Research Article| Volume 25, ISSUE 4, P873-885, December 1998

Insulin Resistance and Preeclampsia

  • Kathleen M. Berkowitz
    Address reprint requests to: Kathleen M. Berkowitz, MD, Department of Perinatology, Long Beach Memorial Medical Center, 2801 Atlantic Avenue, Long Beach, CA 90801
    From the California Diabetes and Pregnancy Program; and Long Beach Memorial Medical Center, Long Beach, California
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      Insulin resistance syndrome is a cluster of physiologic abnormalities including hyperinsulinemia and glucose intolerance, dyslipidemia, and hypertension. Patients with this cluster of physiologic disturbances are at increased risk for stroke, renal failure, and heart disease. Insulin resistance is the causal mechanism of gestational diabetes and may be involved in the pathogenesis of preeclampsia. Implications of diagnosing a population that may be at future risk for stroke and heart disease are discussed, along with therapeutic strategies that may decrease long-term complications in this group.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Clinics in Perinatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Bergmann R.N.
        • Phillips L.S.
        • Cobelli C.
        Physiologic evaluation of factors controlling glucose tolerance in man. Measurement of insulin sensitivity and beta-cell sensitivity from the response to intravenous glucose.
        J Clin Invest. 1981; 68: 1456-1467
        • Berkowitz K.M.
        • Peters R.
        • Kjos S.L.
        • et al.
        Effect of troglitazone on insulin sensitivity and pancreatic B-cell function in women at high risk for non-insulin dependent diabetes mellitus.
        Diabetes. 1996; 45: 1572-1579
        • Berkowitz K.M.
        • Reyes C.R.
        • Sadaat P.
        • et al.
        Comparison of biochemical indices of maturation of the fetal lung in reliably dated diabetic and non-diabetic pregnancies.
        J Reprod Med. 1997; 42
        • Birdsall M.A.
        Association between polycystic ovarian syndrome and extent of coronary artery disease in women having cardiac catheterization.
        Ann Intern Med. 1997; 126: 32-35
        • Buchanon T.A.
        • Metzger B.E.
        • Freinkel N.
        • et al.
        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: 1008-1014
        • Byyny R.L.
        • Lo Verde M.
        • Lloyd S.
        • et al.
        Cytosolic calcium and insulin resistance in elderly patients with essential hypertension.
        Am J Hypertens. 1992; 5: 459-464
        • Canessa M.
        Erythrocyte sodium-lithium countertransport: Another link between essential hypertension and diabetes.
        Curr Opin Nephrol Hypertens. 1994; 3: 511-517
        • Capaldo B.
        • Lembo G.
        • Napoli
        • et al.
        Skeletal muscle is a primary site of insulin resistance in essential hypertension.
        Metabolism. 1991; 40: 1320-1322
        • Christlieg A.R.
        Renin, angiotensin and norephinephrine in alloxan diabetes.
        Diabetes. 1974; 23: 962-970
        • Cioffi F.J.
        • Amorosa L.F.
        • Vintzileos A.M.
        • et al.
        Relationship of insulin resistance and hyperinsulinemia to blood pressure during pregnancy.
        J Matern Fetal Med. 1997; 6: 174-179
        • Crave J.
        • Fimbal S.
        • Lejeune H.
        • et al.
        Effects of diet and metformin administration on sex hormone binding globulin, androgens, and insulin in hirsute and obese women.
        J Clin Endocrinol Metab. 1995; 80: 2057-2062
        • DeFronzo R.A.
        • Goodman A.M.
        • et al.
        Efficacy of Metformin in patients with noninsulin dependent diabetes mellitus.
        N Engl J Med. 1995; 333: 541-549
        • Freinkel N.
        • Metzger B.E.
        • Phelps R.L.
        • et al.
        Gestational diabetes mellitus: Heterogeneity of maternal age, weight, insulin secretion, HLA antigens, and islet cell antibodies and the impact of maternal metabolism on pancreatic B-cell function and somatic growth in the offspring.
        Diabetes. 1985; 34: 1-7
        • Fuh M.M.
        • Yin C.S.
        • Pei D.
        • et al.
        Resistance to insulin-mediated glucose uptake and hyperinsulinemia in women who had pre-eclampsia in pregnancy.
        Am J Hypertens. 1995; 8: 768-771
        • Gilbert R.E.
        • Jerums G.
        • Cooper M.E.
        Diabetes and hypertension: Prognostic and therapeutic considerations.
        Blood Press. 1995; 4: 329-338
        • Graves S.W.
        • Lincoln K.
        • Cook S.L.
        • et al.
        Digitalis-like factor and digoxin-like immunore-active factor in diabetic women with pre-eclampsia, transient hypertension of pregnancy and normotensive pregnancy.
