Diabetes Gestacional

Update on Gestational Diabetes
Gabriella Pridjian,
KEYWORDS  Gestational diabetes  Pregnancy complications  Glyburide  Insulin
MD*,

Tara D. Benjamin,

MD

Gestational diabetes mellitus (GDM), diabetes first diagnosed in pregnancy, complicates about 5% to 10% of pregnancies, which is an expected wide range of prevalence, given the variation in populations studied, the currentvariability in screening and diagnosis,1 and a recent disproportionate increase in younger, obese women.2
GLUCOSE METABOLISM AND GESTATIONAL DIABETES

In normal pregnancy, directly or indirectly, the growth of the fetal-placental unit increases cortisol, growth hormone, human placental lactogen, estrogen, progesterone, and prolactin, which in concert lead to hyperinsulinemia, insulin resistance,fasting hypoglycemia, and postprandial hyperglycemia.3–5 A progressive transition of fuel sources occurs so that by the third trimester, the metabolic fuel to meet the demands of the fetus changes from predominately maternal carbohydrate to fat. Pregnancy is characterized by increased and adaptive pancreatic beta-cell function to compensate for decreased insulin sensitivity and increased requirements.6Morphologically, maternal pancreatic hypertrophy and hyperplasia occur.7 In response to elevated insulin levels, peripheral muscle glucose use and tissue glycogen storage increase in an effort to maintain normal insulin sensitivity in the first trimester of pregnancy.8–10 As gestation advances, these responses become inadequate to meet the energy requirements of the fetus, and insulin resistancedevelops.11,12 Insulin resistance in normal pregnancy is estimated to increase by 40% to 70%, predominately in the third trimester. In a longitudinal study of healthy pregnant women using the hyperinsulinemic-euglycemic clamp, Catalano and colleagues11 found a 56% decrease in insulin sensitivity in nonobese women by late pregnancy. Using the euglycemic-hyperinsulinemic clamp, Sivan andcolleagues13 demonstrated that healthy women developed insulin resistance mostly in the third trimester and showed a 40% reduction in peripheral glucose uptake by muscle in the third trimester compared with the nonpregnant state. Using a minimal model technique, Buchanan

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Tulane University Medical School, 1430 Tulane Avenue,SL11, New Orleans, LA 70112, USA * Corresponding author. E-mail address: Pridjian@Tulane.edu Obstet Gynecol Clin N Am 37 (2010) 255–267 doi:10.1016/j.ogc.2010.02.017 obgyn.theclinics.com 0889-8545/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved.

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and colleagues14 found that insulin sensitivity in normal pregnant women was reduced to about one-third ofthat of nonpregnant women of similar weight and age. Furthermore, the reduction in insulin sensitivity was compensated by reciprocal increase of the first and second phase insulin response. There seems to be no significant change in insulin receptor binding in pregnancy15; thus insulin resistance in normal pregnancy is likely related to postreceptor handling of glucose. Postreceptor mechanismscontributing to insulin resistance include (1) impaired tyrosine kinase activity,16 which is normally responsible for the phosphorylation of cellular substrates; (2) decreased expression of insulin receptor substrate-1, a cytosolic protein that binds phosphorylated intracellular substrates and transmits signals downstream17; and (3) decreased expression of the GLUT4 glucose transport protein inadipose tissue, which promotes glucose uptake.18 The cytokine tumor necrosis factor a19 and leptin may also be involved in insulin resistance seen in normal pregnancy.20,21 Compared with normal pregnant women, women with GDM have impaired beta-cell function and reduced beta-cell adaptation resulting in insufficient insulin secretion to maintain normal glycemia. Women with GDM, and more so obese women...