What is Latent Autoimmune Diabetes in Adults (LADA), also known as Diabetes 1.5?

Latent Autoimmune Diabetes in Adults (LADA): Understanding Diabetes 1.5

Diabetes 1.5, also known as Latent Autoimmune Diabetes in Adults (LADA), is an autoimmune form of diabetes that shares characteristics of both type 1 and type 2 diabetes, featuring a slower autoimmune destruction of pancreatic beta cells that leads to progressive insulin deficiency over time.

What is LADA (Diabetes 1.5)?

LADA is classified within the spectrum of type 1 diabetes but with distinct characteristics:

• Autoimmune basis: Like type 1 diabetes, LADA involves autoimmune destruction of pancreatic beta cells, with presence of autoantibodies such as:

  • Glutamic acid decarboxylase (GAD65) antibodies
  • Islet cell antibodies
  • Insulin autoantibodies
  • Tyrosine phosphatase (IA-2 and IA-2β) antibodies
  • Zinc transporter 8 (ZnT8) antibodies 1

• Slower progression: Unlike classic type 1 diabetes, beta cell destruction occurs more gradually in LADA, allowing patients to remain insulin-independent for at least 6 months after diagnosis 2

• Age of onset: Typically diagnosed in adults over 35 years of age 1

• Initial presentation: Often initially misdiagnosed as type 2 diabetes due to:

  • Adult age of onset
  • Lack of immediate insulin requirement
  • Possible presence of insulin resistance features 1

Diagnostic Features

LADA is distinguished from typical type 2 diabetes by:

1. Presence of autoantibodies: Particularly GAD antibodies, which are the most common marker 1

2. Clinical presentation:

   • Adult-onset (typically >35 years)
   • Initial presentation similar to type 2 diabetes
   • No immediate need for insulin therapy
   • Often leaner body habitus than typical type 2 diabetes patients
   • May have personal or family history of other autoimmune conditions 1

3. Disease progression:

   • Faster decline in beta cell function compared to type 2 diabetes
   • Earlier insulin dependency (usually within 5 years of diagnosis) 2
   • Patients with multiple autoantibodies progress to insulin dependency faster than those with single antibody positivity 2

Clinical Significance

Understanding LADA is important because:

• It accounts for approximately 5-10% of all diabetes cases initially classified as type 2 diabetes 3
• Proper identification affects treatment decisions and disease management
• The progressive nature of beta cell destruction requires different monitoring and treatment approaches than typical type 2 diabetes

Diagnostic Challenges

A key challenge in LADA diagnosis is distinguishing it from type 2 diabetes:

• Standardized islet autoantibody tests are recommended for adults with phenotypic risk factors that overlap with type 1 diabetes (younger age at diagnosis, unintentional weight loss, ketoacidosis, or rapid progression to insulin treatment) 1
• Single antibody positivity in patients with typical type 2 diabetes features may represent false positives 4
• The heterogeneity of LADA may represent a mixed population of true autoimmune diabetes and non-autoimmune diabetes with false-positive antibody results 4

Treatment Implications

The progressive autoimmune nature of LADA has important treatment implications:

• Insulin therapy is often required earlier than in type 2 diabetes
• Beta cell preservation strategies may be beneficial
• Monitoring for more rapid progression to insulin dependence is necessary
• Patients may benefit from early insulin therapy rather than prolonged trials of oral medications 2

Pitfalls to Avoid

1. Misdiagnosis: Failing to consider LADA in adults presenting with new-onset diabetes who don't fit typical type 1 or type 2 profiles

2. Delayed appropriate therapy: Not recognizing the faster progression to insulin dependence compared to type 2 diabetes

3. Overdiagnosis: Testing for autoantibodies in patients with clear clinical features of type 2 diabetes may lead to false positives and unnecessary treatment changes 4

4. Comorbidity oversight: Failing to screen for other autoimmune conditions that are more common in LADA patients

In summary, LADA represents an important clinical entity that bridges the traditional division between type 1 and type 2 diabetes, characterized by autoimmune destruction of beta cells with a slower progression than classic type 1 diabetes but faster than type 2 diabetes.