Undue Increase in Insulin Resistance during Pregnancy may Manifest Pregnancy-induced Hypertension and Gestational Diabetes

 

 Buy Article Permissions and Reprints

Introduction

Pregnancy-induced hypertension (PIH), including gestational hypertension (GH) and pre-eclampsia (PE), complicates up to 8 % of pregnancies and is one of leading causes of maternal and perinatal morbidity and mortality [1] [2] [3]. Its pathogenesis and etiology remain poorly understood; moreover, recent trials have not shown the use of aspirin and calcium supplement to be effective in reducing the incidence of pre-eclampsia [4] [5]. Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy, and is associated with significantly adverse pregnancy outcomes [6] [7]. The effectiveness of GDM management is uncertain [8]. Moreover, the implications of the two diseases are not only limited to perinatal health for mothers and their offspring, but GDM and PIH may also have a long-term impact on the health of the mother - for example, increased risk of type 2 diabetes mellitus (T2DM) [9] and/or cardiovascular disease (CVD) [10].

Pregnancy is a state of physiological insulin resistance (IR); IR increases with advancing pregnancy, starting at conception and lasting through to late pregnancy [11]. The increase is most marked between 16 and 26 weeks of gestation [12]. In the past decade, evidence has accumulated on the association between IR in pregnancy and PIH and between IR and GDM. Investigations into the possible causal relationships between IR and PIH and between IR and GDM may lead to new strategies for the prevention and management of two diseases, and these strategies may also improve maternal health in the long run.

