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Pregestational diabetes mellitus: Glycemic control during pregnancy

Michael F Greene, MD
Rhonda Bentley-Lewis, MD, MBA, MMSc
Section Editors
David M Nathan, MD
Susan M Ramin, MD
Deputy Editor
Vanessa A Barss, MD, FACOG


Maintenance of maternal blood glucose concentration at or near normoglycemic levels is the goal of medical management of pregestational diabetes (ie, diabetes diagnosed before pregnancy, type 1 or type 2 diabetes mellitus) because it decreases the likelihood of adverse maternal, fetal, and newborn outcomes. Ideally, good glycemic control is achieved before conception and maintained through the postpartum period.

The medical management of pregestational diabetes mellitus during pregnancy will be discussed here. Multiple additional aspects of pregnancy complicated by diabetes are reviewed separately:

Optimizing glucose control before pregnancy (see "Pregestational diabetes: Preconception counseling, evaluation, and management", section on 'Preconception evaluation and management')

Fetal and maternal risks of pregnancy in women with pregestational diabetes (see "Pregestational diabetes: Preconception counseling, evaluation, and management", section on 'Fetal and neonatal risks' and "Pregestational diabetes: Preconception counseling, evaluation, and management", section on 'Obstetric complications' and "Pregestational diabetes: Preconception counseling, evaluation, and management", section on 'Maternal medical risks')

Obstetric management of pregnancy in women with pregestational diabetes (see "Pregestational diabetes mellitus: Obstetrical issues and management")


