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Am J Perinatol 2021; 38(06): 535-543
DOI: 10.1055/s-0040-1718579
SMFM Fellowship Series Article

Insulin Dosing, Glycemic Control, and Perinatal Outcomes in Pregnancies Complicated by Type-2 Diabetes

Hugh C.G. Nadeau 
1   Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma
,
Marta E. Maxted
1   Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma
,
Devika Madhavan
2   Department of Medicine, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma
,
Stephanie L. Pierce
1   Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma
,
Maisa Feghali
3   Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Women's Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Christina Scifres
4   Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana
› Author Affiliations Funding M.F. is supported by the National Institutes of Health through grant number K23 HD092893. The funding source had no involvement in the preparation, analysis, and interpretation of the data or submission of this report.
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Abstract

Objective This study aimed to evaluate the prevalence of severe insulin resistance (insulin requirements ≥2 units/kg) at delivery and the relationship between severe insulin resistance, glycemic control, and adverse perinatal outcomes in pregnant women with type-2 diabetes mellitus.

Study Design This is a retrospective cohort study of women with type-2 diabetes mellitus who delivered between January 2015 and December 2017 at a tertiary academic medical center. Maternal demographic information, self-monitored blood sugars, and insulin doses were abstracted from the medical record. Multivariable logistic regression was used to identify maternal baseline characteristics associated with severe insulin resistance at delivery.

Results Overall 72/160 (45%) of women had severe insulin resistance. Women in the severe insulin resistance group demonstrated evidence of suboptimal glycemic control as evidenced by higher mean hemoglobin A1c (HbA1c) values (7.2 [ ±  1.1] vs. 6.6 [ ±  1.3%], p = 0.003), higher mean fasting (104.0 [ ±  17.4] vs. 95.2 [ ±  11.7 mg/dL], p < 0.001) and postprandial glucose values (132.4 [ ±  17.2] vs. 121.9 [ ± 16.9 mg/dL]), p < 0.001), and a higher percentage of total glucose values that were elevated above targets (37.7 [95% confidence interval (CI): 26.8–50] vs. 25.6 [95% CI: 13.3–41.3%], p < 0.001). Maternal HbA1c ≥6.5% and insulin use prior to pregnancy were associated with a higher prevalence of severe insulin resistance, while Hispanic ethnicity and non-White race were associated with a lower prevalence of severe insulin resistance. The rates of adverse perinatal outcomes including large for gestational age (LGA) birth weight, cesarean delivery, and hypertensive disorders of pregnancy did not differ between groups.

Conclusion Severe insulin resistance is common among pregnant women with type-2 diabetes, and it is associated with suboptimal glycemic control. Future studies are necessary to develop strategies to identify women with severe insulin resistance early in pregnancy and facilitate adequate insulin dosing.

Key Points

  • Severe insulin resistance is common.

  • BMI does not predict severe insulin resistance.

  • Suboptimal glycemic control is common.

Keywords

type-2 diabetes - insulin - severe insulin resistance

Authors' Contributions

H.C.G.N.: investigation, data curation, and writing the original draft; M.M.M.: investigation, writing, review, and editing; D.M.: investigation, writing, review, and editing; S.L.P.: writing, review, and editing; M.F.: conceptualization, writing, review, and editing; C.S.: conceptualization, methodology, formal analysis, investigation, and writing the original draft.


Note

Data from the were presented in part at the American Diabetes Association 79th Scientific Sessions, June 7–11, 2019, San Francisco, CA.




Publication History

Received: 03 April 2020

Accepted: 07 September 2020

Article published online:
16 October 2020

© 2020. Thieme. All rights reserved.

