Lipid Infusion Research Articles

L-carnitine infusion does not alleviate lipid-induced insulin resistance and metabolic inflexibility.

BackgroundLow carnitine status may underlie the development of insulin resistance and metabolic inflexibility. Intravenous lipid infusion elevates plasma free fatty acid (FFA) concentration and is a model for simulating insulin resistance and metabolic inflexibility in healthy, insulin sensitive volunteers. Here, we hypothesized that co-infusion of L-carnitine may alleviate lipid-induced insulin resistance and metabolic inflexibility.MethodsIn a randomized crossover trial, eight young healthy volunteers underwent hyperinsulinemic-euglycemic clamps (40mU/m2/min) with simultaneous infusion of saline (CON), Intralipid (20%, 90mL/h) (LIPID), or Intralipid (20%, 90mL/h) combined with L-carnitine infusion (28mg/kg) (LIPID+CAR). Ten volunteers were randomized for the intervention arms (CON, LIPID and LIPID+CAR), but two dropped-out during the study. Therefore, eight volunteers participated in all three intervention arms and were included for analysis.ResultsL-carnitine infusion elevated plasma free carnitine availability and resulted in a more pronounced increase in plasma acetylcarnitine, short-, medium-, and long-chain acylcarnitines compared to lipid infusion, however no differences in skeletal muscle free carnitine or acetylcarnitine were found. Peripheral insulin sensitivity and metabolic flexibility were blunted upon lipid infusion compared to CON but L-carnitine infusion did not alleviate this.ConclusionAcute L-carnitine infusion could not alleviated lipid-induced insulin resistance and metabolic inflexibility and did not alter skeletal muscle carnitine availability. Possibly, lipid-induced insulin resistance may also have affected carnitine uptake and may have blunted the insulin-induced carnitine storage in muscle. Future studies are needed to investigate this.

Follistatin-like 1 as a Novel Adipomyokine Related to Insulin Resistance and Physical Activity.

Follistatin-like protein-1 (FSTL-1) is considered to be an adipokine or myokine that could be a potential regulator of metabolism. Our purpose is to investigate the relationship between circulating FSTL-1 levels and insulin resistance (IR) in type 2 diabetes mellitus (T2DM) and to identify the regulatory factors. FSTL-1 expression in C57BL/6J and db/db mice was examined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blots. Serum FSTL-1 levels were measured by enzyme-linked immunosorbent assay in 298 T2DM patients and 202 healthy controls. Changes in the circulating FSTL-1 level were observed during the oral glucose tolerance test, EHC (euglycemic-hyperinsulinemic clamp), lipid infusion, acute exercise, and cold-exposure test. We found that FSTL-1 protein expression in the adipose tissue of db/db mice was significantly higher than that of wild-type mice. Importantly, circulating FSTL-1 levels in T2DM and overweight/obese participants were higher than those in healthy and lean individuals, and was related to HOMA-IR, adiponectin, and obesity- and metabolism-related parameters. In the intervention study, 45 minutes of physical activity was found to significantly increase the circulating FSTL-1 concentration in young, healthy participants. Further, FSTL-1 protein expression in adipose tissue rose dramatically in response to physical activity in mice. Hyperinsulinemia during EHC and acute elevated FFA induced by lipid infusion resulted in a significant decrease in the circulating FSTL-1 levels. However, no change was found in the circulating FSTL-1 levels in response to the oral glucose challenge or cold-exposure test. FSTL-1 may be an adipomyokine associated with insulin resistance and physical activity, and circulating FSTL-1 levels are increased in patients with T2DM.

