Linda Wykes

Body composition and energy expenditure in adolescents with cerebral palsy or myelodysplasia

ABSTRACT: We measured body composition, resting metabolic rate (RMR), and total energy expenditure (TEE) in a group of adolescents with cerebral palsy (CP) and myelodysplasia (M) aged 13− to 20-y-old using indirect calorimetry and the doubly labeled water method. Fat-free mass (FFM), RMR, and TEE were significantly lower in both the CP and M groups than comparable measurements in a control group of normal adolescent males and females. The ratio of TEE to RMR did not differ between controls and ambulatory M and CP subjects. However, TEE/RMR was significantly lower in the nonambulatory M and CP subjects than in controls (p < 0.01). Our data indicate that energy requirements are reduced in both populations because both FFM and activity are decreased. Although energy requirements were decreased in both groups, the relationships between FFM and body weight differed. FFM and body weight were significantly correlated with RMR only in the M group. These data suggest that the type of paralysis in a handicapped population may affect resting energy expenditure.

Epidural blockade modifies perioperative glucose production without affecting protein catabolism

Background Epidural blockade with local anesthetic has been shown to blunt the increase in plasma glucose concentration during and after abdominal surgery. The aim of the study was to test the hypothesis that epidural blockade inhibits this hyperglycemic response by attenuating endogenous glucose production. The authors further examined if the modification of glucose production by epidural blockade has an impact on perioperative protein catabolism. Methods Sixteen patients undergoing colorectal surgery received either general anesthesia and epidural blockade with local anesthetic (n = 8) or general anesthesia alone (control, n = 8). Glucose and protein kinetics were assessed by stable isotope tracer technique ([6,6-2H2]glucose, L-[1-13C]leucine) during and 2 h after surgery. Plasma concentrations of glucose, lactate, free fatty acids (FFA), cortisol, glucagon, and insulin were also determined. Results Epidural blockade blunted the perioperative increase in the plasma concentration of glucose, cortisol, and glucagon when compared with the control group (P < 0.05). Plasma concentrations of lactate, FFA, and insulin did not change. Intra- and postoperative glucose production was lower in patients with epidural blockade than in control subjects (intraoperative, epidural blockade 8.2 ± 1.9 vs. control 10.7 ± 1.4 &mgr;mol·kg−1·min−1, P < 0.05; postoperative, epidural blockade 8.5 ± 1.8 vs. control 10.5 ± 1.2 &mgr;mol·kg−1·min−1, P < 0.05), whereas glucose clearance decreased to a comparable extent in both groups (P < 0.05). Protein breakdown (P < 0.05), protein synthesis (P < 0.05), and amino acid oxidation (P > 0.05) decreased with both anesthetic techniques. Conclusions Epidural blockade attenuates the hyperglycemic response to surgery through modification of glucose production. The perioperative suppression of protein metabolism was not influenced by epidural blockade.

Parenteral nutrition selectively decreases protein synthesis in the small intestine

We investigated the effects of an elemental diet fed parenterally or enterally on total mucosal protein and lactase phlorizin hydrolase (LPH) synthesis. Catheters were placed in the stomach, jugular vein, and carotid artery of 12 3-day-old pigs. Half of the animals were given an elemental regimen enterally and the other half parenterally. Six days later, animals were infused intravenously with [2H3]leucine for 6 h and killed, and the midjejunum of each animal was collected for analysis. The weight of the midjejunum was 8 +/- 1.5 and 17 +/- 1.6 g in parenterally fed and enterally fed piglets, respectively. LPH activities (mumol.min-1.g protein-1) were significantly higher in parenterally vs. enterally fed piglets. Total small intestinal LPH activities were lower in parenterally vs. enterally fed animals. The abundance of LPH mRNA relative to elongation factor-1 alpha mRNA was not different between groups. The fractional synthesis rate of total mucosal protein and LPH was significantly lower in parenterally fed animals (67 +/- 7 and 66 +/- 7%/day, respectively) than in enterally fed animals (96 +/- 7 and 90 +/- 6%/day, respectively). The absolute synthesis rate (the amount of protein synthesized per gram of mucosa) of total mucosal protein was significantly lower in parenterally fed than in enterally fed piglets. However, the absolute synthesis rate of LPH was unaffected by the route of nutrient administration. These results suggest that the small intestine partially compensates for the effects of parenteral feeding by maintaining the absolute synthesis rate of LPH at the same levels as in enterally fed animals.

