Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus

Abstract

This article reviews maternal metabolic strategies for accommodating fetal nutrient requirements in normal pregnancy and in gestational diabetes mellitus (GDM). Pregnancy is characterized by a progressive increase in nutrient-stimulated insulin responses despite an only minor deterioration in glucose tolerance, consistent with progressive insulin resistance. The hyperinsulinemic-euglycemic glucose clamp technique and intravenous-glucose-tolerance test have indicated that insulin action in late normal pregnancy is 50-70% lower than in nonpregnant women. Metabolic adaptations do not fully compensate in GDM and glucose intolerance ensues. GDM may reflect a predisposition to type 2 diabetes or may be an extreme manifestation of metabolic alterations that normally occur in pregnancy. In normal pregnant women, basal endogenous hepatic glucose production (R(a)) was shown to increase by 16-30% to meet the increasing needs of the placenta and fetus. Total gluconeogenesis is increased in late gestation, although the fractional contribution of total gluconeogenesis to R(a), quantified from (2)H enrichment on carbon 5 of glucose (65-85%), does not differ in pregnant women after a 16-h fast. Endogenous hepatic glucose production was shown to remain sensitive to increased insulin concentration in normal pregnancy (96% suppression), but is less sensitive in GDM (80%). Commensurate with the increased rate of glucose appearance, an increased contribution of carbohydrate to oxidative metabolism has been observed in late pregnancy compared with pregravid states. The 24-h respiratory quotient is significantly higher in late pregnancy than postpartum. Recent advances in carbohydrate metabolism during pregnancy suggest that preventive measures should be aimed at improving insulin sensitivity in women predisposed to GDM. Further research is needed to elucidate the mechanisms and consequences of alterations in lipid metabolism during pregnancy.

Effect of placental function on fatty acid requirements during pregnancy

“…A metabolic cost that has to be met before any DHA is available to the fetus is the obligatory loss of DHA during normal fatty acid oxidation in the mother and fetus. The theoretical rate of oxidation can be calculated from the rate of maternal energy expenditure (9453 MJ/day (Butte, 2000)), the proportion of that energy derived from fat (30% (Butte, 2000)) and the energy content of fat (39 kJ/g). The final part of the calculation, and the most difficult to estimate, requires information on the proportion of DHA in the oxidised fat.…”

“…Figure 2 Fatty acids may be found in the blood and tissues linked to other molecules by ester bonds; triglyceride (TG), phospholipid (PL) and cholesterol ester (CE); or as non-esterified fatty acids NEFA. AA and DHA as a proportion of total fatty acids are shown for the diet of pregnant mothers (Lakin et al, 1998), 1 the adipose tissue (Leaf et al, 1995), 2 maternal and cord blood plasma phospholipids (Otto et al, 1997), 3 triglyceride (Berghaus et al, 2000), 4 cholesterol ester (Hoving et al, 1994), 5 and NEFA (Benassayag et al, 1999), 6 the placental microvillous and basal membranes (Powell et al, 1999), 7 and adipose tissue and brain at birth (Clandinin et al, 1981 Figure 3 The theoretical rate of oxidation was calculated from the rate of maternal energy expenditure (9453 MJ/day), the proportion of that energy derived from fat (30%), the energy content of fat (39 kJ/g) (Butte, 2000) and the proportion of DHA in the oxidised fat (0.1% DHA; Figure 2). The DHA content of fetal tissues was calculated from the lean mass (calculated as body weight minus the weight of fat, skeleton and skin (Widdowson, 1974)), the fat mass (Widdowson, 1974) and the weight of the placenta (Hytten, 1974) and brain (Clandinin et al, 1980) and the fat and DHA concentration of the brain (Clandinin et al, 1980;Jamieson et al, 1999), placenta (Widdowson & Spray, 1951;Lakin et al, 1998) and adipose tissue (Clandinin et al, 1981).…”

“…Although the net loss of maternal fat is small, the very high fasting lipid levels suggest that the maternal stores are turning over much faster than in the nonpregnant state. Also, the overall proportion of fat oxidised at this time appears to be reduced in the pregnant mother (Butte, 2000) implying that the purpose of this mobilisation is to provide fatty acids for the fetus. The maternal circulating concentrations of triacylglycerol (TG) (Darmady & Postle, 1982), phospholipids (PL) and nonesterified fatty acid (NEFA) (McDonald et al, 1975), all increase throughout gestation ( Figure 5) and this is particularly striking for maternal TG, which increases 2.5-fold over the course of gestation (Darmady & Postle, 1982).…”

Many ways to die, one way to arrive: how selection acts through pregnancy

“…The many physiological compromises of pregnancy make it a tremendous challenge for both mothers and infants and a potential selective force. In order to provide for the growing fetus, mothers increase blood sugar [2], blood volume, and hemoglobin count [3]; remodel uterine arteries [4]; and decrease vascular resistance [5]. These changes put the mother at risk of diabetes, high blood pressure, strokes, hemorrhaging, and seizures [2, 6--8].…”

Physiological changes in pregnancy

“…30 Insulin-secreting pancreatic beta-cells undergo hyperplasia, resulting in increased insulin secretion and increased insulin sensitivity in early pregnancy, followed by progressive insulin resistance. 31 Maternal insulin resistance begins in the second trimester and peaks in the third trimester. This is the result of increasing secretion of diabetogenic hormones such as human placental lactogen, growth hormone, progesterone, cortisol and prolactin.…”