Differences Between Stage 1 and Stage 2 Type 1 Diabetes
The key difference between stage 1 and stage 2 type 1 diabetes is that stage 1 has normoglycemia while stage 2 has dysglycemia, though both stages are presymptomatic and characterized by autoimmunity. 1
Diagnostic Characteristics
Stage 1 Type 1 Diabetes
- Defined by the presence of multiple islet autoantibodies (two or more) 1
- Normal blood glucose levels (normoglycemia) 1
- No impaired fasting glucose (IFG), no impaired glucose tolerance (IGT), and normal A1C 1
- Presymptomatic - patients do not yet experience classic diabetes symptoms 1
- 5-year risk of developing symptomatic type 1 diabetes is approximately 44% 1
Stage 2 Type 1 Diabetes
- Continued presence of islet autoantibodies (usually multiple) 1
- Dysglycemia, which may be defined by one or more of the following criteria: 1
- Impaired fasting glucose (IFG): FPG 100–125 mg/dL (5.6–6.9 mmol/L)
- Impaired glucose tolerance (IGT): 2-hour plasma glucose 140–199 mg/dL (7.8–11.0 mmol/L)
- A1C 5.7–6.4% (39–47 mmol/mol)
- ≥10% increase in A1C
- Still presymptomatic - patients do not yet experience classic diabetes symptoms 1
- Higher risk of progression - 60% risk by 2 years and 75% risk within 5 years of developing clinical type 1 diabetes 1
Disease Progression and Risk
- Both stages represent presymptomatic autoimmune destruction of pancreatic β-cells 1
- Progression from stage 1 to stage 2 indicates advancing disease with deteriorating glycemic control 1
- The risk of progression varies based on several factors: 1
- Number, titer, and specificity of autoantibodies
- Age of autoantibody seroconversion
- Genetic risk factors (particularly HLA associations)
Monitoring Recommendations
- For stage 1, regular monitoring of glycemic status is recommended to detect progression to stage 2 1
- For stage 2, more intensive monitoring is advised due to the higher risk of progression to symptomatic (stage 3) type 1 diabetes 1
- A consensus guidance provides specific recommendations on what should be monitored and how frequently in individuals with presymptomatic type 1 diabetes 1
Clinical Implications
- Neither stage 1 nor stage 2 requires insulin therapy yet, as both are presymptomatic 1, 2
- Stage 2 represents a critical window for potential intervention to delay progression to symptomatic disease 2
- Clinical trials are being conducted to test various methods of preventing or delaying progression from stages 1 and 2 to symptomatic type 1 diabetes 1, 3
- When multiple islet autoantibodies are identified in either stage, referral to a specialized center for further evaluation and/or consideration of clinical trials should be considered 1
Progression to Stage 3 (Clinical Diabetes)
- Stage 3 is characterized by: 1
- Overt hyperglycemia
- Symptomatic presentation (polyuria, polydipsia, weight loss)
- Standard diagnostic criteria for diabetes
- May have reduced or absent autoantibodies at this stage
- The rate of β-cell destruction varies significantly between individuals, being more rapid in children and slower in adults 1
Key Pitfalls to Avoid
- Failing to recognize that both stage 1 and stage 2 are presymptomatic, despite stage 2 showing laboratory evidence of dysglycemia 1
- Overlooking the opportunity for intervention in stage 2 to potentially delay progression to insulin-dependent diabetes 2
- Not considering referral to specialized centers or clinical trials for individuals identified with multiple islet autoantibodies 1
- Underestimating the risk of rapid progression to symptomatic diabetes, particularly in children with stage 2 disease 1
Understanding these stages allows for early identification of at-risk individuals and potential interventions to delay progression to symptomatic type 1 diabetes, which could significantly impact long-term morbidity and mortality 3, 2.