Most Common Cause of Adult-Onset Type 1 Diabetes
The most common cause of adult-onset type 1 diabetes is autoimmune destruction of pancreatic beta cells, characterized by the presence of islet cell autoantibodies. 1
Pathophysiology of Adult-Onset Type 1 Diabetes
Adult-onset type 1 diabetes results from a cellular-mediated autoimmune destruction of the beta cells in the pancreas, leading to absolute insulin deficiency. This autoimmune process is marked by the presence of specific autoantibodies:
- Islet cell autoantibodies
- Autoantibodies to insulin
- Autoantibodies to glutamic acid decarboxylase (GAD65)
- Autoantibodies to tyrosine phosphatases IA-2 and IA-2β
- Autoantibodies to zinc transporter 8 (ZnT8)
One or more of these autoantibodies are present in 85-90% of individuals when hyperglycemia is initially detected 1. The disease also has strong HLA associations, particularly with DQA, DQB, and DRB genes, which can be either predisposing or protective 1.
Key Differences Between Adult-Onset and Childhood-Onset Type 1 Diabetes
Adult-onset type 1 diabetes differs from childhood-onset in several important ways:
- Rate of beta-cell destruction: Typically slower in adults compared to children 1
- Presentation: Adults may not present with the classic symptoms seen in children 1
- Initial insulin dependence: Adults may not require insulin at diagnosis and can experience a "honeymoon period" with decreased insulin needs for months or years 1
- Misdiagnosis risk: Up to 40% of adults with new-onset type 1 diabetes are initially misdiagnosed as having type 2 diabetes 2
Latent Autoimmune Diabetes in Adults (LADA)
A significant subset of adult-onset type 1 diabetes is classified as Latent Autoimmune Diabetes in Adults (LADA), characterized by:
- Slower progression of beta-cell destruction
- Positive autoantibodies (particularly GAD antibodies)
- Initial non-insulin dependence that progresses to insulin dependence over time
- Patients are generally leaner and younger at diabetes onset compared to type 2 diabetes 3
LADA represents a slowly progressive form of autoimmune diabetes where patients may not require insulin for at least 6 months after diagnosis 4.
Diagnostic Approach
To diagnose adult-onset type 1 diabetes, the following tests are recommended:
Islet autoantibody testing:
- GAD antibodies (most sensitive in adults)
- IA-2 antibodies
- ZnT8 antibodies
- Insulin autoantibodies (only useful in patients not previously treated with insulin) 2
C-peptide measurement:
- Collected randomly with concurrent glucose measurement
- Low or undetectable levels (<0.6 ng/mL or <200 pmol/L) indicate type 1 diabetes 2
Clinical Considerations
When laboratory results are indeterminate, consider:
- Age (<35 years suggests type 1 diabetes)
- Body habitus (BMI <25 kg/m² suggests type 1 diabetes)
- Family history of autoimmune diseases
- Inability to achieve glycemic goals on non-insulin therapies 2
Management Implications
The identification of adult-onset type 1 diabetes has important treatment implications:
- Patients will eventually require insulin therapy for survival
- Early insulin therapy may help preserve remaining beta-cell function
- Sulfonylureas may accelerate beta-cell failure in LADA patients 2
- Regular monitoring for complications is essential, as patients with type 1 diabetes are at higher risk for both microvascular and macrovascular complications 5
Idiopathic Type 1 Diabetes
It's worth noting that a small subset of adult-onset type 1 diabetes has no known etiology. These patients have permanent insulinopenia and are prone to ketoacidosis but have no evidence of autoimmunity. This form is more common in individuals of African or Asian ancestry and is strongly inherited 1.