Perioperative glucose infusion and the catabolic response to surgery: the effect of epidural block.

Although the nitrogen-sparing properties of epidural block and i.v. glucose on the days after surgical trauma have been well established, their metabolic effects during the acute phase of the stress response remain unclear. Therefore, in this study we investigated the effect of epidural block on glucose and protein kinetics during and immediately after surgery in patients receiving i.v. glucose at 2 mg x kg(-1) x min(-1). Sixteen patients undergoing colorectal surgery received either general anesthesia with epidural block with bupivacaine (EDA; n = 8) or general anesthesia alone (control; n = 8). Glucose and protein kinetics were determined during and 2 h after the operation by stable isotope tracers [6,6-(2)H(2)]glucose and L-[1-(13)C]leucine. Plasma concentrations of glucose, insulin, cortisol, and glucagon were also determined. Epidural block attenuated the perioperative increase in plasma glucose concentration (P < 0.05). The rate of appearance of glucose (R(a) glucose) and endogenous glucose production (EGP) were slower in the EDA group than in control subjects during (R(a) glucose, EDA 13.2 +/- 1.0 versus control 15.3 +/- 1.8 micromol x kg(-1) x min(-1); P < 0.05; EGP, EDA 1.2 +/- 1.2 versus control 3.8 +/- 1.7 micromol x kg(-1) x min(-1); P < 0.05) and after the operation (P > 0.05). Whereas protein breakdown and amino acid oxidation decreased in both groups (P < 0.05), whole-body protein synthesis remained unchanged. Insulin levels increased with both anesthetic techniques (P < 0.05). Intraoperative plasma concentrations of cortisol and glucagon were smaller in the EDA group (P < 0.05). The intraoperative suppression of EGP by exogenous glucose was more pronounced in the presence of epidural block. However, epidural block failed to exert a protein-sparing effect during the acute phase of the stress response in patients receiving i.v. glucose.

Protein Anabolic Responses to a Fed Steady State in Healthy Aging

BACKGROUND Protein anabolism in response to feeding may be impaired with aging. To determine if this could contribute to muscle loss, we studied fed-state metabolic responses in healthy, non-sarcopenic elderly women. METHODS Whole-body [(3)H]glucose and protein ([(13)C]leucine) kinetics were measured, and muscle protein fractional synthesis rate ([(2)H(5)]phenylalanine) and signaling events were assessed from vastus lateralis biopsies in eight elderly (73 ± 3 years) and eight young women (24 ± 1 years), using a simulated fed steady-state clamp. RESULTS Both groups had similar muscle and lean body mass indices and activity level. During insulin, glucose (8 mmol/L), and amino acid (AA; 2× fasting) infusions, serum insulin was lower in the elderly women and C-peptide increased less. Glucose uptake was stimulated, and production suppressed similarly. Suppression of whole-body protein breakdown was less in the elderly women, leading to lower AA infusion rates, oxidation, and net positive protein balance, but differences were not present when adjusted for serum insulin. Whole-body protein synthesis and muscle protein fractional synthesis rate increased similarly. Similar increases in phosphorylated Akt(Ser473), PRAS40(Thr246), FoxO3a(Thr32), and rpS6(Ser240/244) indicated no alterations in insulin/nutrient signaling with aging. CONCLUSIONS Both whole-body and muscle fed-state protein anabolic responses were preserved, as was insulin sensitivity of glucose metabolism, in active, healthy elderly women. This is consistent with other factors such as sedentarity, low protein intake, and concurrent diseases, being responsible for the sarcopenia of aging.

