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

Abstract

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 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 < 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 refeeding. During 42 h of fasting, gluconeogenesis was higher in lactating women compared with nonlactating controls (7.7 +/- 0.4 vs. 6.5 +/- 0.2 micromol kg(-1) min(-1), P < 0.05), whereas glycogenolysis was suppressed to similar values (0.4 +/- 0.1 vs. 0.9 +/- 0.2 micromol 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.

Fig. 1.

Mean ± SE concentrations of plasma glucose, insulin, C-peptide, and glucagon in the nonlactating (□; n = 6) and lactating (▪; n = 6) women during the fasting (left) and refeeding (right) states. Statistics were carried out using repeated-measures ANOVA denoting differences over time (A), differences between groups (B), and difference due to interaction of group and time (AB).

Fig. 2.

Mean ± SE plasma concentrations of lactate in the nonlactating (□; n = 6) and lactating (▪; n = 6) women during fasting and refeeding. Statistics were carried out using repeated-measures ANOVA denoting differences over time (A), differences between groups (B), and difference due to interaction of group and time (AB). BUN, blood urea nitrogen; FFA, free fatty acids; β-OH-BT, β-hydroxybutyrate.

Fig. 3.

Rates of glucose appearance, glucose production, gluconeogenesis, and glycogenolysis in the nonlactating (□) and the lactating (▪) women following 14 and 42 h of fasting and 6 h of refeeding. Values are means ± SE. All parameters are expressed as μmol·kg⁻¹·min⁻¹. All calculations are based on total body weight (kg). *P (nonpaired) < 0.05; **P (nonpaired) < 0.01, nonlactating (n = 6) vs. lactating (n = 6) women.

Fig. 4.

Rates of appearance of leucine and urea and rates of proteolysis, protein oxidation, and synthesis in the nonlactating (□) and the lactating (▪) women following 14 and 42 h of the fasting and 6 h of refeeding. Values are means ± SE. All calculations are based on total body weight (kg). *P (nonpaired) < 0.05; **P (nonpaired) < 0.01, controls (n = 6) vs. lactating (n = 6) women.