References

• 1 Sumnulu I, Ildeniz M, Ozel N. The incidence of pregnancy induced hypertension in southeast Turkey.  Int J Gynaecol Obstet. 1989;  28 (3) 211-215
  CrossrefPubMedGoogle Scholar
• 2 Acien P, Lloret G, Lloret M. Perinatal morbidity and mortality in pregnancy hypertensive disorders: prognostic value of the clinical and laboratory findings.  Int J Gynaecol Obstet. 1990;  32 (3) 229-235
  CrossrefPubMedGoogle Scholar
• 3 Roberts J M, Pearson G, Cutler J, Lindheimer M. Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy.  Hypertension. 2003;  41 (3) 437-445
  CrossrefPubMedGoogle Scholar
• 4 Caritis S, Sibai B, Hauth J, Lindheimer M D, Klebanoff M, Thom E. et al . Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.  N Engl J Med. 1998;  338 (11) 701-705
  CrossrefPubMedGoogle Scholar
• 5 Levine R J, Hauth J C, Curet L B, Sibai B M, Catalano P M, Morris C D. et al . Trial of calcium to prevent preeclampsia.  N Engl J Med. 1997;  337 (2) 69-76
  CrossrefPubMedGoogle Scholar
• 6 Sermer M, Naylor C D, Gare D J, Kenshole A B, Ritchie J W, Farine D. et al . Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes Project.  Am J Obstet Gynecol. 1995;  173 (1) 146-156
  CrossrefPubMedGoogle Scholar
• 7 Yang X, Hsu-Hage B, Zhang H, Zhang C, Zhang Y. Women with impaired glucose tolerance during pregnancy have significantly poor pregnancy outcomes.  Diabetes Care. 2002;  25 (9) 1619-1624
  PubMedGoogle Scholar
• 8 Garner P, Okun N, Keely E, Wells G, Perkins S, Sylvain J. et al . A randomized controlled trial of strict glycemic control and tertiary level obstetric care versus routine obstetric care in the management of gestational diabetes: a pilot study.  Am J Obstet Gynecol. 1997;  177 (1) 190-195
  CrossrefPubMedGoogle Scholar
• 9 Cheung N W, Byth K. Population health significance of gestational diabetes.  Diabetes Care. 2003;  26 (7) 2005-2009
  CrossrefPubMedGoogle Scholar
• 10 Jonsdottir L S, Arngrimsson R, Geirsson R T, Sigvaldason H, Sigfusson N. Death rates from ischemic heart disease in women with a history of hypertension in pregnancy.  Acta Obstet Gynecol Scand. 1995;  74 (10) 772-776
  PubMedGoogle Scholar
• 11 Catalano P M, Tyzbir E D, Roman N M, Amini S B, Sims E A. Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women.  Am J Obstet Gynecol. 1991;  165 (6 Pt 1) 1667-1672
  CrossrefPubMedGoogle Scholar
• 12 Stanley K, Fraser R, Bruce C. Physiological changes in insulin resistance in human pregnancy: longitudinal study with the hyperinsulinaemic euglycaemic clamp technique.  Br J Obstet Gynaecol. 1998;  105 (7) 756-759
  PubMedGoogle Scholar
• 13 Kaaja R, Tikkanen M J, Viinikka L, Ylikorkala O. Serum lipoproteins, insulin, and urinary prostanoid metabolites in normal and hypertensive pregnant women.  Obstet Gynecol. 1995;  85 (3) 353-356
  CrossrefPubMedGoogle Scholar
• 14 Solomon C G, Carroll J S, Okamura K, Graves S W, Seely E W. Higher cholesterol and insulin levels in pregnancy are associated with increased risk for pregnancy-induced hypertension.  Am J Hypertens. 1999;  12 (3) 276-282
  CrossrefPubMedGoogle Scholar
• 15 Tripathy C, Malik S, Shah P, Lakshmy R, Tripathy D. Serum insulin and lipid profile in normal pregnant and pregnancy-induced hypertensive women from North India.  Aust N Z J Obstet Gynaecol. 1999;  39 (3) 321-323
  PubMedGoogle Scholar
• 16 Martinez Abundis E, Gonzalez Ortiz M, Quinones Galvan A, Ferrannini E. Hyperinsulinemia in glucose-tolerant women with preeclampsia. A controlled study.  Am J Hypertens. 1996;  9 (6) 610-614
  CrossrefPubMedGoogle Scholar
• 17 Bartha J L, Comino-Delgado R. Carbohydrate metabolism. Evaluation in women with de novo hypertension in late pregnancy.  J Reprod Med. 1997;  42 (8) 489-496
  PubMedGoogle Scholar
• 18 Martin A, O’Sullivan A J, Brown M A. Body composition and energy metabolism in normotensive and hypertensive pregnancy.  Bjog. 2001;  108 (12) 1263-1271
  CrossrefPubMedGoogle Scholar
• 19 Roberts R N, Henriksen J E, Hadden D R. Insulin sensitivity in pre-eclampsia.  Br J Obstet Gynaecol. 1998;  105 10) 1095-1100
  PubMedGoogle Scholar
• 20 Kaaja R, Laivuori H, Laakso M, Tikkanen M J, Ylikorkala O. Evidence of a state of increased insulin resistance in preeclampsia.  Metabolism. 1999;  48 (7) 892-896
  CrossrefPubMedGoogle Scholar