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  • References

  • 1 Geiss LS, Wang J, Cheng YJ. et al. Prevalence and incidence trends for diagnosed diabetes among adults aged 20 to 79 years, United States, 1980-2012. JAMA 2014; 312 (12) 1218-1226
    CrossrefPubMedGoogle Scholar
  • 2 Feig DS, Palda VA. Type 2 diabetes in pregnancy: a growing concern. Lancet 2002; 359 (9318): 1690-1692
    CrossrefPubMedGoogle Scholar
  • 3 Feig DS, Hwee J, Shah BR, Booth GL, Bierman AS, Lipscombe LL. Trends in incidence of diabetes in pregnancy and serious perinatal outcomes: a large, population-based study in Ontario, Canada, 1996-2010. Diabetes Care 2014; 37 (06) 1590-1596
    CrossrefPubMedGoogle Scholar
  • 4 Clausen TD, Mathiesen E, Ekbom P, Hellmuth E, Mandrup-Poulsen T, Damm P. Poor pregnancy outcome in women with type 2 diabetes. Diabetes Care 2005; 28 (02) 323-328
    CrossrefPubMedGoogle Scholar
  • 5 Brydon P, Smith T, Proffitt M, Gee H, Holder R, Dunne F. Pregnancy outcome in women with type 2 diabetes mellitus needs to be addressed. Int J Clin Pract 2000; 54 (07) 418-419
    CrossrefPubMedGoogle Scholar
  • 6 Dunne F. Type 2 diabetes and pregnancy. Semin Fetal Neonatal Med 2005; 10 (04) 333-339
    CrossrefPubMedGoogle Scholar
  • 7 Murphy HR, Steel SA, Roland JM. East Anglia Study Group for Improving Pregnancy Outcomes in Women with Diabetes (EASIPOD). et al. Obstetric and perinatal outcomes in pregnancies complicated by type 1 and type 2 diabetes: influences of glycaemic control, obesity and social disadvantage. Diabet Med 2011; 28 (09) 1060-1067
    CrossrefPubMedGoogle Scholar
  • 8 Holman N, Lewis-Barned N, Bell R. NHS Diabetes in Pregnancy Dataset Development Group. et al. Development and evaluation of a standardized registry for diabetes in pregnancy using data from the Northern, North West and East Anglia regional audits. Diabet Med 2011; 28 (07) 797-804
    CrossrefPubMedGoogle Scholar
  • 9 Knight KM, Pressman EK, Hackney DN, Thornburg LL. Perinatal outcomes in type 2 diabetic patients compared with non-diabetic patients matched by body mass index. J Matern Fetal Neonatal Med 2012; 25 (06) 611-615
    CrossrefPubMedGoogle Scholar
  • 10 Ali MK, Bullard KM, Gregg EW. Achievement of goals in U.S. diabetes care, 1999-2010. N Engl J Med 2013; 369 (03) 287-288
    CrossrefPubMedGoogle Scholar
  • 11 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 (6 Pt 1): 1667-1672
    CrossrefPubMedGoogle Scholar
  • 12 Catalano PM, Huston L, Amini SB, Kalhan SC. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol 1999; 180 (04) 903-916
    CrossrefPubMedGoogle Scholar
  • 13 Lane WS, Cochran EK, Jackson JA. et al. High-dose insulin therapy: is it time for U-500 insulin?. Endocr Pract 2009; 15 (01) 71-79
    CrossrefPubMedGoogle Scholar
  • 14 Ovalle F. Clinical approach to the patient with diabetes mellitus and very high insulin requirements. Diabetes Res Clin Pract 2010; 90 (03) 231-242
    CrossrefPubMedGoogle Scholar
  • 15 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin no. 201: pregestational diabetes mellitus. Obstet Gynecol 2018; 132 (06) e228-e248
    CrossrefPubMedGoogle Scholar
  • 16 Blum AK. Insulin use in pregnancy: an update. Diabetes Spectr 2016; 29 (02) 92-97
    CrossrefPubMedGoogle Scholar
  • 17 International Hypoglycaemia Study Group. Glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should be reported in clinical trials: a joint position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2017; 40 (01) 155-157
    CrossrefPubMedGoogle Scholar
  • 18 Adamkin DH. Committee on Fetus and Newborn. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011; 127 (03) 575-579
    CrossrefPubMedGoogle Scholar
  • 19 St John EB, Carlo WA. Respiratory distress syndrome in VLBW infants: changes in management and outcomes observed by the NICHD Neonatal Research Network. Semin Perinatol 2003; 27 (04) 288-292
    CrossrefPubMedGoogle Scholar
  • 20 Talge NM, Mudd LM, Sikorskii A, Basso O. United States birth weight reference corrected for implausible gestational age estimates. Pediatrics 2014; 133 (05) 844-853
