Biomedical subjects

M W Haymond

Publications and source records attributed to M W Haymond.

At least 19 recordsLinked to original sources

PubMed2000

The reciprocal pool model for the measurement of gluconeogenesis by use of [U-(13)C]glucose.

To improve upon the [U-(13)C]glucose method to estimate "gluconeogenesis" as described by J. Katz and J. A. Tayek (Am. J. Physiol. Endocrinol. Metab. 272: E476-E484, 1997, and 275: E537-E542, 1998), we describe the reciprocal pool model by using only the isotopomer data of plasma glucose during infusion of [U-(13)C]glucose. The glucose pool serves as both precursor and product for the calculation of the fraction of molecules generated by gluconeogenesis and to correct for exchange and loss of labeled carbon at the level of the tricarboxylic acid cycle. We have applied this model to both our own data and those of other investigators using [U-(13)C]glucose and have demonstrated excellent agreement between the Katz and Tayek model and our reciprocal pool model. When we compare the results of the reciprocal pool model with those of Hellerstein ([2-(13)C]glycerol) and Landau ((2)H(2)O-glucose-C-5), the results are similar in short- and long-term fasted adult humans. Finally, when we apply the reciprocal pool model to our data from premature infants, it is clear that we account for the inflow of unlabeled glycerol and presumably amino acids. This is not surprising, because the vast majority of gluconeogenesis is the result of recycling of glucose and pyruvate carbon.

Adult↗

PubMed1999

Quantitation of monosaccharide isotopic enrichment in physiologic fluids by electron ionization or negative chemical ionization GC/MS using di-O-isopropylidene derivatives.

The aldonitrile pentaacetate and other derivatives lack ions in the electron ionization (EI) spectra possessing an intact hexose structure and thus must be analyzed by chemical ionization GC/MS in order to study multiple isotopomers. We report methods for quantitation of hexose di-O-isopropylidene acetate (IPAc) or pentafluorobenzoyl (PFBz) esters. These were prepared in a two-step procedure using inexpensive reagents that do not adversely impact the isotopomer structure of the sugar. The acetate derivative possesses an abundant [M - CH3] ion in the EI spectrum which is suitable for quantitative analysis of isotopomers. The negative chemical ionization (NCI) spectrum of the corresponding pentafluorobenzoyl derivative has a dominant molecular anion. Moreover, the PFBz derivative is about 100-fold more sensitive than the acetate, which offers some advantages for analysis of minor hexoses found in plasma. Isotopic calibration curves of [U-13C]glucose are linear over the 0.1-60% tracer/tracee range tested. The useful range for isotopic tracer studies is 25-2500 pmol for EI analysis of the acetate derivative and 0.1-55 pmol for NCI analysis of PFBz derivative (sample amount injected). For most studies where sample size is not limited, EI-GC/MS analysis of the IPAc derivative is preferred. NCI-GC/MS analysis is reserved when sample size is limiting or when studies involve hexoses other than glucose that are normally present at low concentration.

Alkenes↗

PubMed1999

Controlling the sugar bowl. Regulation of glucose homeostasis in children.

In this article, the authors have attempted to provide a reasonable, working, and dynamic model incorporating a number of factors that are known to be involved in the regulation of glucose homeostasis in infants, children, and adults. Through the understanding of this model and its application, it is hoped that some of the authors' speculations regarding the pathophysiology of hyperglycemia and hypoglycemia might be challenged and either supported or rejected. In the meantime, the model can provide a framework for several of the facts and observations about the regulation of glucose homeostasis.

Blood Glucose↗

PubMed1999

Nutritional and metabolic endpoints.

None of the metabolic indicators which have been used to date provides a single or necessarily ideal endpoint for interventional management in wasting disorders. Some of these indicators may provide better endpoints for the acute rather than the chronic wasting conditions. In addition, it is imperative that more than one endpoint be selected to be assured that there is concordance in the findings. However, prior to the selection of any endpoint measure, the investigators involved must be fully cognizant of the potential pitfalls and errors that can occur in every one of the selected methodologies. In anticipating these potential problems, developing strategies for the interpretation of the data is critical at the outset of any interventional management strategy. The manufacturers, the regulators and the investigators involved in the interventional management of chronic and acute wasting disorders must agree on the endpoints to be used and these endpoints must provide the most appropriate and valid information. Selection of nutritional and metabolic endpoints must be in part dependent on the disease process involved, the potential magnitude of the interventional effect and must be utilized in the context of a carefully designed experimental protocol with a well focused question(s).

