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AUTOIMMUNE MECHANISM OF T1D

 

T1D IS MORE THAN LACK OF INSULIN-IT’S DEFINED BY THE IMPACT OF BETA-CELL DESCRUCTION

T1D is an autoimmune condition characterized by the progressive and irreversible loss of beta cells1,2

MECHANISM OF DISEASE 

Autoimmunity in action: T cell-driven pathogenesis of autoimmune T1D3-8 

A cell

An autoimmune trigger initiates loss of immune tolerance.*

An antigen-presenting cell (APC)

Antigen-presenting cells (APCs) process beta-cell autoantigens and migrate to lymph nodes.

Lymph nodes

In the lymph nodes, APCs drive clonal expansion of :

Autoreactive CD4+ 
T cells (helper T cells)

CD4+ T cells4-6:

  • promote responses by effector CD8+ T cells

  • stimulate autoantibody production

Autoreactive CD8+
T cells (cytotoxic T cells)

CD8+ T cells4-6:

  • mediate beta-cell death in a contact-dependent manner through perforin and granzyme secretion
     

B cells

B cells4-6:

  • act as APCs to activate autoreactive T cells


*The precise mechanism that leads to the loss of immune tolerance has not been fully defined.6

T1D=type 1 diabetes.

IMPACT OF AGE ON T1D PROGRESSION

The younger a person is at the onset of T1D, the greater the severity of beta-cell destruction9-12

Beta cells and a lightning bolt

THE AGGRESSIVENESS OF INSULITIS TYPICALLY VARIES WITH AGE...

Patients receiving a diagnosis before the age of 7 years display a more aggressive profile than patients aged 13 years or older.9,11

A staggered down arrow

...RESULTS IN DIFFERENTIAL RATES OF BETA LOSS

In young patients, beta-cell loss is rapid and extensive; those diagnosed in their teens or later may still retain a measurable beta-cell reserve.9-11

BETA-CELL DESTRUCTION IS A WARNING SIGN OF LOSS OF INSULIN PRODUCTION, EVEN IF THE PATIENT SHOWS NO SYMPTOMS1,2,13

Many patients still have some beta-cell function in Stage 3 T1D: beta-cell function decline presents differently and happens at different rates1,2

A chart showing decreasing beta cell function

THE HONEYMOON PHASE IN STAGE 313:

  • A temporary period of improved blood sugar control that occurs in some people with newly diagnosed Stage 3 T1D who are just starting insulin

  • The pancreas may still produce some insulin, which may reduce the amount of external insulin injections needed

Duration and characteristics:

  • Typically lasts for a few weeks to a few years

  • Blood sugar levels may be easier to control, requiring less insulin

  • Endogenous insulin may reduce the amount of external insulin needed, but only for a short period of time

  • The duration and intensity of the honeymoon phase vary widely among individuals

EVEN REMAINING BETA CELLS CAN HAVE AN IMPACT ON GLYCEMIC REGULATION

A staggered down arrow

Residual beta-cell function can reduce risk of T1D complications, including21-28:

  • Hypoglycemia

  • Retinopathy

  • Nephropathy

  • Neuropathy

Beta cells

Residual beta cells can help maintain glucose homeostasis to impact the likelihood of time in range and achieving target hemoglobin A1c (HbA1c)21,29

A palm facing up and a medical cross

Research on T1D suggests that timely disease management approaches may influence cellular processes, which could potentially impact disease progression and long-term outcomes28,30,31

NOT MEETING GLYCEMIC TARGETS IS ASSOCIATED WITH DIABETES-RELATED STRESS34

Key factors34:

 

A blood glucose monitor

Suboptimal glycemic control

An hourglass with all the sand at the bottom

Potential long-term complications
 

A droplet with a magnifying glass over it

Fear of hypoglycemia

Two hands holding a heart symbol

Self-care burden

References

  1. Scheiner G, Weiner S, Kruger D, Pettus J. Screening for type 1 diabetes: role of the diabetes care and education specialist. ADCES Pract. 2022;10(5):20-25.

  2. 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.

  3. Addissouky TA, Ali MMA, El Sayed IET, et al. Type 1 diabetes mellitus: retrospect and prospect. Bull Natl Res Cent. 2024;48(42):1-15.

  4. Burrack AL, Martinov T, Fife BT. T cell-mediated beta cell destruction: autoimmunity and alloimmunity in the context of type 1 diabetes. Front Endocrinol. 2017;8:343.

  5. Houeiss P, Luce S, Boitard C. Environmental triggering of type 1 diabetes autoimmunity. Front Endocrinol. 2022;13:933965.

  6. Nagy G, Szekely TE, Somogyi A, et al. New therapeutic approaches for type 1 diabetes: disease-modifying therapies. World J Diabetes. 2022;13(10):835-850.

  7. Sauls RS, McCausland C, Taylor BN. Histology, T-cell lymphocyte. In: StatPearls. StatPearls Publishing; 2023.

  8. Pugliese A. Insulitis in the pathogenesis of type 1 diabetes. Pediatr Diabetes. 2016;17(suppl 22):31-36.

  9. Leete P, Mallone R, Richardson SJ, et al. The effect of age on the progression and severity of type 1 diabetes: potential effects on disease mechanisms. Curr Diab Rep. 2018;18(11):115.

