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Optimizing Insulin Therapy in Pregnant Women with Type 1 Diabetes Mellitus

  • Therapy In Practice
  • Published:
Treatments in Endocrinology

Abstract

Pregnancy complicated by type 1 diabetes mellitus is associated with an increased risk of complications in the mother and infant. Normal or near normal glycemic control prior to and during pregnancy reduces many of these risks to levels observed in the general population.

This degree of glycemic control is generally achievable only with intensive insulin therapy: multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) via an insulin pump. These therapeutic regimens have been found to result in comparable glycemic control, although CSII provides increased flexibility in terms of patient lifestyle, and may reduce the incidence of hypoglycemia.

Frequent home blood glucose monitoring is imperative during pregnancy in order to optimize glycemic control and reduce the risk of hypoglycemia. Furthermore, insulin requirements change significantly over the course of pregnancy.

The new short-acting insulin analogs, insulin lispro and insulin aspart, have pharmacodynamic properties which make them ideal for use during pregnancy. Although the number of published studies evaluating the use of insulin lispro during pregnancy is limited, the majority support its safety. No studies of insulin aspart in pregnancy have been published in full.

In addition to optimization of glycemic control, frequent assessment for development and/or progression of microvascular complications is necessary during pregnancy.

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References

  1. Healy K, Jovanovic-Peterson L, Peterson CM. Pancreatic disorders of pregnancy: pregestational diabetes. Endocrinol Metab Clin North Am 1995; 24: 73–101

    PubMed  CAS  Google Scholar 

  2. Langer O, Conway DL. Level of glycemia and perinatal outcome in pregestational diabetes. J Matern Fetal Med 2000; 9: 35–41

    Article  PubMed  CAS  Google Scholar 

  3. McElvy SS, Miodovnik M, Rosenn B, et al. A focused preconceptional and early pregnancy program in women with type 1 diabetes reduces perinatal mortality and malformation rates to general population levels. J Matern Fetal Med 2000; 9: 14–20

    Article  PubMed  CAS  Google Scholar 

  4. Jovanovic-Peterson L, Peterson CM, Reed GF, et al. National Institute of Child Health and Human Development — Diabetes in Early Pregnancy Study. Maternal postprandial glucose levels and infant birth weight: the diabetes in early pregnancy study. Am J Obstet Gynecol 1991; 164: 103–11

    PubMed  CAS  Google Scholar 

  5. Combs CA, Gunderson E, Kitzmiller JL, et al. Relationship of fetal macrosomia to maternal postprandial glucose control during pregnancy. Diabetes Care 1992; 15: 1251–7

    Article  PubMed  CAS  Google Scholar 

  6. de Veciana M, Major CA, Morgan MA, et al. Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. N Engl J Med 1995; 333: 1237–41

    Article  PubMed  Google Scholar 

  7. Vajo Z, Duckworth WC. Genetically engineered insulin analogs: diabetes in the new millenium. Pharmacol Rev 2000; 52: 1–9

    PubMed  CAS  Google Scholar 

  8. Rosenn B, Miodovnik M, Combs CA, et al. Pre-conception management of insulin-dependent diabetes: improvement of pregnancy outcome. Obstet Gynecol 1991; 77: 846–9

    PubMed  CAS  Google Scholar 

  9. Goldman JA, Dicker D, Feldberg D, et al. Pregnancy outcome in patients with insulin-dependent diabetes mellitus with preconception diabetic control: a comparative study. Am J Obstet Gynecol 1986; 155: 293–7

    PubMed  CAS  Google Scholar 

  10. Holing EV, Beyer CS, Brown ZA, et al. Why don’t women with diabetes plan their pregnancies? Diabetes Care 1988; 21: 889–95

    Article  Google Scholar 

  11. Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications (technical review). Diabetes Care 2002; 25: S136–8

    Article  Google Scholar 

  12. Miodovnik M, Mimouni F, Tsang RC, et al. Elevated maternal glycohemoglobin in early pregnancy and spontaneous abortion among insulin-dependent diabetic women. Am J Obstet Gynecol 1985; 153: 439–42

    PubMed  CAS  Google Scholar 

  13. Kitzmiller JL, Buchanan TA, Kjos S, et al. Pre-conception care of diabetes, congenital malformation, and spontaneous abortions. Diabetes Care 1996; 19: 514–41

    PubMed  CAS  Google Scholar 

  14. Kitzmiller JL, Gavin LA, Gin GD, et al. Preconception care of diabetes: glycemic control prevents congenital anomalies. JAMA 1991; 265: 731–6

