screening, diagnosis & management of gestational diabetes, different modalities of treatment, complication of GD, macrosomia

1. GESTATIONAL
DIABETES

2. • Gestational diabetes mellitus (GDM) is
defined as any abnormal carbohydrate
intolerance that begins or first recognized
during pregnancy.
• Gestational diabetes mellitus complicates
2% to 5% of all pregnancies. The
incidence of GDM is rising, paralleling to
the rise in type 2 diabetes and obesity
prevalence.

3. Pathophysiology
• Relative pancreatic β-cell dysfunction.
• post-receptor defects
• Immunological: antigenic load of the
fetus. It has been postulated that the
development of DM in patients who have
undergone organ transplantation is analogous to
GDM development. (Oztekin , 2007)

4. Screening & Diagnosis
• High risk ( one of the following)
– Marked obesity.
– First-degree relative with diabetes.
– Previous gestational diabetes, large-for-
gestational age baby, or unexplained stillbirth.
– Polycystic ovarian syndrome.

5. Screening & Diagnosis
• Low risk ( all of the following)
1. Age < 25 y.
2. Normal weight.
3. Have no family history of diabetes mellitus.
• Intermediate risk.
includes women who does not fall either into low
or high-risk group.

6. • According to American Diabetes Association
[ADA], women belonging to high risk should
undergo glucose testing as soon as possible. If
they have a negative result, they should be
rechecked between 24 and 28 weeks of
gestation.
• Those with intermediate risk require screening
at 24—28 weeks.
• Screening for women falling into low risk
category not recommended.

7. How?
(1) One-step approach–—suitable for high-
risk patients/population. A diagnostic oral
glucose tolerance test without prior
screening is acceptable.

8. (2) Two-step approach–—in this 1st
perform initial screening test by measuring
plasma glucose 1 h after 50 g oral glucose
load (glucose challenge test). A 1 h value
> 140 mg/dl identifies 80% of women with
GDM.
• Lowering down the threshold to 130 mg/dl
increases the sensitivity to 90% but
increase the cost.

9. • Diagnostic criteria of GDM following OGTT ( 100 g
glucose load ) ( Carpenter & Coustan, 1982 )
Plasma glucose
level mg/dl
fasting 95
1 H 180
2 H 155
3 H 140

10. • World health organization (WHO) have
proposed different diagnostic criteria for
the diagnosis of GDM.
• It is based on 75 g OGTT with diagnosis
being confirmed if either the fasting
plasma glucose > 126 mg/dl or 2 h plasma
glucose > 140 mg/dl.

11. • The Hyperglycemia and adverse pregnancy
outcomes (HAPO) study was designed to determine
the actual levels of blood glucose during a 75-g OGTT
performed between 24 and 32 weeks of pregnancy,
lower than that of overt diabetes, that predicted adverse
perinatal outcomes.
• The study showed a continuous relationship between
maternal hyperglycaemia and the adverse pregnancy
outcomes of LGA babies, primary caesarean section,
clinically defined hypoglycaemia and cord C-peptide
>90th percentile, (Metzger et al, 2008).

12. • Based on HAPO study the international
association of diabetes and pregnancy
study groups (IADPSG) consensus
recommended.
– Cut-off level for fasting 92 md/dl & 2 hrs 153
mg/dl.
– Selective screening based on risk factors for
GDM has not been recommended.

13. – A screening test to be performed at the first
prenatal visit to avoid late diagnosis of pre-
existing overt diabetes by HbA1c test for this
screen, but the use of fasting plasma glucose
or random blood glucose was suggested as
alternative options if HbA1c testing is not
feasible.
(International Association of Diabetes in Pregnancy
Groups Consensus Panel, 2010)

14. Prevention
• Prevention of obesity.
• Weight loss of 4.5 kg between pregnancies has
been shown to reduce the risk of developing
GDM in a subsequent pregnancy by 40% (Callaway
et al, 2006).
• Life style modification & Exercise.

15. TREATMENT

16. The goals of treatment
– Mean blood glucose: 90 to 105 mg/dl
– Fasting blood glucose: 60 to 90 mg/dl.
– Pre-prandial blood glucose: 80 to 95 mg/dl.
– Postprandial blood glucose: less than 120
mg/dl.
– Hemoglobin A1c levels of less than 6.0%.
(kitzmiller , 2008)

17. Continuous glucose monitoring
system (CGMS)
• Recently, several companies have attempted to
develop a new technology that measures
continuous glucose. The MiniMed CGM System
(Sylmar, CA, USA).
• The system measures glucose levels every 10s,
based on the electrochemical detection of
glucose by its reaction with glucose oxidase.
• It stores an average value every 5 min for a total
of 288 measurements per day.

