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Insulin in hyperglycemia in pregnancy
This document discusses the use of insulin in managing hyperglycemia during pregnancy. It begins by defining failure to manage blood glucose levels through medical nutrition therapy alone as an indication for insulin therapy. Guidelines recommend starting insulin if targets are not met within 2 weeks of nutrition management or if safety and growth parameters like weight gain are not being met. The document reviews types of insulin including human and analog varieties, providing evidence that various insulins can safely achieve targets when used as part of a basal-bolus regimen individualized to the patient's condition and blood glucose levels. The overall goal of insulin therapy in pregnancy is to maintain blood glucose within defined targets to support fetal and maternal health.
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Insulin in hyperglycemia in pregnancy
- 1. Insulin Use In HyperglycemiaIn Pregnancy Nemencio A. Nicodemus Jr., MD, FPCP, FPSEDM Professor, University of the Philippines-College of Medicine Past President, Philippine Society of Endocrinology, Diabetes & Metabolism Regent, Philippine College of Physicians Philippine Society of Maternal Fetal Medicine, Inc 21st Annual Convention, November 30, 2019 Crowne Plaza Manila Galleria
- 2. Session Objectives üDefine failureof MNT for hyperglycemia in pregnancy üIndications for the use of insulin for hyperglycemia in pregnancy üGuidelines for the use of insulin for hyperglycemia in pregnancy
- 3. Fasting and postprandial glucose levels aremaintained within range by proportionate insulin secretion
- 4. Capillary blood glucose Totalinsulin requirement
- 5. Hormones in PregnancyThat Have Diabetogenic Potential Hormones Peak Elevation Diabetogenic Potency Prolactin 10 weeks Weak Estradiol 26 weeks Very Weak hCS 26 weeks Moderate Cortisol 26 weeks Very strong Progesterone 32 weeks Strong Carr, et al. Clinical Diabetes, 16(1), 1998
- 6. Blood Glucose Parameters MonitoredDuring Pregnancy Pre-existing diabetes • Fasting • Postprandial • Preprandial* • A1c Gestational diabetes • Fasting • Postprandial American Diabetes Association. 13. Management of diabetes in pregnancy: Standards of Medical Care in Diabetes 2018. Diabetes Care 2018;41(Suppl. 1):S137–S143 *In those using insulin pumps or basal-bolus therapy
- 7. Recommended Targets ForWomen With Diabetes In Pregnancy* • <95 mg/dL (5.3 mmol/L) Fasting • <140 mg/dL (7.8 mmol/L) One-hour postprandial • <120 mg/dL (6.7 mmol/L) Two-hour postprandial *Type 1, Type 2 and GDM and or American Diabetes Association. 13. Management of diabetes in pregnancy: Standards of Medical Care in Diabetes 2018. Diabetes Care 2018;41(Suppl. 1):S137–S143 POGS CPG on DM in Pregnancy, 3rd ed, November 2018
- 8. J Clin EndocrinolMetab 98: 4319–4324, 2013 Outcomes of interest: Macrosomia, LGA, Hypoglycemia, Hyperbilirubinemia, Preeclampsia
- 9. FBG <90 mg/dLwas the one most strongly associated with reduced risk of macrosomia during 3rd trimester Prutsky GJ, et l. J Clin Endocrinol Metab 98: 4319–4324, 2013
- 10. Individualized A1c TargetsDuring Pregnancy < 6.0% 6.0 - 6.5% < 7.0% General recommendation • Adverse outcomes increase with A1C ≥6.5% May be optimal if this can be achieved without significant hypoglycemia • Lowest risk of large-for- gestational-age infant If necessary to prevent hypoglycemia American Diabetes Association. 13. Management of diabetes in pregnancy: Standards of Medical Care in Diabetes 2018. Diabetes Care 2018;41(Suppl. 1):S137–S143
- 11. Management of GDM Monitoring SMBG Pharmacologic InsulinOral agents Lifestyle Nutrition Exercise
- 12. Benefits And Harmsof Treating GDM: Meta-Analysis To summarize evidence about the maternal and neonatal benefits and harms of treating GDM 15 electronic databases from 1995 to May 2012, including randomized controlled trials and cohort studies of women without known preexisting diabetes All studies compared diet modification, glucose monitoring, and insulin as needed with no treatment Hartling L, et al. Ann Intern Med. 2013;159:123-129.
