Diabetes 1.5: Understanding Latent Autoimmune Diabetes in Adults (LADA)
Diabetes 1.5, also known as Latent Autoimmune Diabetes in Adults (LADA), is a unique form of diabetes that shares characteristics of both type 1 and type 2 diabetes, featuring autoimmune destruction of pancreatic β-cells with a slower progression than typical type 1 diabetes.
Definition and Classification
LADA is formally classified within the spectrum of type 1 diabetes but presents with some clinical features that overlap with type 2 diabetes. It is characterized by:
- Autoimmune destruction of pancreatic β-cells (like type 1 diabetes)
- Slower progression of β-cell failure compared to classic type 1 diabetes
- Initial insulin independence at diagnosis (unlike typical type 1 diabetes)
- Eventual need for insulin therapy as β-cell function declines
The European Society of Cardiology defines LADA as a form of immune-mediated diabetes that occurs in adults, with autoantibodies targeting pancreatic β-cell proteins such as glutamic acid decarboxylase (GAD), islet antigen 2 (IA-2), insulin, or zinc transporter protein 1.
Diagnostic Features
LADA can be identified by the following characteristics:
- Onset typically in adulthood (>30 years of age)
- Presence of islet autoantibodies, particularly GAD antibodies (most common)
- No immediate requirement for insulin at diagnosis
- Gradual progression to insulin dependence, usually within 5 years of diagnosis
- May present with features of metabolic syndrome (like type 2 diabetes)
According to the American Diabetes Association, testing for islet autoantibodies is recommended for classification of diabetes in adults who have phenotypic risk factors that overlap with those for type 1 diabetes (younger age at diagnosis, unintentional weight loss, ketoacidosis, or short time to insulin treatment) 1.
Pathophysiology
The pathophysiology of LADA involves:
- Autoimmune destruction of β-cells, similar to type 1 diabetes
- Genetic overlap with type 1 diabetes, particularly HLA associations
- Possible role of insulin resistance, similar to type 2 diabetes
- Slower rate of β-cell destruction compared to classic type 1 diabetes
Studies have shown that LADA patients with multiple islet antibodies develop β-cell failure within 5 years, whereas those with only GAD antibodies or islet cell antibodies may develop β-cell failure after 5 years 2.
Clinical Significance
LADA is clinically significant because:
- It accounts for approximately 10% of all diabetes cases initially classified as type 2 diabetes 3
- It is often misdiagnosed as type 2 diabetes due to adult onset and initial insulin independence
- Patients with LADA progress to insulin dependence more rapidly than those with type 2 diabetes
- Early identification can lead to more appropriate treatment strategies
Differences from Type 1 and Type 2 Diabetes
LADA differs from classic type 1 diabetes in:
- Later age of onset (adulthood vs. childhood/adolescence)
- Slower progression of β-cell failure
- Initial period of insulin independence
LADA differs from type 2 diabetes in:
- Presence of islet autoantibodies
- Faster progression to insulin dependence
- Less prominent role of insulin resistance
- Lower response to oral antidiabetic medications over time
Associated Conditions
Like type 1 diabetes, LADA patients are at increased risk for other autoimmune conditions:
Clinical Implications and Management
Early identification of LADA is important for appropriate management:
Screening for autoantibodies (particularly GAD antibodies) should be considered in adults with newly diagnosed diabetes who:
- Are not obese
- Have personal or family history of autoimmune disease
- Show poor response to oral antidiabetic medications
- Rapidly progress to insulin dependence
Treatment considerations:
- Early insulin therapy may be beneficial to preserve remaining β-cell function
- Oral agents may be less effective long-term compared to their use in type 2 diabetes
- Regular monitoring of β-cell function is important to adjust therapy
Conclusion
Diabetes 1.5 (LADA) represents an important subtype of diabetes that challenges the traditional type 1/type 2 classification. Recognizing this condition is crucial for appropriate management and patient education regarding disease progression. As our understanding of diabetes heterogeneity increases, more personalized approaches to diagnosis and treatment will likely emerge.