    Article  PubMed  CAS  Google Scholar 

  15. Diamond MP, Reece EA, Caprio S, et al. Impairment of counterregulatory hormone responses to hypoglycemia in pregnant women with insulin-dependent diabetes mellitus. Am J Obstet Gynecol 1992; 166: 70–7

    PubMed  CAS  Google Scholar 

  16. Rosenn BM, Miodovnik M, Khoury JC, et al. Counterregulatory hormonal responses to hypoglycemia during pregnancy. Obstet Gynecol 1996; 87: 568–74

    Article  PubMed  CAS  Google Scholar 

  17. Rosenn BM, Miodovnik M, Holcberg G, et al. Hypoglycemia: the price of intensive insulin therapy for pregnant women with insulin-dependent diabetes mellitus. Obstet Gynecol 1995; 85: 417–22

    Article  PubMed  CAS  Google Scholar 

  18. Rosenn GM, Miodovnik M. Glycemic control in the diabetic pregnancy: is tighter always better? J Matern-Fetal Med 2000; 9: 29–34

    Article  PubMed  CAS  Google Scholar 

  19. Ter Braak EW, Evers IM, Willem Erkelens D, et al. Maternal hypoglycemia during pregnancy in type 1 diabetes: maternal and fetal consequences. Diabetes Metab Res Rev 2002 Mar–Apr; 18(2): 96–105

    Article  PubMed  Google Scholar 

  20. Jovanovic L, editor. Medical management of pregnancy complicated by diabetes. 3rd ed. Alexandria (VA): American Diabetes Association, 2000

    Google Scholar 

  21. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–86

    Article  Google Scholar 

  22. Gabbe SG, Holing E, Temple P, et al. Benefits, risks, costs, and patient satisfaction associated with insulin pump therapy for the pregnancy complicated by type 1 diabetes mellitus. Am J Obstet Gynecol 2000; 182: 1283–91

    Article  PubMed  CAS  Google Scholar 

  23. Lenhard MJ, Reeves GD. Continuous subcutaneous insulin infusion: a comprehensive review of insulin pump therapy. Arch Intern Med 2001; 161(9): 2293–300

    Article  PubMed  CAS  Google Scholar 

  24. Gabbe SG. New concepts and applications in the use of the insulin pump during pregnancy. J Matern Fetal Med 2000; 9: 42–5

    Article  PubMed  CAS  Google Scholar 

  25. Heinemann L, Woodworth J. Pharmacokinetics and glucodynamics of insulin lispro. Drugs Today 1998; 34Suppl. 3: 23–36

    CAS  Google Scholar 

  26. Home PD, Barriocanal L, Lindholm A. Comparative pharmacokinetics and pharmacodynamics of the novel rapid-acting insulin analogue, insulin aspart, in healthy volunteers. Eur J Clin Pharmacol 1999; 55: 199–203

    Article  PubMed  CAS  Google Scholar 

  27. Home PD, Lindholm A, Hylleberg B, et al. Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1 diabetic patients. UK Insulin Aspart Study Group. Diabetes Care 1998; 21: 1904–9

    Article  PubMed  CAS  Google Scholar 

  28. Anderson JH, Koivisto VA. Clinical studies on insulin lispro. Drugs Today 1998; 34Suppl. C: 37–50

    CAS  Google Scholar 

  29. Anderson JH, Brunelle RL, Koivisto VA, et al. Reduction of postprandial hyper-glycemia and frequency of hypoglycemia in IDDM patients in insulin-analog treatment. Diabetes 1997; 46: 265–70

    Article  PubMed  CAS  Google Scholar 

  30. Zinman B, Tildesley H, Chiasson J-L, et al. Insulin lispro in CSII: results of a double-blind crossover study. Diabetes 1997; 46: 440–3

    Article  PubMed  CAS  Google Scholar 

  31. Lalli C, Ciofetta M, Del Sindaco P, et al. Long-term intensive treatment of type 1 diabetes with the short-acting insulin analog lispro in variable combination with NPH insulin at mealtime. Diabetes Care 1999; 22: 468–77

    Article  PubMed  CAS  Google Scholar 

  32. Ebeling P, Jansson P-A, Smith U, et al. Strategies towards improved control during insulin lispro therapy in IDDM: importance of basal insulin. Diabetes Care 1997; 20: 1287–9

    Article  PubMed  CAS  Google Scholar 

  33. Diamond T, Kormas N. Possible adverse fetal effect of insulin lispro. N Engl J Med 1997; 337: 1009–10

    Article  PubMed  CAS  Google Scholar 

  34. Kitzmiller JL, Main E, Ward B, et al. Insulin lispro and the development of pro-liferative diabetic retinopathy during pregnancy. Diabetes Care 1999; 22: 874–6

