Top

16-08-2018 | Pregnancy | Review | Article

Glucose Targets and Insulin Choice in Pregnancy: What Has Changed in the Last Decade?

Journal: Current Diabetes Reports

Authors: Siobhán Bacon, Denice S. Feig

Publisher: Springer US

Abstract

Purpose of Review

To review current glycaemic targets and the potential use of newer insulin formulations in pregnancy.

Recent Findings

The impact of stricter glycaemic control on perinatal outcomes remains controversial, showing conflicting results. Current ongoing randomised trials investigating the role of tighter glucose targets in pregnancy should help clarify the benefit of tighter glucose control. Optimal timing for self-monitoring blood glucose (SMBG) remains debatable. Data suggest that post-prandial SMBG, particularly at 1 h, offers the best prediction of adverse perinatal outcome. To achieve these targets, insulin is the standard therapy. Novel insulin formulations offer benefits outside of pregnancy. Recent data on the use of new insulins in pregnancy (e.g. insulin degludec and glargine (U 300)) is limited to case reports.

Summary

Glycaemic targets have remained unchanged in the last decade. Studies using stricter glycaemic targets may improve perinatal outcomes. Newer insulin formulations may offer increased flexibility and glycaemic control. Clinicians caring for women with diabetes striving to minimise adverse perinatal outcomes will find this review of interest.

Sheffield JS, Butler-Koster EL, Casey BM, McIntire DD, Leveno KJ. Maternal diabetes mellitus and infant malformations. Obstet Gynecol. 2002;100(5 Pt 1):925–30.PubMed

Sharpe PB, Chan A, Haan EA, Hiller JE. Maternal diabetes and congenital anomalies in South Australia 1986-2000: a population-based cohort study. Birth Defects Res Part A. 2005;73(9):605–11. https://doi.org/10.1002/bdra.20172.CrossRef

Casson IF, Clarke CA, Howard CV, McKendrick O, Pennycook S, Pharoah PO, et al. Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study. BMJ. 1997;315(7103):275–8.CrossRefPubMedPubMedCentral

Cyganek K, Hebda-Szydlo A, Katra B, Skupien J, Klupa T, Janas I, et al. Glycemic control and selected pregnancy outcomes in type 1 diabetes women on continuous subcutaneous insulin infusion and multiple daily injections: the significance of pregnancy planning. Diabetes Technol Ther. 2010;12(1):41–7. https://doi.org/10.1089/dia.2009.0081.CrossRefPubMed

Chatfield J. ACOG issues guidelines on fetal macrosomia. American College of Obstetricians and Gynecologists. Am Fam Physician. 2001;64(1):169–70.PubMed

Langer O, Mazze R. The relationship between large-for-gestational-age infants and glycemic control in women with gestational diabetes. Am J Obstet Gynecol. 1988;159(6):1478–83.CrossRefPubMed

Hernandez TL. Glycemic targets in pregnancies affected by diabetes: historical perspective and future directions. Curr Diab Rep. 2015;15(1):565. https://doi.org/10.1007/s11892-014-0565-2.CrossRefPubMed

O’Sullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pregnancy. Diabetes. 1964;13:278–85.PubMed

Metzger BE, Phelps RL, Freinkel N, Navickas IA. Effects of gestational diabetes on diurnal profiles of plasma glucose, lipids, and individual amino acids. Diabetes Care. 1980;3(3):402–9.CrossRefPubMed

10.

Jovanovic-Peterson L, Peterson CM, Reed GF, Metzger BE, Mills JL, Knopp RH, 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(1 Pt 1):103–11.CrossRefPubMed

11.

Combs CA, Gunderson E, Kitzmiller JL, Gavin LA, Main EK. Relationship of fetal macrosomia to maternal postprandial glucose control during pregnancy. Diabetes Care. 1992;15(10):1251–7.CrossRefPubMed

12.

Hernandez TL, Friedman JE, Van Pelt RE, Barbour LA. Patterns of glycemia in normal pregnancy: should the current therapeutic targets be challenged? Diabetes Care. 2011;34(7):1660–8. https://doi.org/10.2337/dc11-0241.CrossRefPubMedPubMedCentral

13.

