Diabetes mellitus type 1 – etiology, pathogenesis, and clinical manifestations.
Type 1 diabetes mellitus is a chronic autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreatic islets of Langerhans, leading to absolute insulin deficiency.
Etiology (Causes)
- 1 Genetic predisposition
- Strong association with HLA class II genes, especially:
- HLA-DR3, DR4.
- HLA-DQ2, DQ8 .
- Concordance rate higher in monozygotic twins (~30–50%).
- 2 Autoimmune factors
- Presence of autoantibodies against:
- Glutamic acid decarboxylase (GAD65).
- Insulin (IAA).
- Islet cell antigens (ICA).
- Tyrosine phosphatase IA-2 .
- Lymphocytic infiltration ("insulitis") leads to β- cell destruction.
- 3 Environmental triggers
- Viral infections (e.g., Coxsackievirus B, rubella).
- Early exposure to cow's milk proteins (possible hypothesis).
- Certain toxins or dietary factors.
Pathogenesis
- 1 Autoimmune β- cell destruction
- Trigger: environmental factor in genetically susceptible individuals.
- Activation of autoreactive T cells → attack on pancreatic β- cells.
- Progressive reduction of β- cell mass → decreasing insulin production.
- 2 Metabolic consequences of insulin deficiency
Hyperglycemia
- ↓ Glucose uptake (especially in muscle and adipose tissue).
- ↑ Hepatic gluconeogenesis and glycogenolysis.
Lipolysis and ketogenesis
- ↑ Breakdown of triglycerides → free fatty acids.
- Free fatty acids converted in liver to ketone bodies → ketoacidosis.
Protein catabolism
- ↑ Proteolysis → muscle wasting and weight loss.