P43 Concentrated standardised PN to optimise nutrition in preterm infants

BackgroundIn 2010, the NCEPOD1 report demonstrated a lack of good nutritional care for preterm infants. Since that time various approaches have evolved including standardisation of PN,2 concentrated standardised PN3 and publication of a national framework from BAPM.4 The delivery of nutrition to preterm infants on our unit has been continuously monitored, evaluated and adapted.AimsThe aim of this audit was to evaluate whether reformulating our PN recipes would improve nutritional intake and thus growth parameters over the first 14 days after birth.MethodsData was collected from our EPMA system and analysed retrospectively from all infants born at our unit <28 weeks gestation or <1Kg from 16/4/2016 to 15/4/2017 (audit 1) and from 1/6/2018 to 31/5/2019 (audit 2).ResultsData from a total of 33 patients was analysed using Excel™. The mean gestation and weight were similar for both audit cycles. Audit 1: gestation 26.5 weeks, weight 0.75 kg; audit 2: gestation 26.7 weeks, weight 0.74 kg. The average time from birth to PN was less in audit 2 (12 hrs 8 mins vs 13 hrs 12 mins), however the time from PN being prescribed to being administered took over 3 times longer (5 hrs 1 min vs 1 hr 30 mins). No patient received PN within 6 hours of birth in audit 2 compared to 20% in audit 1. The average nitrogen intake was higher in audit 2 than audit 1 (0.41 g/kg/day vs 0.36 g/kg/day) and the highest protein intake increased from 0.55 g/kg/day to 0.69 g/kg/day respectively; the average energy intake decreased from 73.5 kcal/kg/day in audit 1 to 68 kcal/kg/day in audit 2. The non-nitrogen energy to nitrogen ratio was lower in audit 2 versus audit 1 (165.3 kcal/g nitrogen vs 204.7 kcal/g nitrogen). There was no change in the percentage of patients requiring insulin: 40%. More patients had started receiving lipid infusion in the first 2 days after birth in audit 2 compared to audit 1 (94% compared to 33%). Both audits had 2 patients that had still not reached their birth weight by day 14, however the patients in audit 2 gained on average 9.12 g/kg/day compared to 4.96 g/kg/day in audit 1.ConclusionReformulating the PN resulted in higher nitrogen intakes and higher weight gain by day 14, although the full benefit may not have been achieved due to the lower kcal intake and non-nitrogen energy to nitrogen ratio. The time from birth to PN and the time taken to administer PN once prescribed were longer so work needs to be done on addressing these issues and reducing barriers to nutrition. The total nitrogen intake with PN and EN also needs to be reviewed to prevent excessive nitrogen intake which may result if enteral feeds increase and the rate of PN is maintained.ReferencesStewart JAD, Mason DG, Smith N, Protopapa K, Mason N, on behalf of CEPOD. 2010. A mixed bag; an enquiry into the care of hospital patients receiving parenteral. https://www.ncepod.org.uk/2010report1/downloads/PN_report.pdf Accessed 03/07/2019Paediatric Chief Pharmacists Group. Improving Practice and Reducing Risk in the Provision of Parenteral Nutrition for Neonates and Children. 2011Morgan C, Radbone L, Birch J. 2016 The Neonatal Parenteral Nutrition (PN) QIPP Toolkit https://www.networks.nhs.uk/nhs-networks/staffordshire-shropshire-and-black-country-newborn/documents/documents/national-toolkit-for-standardising-pn Accessed 03/07/2019British Association of Perinatal Medicine. The Provision of Parenteral Nutrition within Neonatal Services – A Framework for Practice. 2016. https://www.bapm.org/sites/default/files/files/Parenteral%20Nutrition%20April%202016.pdf Accessed 03/07/2019

Evaluating acute inflammation's effects on hepatic triglyceride content in experimentally induced hyperlipidemic dairy cows in late lactation

Inflammation appears to be a predisposing factor and key component of hepatic steatosis in a variety of species. Objectives were to evaluate effects of inflammation [induced via intravenous lipopolysaccharide (LPS) infusion] on metabolism and liver lipid content in experimentally induced hyperlipidemic lactating cows. Cows (765 ± 32 kg of body weight; 273 ± 35 d in milk) were enrolled in 2 experimental periods (P); during P1 (5 d), baseline data were obtained. At the start of P2 (2 d), cows were assigned to 1 of 2 treatments: (1) intralipid plus control (IL-CON; 3 mL of saline; n = 5) or (2) intralipid plus LPS (IL-LPS; 0.375 μg of LPS/kg of body weight; n = 5). Directly following intravenous bolus (saline or LPS) administration, intralipid (20% fat emulsion) was intravenously infused continuously (200 mL/h) for 16 h to induce hyperlipidemia during which feed was removed. Blood samples were collected at -0.5, 0, 4, 8, 12, 16, 24, and 48 h relative to bolus administration, and liver biopsies were obtained on d 1 of P1 and at 16 and 48 h after the bolus. By experimental design (feed was removed during the first 16 h of d 1), dry matter intake decreased in both treatments on d 1 of P2, but the magnitude of reduction was greater in LPS cows. Dry matter intake of IL-LPS remained decreased on d 2 of P2, whereas IL-CON cows returned to baseline. Milk yield decreased in both treatments during P2, but the extent and duration was longer in LPS-infused cows. Administering LPS increased circulating LPS-binding protein (2-fold) at 8 h after bolus, after which it markedly decreased (84%) below baseline for the remainder of P2. Serum amyloid A concentrations progressively increased throughout P2 in IL-LPS cows (3-fold, relative to controls). Lipid infusion gradually increased nonesterified fatty acids and triglycerides in both treatments relative to baseline (3- and 2.5-fold, respectively). Interestingly, LPS infusion blunted the peak in nonesterified fatty acids, such that concentrations peaked (43%) higher in IL-CON compared with IL-LPS cows and heightened the increase in serum triglycerides (1.5-fold greater relative to controls). Liver fat content remained similar in IL-LPS relative to P1 at 16 h; however, hyperlipidemia alone (IL-CON) increased liver fat (36% relative to P1). No treatment differences in liver fat were observed at 48 h. In IL-LPS cows, circulating insulin increased markedly at 4 h after bolus (2-fold relative to IL-CON), and then gradually decreased during the 16 h of lipid infusion. Inducing inflammation with simultaneous hyperlipidemia altered the characteristic patterns of insulin and LPS-binding protein but did not cause fatty liver.