• Middleton P, Crowther CA, Simmonds L. Different intensities of glycaemic control for pregnant women with pre-existing diabetes. Cochrane Database Syst Rev. 2016(5):CD008540. doi:https://doi.org/10.1002/14651858.CD008540.pub4. Analysis of different intensities of glycaemic control in pre-gestational diabetes. The study demonstrated that there was limited evidence but fewer women with preeclampsia, caesarean sections and LGA offspring in those in the “tight-moderate” group compared to the “loose group” for glucose targets.

14.

Martis R, Brown J, Alsweiler J, Crawford TJ, Crowther CA. Different intensities of glycaemic control for women with gestational diabetes mellitus. Cochrane Database Syst Rev. 2016;4:CD011624. https://doi.org/10.1002/14651858.CD011624.pub2.CrossRefPubMed

15.

Prutsky GJ, Domecq JP, Wang Z, Carranza Leon BG, Elraiyah T, Nabhan M, et al. Glucose targets in pregnant women with diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2013;98(11):4319–24. https://doi.org/10.1210/jc.2013-2461.CrossRefPubMed

16.

de Veciana M, Major CA, Morgan MA, Asrat T, Toohey JS, Lien JM, et al. Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. N Engl J Med. 1995;333(19):1237–41. https://doi.org/10.1056/NEJM199511093331901.CrossRefPubMed

17.

Durnwald CP, Mele L, Spong CY, Ramin SM, Varner MW, Rouse DJ, et al. Glycemic characteristics and neonatal outcomes of women treated for mild gestational diabetes. Obstet Gynecol. 2011;117(4):819–27. https://doi.org/10.1097/AOG.0b013e31820fc6cf.CrossRefPubMedPubMedCentral

18.

Sivan E, Weisz B, Homko CJ, Reece EA, Schiff E. One or two hours postprandial glucose measurements: are they the same? Am J Obstet Gynecol. 2001;185(3):604–7. https://doi.org/10.1067/mob.2001.117184.CrossRefPubMed

19.

Ben-Haroush A, Yogev Y, Chen R, Rosenn B, Hod M, Langer O. The postprandial glucose profile in the diabetic pregnancy. Am J Obstet Gynecol. 2004;191(2):576–81. https://doi.org/10.1016/j.ajog.2004.01.055.CrossRefPubMed

20.

Weisz B, Shrim A, Homko CJ, Schiff E, Epstein GS, Sivan E. One hour versus two hours postprandial glucose measurement in gestational diabetes: a prospective study. J Perinatol. 2005;25(4):241–4. https://doi.org/10.1038/sj.jp.7211243.CrossRefPubMed

21.

Ozgu-Erdinc AS, Iskender C, Uygur D, Oksuzoglu A, Seckin KD, Yeral MI, et al. One-hour versus two-hour postprandial blood glucose measurement in women with gestational diabetes mellitus: which is more predictive? Endocrine. 2016;52(3):561–70. https://doi.org/10.1007/s12020-015-0813-5.CrossRefPubMed

22.

Kjos SL, Schaefer-Graf U, Sardesi S, Peters RK, Buley A, Xiang AH, et al. A randomized controlled trial using glycemic plus fetal ultrasound parameters versus glycemic parameters to determine insulin therapy in gestational diabetes with fasting hyperglycemia. Diabetes Care. 2001;24(11):1904–10.CrossRefPubMed

23.

Kjos SL, Schaefer-Graf UM. Modified therapy for gestational diabetes using high-risk and low-risk fetal abdominal circumference growth to select strict versus relaxed maternal glycemic targets. Diabetes Care. 2007;30(Suppl 2):S200–5. https://doi.org/10.2337/dc07-s216.CrossRefPubMed

24.

Aydin Y, Berker D, Direktor N, Ustun I, Tutuncu YA, Isik S, et al. Is insulin lispro safe in pregnant women: does it cause any adverse outcomes on infants or mothers? Diabetes Res Clin Pract. 2008;80(3):444–8. https://doi.org/10.1016/j.diabres.2008.02.004.CrossRefPubMed

25.

Murphy HR, Elleri D, Allen JM, Harris J, Simmons D, Rayman G, et al. Pathophysiology of postprandial hyperglycaemia in women with type 1 diabetes during pregnancy. Diabetologia. 2012;55(2):282–93. https://doi.org/10.1007/s00125-011-2363-6.CrossRefPubMed

26.

