Description

• Chronic disease caused by pancreatic insufficiency (deficiency) of insulin production
• Results in hyperglycemia and end-organ complications (e.g., accelerated atherosclerosis, neuropathy, nephropathy, and retinopathy)
• Features include:
  • Patients are insulinopenic and require insulin.
  • Ketosis
  • Usually rapid onset
  • Nutritional status: Normal or thin physique
• System(s) affected: Endocrine/Metabolic

• During embryogenesis, hyperglycemia increases the incidence of congenital malformations. Tight control of blood sugar prior to conception is important.
• Women with microalbuminuria during the 1st trimester are at increased risk for preeclampsia and preterm delivery.
• A safe pregnancy is possible with vaginal delivery of a term baby. Close monitoring of blood sugar during labor is important.

Epidemiology

• Mean age of onset 8–12 years, peaking in adolescence
• Onset 1.5 years earlier in girls than boys
• Rapid decline in incidence after adolescence
• Overall incidence increasing worldwide
• Age of presentation has a bimodal distribution, being highest at ages 4–6 and 10–14 years.

• 15/100,000 per year
• Racial predilection for whites
• African Americans have lowest overall incidence.

• Although onset is usually before the age of 19 years, true type 1 diabetes can occur for the 1st time in patients who are well into their 30s.
• Young children are more likely to present in diabetic ketoacidosis (DKA) due to atypical presentation and because they may not express thirst or obtain fluids as readily as older children or adults.

Risk Factors

• Certain human leukocyte antigen (HLA) types
• Presence of a specific 64,000 mw protein may be responsible for antibody formation.
• Family history: Insulin-dependent or noninsulin-dependent diabetes in any 1st-degree relatives
• Dietary factors: Breastfeeding may provide a degree of protection against the disease, whereas exposure to cow's milk at an early age is associated with an increased risk of the disease.
• Maternal age at birth may play a role (1).
• Slightly greater risk for a child if the father has type 1 diabetes

• Mode of genetic expression not clear
• Genes located on major histocompatibility complex on chromosome 6
• HLA DR3 and DR4 are individually associated with an increased risk; if a person is carrying both susceptibility genes, the relative risk is increased.
• HLA B8 and B15 also associated with increased risk

Pathophysiology

• Alteration in immunologic integrity, placing the β-cell at special risk for inflammatory damage, accounts for most cases.
• Autoantibodies to islet cells, glutamic acid decarboxylase (GAD), tyrosine phosphatase antibodies, and insulin identified in certain cases (type 1A diabetes)
• Some idiopathic cases (type 1B) have no evidence of autoimmune or other reason for β-cell damage.

Etiology

• Inherited defect
• Associated environmental triggers (none has been verified):
  • Viruses (e.g., mumps, coxsackie, cytomegalovirus, and hepatitis viruses)
  • Diet high in nitrosamines
  • Environmental toxins
• Emotional and physical stress

Commonly Associated Conditions

• Autoimmune diseases, such as celiac disease, hypothyroidism, and Addison disease:
  • Screening regularly for hypothyroidism is particularly important in females.
• Diabetes mellitus can also be seen as part of multiple endocrine adenomatosis.