Insulin in pregnancy

Dr. Kyar Nyo Soe Myint

Consultant Endocrinologist
University of Medicine 2, NOGTH

Insulin & Pregnancy Dr.KNSM 1

 Aim of Insulin Therapy in pregnancy

• The goal is to achieve normal plasma glucose through the day

without any hypoglycemia.

• The most effectual approach to accomplish optimal glycemic

control is to mimic physiologic insulin levels through frequent
administration.

Insulin has been used in pregnancy since 1922

The Journal of Obstetrics and Gynecology of India (March–April 2014) 64(2):82–90

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 Rationale of treatment of hyperglycemia in pregnancy

 Maternal hyperglycemia increases fetal and maternal mortality and

morbidity.
 Excess birth weight is associated with elevated postprandial glucose
 Infants who experience hyperinsulinemia in utero are more likely to
develop obesity, HTN and diabetes later in life.
 Extremely tight control (mean daily glucose <87 mg/dL) is associated
with restricted fetal growth.
 Elevated glucose and rapid normalization  maternal progression of
existing retinopathy and nephropathy, increased frequency of
preeclampsia and preterm labor.

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 Types of Diabetes in pregnancy
ကိုယ်ဝန်မ ဆောင်မီ
ကတည််းကရှိ ောဆီ်းခ ျို

Pre-existing Type1 &

Type 2 DM ကိုယ်ဝန် ဆောင်ဆ်းီ ခ ျို

Gestational
Diabetes in
pregnancy diabetes
GDM (90%)

First recognition
Undiagnosed DM
(overt DM)

ကိုယ်ဝန်မ ဆောင်မက ီ တည််းကရှိ န

ော်လည််းကယ
ို ဝ
် န် ဆောင်မှိ ော
Insulin & Pregnancy Dr.KNSM ဆီ်းခ ျို 4
 Risk factors for Screening of GDM
High risk (one or more) Low risk (all)
• BMI above 30 kg/m² • Age <25 years AND
• Previous macrosomic baby (≥4 kg) • Weight normal before
• Previous GDM pregnancy AND
• First-degree relative with diabetes • No history of abnormal
• Family origin with a high glucose metabolism AND
prevalence of diabetes (South • No history of poor obstetric
Asian) outcome
• Poor Obstetric outcome (congenital
anomalies, history of early neonatal death, unexplained
fetal death, miscarriages)

Joslin Diabetes Center and Joslin Clinic Guideline for Detection and Management of Diabetes in Pregnancy, 2005
Insulin & Pregnancy Dr.KNSM 5
 Screening strategy (OGTT) to detect GDM

Routine ANC care + Risk for DM?

do not meet low or High risk
Low risk
high risk

Screen (OGTT) as soon

as possible
Screen (OGTT) 24 to 28
No screening required
week

Abnormal OGTT
normal
Treat

Repeat (OGTT) at 24 to
28 week
Joslin Diabetes Center and Joslin Clinic Guideline for Detection and Management of Diabetes in Pregnancy.

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• Pre-existing DM – Insulin +/- Metformin

• GDM Medical Nutrition Therapy

+/-
Insulin / +Metformin

Metformin and glyburide should not be used as

first-line agents, as both cross the placenta to
the fetus. (ADA 2019)

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 Oral medications in GDM
Good Bad

Metformin lower risk of neonatal Lower maternal weight gain

hypoglycemia increased incidence of
less maternal weight prematurity
gain less likely to be successful as
monotherapy
No long term data

The Offspring Follow-Up (MiG TOFU) study’s analyses of 7- to 9-year-old offspring, 9-year-
old offspring exposed to metformin for the treatment of GDM were larger than Insulin
(ADA 2019)

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 no evidence of a difference between groups Insulin vs OHA

• Fetus -risk of perinatal death, being born (LGA), a composite of

serious neonatal outcomes or neurosensory disability in
childhood
• Maternal - hypoglycaemia, glycaemic control, PPH

• Insulin was associated with an increase in gestational weight

gain compared with OHA
Cochrane Database of Systematic Reviews 2017, Issue 11. Art. No.: CD012037.
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How many of pregnant women need insulin?