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Literature review current through: Sep 2016. | This topic last updated: Oct 4, 2016.
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  1. Moy FM, Ray A, Buckley BS. Techniques of monitoring blood glucose during pregnancy for women with pre-existing diabetes. Cochrane Database Syst Rev 2014; :CD009613.
  2. American Diabetes Association. 12. Management of Diabetes in Pregnancy. Diabetes Care 2016; 39 Suppl 1:S94.
  3. Jovanovic-Peterson L, Peterson CM, Reed GF, et al. Maternal postprandial glucose levels and infant birth weight: the Diabetes in Early Pregnancy Study. The National Institute of Child Health and Human Development--Diabetes in Early Pregnancy Study. Am J Obstet Gynecol 1991; 164:103.
  4. Jovanovic LG. Using meal-based self-monitoring of blood glucose as a tool to improve outcomes in pregnancy complicated by diabetes. Endocr Pract 2008; 14:239.
  5. Herranz L, Pallardo LF, Hillman N, et al. Maternal third trimester hyperglycaemic excursions predict large-for-gestational-age infants in type 1 diabetic pregnancy. Diabetes Res Clin Pract 2007; 75:42.
  6. Hawkins JS. Glucose monitoring during pregnancy. Curr Diab Rep 2010; 10:229.
  7. ACOG Committee on Practice Bulletins. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Number 60, March 2005. Pregestational diabetes mellitus. Obstet Gynecol 2005; 105:675.
  8. Gandhi RA, Brown J, Simm A, et al. HbA1c during pregnancy: its relationship to meal related glycaemia and neonatal birth weight in patients with diabetes. Eur J Obstet Gynecol Reprod Biol 2008; 138:45.
  9. Mosca A, Paleari R, Dalfrà MG, et al. Reference intervals for hemoglobin A1c in pregnant women: data from an Italian multicenter study. Clin Chem 2006; 52:1138.
  10. Radder JK, van Roosmalen J. HbA1c in healthy, pregnant women. Neth J Med 2005; 63:256.
  11. Nielsen LR, Ekbom P, Damm P, et al. HbA1c levels are significantly lower in early and late pregnancy. Diabetes Care 2004; 27:1200.
  12. Herranz L, Saez-de-Ibarra L, Grande C, Pallardo LF. Non-glycemic-dependent reduction of late pregnancy A1C levels in women with type 1 diabetes. Diabetes Care 2007; 30:1579.
  13. Lurie S. Changes in age distribution of erythrocytes during pregnancy: a longitudinal study. Gynecol Obstet Invest 1993; 36:141.
  14. Jensen DM, Korsholm L, Ovesen P, et al. Peri-conceptional A1C and risk of serious adverse pregnancy outcome in 933 women with type 1 diabetes. Diabetes Care 2009; 32:1046.
  15. Nielsen GL, Møller M, Sørensen HT. HbA1c in early diabetic pregnancy and pregnancy outcomes: a Danish population-based cohort study of 573 pregnancies in women with type 1 diabetes. Diabetes Care 2006; 29:2612.
  16. Suhonen L, Hiilesmaa V, Teramo K. Glycaemic control during early pregnancy and fetal malformations in women with type I diabetes mellitus. Diabetologia 2000; 43:79.
  17. Whiteman VE, Homko CJ, Reece EA. Management of hypoglycemia and diabetic ketoacidosis in pregnancy. Obstet Gynecol Clin North Am 1996; 23:87.
  18. Middleton P, Crowther CA, Simmonds L. Different intensities of glycaemic control for pregnant women with pre-existing diabetes. Cochrane Database Syst Rev 2016; :CD008540.
  19. Riskin-Mashiah S, Damti A, Younes G, Auslander R. Normal fasting plasma glucose levels during pregnancy: a hospital-based study. J Perinat Med 2011; 39:209.
  20. Mills JL, Jovanovic L, Knopp R, et al. Physiological reduction in fasting plasma glucose concentration in the first trimester of normal pregnancy: the diabetes in early pregnancy study. Metabolism 1998; 47:1140.
  21. ter Braak EW, Evers IM, Willem Erkelens D, Visser GH. Maternal hypoglycemia during pregnancy in type 1 diabetes: maternal and fetal consequences. Diabetes Metab Res Rev 2002; 18:96.
  22. Rosenn BM, Miodovnik M. Glycemic control in the diabetic pregnancy: is tighter always better? J Matern Fetal Med 2000; 9:29.
  23. Chew EY, Mills JL, Metzger BE, et al. Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study. Diabetes Care 1995; 18:631.
  24. Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes. Lancet 1993; 341:1306.
  25. Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 1998; 116:874.
  26. Kanda E, Matsuda Y, Makino Y, Matsui H. Risk factors associated with altered fetal growth in patients with pregestational diabetes mellitus. J Matern Fetal Neonatal Med 2012; 25:1390.
  27. Langer O, Levy J, Brustman L, et al. Glycemic control in gestational diabetes mellitus--how tight is tight enough: small for gestational age versus large for gestational age? Am J Obstet Gynecol 1989; 161:646.
  28. Carl J, Christensen M, Mathiesen O. Human placental lactogen (hPL) model for the normal pregnancy. Placenta 1991; 12:289.
  29. Glueck CJ, Goldenberg N, Pranikoff J, et al. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Hum Reprod 2004; 19:1323.