972-P: Liraglutide Attenuates Lipid-Induced Microvascular Insulin Resistance in Humans

Insulin recruits skeletal and cardiac muscle microvasculature to increase insulin and nutrient delivery, but this action is lost in insulin resistant states. Glucagon-like peptide 1 (GLP-1) improves microvascular perfusion in humans with obesity and the GLP-1 receptor agonist liraglutide attenuates muscle microvascular insulin resistance (IR) in rodents. To examine whether GLP-1 receptor agonism improves insulin’s microvascular actions in humans with acute IR, 18 healthy human subjects randomly received a systemic infusion of either saline or lipid emulsion (20%, 45 mL x 1 h and then 30 mL x 4 h) for 5 h or lipid emulsion for 5 h + liraglutide pre-treatment (0.6, 1.2, then 1.8 mg daily SC each x 2 days) with euglycemic insulin clamp (1 mU/kg/min) superimposed for the last 120 min. Skeletal and cardiac muscle microvascular blood volume (MBV), flow-mediated dilation (FMD), pulse wave velocity (PWV), and augmentation index (AI) were determined before and after insulin clamp. Compared with saline admission, insulin failed to increase MBV following lipid infusion in both skeletal (28.4 ± 14.1% vs. -1.3 ± 9.6% respectively, p=0.011) and cardiac (28.4 ± 14.1% vs. -1.3 ± 8.9%, p=0.027) muscle, consistent with acute IR induced by lipid infusion in both microvascular beds. Liraglutide pre-treatment improved insulin-mediated increases in MBV in the presence of lipid infusion in skeletal (8.9 ± 13.5%, p=0.117 vs. saline) and cardiac (12.6 ± 12.1%, p=0.101 vs. saline) muscle. There was no significant change in PWV, AI, or FMD amongst admissions. Glucose infusion rates were not significantly different amongst admissions (saline 6.02 ± 0.52, lipid 5.58 ± 0.62, vs. liraglutide + lipid 5.46 ± 0.46 mg/kg/min). In conclusion, liraglutide pretreatment effectively ameliorates lipid-induced skeletal and cardiac muscle microvascular IR in healthy humans. These data provide a mechanistic insight into the metabolic and cardiovascular benefits of GLP-1 receptor agonism seen in humans with obesity and type 2 diabetes. Disclosure K. Love: None. L. Jahn: None. L. Hartline: None. Z. Liu: None. Funding American Diabetes Association (1-17-ICST-059 to Z.L.); National Institutes of Health (1R01DK102359-01A1)

One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension

Aims/hypothesisPhysical inactivity, low mitochondrial function, increased intramyocellular lipid (IMCL) deposition and reduced insulin sensitivity are common denominators of chronic metabolic disorders, like obesity and type 2 diabetes. Yet, whether low mitochondrial function predisposes to insulin resistance in humans is still unknown.MethodsHere we investigated, in an intervention study, whether muscle with low mitochondrial oxidative capacity, induced by one-legged physical inactivity, would feature stronger signs of lipid-induced insulin resistance. To this end, ten male participants (age 22.4 ± 4.2 years, BMI 21.3 ± 2.0 kg/m2) underwent a 12 day unilateral lower-limb suspension with the contralateral leg serving as an active internal control.ResultsIn vivo, mitochondrial oxidative capacity, assessed by phosphocreatine (PCr)-recovery half-time, was lower in the inactive vs active leg. Ex vivo, palmitate oxidation to 14CO2 was lower in the suspended leg vs the active leg; however, this did not result in significantly higher [14C]palmitate incorporation into triacylglycerol. The reduced mitochondrial function in the suspended leg was, however, paralleled by augmented IMCL content in both musculus tibialis anterior and musculus vastus lateralis, and by increased membrane bound protein kinase C (PKC) θ. Finally, upon lipid infusion, insulin signalling was lower in the suspended vs active leg.Conclusions/interpretationTogether, these results demonstrate, in a unique human in vivo model, that a low mitochondrial oxidative capacity due to physical inactivity directly impacts IMCL accumulation and PKCθ translocation, resulting in impaired insulin signalling upon lipid infusion. This demonstrates the importance of mitochondrial oxidative capacity and muscle fat accumulation in the development of insulin resistance in humans.Trial registrationClinicalTrial.gov NCT01576250.FundingPS was supported by a ‘VICI’ Research Grant for innovative research from the Netherlands Organization for Scientific Research (Grant 918.96.618).