Amino Acids↗

PubMed1999

Body composition as a clinical endpoint in the treatment of growth hormone deficiency.

Endpoints in the treatment and management of adults with growth hormone (GH) deficiency (GHD) can be problematic. Changes in body composition with recombinant human GH (rhGH) treatment may be one of the most objective measures that could be applied in judging the effectiveness and long-term efficacy. The relative strengths and weaknesses of measures of body composition and their potential for clinical utility in the setting of rhGH replacement in GHD in adults are discussed. Measurement of changes in body fat, regardless of the method employed, from pretreatment baseline through 2-6 months of treatment may be quite useful in demonstrating the efficacy of rhGH in each patient. Other changes in body composition are compromised by the imprecision of the measurements, shifts in extracellular water, and the small real changes which occur in bone and muscle in the GHD subject. Use of body composition measures of change in fat content as an endpoint in determining the efficacy of rhGH treatment in adults with GHD cannot be implemented on the basis of current data and would require a carefully designed prospective, controlled study. Until such criteria are established and accepted, endocrinologists must continue to manage these patients purely on the basis of their clinical judgment.

Adipose Tissue↗

PubMed1999

Gluconeogenesis in very low birth weight infants receiving total parenteral nutrition.

Very low birth weight (VLBW) infants are dependent on total parenteral nutrition (TPN) to prevent hypoglycemia and provide a sufficient energy intake. However, diminished tolerance for parenteral glucose delivered at high rates frequently provokes hyperglycemia. We hypothesized that when their glucose supply is reduced to prevent hyperglycemia, VLBW infants can maintain normoglycemia via gluconeogenesis from glycerol and amino acids. Twenty infants born at 27 +/- 0.2 (mean +/- SE) gestational weeks and having a birth weight of 996 +/- 28 g, received lipids (1.6 +/- 0.1 mg x kg(-1) x min(-1)), protein (2.2 +/- 0.1 mg x kg(-1) x min(-1)), and glucose (3.1 +/- 0.1 mg x kg(-1) x min(-1) [17.1 +/- 0.2 micromol x kg(-1) x min(-1)]) parenterally over a period of 8-12 h on day 5.0 +/- 0.2 of life. Gluconeogenesis was estimated using [U-13C]glucose (n = 8) or [2-(13)C] glycerol (n = 6) and mass isotopomer distribution analysis (MIDA), or 2H2O (n = 6) and the rate of deuterium incorporation in carbon 6 of glucose. Blood glucose averaged 3.0 +/- 0.1 mmol/l; plasma glucose appearance rate (glucose Ra), 28.8 +/- 1.1 micromol x kg(-1) x min(-1); and glucose production rate (GPR), 10.7 +/- 1.0 micromol x kg(-1) x min(-1). The [U-13C]glucose and [2-(13)C]glycerol tracers provided similar estimates of gluconeogenesis, averaging 28 +/- 2 and 26 +/- 2% of glucose Ra and 72 +/- 5 and 73 +/- 9% of GPR, respectively. Glycerol contributed 64 +/- 5% of total gluconeogenesis. Gluconeogenesis measured by 2H2O, which does not include the contribution from glycerol, was comparable to the nonglycerol fraction of gluconeogenesis derived by the [2-(13)C]glycerol MIDA. We conclude that in VLBW infants receiving TPN, normoglycemia was maintained during reduced glucose infusion by glucose production primarily derived from gluconeogenesis, and that glycerol was the principal gluconeogenic substrate.

Blood Glucose↗

PubMed1998

Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism.

