Breastfeeding is recommended for infants for the first year of life and provides health benefits for both mother and baby. While sulfonylureas like glipizide were previously discouraged during breastfeeding due to transfer into breastmilk, recent studies found negligible levels of glyburide and glipizide in breastmilk. Metformin is also considered safe during breastfeeding as studies found low levels in breastmilk below 10% of the maternal dose, with no adverse effects seen in infants. Therefore, sulfonylureas and metformin appear to be compatible with breastfeeding for diabetic mothers.

1. Diabetes and Lactation
Alaa Wafa . MD
Associate Professor of Internal Medicine
Diabetes & Endocrine Unit.
Mansoura University

2. Question
My patient was taking glipizide for type 2 DM.
Now, she is pregnant and taking insulin instead.
She is very anxious to return to her previous
treatment immediately after delivery because of
the pain and hurdles associated with the
administration of insulin.
Can sulfonylurea cross into human milk
and, if so, is it safe for her to breastfeed
her infant?

3. Since 1986, the American Diabetes Association has recommended that diabetic women should
be encouraged to breastfeed .
Recommendations from the Fourth International Workshop-Conference on Gestational
Diabetes Mellitus encouraged women to breastfeed, although data demonstrating efficacy
were lacking
American Diabetes Association: Position statement on gestational diabetes mellitus. Diabetes Care 9:430–431, 1986
American Diabetes Association: Gestational diabetes mellitus (Position Statement). Diabetes Care 27 (Suppl. 1):S88–S90, 2004

4. Breastfeeding is recommended as the preferred
method of infant feeding for the first year of life
or longer, and exclusive breastfeeding is
recommended for the first 6 months of life .
The Institute of Medicine defines exclusive
breastfeeding as an infant's consumption of
human milk with no supplementation of any type
(no water, juice, nonhuman milk, or foods) except
for vitamins, minerals, and medications
• Institute of Medicine: Nutrition During Lactation. Washington, DC, National Academy Press, 1991

6. Benefits of lactation
 Breastfeeding provides important health benefits to both
women and their offspring.
 Lactation improves glucose tolerance in the early
postpartum period
 Health benefits of lactation for women include a lower
risk of breast and ovarian cancer and possibly protection
against type 2 diabetes
• Collaborative Group on Hormonal Factors in Breast Cancer: Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries,
including 50302 women with breast cancer and 96973 women without the disease. Lancet 360:187–195, 2002
• ↵ Stuebe AM, Rich-Edwards JW, Willett WC, Manson JE, Michels KB: Duration of lactation and incidence of type 2 diabetes. JAMA 294:2601–2610, 2005

7. Benefits of lactation
For the offspring, breastfeeding confers protection against both
undernutrition and overnutrition during early childhood and may
lower risk of developing obesity, hypertension, cardiovascular
disease, and diabetes later in life .
 Postnatal feeding is one of several critical or sensitive
developmental periods hypothesized to result in “metabolic
programming” of future chronic disease risk
Arenz S, von Kries R: Protective effect of breastfeeding against obesity in childhood: can a meta-analysis of observational studies help to validate the
hypothesis? Adv Exp Med Biol 569:40–48, 2005
Ravelli AC, van der Meulen JH, Osmond C, Barker DJ, Bleker OP: Infant feeding and adult glucose tolerance, lipid profile, blood pressure, and obesity.
Arch Dis Child 82:248–252, 2000

8. LACTATION AND SUBSEQUENT
OBESITY AND DIABETES IN
WOMEN

9. LACTATION AND SUBSEQUENT
OBESITY AND DIABETES IN WOMEN
• Lactation may have lasting effects on risk factors that influence
future chronic disease risk for women . .
• Longer duration of breastfeeding has also been associated with
lower maternal weight gain 10–15 years later .
• Lactation may also influence long-term regulation of body weight as
well as regional fat distribution in women

10. Lactogenesis in Diabetic women
• Lactation may be more difficult for women with DM because
both maternal diabetes and obesity can delay the onset of
lactogenesis .
• Furthermore, medical management of their newborns that
involves provision of supplemental milk feedings may interfere
with maternal milk production.
• In obese women, lactogenesis may be impaired because of
lower physiological levels of prolactin in response to suckling .
• Delayed milk production may lead to lower rates of
breastfeeding and shorter duration among obese women .