The Anabolic Effect of Epidural Blockade Requires Energy and Substrate Supply

Background The authors examined the hypothesis that continuous thoracic epidural blockade with local anesthetic and opioid, in contrast to patient-controlled intravenous analgesia with morphine, stimulates postoperative whole body protein synthesis during combined provision of energy (4 mg · kg−1 · min−1 glucose) and amino acids (0.02 ml · kg−1 · min−1 Travasol™ 10%, equivalent to approximately 2.9 g · kg−1 · day−1). Methods Sixteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding) on the second day after colorectal surgery performed with or without perioperative epidural blockade. Protein synthesis, breakdown and oxidation, glucose production, and clearance were measured by l-[1-13C]leucine and [6,6-2H2]glucose. Results Epidural blockade did not affect protein and glucose metabolism in the fasted state. Parenteral alimentation decreased endogenous protein breakdown and glucose production to the same extent in both groups. Administration of glucose and amino acids was associated with an increase in whole body protein synthesis that was modified by the type of analgesia, i.e., protein synthesis increased by 13% in the epidural group (from 93.3 ± 16.6 to 104.5 ± 11.1 &mgr;mol · kg−1 · h−1) and by 4% in the patient-controlled analgesia group (from 90.0 ± 27.1 to 92.9 ± 14.8 &mgr;mol · kg−1 · h−1;P = 0.054). Conclusions Epidural blockade accentuates the stimulating effect of parenteral alimentation on whole body protein synthesis.

Postoperative Protein Sparing With Epidural Analgesia and Hypocaloric Dextrose

Objective:We examined the hypothesis that epidural analgesia prevents the increase in amino acid oxidation after elective colorectal surgery in patients receiving hypocaloric infusion of dextrose. Summary Background Data:Increased oxidative protein loss after surgery may adversely affect postoperative outcome. We have previously shown that effective segmental pain relief by epidural analgesia improves postoperative substrate utilization, resulting in less protein catabolism. Methods:We randomly allocated 10 patients to receive general anesthesia combined with epidural analgesia using bupivacaine/fentanyl and 10 to receive general anesthesia followed by patient-controlled analgesia with intravenous morphine. All patients received a peripheral 72-hour infusion of dextrose 10% from the day before until the second day after surgery. The dextrose infusion rate was adjusted to provide 50% of the patients’ resting energy expenditure. The primary end point was whole-body leucine oxidation as determined by a stable isotope tracer technique (l-[1-13C]leucine). Results:In the intravenous analgesia group, leucine oxidation increased from 19 ± 4 to 28 ± 6 &mgr;mol kg−1 h−1 after surgery. Epidural analgesia prevented this increase of leucine oxidation (preoperative 21 ± 6 &mgr;mol kg−1 h−1, postoperative 21 ± 5 &mgr;mol kg−1 h−1). This difference was statistically significant (P = 0.01; analysis of variance for repeated measures). Conclusion:Perioperative epidural analgesia and hypocaloric dextrose infusion suppress the postoperative increase in amino acid oxidation, thereby saving more than 100 g of lean body mass per day.

Type 2 diabetes mellitus and the catabolic response to surgery.

Background:The authors tested the hypothesis that the catabolic responses to colorectal surgery are amplified in the presence of type 2 diabetes mellitus. Methods:Seven nondiabetic and seven diabetic patients underwent a 6-h stable isotope infusion study (3 h fasted, 3-h glucose infusion at 4 mg · kg−1 · min−1) on the second postoperative day. Leucine rate of appearance (Ra), leucine oxidation, nonoxidative leucine disposal, and glucose Ra were assessed by L-[1-13C]leucine and [6,6-2H2]glucose. Circulating concentrations of glucose, lactate, insulin, glucagon, and cortisol also were determined. Results:Diabetic patients had a higher leucine oxidation than nondiabetic patients (P = 0.0003), whereas leucine Ra and nonoxidative leucine disposal were not different. Administration of glucose did not affect leucine kinetics regardless of whether patients were diabetic. In diabetic patients, glucose Ra was greater than in the nondiabetic group (P = 0.0032). Glucose infusion suppressed the endogenous glucose Ra to a lesser extent in diabetic than in nondiabetic patients (P = 0.0048). Plasma glucose concentrations were higher in diabetic than in nondiabetic patients (P = 0.0203), both in the postabsorptive and the fed state. Circulating concentrations of glucagon were higher (P = 0.0065) and concentrations of insulin were lower (P = 0.0146) in the presence of diabetes, resulting in a lower insulin/glucagon ratio (P = 0.0002). In diabetic patients, the insulin/glucagon ratio increased during glucose infusion to a lesser extent than in the nondiabetic group (P = 0.0014). Conclusion:Protein catabolism after colorectal surgery is increased in patients with type 2 diabetes mellitus as reflected by an increased oxidative protein loss.

