Treatment of diabetes in pregnancy

1. D R . P . S H A R A T H C H A N D R A
P O S T G R A D U A T E
D R . K . S A N J E E V I
P R O F E S S O R
D R . P . G A N D I A H
H . O . D
D E P A R T M E N T O F M E D I C I N E
S . V . S . M . C
Diabetes in pregnancy

2. Diabetes mellitus
 A metabolic condition characterized by
chronic hyperglycemia as a result of
defective insulin secretion, insulin
action or both.
 Type I (IDDM)
 Type II (NIDDM)
 Gestational diabetes
 Others
 Genetic mutations of β-cell function—
MODY
 Genetic defects in insulin action
 Genetic syndromes—Down, Klinefelter,
Turner
 Diseases of the exocrine pancreas—
pancreatitis, cystic fibrosis
 Endocrinopathies—Cushing syndrome,
pheochromocytoma
 Drug or chemical induced—
glucocorticosteroids, thiazides, β-
adrenergic agonists
 Infections—congenital rubella,
cytomegalovirus, coxsackievirus

3. Diabetes in pregnancy
 Pregnancy predisposes to persistent hyperglycaemia
due to
 ↑ placental hormones
 ↑ plasma cortisol
 A state of insulin resistance
 Further aggravated by ↑body weight and ↑ caloric
intake during pregnancy

4. Diabetes in pregnancy
 Women with diabetes during
pregnancy can be divided into
1. Pregestational / Overt
diabetes.
2. Gestational diabetes.
 African American, Native
American, Asian, and
Hispanic women are at
higher risk for gestational
diabetes compared with
other races.
 The increasing incidence of
gestational diabetes during
the past 15 years is due to
similar statistics for obesity.

5. Diabetes in pregnancy
 Common medical complication of pregnancy.
 Diabetes in pregnancy is associated with risks to the
woman and to the developing fetus.
 Miscarriage, pre-eclampsia, preterm labour and
congenital malformations in fetus are more common
in women with pre-existing diabetes

6. White classification in pregnancy

7. Pregestational / overt diabetes
 Diabetes that antedates pregnancy is called
pregestational or overt diabetes.
 Because of differences in age specific incidences of
the two types of diabetes in relation to childbearing
years, most of the patients with overt diabetes have
type I diabetes.
 There is an increasing prevalance of pregestational
type II diabetes and can be attributed to
 Increasing prevalance of obesity and Type II DM in the young
 Delayed childbearing into the 3rd and 4th decades.

8. Pregestational / overt diabetes
 Pregnancies complicated by overt diabetes
(TypeI/typeII) carry additional risk to both mother
and the fetus
 Metabolic derangements are present right from the
time of conception, during blastogenesis and
embryogenesis increase the risk of spontaneous
abortions and congenital malformations.
 The presence of placental vasculopathy in patients of
diabetes severely affects the flow of blood and other
substrates to the fetus.

9. According to ADA IADPSG
1. Random plasma glucose
>200mg/dl along with
classic signs like
polyuria, polydypsia and
unexplained weight loss.
2. Fasting plasma glucose
levels >125mg/dl
1. Random plasma
glucose of atleast
200mg/dl plus other
signs.
2. Fasting plasma
glucose of atleast 126
mg/dl
3. HbA1c of atleast 6.5%
Diagnosis of overt diabetes

10. Effect of pregnancy on diabetes
• Increase requirement for insulin doses
• Nephropathy , autonomic neuropathy may
deteriorate
• Progress in diabetic retinopathy (2X)
• Hypoglycemia
• Diabetic ketoacidosis

11. Impact of overt diabetes on pregnancy
 The likelihood of successful
outcomes with overt
diabetes is related
somewhat to the degree of
glycemic control, but more
importantly, to the degree
of underlying
cardiovascular or renal
disease.
 Thus, advancing stages of
the White classification, are
inversely related to
favourable pregnancy
outcomes.