18. Medical nutrition therapy (MNT) and
exercise
• The calculated daily calorie intake is
based on prepregnant body weight. For
body mass index 20-25, 25-34 and >34
kg/m2, the respective calories intake are
30, 25 and 20 kcal/kg (American diabetic
association, 2004).

19. • American Diabetes Association advice a 55%
carbohydrate component at the diet.
• the euglycemic diet decreases carbohydrate content to
40% and incorporates more fat
• The diet also recommends the following overall caloric
distribution: 12.5% at breakfast, 28% at both lunch and
dinner, and the remainder divided among 3 snacks.
• There is also a limitation of carbohydrates to 33% at
breakfast, as insulin resistance appears to be greatest in
the morning.
(Jovanovic L, 2004)

20. ‫السكر‬ ‫لمرضى‬ ‫الغذائى‬ ‫النظام‬
•
‫ا‬
....‫الفطار‬
1) ‫مدمس‬ ‫فول‬ -2. ‫نحل‬ ‫عسل‬ ‫ملعقة‬ ‫أو‬ ‫مسلوقة‬ ‫بيضة‬ ‫أو‬ ( ‫معلقة‬
2) -50-100.‫المرتفع‬ ‫الدم‬ ‫ضغط‬ ‫لمرضى‬ ‫الملح‬ ‫قليل‬ ( ‫الدسم‬ ‫قليل‬ ) ‫أبيض‬ ‫جبن‬ ( ‫جرام‬
3‫أو‬ ‫زبادى‬ ‫لبن‬ ‫كوب‬ -2/3‫يفضل‬ ) ‫لبن‬ ‫كوب‬1/2. ( ‫الدسم‬ ‫منزوع‬ ‫أو‬ ‫دسم‬
4-1/2.‫بلدى‬ ‫خبز‬ ‫رغيف‬
5. ‫فاكهة‬ ‫ثمرة‬ ‫أو‬ ‫خيار‬ ‫أو‬ ‫طماطم‬ -
....‫الغذاء‬
1) ‫اللحوم‬ -100‫أو‬ ‫مسلوقة‬ ‫فرخة‬ ‫ربع‬ ‫أو‬ ‫حمراء‬ ‫لحمة‬ ‫جم‬200.(‫أسماك‬ ‫جم‬
2)‫النشويات‬ -3/4‫أو‬ ‫بلدى‬ ‫خبز‬ ‫رغيف‬6‫أو‬ ‫أرز‬ ‫ملعق‬6.( ‫مكرونة‬ ‫ملعق‬
3(‫خبيزة‬ - - ‫بامية‬ - ‫كوسة‬ - ‫سبانخ‬ - ‫ملوخية‬ - ‫خضراء‬ ‫فاصوليا‬ - ‫خضراء‬ ‫بسلة‬ - ‫باذنجان‬ - ‫قرنبيط‬ - ‫)كرنب‬ ‫الخضروات‬ -
4. ‫الفاكهة‬ -
....‫العشاء‬
1-100. ‫أبيض‬ ‫جبن‬ ‫جم‬
2) ‫مدمس‬ ‫فول‬ -2‫ملعقة‬() ‫طعمية‬ ‫أو‬2.‫مسلوقة‬ ‫بيضة‬ ‫أو‬ ‫عدس‬ ‫طبق‬ ‫أو‬ ( ‫الحجم‬ ‫متوسط‬ ‫قرص‬
3. ‫زبادى‬ ‫لبن‬ ‫كوب‬ -
4-12..‫بلدى‬ ‫خبز‬ ‫رغيف‬
....‫الفاكهة‬
) ‫تفاح‬1) ‫البرتقـــال‬ - ( ‫ثمرة‬2‫ثمــــرة‬- () ‫الجوافة‬2) ‫الكمثــــرى‬ - ( ‫ثمـــرة‬2) ‫اليوسفـــــى‬ -( ‫ثمــــرة‬2) ‫كنتـــــــالوب‬ ‫أو‬ ‫بطيــــخ‬ - (‫ثـــــمرة‬2) ‫العنب‬ -( ‫الحجم‬ ‫متوسط‬ ‫قطعة‬12‫البلح‬ - ( ‫الحجم‬ ‫متوسطة‬ ‫)ثمرة‬ ‫المانجو‬ - (‫حبة‬
)4) ‫الخوخ‬ - ( ‫ثمرة‬2) ‫المشمش‬ ‫أو‬ ‫البرقوق‬ - ( ‫ثمرة‬3. ( ‫ثمرة‬
... : ‫تحفظ‬ ‫بدون‬ ‫بها‬ ‫مسموح‬ ‫مأكول ت‬
1‫البصل‬ -‫الجرجير‬ - ‫المقدونس‬ - ‫الكرفس‬ - ‫الخيار‬ - ‫الفجل‬ - ‫الخس‬ - ‫الخضر‬ ‫الفلفل‬ -
2.(‫المرتفع‬ ‫الدم‬ ‫ضغط‬ ‫مرضى‬ ‫فى‬ ‫الكثار‬ ‫عدم‬ ‫فيراعى‬ ‫الملح‬ ‫عدا‬ ‫)ما‬ ‫التوابل‬ -
3.‫سكر‬ ‫بدون‬ ‫الغازية‬ ‫والمياه‬ ‫الصناعية‬ ‫المحليات‬ -
....:‫الممنوعا ت‬
1.‫المولد‬ ‫حلوى‬ ‫و‬ ‫المكسرات‬ ‫و‬ ‫الشامية‬ ‫-الحلويات‬
2.‫الطحينة‬ ‫و‬ ‫الطحينية‬ ‫الحلوة‬ , ‫الشوكولتة‬ , ‫السود‬ ‫العسل‬ -
3.‫المربى‬ ‫و‬ ‫الجاتوهات‬ ‫و‬ ‫التورتات‬ -
4.‫الكحولية‬ ‫المواد‬ ‫الروحيةو‬ ‫المشروبات‬ -
....:‫بالدم‬ ‫السكر‬ ‫انضباط‬ ‫على‬ ‫للمحافظة‬
1.‫الغذائى‬ ‫بالنظام‬ ‫-اللتزام‬
2.‫المثالى‬ ‫الوزن‬ ‫الى‬ ‫-الوصول‬
3.‫كالمشى‬ ‫اليومية‬ ‫-الرياضة‬
4‫النفعال‬ ‫-عدم‬ .

