What is the difference between type 1 (T1DM) and type 2 (T2DM) diabetes mellitus?

Key Differences Between Type 1 and Type 2 Diabetes Mellitus

Type 1 and type 2 diabetes mellitus fundamentally differ in their etiology, with type 1 being caused by autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency, while type 2 is characterized by insulin resistance and relative insulin deficiency. 1

Etiology and Pathophysiology

Type 1 Diabetes Mellitus

• Cause: Autoimmune destruction of pancreatic beta cells 2, 1
• Insulin Status: Absolute insulin deficiency requiring lifelong exogenous insulin 1
• Genetic Component: Associated with specific HLA alleles, but weaker genetic link than T2DM 1, 3
• Autoantibodies: Positive for GAD65, insulin, IA-2, ZnT8 antibodies 1
• Metabolic State: Characterized by "hyperglycemic dysmetabolism based on insulin deficiency" 2
• Ketosis Risk: High susceptibility to ketosis and diabetic ketoacidosis 2, 1

Type 2 Diabetes Mellitus

• Cause: Combination of insulin resistance and inadequate insulin secretion 2, 1
• Insulin Status: Relative insulin deficiency with initial hyperinsulinemia 2, 1
• Genetic Component: Stronger genetic association than T1DM 3
• Autoantibodies: Typically negative 1
• Metabolic State: Often begins as "euglycemic dysmetabolism" even before hyperglycemia develops 2
• Ketosis Risk: Lower susceptibility to ketosis, except in certain ethnic minorities 1

Clinical Presentation

Type 1 Diabetes Mellitus

• Age of Onset: Typically in children and adolescents, but can occur at any age 2, 1
• Onset Speed: Rapid and symptomatic 1
• Initial Symptoms: Polyuria, polydipsia, weight loss 1, 4
• Presentation: Approximately one-third present with diabetic ketoacidosis 1
• Body Habitus: Usually normal weight 1

Type 2 Diabetes Mellitus

• Age of Onset: Traditionally in adults, but increasingly seen in younger populations 2, 1
• Onset Speed: Gradual and often asymptomatic 1
• Initial Symptoms: May be subtle or absent for years 1
• Presentation: Less commonly presents with ketoacidosis 1
• Body Habitus: Often associated with obesity, particularly central adiposity 1, 5
• Comorbidities: Frequently presents with hypertension, dyslipidemia, and other components of metabolic syndrome 1, 5

Diagnostic Considerations

Laboratory Findings

• C-peptide Levels:
  • T1DM: Low or undetectable 1
  • T2DM: Normal or elevated, especially early in disease 1
• Autoantibodies:
  • T1DM: Positive for islet cell antibodies 1
  • T2DM: Typically negative 1
• Diagnostic Criteria (same for both types):
  • Fasting plasma glucose ≥126 mg/dL
  • 2-hour plasma glucose ≥200 mg/dL during OGTT
  • HbA1c ≥6.5%
  • Random plasma glucose ≥200 mg/dL with symptoms 1

Special Considerations

• LADA (Latent Autoimmune Diabetes in Adults): A form of T1DM with slow progression in adults, with positive autoantibodies but initial presentation similar to T2DM 1
• MODY (Monogenic Diabetes): Consider in patients with atypical features, especially with strong family history and mild hyperglycemia 1

Treatment Approaches

Type 1 Diabetes Mellitus

• Primary Treatment: Lifelong exogenous insulin therapy 1
• Insulin Regimen: Typically basal-bolus insulin or insulin pump 1
• Monitoring: Regular blood glucose monitoring essential; continuous glucose monitoring systems beneficial 1
• Goal: Prevent ketoacidosis, maintain near-normal glucose levels 1

Type 2 Diabetes Mellitus

• Initial Treatment: Lifestyle modifications (diet, exercise, weight loss) 1
• Pharmacotherapy: Oral antidiabetic medications as first-line therapy 1
• Insulin: May be required over time as beta cell function declines 1
• Goal: Manage hyperglycemia and associated cardiovascular risk factors 1

Complications

Both types share similar long-term complications:

• Microvascular: Retinopathy, nephropathy, neuropathy
• Macrovascular: Cardiovascular disease, cerebrovascular disease, peripheral arterial disease
• Acute Emergencies: Diabetic ketoacidosis (more common in T1DM), hyperosmolar hyperglycemic state (more common in T2DM) 1

Clinical Pearls and Pitfalls

• Misdiagnosis Risk: The distinction between T1DM and T2DM is not always clear-cut, especially in overweight youth or adults with acute presentation 2
• Treatment Initiation: Insulin therapy should be initiated for children and adolescents with diabetes who are ketotic or in diabetic ketoacidosis when the distinction between T1DM and T2DM is unclear 2
• Autoimmune Associations: T1DM is associated with other autoimmune disorders, particularly autoimmune thyroid disease 2
• Double Diabetes: Some patients may have features of both types, requiring complex treatment regimens addressing both insulin deficiency and insulin resistance 1

Understanding these fundamental differences is crucial for appropriate diagnosis, treatment selection, and long-term management to optimize outcomes and reduce complications.