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Title: Continuous parenteral and enteral nutrition induces metabolic dysfunction in neonatal pigs

item STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)
item PUIMAN, PATRYCIA - Erasmus Medical Center
item CUI, LIWEI - Children'S Nutrition Research Center (CNRC)
item CHANG, XIAOYAN - Children'S Nutrition Research Center (CNRC)
item BENIGHT, NANCY - Children'S Nutrition Research Center (CNRC)
item BAUCHART-THEVRET, CAROLINE - Children'S Nutrition Research Center (CNRC)
item HARTMAN, BOLETTE - University Of Copenhagen
item HOLST, JENS - University Of Copenhagen
item Burrin, Douglas - Doug

Submitted to: Journal of Parenteral and Enteral Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2012
Publication Date: 9/1/2012
Citation: Stoll, B., Puiman, P.J., Cui, L., Chang, X., Benight, N.M., Bauchart-Thevret, C., Hartman, B., Holst, J.J., Burrin, D.G. 2012. Continuous parenteral and enteral nutrition induces metabolic dysfunction in neonatal pigs. Journal of Parenteral and Enteral Nutrition. 36(5):538-550.

Interpretive Summary: Thousands of premature infants born in the United States every year are unable to handle normal oral (enteral) feeding, and instead receive parenteral (intravenous) nutrition (PN). Our previous studies using the neonatal piglet as a model of human premature infants showed that PN induces metabolic dysfunction. This dysfunction was marked by accumulation of fat in the liver and a condition of glucose intolerance known as insulin resistance. Insulin triggers cells to take up glucose from the blood and use it for energy and insulin resistance leads to increased blood glucose similar to what happens in adolescents who have type 2 diabetes. In this study we used neonatal piglets to further test how feeding patterns contribute to these metabolic dysfunctions. We compared piglets fed either intravenous or enteral nutrition, continuous or intermittent nutrition, or polymeric or elemental nutrition. The latter comparison tested normal cow's milk formula with a mixture of purified nutrients that were both match to the same nutritional content. Our results showed that the intermittent feeding pattern produced the optimum metabolic function and was more important than whether feeding occurred by enteral vs PN route. We also showed that feeding a polymeric vs. elemental nutrition resulted in improved insulin sensivity and greater stimulation of the gut. In addition, the optimal metabolic function was associated with increased secretion of key gut hormones that improve insulin sensitivity. These findings suggest that hospitalized premature infants should be given intermittent or bolus feedings during the early period after birth to maintain optimum metabolic function.

Technical Abstract: We previously showed that parenteral nutrition (PN) compared with formula feeding results in hepatic insulin resistance and steatosis in neonatal pigs. The current aim was to test whether the route of feeding (intravenous [IV] vs enteral) rather than other feeding modalities (diet, pattern) had contributed to the outcome. Neonatal pigs were fed enterally or parenterally for 14 days with 1 of 4 feeding modalities as follows: (1) enteral polymeric formula intermittently (FORM), (2) enteral elemental diet (ED) intermittently (IEN), (3) enteral ED continuously (CEN), and (4) parenteral ED continuously (PN). Subgroups of pigs underwent IV glucose tolerance tests (IVGTT) and hyperinsulinemic-euglycemic clamps (CLAMP). Following CLAMP, pigs were euthanized and tissues collected for further analysis. Insulin secretion during IVGTT was significantly higher and glucose infusion rates during CLAMP were lower in CEN and PN than in FORM and IEN. Endogenous glucose production rate was suppressed to zero in all groups during CLAMP. In the fed state, plasma glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide (GLP)–1, and GLP-2 were different between feeding modalities. Insulin receptor phosphorylation in liver and muscle was decreased in IEN, CEN, and PN compared with FORM. Liver weight was highest in PN. Steatosis and myeloperoxidase (MPO) activity tended to be highest in PN and CEN. Enterally fed groups had higher plasma GLP-2 and jejunum weight compared with PN. PN and enteral nutrition (EN) when given continuously as an elemental diet reduces insulin sensitivity and the secretion of key gut incretins. The intermittent vs continuous pattern of EN produced the optimal effect on metabolic function.