medical education

1. By
Dr / Mohamed Gaber Hamed, MD
Zagazig Endocrinology & Diabetes Unit
Internal Medicine Department
CASE STUDY

2. A 36-year-old lady office secretary with history of
polycystic ovarian syndrome has conceived by
ovulation induction.
Her dad has hypertension and her mother has
diabetes for 12 years.
On examination, she is 160 cm, weighs 92 kg, and
physical examination shows acanthosis, hirsutism,
her BP is 140/90 mm Hg.

3. Other systemic examination is unremarkable.
Her physician had explained the possible risk of
the possibility of having gestational diabetes.
When she was screened at 24 weeks of conception
for gestational diabetes the results of her
oral glucose tolerance test was as follow:
Fasting: ≥ 103mg/dL
1hour: ≥ 204mg/dL
2hour: ≥ 172mg/dL

4. She was told the gestational diabetes can be
controlled with diet and exercise and was
referred to a dietician in the hospital for a
consult as a first step of treatment.

5. What is the definition of diabetes in
pregnancy?

6. Varying degree of glucose intolerance diagnosed or
recognized for the first time during pregnancy is
gestational diabetes. It may be associated with other
components of metabolic syndrome independent of
other factors in the next 3 years.

7. However, in recent days type 2 diabetes is seen in
adolescent and young adults making it possible that
type 2 diabetes is recognized first time during
screening in pregnancy.
Gestational diabetes mellitus (GDM) accounts for 90%
of cases of diabetes mellitus in pregnancy, while
preexisting type 2 diabetes accounts for 8% of those
diagnosed in pregnancy. In future this number is likely
to increase.

8. What are the differences in a patient with
preexisting diabetes and gestational
diabetes?

10. When to screen for hyperglycemia in
pregnancy?

11. Every pregnant woman should be screened for hyperglycemia as
early as possible (first contact visit or preferably <12 weeks); if not,
there is a probability of missing preexisting diabetes.
With the current IADPSG guidelines, women with fasting plasma
glucose of 92–125 mg/dl in the first trimester, which is currently
categorized as GDM, will also remain undiagnosed. If the screening
test is negative at first trimester, retesting is recommended in all
women between 24 and 28 weeks of gestation.
The retesting at 24–28 weeks is recommended as insulin resistance
peaks at this time due to rising concentration of progesterone,
human placental lactogen, prolactin, cortisol, and growth hormone.

12. How to screen for hyperglycemia at first
trimester?

13. At first antenatal visit, a pregnant woman can be
screened with fasting plasma glucose (FPG) or
random plasma glucose (RPG) or HbA1c. FPG ≥126
mg/dl or RPG ≥200 mg/dl or HbA1c ≥6.5% confirms
the diagnosis of preexisting diabetes; however, it
requires confirmation on a subsequent day in case of
equivocal hyperglycemia. A FPG value of 92–125
mg/dl establishes the diagnosis of GDM at the first
trimester of pregnancy.

14. How to screen for hyperglycemia at 24–28
weeks of gestation?

15. There are two approaches to screen for hyperglycemia
at 24–28 weeks of gestation: a one-step approach or
two-step approach. A one-step approach involves
screening with a 75-g 2-h oral glucose tolerance test
(OGTT).
The two-step approach includes a 50-g oral glucose
challenge test (GCT) irrespective of time of the day and
meal intake, and if 1-h plasma glucose value ≥140
mg/dl, then a 100-g 3-h OGTT should be performed.

17. Diagnostic pathway for overt diabetes in pregnancy and
gestational diabetes

18. What are the maternal risks associated
with GDM?

19. Women with GDM have an increased risk of
preeclampsia, fetal loss, difficult labor, and future
risk of developing T2DM.

20. What are the fetal risks associated with
GDM?

21. Macrosomia (>4 kg), intrauterine death (if FPG >105
mg/dl), neonatal hypoglycemia, polycythemia (chronic
fetal hypoxia due to lung immaturity), hypocalcemia
(functional hypoparathyroidism due to hypo-
magnesemia), and hyperbilirubinemia (associated
with polycythemia) are the immediate risks to the
fetus.Further, these newborns are at future risk of
developing obesity and
T2DM

22. What are the glycemic targets in a patient
with hyperglycemia during pregnancy?

23. The glycemic targets in patients with hyperglycemia
during pregnancy, either GDM or overt diabetes, are
similar.
These include FPG <95 mg/dl (ideally <90 mg/dl), 1-
h PPG ≤140 mg/dl, and 2-h PPG ≤120 mg/dl,
provided these targets can be achieved without an
undue risk of hypoglycemia.
In addition, in women with overt diabetes, HbA1C
should be maintained ≤6.5%.

