Insulin

Drug Levels and Effects:




Summary of Use during Lactation:


In general, mothers with diabetes using insulin may nurse their infants. Limited information on the newer biosynthetic insulins (i.e., aspart, detemir, glargine glulisine, lispro) indicates that they are probably secreted into breastmilk. Insulin is a normal component of breastmilk and may decrease the risk of type 1 diabetes in breastfed infants.[1][2][3] Pasteurization of milk by the Holder method reduces the concentration of insulin in milk by about half.[4].

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

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.[11]

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.[5][12] Mothers with type 1 diabetes also discontinue nursing at a higher rate during the first week postpartum.[13][14] Once established, lactation persists as long in mothers with diabetes as in mothers without diabetes.[12][15] However, as in women without diabetes, smoking has a strong negative impact on lactation among mothers with type 1 diabetes.[7][16] 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.[17]


Drug Levels:


Maternal Levels.

Insulin is normally present in breastmilk.[18][19] 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.[1] 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.[20]

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.[4]

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.[21]

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.[1][2]


Possible Effects on Lactation:


Proper insulin levels are necessary for lactation.[22] 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.[12][23]

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.[7]


References:


1. 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
2. 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
3. Tiittanen M , Paronen J, Savilahti E et al. Dietary insulin as an immunogen and tolerogen. Pediatr Allergy Immunol. 2006;17:538-43. PMID:17014631
4. 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
5. 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
6. Davies HA, Clark JD, Dalton KJ, Edwards OM. Insulin requirements of diabetic women who breast feed. BMJ. 1989;298:1357-8. PMID:2502253
7. 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
8. 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
9. 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
10. da Costa TH, Bluck LJ. High lactation index is associated with insulin sensitivity. J Nutr Biochem. 2011;22:446-9. PMID:20655718
11. 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
12. 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
13. 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
14. Hummel S, Winkler C, Schoen S et al. Breastfeeding habits in families with type 1 diabetes. Diabet Med. 2007;24:671-6. PMID:17403118
15. 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
16. 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
17. 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
18. 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
19. Koldovsky O. Hormones in milk. Vitam Horm. 1995;50:77-149. PMID:7709605
20. 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
21. 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
22. Benz J. The galactopharmacopedia. Antidiabetic agents and lactation. J Hum Lact. 1992;8:27-8. PMID:1558654
23. 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



Substance Identification:




Substance Name:

Insulin

CAS Registry Number:

11061-68-0

Drug Class:


  • Hypoglycemic Agents


  • Administrative Information:




    LactMed Record Number:


    147


    Last Revision Date:


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