  30. Glueck CJ, Bornovali S, Pranikoff J, et al. Metformin, pre-eclampsia, and pregnancy outcomes in women with polycystic ovary syndrome. Diabet Med 2004; 21:829.
  31. Glueck CJ, Goldenberg N, Wang P, et al. Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy. Hum Reprod 2004; 19:510.
  32. Glueck CJ, Pranikoff J, Aregawi D, Wang P. Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome. Fertil Steril 2008; 89:625.
  33. Kitzmiller JL, Block JM, Brown FM, et al. Managing preexisting diabetes for pregnancy: summary of evidence and consensus recommendations for care. Diabetes Care 2008; 31:1060.
  34. Institute of Medicine and National Research Council. Weight Gain During Pregnancy: Reexamining the Guidelines, Rasmussen KM, Yaktine AL (Eds), National Academies Press, Washington, DC 2009.
  35. Hillier TA, Pedula KL, Vesco KK, et al. Excess gestational weight gain: modifying fetal macrosomia risk associated with maternal glucose. Obstet Gynecol 2008; 112:1007.
  36. Scifres CM, Feghali MN, Althouse AD, et al. Effect of excess gestational weight gain on pregnancy outcomes in women with type 1 diabetes. Obstet Gynecol 2014; 123:1295.
  37. Secher AL, Parellada CB, Ringholm L, et al. Higher gestational weight gain is associated with increasing offspring birth weight independent of maternal glycemic control in women with type 1 diabetes. Diabetes Care 2014; 37:2677.
  38. Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care 2003; 26 Suppl 1:S51.
  39. Harris JA, Benedict FG. A Biometric Study of Human Basal Metabolism. Proc Natl Acad Sci U S A 1918; 4:370.
  40. Mifflin MD, St Jeor ST, Hill LA, et al. A new predictive equation for resting energy expenditure in healthy individuals. Am J Clin Nutr 1990; 51:241.
  41. Bertorelli AM. Nutritional management. In: Diabetes Complicating Pregnancy, 2nd ed, Brown FM, Hare JW (Eds), Wiley-Liss, New York 1995. p.88.
  42. Mestman JH. Outcome of diabetes screening in pregnancy and perinatal morbidity in infants of mothers with mild impairment in glucose tolerance. Diabetes Care 1980; 3:447.
  43. American Diabetes Association. 3. Foundations of Care and Comprehensive Medical Evaluation. Diabetes Care 2016; 39 Suppl 1:S23.
  44. Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2013; 98:4227.
  45. Wilson RD, Johnson JA, Wyatt P, et al. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can 2007; 29:1003.
  46. Hirsch IB. Insulin analogues. N Engl J Med 2005; 352:174.
  47. Wyatt JW, Frias JL, Hoyme HE, et al. Congenital anomaly rate in offspring of mothers with diabetes treated with insulin lispro during pregnancy. Diabet Med 2005; 22:803.
  48. Hod M, Damm P, Kaaja R, et al. Fetal and perinatal outcomes in type 1 diabetes pregnancy: a randomized study comparing insulin aspart with human insulin in 322 subjects. Am J Obstet Gynecol 2008; 198:186.e1.
  49. Mathiesen ER, Kinsley B, Amiel SA, et al. Maternal glycemic control and hypoglycemia in type 1 diabetic pregnancy: a randomized trial of insulin aspart versus human insulin in 322 pregnant women. Diabetes Care 2007; 30:771.
  50. Bhattacharyya A, Brown S, Hughes S, Vice PA. Insulin lispro and regular insulin in pregnancy. QJM 2001; 94:255.
  51. Mathiesen ER, Hod M, Ivanisevic M, et al. Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes. Diabetes Care 2012; 35:2012.
  52. Lepercq J, Lin J, Hall GC, et al. Meta-Analysis of Maternal and Neonatal Outcomes Associated with the Use of Insulin Glargine versus NPH Insulin during Pregnancy. Obstet Gynecol Int 2012; 2012:649070.
  53. Jovanovic L, Knopp RH, Brown Z, et al. Declining insulin requirement in the late first trimester of diabetic pregnancy. Diabetes Care 2001; 24:1130.
  54. Steel JM, Johnstone FD, Hume R, Mao JH. Insulin requirements during pregnancy in women with type I diabetes. Obstet Gynecol 1994; 83:253.
  55. García-Patterson A, Gich I, Amini SB, et al. Insulin requirements throughout pregnancy in women with type 1 diabetes mellitus: three changes of direction. Diabetologia 2010; 53:446.
  56. Steel JM, Johnstone FD, Hepburn DA, Smith AF. Can prepregnancy care of diabetic women reduce the risk of abnormal babies? BMJ 1990; 301:1070.
  57. Mayfield JA, White RD. Insulin therapy for type 2 diabetes: rescue, augmentation, and replacement of beta-cell function. Am Fam Physician 2004; 70:489.
  58. Langer O, Anyaegbunam A, Brustman L, et al. Pregestational diabetes: insulin requirements throughout pregnancy. Am J Obstet Gynecol 1988; 159:616.
  59. Coustan DR, Reece EA, Sherwin RS, et al. A randomized clinical trial of the insulin pump vs intensive conventional therapy in diabetic pregnancies. JAMA 1986; 255:631.
  60. Rudolf MC, Coustan DR, Sherwin RS, et al. Efficacy of the insulin pump in the home treatment of pregnant diabetics. Diabetes 1981; 30:891.
  61. Ranasinghe PD, Maruthur NM, Nicholson WK, et al. Comparative effectiveness of continuous subcutaneous insulin infusion using insulin analogs and multiple daily injections in pregnant women with diabetes mellitus: a systematic review and meta-analysis. J Womens Health (Larchmt) 2015; 24:237.
