secretion as a function of increased progesterone. Motility of the small intestine is also reduced during gestation; however, except for enhanced iron absorption, nutrient absorption is unchanged. These physiologic changes may affect the pattern of gestational weight gain in early gestation.

Changes in protein and nitrogen metabolism occur in early pregnancy, presumably in response to pregnancy-related hormones (Kalhan, 2000). Serum total α-amino nitrogen deceases, as does the rate of urea synthesis and the rate of transamination of branched-chain amino acids, which are aimed at conservation of nitrogen and protein accretion in pregnancy. Protein turnover on a weight basis, however, does not change (Kalhan, 2000). Serum total protein and albumin fall progressively and by term are 30 percent lower than nonpregnant values (Hytten and Chamberlain, 1991). The concentrations of binding proteins for corticosteroids, sex steroids, thyroid hormones, and vitamin D also increase.

Changes in carbohydrate and lipid metabolism occur during pregnancy to ensure a continuous supply of nutrients to the growing fetus (Butte, 2000). In early pregnancy, glucose tolerance is normal or improved slightly, and peripheral (muscle) sensitivity to insulin and hepatic basal glucose production are normal or increase by as much as 15 percent (Catalano et al., 1991, 1992, 1993). As pregnancy advances, nutrient-stimulated insulin responses increase progressively despite only minor deterioration in glucose tolerance, which is consistent with progressive insulin resistance (Kühl, 1991). In late pregnancy, insulin action is 50-60 percent lower than in nonpregnant state (Ryan et al., 1985; Buchanan et al., 1990; Catalano et al., 1991, 1992, 1993). By the third trimester, basal and 24-hour mean insulin concentrations may double (Lesser and Carpenter, 1994). The first and second phases of insulin release increase threefold by late pregnancy (Catalano et al., 1991). These alterations in maternal insulin sensitivity affect not only glucose metabolism but also lipid metabolism, resulting in a decreased ability of insulin to suppress lipolysis (Catalano et al., 2002).

Alterations in maternal physiology during pregnancy are mediated by placental factors, as evidenced by the significant increase in maternal insulin sensitivity that occurs within days after delivery of the fetus and placenta (Ryan et al., 1985). Alterations in maternal metabolism have generally been ascribed to placental hormones, such as hPL, progesterone, and estrogen (Kalkhoff et al., 1979; Ryan and Enns, 1988). Recently, Kirwan et al. (2002) reported that circulating cytokines (i.e., TNF-α concentration) were inversely correlated with insulin sensitivity.

The metabolic changes in insulin sensitivity that occur during pregnancy are modified by inflammatory factors (Friedman et al., 1999, 2008). In women with normal glucose tolerance during pregnancy who lose significant weight postpartum, there is a return to normal metabolic function. However, in women with GDM, particularly if there is no decrease in post-



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