    CrossrefPubMedGoogle Scholar
  • 21 ACOG practice bulletin no. 202: gestational hypertension and preeclampsia. Obstet Gynecol 2019; 133 (01) e1-e25
    Google Scholar
  • 22 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin no. 203: chronic hypertension in pregnancy. Obstet Gynecol 2019; 133 (01) e26-e50
    CrossrefPubMedGoogle Scholar
  • 23 Ryan EA. Hormones and insulin resistance during pregnancy. Lancet 2003; 362 (9398): 1777-1778
    CrossrefPubMedGoogle Scholar
  • 24 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 2004; 14 (01) 67-70
    PubMedGoogle Scholar
  • 25 Jovanovic L, Druzin M, Peterson CM. Effect of euglycemia on the outcome of pregnancy in insulin-dependent diabetic women as compared with normal control subjects. Am J Med 1981; 71 (06) 921-927
    CrossrefPubMedGoogle Scholar
  • 26 Langer O, Anyaegbunam A, Brustman L, Guidetti D, Levy J, Mazze R. Pregestational diabetes: insulin requirements throughout pregnancy. Am J Obstet Gynecol 1988; 159 (03) 616-621
    CrossrefPubMedGoogle Scholar
  • 27 Steel JM, Johnstone FD, Hume R, Mao JH. Insulin requirements during pregnancy in women with type I diabetes. Obstet Gynecol 1994; 83 (02) 253-258
    PubMedGoogle Scholar
  • 28 García-Patterson A, Gich I, Amini SB, Catalano PM, de Leiva A, Corcoy R. Insulin requirements throughout pregnancy in women with type 1 diabetes mellitus: three changes of direction. Diabetologia 2010; 53 (03) 446-451
    CrossrefPubMedGoogle Scholar
  • 29 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 (04) 324.e1-324.e5
    CrossrefPubMedGoogle Scholar
  • 30 American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019; 42 (Suppl. 01) S90-S102
    CrossrefPubMedGoogle Scholar
  • 31 Binder C. Absorption of injected insulin. A clinical-pharmacological study. Acta Pharmacol Toxicol (Copenh) 1969; 27 (Suppl. 02) 1-84
    PubMedGoogle Scholar
  • 32 Zuckerwise LC, Werner EF, Pettker CM, McMahon-Brown EK, Thung SF, Han CS. Pregestational diabetes with extreme insulin resistance: use of U-500 insulin in pregnancy. Obstet Gynecol 2012; 120 (2 Pt 2): 439-442
    CrossrefPubMedGoogle Scholar
  • 33 Eby EL, Curtis BH, Gelwicks SC. et al. Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study. BMJ Open Diabetes Res Care 2015; 3 (01) e000074
    CrossrefPubMedGoogle Scholar
  • 34 Cochran E, Musso C, Gorden P. The use of U-500 in patients with extreme insulin resistance. Diabetes Care 2005; 28 (05) 1240-1244
    CrossrefPubMedGoogle Scholar
  • 35 Crasto W, Jarvis J, Hackett E. et al. Insulin U-500 in severe insulin resistance in type 2 diabetes mellitus. Postgrad Med J 2009; 85 (1002): 219-222
    CrossrefPubMedGoogle Scholar
  • 36 Lane WS. Use of U-500 regular insulin by continuous subcutaneous insulin infusion in patients with type 2 diabetes and severe insulin resistance. Endocr Pract 2006; 12 (03) 251-256
    CrossrefPubMedGoogle Scholar
  • 37 Berry DC, Thomas SD, Dorman KF. et al. Rationale, design, and methods for the medical optimization and management of pregnancies with overt type 2 diabetes (MOMPOD) study. BMC Pregnancy Childbirth 2018; 18 (01) 488
    CrossrefPubMedGoogle Scholar
  • 38 Feig DS, Murphy K, Asztalos E. MiTy Collaborative Group. et al. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multi-center randomized controlled trial. BMC Pregnancy Childbirth 2016; 16 (01) 173
    CrossrefPubMedGoogle Scholar
  • 39 Wulffelé MG, Kooy A, Lehert P. et al. Combination of insulin and metformin in the treatment of type 2 diabetes. Diabetes Care 2002; 25 (12) 2133-2140
    CrossrefPubMedGoogle Scholar
  • 40 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 (07) 1660-1668
    CrossrefPubMedGoogle Scholar
  • 41 Nielsen LR, Ekbom P, Damm P. et al. HbA1c levels are significantly lower in early and late pregnancy. Diabetes Care 2004; 27 (05) 1200-1201
    CrossrefPubMedGoogle Scholar
  • 42 Dimitriadis G, Mitrou P, Lambadiari V, Maratou E, Raptis SA. Insulin effects in muscle and adipose tissue. Diabetes Res Clin Pract 2011; 93 (Suppl. 01) S52-S59
    CrossrefPubMedGoogle Scholar