An official website of the United States government
The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before
sharing sensitive information, make sure you’re on a federal
government site.
The site is secure.
The https:// ensures that you are connecting to the
official website and that any information you provide is encrypted
and transmitted securely.
1 Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
2 Department of Paediatrics, National Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, U.K.
3 Wellcome Centre for Human Genetics, University of Oxford, Oxford, U.K.
4 Cardiff University School of Medicine, Cardiff, U.K.
5 Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
6 Benaroya Research Institute, Seattle, WA.
7 Sanford Health, Sioux Falls, SD.
8 Pacific Northwest Research Institute, Seattle, WA.
9 Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
10 Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
11 Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
12 Bristol Medical School, University of Bristol, Bristol, U.K.
13 JDRF, New York, NY.
14 Department of Endocrinology, UZ Gasthuisberg, KU Leuven, Leuven, Belgium.
15 Departments of Diabetes and Endocrinology and Population Health and Immunity, Royal Melbourne Hospital and Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
16 Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
17 Kinder und Jugendkrankenhaus Auf der Bult, Hannover, Germany.
18 Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
19 School of Medicine, Technical University of Munich, Munich, Germany.
20 Department of Immunobiology and Department of Internal Medicine, Yale University, New Haven, CT.
1 Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
2 Department of Paediatrics, National Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, U.K.
3 Wellcome Centre for Human Genetics, University of Oxford, Oxford, U.K.
4 Cardiff University School of Medicine, Cardiff, U.K.
5 Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
6 Benaroya Research Institute, Seattle, WA.
7 Sanford Health, Sioux Falls, SD.
8 Pacific Northwest Research Institute, Seattle, WA.
9 Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
10 Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
11 Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
12 Bristol Medical School, University of Bristol, Bristol, U.K.
13 JDRF, New York, NY.
14 Department of Endocrinology, UZ Gasthuisberg, KU Leuven, Leuven, Belgium.
15 Departments of Diabetes and Endocrinology and Population Health and Immunity, Royal Melbourne Hospital and Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
16 Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
17 Kinder und Jugendkrankenhaus Auf der Bult, Hannover, Germany.
18 Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
19 School of Medicine, Technical University of Munich, Munich, Germany.
20 Department of Immunobiology and Department of Internal Medicine, Yale University, New Haven, CT.
Most screening programs to identify individuals at risk for type 1 diabetes have targeted relatives of people living with the disease to improve yield and feasibility. However, ∼90% of those who develop type 1 diabetes do not have a family history. Recent successes in disease-modifying therapies to impact the course of early-stage disease have ignited the consideration of the need for and feasibility of population screening to identify those at increased risk. Existing population screening programs rely on genetic or autoantibody screening, and these have yielded significant information about disease progression and approaches for timing for screening in clinical practice. At the March 2021 Type 1 Diabetes TrialNet Steering Committee meeting, a session was held in which ongoing efforts for screening in the general population were discussed. This report reviews the background of these efforts and the details of those programs. Additionally, we present hurdles that need to be addressed for successful implementation of population screening and provide initial recommendations for individuals with positive screens so that standardized guidelines for monitoring and follow-up can be established.
Duality of Interest. E.K.S. and M.R. received compensation from Medscape for a continuing medical education event focused on general population screening. M.R. has consulted for Provention Bio and Janssen Research & Development. R.E.J.B. received speaking honoraria from Springer Healthcare and Eli Lilly and reports sitting on the Novo Nordisk UK Foundation Research Selection Committee on a voluntary basis. C.D. has served on advisory boards for Provention Bio, Quell Therapeutics, and Viela Bio. K.C.H. has consulted for Provention Bio, Viela Bio, and Merck; is on the scientific advisory board for Nextimmune; is named as a co-inventor on a patent application to use teplizumab for delay of type 1 diabetes; and was the principle investigator on a trial of AG019 (Precigen) in the U.S. K.C.H. is also a co-inventor on a patent for delay or prevention of T1D with teplizumab but has assigned all rights. No other potential conflicts of interest relevant to this article were reported.
Figures
Figure 1
Definitions of stages of type…
Figure 1
Definitions of stages of type 1 diabetes (26,63). *Dysglycemia defined as fasting glucose…
Figure 1
Definitions of stages of type 1 diabetes (26,63). *Dysglycemia defined as fasting glucose level of 110–125 mg/dL, or 2-h postprandial plasma glucose of >140 and <200 mg/dL, or an intervening glucose value at 30, 60, or 90 min >200 mg/dL during an OGTT. An HbA1c of 5.7–6.4% or a 10% increase in HbA1c levels in those with multiple AAs has also been suggested as criteria for stage 2 (26). However, in general, increased HbA1c levels have variable performance as a predictive marker for type 1 diabetes (T1D). **Because some patients are actually asymptomatic at the time that they cross the threshold for glucose-based criteria for type 1 diabetes, some investigators have proposed 3a and 3b subtypes of stage 3 based on the presence of clinical symptoms, which may be useful in guiding degree of clinical intervention (i.e., insulin dosing). ADA, American Diabetes Association; N/A, not applicable.
Figure 2
Considerations for approaches to general…
Figure 2
Considerations for approaches to general population screening: combined genetic/AA-based screening versus an AA-based…
Figure 2
Considerations for approaches to general population screening: combined genetic/AA-based screening versus an AA-based approach. T1D, type 1 diabetes.
Figure 3
Logistical needs and uncertainties that…
Figure 3
Logistical needs and uncertainties that remain to be answered for optimal implementation and…
Figure 3
Logistical needs and uncertainties that remain to be answered for optimal implementation and sustainability of large-scale general population screening for type 1 diabetes (T1D).
Herold KC, Bundy BN, Long SA, et al.; Type 1 Diabetes TrialNet Study Group . An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med 2019;381:603–613
-
PMC
-
PubMed
Sims EK, Bundy BN, Stier K, et al.; Type 1 Diabetes TrialNet Study Group . Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med 2021;13:eabc8990
-
PMC
-
PubMed
Foster NC, Beck RW, Miller KM, et al. State of type 1 diabetes management and outcomes from the T1D Exchange in 2016-2018. Diabetes Technol Ther 2019;21:66–72
-
PMC
-
PubMed
Rawshani A, Sattar N, Franzén S, et al. Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet 2018;392:477–486
-
PMC
-
PubMed
Livingstone SJ, Levin D, Looker HC, et al.; Scottish Diabetes Research Network epidemiology group; Scottish Renal Registry . Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA 2015;313:37–44
-
PMC
-
PubMed