying therapies. Current tools for predicting risk require multiple blood samples taken during an OGTT. Our aim was to develop and validate a simpler tool based on a single blood draw. Methods Models to predict disease progression using a single OGTT time point (0, 30, 60, 90 or 120 min) were developed using TrialNet data collected from relatives with type 1 diabetes and validated in independent populations at high genetic risk of type 1 diabetes (TrialNet, Diabetes Prevention Trial-Type 1, The Environmental Determinants of Diabetes in the Young [1]) and in a general population of Bavarian children who participated in Fr1da. Results Cox proportional hazards models combining plasma glucose, C-peptide, sex, age, BMI, HbA(1c) and insulinoma antigen-2 autoantibody status predicted disease progression in all populations. In TrialNet, the AUC for receiver operating characteristic curves for models named M-60, M-90 and M-120, based on sampling at 60, 90 and 120 min, was 0.760, 0.761 and 0.745, respectively. These were not significantly different from the AUC of 0.760 for the gold standard Diabetes Prevention Trial Risk Score, which requires five OGTT blood samples. In TEDDY, where only 120 min blood sampling had been performed, the M-120 AUC was 0.865. In Fr1da, the M-120 AUC of 0.742 was significantly greater than the M-60 AUC of 0.615. Conclusions/interpretation Prediction models based on a single OGTT blood draw accurately predict disease progression from stage 1 or 2 to stage 3 type 1 diabetes. The operational simplicity of M-120, its validity across different at-risk populations and the requirement for 120 min sampling to stage type 1 diabetes suggest M-120 could be readily applied to decrease the cost and complexity of risk stratification.

引用

页码：2432 / 2444

页数：13

共 34 条

[1]

[Anonymous], 2020, Diabetes Care, V43, pS14, DOI DOI 10.2337/DC20-S002

[2] Type 1 Diabetes TrialNet: A Multifaceted Approach to Bringing Disease-Modifying Therapy to Clinical Use in Type 1 Diabetes [J].

Bingley, Polly J. ;

Wherrett, Diane K. ;

Shultz, Ann ;

Rafkin, Lisa E. ;

Atkinson, Mark A. ;

Greenbaum, Carla J. .

DIABETES CARE, 2018, 41 (04) :653-661

[3] Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity [J].

Bonifacio, Ezio ;

Mathieu, Chantal ;

Nepom, Gerald T. ;

Ziegler, Anette-G. ;

Anhalt, Henry ;

Haller, Michael J. ;

Harrison, Leonard C. ;

Hebrok, Matthias ;

Kushner, Jake A. ;

Norris, Jill M. ;

Peakman, Mark ;

Powers, Alvin C. ;

Todd, John A. ;

Atkinson, Mark A. .

DIABETOLOGIA, 2017, 60 (01) :35-38

[4]

Calcagno V, 2010, J STAT SOFTW, V34, P1

[5] Combined positivity for HLA DQ2/DQ8 and IA-2 antibodies defines population at high risk of developing type 1 diabetes [J].

Decochez, K ;

Truyen, I ;

Van der Auwera, B ;

Weets, I ;

Vandemeulebroucke, E ;

De Leeuw, IH ;

Keymeulen, B ;

Mathieu, C ;

Rottiers, R ;

Pipeleers, DG ;

Gorus, FK .

DIABETOLOGIA, 2005, 48 (04) :687-694

[6] Tests of calibration and goodness-of-fit in the survival setting [J].

Demler, Olga V. ;

Paynter, Nina P. ;

Cook, Nancy R. .

STATISTICS IN MEDICINE, 2015, 34 (10) :1659-1680

[7]

*DIAB PREV TRIAL T, 2005, DIABETES CARE, V28, P1068

[8] The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes [J].

Fourlanos, Spiros ;

Varney, Michael D. ;

Tait, Brian D. ;

Morahan, Grant ;

Honeyman, Margo C. ;

Colman, Peter G. ;

Harrison, Leonard C. .

DIABETES CARE, 2008, 31 (08) :1546-1549

[9] Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes A Randomized Clinical Trial [J].

Greenbaum, C. ;

Atkinson, M. ;

Baidal, D. ;

Battaglia, M. ;

Bingley, P. ;

Bosi, E. ;

Buckner, J. ;

Clements, M. ;

Colman, P. ;

DiMeglio, L. ;

Evans-Molina, C. ;

Gitelman, S. ;

Goland, R. ;

Gottlieb, P. ;

Herold, K. ;

Knip, M. ;

Krischer, J. ;

Lernmark, A. ;

Moore, W. ;

Moran, A. ;

Muir, A. ;

Palmer, J. ;

Peakman, M. ;

Philipson, L. ;

Raskin, P. ;

Redondo, M. ;

Rodriguez, H. ;

Russell, W. ;

Spain, L. ;

Schatz, D. A. ;

Sosenko, J. ;

Wherrett, D. ;

Wilson, D. ;

Winter, W. ;

Ziegler, A. ;

Anderson, M. ;

Antinozzi, P. ;

Benoist, C. ;

Blum, J. ;

Bourcier, K. ;

Chase, P. ;

Clare-Salzler, M. ;

Clynes, R. ;

Cowie, C. ;

Eisenbarth, G. ;

Fathman, C. G. ;

Grave, G. ;

Harrison, L. ;

Hering, B. ;

Insel, R. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2017, 318 (19) :1891-1902

[10] Ketoacidosis at diagnosis of type 1 diabetes: Effect of prospective studies with newborn genetic screening and follow up of risk children [J].

Hekkala, Anne M. ;

Ilonen, Jorma ;

Toppari, Jorma ;

Knip, Mikael ;

Veijola, Riitta .

PEDIATRIC DIABETES, 2018, 19 (02) :314-319

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