Mechanisms to conserve glucose in lactating women during a 42-h fast

Abstract

Mohammad MA, Sunehag AL, Chacko SK, Pontius AS, Maningat PD, Haymond MW. Mechanisms to conserve glucose in lactating women during a 42-h fast. Am J Physiol Endocrinol Metab 297: E879 -E888, 2009. First published August 4, 2009 doi:10.1152/ajpendo.00364.2009Little 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 nonlactating controls were studied during 42 h of fasting and 6 h of refeeding. Glucose and protein kinetic parameters were measured using stable isotopes and 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 Ͻ 0.05) in lactating women. Glucagon, FFA, and ␤-hydroxybutyrate concentrations increased with fasting time (P Ͻ 0.001) and were higher (P Ͻ 0.0001) in lactating women during both fasting and refeeding. During 42 h of fasting, gluconeogenesis was higher in lactating women compared with nonlactating controls (7.7 Ϯ 0.4 vs. 6.5 Ϯ 0.2 mol⅐kg Ϫ1 ⅐min Ϫ1, P Ͻ 0.05), whereas glycogenolysis was suppressed to similar values (0.4 Ϯ 0.1 vs. 0.9 Ϯ 0.2 mol⅐kg Ϫ1 ⅐min Ϫ1 , respectively). Mammary hexoneogenesis did not increase with the duration of fasting. Carbohydrate oxidation was lower and fat and protein oxidations higher (P Ͻ 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. stable isotopes; gluconeogenesis; lactation; milk; production USING NEW TECHNIQUES TO MEASURE GLUCONEOGENESIS in vivo, we (4,12,18,30) and others (13, 15) demonstrated that gluconeogenesis accounts for ϳ50% (ranging from 35 to 75%) of glucose production following an overnight fast. During carbohydrate (CHO) absorption, plasma glucose and insulin concentrations increase simultaneously, but plasma glucose concentrations remain in a very narrow range in normal individuals. This fine control is mediated by glucose-induced increase in plasma insulin, leading to increasing peripheral glucose utilization and glycogen synthesis, whereas hepatic glucose production is decreasing as a result of inhibited glycogenolysis (22). In contrast, during fasting, plasma glucose and insulin concentrations decrease and plasma FFA, ketone bodies, and glucagon concentrations increase (22), resulting in decreased glucose utilization and/or potentially increased glu...

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“…The lack of a truly parallel relationship between the expression of glucose transporters (5/8) and the increase in lactose synthesis suggests that glucose transport per se is not a rate-limiting step for lactose synthesis in humans. Although glucose availability may be critical only in animals with high demand for lactation (e.g., rodents), this may not be the case in humans, because the relative demand is low and women have significant potential reserves (diet, glycogen, hexoneogenesis, and gluconeogenesis) (15,32).…”

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“…During feeding, hexoneogenesis contributes 20% of the carbon in lactose (10 and 30% of glucose and galactose, respectively) (20,26,27). Over a 14-to 42-h fast, hexoneogenesis increases to account for ϳ40% of lactose production (ϳ30% of glucose and ϳ50% of galactose) (18,20,21,26,27). However, the precursor carbon source for hexoneogenesis remains largely unknown.…”

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