Diabetes Mellitus, Type 1

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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 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/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).
  • Preconception counseling should address importance of glycemic control as close to normal as safely possible (goal A1c <6.5%) to reduce congenital anomalies.
  • 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)[B].
  • HbA1c is slightly lower during pregnancy due to increased red blood cell turnover. The HbA1c target should ideally be <6% if achieved without hypoglycemia, but can be relaxed to <7% if necessary to prevent hypoglycemia (1)[B].
  • Women with T1DM should be prescribed low-dose aspirin 60 to 150 mg/day (81 mg/day) until the baby is born (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 is 21.7/100,000 cases per year in patients aged 0–19 years (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.

Prevalence
The prevalence of type 1 diabetes of the entire U.S. ranges from 2.6/1,000 to 3.7/1,000 (5).

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

Genetics
  • The disease has strong human leukocyte antigen (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 (6).

Risk Factors

  • HLA variations account for ~40% of the genetic risk for T1DM (6).
  • 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:
    • 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%) (6).

General Prevention

  • Several studies have demonstrated that measuring islet cell autoantibodies may identify individuals at risk for T1DM (1).
  • 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 (www.diabetestrialnet.org) (1).
  • Numerous clinical trials are currently being conducted to prevent type 1 diabetes (www.clinicaltrials.gov) (1).

Commonly Associated Conditions

  • Autoimmune diseases, such as Addison disease, celiac disease, autoimmune hepatitis, pernicious anemia, myasthenia gravis, vitiligo, Graves disease and Hashimoto hypothyroidism.
  • T1DM can also be seen as part of autoimmune polyendocrine syndromes.

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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 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/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).
  • Preconception counseling should address importance of glycemic control as close to normal as safely possible (goal A1c <6.5%) to reduce congenital anomalies.
  • 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)[B].
  • HbA1c is slightly lower during pregnancy due to increased red blood cell turnover. The HbA1c target should ideally be <6% if achieved without hypoglycemia, but can be relaxed to <7% if necessary to prevent hypoglycemia (1)[B].
  • Women with T1DM should be prescribed low-dose aspirin 60 to 150 mg/day (81 mg/day) until the baby is born (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 is 21.7/100,000 cases per year in patients aged 0–19 years (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.

Prevalence
The prevalence of type 1 diabetes of the entire U.S. ranges from 2.6/1,000 to 3.7/1,000 (5).

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

Genetics
  • The disease has strong human leukocyte antigen (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 (6).

Risk Factors

  • HLA variations account for ~40% of the genetic risk for T1DM (6).
  • 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:
    • 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%) (6).

General Prevention

  • Several studies have demonstrated that measuring islet cell autoantibodies may identify individuals at risk for T1DM (1).
  • 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 (www.diabetestrialnet.org) (1).
  • Numerous clinical trials are currently being conducted to prevent type 1 diabetes (www.clinicaltrials.gov) (1).

Commonly Associated Conditions

  • Autoimmune diseases, such as Addison disease, celiac disease, autoimmune hepatitis, pernicious anemia, myasthenia gravis, vitiligo, Graves disease and Hashimoto hypothyroidism.
  • T1DM can also be seen as part of autoimmune polyendocrine syndromes.

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