The talk focuses on the use of insulin in the management of hyperglycaemia in pregnancy/GDM.

1. Insulin Use In
Hyperglycemia In 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 failure of 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
are maintained
within range by
proportionate
insulin secretion

4. Capillary blood glucose
Total insulin requirement

5. Hormones in Pregnancy That
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
Monitored During 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 For Women
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 Endocrinol Metab 98: 4319–4324, 2013
Outcomes of interest:
Macrosomia, LGA, Hypoglycemia, Hyperbilirubinemia, Preeclampsia

9. FBG <90 mg/dL was 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 Targets During 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
Insulin Oral agents
Lifestyle
Nutrition Exercise

12. Benefits And Harms of 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 treatment of GDM based on data from RCTs: Meta-Analysis
Hartling L, et al. Ann Intern Med. 2013;159:123-129.

14. Effect of treatment of GDM On Pre-eclampsia: Meta-Analysis
Hartling L, et al. Ann Intern Med. 2013;159:123-129.

15. Effect of treatment of 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
Insulin Oral agents
Lifestyle
Nutrition Exercise

17. Absolute Indications For
Insulin In 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 When Insulin 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
before initiating 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 When Insulin 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 CPG on
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 Vs Analog Insulin

23. Action Profiles of Human Insulins and
Insulin Analogs
23

24. • 310 type 1 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 pregnancy was 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 glucose during 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 during pregnancy 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 Endpoint Was 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 Perinatal Outcomes 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 During Pregnancy
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 CPG on
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 Dosage Regimen 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 Protocol For GDM
IDF GDM Model of Care Implementation Protocol, 2015

34. Summary
MNT is an essential 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

35. Email: nanicodemus@up.edu.ph
Twitter: @doknemie