• 21 Caruso A, Ferrazzani S, de Carolis S, Lucchese A, Lanzone A, de Santis L. et al . Gestational hypertension but not pre-eclampsia is associated with insulin resistance syndrome characteristics.  Hum Reprod. 1999;  14 (1) 219-223
  CrossrefPubMedGoogle Scholar
• 22 Wolf M, Sandler L, Jimenez-Kimble R, Shah A, Ecker J L, Thadhani R. Insulin resistance but not inflammation is associated with gestational hypertension.  Hypertension. 2002;  40 (6) 886-891
  CrossrefPubMedGoogle Scholar
• 23 Wolf M, Sandler L, Munoz K, Hsu K, Ecker J L, Thadhani R. First trimester insulin resistance and subsequent preeclampsia: a prospective study.  J Clin Endocrinol Metab. 2002;  87 (4) 1563-1568
  CrossrefPubMedGoogle Scholar
• 24 Bjercke S, Dale P O, Tanbo T, Storeng R, Ertzeid G, Abyholm T. Impact of insulin resistance on pregnancy complications and outcome in women with polycystic ovary syndrome.  Gynecol Obstet Invest. 2002;  54 (2) 94-98
  CrossrefPubMedGoogle Scholar
• 25 Bowes S B, Hennessy T R, Umpleby A M, Benn J J, Jackson N C, Boroujerdi M A. et al . Measurement of glucose metabolism and insulin secretion during normal pregnancy and pregnancy complicated by gestational diabetes.  Diabetologia. 1996;  39 (8) 976-983
  CrossrefPubMedGoogle Scholar
• 26 Persson B, Edwall L, Hanson U, Nord E, Westgren M. Insulin sensitivity and insulin response in women with gestational diabetes mellitus.  Horm Metab Res. 1997;  29 (8) 393-397
  PubMedGoogle Scholar
• 27 Catalano P M, Tyzbir E D, Wolfe R R, Calles J, Roman N M, Amini S B. et al . Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes.  Am J Physiol. 1993;  264 (1 Pt 1) E60-67
  PubMedGoogle Scholar
• 28 Catalano P M, Huston L, Amini S B, Kalhan S C. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus.  Am J Obstet Gynecol. 1999;  180 (4) 903-916
  CrossrefPubMedGoogle Scholar
• 29 Buchanan T A, Metzger B E, Freinkel N, Bergman R N. Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes.  Am J Obstet Gynecol. 1990;  162 (4) 1008-1014
  Google Scholar
• 30 Vambergue A, Nuttens M C, Goeusse P, Biausque S, Lepeut M, Fontaine P. Pregnancy induced hypertension in women with gestational carbohydrate intolerance: the diagest study.  Eur J Obstet Gynecol Reprod Biol. 2002;  102 (1) 31-35
  CrossrefPubMedGoogle Scholar
• 31 Roach V J, Hin L Y, Tam W H, Ng K B, Rogers M S. The incidence of pregnancy-induced hypertension among patients with carbohydrate intolerance.  Hypertens Pregnancy. 2000;  19 (2) 183-189
  CrossrefPubMedGoogle Scholar
• 32 Yang X, Zhang H, Dong L, Yu S, Guo Z, Hsu-Hage B. The effect of glucose levels on fetal birth weight: a study of Chinese gravidas in Tianjin, China.  J Diabetes Complications. 2004;  18 (1) 37-41
  CrossrefPubMedGoogle Scholar
• 33 Yang X, Hsu-Hage B, Dong L, Shao P, Wang H, Tian H. et al . Intensive diabetes management may improve pregnancy: outcomes in Chinese gravidas with impaired glucose tolerance.  Diabetes Care. 2003;  26 (1) 254-255
  CrossrefPubMedGoogle Scholar
• 34 Pan X R, Li G W, Hu Y H, Wang J X, Yang W Y, An Z X. et al . Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study.  Diabetes Care. 1997;  20 (4) 537-544
  CrossrefPubMedGoogle Scholar
• 35 Knowler W C, Barrett-Connor E, Fowler S E, Hamman R F, Lachin J M, Walker E A. et al . Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.  N Engl J Med. 2002;  346 (6) 393-403
  CrossrefPubMedGoogle Scholar
• 36 Tuomilehto J, Lindstrom J, Eriksson J G, Valle T T, Hamalainen H, Ilanne-Parikka P. et al . Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.  N Engl J Med. 2001;  344 (18) 1343-1350
  CrossrefPubMedGoogle Scholar
• 37 Chiasson J L, Josse R G, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial.  Lancet. 2002;  359 (9323) 2072-2077
  CrossrefPubMedGoogle Scholar
• 38 Glueck C J, Wang P, Kobayashi S, Phillips H, Sieve-Smith L. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome.  Fertil Steril. 2002;  77 (3) 520-525
  CrossrefPubMedGoogle Scholar
• 39 Norden L indeberg, Hanson U. Hypertension and factors associated with metabolic syndrome at follow-up at 15 years in women with hypertensive disease during first pregnancy.  Hypertens Pregnancy. 2000;  19 (2) 191-198
  CrossrefPubMedGoogle Scholar
• 40 He S, Silveira A, Hamsten A, Blomback M, Bremme K. Haemostatic, endothelial and lipoprotein parameters and blood pressure levels in women with a history of preeclampsia.  Thromb Haemost. 1999;  81 (4) 538-542