Information on local anesthetics and toxicity for doctors in surgical department of Karadeniz Technical University Medical Faculty Hospital

Aim: Local anesthetics are commonly used in surgical interventions and anesthesia applications. The aim of this study was to increase the sensitivity of local anesthetic toxicity to the presence of symptoms, precautions to be taken and the use of 20% lipid infusion for treatment. Material and Methods: The questionnaire was applied on 160 of 205 physicians who were prescribed local anesthetics.Results: Of the 160 participants included in the study, 108 (67.5%) were research assistants, 47 (29.4%) were faculty members and the remaining 5 (3.1%) were expert medical practitioners. 63 of the participants (39.4%) had been working in the medical profession for more than 5 years. While 42.5% of the participants administered local anesthetics every day, 33.1% had not received any training in the area. On the basis of their training status, it was the anesthetists among specialist doctors who were the most trained in anesthetics with a statistically high rate of 86.3%. Thirty-three of the surveyed physicians (20.6%) who responded stated that they had experienced a case of local anesthetic toxicity previously. The most frequent answer to the question in early findings concerning local anesthetic toxicity was anaphylaxis (74.4%). 38.1% of the participants had not heard the use of 20% lipid solution in local anesthetic toxicity. Although there was 20% lipid solution in the university hospital where the research was conducted, 31.9% of the participants knew this.Conclusion: Although local anesthetic toxicity is rare, it frequently occurs in clinical practice. Therefore, physicians should have general knowledge regarding local anesthetic drugs, maximum doses, side effects, toxicity symptoms and the required treatment in the case of toxicity. We also think local anesthetic toxicity should be included in annual training programs and practical applications by other clinical branches that apply local anesthetic drugs as we currently do at our Clinic and physicians should be given appropriate guidance.

Effect of short-term administration of lipid emulsion on endothelial glycocalyx integrity in ICU patients - A microvascular and biochemical pilot study.

Endothelial glycocalyx (EG) is a carbohydrate-rich vascular lining of the apical surface of endothelial cells. It has been proved to have an essential role in vascular homeostasis. Lipid emulsions as part of parenteral nutrition (PN) are widely used in patients in the setting of critical care and perioperative medicine. Due to their structure, lipids may potentially interact with EG. The aim of the study was to evaluate the effect of lipid emulsion on EG. To assess the influence of lipid emulsion on EG integrity in ICU patients using a videomicroscopic and biochemical methods. Patients in surgical ICU after major abdominal surgery or cardio surgery and in general ICU were assessed for eligibility for this pilot observational study in University Hospital. The study was performed during the first day of adding lipids as a part of their PN. The patients were given the SMOFlipid 20% for 6 hours in prescribed dose of approx. 1 g/kg of body weight. EG integrity was measured indirectly by automated sublingual videomicroscopy calculating a parameter PBR which describes the amount of lateral deviation of red blood cells from the central column and by levels of syndecan-1 and syndecan-4 in plasma as EG degradational products. Measurements were performed before lipid administration (T0) and 30 minutes after (T6) the infusion of lipid emulsion was completed. The statistical analysis was performed at the level of significance p < 0.05, data are expressed as mean ± standard deviation (SD) and for PBR as median and interquartile range (IQR). Fifteen patients were studied, from them 9 included in final analysis. PBR (expressed in μm) increased after the lipid infusion with no statistical significance (T0 = 2.10; 1.97-2.33 vs. 2.28; 2.11-2.45, p = 0.13). At T6 both syndecans showed statistically significant decrease in their particular levels. Syndecan-1 at T0 = 2580±1013 ng/l, resp. at T6 = 2365±1077 ng/l, p = 0.02; syndecan-4 at T0 = 134±29 ng/l, resp. at T6 = 123±43 ng/l, p = 0.04. In our study, we showed that six hours long SMOFlipid 20% infusion had no detrimental effect on the EG integrity as assessed by PBR value and by syndecan-1 and syndecan-4 plasmatic levels. Observed decrease of syndecans shortly after lipid infusion allows us to hypothesize even possibly protecting effect of lipids on EG.

