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 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
  • HbA1c is slightly lower during pregnancy due to increased RBC 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].
  • Dilated eye examinations should occur before pregnancy or in the 1st trimester and monitored every trimester and 1-year postpartum (1)[B].
  • Women with T1DM should be prescribed low-dose aspirin 60 to 150 mg/day (usual dose 81 mg/day) by the end of the 1st trimester in order to lower the risk of preeclampsia (if no contraindication) (1)[C].

Epidemiology

Age of presentation is bimodal: at 4 to 6 years of age and at 10 to 14 years of age (early puberty) (2).

Incidence
  • 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

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

Prevalence
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 three 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).

Genetics
  • 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

  • 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.
    • Offspring of fathers with diabetes are at a higher risk (~12%) than offspring of mothers with diabetes (~6%) (5).

General Prevention

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).

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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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 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
  • HbA1c is slightly lower during pregnancy due to increased RBC 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].
  • Dilated eye examinations should occur before pregnancy or in the 1st trimester and monitored every trimester and 1-year postpartum (1)[B].
  • Women with T1DM should be prescribed low-dose aspirin 60 to 150 mg/day (usual dose 81 mg/day) by the end of the 1st trimester in order to lower the risk of preeclampsia (if no contraindication) (1)[C].

Epidemiology

Age of presentation is bimodal: at 4 to 6 years of age and at 10 to 14 years of age (early puberty) (2).

Incidence
  • 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

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

Prevalence
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 three 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).

Genetics
  • 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

  • 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.
    • Offspring of fathers with diabetes are at a higher risk (~12%) than offspring of mothers with diabetes (~6%) (5).

General Prevention

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).

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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