24. How to initiate treatment in GDM?

25. Medical nutrition therapy (MNT) is recommended for all women with
GDM or overt diabetes with the aim to provide adequate nutrition
for appropriate trimesterspecific weight gain. One of the key
components of MNT is to restrict the carbohydrate intake to 35–
45% of total calories ingested.
Pregnant women with normal preconceptional BMI should increase
their caloric intake by 360 and 475 kcal/ day during the second and
third trimester, respectively.
Obese women are recommended to restrict their calorie intake by
one-third of their prepregnancy intake but should at least ensure
intake of 1,600 kcal/day to prevent starvation ketosis.

26. This should be complemented with moderate physical
activity for 30 min a day comprising of aerobic and non-
weight- bearing exercises.
An initial trial of MNT and lifestyle modifications for 2
weeks is recommended in all patients with GDM, and if
it fails to achieve FPG ≤95 mg/dl and 2-h PPG ≤120
mg/dl, then insulin therapy should be initiated.
However, in patients with overt diabetes insulin therapy
should be initiated along with MNT.

27. How to initiate insulin therapy in GDM?

28. Insulin is a category B drug (no risk of teratogenicity based on
animal data), and at physiological levels, it does not cross the
placenta.
Therefore, it is the preferred treatment during pregnancy. Treatment
should be tailor-made according to the requirements of the patient. If
the patient has fasting hyperglycemia, NPH insulin/detemir should
be initiated at a dose of 0.1–0.2 units/kg/day.

29. In case of postprandial hyperglycemia, regular/lispro/aspart
should be initiated at a dose of 0.1 units/kg preprandially to target
the corresponding postprandial blood glucose level. However,
patients with both fasting and postprandial hyperglycemia should
be started on basal–bolus regimen.
The dose of insulin should be titrated based on SMBG profile.
Patients with overt diabetes may require higher doses of insulin,
even at initiation. However, with advancing pregnancy, insulin
requirement progressively increases both in women with GDM
and overt diabetes.

30. What is the role of metformin during first
trimester of pregnancy?

31. Patients with polycystic ovarian disease who conceive on
metformin were initially recommended to continue the drug
during the first trimester to prevent fetal loss. In addition, the use
of metformin during first trimester was thought to reduce the risk
of GDM in women with PCOS.
However, the available evidence does not support these benefits
of metformin therapy during pregnancy, and the only indication
for continuing metformin during first trimester in women with
PCOS is the concurrent presence of T2DM. Follow-up data of
infants born to mother treated with metformin (2.5 g/day) did not
show any teratogenicity, or adverse effects on birth weight/birth
length, or motor and social development.

32. What is the status of oral antidiabetics in
the management of GDM?

33. Sulfonylureas are known to cross the placenta and have been
associated with increased neonatal hypoglycemia.
Concentrations of glyburide in umbilical cord plasma are
approximately 50–70% of maternal levels (American Diabetes
Association, 2022).
Glyburide was associated with a higher rate of neonatal
hypoglycemia, macrosomia,and increased neonatal abdominal
circumference than insulin or metformin in meta-analyses and
systematic reviews.
Glyburide failed to be found noninferior to insulin based on a
composite outcome of neonatal hypoglycemia, macrosomia,
and hyperbilirubinemia .Long-term safety data for offspring
exposed to glyburide are not available (American Diabetes
Association, 2022)

34. How to manage diabetes during lactation?

35. The best treatment option to manage diabetes during lactation is
possibly insulin.
However, metformin and second-generation sulfonylureas
(glibenclamide and glipizide) have been safely used in lactating
women.
This is supported by the fact that the use of metformin had no
adverse effect on infant growth and motor and social
development during first 6 months of life.
Glibenclamide and glipizide are extensively bound to circulating
proteins and hence not secreted into breast milk. However, there
is no data regarding the use of glimepiride or gliclazide during
lactation.