Diabetes Mellitus, Type I
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.
- Most common endocrine disorder of childhood
- More common in whites of Northern European descent
- 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 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.
- 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.
- 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.
- 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
- After prolonged hyperglycemia: vascular complications:
- (See “Patient Monitoring” for screening recommendations.)
- Peripheral vascular disease
- Cardiovascular disease
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