The effect of early versus late lipid infusion in parenteral nutrition on the biochemical and cortical auditory evoked potential parameters in preterm neonates

BackgroundAs brain activity depends greatly on the functions provided by lipid membranes, dietary fat in early life can affect the developing nervous system. Despite the adoption of an early more aggressive parenteral nutrition approach with amino acid infusions still reluctance to the early use of intravenous lipids in neonates.AimTo compare the effect of delayed versus early introduction of intravenous lipid in preterm on the biochemical parameters and on brain development by the cortical auditory evoked potential (CAEP) latency and amplitude.MethodsThis is a comparative study included 49 neonates admitted at the ain shams university NICUs. Participants were divided into two groups: 26 in group of early lipid infusion and 23 in late lipid infusion, Demographic data, and biochemical parameters were documented during the 1st 2 weeks of life. The CAEP was performed at age of 6 months. The latency and amplitude of P1 were recorded and compared between both groups.ResultsIn the present work we found that group of early lipid infusion had reach their full oral intake earlier with shorter duration of parenteral nutrition and length of stay. They had better weight gain and significantly better glucose level control than group of late lipid infusion. There was no significant difference in the other chemical parameters between both groups expect for the higher incidence of cholestasis in the group of late lipid infusion. At 6 months of age, the group of early lipid infusion had significantly shorter latency and amplitude of P1 than the group of late lipid infusion.ConclusionEarly effective nutrition positively affect feeding tolerance and weight gain and maturation of higher brain centers brain.

Athletes feature greater rates of muscle glucose transport and glycogen synthesis during lipid infusion.

BACKGROUNDInsulin resistance results from impaired skeletal muscle glucose transport/phosphorylation, linked to augmented lipid availability. Despite greater intramuscular lipids, athletes are highly insulin sensitive, which could result from higher rates of insulin-stimulated glycogen synthesis or glucose transport/phosphorylation and oxidation. Thus, we examined the time course of muscle glycogen and glucose-6-phosphate concentrations during low and high systemic lipid availability.METHODSEight endurance-trained and 9 sedentary humans (VO2 peak: 56 ± 2 vs. 33 ± 2 mL/kg/min, P < 0.05) underwent 6-hour hyperinsulinemic-isoglycemic clamp tests with infusions of triglycerides or saline in a randomized crossover design. Glycogen and glucose-6-phosphate concentrations were monitored in vastus lateralis muscles using 13C/31P magnetic resonance spectroscopy.RESULTSAthletes displayed a 25% greater (P < 0.05) insulin-stimulated glucose disposal rate (Rd) than sedentary participants. During Intralipid infusion, insulin sensitivity remained higher in the athletes (ΔRd: 25 ± 3 vs. 17 ± 3 μmol/kg/min, P < 0.05), supported by higher glucose transporter type 4 protein expression than in sedentary humans. Compared to saline infusion, AUC of glucose-6-phosphate remained unchanged during Intralipid infusion in athletes (1.6 ± 0.2 mmol/L vs. 1.4 ± 0.2 [mmol/L] × h, P = n.s.) but tended to decrease by 36% in sedentary humans (1.7 ± 0.4 vs. 1.1 ± 0.1 [mmol/L] × h, P < 0.059). This drop was accompanied by a 72% higher rate of net glycogen synthesis in the athletes upon Intralipid infusion (47 ± 9 vs. 13 ± 3 μmol/kg/min, P < 0.05).CONCLUSIONAthletes feature higher skeletal muscle glucose disposal and glycogen synthesis during increased lipid availability, which primarily results from maintained insulin-stimulated glucose transport with increased myocellular glucose-6-phosphate levels for subsequent glycogen synthesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01229059.FUNDINGGerman Federal Ministry of Health (BMG).

Practical management of home parenteral nutrition in infancy

The child born today with chronic intestinal failure (IF) can expect to survive throughout childhood and into adult life even if dependent on parenteral nutrition (PN) support.The three major aetiologies of chronic IF are short bowel syndrome (SBS), intestinal dysmotility and mucosal disease. SBS is the commonest of these conditions in infancy, most frequently subsequent to resection for necrotising enterocolits (NEC).The focus of IF management is to ensure appropriate weight gain and growth whilst minimising complications (related to underlying disease as well as to PN) and aiming for intestinal autonomy. Strategies to avoid complications and aid PN weaning include early oral/enteral feed introduction, ‘cycling’ PN as soon as tolerated, limiting lipid infusions and discharging home on overnight PN with formally trained parents. A newer treatment for SBS is GLP-2 analogue. Multidisciplinary care in a specialist intestinal rehabilitation centre with collaboration with local professional support is key to success.

