Can type 1 diabetes be detected years before symptom onset?

Key Takeaway

Autoimmunity leads to destruction of beta cells, resulting in decreased insulin production²

Progression of T1D to symptomatic disease may take months to years³

Other associated autoimmune diseases are associated with an increased risk of developing T1D⁴

Development and progression of T1D has four distinct stages³

Early identification of individuals at risk of T1D demonstrates multiple potential benefits^6,9-12

Is the pathogenesis of T1D poorly understood?

The pathogenesis of T1D involves a complex interaction between the beta cells and immune system.1 It begins when the autoreactive T cells recognise and destroy the pancreatic beta cells. This leads to a critical decline in insulin levels, which in turn causes ineffective control of blood glucose levels. Eventually, the remaining beta cells become insufficient to maintain normal blood glucose reducing insulin secretion and leading to T1D.²

Lately, many autoantigens responsible for triggering immune-mediated destruction of beta cells have been identified; however, the triggering factors for this autoimmune response remain poorly understood.^2,3 

The figure below illustrates one of the potential mechanisms behind the triggering of the autoimmune response.

A potential mechanism for triggering autoimmune response²

Does the onset of T1D begin long before symptoms appear?

In general,  T1D is a disease continuum that progresses sequentially through identifiable stages before symptoms appear. The rate of progression of T1D from the stage of autoimmune response to symptomatic disease varies among individuals and may take from few months to decades.³

Genetic susceptibility and genetic risk detection of T1D

It is noteworthy that people living with other associated autoimmune diseases, such as coeliac disease, autoimmune thyroid disease, are at an increased risk of developing T1D than the general population.⁴ Shared genetic risk factors and immune system dysregulation are potentially implicated both in polyautoimmunity (occurrence of ≥2 autoimmune diseases in a single patient) and family autoimmunity (presence of ≥2 autoimmune diseases in members of a nuclear family) among individuals with T1D.⁵ 

Currently, first- or second-degree relatives of individuals with T1D or paediatric population are being screened for increased risk of developing T1D in the research setting.³

For additional information on common genetic risk factors linked to T1D, please read this article.

What are the stages of T1D?

The Breakthrough T1D (formerly JDRF), the Endocrine Society, and the International Society for Pediatric and Adolescent Diabetes (ISPAD) have proposed four distinct stages of development and progression of T1D, starting with the stage of activation of autoimmune response against the beta cells through symptomatic T1D.³
 

Progressive destruction of beta-cell function through different stages of T1D^3,6

In Stage 1, two or more autoantibodies against the pancreatic islets are detectible in the peripheral circulation which serve as a marker of autoimmunity. Beta-cell number and function begins to decline but are adequate to maintain normoglycaemia.³

In Stage 2, progressive beta-cell damage compromises insulin production, and glycaemic control cannot be maintained consistently, resulting in dysglycaemia. Autoantibodies persist in the peripheral circulation.³

In Stage 3, beta-cell function is reduced such that blood glucose levels are consistently elevated and treatment with insulin is eventually required. Clinical symptoms of T1D appear, including polyuria, polydipsia, weight loss, fatigue, and diabetic ketoacidosis (DKA).³

Stage 4 is indicative of longstanding T1D involving insulin dependence and requiring long term management of the condition.¹²

The below figure illustrates the four distinct stages of  T1D.

Can T1D be identified before symptom onset?

Conventionally, T1D is diagnosed after onset of clinical symptoms. However, latest research evidence on pathophysiological mechanisms leading to development and progression of T1D enable us to identify T1D in its presymptomatic stages (Stage 1 and Stage 2 as described above).³

Early detection of presymptomatic stages through screening for autoantibodies provides an opportunity for earlier monitoring and intervention strategies aimed at delaying progression to symptomatic T1D.³

Early identification of individuals at risk of T1D has a range of potential benefits^6,9–11

The figure below illustrates the potential benefits of early identification of individuals at risk of T1D.