11. Biological plausibility for breastfeeding and
lower risk of overweight and diabetes
• The average daily milk volume consumed by an
infant increases from 50 ml on day 1 to 500 ml by
day 5 of life .
• Macronutrient composition (i.e., protein, fat,
lactose content) of breast milk may influence
hormonal responses that influence metabolic
programming of body fat and rates of growth.
• Levels of insulin, leptin, and ghrelin that regulate
energy homeostasis in early neonatal life may be
affected by the mode of infant feeding

12. Postulated mechanisms: constituents of breast
milk and metabolic programming
• Breastfeeding may exert protective biologic effects through
behavioral and hormonal mechanisms that influence
metabolic programming.
• Breast milk contains bioactive substances that may
influence regulation of energy balance and fat deposition
and has less protein relative to formula milk..
• Leptin levels have been reported to be higher for breastfed
than formula-fed infants .
• The circulating leptin levels were not only related to
adipose tissue production, but may be contributed from
human milk

13. Lactation: immediate and post-weaning
effects on maternal metabolic parameters
• Lactation markedly alters maternal fuel metabolism and increases
energy expenditure by 15–25%
• .
• The 400–500 kcal/day required for milk production during the
first 6 months by exclusively breastfeeding women is derived from
maternal dietary intake, with an additional 170 kcal/day mobilized
from fat stores .
• About 50 g/day glucose is diverted for lactogenesis (the process of
milk synthesis and secretion) via non–insulin-mediated pathways
of uptake by the mammary gland .
Thus, lactating women exhibit lower blood glucose and insulin
concentrations along with higher rates of glucose production and lipolysis
compared with nonlactating women

14. Antidiabetic drugs
&
Lactation

15. Sulphonlyurea
&
Lactation

16. Sulfonylureas and lactation
• To date, the use of sulfonylureas during
breast-feeding has been discouraged.
Earlier studies with two first-generation
sulfonylureas, showed that there was
significant transfer of these drugs into
breast milk

18. • Mothers who had recently delivered were given a single
dose of glyburide, 5 mg (n = 6) or 10 mg (n = 2), and
maternal blood and milk were tested at 8 hours after the
dose.
• Another group of mothers (N = 5) received daily doses of
glyburide (nonmicronized 5 mg) or glipizide (immediate-
release 5 mg).
• Neither glyburide nor glipizide could be detected in
breast milk.
• Blood glucose levels were normal in all infants who
were exclusively breastfed (glyburide [n = 1], glipizide [n
= 2]).
• Based on these data, maternal exposure to these drugs
seems unlikely to exert any clinically significant
pharmacologic action on breastfed infants

19. CONCLUSIONS—Neither glyburide nor glipizide were
detected in breast milk, and hypoglycemia was not
observed in the three nursing infants. Both agents, at the
doses tested, appear to be compatible with breast-
feeding.

20. Glyburide Breastfeeding Warnings
 There is limited data which suggests negligible levels of this
drug are present in breast milk.
 A study in 8 women receiving a single-dose shortly after delivery
estimates the maximum dose a fully breastfed infant would receive with 5
and 10 mg doses at less than 1.5% and less than 0.7% of the maternal
weight-adjusted dose, respectively.
Due to the limited data available and the potential
for hypoglycemia in the nursing infant, the
manufacturer suggests women who are not able to
manage their blood sugar on diet alone consider
insulin therapy while breastfeeding

21. Metformin& breastfeeding

23. 5 women taking a median dose of 1500 mg/d of metformin had average breast milk levels
of 0.27 mg/L, amounting to an estimated 0.28% of the maternal weight-adjusted dose
ingested by the infant. Very low or undetectable concentrations of metformin were
observed in the plasma of the 4 babies studied.
CONCLUSIONS/INTERPRETATION:
The concentrations of metformin in breast milk were generally low and the mean
infant exposure to the drug was only 0.28% of the weight-normalized maternal
dose. As this is well below the 10% level of concern for breastfeeding, and
because the infants were healthy, we conclude that metformin use by
breastfeeding mothers is safe. Nevertheless, each decision to breastfeed should
be made after conducting a risk:benefit analysis for each mother and her infant

