Stages of T1D

Unravel the presymptomatic story behind T1D

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Once two or more autoantibodies develop and a patient begins experiencing dysglycemia, progression to clinical onset T1D is inevitable. It's not a matter of IF, but WHEN.

Type 1 diabetes mellitus is a chronic autoimmune-mediated disease that attacks pancreatic beta cells and is distinct from type 2 diabetes.1-3

Damage to beta cells begins months to years before the onset of T1D symptoms; those at increased risk may not be aware of the permanent beta-cell loss that is occurring.2,3

The decline in beta-cell function occurs in 3 distinct stages4,5

Stages 1 through 3 beta cell decline in patients with Type 1 diabetes graphicStages 1 through 3 beta cell decline in patients with Type 1 diabetes graphic

(Stage 3 includes the “honeymoon phase,” a period following clinical diagnosis when the pancreas is still able to produce a sufficient amount of insulin to reduce exogenous insulin needs and aid blood glucose control.)6

The presence of autoantibodies is a strong predictor of T1D5

In T1D, autoantibodies attach to healthy beta cells, targeting them for autoimmune-mediated destruction. Most patients who test positive for 2 or more autoantibodies will progress to stage 3 T1D given enough time5,7:

Stage 1 and 2 T1D risks infographicStage 1 and 2 T1D risks infographic

Progression from stage 1 (presymptomatic) to stage 3 (clinical onset) occurs more rapidly the younger a patient is.5

Islet autoantibodies: glutamic acid decarboxylase antibody (GADA), insulin (IAA), IA-2 antigen (IA-2A), zinc transporter 8 (ZnT8A), and islet-cell Ab (ICA).

Understanding the 3 stages of progression and the role of autoantibodies in T1D is critical to avoiding DKA at clinical onset8,9

1. American Diabetes Association. Learn the genetics of diabetes. Accessed September 3, 2020.

2. 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(7):603-613.

3. Ziegler AG, Rewers M, Simell O, et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013;309(23):2473-2479.

4. Couper JJ, Haller MJ, Greenbaum CJ, et al. ISPAD Clinical Practice Consensus Guidelines 2018: stages of type 1 diabetes in children and adolescents. Pediatr Diabetes. 2018;19(suppl 27):20-27.

5. Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964-1974.

6. JDRF. Honeymoon phase. Accessed October 19, 2020.

7. Xie Z, Chang C, Zhou Z. Molecular mechanisms in autoimmune type 1 diabetes: a critical review. Clin Rev Allergy Immunol. 2014;47(2):174-192.

8. Barker JM, Goehrig SH, Barriga K, et al; DAISY study. Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up. Diabetes Care. 2004;27(6):1399-1404.

9. Elding Larsson H, Vehik K, Bell R, et al. Reduced prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in young children participating in longitudinal follow-up. Diabetes Care. 2011;34(11):2347-2353.