Diabetes Mellitus, Type I

Basics

Description

Type 1 diabetes is an autoimmune disorder that causes pancreatic β-cell destruction. This destruction leads to insulin deficiency that results in hyperglycemia and disrupts energy storage and metabolism. Severe insulin deficiency can lead to ketosis, acidosis, dehydration, shock, and death.

Epidemiology

  • Most common endocrine disorder of childhood
  • More common in whites of Northern European descent

Incidence

  • Annual U.S. incidence is <19/100,000 in children 10 to 19 years old.
  • Incidence of type 1 diabetes is rising by 3% per year overall and faster in young children.

Prevalence

  • Prevalence of type 1 diabetes in youth 0 to 19 years in United States is <2/1,000.
  • Note: At least 2% of diabetes in children may be due to maturity-onset diabetes of youth (MODY) or other genetic forms.

Risk Factors

Genetics

  • Increased susceptibility to type 1 diabetes associated with HLA region of chromosome 6, 5-fold greater risk with MHC antigen types DR3 and DR4
  • MODY is a group of autosomal dominant syndromes of partial insulin deficiency due to monogenic defects of pancreatic development or insulin secretion; they comprise a small fraction of childhood diabetes.

Pathophysiology

  • Loss of pancreatic β cells results in insulin deficiency, leading to hyperglycemia and predominance of catabolic processes.
  • Hyperglycemia causes hyperosmolality, polyuria, and damage to small blood vessels.
  • Catabolic processes produce ketosis, weight loss, and metabolic acidosis.

Etiology

  • An environmental trigger (likely viral) induces expression of antigens on β-cell surface.
  • Recruitment of cytotoxic lymphocytes
  • Production of anti-insulin and anti-islet cell anti-bodies (including GAD65, ICA512, ZnT8)
  • Progressive inflammatory, autoimmune loss of β-cell mass results in insulin deficiency.
  • Autoimmunity precedes hyperglycemia; development of two or more antibodies will inevitably lead to dysglycemia due to type 1 diabetes.
  • The autoimmune destruction of β cells is more likely in genetically susceptible persons.

Commonly Associated Conditions

  • Autoimmune thyroid disease
    • Hashimoto (hypothyroidism) more common than Graves (hyperthyroidism)
  • Celiac disease
  • More rarely other autoimmune diseases, such as alopecia areata, rheumatoid arthritis
  • Depression
  • After prolonged hyperglycemia: vascular complications:
    • Microvascular
      • Nephropathy
      • Retinopathy
      • Neuropathy
      • (See “Patient Monitoring” for screening recommendations.)
    • Macrovascular
      • Peripheral vascular disease
      • Cardiovascular disease

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