        Am J Hypertens. 1995; 8: 5-11
        • Greco P.
        • Loverro G.
        • Selvaggi L.
        Does gestational diabetes represent an obstetric risk factor?.
        Gynecol Obstet Invest. 1994; 37: 242-245
        • Gu H.
        • Rong L.
        • Sai J.Y.
        Insulin resistance and pregnancy-induced hypertension.
        Chung Hua Fu Chan Ko Tsa Chih. 1994; 29: 711-713
        • Harano Y.
        • Suzuki M.
        • Shinozaki K.
        • et al.
        Clinical impact of insulin resistance syndrome in cardiovascular diseases and its therapeutic approach.
        Hypertens Res. 1996; 19: S81-S85
        • Hollingsworth D.R.
        • Grundy S.M.
        Pregnancy-associated hypertriglyceridemia in normal and diabetic women: Differences in insulin-dependent, non-insulin dependent and gestational diabetes.
        Diabetes. 1981; 31: 1092
        • Holte J.
        • Gennarelli G.
        • Berne C.
        • et al.
        Elevated ambulatory day-time blood pressure in women with polycystic ovary syndrome: A sign of a prehypertensive state?.
        Hum Reprod. 1996; 11: 23-28
        • Iwase M.
        • Wada M.
        • Wakisaka M.
        • et al.
        Effects of maternal diabetes on blood pressure and glucose tolerance in offspring of spontaneously hypertensive rates: Relation to birth weight.
        Clin Sei. 1995; 89: 255-260
        • Jacober S.J.
        • Morris D.A.
        • Sower J.R.
        Postpartum blood pressure and insulin sensitivity in African-American women with recent pre-eclampsia.
        Am J Hypertens. 1994; 7: 933-936
        • Kalkhoff R.K.
        • Kissebah A.H.
        • Kim H.J.
        Carbohydrate and lipid metabolism during normal pregnancy: Relationship to gestational hormones.
        in: Merkatz I.R. Adam P.A.J. The Diabetic Pregnancy: A Perinatal Perspective. Grune & Stratton, New York1979: 3
        • Kjos S.L.
        • Peters R.K.
        • Xiang A.
        • et al.
        Predicting future diabetes in Latino women with gestational diabetes: Utility of early postpartum glucose tolerance testing.
        Diabetes. 1995; 44: 586-591
        • Laivuori H.
        • Tikkanen M.J.
        • Ylikorkala O.
        Hyperinsulinemia 17 years after pre-eclamptic first pregnancy.
        J Clin Endocrinol Metab. 1996; 81: 2908-2911
        • Lanzone A.
        • Caruso A.
        • Disimone N.
        • et al.
        Polycystic ovarian disease: A risk factor for gestational diabetes?.
        J Reprod Med. 1995; 40: 312-316
        • Levy J.
        • Zemei M.B.
        • Sowers J.R.
        Role of cellular calcium metabolism in abnormal glucose metabolism and diabetic hypertension.
        Am J Med. 1989; 87: 7S-16S
        • Levy M.T.
        • Jacoaber S.J.
        • Sowers J.R.
        Hypertensive disorders of pregnancy in southwestern Navajo Indians.
        Arch Intern Med. 1994; 154: 2181-2183
        • Martinez A.E.
        • Gonzales O.M.
        • Quninones G.A.
        • et al.
        Hyperinsulinemia in glucose-tolerant women with pre-eclampsia: A controlled study.
        Am J Hypertens. 1996; 9: 610-614
        • McCarthy M.F.
        Insulin resistance—not hyperinsulinemia—is pathogenic in essential hypertension.
        Med Hypotheses. 1994; 42: 226-236
        • Metzger B.E.
        • Cho N.H.
        • Roston S.M.
        • et al.
        Prepregnancy weight and antepartum insulin secretion predict glucose tolerance five years after gestational diabetes mellitus.
        Diabetes Care. 1995; 16: 1598-1605
        • Modan M.
        • Halkin H.
        • Almog S.
        • et al.
        Hyperinsulinemia: A link between hypertension, obesity and glucose intolerance.
        J Clin Invest. 1985; 75: 809-817
        • Nolan J.J.
        • Ludvik M.D.
        • Beerdsen R.N.
        • et al.
        Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone.
        N Engl J Med. 1994; 331: 1188-1193
        • O’Hare J.A.
        The enigma of insulin resistance and hypertension.
        Am J Med. 1988; 84: 505-511
        • O’Hare J.A.
        • Minaker K.
        • Young J.B.
        • et al.
        Insulin increases plasma norepinephrine (NE) and lowers plasma potassium equally in lean and obese men.
        Clin Res. 1985; 33: 441A
        • Olefsky J.M.
