Pathophysiology and Management of Type 1 Diabetes
Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency that requires lifelong insulin therapy. 1 This autoimmune process progresses through distinct stages before clinical manifestation of the disease.
Pathophysiology
Autoimmune Process
Type 1 diabetes develops through three distinct stages 1:
- Stage 1: Multiple autoantibodies with normoglycemia
- Stage 2: Multiple autoantibodies with dysglycemia
- Stage 3: Clinical diabetes with symptoms
The autoimmune destruction targets pancreatic β-cells, with islet autoantibodies (against insulin, GAD65, IA-2, and ZnT8) appearing months to years before symptom onset 1
Hormonal Imbalance
- Insulin deficiency: Primary defect resulting from β-cell destruction 2
- Glucagon dysregulation: Impaired secretion and inability to release glucagon in response to hypoglycemia 1
- Amylin deficiency: Contributes to poor postprandial glucose control as amylin is normally co-secreted with insulin 1
Metabolic Consequences
- Severe insulin deficiency leads to:
Diagnosis
Diagnostic Criteria
- Fasting blood glucose ≥1.26 g/L (7.0 mmol/L) on two occasions 2
- Plasma blood glucose ≥2 g/L (11.1 mmol/L) at 2 hours after oral glucose tolerance test 2
- HbA1c >6.5% (in some countries) 2
- Presence of clinical symptoms (polyuria/polydipsia) with hyperglycemia 1
Differentiating Type 1 from Type 2 Diabetes
- Autoantibody testing: The American Diabetes Association recommends testing for GAD autoantibodies first, followed by IA-2 and/or ZnT8 if negative 1
- C-peptide measurement: Levels <200 pmol/L (<0.6 ng/mL) suggest significant insulin deficiency (type 1), while levels >600 pmol/L (>1.8 ng/mL) suggest preserved insulin secretion (type 2) 1
- Clinical presentation: Higher glucose levels (>360 mg/dL or 20 mmol/L) and classic symptoms of polyuria/polydipsia are more common in type 1 diabetes 1
Management
Insulin Therapy
- Basal-bolus regimen: The mainstay of treatment involves either multiple daily injections or continuous subcutaneous insulin via pump 3
- Typically consists of:
- Insulin glargine administered once daily at bedtime has been shown to be as effective as NPH insulin in controlling HbA1c and fasting glucose in both adults and pediatric patients with type 1 diabetes 3
Monitoring
- Regular blood glucose monitoring is essential
- Continuous glucose monitoring systems have improved glycemic control and decreased hypoglycemia risk 1
- Automated insulin delivery systems (hybrid closed-loop systems) represent advanced management options 1
Complications and Prognosis
- Despite improved treatments, most patients with type 1 diabetes still develop microvascular and macrovascular complications 1
- Regular screening for hypertension and other associated conditions is recommended 1
Common Pitfalls and Caveats
- Misdiagnosis: Up to 40% of adults with new-onset type 1 diabetes are misdiagnosed as having type 2 diabetes 1
- Age-based assumptions: Both type 1 and type 2 diabetes can occur at any age, so diagnosis should not be based solely on age 1
- Autoantibody limitations: 5-10% of people with type 1 diabetes do not have detectable autoantibodies 1
- HbA1c reliability: May be unreliable in conditions affecting red blood cell turnover or in presence of hemoglobin variants 1
- Monogenic diabetes: Should be considered in patients with atypical features, especially with strong family history and mild hyperglycemia 1
By understanding the pathophysiology and implementing appropriate management strategies, the goal is to minimize complications and improve quality of life for individuals with type 1 diabetes.