What is the diagnostic approach for Latent Autoimmune Diabetes in Adults (LADA), also known as latent onset Type 1 Diabetes Mellitus (Type 1 DM)?

From the Guidelines

Diagnosing Latent Autoimmune Diabetes in Adults (LADA) requires a combination of clinical assessment and laboratory testing, with a focus on identifying autoantibodies, particularly glutamic acid decarboxylase (GAD) antibodies, islet cell antibodies (ICA), or insulin autoantibodies (IAA), as outlined in the most recent guidelines 1. The diagnosis should be suspected in adults who present with gradual onset of diabetes symptoms but don't fit the typical type 2 diabetes profile. Key diagnostic tests include:

• Measuring fasting blood glucose (levels ≥126 mg/dL suggest diabetes)
• Hemoglobin A1C (≥6.5% indicates diabetes)
• An oral glucose tolerance test
• Measuring C-peptide levels, which are typically low or normal at diagnosis but decline more rapidly than in type 2 diabetes The presence of autoantibodies is a key distinguishing feature of LADA from type 2 diabetes, and early identification is important because these patients benefit from earlier insulin therapy rather than prolonged treatment with medications targeting insulin resistance, as supported by recent studies 1. Some key characteristics of LADA include:
• Autoimmunity, with the presence of multiple islet autoantibodies
• Dysglycemia, with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)
• Presymptomatic or symptomatic presentation
• Diagnostic criteria, including multiple islet autoantibodies, dysglycemia, and/or diabetes by standard criteria It is essential to note that the rate of beta-cell destruction is variable, and adults with LADA may retain sufficient beta-cell function to prevent diabetic ketoacidosis (DKA) for many years, but eventually become dependent on insulin for survival, as highlighted in recent guidelines 1.

From the Research

Diagnostic Approach for Latent Autoimmune Diabetes in Adults (LADA)

The diagnostic approach for LADA involves several key factors, including:

• The presence of autoantibodies, such as glutamic acid decarboxylase (GAD) antibodies, which indicate an underlying autoimmune process 2, 3, 4
• C-peptide levels, which are critical diagnostic biomarkers in LADA 3
• Age and phenotypic features, such as early age at diagnosis, lower BMI, and reduced beta-cell function, which are consistent with type 1 diabetes 2
• The use of oral glucose tolerance testing (OGTT) and alternative indexes, such as the OGTT prediction index, which can predict type 1 diabetes and LADA 5

Biomarkers and Diagnostic Tools

The following biomarkers and diagnostic tools are used to diagnose LADA:

• Islet cell antibodies (ICAs) and antibodies to glutamic acid decarboxylase (anti-GAD) 2
• C-peptide levels 3
• Rapid test reverse-flow immunochromatography for glutamic acid decarboxylase 65 kDa (GAD65) 4
• Oral glucose tolerance testing (OGTT) and alternative indexes, such as the OGTT prediction index 5

Challenges and Limitations

There are several challenges and limitations in diagnosing LADA, including:

• The feasibility of autoantibody testing 3
• The need for large randomized controlled trials to compare the efficacy of different available treatment options 3
• The lack of understanding of the disease at the research level and in clinical practice 3