TREATMENT OF ACUTE BUPROPRIONE TOXICITY WITH LIPID INFUSION AND PLASMAPHERESIS

SESSION TITLE: Plasmapheresis to the Rescue SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/21/2019 3:15 PM - 4:15 PM INTRODUCTION: Bupropion is an atypical antidepressant used to treat major depressive disorder and other psychiatric conditions. The toxic side effects of bupropion include seizures, tachycardia, arrhythmias, and death. These side effects are dose and formulary dependent. We describe a case of acute bupropion toxicity from a suicide attempt with symptoms, which was treated with Intralipid infusion along with serial plasmapheresis. CASE PRESENTATION: A 19-year-old male was transferred from an outside hospital for suicide attempt with ingestion of 40 tablets of 150 mg sustained released (SR) bupropion for a total dose of 9 gm. He was not a candidate for any activated charcoal. The patient developed tonic-clonic seizures and the decision was made to initiate a bolus of 140 mL of 20% Intralipid before and during transport. On admission to our hospital he developed status epilepticus and had QTc prolongation (467 and 487). He was started on 800 mL lipid infusion immediately followed by serial plasmapheresis. The triglyceride levels were closely monitored. The patient received a total of 940 mL (140 mL bolus plus 800 mL continuous infusion) of intralipid along with 3 sessions of plasmapheresis. He remained seizure free and his QTc normalized and was successfully extubated. DISCUSSION: Bupropion is a highly lipid soluble and protein-bound medication. Mild toxicity includes dry mouth, nausea, insomnia, dizziness. Life-threatening toxicities include seizure and arrhythmias. Seizures are generally seen with an overdose of bupropion. Ingestion of 4.5-9 g of bupropion increases the likelihood of seizures. Treatment is mostly symptomatic and with benzodiazepines. Lipid infusions can be used as lipid rescue therapy for acute cardiovascular collapses. The mechanism is the same as the use of lipid infusion as rescue therapy in case of local anesthetic, tricyclic antidepressants or serotonin-specific reuptake inhibitor toxicities. The proposed mechanism involves lipids from the infusion binding to the offending drug and pulling it from the target tissue preventing its accumulation and minimizing the toxic effects. Despite several reports there seem to be increased risks and compilations associated with lipid infusions like acute respiratory distress syndrome, hypertriglyceridemia, pancreatitis, and cardiac toxicity. There are not many reports of the use of plasmapheresis in a timely manner (depending on the half-life of the drug) for an SR drug after lipid infusion to promote removal of all the lipid molecules including those bound to the offending drug thereby preventing toxicity from the drug and lipid infusion as well. In our case combination of both helped in stabilizing and treating the patient. CONCLUSIONS: Use of lipid infusion in conjugation with plasmapheresis for the treatment of acute bupropion toxicity with symptoms allows safe use of lipid infusion and ensures complete removal of offending drug. Reference #1: Tolentino Stephanie; Gharpure, Varsha; Tsifansky, Michael Critical Care Medicine: December 2013 Reference #2: Intravenous lipid emulsion in clinical toxicology Leelach Rothschild,corresponding author1 Sarah Bern,1 Sarah Oswald,1 and Guy Weinbergcorresponding author1,2 DISCLOSURES: No relevant relationships by Praful Tewari, source=Web Response

Abstract P3011: Role of CD36 in Insulin Mediated Microvascular Vasodilation in African Americans

CD36 is a membrane protein involved in fatty acids uptake that is expressed in the endothelium, which has been associated with endothelial dysfunction in African Americans (AA). One in four AA is G-allele carriers for coding CD36 SNP rs3211938, which results in ~50% reduction in its expression. We reported that potentiating nitric oxide action (NO) with sildenafil restored endothelial dysfunction in conduit arteries in G-allele carriers. In this study, we tested the hypothesis that in G-allele carriers, sildenafil would improve insulin-induced microvascular recruitment (MBV) in response to fat infusion. We recruited 25 healthy AA (17 non-carriers [ages 34 ± 7.4] and eight G-allele carriers [42 ± 7.4 yrs]). Subjects underwent three visits: Visit 1: Saline infusion and hyperinsulinemic euglycemic clamp (HIE clamp). Visit 2: Lipid infusion and HIE clamp and Visit 3: Lipid infusion and HIE clamp after a four-week sildenafil treatment (60 mg/day). During each visit, the subjects underwent an assessment of MBV at baseline (bsl), after 3-hour insulin (Ins) infusion (40mu/m 2 /min) and after Ins and L-arginine (10mg/kg/min) for 30 min. infusion (Ins+L-arg). Ins+L-arg (saline day) increased the % change in MBV in both groups. However, this increase was less in carriers as compared to non-carriers (13.6±42.4 and 38.9±74.4), Fig. A. Intralipid (IL) infusion increased MBV but only in non-carriers, Fig. B . Treatment with sildenafil in the presence of IL infusion induced a decline in MBV in G-allele carriers Fig. C . In conclusion, healthy AAs with CD36 deficiency had a poor insulin-induced microvascular recruitment and appeared to be worsened by potentiating NO function with sildenafil.