  10. Marcovecchio ML, Hendriks AEJ, Delfin C, et al; INNODIA consortium. The INNODIA Type 1 Diabetes Natural History Study: a European cohort of newly diagnosed children, adolescents and adults. Diabetologia. 2024;67(6):995-1008.

  11. Leete P, Willcox A, Krogvold L, et al. Differential insulitic profiles determine the extent of β-cell destruction and the age at onset of type 1 diabetes. Diabetes. 2016;65(5):1362-1369.

  12. Poudel A, Savari O, Striegel DA, et al. Beta-cell destruction and preservation in childhood and adult onset type 1 diabetes. Endocrine. 2015;49(3):693-702.

  13. Understanding A1C diagnosis. American Diabetes Association. Accessed March 6, 2026. https://www.diabetes.org/a1c

  14. Phillip M, Achenbach P, Addala A, et al. Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetes Care. 2024;47(8):1276-1298.

  15. American Diabetes Association Professional Practice Committee. 2. Diagnosis and classification of diabetes: standards of care in diabetes—2025. Diabetes Care. 2025;48(suppl 1):S27-S49. 

  16. The stages of type 1 diabetes and why they’re important. Breakthrough T1D. Accessed March 7, 2026. https://breakthrought1d.org.au/app/uploads/2025/03/Stages-of-T1D-V2.pdf

  17. American Diabetes Association Professional Practice Committee for Diabetes. Standards of care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S1-S371.

  18. Gitelman SE, Evans-Molina C, Guolo A, et al. β-cell glucose sensitivity to assess changes in β-cell function in recent-onset stage 3 type 1 diabetes. Diabetes. 2023;72(9):1289-1296.

  19. Kawasaki E. Anti-islet autoantibodies in type 1 diabetes. Int J Mol Sci. 2023;24(12):10012.

  20. Wang YN, Li R, Huang Y, et al. The role of B cells in the pathogenesis of type 1 diabetes. Front Immunol. 2024;15:1450366.

  21. Sørensen JS, Johannesen J, Pociot F, et al; Danish Society for Diabetes in Childhood and Adolescence. Residual β-cell function 3-6 years after onset of type 1 diabetes reduces risk of severe hypoglycemia in children and adolescents. Diabetes Care. 2013;36(11):3454-3459. 

  22. Gubitosi-Klug RA, Braffett BH, Hitt S, et al; DCCT/EDIC Research Group. Residual β cell function in long-term type 1 diabetes associates with reduced incidence of hypoglycemia. J Clin Invest. 2021;131(3):e143011. 

  23. Jeyam A, Colhoun H, McGurnaghan S, et al; SDRNT1BIO Investigators. Clinical impact of residual C-peptide secretion in type 1 diabetes on glycemia and microvascular complications. Diabetes Care. 2021;44(2):390-398. 

  24. Palmer JP, Fleming GA, Greenbaum CJ, et al. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve β-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes. 2004;53(1):250-264.

  25. Lachin JM, McGee P, Palmer JP; DCCT/EDIC Research Group. Impact of C-peptide preservation on metabolic and clinical outcomes in the Diabetes Control and Complications Trial. Diabetes. 2014;63(2):739-748. 

  26. Steffes MW, Sibley S, Jackson M, et al. β-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care. 2003;26(3):832-836. 

  27. Leighton E, Sainsbury CAR, Jones GC. A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017;8(3):475-487. 

  28. Nathan DM. Realising the long-term promise of insulin therapy: the DCCT/EDIC study. Diabetologia. 2021;64(5):1049-1058.

  29. Fuhri Snethlage CM, McDonald TJ, Oram RD, et al. Residual β-cell function is associated with longer time in range in individuals with type 1 diabetes. Diabetes Care. 2024;47(7):1114-1121.

  30. Islam K, Islam R, Nguyen I, et al. Diabetes mellitus and associated vascular disease: pathogenesis, complications, and evolving treatments. Adv Ther. 2025;42(6):2659-2678.

  31. Noso S, Babaya N, Hiromine Y, et al. Metabolic signatures of β-cell destruction in type 1 diabetes. J Diabetes Investig. 2023;14(1):48-57.

  32. Kramer CK, Retnakaran R, Zinman B. Insulin and insulin analogs as antidiabetic therapy: a perspective from clinical trials. Cell Metab. 2021;33(4):740-747.

  33. Laffel LM, Kanapka LG, Beck RW, et al; CGM Intervention in Teens and Young Adults with T1D (CITY) Study Group. Effect of continuous glucose monitoring on glycemic control in adolescents and young adults with type 1 diabetes: a randomized clinical trial. JAMA. 2020;323(23):2388-2396.

  34. Rodriguez-Munoz A, Picon-Cesar MJ, Tinahones FJ, et al. Type 1 diabetes–related distress: current implications in care. Eur J Intern Med. 2024;125:19-27.

 

MAT-US-2504444-v2.0-03/2026