The present study was designed to determine whether sodium phenylbutyrate (phi B) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g.kg-1.day-1) of phi B were administered for 24 h before study: postabsorptive plasma glutamine concentration declined in a dose-dependent manner, achieving an approximately 25% decline for a dose of 0.36 g phi B.kg-1.day-1. A second group of six healthy adults received 5-h infusions of L-[1-14C]leucine and L-[1-13C]glutamine in the postabsorptive state on two separate days: 1) under baseline conditions and 2) after 24 h of oral treatment with phi B (0.36 g.kg-1.day-1) in a randomized order. The 24-h phenylbutyrate treatment was associated with 1) an approximately 26% decline in plasma glutamine concentration from 514 +/- 24 to 380 +/- 15 microM (means +/- SE; P < 0.01 with paired t-test) with no change in glutamine appearance rate or de novo synthesis; 2) no change in leucine appearance rate (Ra), an index of protein breakdown (123 +/- 7 vs. 117 +/- 5 mumol.kg-1.h-1; not significant); 3) an approximately 22% rise in leucine oxidation (Ox) from 23 +/- 2 to 28 +/- 2 mumol.kg-1.h-1 (P < 0.01), resulting in an approximately 11% decline in nonoxidative leucine disposal (NOLD = Ra-Ox), an index of protein synthesis, from 100 +/- 6 to 89 +/- 5 mumol.kg-1.h-1 (P < 0.05). The data suggest that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a "glutamine trap" to create a model of glutamine depletion; 2) a moderate decline in plasma glutamine does not enhance rates of endogenous glutamine production; and 3) a short-term depletion of plasma glutamine decrease estimates of whole body protein synthesis.

Adult↗

PubMed1998

Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy.

We determined whether glutamine has a protein anabolic effect in six 8-13-y-old boys with Duchenne muscular dystrophy. Children received a 5-h i.v. infusion of L-[1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state on two consecutive days while drinking: 1) flavored water on one day, and 2) the same drink mixed with L-glutamine (800 micromol x kg[-1] x h[-1]), the other day. Oral glutamine administration was associated with an 8% decrease in leucine release from protein breakdown, from 116 +/- 5 to 107 +/- 6 micromol x kg(-1) h(-1) (p < 0.01), and a 35% decrease in leucine oxidation rate from 23 +/- 2 to 15 +/- 2 micromol x kg(-1) x h(-1) (p < 0.01), resulting in no change in the nonoxidative leucine disposal, an index of protein synthesis. Whole body glutamine exchange in plasma doubled from 321 +/- 22 to 623 +/- 24 micromol x kg(-1) x h(-1), p < 0.01, but glutamine from protein degradation and glutamine de novo synthesis both decreased (91 +/- 4 versus 84 +/- 5 micromol x kg(-1) x h(-1), p < 0.01, and 230 +/- 21 versus 163 +/- 25 micromol x kg(-1) x (h-1), p = 0.02, respectively). These data suggest that acute oral glutamine administration might have a protein-sparing effect in children with Duchenne muscular dystrophy, decreasing estimates of whole body protein degradation and glutamine de novo synthesis, therefore sparing nitrogen precursors.

Administration, Oral↗

PubMed1998

Ovarian hyperandrogenism is associated with insulin resistance to both peripheral carbohydrate and whole-body protein metabolism in postpubertal young females: a metabolic study.

The role of endogenous androgens in enhancing the body's protein anabolic capacity has been controversial. To examine this question we chose to study whole-body protein and glucose kinetics in a group of 21 young, postpubertal females (16.3 +/- 0.6 yr), 8 of whom had clinical and laboratory evidence of ovarian hyperandrogenism (OH) (BMI = 37.8 +/- 1.3 kg/m2). We used L-[1-13C]leucine and [6,6,2H2]glucose tracer infusions before and after suppression of their endogenous androgens with estrogen/progesterone supplementation in the form of Triphasil for 4 weeks. Their baseline data were also compared with those of similar aged girls, 7 obese (OB) (BMI = 36.4 +/- 1.5) and 6 lean (LN) (BMI = 20.9 +/- 0.7) who were normally menstruating and had no evidence of androgen excess. Despite comparable glucose concentrations, both OH and OB groups had significant hyperinsulinemia (OH > OB), both basally and after iv glucose stimulation, as compared to LN controls (basal insulin: OH, 252 +/- 52 pmol/L; OB, 145 +/- 41; LN, 60 +/- 9, P = 0.009 OH vs. LN; peak insulin: OH, 2052 +/- 417; OB, 1109 +/- 127, LN, 480 +/- 120, P = 0.0009 OH vs. LN). The rate of appearance (Ra) of glucose, a measure of glucose production, was greater in the LN controls than in the OH or OB groups (OH, 2.0 +/- 0.1 mg/kg.fat free mass.min; OB, 1.9 +/- 0.1; LN, 3.3 +/- 0.1, P < 0.004 vs. LN). Calculated total rates of whole-body protein breakdown (leucine Ra), oxidation, and protein synthesis (nonoxidative leucine disposal) were substantially higher in the OH and OB groups as compared with LN controls (P < 0.04 vs. LN); however, when data are expressed on a per kilogram of fat free mass basis, the OH group had higher rates of proteolysis than the OB and LN, with indistinguishable rates between the latter two groups. None of the above-mentioned parameters changed after 1 month of administration of Triphasil, despite marked improvement in circulating testosterone and free testosterone concentrations after treatment (testosterone, -50%, P = 0.003; free testosterone, -70%, P = 0.02). We conclude that obesity in young postpubertal females is associated with insulin resistance for both peripheral carbohydrate and protein metabolism, and that patients with the OH syndrome have even greater insulin resistance as compared with simple obesity, regardless of treatment for the androgen excess. Carefully designed studies targeting interventions to improve both the hyperandrogenic and hyperinsulinemic state may prove useful even in the early juvenile stages of this disease.