24. A second study looking at breast milk transfer of metformin enrolled 7 women who took
1000 mg/d of the drug. The milk concentrations observed were similar to those of the
previous study, with estimated doses ingested by the infants below 1% of the maternal
weight-adjusted dose
CONCLUSION:
Metformin is excreted into breast milk, but the amounts
seem to be clinically insignificant. No adverse effects on the
blood glucose of the 3 nursing infants were measured

25. CONCLUSION:
Metformin appears to be "safe" during lactation because of low infant exposure.
The unusual concentration-time profile for metformin in milk suggests that the
transfer of metformin into milk is not solely dependent on passive diffusion

26. A prospective study followed 61 breastfed and 50 formula-
fed infants born to 92 mothers with polycystic ovary
syndrome taking 1.5 to 2.55 g of metformin daily throughout
pregnancy and lactation.
Conclusion
Metformin use during lactation had no adverse effects on
breastfed infants’ growth, motor-social development, or
intercurrent illnesses, compared with formula-fed infants.

27. • Metformin is considered a first-line agent for the
treatment of type 2 diabetes, and has also been
proposed as a useful drug for the management of
gestational diabetes.
• The very limited amounts of metformin observed in
breast milk are highly unlikely to lead to substantial
exposure in the breastfed baby.
• Metformin can be considered a safe medication for the
treatment of type 2 diabetes in a breastfeeding
mother.

28. Conclusions

29. Conclusions :Use of oral
hypoglycemic and lactation
• The available data suggest that the levels of glyburide and glipizide in
milk are negligible and would not be expected to cause adverse effects
in breastfed infants;
• Treatment with metformin during lactation is unlikely to lead to toxicity
in the breastfed infant. Given the safety profile of metformin, as
compared with sulfonylureas, it is advisable to consider metformin as
first-line treatment during lactation if this drug is appropriate for the
particular patient. Nevertheless, second-generation sulfonylureas are
also likely to be safe during lactation.
• However, as data are based on a single study with a limited sample
size, monitoring of the breastfed infant for signs of hypoglycemia is
advisable during maternal therapy with any of these agents.
• Other oral medications currently used for the treatment of type 2
diabetes, such as the thiazolidinediones and acarbose,DPP-4 inhibitors
have not been studied in the lactation period

30. Insulin and lactation

31. Insulin and lactation
• Mothers with diabetes using insulin may
nurse their infants.
• Insulin is a normal component of breastmilk
and may decrease the risk of type 1 diabetes
in breastfed infants.

32. Insulin requirements are reduced postpartum
in women with type 1 diabetes.
 In one study, insulin requirements were lower than prepregnancy dosage only
during the first week postpartum: 54% of prepregnancy dosage on day 2 and 73%
on day 3 postpartum. On day 7 postpartum, insulin dosage returned to
prepregnancy requirements.
 Another study found that dosage requirements did not return to normal for up to
6 weeks in some mothers.
 A third study found that at 4 months postpartum, patients with type 1 diabetes
who exclusively breastfed had an average of 13% lower (range -52% to +40%)
insulin requirement than their prepregnancy requirement Breastfeeding appears
to improve postpartum glucose tolerance in mothers with gestational diabetes
mellitus and in normal women.

33. Insulin requirements are reduced postpartum
in women with type 1 diabetes.
A small, well-controlled study of women with type 1
diabetes mellitus using continuous subcutaneous
insulin found that the average basal insulin
requirement in women with type 1 diabetes who
breastfed was 0.21 units/kg daily and the total insulin
requirement was 0.56 units/kg daily.
 In similar women who did not breastfeed, the basal
insulin requirement was 0.33 units/kg daily and the
total insulin requirement was 0.75 units/kg daily.
The 36% lower basal insulin requirement was thought
to be caused by glucose use for milk production.

