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Diabetes mellitus is associated with the significant risks of developmental defects and stillbirth for the fetus, organ dysfunction for the mother during pregnancy, and increased lifetime likelihood for developing hypertensive disease, dyslipidemias, and progressive glucose intolerance. Physicians who care for pregnant women must be aware of the interplay between the physiologic changes of pregnancy and diabetes in order to optimize outcomes for both parturient and neonate.
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EPIDEMIOLOGY AND ETIOLOGY OF DIABETES
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Diabetes mellitus is a heterogeneous group of endocrine disorders characterized by elevated glucose levels, caused by a deficiency of insulin secretion or insulin resistance in peripheral tissue. Diabetes occurs in approximately 11% of the US population, with an additional 35% exhibiting symptoms of prediabetes. The prevalence has increased by 128% from 1988 to 2008, largely due to soaring rates of obesity.1,2 The incidence of preexisting diabetes during pregnancy grew from 10% to 21% between 1999 and 2005.3
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Insulin is a peptide hormone secreted by the β cells in the pancreatic islets of Langerhans that binds to insulin cell surface receptors in the liver, skeletal muscle, and adipose tissue. Insulin binding causes a conformational change in the α portion of the receptor, which activates kinase domains on its intracellular β subunits. Autophosphorylation of tyrosine residues initiates a series of signaling events that increases translocation of glucose transporter type 4 (GLUT4) from storage vesicles to the cell membrane. Insulin is critical in modulating maternal glucose, fat, and protein metabolism. Normal glucose metabolism represents a balance between insulin and the counteractive effects of glucagon, cortisol, epinephrine, and growth hormone.
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PATHOPHYSIOLOGY AND RISK FACTORS FOR DIABETES IN PREGNANCY
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Diabetes that is diagnosed before pregnancy is described by the standard classification as either type 1 or type 2. A third type, gestational diabetes, refers to a glycemic disorder discovered during pregnancy in the absence of preexisting metabolic disease. Individuals who have impaired fasting glucose (IFG) are referred to as having prediabetes, and they have a higher risk of developing future diabetes. As expected, IFG and impaired glucose tolerance (IGT) are associated with obesity, particularly abdominal obesity, dyslipidemia, and hypertension.
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Patients with type 1 diabetes (T1D) account for approximately 5% to 10% of those with the disease. This term includes patients previously referred to as insulin-dependent diabetes mellitus, or juvenile-onset diabetes mellitus. T1D is due to an absolute deficiency of insulin secretion following the cell-mediated autoimmune destruction of the β cells of the pancreas. Biomarkers of this immune destruction include autoantibodies to islet cells, insulin itself, glutamic acid decarboxylase, and tyrosine phosphatases IA-2 and IA-2β. One or more of these autoantibodies is present when fasting hyperglycemia is initially detected. There is also a strong association with human leukocyte antigen (HLA) types linked to DQA and DQB genes and influenced by DRB genes. These ...