- 13. Effect of treatmentof GDM based on data from RCTs: Meta-Analysis Hartling L, et al. Ann Intern Med. 2013;159:123-129.
- 14. Effect of treatmentof GDM On Pre-eclampsia: Meta-Analysis Hartling L, et al. Ann Intern Med. 2013;159:123-129.
- 15. Effect of treatmentof GDM On Maternal Weight Gain: Meta- Analysis Hartling L, et al. Ann Intern Med. 2013;159:123-129.
- 16. Management of GDM Monitoring SMBG Pharmacologic InsulinOral agents Lifestyle Nutrition Exercise
- 17. Absolute Indications For InsulinIn Pregnancy • High Hba1c • Ketonuria Significant diabetes- related morbidity • Associated renal dysfunction • Associated hepatic dysfunction Significant medical morbidity • Macrosomia • IUGR • Hydramnios Significant obstetric morbidity • Antenatal corticosteroid therapy Expected deterioration of glycemic control Kalra B et al. N Am J Med Sci. 2015 Jan; 7(1): 6–12.
- 18. Guidelines On WhenInsulin Is Recommended For GDM • Treatment of choiceIDF 2009 • If women do not achieve glycemic targets within 2 weeks from nutritional therapy aloneCDA 2013 • Poor glycemic control (above treatment targets) in spite of dietary and lifestyle interventionsNZGG 2014 • if metformin is contraindicated or unacceptable to the womanNICE 2015 IDF: International Diabetes Federation; CDA: Canadian Diabetes Association; NZGG: New Zealand Guidelines Group; NICE: The National Institute for Health and Care Excellence Zhang et al. BMC Pregnancy and Childbirth (2019) 19:200
- 19. Things to consider beforeinitiating insulin Does the patient have pre- gestational diabetes? What is the Age Of Gestation? How high are blood glucose levels? What is the weight gain?
- 20. Guidelines On WhenInsulin Is Recommended For GDM: FIGO 2015 First-line treatment in women at high risk of failing on OAD therapy • Diagnosis of diabetes < 20 weeks of gestation • Need for pharmacologic therapy > 30 weeks • Fasting plasma glucose levels > 110 mg/dL • 1-h postprandial glucose > 140 mg/dL • Pregnancy weight gain > 12 kg Zhang et al. BMC Pregnancy and Childbirth (2019) 19:200
- 21. 2018 POGS CPGon Diabetes in Pregnancy N. Nicodemus in POGS CPG on DM in Pregnancy, 3rd ed, November 2018 Subcutaneous Insulin should be used to achieve glycemic targets, when they are not achieved with medical nutrition therapy and lifestyle changes Multiple daily doses of insulin may be necessary to allow for the achievement and maintenance of target blood glucose levels (both fasting and postprandial)
- 22. Human Insulin VsAnalog Insulin
- 23. Action Profiles ofHuman Insulins and Insulin Analogs 23
- 24. • 310 type1 diabetic women • Randomized to Idet or NPH up to 12 months before pregnancy or at 8–12 weeks gestation • Glycemic control as measured by A1C at 36 gestational weeks • Open-label, randomized, parallel-group study Mathiesen et al. Diabetes Care 2012;doi:10.2337/dc11-2264
- 25. HbA1c during pregnancywas comparable between insulin detemir and NPH insulin in women with T1DM GW, gestational week; IDet, insulin detemir; NPH, neutral protamine Hagedorn; PP, postpartum; SE, standard error Mathiesen et al. Diabetes Care 2012;doi:10.2337/dc11-2264