Anticatabolic Effects of Avoiding Preoperative Fasting by Intravenous Hypocaloric Nutrition : A Randomized Clinical Trial

Objective:We tested the hypothesis that the avoidance of preoperative fasting by hypocaloric nutrition attenuates protein catabolism after surgery. Summary Background Data:Prolonged fasting before major abdominal procedures has been demonstrated to accentuate the catabolic response to surgery. Methods:Twenty-two patients undergoing colorectal cancer surgery were randomly assigned to receive glucose and amino acids intravenously starting either 20 hours before the operation or with surgical skin incision. Nutrition was administered until the second postoperative day, with glucose providing 50% and amino acids 20% of each patient’s measured resting energy expenditure. Whole body leucine and glucose kinetics were assessed by l-[1-13C]leucine and [6,6-2H2]glucose before and after surgery. Fractional synthesis rates of muscle protein, albumin, and fibrinogen were determined using primed continuous infusions of l-[2H5]phenylalanine postoperatively, whereas the expression of mRNA of proteolytic genes in muscle (Mafbx/atrogin-1, ubiquitin, Murf 1) was determined by quantitative RT-PCR. Circulating concentrations of glucose, lactate, amino acids, insulin, glucagon, and cortisol were also measured. This study has been registered at ClinicalTrials.gov (Identifier: NCT00614133). Results:Preoperative feeding inhibited endogenous protein breakdown (fasting group: 128 ± 23 &mgr;mol · kg−1 · h−1; nutrition group: 96 ± 22 &mgr;mol · kg−1 · h−1; P = 0.02) and blunted the increase in amino acid oxidation (fasting group: 27 ± 5 &mgr;mol · kg−1 · h−1; nutrition group: 20 ± 5 &mgr;mol · kg−1 · h−1; P = 0.03), resulting in positive whole-body protein balance after surgery (fasting group: −10 ± 4 &mgr;mol · kg−1 · h−1; nutrition group: 1 ± 3 &mgr;mol · kg−1 · h−1; P < 0.001). This anabolic response was associated with decreased muscle proteolytic gene expression and increased hepatic albumin synthesis. Total plasma protein, fibrinogen, and muscle protein synthesis were not affected. Conclusions:Hypocaloric nutrition decreases protein catabolism, with a contribution from the ubiquitin pathway in muscle, and stimulates albumin synthesis after colorectal surgery if initiated 1 day before the operation.

Effect of Epidural blockade on protein, glucose, and lipid metabolism in the fasted state and during dextrose infusion in volunteers

Background To interpret correctly the results from studies performed during surgery and anesthesia it is necessary to dissect the separate effect of the anesthetic technique itself. The purpose of this study was to investigate the metabolic effects of epidural blockade (T7-S1) with bupivacaine 0.25% after 12 h fasting and during administration of 4 mg · kg−1 · min−1 dextrose in six healthy volunteers. Methods Each volunteer was assigned to randomly undergo a 6-h multiple stable isotope infusion study (3 h fasted, 3 h dextrose infusion) with or without epidural blockade. L-[1-13C]leucine, [6,6-2H2]glucose, and [1,1,2,3,3-2H5]glycerol were infused to measure protein synthesis, breakdown, and amino acid oxidation; glucose production and clearance; and lipolysis. Plasma concentrations of glucose, lactate, glycerol, free fatty acids, insulin, and glucagon were determined. Results Epidural blockade with bupivacaine had no influence on protein oxidation, breakdown and synthesis, glucose production, glucose clearance and lipolysis in the fasted state. Plasma concentrations of metabolic substrates and hormones also were not affected. Dextrose infusion significantly increased glucose clearance and plasma concentrations of glucose and insulin, while endogenous glucose production and lipolysis decreased to a similar degree in both groups. Protein synthesis, breakdown, and oxidation did not change during dextrose infusion. Conclusions Epidural blockade with bupivacaine in the absence of surgery has no effect on fasting protein, glucose, and lipid metabolism. Epidural blockade does not modify the inhibitory influence of dextrose administration on endogenous glucose production and lipolysis.