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Review
. 2022 Apr 1;71(4):610-623.
doi: 10.2337/dbi20-0054.

Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective

Emily K Sims  1 , Rachel E J Besser  2   3 , Colin Dayan  4 , Cristy Geno Rasmussen  5 , Carla Greenbaum  6 , Kurt J Griffin  7 , William Hagopian  8 , Mikael Knip  9   10   11 , Anna E Long  12 , Frank Martin  13 , Chantal Mathieu  14 , Marian Rewers  5 , Andrea K Steck  5 , John M Wentworth  15 , Stephen S Rich  16 , Olga Kordonouri  17 , Anette-Gabriele Ziegler  18   19 , Kevan C Herold  20 ; NIDDK Type 1 Diabetes TrialNet Study Group
Affiliations
Review

Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective

Emily K Sims et al. Diabetes. .

Abstract

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.

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Conflict of interest statement

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
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
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
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).
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