- 26. Fasting plasma glucoseduring treatment with insulin detemir or NPH in pregnant women with T1DM FPG, fasting plasma glucose; GW, gestational week; NPH, neutral protamine Hagedorn Mathiesen et al. Diabetes Care 2012;doi:10.2337/dc11-2264
- 27. Major hypoglycaemia duringpregnancy was similar with insulin detemir and NPH insulin NPH, neutral protamine Hagedorn Mathiesen et al. Diabetes Care 2012;doi:10.2337/dc11-2264
- 28. Composite Fetal EndpointWas Similar With Insulin Detemir And NPH Insulin CI, confidence interval; GW, gestational week; IDet, insulin detemir; NPH, neutral protamine Hagedorn Hod M, et al. J Matern Fetal Neonatal Med, 2014; 27(1): 7–13
- 29. Fetal and PerinatalOutcomes Were Similar With Insulin Detemir And NPH Insulin Idet (n=152) NPH (n=158) OR (95% CI) Live Births 90.1% 93.8% 0.61 (0.25 – 1.5) Composite outcome; at least one issue present 62.7% 66.2% 0.86 (0.53 – 1.4) Preterm delivery (<37 weeks) 20.3% 26.5% 0.71 (0.4 – 1.26) LGA (>90th %ile) 46.1% 53.7% 0.74 (0.46 – 1.21) Macrosomia (>4000 g) 18.8% 25.7% 0.67 (0.37 – 1.2) Neonatal hypoglycemia (<24 hrs postdelivery) 11.7% 17.6% 0.65 (0.32 – 1.3) *For IDet and NPH, there were 128 and 136 live births, 11 and 9 early fetal losses, and two and one perinatal deaths, respectively Hod M, et al. J Matern Fetal Neonatal Med, 2014; 27(1): 7–13
- 30. Insulin Therapy DuringPregnancy For Gestational Diabetes May initiate long-acting insulin analog detemir • for those women who require basal insulin • for whom NPH insulin has previously resulted in problematic hypoglycemia Rapid-acting insulin analogs lispro and aspart may be used in preference to regular (soluble) insulin Blumer I, et al. J Clin Endocrinol Metab 98: 4227–4249, 2013
- 31. 2018 POGS CPGon Diabetes in Pregnancy NPH insulin should be initiated as basal insulin • Insulin detemir may be alternatively used in women who experience problematic hypoglycemia with NPH insulin Regular (soluble) insulin should be used to achieve postprandial glucose targets • Rapid-acting insulin analogues (insulin aspart, lispro) may be alternatively used in women who experience problematic hypoglycemia with Regular insulin POGS CPG on DM in Pregnancy, 3rd ed, November 2018
- 32. Insulin Starting DosageRegimen For Diabetic Pregnancy: Basal-bolus Schedule • Calculate TDD: Patient’s current weight (in kg) x insulin dose based on gestational age • Give ½ as basal insulin in one dose or split equally into 2 doses • Give ½ as bolus insulin split equally into 3 doses before each meal Gestational age (weeks) 0 – 12 13 – 28 29 – 34 35 - 40 Insulin dose 0.7 unit 0.8 unit 0.9 unit 1.0 unit Coustan DR. Medical Management of Pregnancy Complicated by Diabetes, 5th ed. ADA 2013
- 33. IDF Management ProtocolFor GDM IDF GDM Model of Care Implementation Protocol, 2015
- 34. Summary MNT is anessential part of the management of hyperglycemia in pregnancy • Failure to achieve glycemic targets within 2 weeks warrants additional pharmacologic treatment, primarily insulin The use of insulin must take into consideration pre-existing diabetes, AOG, current glucose levels and weight gain Insulin treatment must cover both fasting and postprandial glucose excursions • With preference to human recombinant insulins in local guidelines
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