    Article  PubMed  CAS  Google Scholar 

  35. Jovanovic L, Ilic S, Pettitt DJ, et al. Metabolic and immunological effects of insulin lispro in gestational diabetes. Diabetes Care 1999; 22: 1422–7

    Article  PubMed  CAS  Google Scholar 

  36. Bhattacharyya A, Vice PA. Insulin lispro, pregnancy, and retinopathy. Diabetes Care 1999; 22: 2101–2

    Article  PubMed  CAS  Google Scholar 

  37. Bhattacharyya A, Brown S, Hughes S, et al. Insulin lispro and regular insulin in pregnancy. QJM 2001; 94: 255–60

    Article  PubMed  CAS  Google Scholar 

  38. Buchbinder A, Miodovnik M, McElvy S, et al. Is insulin lispro associated with the development or progression of diabetic retinopathy during pregnancy? Am J Obstet Gynecol 2000; 183: 1162–5

    Article  PubMed  CAS  Google Scholar 

  39. Garg SK, Anil S, Gottlieb P, et al. Better glycemic control and reduced need for Caesarian sections with insulin lispro treated pregnancies in type 1 diabetes [abstract]. Diabetes 2001; 50Suppl. 2: A383

    Google Scholar 

  40. Jovanovic L. Retinopathy risk: what is responsible? Hormones, hyperglycemia, or Humalog? Diabetes Care 1999; 22: 846–7

    Article  PubMed  CAS  Google Scholar 

  41. Brunelle RL, Llewelyn J, Anderson Jr JH, et al. Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes. Diabetes Care 1998; 21: 1726–31

    Article  PubMed  CAS  Google Scholar 

  42. Rassmusen SA, Moore CA, Paulozzi LJ, et al. Risk for birth defects among premature infants: a population-based study. J Pediatr 2001; 138: 668–73

    Article  Google Scholar 

  43. Montgomery A, Miller L. Using the Colorado birth defects monitoring program to connect families with services for children with special needs. Teratology 2001; 64: S42–6

    Article  PubMed  Google Scholar 

  44. Horton Jr WE, Sadler TW. Effects of maternal diabetes on early embryogenesis: alterations in morphogenesis produced by the ketone body, B-hydroxybutyrate. Diabetes 1983; 32: 610–6

    Article  PubMed  CAS  Google Scholar 

  45. Jovanovic L, Knopp RH, Brown Z, et al. Declining insulin requirements in the late first trimester of diabetic pregnancy. Diabetes Care 2001; 24: 1130–6

    Article  PubMed  CAS  Google Scholar 

  46. Reece EA, Homko CJ. Diabetes mellitus in pregnancy: what are the best treatment options? Drug Saf 1998; 18(3): 209–20

    Article  PubMed  CAS  Google Scholar 

  47. Jovanovic L, Peterson CM. Insulin and glucose requirements during the first stage of labor in insulin-dependent diabetic women. Am J Med 1983; 75: 607–12

    Article  PubMed  CAS  Google Scholar 

  48. Jovanovic L, Peterson CM. Optimal insulin delivery for the pregnant diabetic patient. Diabetes Care 1982; 5Suppl. 1: 24–37

    PubMed  Google Scholar 

  49. Garg S, Susaria K, Jackson W, et al. Insulin lispro (Humalog®) and the renal and retinal complications of type 1 diabetes [abstract]. Diabetologia 1997; 40: 501

    Google Scholar 

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Acknowledgements

This research was supported by Grant Number M01RR00069 General Clinical Research Centers Program, National Centers for Research Resources at NIH, the Children’s Diabetes Foundation at Denver, and Diabetes Endocrine Research Center (Grant Number NIP30DK57516).

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Authors and Affiliations

  1. Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA

    Peter A. Gottlieb, Bhavani Chillara &  Satish K. Garg

  2. Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA

    Peter A. Gottlieb, Juan P. Frias &  Satish K. Garg

  3. Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado, CO 80262, USA

    Peter A. Gottlieb, Juan P. Frias, Kelly A. Peters, Bhavani Chillara &  Satish K. Garg

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  1. Peter A. Gottlieb
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  2. Juan P. Frias
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  5. Satish K. Garg
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Correspondence to Satish K. Garg.

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Gottlieb, P.A., Frias, J.P., Peters, K.A. et al. Optimizing Insulin Therapy in Pregnant Women with Type 1 Diabetes Mellitus. Mol Diag Ther 1, 235–240 (2002). https://doi.org/10.2165/00024677-200201040-00005

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