Adolescent↗

PubMed1997

rhIGF-I administration in humans: differential metabolic effects of bolus vs. continuous subcutaneous delivery.

The metabolic effects of recombinant human insulin-like growth factor I (rhIGF-I) were compared using bolus vs. continuous subcutaneous infusions. Subjects (n = 5, 29 +/- 3 yr) received rhIGF-I as subcutaneous infusions by a Minimed pump (200 microg x kg(-1) x day(-1) over 16 h/day), and their data were compared with those of subjects (n = 6, 24 +/- 2 yr) who received subcutaneous 200 microg x kg(-1) x day(-1) injections twice a day. L-[1-14C]leucine and [6,6-2H2]glucose infusion studies and indirect calorimetry were performed, and total and free IGF-I, insulin, and glucose concentrations were measured before and after 5-7 days of rhIGF-I. Estimates of protein breakdown, oxidation, and synthesis did not change after pump therapy; in contrast, after bolus doses, protein oxidation decreased (P = 0.001) and whole body protein synthesis increased (P = 0.04). There was no change in lipid oxidation after pump treatment, whereas the bolus group had lower lipid oxidation (P = 0.035). Both treatment modalities increased glucose oxidation (P < 0.02) and glucose production rates (P < 0.03). Overnight fasting insulin concentrations decreased in both groups, whereas plasma glucose remained invariant in the bolus group and decreased modestly in the pump group. Total IGF-I concentrations increased comparably in both groups, but the increase in free IGF-I was greater in the bolus-treated group (P = 0.001). We conclude that, in GH-sufficient postabsorptive individuals, the metabolic effects of rhIGF-I are in part dependent on the mode of administration, with a robust protein-anabolic effect when rhIGF-I is given as twice daily bolus injections but no detectable effect on protein turnover after a continuous mode of delivery. There were higher free IGF-I levels in the bolus-treated subjects, suggesting that this form of the molecule may be important for mediating IGF-I's protein-anabolic effects at the tissue level. The data also suggest that carbohydrate metabolism is more responsive than protein metabolism to the continuous subcutaneous modality of rhIGF-I administration. Even though the mechanism of these differences in metabolic effects is not entirely clear, it should be taken into account when patients are given rhIGF-I as prolonged treatment.

Adult↗

PubMed1997

Role of glutamine as a glucose precursor in fasting humans.