Boskovic R, Feig DS, Derewlany L, Knie B, Portnoi G, Koren G. Transfer of insulin lispro across the human placenta: in vitro perfusion studies. Diabetes Care. 2003;26(5):1390–4.CrossRefPubMed

27.

Pollex EK, Feig DS, Lubetsky A, Yip PM, Koren G. Insulin glargine safety in pregnancy: a transplacental transfer study. Diabetes Care. 2010;33(1):29–33. https://doi.org/10.2337/dc09-1045.CrossRefPubMed

28.

Kurtzhals P, Schaffer L, Sorensen A, Kristensen C, Jonassen I, Schmid C, et al. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes. 2000;49(6):999–1005.CrossRefPubMed

29.

Pollex E, Moretti ME, Koren G, Feig DS. Safety of insulin glargine use in pregnancy: a systematic review and meta-analysis. Ann Pharmacother. 2011;45(1):9–16. https://doi.org/10.1345/aph.1P327.CrossRefPubMed

30.

Wang H, Wender-Ozegowska E, Garne E, Morgan M, Loane M, Morris JK, et al. Insulin analogues use in pregnancy among women with pregestational diabetes mellitus and risk of congenital anomaly: a retrospective population-based cohort study. BMJ Open. 2018;8(2):e014972. https://doi.org/10.1136/bmjopen-2016-014972.CrossRefPubMedPubMedCentral

31.

Lv S, Wang J, Xu Y. Safety of insulin analogs during pregnancy: a meta-analysis. Arch Gynecol Obstet. 2015;292(4):749–56. https://doi.org/10.1007/s00404-015-3692-3.CrossRefPubMed

32.

McCance DR, Damm P, Mathiesen ER, Hod M, Kaaja R, Dunne F, et al. Evaluation of insulin antibodies and placental transfer of insulin aspart in pregnant women with type 1 diabetes mellitus. Diabetologia. 2008;51(11):2141–3. https://doi.org/10.1007/s00125-008-1120-y.CrossRefPubMed

33.

Pettitt DJ, Ospina P, Howard C, Zisser H, Jovanovic L. Efficacy, safety and lack of immunogenicity of insulin aspart compared with regular human insulin for women with gestational diabetes mellitus. Diabet Med. 2007;24(10):1129–35. https://doi.org/10.1111/j.1464-5491.2007.02247.x.CrossRefPubMedPubMedCentral

34.

Mathiesen ER, Kinsley B, Amiel SA, Heller S, McCance D, Duran S, 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(4):771–6. https://doi.org/10.2337/dc06-1887.CrossRefPubMed

35.

Heise T, Hovelmann U, Brondsted L, Adrian CL, Nosek L, Haahr H. Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart. Diabetes Obes Metab. 2015;17(7):682–8. https://doi.org/10.1111/dom.12468.CrossRefPubMedPubMedCentral

36.

Carracher AM, Marathe PH, Close KL. Diabetes news. J Diab. 2018;10:541–5. https://doi.org/10.1111/1753-0407.12661.CrossRef

37.

Bowering K, Case C, Harvey J, Reeves M, Sampson M, Strzinek R, et al. Faster aspart versus insulin aspart as part of a basal-bolus regimen in inadequately controlled type 2 diabetes: the onset 2 trial. Diabetes Care. 2017;40(7):951–7. https://doi.org/10.2337/dc16-1770.CrossRefPubMed

38.

Bode BW, Johnson JA, Hyveled L, Tamer SC, Demissie M. Improved postprandial glycemic control with faster-acting insulin aspart in patients with type 1 diabetes using continuous subcutaneous insulin infusion. Diabetes Technol Ther. 2017;19(1):25–33. https://doi.org/10.1089/dia.2016.0350.CrossRefPubMedPubMedCentral

39.

Schuster MW, Chauhan SP, McLaughlin BN, Perry KG Jr, Morrison JC. Comparison of insulin regimens and administration modalities in pregnancy complicated by diabetes. J Miss State Med Assoc. 1998;39(2):51–5.PubMed

40.

