Impact of Insulin Resistance on PregnancyIntroduction: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.Citations:Butte NF. Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr 2000.Catalano PM, Ehrenberg HM. The short and long term implications of maternal obesity on the mother and her offspring. British Journal of Obstetrics & Gynecology.
2006; Catalano PM, Huston L, Kalhan SC, Amini SB: Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol, 1999Catalano PM, Nizielski SE, Preston L, Shao J, Friedman JE, Qiao L: Downregulated IRS-1 and PPARgamma in obese women with gestational diabetes: relationship to FFA during pregnancy. Am J Physiol Endocrinol Metab 282: 2002Catalano PM, Tyzbir ED, Calles J, Wolfe RR, Roman NM, Sims EA, Amini SB: Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes. Am J Physiol, 1993.Cunningham F, Lenevo K, Hauth J, Bloom S, Wenstrom K. In, Gilstrap L: Williams Obstetrics.
22nd ed. USA: McGraw Hill; 2005. Maternal physiology.Friedman JE, Ishizuka T, Huston L, Shao J, Catalano P, Highman T: Impaired glucose transport and insulin receptor tyrosine phosphorylation in skeletal muscle from obese women with gestational diabetes. Diabetes, 1999.Homko CJ, Sivan E, Boden G, Reece EA: Fuel metabolism during pregnancy.
Semin Reprod Endocrinol, 1999 Hunter S, Garvey W. Insulin Action and IR: Diseases Involving Defects in Insulin Receptors, Signal Transduction, and the Glucose Transport Effector System. Am J Med. 1998.
Karam JH. Pancreatic Hormones and Diabetes Mellitus. In: Greenspan FS, Strewler GJ, editors. Basic and Clinical Endocrinology. Appleton & Lange, Stamford CT USA; 1997.Knopp RH, Chapman M, Wahl PW, Bergelin RO, Irvine S.
, Warth MR, Relationship of lipoprotein lipids to mild fasting hyperglycemia and diabetes in pregnancy. Diabetes Care. 1980.McLachlan K, O’Neal D, Alford F., Jenkins A, Do adiponectin, TNF?, leptin and CRP relate to IR in pregnancy? Studies in women with and without gestational diabetes, during and after pregnancy. Diabetes Metab Res Rev. 2006.R.
C. Hickner, S. B. Racette, E. F. Binder, W.
M. Kohrt, J. S. Fisher; Suppression of Whole Body and Regional Lipolysis by Insulin: Effects of Obesity and Exercise, The Journal of Clinical Endocrinology ; Metabolism, Volume 84, Issue 11, 1 November 1999.Roman-Drago N, Catalano P, Sims E.
, Amini S. Longitudinal changes in body composition and energy balance in lean women with normal and abnormal glucose tolerance during pregnancy. Am J Obstet Gynecol. 1998.Solomon, C. G., ; Seely, E.
W. (2001). Brief review: hypertension in pregnancy: a manifestation of the insulin resistance syndrome.
Hypertension.Thadhani, R., Mutter, W. P.
, Levine, R. J., Wolf, M., Sukhatme, V. P., Taylor, R.
N., …
; Karumanchi, S. A. (2004). First trimester placental growth factor and soluble fms-like tyrosine kinase 1 and risk for preeclampsia.
The Journal of Clinical Endocrinology ; Metabolism.Wheatcroft SB, Williams IL, Kearney MT, Shah AM. Pathophysiological implications of insulin resistance on vascular endothelial function. Diabet Med. 2003.Wolf, M., Sandler, L., Hsu, K.
, Ecker, Mun?oz, K., J. L., ; Thadhani, R.
(2002). First trimester insulin resistance and subsequent preeclampsia: a prospective study. The Journal of Clinical Endocrinology ; Metabolism.World Health Organization. Obesity: Preventing and Managing the Global Epidemic Report of a WHO Consultation Technical Report Series. World Health Organization, Geneva 2000.