  PubMedGoogle Scholar
• 41 Irgens H U, Reisaeter L, Irgens L M, Lie R T. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study.  Bmj. 2001;  323 (7323) 1213-1217
  CrossrefPubMedGoogle Scholar
• 42 Kestenbaum B, Seliger S L, Easterling T R, Gillen D L, Critchlow C W, Stehman-Breen C O. et al . Cardiovascular and thromboembolic events following hypertensive pregnancy.  Am J Kidney Dis. 2003;  42 (5) 982-989
  CrossrefPubMedGoogle Scholar
• 43 Persson B, Hanson U, Hartling S G, Binder C. Follow-up of women with previous GDM. Insulin, C-peptide, and proinsulin responses to oral glucose load.  Diabetes. 1991;  40 (Suppl 2) 136-141
  PubMedGoogle Scholar
• 44 Hanson U, Persson B, Hartling S G, Binder C. Increased molar proinsulin-to-insulin ratio in women with previous gestational diabetes does not predict later impairment of glucose tolerance.  Diabetes Care. 1996;  19 (1) 17-20
  PubMedGoogle Scholar
• 45 Damm P, Kuhl C, Bertelsen A, Molsted-Pedersen L. Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus.  Am J Obstet Gynecol. 1992;  167 (3) 607-616
  PubMedGoogle Scholar
• 46 Albareda M, Caballero A, Badell G, Piquer S, Ortiz A, de Leiva A. et al . Diabetes and abnormal glucose tolerance in women with previous gestational diabetes.  Diabetes Care. 2003;  26 (4) 1199-1205
  CrossrefPubMedGoogle Scholar
• 47 Benjamin E, Winters D, Mayfield J, Gohdes D. Diabetes in pregnancy in Zuni Indian women. Prevalence and subsequent development of clinical diabetes after gestational diabetes.  Diabetes Care. 1993;  16 (9) 1231-1235
  PubMedGoogle Scholar
• 48 Aberg A E, Jonsson E K, Eskilsson I, Landin-Olsson M, Frid A H. Predictive factors of developing diabetes mellitus in women with gestational diabetes.  Acta Obstet Gynecol Scand. 2002;  81 (1) 11-16
  CrossrefPubMedGoogle Scholar
• 49 Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M. et al . Cardiovascular morbidity and mortality associated with the metabolic syndrome.  Diabetes Care. 2001;  24 (4) 683-689
  CrossrefPubMedGoogle Scholar
• 50 Solomon C G, Seely E W. Brief review: hypertension in pregnancy : a manifestation of the insulin resistance syndrome?.  Hypertension. 2001;  37 (2) 232-239
  PubMedGoogle Scholar
• 51 Seely E W, Solomon C G. Insulin resistance and its potential role in pregnancy-induced hypertension.  J Clin Endocrinol Metab. 2003;  88 (6) 2393-2398
  CrossrefPubMedGoogle Scholar
• 52 Chen H, Sullivan G, Yue L Q, Katz A, Quon M J. QUICKI is a Useful Index of Insulin Sensitivity in Subjects with Hypertension.  Am J Physiol Endocrinol Metab. 2003;  284 (4) E804-812
  PubMedGoogle Scholar
• 53 Kirwan J P, Huston-Presley L, Kalhan S C, Catalano P M. Clinically useful estimates of insulin sensitivity during pregnancy: validation studies in women with normal glucose tolerance and gestational diabetes mellitus.  Diabetes Care. 2001;  24 (9) 1602-1607
  Google Scholar
• 54 Bartha J L, Romero-Carmona R, Torrejon-Cardoso R, Comino-Delgado R. Insulin, insulin-like growth factor-1, and insulin resistance in women with pregnancy-induced hypertension.  Am J Obstet Gynecol. 2002;  187 (3) 735-740
  CrossrefPubMedGoogle Scholar
• 55 Thadhani R, Ecker J L, Mutter W P, Wolf M, Smirnakis K V, Sukhatme V P. et al . Insulin resistance and alterations in angiogenesis: additive insults that may lead to preeclampsia.  Hypertension. 2004;  43 (5) 988-992
  CrossrefPubMedGoogle Scholar
• 56 Sowers J R, Saleh A A, Sokol R J. Hyperinsulinemia and insulin resistance are associated with preeclampsia in African-Americans.  Am J Hypertens. 1995;  8 (1) 1-4
  CrossrefPubMedGoogle Scholar
• 57 Yasuhi I, Hogan J W, Canick J, Sosa M B, Carpenter M W. Midpregnancy serum C-peptide concentration and subsequent pregnancy-induced hypertension.  Diabetes Care. 2001;  24 (4) 743-747
  PubMedGoogle Scholar
• 58 Sattar N, Ramsay J, Crawford L, Cheyne H, Greer I A. Classic and novel risk factor parameters in women with a history of preeclampsia.  Hypertension. 2003;  42 (1) 39-42
  CrossrefPubMedGoogle Scholar

Dr. Xilin Yang

Centre for Epidemiology and Biostatistics · 5/F · School of Public Health

Prince of Wales Hospital · Shatin · N.T. · Hong Kong

Phone: +(852)2252-8722

Fax: +(852)2645-3098 ·

Email: yang.xilin@cuhk.edu.hk