12. Effects on the fetus
Spontaneous abortions
 Risk of abortions is directly related to glycemic control and
HbA1c levels.
Pre-term delivery
Malformations
 4x increased risk of isolated cardiac defects and 2x increased
risk of non cardiac defects
 Risk of abortions is directly related to glycemic control and
HbA1c levels.
 Due to hyperglycemia induced oxidative stress and increased
apoptosis

13. Effects on the fetus

14. Effects on the fetus
 Altered fetal growth
 Growth may be diminished due to malformations and substrate
deprivations due to placental insufficiency
 Fetal overgrowth(macrosomia) is a more common and is due to
maternal hyperglycemia and fetal hyperinsulinemia.
 Raised HC/AC ratios, Increased risk of shoulder dystocia or cesarean
delivery.
 Unexplained fetal deaths
 3-4x higher risk of fetal death, typically without an identifiable cause.
 7x higher in women with hypertension with overt diabetes.
 The infants are typically LGA and die before labour usually after
35weeks of gestation.
 Due to poor glycemic control and fetal lactic acidosis.

15. Effects on the fetus
Hydramnios
 May be due to fetal polyuria
 Raised amniotic fluid glucose levels
 Women with poor HbA1c levels in third trimester are more
likely to have hydramnios.
Hypoglycemia
 Rapid drop of blood glucose post delivery
 Due to fetal beta cell hyperplasia induced by chronic maternal
hyperglycemia.
 Strict maternal glycemic control reduces the risk of fetal
hypoglycemia.

16. Effects on the fetus
Polycythemia and hyperbilirubinemia
 Increased EPO levels due to fetal hypoxia and IGF
 May lead to renal vein thrombosis.
 Polycythemia leads to increased bilirubun load.
Hypertrophic Cardiomyopathy
 Mostly affects the interventricular septum and ventricular
wall.
 In most of the affected, it resolves after delivery.
Hypocalcemia
Cognitive impairment
Inheritance of diabetes

17. Maternal effects
 Diabetes in pregnancy cause serious effects on
maternal welfare.
 Maternal death is uncommon, but rates in women
with diabetes are still increased.
 Deaths resulted from diabetic ketoacidosis,
hypoglycemia, hypertension, and infection.
 Especially morbid is ischemic heart disease and in
few studies, only half of the women with coronary
artery disease survived pregnancy.

18. Maternal effects
 The incidence of chronic
and gestational
hypertension and
especially preeclampsia
is remarkably increased
in diabetic mothers.
 Diabetics with coexistent
chronic hypertension
were almost 12 times
more likely to develop
preeclampsia.

19. Maternal effects
 Diabetic nephropathy
 Diabetes is a leading cause of ESRD
 Microalbuminuria, macroalbuminuria, hypertension.
 Diabetic retinopathy
 Retinal vasculopathy is a highly specific complication of diabetes.
 Nonproliferative retinopathy: Microaneurysms, blot hemorrhages,
hard exudates.
 Preproliferative retinopathy: Retinal ischemia and infarctions that
appear as cotton wool exudates.
 Proliferative retinopathy: In response to ischemia, there is
neovascularization on the retinal surface and out into the vitreous
cavity.

20. Neovascularisation

21. Maternal effects
 Diabetic neuropathy
 Peripheral neuropathy is uncommon in pregnant women but
diabetic gastroparesis is very troublesome.
 It causes nausea and vomiting, nutritional problems, and
difficulty with glucose control.
 Metoclopramide and H2-receptor antagonists(ranitidine) may
help.