OR19: Striatal Activity Decreases Following the Intragastric Infusion of Glucose and Lipids in Lean Humans

OR19: Striatal Activity Decreases Following the Intragastric Infusion of Glucose and Lipids in Lean Humans

SUN-PO001: Comparative Study Between Conventional Fasting Versus Overnight Infusion of Lipid or Carbohydrate on Insulin and Free Fattyacids in Obese Patients Undergoing Elective On-Pump Coronary Artery Bypass Grafting. A Prospective Randomized Trial

SUN-PO001: Comparative Study Between Conventional Fasting Versus Overnight Infusion of Lipid or Carbohydrate on Insulin and Free Fattyacids in Obese Patients Undergoing Elective On-Pump Coronary Artery Bypass Grafting. A Prospective Randomized Trial

Relationship between symptoms during a gastric emptying study and intestinal chemosensitivity with daily symptoms.

Non-ulcer dyspepsia (NUD) is a heterogeneous disorder, which is characterized by upper gastrointestinal symptoms and sensorimotor disturbances, including abnormal gastric emptying (GE) and increased intestinal chemosensitivity, and associated with greater plasma glucagon-like peptide-1 (GLP-1) levels during duodenal lipid infusion. However, the relationship(s) between these disturbances and daily symptoms in NUD is variable. We hypothesize that abnormal GE and symptoms during a GE study and during duodenal lipid infusion are associated with the severity of daily symptoms and that GLP-1 mediates symptoms during duodenal lipid infusion in NUD. Gastric emptying of solids, symptoms during the GE study and duodenal lipid infusion, and daily gastrointestinal symptoms (2week diary) were measured in 24 healthy controls and 40 NUD patients. During duodenal lipid infusion, participants received the GLP-1 antagonist exendin 9-39 or placebo. In controls and patients, GE of solids was normal in 75% and 75%, delayed in 8% and 12.5%, or rapid in 17% and 12.5%, respectively. No controls but 26 patients (65%) had severe symptoms during the GE study. During lipid infusion, gastrointestinal symptoms were greater (P=.001) in patients and not affected by exendin. Symptoms during GE study and lipid infusion accounted for respectively 62% and 37% of variance in daily symptom severity. In NUD, symptoms during a GE study and to a lesser extent during lipid infusion explain the variance in daily symptoms. Intestinal chemosensitivity is not reduced by GLP-1 antagonist. Assessment of symptoms during a GE study may provide a useful biomarker for NUD in research and clinical practice.

Intralipid infusion in paediatric patient with quetiapine and lamotrigine intoxication

We present a case of the acute intoxication of a 17-year-old patient after ingestion of 6 g of quetiapine in combination with 1 g of lamotrigine. Due to the severe tachycardia, hypertension, and prolonged QTc without improvement after standard treatment, the patient was treated with Intralipid 20% intravenous infusion recommended by the Toxicologic Information Centre. After lipid infusion, the QTc rapidly normalised and tachycardia resolved to sinus rhythm. The patient was transferred to psychiatry intensive care on the third day after admission. [GRAPHICS] .

Malassezia furfur Emergence and Candidemia Trends in a Neonatal Intensive Care Unit During 10 Years: The Experience of Fluconazole Prophylaxis in a Single Hospital.

Background:Because Candida spp is a major cause of mortality and morbidity in preterm infants, fluconazole prophylaxis has been suggested by some experts and hospital policy. In our hospital, fluconazole prophylaxis was used in eligible preterm infants and set as the neonatal intensive care unit (NICU) practice in 2014.Purpose:This study focused on fungal bloodstream infections and aimed to evaluate the benefit and harm of fluconazole prophylaxis.Methods/Search Strategy:This retrospective, descriptive study involved medical record reviews in our hospital from April 2005 to October 2016. NICU patients were included if Candida species, yeast-like organisms, or Malassezia species were cultured from their venous catheter tips or blood cultures.Findings/Results:After fluconazole prophylaxis, cases of Candida spp decreased and those of Malassezia furfur emerged. We reviewed 19 cases of catheter-related M furfur colonization and 1 case of M furfur fungemia. The gestational age was 27.3 ± 2.0 weeks and birth weight was 959.2 ± 229.8 g. Hyperalimentation with lipid infusion was used in all cases. All of the neonates survived with antifungal agent use.Implications for Practice:This study highlights that prophylactic fluconazole may be an associated factor of Malassezia colonization; M furfur remains a potential concern for fungemia in the care of premature infants and thus requires our attention.Implications for Research:Future studies should further investigate the incidence and impact of noncandidal fungal infections with fluconazole prophylaxis use in premature infants.