Hompesch M, Ocheltree SM, Wondmagegnehu ET, Morrow LA, Kollmeier AP, Campaigne BN, et al. Pharmacokinetics and pharmacodynamics of insulin lispro protamine suspension compared with insulin glargine and insulin detemir in type 2 diabetes. Curr Med Res Opin. 2009;25(11):2679–87. https://doi.org/10.1185/03007990903223739.CrossRefPubMed

41.

Dalfra MG, Soldato A, Moghetti P, Lombardi S, Vinci C, De Cata AP, et al. Diabetic pregnancy outcomes in mothers treated with basal insulin lispro protamine suspension or NPH insulin: a multicenter retrospective Italian study. J Matern Fetal Neonatal Med. 2016;29(7):1061–5. https://doi.org/10.3109/14767058.2015.1033619.CrossRefPubMed

42.

Lepercq J, Lin J, Hall GC, Wang E, Dain MP, Riddle MC, 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;2012:649070–11. https://doi.org/10.1155/2012/649070.CrossRefPubMedPubMedCentral

43.

• Suffecool K, Rosenn B, Niederkofler EE, Kiernan UA, Foroutan J, Antwi K, et al. Insulin detemir does not cross the human placenta. Diabetes Care. 2015;38(2):e20–1. https://doi.org/10.2337/dc14-2090. Transplacental pharmacokinetic study demonstrating undetectable insulin detemir in foetal circulation indicating no transplacental passage. CrossRefPubMed

44.

Hod M, Mathiesen ER, Jovanovic L, McCance DR, Ivanisevic M, Duran-Garcia S, et al. A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetes. J Matern Fetal Neonatal Med. 2014;27(1):7–13. https://doi.org/10.3109/14767058.2013.799650.CrossRefPubMed

45.

Herrera KM, Rosenn BM, Foroutan J, Bimson BE, Al Ibraheemi Z, Moshier EL, et al. Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes. Am J Obstet Gynecol. 2015;213(3):426.e1–7. https://doi.org/10.1016/j.ajog.2015.06.010.CrossRef

46.

Mathiesen ER, Damm P, Jovanovic L, McCance DR, Thyregod C, Jensen AB, et al. Basal insulin analogues in diabetic pregnancy: a literature review and baseline results of a randomised, controlled trial in type 1 diabetes. Diabetes Metab Res Rev. 2011;27(6):543–51. https://doi.org/10.1002/dmrr.1213.CrossRefPubMed

47.

• Mathiesen ER, Andersen H, Kring SI, Damm P. Design and rationale of a large, international, prospective cohort study to evaluate the occurrence of malformations and perinatal/neonatal death using insulin detemir in pregnant women with diabetes in comparison with other long-acting insulins. BMC Pregnancy Childbirth. 2017;17(1):38. https://doi.org/10.1186/s12884-016-1177-4. Study conducted to evaluate the risk for major congenital anomaly associated with first trimester exposure to insulin analogues when compared to human insulin. There was no associated increased risk for major congenital anomaly in the insulin analogue-treated group. CrossRefPubMedPubMedCentral

48.

Zhang XW, Zhang XL, Xu B, Kang LN. Comparative safety and efficacy of insulin degludec with insulin glargine in type 2 and type 1 diabetes: a meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55(5):429–41. https://doi.org/10.1007/s00592-018-1107-1.CrossRefPubMed

49.

Milluzzo A, Tumminia A, Scalisi NM, Frittitta L, Vigneri R, Sciacca L. Insulin degludec in the first trimester of pregnancy: report of two cases. J Diabetes Investig. 2017;9:629–31. https://doi.org/10.1111/jdi.12721.CrossRefPubMedCentral

50.

Formoso G, Ginestra F, Di Dalmazi G, Consoli A. Empagliflozin, metformin and insulin degludec, during pregnancy: a case report. Acta Diabetol. 2018;55:759–61. https://doi.org/10.1007/s00592-018-1134-y.CrossRefPubMed

51.

Okeigwe I, Yeaton-Massey A, Kim S, Vargas JE, Murphy EJ. U-500R and aspart insulin for the treatment of severe insulin resistance in pregnancy associated with pregestational diabetes. J Perinatol. 2013;33(3):235–8. https://doi.org/10.1038/jp.2012.70.CrossRefPubMed

Medicine Matters Diabetes

Abstract

Purpose of Review

Recent Findings

Summary