Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile

Abstract

-In preterm infants, both hypo-and hyperglycemia are a frequent problem. Intravenous lipids can affect glucose metabolism by stimulation of gluconeogenesis by providing glycerol, which is a gluconeogenic precursor, and/or free fatty acids (FFA), which are stimulants of the rate of gluconeogenesis. In 25 preterm infants, glucose production and gluconeogenesis were measured using stable isotope techniques during a 6-h infusion of glucose only, glucose plus glycerol, or glucose plus an intravenous lipid emulsion. Two lipid emulsions differing in FFA composition were used: Intralipid (ϳ60% polyunsaturated FFA) and Clinoleic (ϳ60% monounsaturated FFA). The rate of glucose infusion was 22 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 in all groups. During the study infusion, the FFA concentrations were higher in both lipid groups vs. the glycerol group (P Ͻ 0.001). Compared with baseline, the glucose production rate increased in the Intralipid group, whereas it decreased in the other groups (P ϭ 0.002) due to a significant increase in gluconeogenesis in the Intralipid group (P ϭ 0.016). The plasma glucose concentration was significantly higher during Intralipid infusion vs. the other groups (P ϭ 0.046). Our conclusion was that Intralipid enhanced glucose production by increasing gluconeogenesis in preterm infants. This can be ascribed to the stimulatory effect of FFA in addition to any effect of glycerol alone. The lack of stimulation of gluconeogenesis in the Clinoleic vs. the Intralipid group suggests that different classes of fatty acids exert different effects on glucose kinetics in preterm infants.glycerol; fatty acids unsaturated; stable isotopes; mass isotopomer distribution analysis IN PRETERM INFANTS, disturbances in glucose metabolism are a frequent problem. Both hypo-and hyperglycemia can occur (20). Hypoglycemia occurs mostly in the first days after birth. Despite routine intravenous glucose supply, the incidence of hypoglycemia is still ϳ20% in our Neonatal Intensive Care Unit, a referral unit for infants Ͻ32 wk gestational age. Besides hypoglycemia, hyperglycemia is a mounting phenomenon in neonatal medicine, especially in sick and/or low-birth-weight infants.Free fatty acids (FFA) could play a role in the pathophysiology of both hypo-and hyperglycemia, because they are well-known stimulants of the rate of gluconeogenesis (11).Because plasma FFA concentrations in preterm infants are much lower than in adults (18,19,49), the lack of FFA could be involved in restricted capacity for gluconeogenesis, predisposing these infants for hypoglycemia. On the other hand, very preterm infants routinely receive parenteral nutrition (including gradually increasing amounts of lipids) because enteral nutrition is not tolerated in sufficient amounts. Intravenous lipid emulsions contain FFA and could, therefore, play a role in the pathophysiology of hyperglycemia in preterm infants, a mechanism comparable with those described in adults with diabetes (11).In healthy postabsorptive adults, FFA stimulate gluconeogenesis with a concomitant decrease in...

Short Bowel Syndrome in the NICU

“…About 50% of the fatty acids present in soy-based formulations are the omega-6 polyunsaturated fatty acids such as linoleic acid, which is a cause of concern because linoleic acid may have immunosuppressive and pro-inflammatory effects (55). Soy lipid formulations have also been linked to impaired glucose homeostasis, where gluconeogenesis was increased but the normal reduction in glycogenolysis was inhibited (75). …”

Lipids for parenteral nutrition in neonates

“…Soybean oil-based lipid emulsions have been shown to enhance glucose production via gluconeogenesis and glycogenolysis [25], which may contribute to impaired glucose tolerance in very preterm neonates necessitating a reduction in glucose concentration in parenteral nutrition and thereby reducing total caloric intake. Studies in preterm infants have documented higher total carbohydrate intake in the olive oil group supporting the evidence of impaired glucose tolerance with soybean oil emulsions [22 ].…”

Olive oil in parenteral nutrition

“…ClinOleic represents an alternative to soybean oil based emulsions because it reduces the supply of linoleic acid. Randomized clinical trials have investigated the effect of ClinOleic compared with other lipid emulsions on the plasma fatty acid profile in preterm infants, infants aged 2 months to 3 years on TPN and children aged 1-9 years on home parenteral nutrition (HPN) ( Table 3) [36][37][38][39][40][41]42 ]. Eight-day infusions of ClinOleic in preterm infants increased plasma phospholipid oleic, linoleic, a-linolenic and g-linolenic acids and decreased plasma phospholipid arachidonic and docosahexaenoic acids [40].…”

“…Although premature infants are prone to disturbances in glucose metabolism, to our knowledge only one study has addressed this in terms of the fatty acid composition of infused emulsions. In an elegant study van Kempen et al [42 ] investigated glucose metabolism in premature infants with a postnatal age between 1 and 8 days, who were randomly assigned to receive either Olive oil in parenteral nutrition Sala-Vila et al 169 ClinOleic or Intralipid for 6 h. Infants allocated to Intralipid showed enhanced glucose production (and a higher blood glucose concentration) due to increased gluconeogenesis and maintenance of glycogenolysis. This suggests a dysregulation between glycogen metabolism and gluconeogenesis in infants receiving Intralipid that does not occur if ClinOleic is used.…”