Adipose tissue protects against sepsis-induced muscle weakness in mice: from lipolysis to ketones

BackgroundICU-acquired weakness is a debilitating consequence of prolonged critical illness that is associated with poor outcome. Recently, premorbid obesity has been shown to protect against such illness-induced muscle wasting and weakness. Here, we hypothesized that this protection was due to increased lipid and ketone availability.MethodsIn a centrally catheterized, fluid-resuscitated, antibiotic-treated mouse model of prolonged sepsis, we compared markers of lipolysis and fatty acid oxidation in lean and obese septic mice (n = 117). Next, we compared markers of muscle wasting and weakness in septic obese wild-type and adipose tissue-specific ATGL knockout (AAKO) mice (n = 73), in lean septic mice receiving either intravenous infusion of lipids or standard parenteral nutrition (PN) (n = 70), and in lean septic mice receiving standard PN supplemented with either the ketone body 3-hydroxybutyrate or isocaloric glucose (n = 49).ResultsObese septic mice had more pronounced lipolysis (p ≤ 0.05), peripheral fatty acid oxidation (p ≤ 0.05), and ketogenesis (p ≤ 0.05) than lean mice. Blocking lipolysis in obese septic mice caused severely reduced muscle mass (32% loss vs. 15% in wild-type, p < 0.001) and specific maximal muscle force (59% loss vs. 0% in wild-type; p < 0.001). In contrast, intravenous infusion of lipids in lean septic mice maintained specific maximal muscle force up to healthy control levels (p = 0.6), whereas this was reduced with 28% in septic mice receiving standard PN (p = 0.006). Muscle mass was evenly reduced with 29% in both lean septic groups (p < 0.001). Lipid administration enhanced fatty acid oxidation (p ≤ 0.05) and ketogenesis (p < 0.001), but caused unfavorable liver steatosis (p = 0.01) and a deranged lipid profile (p ≤ 0.01). Supplementation of standard PN with 3-hydroxybutyrate also attenuated specific maximal muscle force up to healthy control levels (p = 0.1), but loss of muscle mass could not be prevented (25% loss in both septic groups; p < 0.001). Importantly, this intervention improved muscle regeneration markers (p ≤ 0.05) without the unfavorable side effects seen with lipid infusion.ConclusionsObesity-induced muscle protection during sepsis is partly mediated by elevated mobilization and metabolism of endogenous fatty acids. Furthermore, increased availability of ketone bodies, either through ketogenesis or through parenteral infusion, appears to protect against sepsis-induced muscle weakness also in the lean.

2118-P: Evidence of GIP-Induced Regulation of Fatty Acid Desaturase 2 (FADS2) Gene Expression in Subcutaneous Adipose Tissue

The incretin glucose-dependent insulinotropic polypeptide (GIP) is an important regulator of postprandial metabolism by stimulating insulin secretion and inhibiting lipolysis in the adipocytes. GIP is also involved in the development of the low-grade tissue inflammation upon high-fat and high-sucrose diet, but complete mechanisms of this action remain poorly understood. Fatty acid (FA) composition affects the obesity-associated low-grade inflammation. Recently human studies showed that fatty acid desaturase 2 (FADS2) gene polymorphism is associated with FA metabolism and adipose tissue inflammation. Here we aimed to investigate the effect on GIP infusion on the FADS2 gene expression in subcutaneous adipose tissue (SAT) and FA composition in humans. Eleven male subjects without diabetes (age: 36.9 ± 1.9 years; body mass index 32.2 ± 1.0 kg/m2) underwent saline infusion (0.9% NaCl), GIP infusion at an infusion rate of 2.0 pmol kg−1min−1, lipid infusion (Intralipid 20% emulsion for infusion) or combined GIP and lipid infusion of 4 hours duration. SAT biopsies were taken at −40 min and 240 min of infusions and FADS2 mRNA levels were detected by real-time PCR. FA compositions were measured in plasma at 0 and 240 minutes of each test by LCMS. FADS2 desaturating activity was calculated as a ratio of 18:3n-6 to 18:2n-6 FA, 20:3n-6 to 20:2n-6 FA, 22:4n-5 to 22:4n-6 FA and C22:6n-3 to C22:5n3 FA. FADS2 gene expression was increased after GIP, lipid and combined GIP and lipid infusion (p&amp;lt;0.01) compared to saline infusion. 18:3n-6 to 18:2n-6 FA ratio was significantly down-regulated at the end of GIP+lipid and lipid infusion but did not change after the GIP infusion alone. The observed GIP-dependent upregulation of FADS2 gene in adipose tissue may influence regulation of adipose tissue inflammation in postprandial state and in obesity. The observed down-regulation of 18:3n-6 to 18:2n-6 ratio reflects the saturation of enzyme capacity by substrate overload during the experiments Disclosure O. Ramich: None. A.F. Pfeiffer: Advisory Panel; Self; Abbott, Berlin-Chemie AG, Novo Nordisk A/S. Speaker's Bureau; Self; Lilly Diabetes, Novartis AG, Sanofi-Aventis Deutschland GmbH. N.N. Rudovich: None.