22. Maternal effects
 Diabetic ketoacidosis
 Develops in ~1% of diabetic pregnancies.
 Pregnant women usually develop ketoacidosis at lower blood
glucose thresholds than when nonpregnant.
 Diabetic ketoacidosis (DKA) may develop with hyperemesis
gravidarum, β-mimetic drugs given for tocolysis, infection, and
corticosteroids given to induce fetal lung maturation.
 The incidence of fetal loss can be as high as 20 percent with
DKA

23. Maternal effects
 Infections:
 Almost all types of infections are increased in diabetic
pregnancies.
 Almost 80 percent of women with type 1 diabetes develop at
least one infection during pregnancy compared with only 25
percent in those without diabetes.
 Common infections include
 Candida vulvovaginitis
 Urinary and respiratory tract infections,
 Puerperal pelvic sepsis.
 Pregestational diabetes is associated with a two- to threefold
increase in wound complications after cesarean delivery.

24. D I A B E T E S T H A T A N T E D A T E S P R E G N A N C Y
Management of overt diabetes

25. Management of Diabetes in Pregnancy
 Because of the
relationship between
pregnancy complications
and maternal glycemic
control,glucose targets
should be aggresively
achieved during
pregnancy.
 Management preferably
should begin before
pregnancy and include
specific goals during
each trimester.

26. Management of Diabetes in Pregnancy
 Preconception councelling:
 Should be educated about achieving good glycemic control
before conception.
 Guidance in achieving preconception management goals.
 Daily folic acid supplementation to reduce the risk of neural
tube defects.
 Nutritional councelling with provision of diet plans.
 Pre-conception goals include (ADA)
1. Fasting and pre-meal glucose levels of 80-110 mg/dl
2. 2hr post prandial glucose 100-129mg/dl
3. HbA1c <7%
4. Avoid hypoglycemia.

27. Management of Diabetes in Pregnancy
 Preconceptional councelling:
 Maternal and fetal risk assesment
 Fundoscopy
 Assesment of renal function
 Serum creatnine
 Spot urinary microalbumin:creatnine ratio
 Protein:creatnine ratio
 Cardiac evaluation by ECG, TMT if
 >35yrs old
 Co-existing hypertension/dyslypidemia/CAD/family
history/smoking/renal disease.
 ACEI’s and ARB’s should be stopped and shifted to alpha-
methyldopa/hydralazine/CCB/Beta-blockers.
 All cholesterol lowering agents and statins are contraindicated
in pregnancy and should be discontinued before conception.

28. Management of Diabetes in Pregnancy
 The following practical self-management skills are essential
for attaining good glycemic control in the preparation for
pregnancy and during pregnancy:
1. Use of appropriate meal plan
2. Self-monitoring of blood glucose
3. Self-administration of insulin and adjustment of insulin
doses
4. Treatment of hypoglycemia (patient and family
members)
5. 5. Incorporate safe physical activity
6. Development of techniques to reduce stress.
The same is applicable in women with gestational
diabetes also.

29. Management of Diabetes in Pregnancy
Diet
 Nutritional planning includes appropriate weight gain
through carbohydrate and caloric modifications based on
height, weight, and degree of glucose intolerance.
 The mix of carbohydrate, protein, and fat is adjusted to meet
the metabolic goals.
 175-g minimum of carbohydrate per day divided into three
meals and 2-4 snacks is to be taken.
 An ideal dietary composition is 55 percent carbohydrate, 20
percent protein, and 25 percent fat, of which < 10 percent is
saturated fat.
 Weight loss is not recommended, but modest caloric
restriction may be appropriate for overweight or obese women

30. Management of Diabetes in Pregnancy
 Insulin therapy: The overtly diabetic pregnant
woman is best treated with insulin.
 Oral hypoglycemic agents are not currently
recommended for overt diabetes.(ACOG)
 Maternal glycemic control can usually be achieved
with multiple daily insulin injections and adjustment
of dietary intake.

31. Insulin therapy

32. Insulin strategies
 Self monitoring of blood glucose is a critical step for
insulin therapy and must be done atleast 4 times a
day.
 Adjusting insulin doses is simpler with self-
monitoring of blood glucose (SMBG) 4 times a day
because each component of the insulin regimen
affects only 1 SMBG value.
 Monitoring before meals and 2 h after a meal and
before driving is recommended.

