Lower Insulin Secretory Response to Glucose Induced by Artificial Nutrition in Children: Prolonged and Total Parenteral Nutrition

Abstract

Long-term parenteral nutrition (TPN) in children is associated with sustained hyperinsulinemia due to a high nutriment infusion flow 12 h/24 h, with plausible lipotoxicity secondary to repeated lipid infusions and with changes in incretin hormone release. The aim of this study was to test whether long-term TPN can lead to an alteration in ␤-cell function. Thirteen children (age 9.5 Ϯ 3.9 y) on total TPN without obvious alternation in glucose tolerance were included. ␤-Cell function was quantified with an intravenous glucose tolerance test (IVGTT) and a graded glucose infusion. R isk factors for type 2 diabetes have been well identified for years. Among them, lipotoxicity, chronic hyperinsulinemia, and alteration in the enteroinsular axis have been debated (1-3). Clinical situations, such long-term long-term parenteral nutrition (TPN), encompassing these metabolic conditions are not frequently studied. In theory, they could lead to alteration in glucose homeostasis or insulin release. In one pediatric cohort followed in two children's hospitals in Paris, the appearance of some cases of chronic and unremitting hyperglycemia during infusion, requiring insulin, suggested that TPN could promote glucose homeostasis disorders.In examples like intestinal mucosa deficiency or neonatal extended intestinal resections, TPN has dramatically changed the prognosis (4,5). Adequate nutrition is now provided to these children as daily home care. However, TPN is a nonphysiologic route of nutrient delivery. Nutrient mixtures are infused nightly over 10 -14 h in sick children in whom caloric needs are equal or greater than in healthy children. High glucose and insulin secretagogue nutrients induce chronic hyperinsulinemia lasting approximately 12 h per day (6). High lipid infusion rates could promote peripheral and central lipotoxicity. Moreover, some intestinal diseases have been shown to be associated with an alternation in incretin hormone release (7).Insulin release in children on TPN was evaluated in one study 10 y ago (8). It was measured during an intravenous glucous tolerance test (IVGTT) and a hyperglycemic clamp. No obvious alterations in insulin release were observed. Patients had an insulin response to IVGTT similar to that of control children of the same age. Insulin release was greater than that in healthy young adults during a hyperglycemic clamp. However, patients were not observed among standardized metabolic conditions. Many of them were not totally dependent on TPN. Indeed, ␤-cell failure could not be reported there.The aim of the study was to test whether metabolic conditions associated with long-term TPN could lead to an alteration ␤-cell function before any obvious alteration in glucose tolerance. METHODSPatients. Thirteen children on long-term TPN were included. Inclusion criteria were the following: children on PN since birth and for at least 5 y, Ͼ80% of their daily caloric intake via the parenteral route, no obvious alternation in glucose tolerance as defined by fasting glycemia (before the beginn...

Chronic Parenteral Nutrition Induces Hepatic Inflammation, Steatosis, and Insulin Resistance in Neonatal Pigs1–3

“…Sections were visualized using a laser scanning microscope (Olympus Fluoview FV 300). Multiple images (15)(16)(17)(18)(19)(20) Hepatic inflammatory gene expression. Quantitative realtime PCR was performed as described (37).…”

“…Minimal enteral feeding accelerates the maturation of gastrointestinal function and the tolerance to full enteral feeding of premature and VLBW infants and thereby reduces the duration of hospitalization (16). Few studies have examined the effect of enteral compared with PN on glucose tolerance and utilization in neonates, but 1 report suggests that chronic PN leads to impaired insulin secretory response (17). Under normal enteral feeding conditions, the gut and liver remove a significant amount (30-40%) of the dietary glucose load by first-pass metabolism (18)(19)(20).…”

Prevention and Treatment of Intestinal Failure-Associated Liver Disease in Children

“…Energy from carbohydrates should be balanced, since animal models and clinical experiences have demonstrated that increased carbohydrate-mediated energy could expose patients to hyperinsulinism and the risk of hepatic steatosis [ 68 , 69 ]. Nevertheless, a word of caution is necessary, because a recent study showed that high-carbohydrate and low-fat parenteral nutrition could reverse IFALD in children [ 70 ].…”

Enhanced oral bioavailability of vancomycin in rats treated with long-term parenteral nutrition

“…Parenteral nutrition (PN) serves as a critical therapy for patients in conditions where oral ingestion is not adequate. In spite of its usefulness, there are also many possible complications, such as catheter-related bloodstream infection (Hvas et al 2014 ), impaired glucose tolerance (Beltrand et al 2007 ), and parenteral nutrition-associated liver disease (Nandivada et al 2013 ). In addition, long-term PN administration can induce intestinal atrophy; the reduction of the mucosal barrier may mediate bacterial translocation (BT), in which the intestinal bacteria and/or their toxic products invade the bloodstream and induce production of inflammatory cytokines, subsequently leading to sepsis and multiple organ failure (Hatakeyama and Matsuda 2014 ; Li et al 1999 ; Sun et al 2006 ).…”