Impact of Insulin Resistance on Pregnancy
In the current developed world, Obesity and Diabetes are reaching wide-ranging proportions in accordance with insulin resistance and its sequelae that is gaining prominence due to it’s almost similar effects as the former ones (World Health Organization(WHO): Obesity, 2000) Understanding the role of insulin and effect of insulin resistance over a wide range of physiological processes and several factors that can influence the production and discharge from the pancreatic beta-cells, also the action of insulin on molecular level to a larger scale, all have it’s implications for much chronic diseases seen in recent times.
In almost every healthy pregnant woman, resistance to the action of insulin on glucose uptake and utilization is prevalent (Roman-Drago et al., 1998). This resistance to insulin, prevalent among most pregnant women, as well as in obese and overweight individual too, occurs due to decreased ability of target tissues such as liver, adipose tissue and muscle to respond to normal circulating concentrations of insulin (Hunter et al., 1998). Insulin resistance during maternity leads to significant use of fats compared to carbohydrates for energy by the mother and this phenomenon causes scarcity of carbohydrates for the developing fetus. Thus, in these cases physiological adaptation of the mother occurs in the form of insulin resistance as it prevents the deprivation of the fetus from carbohydrate by ensuring that suitable amount of carbohydrate is provided to the rapidly growing fetus (Homko et al., 1999).
Several metabolic changes mark the onset of pregnancy and it occurs as pregnancy advances gradually. Firstly, lipolysis occurs to a great extent leading to subsequent fatty acid release in the maternal body. Secondly, with advancement of pregnancy, the maternal body shape changes gradually hence accretion of adipose tissue takes place, throughout the early gestation period, and this phenomenon is followed by insulin resistance which is more frequent over the later stages of pregnancy. In early pregnancy, insulin is released in the circulation in higher concentrations, whereas the sensitivity of the body towards insulin tends to remain unchanged, get decreased, or may even get increased (Catalano et al.,1993). However, as pregnancy proceeds over the later stages, adipose tissue, deposited during the early periods of conception tends to decline gradually , whereas glucose disposal that is mediated by insulin gets worsened by 40–60% compared with pre-pregnancy stages(Huston et al.,1999). Also, during late pregnancy, the ability of insulin to suppress whole-body lipolysis gets reduced to a noticeable extent (Homko et al., 1999), and this further contributes to increased hepatic glucose production, and severe insulin resistance (Friedman et al.,1999 & Metzger et al.,1993)
As normal pregnancy advances, insulin sensitivity gradually declines to 50% of the normal expected value and in the third trimester insulin resistance is greatest (McLachlan et al., 2006). Physiologically, at the complete body level, the actions of insulin are influenced by different hormones and their consecutive effect on the body on large scale. Insulin is one of the dominant hormones in the body, which can regulate several metabolic processes during the fed state, and it functions together with the (Insulin-like Growth Factor-1) IGF-1 and growth hormone. Growth hormones are secreted in a concomitant way along with response to insulin, despite of the presence of other stimuli, hence it prevents the insulin-induced hypoglycaemia (Karam et al., 1997). So, insulin resistance during pregnancy is considered an adaptive response, diverting glucose and lipids to the developing fetus (Butte et al., 2000) and is thought mainly due to the combinatorial effects of human placental lactogen, progesterone, estradiol and cortisol, which act in an antagonistic way against insulin.
The consequence of insulin resistance can be anomalous as observed in pregnancy since it may lead to gestational hypertension and gestational diabetes mellitus (Seely et al., 2003). With no complications at full term, these changes leading to metabolic syndromes, alongside biochemical, physiological, hematological and immunological changes, are reversible after delivery (Cunningham et al., 2005). In other cases, insulin resistance is believed to be apparent at the cellular level via post-receptor defects in insulin signaling, and mechanisms including down-regulation, deficiencies or genetic polymorphisms of tyrosine phosphorylation of the insulin receptor, IRS (Insulin Receptor Substrate) proteins or PIP-3(phosphatidylinositol (3,4,5)-trisphosphate) kinase, or may involve abnormalities of GLUT 4(Glucose Transporter-4) function (Wheatcroft et al., 2003).
Due to a series of these metabolic alterations during normal pregnancy, specifically the 60% decrease in insulin sensitivity, all women are at increased risk of metabolic dysregulation in pregnancy, i.e. gestational diabetes mellitus, fetal overgrowth and preeclampsia. Hence, for the future risk associated with the metabolic syndrome, the phase of pregnancy can be assumed as a metabolic stress test. More importantly, an understanding of these risks provides an opportunity for prevention. Hence, an overall review on the impact of insulin resistance on Pregnancy is done in this research paper to focus on the aspects that causes the resistance of insulin as well as various physiological consequences as an outcome to these changes.
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