33. Insulin strategies
 In overt type I diabetes women, the requirement of
insulin may fall during the first trimester due to
increased insulin sensitivity but requirements
increase in the latter half due to increased circulating
placental hormones.
 The insulin dose is increased from 0.7 U/kg/day in
the first trimester to 0.8 U/kg/day at week 18, 0.9
U/kg/day at week 26,and 1.0 U/kg/day at week 36 in
women who maintained within15% of ideal body
weight.

34. Insulin strategies

35. Insulin strategies
 During the first trimester, there is no difference in
insulin requirement between type 1 and type 2 subjects.
 But type 2 DM patients require a significantly higher
dose of insulin during 2nd trimester(33%increase
compared to 10% for type I DM) and in 3rd trimester
requirement may be raised upto 40%.
 This is attributed to the sudden increase in body mass
and heightened insulin resistance in type 2 diabetes
women during pregnancy.
 The total daily dose may reach upto 200units/day but
main cocern should be good glycemic control.

36. Insulin strategies

37. Insulin strategies
 Increased insulin requirement is inevitable in
pregnant women with type 2 DM and if not
increased in spite of the advancing pregnancy in certain
cases, it is a cause of concern.
 This could be due to poor placental growth,
intrauterine growth retardation, and impending
intrauterine death and proactive identification of the
cause is needed.
 In some cases, fetal beta-cell hypertrophy can handle the
maternal glucose levels and may require less insulin.
 At 36 weeks, placental growth ceases and counter
regulatory hormone production plateaus and there may
be an apparent decline in the insulin requirement.

38. Insulin strategies
 Controlling the fasting plasma glucose concentration
requires pre-dinner or bedtime NPH insulin.
 Pre-dinner administration of NPH insulin, especially if
the dose of NPH is increased in view of the next
morning’s elevated fasting glucose value, has the
likelihood of producing nocturnal hypoglycemia due to
the peak pharmacodynamic action of the intermediate
acting insulin at midnight. This cannot be prevented
even if the patient consumes a bedtime snack.
 Alternative strategy to address nocturnal hypoglycemia is
to shift the pre dinner NPH insulin to bedtime so that the
peak action occurs early in the morning instead of
midnight.

39. Insulin strategies
 Injecting NPH in the morning limits patient’s flexibility
with regard to meal time and exercise patterns as it
exerts its effects for many hours.
 Using 3 injections of regular human insulin or rapid
acting insulin analogs (Humalog/NovoRapid) with each
meal gives a patient more flexibility with regard to eating
and exercise.
 In a few pregnant women, a split/mixed regimen (NPH
and regular or insulin analogs) given in the morning and
evening may achieve good glycemic control.
 Preprandial regular or rapid-acting insulin analogs can
be particularly helpful during the first trimester, when
nausea and anorexia (morning sickness) are common.

40. Management of diabetes in pregnancy
Second trimester
 The glycemic status in the 2nd trimester is more
stable compared to 1st trimester but insulin
requirement is increased.
 Euglycemia with self-monitoring continues to be the
goal in management.
 Fetal echocardiography to screen for congenital
cardiac malformations.
 Maternal serum alpha-fetoprotein determination at
16-20 weeks with targeted sonogram at 18-20 weeks
to detect neural-tube defects.

41. Management of diabetes in pregnancy
Third trimester
 In view of the threat of late-pregnancy fetal death in women
with diabetes, ACOG recommends various fetal surveillance
testing at 32-34 weeks. They include
 Fetal movement count
 Periodic fetal heart rate monitoring
 Intermittent bio-physical profile
 Contraction stress testing
 Mothers are instructed to perform fetal kick counts early in
the 3rd trimester.
 At 34weeks all insulin treated mothers are preferrably
admitted and daily fetal movement counts and FHR
monitoring is done thrice a week.
 Delivery is planned at 38weeks.

