Clinical background

T1D is characterized by autoimmune destruction of insulin-producing pancreatic β cells, progression to hyperglycemia, ketoacidosis, and a need for exogenous insulin (stage 3). About 5% to 10% of all diabetes cases1 are type 1, and the incidence of T1D in the United States is increasing: about 2% annually overall or higher (≥4%) for some minority and racial groups.2

Disease onset can happen at any age; incidence peaks at 10 to 14 years of age but more diagnoses may occur in adults than in children.3 Slowly progressing autoimmune diabetes with an adult onset has been termed latent autoimmune diabetes in adults (LADA), although there is debate on whether this is simply another form of T1D.1

Clinical presentation of T1D may vary with age and differ from T2D. Children often present with polyuria/polydipsia and 25% to 50% present with diabetic ketoacidosis, which is less frequent in adult-onset T1D.1 Adult-onset T1D is usually distinguished from T2D by leaner body mass, family history of diabetes, more rapid progression to insulin dependence, and comorbidities (eg, cancer treatment with immune checkpoint inhibitors or a triggering infection, such as COVID-19).1 In addition, proinsulin-derived C-peptide levels are usually decreased in T1D (due to destruction of insulin-producing β cells) vs elevated in T2D (due to insulin resistance and insulin overproduction).

A hallmark of T1D is its association with autoantibodies (also called islet autoantibodies or IAbs) targeting insulin, tyrosine phosphatase-related islet antigen 2 (IA-2), zinc transporter 8 (ZnT8), and glutamic acid decarboxylase-65 (GAD). Using these 4 antibodies together (Table 1),4-7 T1D can be diagnosed in 93% to 98% of symptomatic patients.8-10 On this basis, the American Diabetes Association recommends screening for T1D using these markers, especially among patients who are at risk (eg, family history of autoimmune diabetes).1

Table 1. Clinical Performance of Diabetes Type 1 Autoantibody Panel (test code 13621) Components

In presymptomatic patients, progression to clinical disease is predicted by persistence of 2 or more T1D autoantibodies, the age at first detection, the target antigen(s), and autoantibody titers.1,11 Consensus guidance has been provided for diagnosing and monitoring individuals with pre-stage 3 diabetes and is based on the number of T1D autoantibodies and glycemic indices. At-home glucose monitoring and patient education are recommended as part of this process (for details, see Consensus Guidance for Monitoring Individuals With Islet Autoantibody–Positive Pre-Stage 3 Type 1 Diabetes | Diabetes Care | American Diabetes Association (diabetesjournals.org).

Laboratory testing plays an important role in both staging T1D (Figure, Table 2) and monitoring disease progression (Table 2),12 which can be delayed by treatment with teplizumab (TZIELD™). This drug is a CD3-directed antibody approved by the US Food and Drug Administration (FDA) for patients ≥8 years old with stage-2 T1D (Table 2).13

Figure. Staging presymptomatic patients using Diabetes Type 1 Autoantibody Panel

Table 2. Pre-Stage 3 T1D and Laboratory Monitoring Recommendations

Quest Diagnostics offers the Diabetes Type 1 Autoantibody Panel (test code 13621) for diagnosis of type 1 diabetes, differentiation from type 2 diabetes, predicting progression to type 1 diabetes, and determining eligibility for teplizumab in conjunction with tests used for establishing glycemic status. See Laboratory Testing for Diabetes Diagnosis and Management for tests used to establish glycemic status.