Insulin use while Breastfeeding

Insulin Levels and Effects while Breastfeeding

Summary of Use during Lactation

Mothers with diabetes using insulin may nurse their infants.[1] Exogenous insulin is excreted into breastmilk, including newer biosynthetic insulins (i.e., aspart, detemir, glargine glulisine, lispro). Insulin is a normal component of breastmilk and may decrease the risk of type 1 diabetes in breastfed infants.[2][3][4] Pasteurization of milk by the Holder method reduces the concentration of insulin in milk by about half.[5]

Insulin requirements are reduced postpartum in women with type 1 diabetes.[1] 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.[6] Another study found that dosage requirements did not return to normal for up to 6 weeks in some mothers.[7] 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.[8] Breastfeeding appears to improve glucose postpartum glucose tolerance in mothers with gestational diabetes mellitus[9][10] and in normal women.[11]

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.[12]

Lactation onset occurs later in patients with type 1 diabetes than in women without diabetes, with a greater delay in mothers with poor glucose control.[6][13] Mothers with type 1 diabetes also discontinue nursing at a higher rate during the first week postpartum.[14][15] Once established, lactation persists as long in mothers with diabetes as in mothers without diabetes.[13][16] However, as in women without diabetes, smoking has a strong negative impact on lactation among mothers with type 1 diabetes.[8][17] Other factors that have been identified as causes of shorter duration of breastfeeding among type 1 diabetic patients are more frequent caesarean sections and earlier delivery.[18] Among patients with gestational diabetes, those treated with insulin have a delayed onset of lactogenesis II compared to those not treated with insulin.[19]

Drug Levels

Maternal Levels. Insulin is normally present in breastmilk.[20][21] In one study, insulin levels in milk were 60 milliunits/L (range 6.5 to 306 milliunits/L) in 42 mothers without diabetes who had full-term infants between 3 and 30 days postpartum.[2] Insulin levels averaged 59 milliunits/L on day 3 postpartum and 40 milliunits/L on day 7 postpartum in 24 mothers without diabetes who had full-term infants. Mothers of preterm infants had nonsignificant changes in milk insulin levels.[22]

In a study of 7 diabetic nursing mothers and 10 nondiabetic nursing mothers, blood glucose was elevated to about 300 mg/dL using a continuous intravenous glucose infusion. Regular pork insulin was then given intravenously to lower the blood glucose. Glucose and insulin were measured in the breastmilk of all the mothers. The milk glucose of women with diabetes approximately tripled during the experiment, but milk glucose remained low in the nondiabetic women. Milk insulin was elevated in the diabetic women, with the peak milk insulin level occurring between 30 to 50 minutes after the intravenous injection. Nine of the 10 nondiabetic women had detectable insulin levels in breastmilk which ranged from 5.1 to 13 milli IU/mL.[23]

Insulin was measured in donor milk from 34 nondiabetic women who were between 1 month and 1 year postpartum. The average insulin concentration was 163 picomoles/L. After pasteurization using the Holder method (62.5 degrees C for 30 min), the average concentration was 88 picomoles/L.[5]

A small study measured breastmilk insulin concentrations in control mothers (n = 5; 1 to 6 months postpartum), mothers with type 1 diabetes mellitus (n = 4; 2 to 5 months postpartum) and type 2 diabetes (n = 5; 5 to 6 months postpartum). No differences were found in the insulin content among the 3 groups and little circadian variation was found. Mothers with type 1 diabetes were well controlled on insulin aspart and insulin glargine. No endogenous insulin was found in their breastmilk, but the milk of 3 of the mothers contained an average 20.5 milliunits/L of insulin, presumed to be of exogenous origin. No indication of paracellular diffusion of insulin was apparent in these women and C-peptide levels in milk were only 5 to 7% those of control mothers. These findings indicate that insulin is likely actively transported into breastmilk.[24]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date. Insulin in breastmilk is thought to be necessary for intestinal maturation of the infant and may help decrease the risk of contracting type 1 diabetes in breastfed infants.[2][3]

Possible Effects on Lactation

Proper insulin levels are necessary for lactation.[25] 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.[13][26]

One-hundred two of 107 consecutive mothers with type 1 diabetes mellitus who delivered were followed at a Danish hospital. Mothers were given prenatal information on breastfeeding and were offered postnatal counseling by a nurse on the benefits of breastfeeding. All infants were admitted to the neonatal intensive care unit at about 2 hours of age for the following 24 hours. When possible, mothers either breastfed or pumped milk for their infants during this time. Mothers were contacted at 5 days and 4 months postpartum to determine their breastfeeding status. The rates of initiation of exclusive and nonexclusive breastfeeding and exclusive formula feeding and the rates at 4 months postpartum were no different from those of the Danish population.[8]

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.[19]

References

1. Ringholm L, Mathiesen ER, Kelstrup L, Damm P. Managing type 1 diabetes mellitus in pregnancy-from planning to breastfeeding. Nat Rev Endocrinol. 2012;8:259-67. PMID: 22965164

2. Shehadeh N, Gelertner L, Blazer S et al. Importance of insulin content in infant diet: suggestion for a new infant formula. Acta Paediatr. 2001;90:93-5. PMID: 11227343

3. Shehadeh N, Shamir R, Berant M et al. Insulin in human milk and the prevention of type 1 diabetes. Pediatr Diabetes. 2001;2(4):175-7. PMID: 15016183

