Horm Metab Res 2013; 45(08): 567-571
DOI: 10.1055/s-0033-1337988
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Mechanism of Insulin Resistance in Normal Pregnancy

K. Hodson
1   Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
2   Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK
,
C. Dalla Man
3   Department of Information Engineering, University of Padua, Padua, Italy
,
F. E. Smith
1   Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
4   Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, UK
,
P. E. Thelwall
1   Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
4   Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, UK
,
C. Cobelli
3   Department of Information Engineering, University of Padua, Padua, Italy
,
S. C. Robson
1   Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
2   Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK
,
R. Taylor
1   Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
2   Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK
4   Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, UK
› Author Affiliations
Further Information

Publication History

received 05 December 2012

accepted 18 February 2013

Publication Date:
02 April 2013 (online)

Abstract

Normal pregnancy is associated with insulin resistance although the mechanism is not understood. Increased intramyocellular lipid is closely associated with the insulin resistance of type 2 diabetes and obesity, and the aim of this study was to determine whether this was so for the physiological insulin resistance of pregnancy. Eleven primiparous healthy pregnant women (age: 27–39 years, body mass index 24.0±3.1 kg/m2) and no personal or family history of diabetes underwent magnetic resonance studies to quantify intramyocellular lipid, plasma lipid fractions, and insulin sensitivity. The meal-related insulin sensitivity index was considerably lower in pregnancy (45.6±9.9 vs. 193.0±26.1; 10−4 dl/kg/min per pmol/l, p=0.0002). Fasting plasma triglyceride levels were elevated 3-fold during pregnancy (2.3±0.2 vs. 0.8±0.1 mmol/l, p<0.01) and the low-density density lipoprotein fraction, responsible for fatty acid delivery to muscle and other tissues, was 6-fold elevated (0.75±0.43 vs. 0.12±0.09 mmol/l; p=0.001). However, mean intramyocellular lipid concentrations of the soleus muscle were not different during pregnancy (20.0±2.3 vs. 19.1±3.2 mmol/l, p=0.64). The pregnancy effect on muscle insulin resistance is distinct from that underlying type 2 diabetes.