  62. Mukhopadhyay A, Farrell T, Fraser RB, Ola B. Continuous subcutaneous insulin infusion vs intensive conventional insulin therapy in pregnant diabetic women: a systematic review and metaanalysis of randomized, controlled trials. Am J Obstet Gynecol 2007; 197:447.
  63. Farrar D, Tuffnell DJ, West J, West HM. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. Cochrane Database Syst Rev 2016; :CD005542.
  64. Roeder HA, Moore TR, Ramos GA. Insulin pump dosing across gestation in women with well-controlled type 1 diabetes mellitus. Am J Obstet Gynecol 2012; 207:324.e1.
  65. Stewart ZA, Wilinska ME, Hartnell S, et al. Closed-Loop Insulin Delivery during Pregnancy in Women with Type 1 Diabetes. N Engl J Med 2016; 375:644.
  66. McManus RM, Ryan EA. Insulin requirements in insulin-dependent and insulin-requiring GDM women during final month of pregnancy. Diabetes Care 1992; 15:1323.
  67. Weiss PA, Hofmann H. Intensified conventional insulin therapy for the pregnant diabetic patient. Obstet Gynecol 1984; 64:629.
  68. Fuglsang J, Lauszus F, Flyvbjerg A, Ovesen P. Human placental growth hormone, insulin-like growth factor I and -II, and insulin requirements during pregnancy in type 1 diabetes. J Clin Endocrinol Metab 2003; 88:4355.
  69. Padmanabhan S, McLean M, Cheung NW. Falling insulin requirements are associated with adverse obstetric outcomes in women with preexisting diabetes. Diabetes Care 2014; 37:2685.
  70. Oka R, Iura T, Miyamoto S. Large decreases in insulin requirement occurred repeatedly in two pregnancies in a type 1 diabetic woman. Acta Diabetol 2006; 43:34.
  71. Spellacy WN, Buhi WC, Birk SA, McCreary SA. Distribution of human placental lactogen in the last half of normal and complicated pregnancies. Am J Obstet Gynecol 1974; 120:214.
  72. Olszewski J, Szczurowicz A, Wójcikowski C. [Changes in levels of human placenta lactogen (hPL), progesterone, and estriol in blood serum and estrogens in urine during gestational diabetes mellitus]. Ginekol Pol 1995; 66:145.
  73. Homko CJ, Sivan E, Reece AE. Is there a role for oral antihyperglycemics in gestational diabetes and type 2 diabetes during pregnancy? Treat Endocrinol 2004; 3:133.
  74. Coetzee EJ, Jackson WP. Oral hypoglycaemics in the first trimester and fetal outcome. S Afr Med J 1984; 65:635.
  75. Coetzee EJ, Jackson WP. Metformin in management of pregnant insulin-independent diabetics. Diabetologia 1979; 16:241.
  76. Langer O, Conway DL, Berkus MD, et al. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000; 343:1134.
  77. Chmait R, Dinise T, Moore T. Prospective observational study to establish predictors of glyburide success in women with gestational diabetes mellitus. J Perinatol 2004; 24:617.
  78. Towner D, Kjos SL, Leung B, et al. Congenital malformations in pregnancies complicated by NIDDM. Diabetes Care 1995; 18:1446.
  79. Koren G. Proceedings of the NIH/FDA Toxicology in Pregnancy conference, Toronto 2000.
  80. Jacobson GF, Ramos GA, Ching JY, et al. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol 2005; 193:118.
  81. Koren G. Glyburide and fetal safety; transplacental pharmacokinetic considerations. Reprod Toxicol 2001; 15:227.
  82. Hellmuth E, Damm P, Mølsted-Pedersen L. Oral hypoglycaemic agents in 118 diabetic pregnancies. Diabet Med 2000; 17:507.
  83. Gilbert C, Valois M, Koren G. Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. Fertil Steril 2006; 86:658.
  84. Cassina M, Donà M, Di Gianantonio E, et al. First-trimester exposure to metformin and risk of birth defects: a systematic review and meta-analysis. Hum Reprod Update 2014; 20:656.
  85. Guideline Development Group. Management of diabetes from preconception to the postnatal period: summary of NICE guidance. BMJ 2008; 336:714.
  86. Garcia-Bournissen F, Feig DS, Koren G. Maternal-fetal transport of hypoglycaemic drugs. Clin Pharmacokinet 2003; 42:303.
  87. Kemball ML, McIver C, Milner RD, et al. Neonatal hypoglycaemia in infants of diabetic mothers given sulphonylurea drugs in pregnancy. Arch Dis Child 1970; 45:696.
  88. Zucker P, Simon G. Prolonged symptomatic neonatal hypoglycemia associated with maternal chlorpropamide therapy. Pediatrics 1968; 42:824.
  89. Chan LY, Yeung JH, Lau TK. Placental transfer of rosiglitazone in the first trimester of human pregnancy. Fertil Steril 2005; 83:955.
  90. Kalyoncu NI, Yaris F, Ulku C, et al. A case of rosiglitazone exposure in the second trimester of pregnancy. Reprod Toxicol 2005; 19:563.
  91. Heerwagen MJ, Miller MR, Barbour LA, Friedman JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol 2010; 299:R711.
  92. American Diabetes Association. Physical activity/exercise and diabetes. Diabetes Care 2004; 27 Suppl 1:S58.
  93. Sigal RJ, Kenny GP, Wasserman DH, et al. Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:1433.