How do you differentiate between Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus?

Differentiating Between Type 1 and Type 2 Diabetes Mellitus

Type 1 and Type 2 diabetes are distinguished primarily by their pathophysiology, with Type 1 resulting from autoimmune β-cell destruction leading to absolute insulin deficiency, while Type 2 stems from progressive loss of β-cell insulin secretion typically on a background of insulin resistance. 1

Key Diagnostic Differences

Pathophysiological Mechanisms

• Type 1 Diabetes:

  • Due to autoimmune β-cell destruction 1
  • Leads to absolute insulin deficiency
  • Includes latent autoimmune diabetes of adulthood
  • High susceptibility to ketosis and diabetic ketoacidosis 2

• Type 2 Diabetes:

  • Progressive loss of adequate β-cell insulin secretion
  • Often occurs with underlying insulin resistance
  • Initial hyperinsulinemia followed by relative insulin deficiency 2
  • Stronger genetic association than Type 1 2

Clinical Presentation

Type 1 Diabetes

• Most discriminating features 1:
  • Younger age at diagnosis (<35 years)
  • Lower BMI (<25 kg/m²)
  • Unintentional weight loss
  • Ketoacidosis at presentation
  • Glucose >360 mg/dL (20 mmol/L) at presentation
• Classic symptoms: polyuria, polydipsia
• Approximately half present with diabetic ketoacidosis (DKA) 1
• May have more variable presentation in adults 1

Type 2 Diabetes

• Often associated with:
  • Older age
  • Obesity (particularly central adiposity)
  • Features of metabolic syndrome
  • Hypertension and dyslipidemia 2
• Typically gradual and often asymptomatic onset 2
• May occasionally present with DKA, particularly in ethnic and racial minorities 1

Diagnostic Tools

Laboratory Testing

1. Autoantibody Testing:

   • Presence of autoantibodies to insulin, glutamic acid decarboxylase (GAD), islet antigen 2 (IA-2), or zinc transporter 8 (ZnT8) suggests Type 1 diabetes 1
   • Multiple confirmed islet autoantibodies indicate high risk for clinical Type 1 diabetes 1

2. C-peptide Measurement:

   • C-peptide values 200-600 pmol/L (0.6-1.8 ng/mL) are usually consistent with Type 1 diabetes 1
   • Higher C-peptide levels typically suggest Type 2 diabetes

3. Standard Diagnostic Criteria (for both types):

   • Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L)
   • 2-hour plasma glucose during OGTT ≥200 mg/dL (11.1 mmol/L)
   • HbA1c ≥6.5% (48 mmol/mol)
   • Random plasma glucose ≥200 mg/dL (11.1 mmol/L) with symptoms 2

Clinical Decision Tool: AABBCC Approach

The American Diabetes Association recommends the AABBCC approach for distinguishing diabetes types 1:

• Age (e.g., <35 years suggests Type 1)
• Autoimmunity (personal or family history of autoimmune disease)
• Body habitus (BMI <25 kg/m² suggests Type 1)
• Background (family history of Type 1)
• Control (inability to achieve glycemic goals on non-insulin therapies)
• Comorbidities (e.g., immune checkpoint inhibitor treatment can cause acute autoimmune Type 1 diabetes)

Important Considerations

1. Misdiagnosis is Common:

   • Up to 40% of adults with new Type 1 diabetes are initially misdiagnosed as having Type 2 diabetes 1
   • Diagnosis may become more obvious over time as the degree of β-cell deficiency becomes clear 1

2. Age is Not Definitive:

   • The traditional paradigm of Type 1 in children and Type 2 in adults is no longer accurate 1
   • Both types can occur in all age groups 1

3. Overlapping Features:

   • Some patients cannot be clearly classified at diagnosis 1
   • A diagnosis of Type 1 does not preclude features classically associated with Type 2 (insulin resistance, obesity) 1

4. Ketosis-Prone Type 2 Diabetes:

   • Some patients, particularly ethnic minorities, may present with Type 2 diabetes and ketosis 1
   • This form is strongly inherited and not HLA-associated 1

By systematically evaluating these clinical and laboratory parameters, clinicians can more accurately differentiate between Type 1 and Type 2 diabetes, leading to appropriate treatment strategies and improved patient outcomes.