Diabetes Mellitus, Type 1
- Type 1 diabetes mellitus (T1DM) is a chronic disease caused by insulin deficiency following β-cell destruction.
- Results in hyperglycemia and potential end-organ complications
- Features include:
- Usually rapid onset
- Absolute insulin dependence
- Polyphagia, polydipsia, polyuria, and nocturia
- Ketosis or diabetic ketoacidosis (DKA)
- Body habitus: usually normal or thin physique at diagnosis
- System(s) affected: endocrine, metabolism, cardiovascular, neurologic, renal, ocular
- T1DM confers maternal and fetal risk (spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia, and neonatal hyperbilirubinemia).
- Preconception counseling should address the importance of glycemic control as close to normal as safely possible to reduce congenital anomalies.
- Glycemic targets during pregnancy: fasting <95 mg/dL, and 1-hour postprandial <140 mg/dL, or 2-hour postprandial <120 mg/dL
- Women with T1DM should be prescribed low-dose aspirin 60 to 150 mg/day (usual dose 81 mg/day) by the end of the first trimester in order to lower the risk of preeclampsia (if no contraindication) (1)[C].
Age of presentation is bimodal: at 4 to 6 years of age and at 10 to 14 years of age (early puberty) (2).
- In the United States, incidence is 23.6/100,000 in non-Hispanic white children and adolescents (3).
- Lower rates in other racial and ethnic groups
In infants and toddlers, symptoms of T1DM may be subtle or masquerade as an intercurrent illness.
The U.S. prevalence of type 1 diabetes ranges from 2.6/1000 to 3.7/1000 (4).
Etiology and Pathophysiology
There are two main categories of T1DM: immune-mediated and idiopathic diabetes (1):
- Immune-mediated diabetes: cellular-mediated autoimmune destruction of β cells of the pancreas (markers: autoantibodies to insulin, GAD65, tyrosine phosphatases IA-2 and IA-2β, including zinc transporter 8 autoantibody [ZnT8A]). Obtain 3 antibody tests (GAD65, IA-2A, ZnT8) to rule out MODY-monogenic diabetes.
- Idiopathic diabetes: no known etiology for permanent insulinopenia; prone to ketoacidosis but have no evidence of autoimmunity
- At least one autoantibody is present in 85–90% of individuals (1).
- HLA associations, with linkage to the DQA and DQB genes, and it is influenced by the DRB genes (HLA-DQA1, HLA-DQB1, and DLA-DRB1). These antibodies can be predisposing or protective (1).
- The major susceptibility locus maps to the HLA class II genes at 6p21 (accounting for 30–50% of genetic T1DM), but there are >40 loci (5).
- Risk factors: viral infections, vitamin D deficiency, perinatal factors (maternal age, history of preeclampsia, neonatal jaundice), high birth weight for gestational age, and lower gestational age at birth
- Increased susceptibility to T1DM is inheritable:
- T1DM in monozygous twins with long-term follow-up is >50%.
- Among first-degree relatives, siblings are at a higher risk (5–10% risk by age 20 years) than offspring.
- Offsprings of fathers with diabetes are at a higher risk (~12%) than offsprings of mothers with diabetes (~6%) (5).
Although there is currently a lack of accepted screening programs, providers should consider referring relatives of those with type 1 diabetes for risk assessment in a clinical research study (http://www.diabetestrialnet.org) (1).
Commonly Associated Conditions
Autoimmune diseases, such as primary adrenal insufficiency (Addison disease), celiac disease, autoimmune hepatitis, pernicious anemia, myasthenia gravis, vitiligo, Graves disease, and Hashimoto hypothyroidism
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