        Pathogenesis of non-insulin dependent diabetes (type II).
        in: DeGroot L.J. Besser G.M. Cahill J.C. Endocrinology. ed 2. WB Saunders, Philadelphia1989: 1369-1388
        • Oren S.
        • Golzman B.
        • Reitblatt T.
        • et al.
        Gestational diabetes mellitus and hypertension in pregnancy: Hemodynamics and diurnal arterial pressure profile.
        J Hum Hypertens. 1996; 10: 505-509
        • O’Sullivan J.B.
        The Boston gestational diabetes studies: Review and perspectives.
        in: Sutherland H.W. Stowers J.M. Pearson D.W.M. Carbohydrate Metabolism in Pregnancy and the Newborn. Springer-Verlag, London1989: 287-294
        • Peters R.K.
        • Kjos S.L.
        • Xiang A.
        • et al.
        Long-term diabetogenic effect of a single pregnancy in women with prior gestational diabetes mellitus.
        Lancet. 1996; 347: 227-230
        • Resnick L.M.
        Cellular ions in hypertension, insulin resistance, obesity and diabetes: A unifying theme.
        J Am Soc Nephrol. 1992; 3: S78-S85
        • Robinson J.G.
        How HRT alters the lipid profile in women with diabetes.
        Medscape/womens health. 1997; 1: 2
        • Rotter J.L.
        • Vadheim C.M.
        • Rimoin D.L.
        Genetics of diabetes mellitus.
        in: Rifkin H. Porte Jr., D. Diabetes Mellitus: Theory and Practice. Elsevier, New York1990: 378-413
        • Rowe J.W.
        • Young J.B.
        • Minaker K.
        • et al.
        Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man.
        Diabetes. 1981; 30: 219-225
        • Rudge M.V.
        • Calderon I.M.
        • Ramos M.D.
        • et al.
        Hypertensive disorders in pregnant women with diabetes mellitus.
        Gynecol Obstet Invest. 1997; 44: 11-15
        • Schaffir J.A.
        • Lockwood C.J.
        • Lapinski R.
        • et al.
        Incidence of pregnancy-induced hypertension among gestational diabetics.
        Am J Perinatol. 1995; 12: 252-254
        • Schmidt M.I.
        • Watson R.L.
        • Duncan B.B.
        • et al.
        Clustering of dyslipidemia, hyperuricemia, diabetes and hypertension and its association with fasting insulin and central and overall obesity in a general population: Atherosclerosis Risk in Communities Study Investigators.
        Metabolism. 1996; 45: 699-706
        • Silverman B.L.
        • Meztger B.E.
        • Cho N.H.
        • et al.
        Impaired glucose tolerance in adolescent offspring of diabetic mothers: Relationship to fetal hyperinsulinemia.
        Diabetes Care. 1995; 18: 611-617
        • Solomon C.G.
        • Graves S.W.
        • Greene M.F.
        • et al.
        Glucose intolerance as a predictor of hypertension in pregnancy.
        Hypertension. 1994; 23: 717-721
        • Sowers J.R.
        • Saleh A.A.
        • Sokol R.J.
        Hyperinsulinemia and insulin resistance are associated with pre-eclampsia in African-American women.
        Am J Hypertens. 1995; 8: 1-4
        • Talbott E.
        • Guzick D.
        • Cleria A.
        • et al.
        Coronary heart disease in women with polycystic ovarian syndrome.
        Arteroscler Thrombovasc Bio. 1995; 15: 821-826
        • Urman B.
        • Sarac E.
        • Dogan L.
        • Gurgan T.
        Pregnancy in infertile PCOD patients: Complications and outcome.
        J Reprod Med. 1997; 42: 501-505
        • Weidmann P.
        • Beretta-Piccoli C.
        • Trost B.N.
        Pressor factors and responsiveness in hypertension accompanying diabetes mellitus.
        Hypertension. 1985; 7: 1133-1142
        • Weidmann P.
        • Bohlen L.
        • de Courten M.
        Insulin resistance and hyperinsulinemia in hypertension.
        J Hypertens. 1995; 13: S65-S72
        • Weidmann P.
        • de Courten M.
        • Boehlen L.
        Insulin resistance, hyperinsulinemia and hypertension.
        J Hypertens. 1993; 11: S27-S38
        • Yen S.C.C.
        • Tsai C.C.
        • Vela P.
        Gestational diabetogenesis: Quantitative analysis of glucose-insulin interrelationship between normal pregnancy and pregnancy with gestational diabetes.
        Am J Obstet Gynecol. 1971; 111: 792-800
        • Zemei M.B.
        Insulin resistance vs. hyperinsulinemia in hypertension: Insulin regulation of Ca2+ transport and ca(2+) regulation of insulin sensitivity.
        J Nutr. 1995; 125: 1738S-1743S