 
  • References

  • 1 Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims EA. Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. Am J Obstet Gynecol 1991; 165: 1667-1672
  • 2 Ravikumar B, Carey PE, Snaar JE, Deelchand DK, Cook DB, Neely RD, English PT, Firbank MJ, Morris PG, Taylor R. Real-time assessment of postprandial fat storage in liver and skeletal muscle in health and type 2 diabetes. Am J Physiol Endocrinol Metab 2005; 288: E789-E797
  • 3 Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 1999; 42: 113-116
  • 4 Herrera E. Metabolic adaptations in pregnancy and their implications for the availability of substrates to the fetus. Eur J Clin Nutr 2000; 54 (Suppl. 01) S47-S51
  • 5 Kautzky-Willer A, Krssak M, Winzer C, Pacini G, Tura A, Farhan S, Wagner O, Brabant G, Horn R, Stingl H, Schneider B, Waldhausl W, Roden M. Increased intramyocellular lipid concentration identifies impaired glucose metabolism in women with previous gestational diabetes. Diabetes 2003; 52: 244-251
  • 6 Kousta E, Lawrence NJ, Godsland IF, Penny A, Anyaoku V, Millauer BA, Cela E, Johnston DG, Robinson S, McCarthy MI. Insulin resistance and beta-cell dysfunction in normoglycaemic European women with a history of gestational diabetes. Clin Endocrinol (Oxf) 2003; 59: 289-297
  • 7 Taylor R, Shulman G. Magnetic Resonance Spectroscopy Studies of Liver and Muscle Glycogen Metabolism in Humans. London: Lippincott, Williams and Wilkins; 2005
  • 8 Dalla Man C, Campioni M, Polonsky KS, Basu R, Rizza RA, Toffolo G, Cobelli C. Two-hour seven-sample oral glucose tolerance test and meal protocol: minimal model assessment of beta-cell responsivity and insulin sensitivity in nondiabetic individuals. Diabetes 2005; 54: 3265-3273
  • 9 Dalla Man C, Caumo A, Cobelli C. The oral glucose minimal model: estimation of insulin sensitivity from a meal test. IEEE Trans Biomed Eng 2002; 49: 419-429
  • 10 van den Boogaart A, van Hecke A, van Huffel P, Graveron-Demilly S, van Ormondt D, de Beer R. MRUI: a graphical user interface for accurate routine MRS data anlaysis. Proceedings of the ESMRMB 13th Annual Meeting 1996: 318
  • 11 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  • 12 Breda E, Cavaghan MK, Toffolo G, Polonsky KS, Cobelli C. Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity. Diabetes 2001; 50: 150-158
  • 13 Van Cauter E, Mestrez F, Sturis J, Polonsky KS. Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 1992; 41: 368-377
  • 14 Bergman RN, Ader M, Huecking K, Van Citters G. Accurate assessment of beta-cell function: the hyperbolic correction. Diabetes 2002; 51 (Suppl. 01) S212-S220
  • 15 Perseghin G, Scifo P, De Cobelli F, Pagliato E, Battezzati A, Arcelloni C, Vanzulli A, Testolin G, Pozza G, Del Maschio A, Luzi L. Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes 1999; 48: 1600-1606
  • 16 Virkamaki A, Korsheninnikova E, Seppala-Lindroos A, Vehkavaara S, Goto T, Halavaara J, Hakkinen AM, Yki-Jarvinen H. Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. Diabetes 2001; 50: 2337-2343
  • 17 Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell 148: 852-871
  • 18 Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, Shulman GI. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 1996; 97: 2859-2865
  • 19 Kirwan JP, Varastehpour A, Jing M, Presley L, Shao J, Friedman JE, Catalano PM. Reversal of insulin resistance postpartum is linked to enhanced skeletal muscle insulin signaling. J Clin Endocrinol Metab 2004; 89: 4678-4684
  • 20 Barbour LA, Shao J, Qiao L, Leitner W, Anderson M, Friedman JE, Draznin B. Human placental growth hormone increases expression of the p85 regulatory unit of phosphatidylinositol 3-kinase and triggers severe insulin resistance in skeletal muscle. Endocrinology 2004; 145: 1144-1150
  • 21 Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-2486
  • 22 Metzger B. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Highlights. American Diabetes Association 67th Annual Scientific Sessions 2007
  • 23 Kjos SL, Buchanan TA. Gestational diabetes mellitus. N Engl J Med 1999; 341: 1749-1756
  • 24 Baker PN, Johnson IR, Harvey PR, Gowland PA, Mansfield P. A three-year follow-up of children imaged in utero with echo-planar magnetic resonance. Am J Obstet Gynecol 1994; 170: 32-33
  • 25 Kok RD, de Vries MM, Heerschap A, van den Berg PP. Absence of harmful effects of magnetic resonance exposure at 1.5 T in utero during the third trimester of pregnancy: a follow-up study. Magn Reson Imaging 2004; 22: 851-854
  • 26 Girard N, Gouny SC, Viola A, Le Fur Y, Viout P, Chaumoitre K, D’Ercole C, Gire C, Figarella-Branger D, Cozzone PJ. Assessment of normal fetal brain maturation in utero by proton magnetic resonance spectroscopy. Magn Reson Med 2006; 56: 768-775
  • 27 Szczepaniak LS, Babcock EE, Schick F, Dobbins RL, Garg A, Burns DK, McGarry JD, Stein DT. Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. Am J Physiol 1999; 276: E977-E989
  • 28 Howald H, Boesch C, Kreis R, Matter S, Billeter R, Essen-Gustavsson B, Hoppeler H. Content of intramyocellular lipids derived by electron microscopy, biochemical assays, and (1)H-MR spectroscopy. J Appl Physiol 2002; 92: 2264-2272
  • 29 Taylor R. Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia 2008; 51: 1781-1789