Porportionof glucose lowering therapy used in Diabetes

and Pregnancy patients (NOGTH)
5%

20%
49% Diet control (MNT)
Metformin
Insulin
26%
Not recorded

Total = 289
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 Absolute indications for insulin in pregnancy
• Significant diabetes-related morbidity
– High HbA1c
– Ketonuria
• Significant medical morbidity
– Associated renal dysfunction
– Associated hepatic dysfunction
• Significant obstetric morbidity
– Macrosomia
– Intrauterine growth retardation
– Hydramnios
• Expected deterioration of glycemia control
• Antenatal corticosteroid therapy
North American Journal of Medical Sciences | Jan 2015 | Volume 7 | Issue 1 |
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 Blood glucose targets in pregnancy

Timing of blood glucose Target

Fasting or pre-prandial ≤ 95 mg/dL (5.3mmol/L)

One-hour postprandial ≤ 140 mg/dL (7.8mmol/L)

Two-hour postprandial ≤ 120 mg/dL 6.7mmol/L)

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 Who should be on insulin in GDM?

• Insulin therapy should be considered if the blood

glucose goals are exceeded on two or more
occasions within a 1 to 2 week interval,

ADIPS in December 2002

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 Immediate treatment with Insulin in GDM

• (a) fasting plasma glucose level ≥126 mg/dL (7.0

mmol/L) at diagnosis
or
• (b) fasting plasma glucose level of between 108~124.2
mg/dL (6.0 and 6.9 mmol/L) + complications s/a
macrosomia or hydramnios

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Insulin requirement in Pregnancy

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 What type of Insulin can be used in
pregnancy
Type of insulin Category (FDA) European medicines
agency (EMA)
Regular insulin B Can be used
Insulin Aspart B Can be used
Insulin Lispro B Can be used
Insulin Detemir B Can be used
NPH B Can be used
Insulin Glargine No human pregnancy data No clinical data
Insulin Glulisine C No clinical data
Insulin Degludec C No clinical data

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 • Human insulin - extensively used during pregnancy,
• pharmacokinetic action of this insulin a considerable segment
of pregnant women with diabetes fail to achieve optimum
glycemic control, mostly the postprandial plasma glucose.

• The best option - insulin analogs (insulin lispro or insulin

aspart)
• improve the postprandial glucose in pregnant women with
both type 1 and type 2 DM are safe and effective.

Dr. V. Seshiah Diabetes Research Institute and Dr Balaji Diabetes Care Centre, # 729, P.H. Road,
Aminjikarai, Chennai - 600 029
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• Isophane (NPH) insulin - is the first-choice long-acting insulin
during pregnancy.

• Insulin Glargine - there are “no well-controlled clinical studies

in pregnant women”

• Insulin glulisine, insulin degludec, inhaled human insulin -

there is no human data during pregnancy

women with diabetes successfully using the long-acting insulin analogs

insulin detemir or insulin glargine preconceptionally may continue with
this therapy before and then during pregnancy.

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 Efficacy and safety of insulin aspart in pregnancy

Rapid-acting bolus analogue insulin may be used over regular insulin for
postprandial glucose control, although perinatal outcomes are similar

The Journal of Obstetrics and Gynecology ofInsulin

India& (March–April
Pregnancy Dr.KNSM
2014) 64(2):82–90 19
 Efficacy and safety of insulin Detemir in pregnancy

 fetal outcomes did not differ between treatments

 there was a significant improvement in fasting plasma glucose with
insulin detemir without an increased incidence of hypoglycemia,
including nocturnal episodes

The Journal of Obstetrics and Gynecology ofInsulin

India& (March–April
Pregnancy Dr.KNSM
2014) 64(2):82–90 20
 Role of pre –mixed regime
• the key to simplifying insulin therapy by reducing injection
frequency.
Premixed human insulin 30 (BHI30)
vs
Biphasic insulin aspart (BIAsp 30)
• maximum serum levels of insulin aspart were 18% higher after
dinner and 35% higher after breakfast the following morning
as compared to human insulin (lower dose in BIAsp30)
No difference in efficacy and tolerability

Medicine Update 2012, Vol. 22

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 Basal bolus vs twice daily

BMJ VOLUME 319 6 NOVEMBER 1999 Insulin & Pregnancy Dr.KNSM 22

 How should insulin be started?