34. Effects on Lactation and Breastmilk
Proper insulin levels are necessary for lactation.
Good glycemic control enhances maternal serum
and milk prolactin concentrations and decreases
the delay in the establishment of lactation that
can occur in mothers with type 1 diabetes.

35. • Eight hundred eighty-three patients with
gestational diabetes were interviewed at 6 to
9 weeks postpartum.
• Those who had been treated with insulin
more frequently reported having a delayed
onset of lactogenesis II (>72 hours)
postpartum than those not treated with
insulin.
• The odds ratio of having delayed lactogenesis
II was 3.17 among insulin-treated mothers.

37. Stanadarad of Medical care in Diabetes
2015
Lactation
• All women should be supported in attempts to nurse their babies, given
immediate nutritional and immunological benefits of breastfeeding for the
baby; there may also be a longer-term metabolic benefit to both mother and
offspring , though data are mixed.
Type 1 Diabetes
• Insulin sensitivity increases in the immediate postpartum period and then
returns to normal over the following 1–2 weeks, and many women will require
significantly less insulin at this time than during the prepartum period. Breast-
feeding may cause hypoglycemia, which may be ameliorated by consuming a
snack (such as milk) prior to nursing. Diabetes self-management often suffers in
the postpartum period.
Type 2 Diabetes
• If the pregnancy has motivated the adoption of a healthier diet, building on
these gains to support weight loss is recommended in the postpartum period.

38. Stanadarad of Medical care in Diabetes
2015
Gestational Diabetes Mellitus
 Because GDM may represent preexisting undiagnosed type 2 diabetes, women with
GDM should be screened for persistent diabetes or prediabetes at 6–12 weeks
postpartum using nonpregnancy criteria and every 1–3 years thereafter depending on
other risk factors.
 Women with a history of GDM have a greatly increased risk of conversion to type 2
diabetes over time and not solely within the 6–12 weeks’ postpartum time frame .
 Interpregnancy or postpartum weight gain is associated with increased risk of
adverse pregnancy outcomes in subsequent pregnancies and earlier progression to
type 2 diabetes.
 Both metformin and intensive lifestyle intervention prevent or delay progression to
diabetes in women with a history of GDM. Of women with a history of GDM and
impaired glucose tolerance, only 5–6 individuals need to be treated with either
intervention to prevent one case of diabetes over 3 years .

40. Blood glucose control, medicines and
breastfeeding
• Women with insulin-treated pre-existing diabetes
should reduce their insulin immediately after birth
and monitor their blood glucose levels carefully to
establish the appropriate dose.
• Explain to women with insulin-treated pre-existing
diabetes that they are at increased risk of
hypoglycaemia in the postnatal period, especially
when breastfeeding, and advise them to have a
meal or snack available before or during feeds.
• Women who have been diagnosed with
gestational diabetes should discontinue blood
glucose-lowering therapy immediately after birth.

41. Blood glucose control, medicines and
breastfeeding
• Women with pre-existing type2 diabetes who are
breastfeeding can resume or continue to take
metformin and glibenclamide immediately after
birth, but should avoid other oral blood glucose-
lowering agents while breastfeeding.
• Women with diabetes who are breastfeeding
should continue to avoid any medicines for the
treatment of diabetes complications that were
discontinued for safety reasons in the
preconception period.

42. Conclusion
The role of breastfeeding in diabetes
• In the mother, breastfeeding has been suggested to reduce
the incidence of type 2 diabetes and reduce the risk of
premenopausal breast cancer and ovarian cancer.
• In the neonate and infant, among other benefits, lactation
confers protection from future both type 1 and type 2
diabetes.
Breastfeeding could be considered a modifiable risk factor for the
development of diabetes and even a potential protective lifestyle measure
from future cardio-metabolic .
Therefore, health care professionals should encourage both women with
and without diabetes to breastfeed their children

43. Conclusion
• Importantly, for diabetic mothers, antidiabetic
treatment itself may affect breastfeeding.
• There is not enough data to allow the use of oral
hypoglycaemic agents.
• Therefore, insulin currently remains the optimal
antidiabetic treatment during lactation.

44. Thank
you
dralaawafa@hotmail.com