4. Tiittanen M , Paronen J, Savilahti E et al. Dietary insulin as an immunogen and tolerogen. Pediatr Allergy Immunol. 2006;17:538-43. PMID: 17014631

5. Ley SH, Hanley AJ, Stone D, O'Connor DL. Effects of pasteurization on adiponectin and insulin concentrations in donor human milk. Pediatr Res. 2011;70:278-81. PMID: 21587097

6. Stanley K, Fraser R, Bruce C. Physiological changes in insulin resistance in human pregnancy: longitudinal study with the hyperinsulinaemic euglycemic clamp technique. Br J Obstet Gynaecol. 1998;105:756-9. PMID: 9692417

7. Davies HA, Clark JD, Dalton KJ, Edwards OM. Insulin requirements of diabetic women who breast feed. BMJ. 1989;298:1357-8. PMID: 2502253

8. Stage E, Norgard H, Damm P, Mathiesen E. Long-term breast-feeding in women with type 1 diabetes. Diabetes Care . 2006;29:771-4. PMID: 16567813

9. O'Reilly MW , Avalos G, Dennedy MC et al. Atlantic DIP: high prevalence of abnormal glucose tolerance post partum is reduced by breast-feeding in women with prior gestational diabetes mellitus. Eur J Endocrinol. 2011;165:953-9. PMID: 21937504

10. Gunderson EP, Hedderson MM, Chiang V et al. Lactation intensity and postpartum maternal glucose tolerance and insulin resistance in women with recent GDM: The SWIFT cohort. Diabetes Care.2012;35:50-6. PMID: 22011407

11. da Costa TH, Bluck LJ. High lactation index is associated with insulin sensitivity. J Nutr Biochem. 2011;22:446-9. PMID: 20655718

12. Riviello C, Mello G, Jovanovic LG. Breastfeeding and the basal insulin requirement in type 1 diabetic women. Endocr Pract. 2009;15:187-93. PMID: 19364685

13. Neubauer SH, Ferris AM, Chase CG et al. Delayed lactogenesis in women with insulin-dependent diabetes mellitus. Am J Clin Nutr. 1993;58(1):54-60. PMID: 8317390

14. Ferris AM, Dalidowitz CK, Ingardia CM et al. Lactation outcome in insulin-dependent diabetic women. J Am Diet Assoc. 1988;88(3):317-22. PMID: 3279099

15. Hummel S, Winkler C, Schoen S et al. Breastfeeding habits in families with type 1 diabetes. Diabet Med. 2007;24:671-6. PMID: 17403118

16. Schoen S, Sichert-Hellert W, Hummel S et al. Breastfeeding duration in families with type 1 diabetes compared to non-affected families: results from BABYDIAB and DONALD studies in Germany. Breastfeed Med. 2008;3:171-5. PMID: 18778212

17. Knudsen A, Pedersen H, Klebe JG. Impact of smoking on the duration of breastfeeding in mothers with insulin-dependent diabetes melllitus. Acta Paediatr. 2001;90:926-30. PMID: 11529544

18. Sorkio S, Cuthbertson D, Barlund S et al. Breastfeeding patterns of mothers with type 1 diabetes: results from an infant feeding trial. Diabetes Metab Res Rev. 2010;26:206-11. PMID: 20474068

19. Matias SL, Dewey KG, Quesenberry CP Jr, Gunderson EP. Maternal prepregnancy obesity and insulin treatment during pregnancy are independently associated with delayed lactogenesis in women with recent gestational diabetes mellitus. Am J Clin Nutr. 2014;99:115-21. PMID: 24196401

20. Kulski JK, Hartmann PE. Milk insulin, GH and TSH: relationship to changes in milk lactose, glucose and protein during lactogenesis in women. Endocrinol Exp. 1983;17:317-26. PMID: 6360660

21. Koldovsky O. Hormones in milk. Vitam Horm. 1995;50:77-149. PMID: 7709605

22. Shehadeh N, Khaesh-Goldberg E, Shamir R et al. Insulin in human milk: postpartum changes and effect of gestational age. Arch Dis Child Fetal Neonatal Ed. 2003;88:F214-6. PMID: 12719395

23. Jovanovic-Peterson L, Fuhrmann K, Hedden K et al. Maternal milk and plasma glucose and insulin levels: studies in normal and diabetic subjects. J Am Coll Nutr. 1989;8:125-31. PMID: 2651503

24. Whitmore TJ, Trengove NJ, Graham DF, Hartmann PE. Analysis of insulin in human breast milk in mothers with type 1 and type 2 diabetes mellitus. Int J Endocrinol. 2012;2012:296368. 22500167

25. Benz J. The galactopharmacopedia. Antidiabetic agents and lactation. J Hum Lact. 1992;8:27-8. PMID: 1558654

26. Ostrom KM, Ferris AM. Prolactin concentrations in serum and milk of mothers with and without insulin-dependent diabetes mellitus. Am J Clin Nutr. 1993;58(1):49-53. PMID: 8317389

Insulin Identification

Substance Name

Insulin

CAS Registry Number

11061-68-0

Drug Class

  • Hypoglycemic Agents

Administrative Information

LactMed Record Number

147

Information from the National Library of Medicine's LactMed Database.

Last Revision Date

2014-02-04

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