DEVELOPMENT AND PREVENTION OF CHILDHOOD OBESITY
Location: Children Nutrition Research Center (Houston, Tx)
Title: Mechanisms to conserve glucose in lactating women during a 42-h fast
| Mohammad, Mahmoud - |
| Sunehag, Agneta - |
| Chacko, Shaji - |
| Pontius, Amy - |
| Maningat, Patricia - |
| Haymond, Morey - |
Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 29, 2009
Publication Date: August 4, 2009
Citation: Mohammad, M.A., Sunehag, A.L., Chacko, S.K., Pontius, A.S., Maningat, P.D., Haymond, M.W. 2009. Mechanisms to conserve glucose in lactating women during a 42-h fast. American Journal of Physiology - Endocrinology and Metabolism.297(4):E879-E888.
Interpretive Summary: This study was conducted to determine whether increasing the duration of fasting from 24 to 42 h in lactating women would result in 1) increased glucose production, 2) decreased glucose utilization by reducing milk production and/or glucose oxidation, and 3) increased utilization of free fatty acids and ketones. The study showed that both the non-lactating and lactating women adjusted to extended fast by reducing glucose demands by the same mechanisms. However, due to the added demands of lactation, the metabolic stress was greater in the lactating compared to non-lactating women. This higher metabolic stress was indicated by lower plasma concentrations of glucose, insulin, and C-peptide, while, higher those of glucagon, free fatty acids, ketones and urea. The lactating women had lower carbohydrate oxidation but higher fat and protein oxidation and increased glucose production by higher gluconeogenesis. The present study concluded that the lactating women as compared to the non-lactating women are at risk for fasting hypoglycemia if fasting is extended beyond 30h. Although milk production and composition were preserved, fasted lactating women were more metabolically stressed and subjected to protein and fat loss.
Little is known about how lactating women accommodate for their increased glucose demands during fasting to avoid maternal hypoglycemia. The objective of this study was to determine whether lactating women conserve plasma glucose by reducing maternal glucose utilization by increasing utilization of FFA, and ketone bodies and/or increasing gluconeogenesis and mammary gland hexoneogenesis. Six healthy exclusively breastfeeding women and six non-lactating controls were studied during 42 h of fasting and 6 h of re-feeding. Glucose and protein kinetic parameters were measured using stable isotopes, GCMS, and energy expenditure and substrate oxidation using indirect calorimetry. After 42 h of fasting, milk production decreased by 16% but remained within normal range. Glucose, insulin, and C-peptide concentrations decreased with the duration of fasting in both groups but were lower (P < 0.05) in lactating women. Glucagon, FFA, and beta-hydroxybutyrate concentrations increased with fasting time (P < 0.001) and were higher (P < 0.0001) in lactating women during both fasting and re-feeding. During 42 h of fasting, gluconeogenesis was higher in lactating women compared with non-lactating controls (7.7 +/- 0.4 vs. 6.5 +/- 0.2 umol.kg–1.min–1, P < 0.05), whereas glycogenolysis was suppressed to similar values (0.4 +/- 0.1 vs. 0.9 +/- 0.2 umol.kg–1.min–1, respectively). Mammary hexoneogenesis did not increase with the duration of fasting. Carbohydrate oxidation was lower and fat and protein oxidations higher (P < 0.05) in lactating women. In summary, lactating women are at risk for hypoglycemia if fasting is extended beyond 30 h. The extra glucose demands of extended fasting during lactation appear to be compensated by increasing gluconeogenesis associated with ketosis, decreasing carbohydrate oxidation, and increasing protein and FFA oxidations.