Stages of T1D Progression

The following transcript has been edited for clarity and length.

Javier Morales, MD: Let me pose a question to our audience: Are you aware that type 1 diabetes progresses through distinct stages? Based on the responses, about two-thirds of our audience recognizes that type 1 diabetes progresses in stages. Now, here's a follow-up question: If you were asked to define these stages, how confident are you in your ability to do so? Kindly select the option that best reflects your confidence level.

The results show that the majority of the audience is somewhat confident, while about a third feel very confident in their understanding. Without further ado, let’s dive into these stages. Natalie, could you guide us through them?

Natalie Bellini, DNP, FNP-BC, BC-ADM, CDCES: Absolutely. The concept of staging type 1 diabetes was first introduced in Diabetes Care back in 2015. Before that, we thought of type 1 diabetes as binary—you either had it or you didn’t. Most patients were diagnosed only after entering full-blown diabetic ketoacidosis (DKA) and requiring insulin, with little attention to earlier stages or interventions.

The science has since evolved, thanks in part to NIH-funded studies like the Diabetes Prevention Trial 1 (DPT-1), which led to TrialNet. These studies focused on first-degree relatives of patients with type 1 diabetes, who have up to a 15-fold increased risk compared to the general population. As a result, we now understand that type 1 diabetes progresses through three distinct stages, each with corresponding ICD-10 codes. Let’s review them.

• Stage 1: In this stage, individuals have two or more autoantibodies associated with type 1 diabetes, indicating that the immune system has begun attacking pancreatic beta cells. Despite this immune activity, blood glucose levels remain completely normal, even after a glucose challenge. A1C levels are also within the normal range, and there are no symptoms or insulin needs at this point. Essentially, the beta cells are still functioning well enough to maintain normal glucose levels.
• Stage 2: As the immune attack progresses, more beta cells are destroyed, leading to dysglycemia, or abnormal glucose levels that fall short of meeting the diagnostic criteria for diabetes. A1C levels are typically between 5.7% and 6.4%, fasting glucose levels are between 100 and 125 mg/dL, and glucose tolerance tests show elevated but non-diagnostic results. Despite these abnormalities, beta cells can still produce sufficient insulin to prevent hyperglycemia under normal conditions. Importantly, patients at this stage are asymptomatic, with no polyuria, polydipsia, or weight loss.
• Stage 3: This is what we traditionally think of as type 1 diabetes. At this stage, the remaining beta cells are no longer able to produce enough insulin, leading to sustained hyperglycemia. Patients require exogenous insulin through injections or pumps. Symptoms include classic signs of diabetes: polyuria (frequent urination), polydipsia (excessive thirst), polyphagia (increased hunger), unexplained weight loss, fatigue, and in some cases, slow wound healing. Blood sugar levels are typically high enough to diagnose diabetes, and many patients present with DKA.

It’s fascinating to note that the introduction of staging has not only enhanced our understanding of type 1 diabetes but has also informed screening and preventive strategies. By identifying patients in stage 1 or 2, we can intervene earlier and potentially reduce the risk of DKA at diagnosis, which, as we’ve seen, has a profound impact on patient outcomes.

Morales: Thank you, Natalie. It’s remarkable how this framework has reshaped our approach to type 1 diabetes. Recognizing these stages opens the door to earlier interventions and better outcomes, and I’m eager to hear more about the implications for screening and treatment.