42. Management of diabetes in pregnancy
Labor
 Labor induction may be attempted when the fetus is not
excessively large and the cervix is considered favorable.
 Cesarean delivery at or near term has frequently been
used to avoid traumatic birth of a large infant, in women
with more advanced diabetes, especially those with
vascular disease.
 The cesarean delivery rate for women with overt diabetes
has remained at approximately 80 percent for the past 35
years at a study hospital.

43. Management of diabetes in pregnancy
Insulin management during labor
1. Usual dose of intermediate-acting insulin is given at bedtime.
2. Morning dose of insulin is withheld.
3. Intravenous infusion of normal saline is begun.
4. Once active labor begins or glucose levels decrease to < 70 mg/dL,
change from saline to 5-percent dextrose and deliver at a rate of
100–150 mL/hr to achieve a glucose level of approximately 100
mg/dL
5. Glucose levels are checked hourly using a bedside meter allowing
for adjustment in the insulin or glucose infusion rate.
6. Regular (short-acting) insulin is administered by intravenous
infusion at a rate of 1.25 U/hr if glucose levels exceed 100 mg/dL.

44. Management of diabetes in pregnancy
Purperium
 women may require virtually no insulin for the first
24 hours of postpartum.
 Infection must be promptly detected and treated.
 Effective contraception is especially important in
women with overt diabetes to allow optimal glucose
control before subsequent conceptions.

45. R E L A T I V E I N S U L I N D E F I C I E N C Y
Gestational diabetes mellitus

46. Diagnosis
 Gestational diabetes is defined as carbohydrate
intollerance of any degree with onset (or) first
recognition during pregnancy.
 It includes diabetes that antedates conception but
remained unrecognised untill pregnancy.
 It is important to identify GDM in view of the
associated fetomaternal risks such as LGA,
macrosomia, birth trauma and fetal demise.
 More than half of women with gestational diabetes
ultimately develop overt diabetes in the ensuing 20
years.

47. Diagnosis
 Different guidelines by the ACOG and the ADA.
 ACOG recommends a two step diagnostic approach.
 The recommended two-step approach begins with
either universal or risk-based selective screening
using a 50-g, 1-hour oral glucose challenge test
followed by a diagnostic 100gm 3hr OGTT.
 For the 50-g screen, the plasma glucose level is
measured 1 hour after a 50-g oral glucose load
without regard to the time of day or time of last meal
 Screen is positive if values lie between 135-140mg/dl.

48. Diagnosis

49. OGTT

50. Maternal and Fetal Effects
 The adverse effects of GDM differ from that of overt
diabetes.
 Unlike in women with overt diabetes, rates of fetal
anomalies do not appear to be substantially
increased.
 But rates of unexplained stillbirths are similar as in
women with overt diabetes.
 The ADA concluded that fasting hyperglycemia > 105
mg/dL may be associated with an increased risk of
fetal death during the final 4 to 8 weeks.

51. Maternal and Fetal Effects
 Fetal macrosomia
 Neonatal hypoglycemia
 Maternal obesity

52. Management of gestational diabetes
 Women with gestational diabetes can be divided into
two functional classes using fasting glucose levels.
1. Medical nutrition therapy
2. Pharmacological therapy

53. Medical nutrition therapy
 Diet: The aim of meal plan is to provide sufficient
calories to sustain adequate nutrition for the mother and
fetus and excess weight gain and postprandial
hyperglycemia are avoided.
 women are advised to divide their calorie consumption,
especially the breakfast by splitting the usual breakfast
into 2 equal halves and consuming the portions with an
interval of 2 h between meals to avoid the undue peak in
plasma glucose levels after ingestion of the total quantity
of breakfast at one time.
 The ACOG recommends a moderate exercise program as
part of the treatment plan for women with gestational
diabetes.

