Diabetes Mellitus, Type 1
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- Type 1 diabetes mellitus (T1DM) is a 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 the following:
- Patients are insulinopenic and require insulin.
- Polyphagia, polydipsia, and polyuria
- Usually rapid onset
- Body habitus: usually normal or thin physique
- System(s) affected: endocrine/metabolic
- Hyperglycemia increases the incidence of congenital malformations. Tight control of blood sugar prior to conception (goal A1C <6.5%) is important (1).
- Family planning should be discussed and effective contraception offered until A1C is within goal range to reduce the risk of congenital anomalies.
- 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.
- Many drugs used to treat diabetic complications are relatively/absolutely contraindicated in pregnancy.
- Perinatal and psychological stressors are associated with T1DM in children.
- Age of onset peaks between 5 and 7 years of age and again around puberty; rapid decline in incidence after adolescence
- Slightly more common in males than females
- Overall incidence is increasing worldwide.
- More cases are diagnosed in the autumn and winter than in spring and summer.
- 18/100,000 per year in the United States (0 to 60/100,000 worldwide) (2)
- Average lifetime prevalence risk of T1DM in the general population is 0.4%.
- Racial predilection for whites
- African Americans have lowest overall incidence.
- Although onset is usually before the age of 19 years, T1DM can occur for the first 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.
Etiology and Pathophysiology
- Genetic predisposition is thought to exist.
- Alteration in immunologic integrity, placing the β-cell at special risk for inflammatory damage
- Autoantibodies present in >90% of patients at presentation: glutamic acid decarboxylase (GAD), insulinoma-associated autoantigen 2 (IA2A), zinc transporter 8 (ZnT8A), and insulin (IAA) (2)
- Associated environmental triggers (none have been verified):
- Vitamin D deficiency
- Infant feeding practices (short-term breastfeeding, early exposure to complex proteins)
- Viruses (e.g., enteroviruses, retroviruses)
- Environmental toxins
- Various epigenetic modifications of gene expression (DNA methylation, histone modifications, and μ-RNA dysregulation) have been noted, further suggesting a role between genetics and environment in the development of T1DM (3).
- T1DM is a polygenic disorder with 40+ loci known to affect susceptibility to the disease (2).
- Genes located on major histocompatibility complex (MHC) on chromosome 6 provide about half of the genetic susceptibility leading to T1DM risk (2).
- HLA class II shows the strongest association with T1DM risk, but class I MHCs also affect risk (2).
- Certain human leukocyte antigen (HLA) types, MHC classes, and autoantibodies (2)
- Increased susceptibility to T1DM is inheritable (3):
- Only 10–15% of newly diagnosed patients with T1DM have a positive family history of T1DM.
- Among autoimmune conditions, T1DM has the highest concordance rates in monozygotic twins.
- Average prevalence risk of T1DM in children of patients with T1DM is ~6%.
- Relative risk for siblings of patients with T1DM is about 15%.
- See environmental triggers above (2).
Commonly Associated Conditions
- Autoimmune diseases, such as celiac disease, vitamin B12 deficiency, and Hashimoto hypothyroidism
- T1DM can also be seen as part of autoimmune polyendocrine syndromes.