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Diabetes Mellitus, Type 1

Diabetes Mellitus, Type 1 is a topic covered in the 5-Minute Clinical Consult.

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Basics

Description

  • Type 1 diabetes mellitus (T1DM) is a chronic disease caused by insulin deficiency following β-cell destruction.
  • Results in hyperglycemia and end-organ complications
  • Features include:
    • Usually rapid onset
    • Absolute insulin dependence
    • Polyphagia, polydipsia, polyuria, and nocturia
    • Ketosis
    • Body habitus: usually normal or thin physique
  • System(s) affected: endocrine/metabolic, cardiovascular, neurologic, renal, ocular
Pregnancy Considerations
  • T1DM confers maternal and fetal risk (spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia, and neonatal hyperbilirubinemia) (1).
  • Preconception counseling should address importance of glycemic control as close to normal as safely possible (goal A1c <6.5%) to reduce congenital anomalies (1).
  • Glycemic targets during pregnancy: fasting <95 mg/dL, and either 1-hour postprandial <140 mg/dL, or 2-hour postprandial <120 mg/dL
  • Dilated eye examinations should occur before pregnancy or in the 1st trimester and then patients should be monitored every trimester and 1-year postpartum (1).
  • Women with T1DM have an increased risk of hypoglycemia in the 1st trimester and have decreased hypoglycemia awareness.
  • Pregnancy is a ketogenic state, and women are at risk for diabetic ketoacidosis (DKA).
  • Women with T1DM should be prescribed low-dose aspirin 60 to 150 mg/day (81 mg/day) (1).

Epidemiology

  • Age of presentation is bimodal: at 4 to 6 years of age and at 10 to 14 years of age (early puberty) (2).
  • No gender difference in overall incidence (3)

Incidence
  • In the United States, incidence in non-Hispanic white children/adolescents is 23.6/100,000. Prevalence is 2.55/1,000 in non-Hispanic white children/adolescents (4).
  • Substantially lower rates in other racial and ethnic groups

Pediatric Considerations
In infants and toddlers, symptoms of T1DM may be subtle or masquerade as an intercurrent illness and thus are frequently misinterpreted or ignored.

Etiology and Pathophysiology

Pathogenesis

  • 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]) (1)
    • Idiopathic diabetes: no known etiology. Patients have permanent insulinopenia and are prone to ketoacidosis but have no evidence of autoimmunity (1).
  • At least one autoantibody is present in 85–90% of individuals (1).
Genetics
  • The disease has strong 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) (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

  • HLA variations account for ~40% of the genetic risk for T1DM (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 (1)
  • Increased susceptibility to T1DM is inheritable:
    • Only 15% of newly diagnosed patients have a positive family history of T1DM.
    • 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.
    • Offspring of diabetic fathers are at a higher risk (~12%) than offspring of diabetic mothers (~6%) (5).

Commonly Associated Conditions

  • Autoimmune diseases, such as celiac disease, vitamin B12 deficiency, autoimmune gastritis, vitiligo, and Hashimoto hypothyroidism
  • T1DM can also be seen as part of autoimmune polyendocrine syndromes.

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Citation

Stephens, Mark B., et al., editors. "Diabetes Mellitus, Type 1." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. 5minute, www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116180/all/Diabetes_Mellitus__Type_1.
Diabetes Mellitus, Type 1. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116180/all/Diabetes_Mellitus__Type_1. Accessed July 20, 2019.
Diabetes Mellitus, Type 1. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116180/all/Diabetes_Mellitus__Type_1
Diabetes Mellitus, Type 1 [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 July 20]. Available from: https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116180/all/Diabetes_Mellitus__Type_1.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Diabetes Mellitus, Type 1 ID - 116180 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116180/all/Diabetes_Mellitus__Type_1 PB - Wolters Kluwer ET - 27 DB - 5minute DP - Unbound Medicine ER -