54. Management of gestational diabetes
 Glucose monitoring: In a study, women with diet-
treated gestational diabetes who used personal
glucose monitors had significantly fewer macrosomic
infants and gained less weight after diagnosis than
women evaluated during clinic visits only.
 The ACOG recommends four-times daily glucose
monitoring performed fasting and either 1 or 2 hours
after each meal.

55. Management of gestational diabetes
Oral hypoglycemic agents
 Several studies proved the safety and efficacy of gliburide
and metformin in the management of gestational
diabetes with results on par with insulin but gliburide
failed to control if FBS is >110mg/dl.
 Metformin treatment for polycystic ovarian disease
throughout pregnancy reduced the incidence of
gestational diabetes.
 Both gliburide and metformin cross the placenta but
have no adverse effects on the perinatal outcome.
 Use of OHA’s for treating GDM donot cause an increase
in adverse effects but may require supplemental insulin
for better control.

56. Management of gestational diabetes
 Insulin is essential if diet control and exercise fail to
achieve euglycemia.
 Insulin doesnot cross the placenta and tight glycemic
control can be achieved.
 The ACOG also recommends that insulin be
considered in women with
 Fasting levels persistantly exceed 95mg/dl
 1-hour postprandial levels that persistently exceed 140 mg/dL
 2-hour levels above 120 mg/dL

57. Management of gestational diabetes
 The initial dose of NPH insulin could be as low as 4 units
and the dose of insulin can be adjusted on follow up.
 A few GDM patients may require combination of short-
acting insulin and intermediate-acting insulin in the
morning and evening.
 If a patient has elevated prelunch blood sugar, regular
insulin is usually necessary in the morning to handle the
post-breakfast hyperglycemia, as there is a lag period
before the intermediate-acting insulin begins to work.
The above regimen of regular and intermediateacting
insulin in the morning controls hyperglycemia

58. Management of gestational diabetes
 If the post-dinner blood sugar is high, a small dose of regular insulin is
necessary before dinner in addition to the regular and intermediate acting
insulin given in the morning.
 Combination of regular- and intermediate-acting insulin before dinner may
be necessary if fasting blood sugar is high.
 This combination of short- and intermediate- acting insulin in the morning
and in the evening is known as split-mixed dosage regimen. In this regimen
two-thirds of the total daily dose of insulin is given in the morning and one-
third in the evening.For each combination, one-third dose should be
regular insulin and two-thirds should be intermediate-acting insulin.
 With this regimen, if the patient continues to have fasting hyperglycemia,
the intermediate-acting insulin has to be given at bedtime instead of pre-
dinner insulin and the dose has to be adjusted.
 Target is to obtain mean fasting levels of 105mg/dl and mean postprandial
values of 120mg/dl for better perinatal outcome.

59. Management of gestational diabetes
Obstetrical management
 For women with gestational diabetes who do not
require insulin, early delivery or other interventions
are seldom required.
 The ACOG recommends fetal surveillance in women
with gestational diabetes and poor glycemic control.
 Insulin-treated women are offered inpatient
admission after 34 weeks’ gestation, and fetal heart
rate monitoring is performed three times each week.

60. Management of gestational diabetes
 Women with gestational diabetes and adequate
glycemic control are managed expectantly
 Elective induction of labor to prevent shoulder
dystocia may be done.
 Elective cesarean delivery should be done if fetal
weight is atleast 4500gms. To avoid brachial plexus
injury.

61. Management of gestational diabetes
Postpartum evaluation
 50% of the women with GDM may develop overt
diabetes within 20years.
 Women diagnosed with gestational diabetes should
undergo evaluation with a 75-g oral glucose tolerance
test at 6 to 12 weeks postpartum and atleast every
3yrs thereafter.
 Recurrent GDM: 40% of women with GDM tend to
develop it again in subsequent pregnancies and
obese women have a greater propensity.

62. Post partum evaluation

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