21. • Exercise can also play an important role in
lifestyle interventions employed to
minimize the complications of diabetes in
pregnancy.
• It is recommended that all pregnant
women “capable of exercising” …….at
least 30 minutes of planned physical
activity each day.

22. Insulin therapy
• The discovery of insulin in 1922 by
Banting is one of the greatest discoveries
in the history of medicine.
• The 1923 Nobel Prize in Physiology and
Medicine was awarded for this landmark
discovery.

23. • Insulin therapy is the most validated
treatment option when MNT fails to
achieve the target glycemic control.
• Lacking a general consensus for the
initiation of insulin.
– Fasting > 95 mg/dl.
– Postprandial >140 mg/dl.
(Reece et al, 2002).

24. • Basal insulin
– NPH
– Long Acting insulin analogues
• Bolus insulin ( mealtime)
– Regular insulin
– Rapid Acting insulin analogues

26. Rapid acting insulin
• With respect to GDM, there have been
several small randomized studies
comparing the use of rapid acting insulin
analogues with regular insulin.
• They have all demonstrated that the rapid
acting analogues are as effective as
regular insulin in the treatment of GDM.
(Pettitt et al, 2007).

27. • To mediate the postprandial peak, a rapid-acting insulin
should be used immediately before each meal.
• There are 2 main types of rapid-acting insulin analogues
that have been investigated and proven safe in
pregnancy: insulin lispro and insulin aspart.
• Compared to regular human insulin, insulin lispro
therapy lowers A1C in women with GDM and has also
been shown to improve the postprandial glucose peak in
comparison with regular insulin.
(Meccaci F et al, 2003)

28. Basal insulin
• The second component of insulin therapy is an
insulin that acts throughout the day as the basal
insulin release.
• The only effective choice is neutral protamine
Hagedorn (NPH) insulin, which has a peak effect
5 to 7 hours after administration.
• Because of the timing of its peak effect, it is
necessary for a pregnant woman to take 3
injections of NPH (1 every 8 hours) in order to
maintain her glucose control with basal insulin.

29. long-acting insulin analogues
• Data regarding the long-acting insulin
analogues are less clear than for rapid-
acting analogues.
• There are a number of case reports and
small case series of glargine being utilized
without the development of pregnancy
complications.
(Price et al, 2007)

30. Continuous Subcutaneous Insulin
Infusion (CSII)

31. Continuous Subcutaneous Insulin
Infusion (CSII)
Absolute Contradictions
• Severe psychiatric disorders
• Progressive ischaemic or proliferative
retinopathy
• Non-educated patient.
• Living with extreme circumstances of either heat
or cold for professional or personal reasons.
• Underwater diving.
• Exposure to high electromagnetic fields.

