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Insulin Receptor (IR)

3.2 Glycosylated hemoglobin (HbA1c) as a diagnostic test for GDM Since 1984, professor Alwan AAS and collaborators have adopted the measurement of HbA1c levels as another index for follow-up of pregnant diabetic patients, and reported a significant relationship between elevated levels of HbA1c late in the third trimester and fetomaternal complications (Al-Dahwi et al., 1986; Al- Dahwi et al., 1987; Al-Dahwi et al., 1988; Al-Dahwi et al., 1989). Recently, the American Diabetic Association (2009) added that HbA1c ≥ 6.5% is another criterion for the diagnosis of diabetes (Nathan, 2009). Therefore we highly recommend the measurement of HbA1c during pregnancy, as an additional diagnostic criteria and to anticipate the maternal and fetal complications if it is abnormally elevated. 4. Pathophysiology of GDM In the pathophysiology of GDM we have to consider two main points. 4.1 Role of feto-placental unit in GDM. 4.2 Role of the adipose tissue in GDM. 4.1 The role of feto-placental unit in the development of GDM The past; In the last century insulin resistance and the decrease in insulin sensitivity during pregnancy is mainly attributed to the increase in the levels of pregnancy-associated hormones as estrogen, progesterone, cortisol, and placental lactogen in the maternal circulation (Ryan, 1988; Hornns, 1985; Ahmed & Shalayel, 1999; Polderman et al., 1994; Barbour et al., 2002). Normally the insulin resistance of the whole body is increased to about three times that seen in the non-pregnant state (Kuhl, 1998; Catalano et al., 1999). The increased resistance is caused by post-insulin receptor events and is probably brought about by the cellular effects of the increased levels of one or all of the above hormones (Davis, 1990). As pregnancy progresses and the placenta grow larger, hormone production also increases and so does the level of insulin resistance. This process usually starts between 20 and 24 weeks of pregnancy. At birth, when the placenta is delivered, the hormone production stops and so does the condition, strongly suggesting that these hormones cause GDM 4.1.1 Feto-placental unit The placenta synthesizes pregnenolone and progesterone from cholesterol. Some of the progesterone enters the fetal circulation and provides the substrate for the formation of cortisol and corticosterone in the fetal adrenal glands. Some of the pregnenolone enters the fetus and, along with pregnenolone synthesized in the fetal liver, is the substrate for the formation of dehydroepiandrosterone sulfate (DHEAS) and 16-hydroxydehydroepiandrosterone sulfate (16-OHDHEAS) in the fetal adrenal. Some 16-hydroxylation also occurs in the fetal liver. DHEAS and 16-OHDHEAS are transported back to the placenta, where DHEAS forms estradiol and 16-OHDHEAS forms estriol. The principal estrogen formed is estriol, and since fetal 16-OHDHEAS is the principal substrate for the estrogens, the urinary estriol excretion of the mother can be monitored as an index of the state of the fetus