Insulin for GDM with mild hyperglycemia

1/3 of post-meal values are ≥ 140 and <180 mg/dl

or
1/3 of fasting values are ≥ 90 and < 120 mg/dl

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• Fasting (FPG) >90 - <120 mg/dl Start with 8 - 20 NPH or levemir
bedtime (0.2 units/kg actual body weight)

• 1-hour post breakfast >140 <180 mg/dl 2 - 4 units of rapid acting

analog (i.e. Lispro, aspart) pre-breakfast

• 1-hour post lunch >140 <180 mg/dl2 - 4 units rapid acting analog
pre-lunch OR Add 4 - 6 units NPH to pre-breakfast injection

• 1-hour post dinner >140 mg/dl, <180 mg/dl2 - 4 units rapid acting
analog predinner

• Both FBS and 1-PP raised Basal bolus OR twice daily premix

California Diabetes and Pregnancy Program Insulin Guidelines adapted from ADA
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Glucose Value Insulin Dose

Before Breakfast Before Lunch Before Dinner Before Sleep

High FBS NPH

normal PP 0.2 units/kg actual body weight
High PP BF Rapid acting 2 - 4 units of rapid acting analog
High PP lunch NPH Rapid acting
4 - 6 units NPH
High PP dinner Rapid acting
High FBS and premix premix
PP
Premix (analog) Premix (analog) Premix (analog)
R R R NPH

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 Insulin therapy Type 2/ obese Type 1, uncontrolled GDM

• multiple daily injection is the best insulin regimen

• Twice daily insulin injection can be given.

Jovanovic, Clin Obstet Gynecol. 2000

(After 16 wk, 5% per week increase in insulin requirement, ADA 2019)
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 INSULIN DOSE AND REGIMEN - QUICK START

• bedtime basal insulin 0.2 units/kg

• premeal bolus rapid-acting insulin analog 0.25 units/kg
divided over 3 meals
• more at breakfast to account for greater insulin resistance
upon rising

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SUGGESTED PREMEAL CORRECTION ALGORITHM - MDI

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• changes by 2–4 units (~10%) in short- and
intermediate-acting insulins every 2–3 days.
CDAPP Sweet Success program

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 How to monitor?

American Association of Clinical Endocrinologist and American

Insulin & Pregnancy Dr.KNSM College of Endocrinology 30
 Monitoring
• Fasting plus pre and post meal until control is acceptable,
• then fasting and post meals (breakfast, lunch, dinner)

variable fasting blood glucose levels

check bedtime and 3 am BG's for 2 or 3 days

differentiate rebound vs dawn phenomena

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 Remember!!!!
• Insulin therapy must be individualized and regularly adapted
to the changing needs of pregnancy

• Intensive insulin therapy with basal-bolus therapy or

continuous subcutaneous insulin infusion (CSII or insulin
pump) therapy is recommended to achieve glycemic targets

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 Injection sites for pregnancy

abdomen is recommended due to its consistent rate of

absorption, thickness of the fat layer underneath the skin and the
ease of use. Insulin & Pregnancy Dr.KNSM 33
 Injection Tips

• Inject straight into the skin

• Rotate injection sites at least 2cm apart
• Avoid the area around the umbilicus
• Use a new needle for each injection

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 Conditions that Increase Insulin Needs
• Advanced pregnancy >24 weeks gestation (placental mediated
insulin resistance)
• Obesity BMI ≥30 (increased insulin resistance)
• Stress such as illness (preterm labor, preeclampsia), surgery
(Cesarean), psychosocial issues
• Infection, especially when accompanied by fever, i.e. UTI,
pyelonephritis
• Medications - betamimetics (terbutaline, ephedrine,
epinephrine) or steroids (dexamethasone, prednisone)

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 Postpartum

• GDM  should discontinue blood glucose-lowering therapy

immediately after birth.

• Pre-existing diabetes  refer back to their routine diabetes

care

• Remind  importance of contraception and the need for

preconception care when planning future pregnancies.

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 Complications associated with insulin therapy

• Neonatal hypoglycemia
• Congenital anomalies – (mitogenesis stimulation by binding
with a higher affinity for IGF-1 receptors. Lispro insulin has a
1.5 and insulin glargine a 6.5 fold increase of receptor
binding)
• Maternal hypoglycecmia
• Weight gain

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 Take home message
• Conventional and insulin analogue have same safety
and efficacy
• Target in pregnancy – FBS<95 mg/dl, 1HPP- <140mg/dl;
2 HPP- <120 mg/dl
• Insulin regimens – basal bolus, basal, premixed
• monitoring – 1 hr post meal for control
• Antenatal corticosteroid therapy – increase insulin dose

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Thank You

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