32. Pulmonary Inhalation of Insulin
• The exubera insulin is a fine powder insulin in
doses of 1 or 3 mg, corresponding to
approximately 3 and 9 units of human insulin.
• Duration of action between that of rapid-acting
analogues and short acting human insulin.
• Patients were three times more likely to choose
insulin when inhaled insulin was available
compared with conventional insulin treatment
(Freemantle et al, 2005).

33. The future:
a closed-loop system (an artificial
pancreas)
one system which monitors glucose levels and
accordingly supplies insulin.
– Safe-delivery device that stores and releases insulin
accurately.
– Accurate, biocompatible glucose-sensing unit.
– Control system that modulates delivery of insulin,
glucose, and may be also glucagon according to
blood glucose levels.
– This process must operate correctly all the time, to
avoid errors leading to severe hypo- or
hyperglycemia.

34. Metformin
• The use of metformin in pregnancy has been
quite controversial with early reports of adverse
effects in those exposed to this drug. ( Hellmuth E
et al, 2000).
• However, metformin used in the treatment of
women with polycystic ovary syndrome (PCOS),
it is postulated to alleviate key pathogenetic
mechanisms such as hyperinsulinaemic insulin
resistance, would reduce the rate of early
pregnancy loss (Jakubowicz et al, 2002).

35. • In a case control study, there was
significant reduction of early pregnancy
loss by continuation of metformin during
pregnancy in 197 cases with polycystic
ovarian disease 8.8% compared to 29.4%
in control group.
( Nawaz & Rizvi, 2010).

36. • Metformin in gestational diabetes study
(MiG Study) 751 women with GDM
randomized to treatment with insulin or
metformin.
• The authors have suggested that
metformin is a safe and effective treatment
for GDM (Rowan et al, 2008).

37. Glibenclamide (Glyburide)
• In 1991 Elliott et al. demonstrated
experimentally that minimal glyburide was
detectable crossing the placenta in an in vitro
placental perfusion model.
• Lack of its significant appearance in the fetal
circulation could also result from a very high
protein binding of the drug.
• glyburide has a protein binding of 99.8%,
compared to 96% percent for tolbutamide. This
means that only 0.2% of circulating glyburide is
free to cross the placenta, compared to 4% of
circulating tolbutamide.

38. • In 2000 Langer et al published the results of
their controlled randomized clinical trial where
glyburide was compared with insulin in treatment
of GDM.
• Ramos et al., 2007 retrospectively compared
the effectiveness of glyburide and insulin for the
treatment of GDM. There were no significant
differences in birth weight, macrosomia,
preeclampsia or cesarean delivery.

39. acarbose
• The use of acarbose in pregnancy seems to be
a good option because it primarily acts in the gut
by delaying carbohydrate absorption and is not
absorbed, thereby having no systemic effects.
However, this drug has not yet been studied well
in pregnancy.
• In a small study by Zarate et al, 6 pregnant
women with moderately elevated levels of
fasting and postprandial blood glucose were
treated with acarbose, after which, the fasting
and postprandial glucose levels normalised.

40. Timing and mode of delivery
• Pregnancy should continue till 40 weeks as in
nondiabetic pregnant women in setting of
adequate glycemic control and no other known
complications.
• Contrary to the general thinking, GDM by itself is
not an indication for cesarean section.
• Even then increased incidence of cesarean
section in pregnancy complicated by GDM is
observed compared to women without diabetes.
This is solely due to overestimation of obstetric
complications.

41. Postpartum follow-up
• Recurrence in subsequent pregnancy. An
estimate of 30—84% recurrence rate has been
reported in a systemic review (Kim et al, 2007).
• development of type 2 DM.(37% versus 2%).
• ADA recommendations for postpartum follow-up
of patients with GDM are:
(1) Measurement of fasting plasma glucose annually.
(2) OGTT with 75 g glucose at 6 week postpartum.
(3) Adequate contraception to avoid pregnancy during
hyperglycemia.

42. Breast feeding
• The use of second-generation
sulfonylureas, glyburide as well as
glipizide, was examined in lactation. Both
drugs appeared to be compatible with
breast-feeding.
• Blood glucose levels were normal in all
infants who were wholly breast-fed (Feig et
al., 2005).

43. THANK YOU