Recently, significant incorporation of labeled carbon into plasma glucose was documented during infusion of 14C-labeled glutamine in postabsorptive humans. Such labeling of plasma glucose can occur as a result of two different processes: either 1) through incorporation of glutamine carbon into glucose via glutamine entering Krebs cycle at alpha-ketoglutarate or 2) through simple fixation of labeled CO2 resulting from oxidation of labeled glutamine. Therefore, these studies were designed to determine 1) whether glutamine contributes carbon to gluconeogenesis other than through mere CO2 fixation, and, if so, 2) whether the apparent transfer of carbon from glutamine to glucose increases with fasting. Eight healthy adults were studied on two consecutive days: once after an overnight (18-h) fast and again on the second day of fasting (42-h fast). On each study day, subjects received a simultaneous 5-h infusion of D-[6,6-2H2lglucose, L-[3,4-13C2lglutamine, and L-[1-14C]leucine. Apparent rates of incorporation of glutamine carbon into glucose were estimated from the appearance of 13C into plasma glucose; glucose and glutamine production rates (appearance rate [Ra]) were determined from plasma [2H2]glucose and [13C2]glutamine enrichments, respectively. The appearance of 14C into plasma glucose was used to correct the measured rates of carbon transfer from glutamine to glucose as a result of CO2 fixation. We observed that of the apparent contribution of labeled glutamine to gluconeogenesis, only 4% occurred as a result of fixation of labeled CO2, while 96% seemed to occur through other routes. We also observed that between 18 and 42 h of fasting, 1) the relative contribution of protein breakdown to glutamine production was enhanced, while that of de novo synthesis declined; 2) the apparent contribution of glutamine to glucose production rose from 8 +/- 1 to 16 +/- 3% of overall glucose Ra; and 3) the relative apparent contribution of glutamine to gluconeogenesis remained constant. From the current data, it cannot be ascertained to what extent the apparent carbon transfer from glutamine to glucose represents a true contribution of glutamine to gluconeogenesis or mere carbon exchange between the trichloroacetic acid cycle and the gluconeogenic pathway. These findings are nevertheless compatible with a role of glutamine as a significant precursor of glucose in fasting humans.

Adult↗

PubMed1996

Metabolic effects of recombinant human insulin-like growth factor-I in humans: comparison with recombinant human growth hormone.

Many of the metabolic actions of growth hormone (GH) are mediated through insulin-like growth factors or somatomedins. Recombinant human insulin-like growth factor-I (rhIGF-I) has a dichotomous insulin-like and GH-like action when used in different clinical situations in humans. Its effects on carbohydrate metabolism show a prominent increase in total insulin sensitivity, causing hypoglycemia in higher doses and maintaining normal glucose homeostasis in lower doses. This polypeptide selectively stimulates whole body protein synthesis with no effect on proteolysis when given in doses of 100 micrograms/ kg subcutaneously twice daily for at least 5-7 days, effects which are indistinguishable from those of GH. This contrasts with the marked suppression of proteolysis observed when higher doses are given, similar to the effects observed with insulin. When used in combination with rhGH, rhIGF-I has a synergistic effect, improving total nitrogen retention in calorically deprived subjects, yet it does not cause any greater enhancement of whole body protein anabolism in normally fed volunteers than giving rhGH and rhIGF-I individually. This suggests a common pathway for IGF-I and GH enhancing protein anabolism in the normally fed state. rhIGF-I also stimulates linear growth in children with defects in the GH receptor. Recent data show that this potent growth factor has a potential advantage over GH in the treatment of severe protein catabolic states, particularly the glucocorticosteroid-dependent model, as it ameliorates the marked increase in protein catabolism caused by the steroids, but without a diabetogenic effect. Here, a brief overview is provided of available human data on the actions of this peptide on carbohydrate, lipid, and protein metabolism, linear growth, and its anabolic effects. rhIGF-I offers promise in the treatment of selective growth disorders and in protein catabolic and insulin-resistant states.

Growth Hormone↗

PubMed1996

Effect of glutamine on leucine metabolism in humans.

The aim of this study was to determine whether the putative protein anabolic effect of glutamine 1) is mediated by increased protein synthesis or decreased protein breakdown and 2) is specific to glutamine. Seven healthy adults were administered 5-h intravenous infusions of L-[1-14C]leucine in the postabsorptive state while receiving in a randomized order an enteral infusion of saline on one day or L-glutamine (800 mumol.kg-1.h-1, equivalent to 0.11 g N/kg) on the other day. Seven additional subjects were studied using the same protocol except they received isonitrogenous infusion of glycine. The rates of leucine appearance (RaLeu), an index of protein degradation, leucine oxidation (OxLeu), and nonoxidative leucine disposal (NOLD), an index of protein synthesis, were measured using the 14C specific activity of plasma alpha-ketoisocaproate and the excretion rate of 14CO2 in breath. During glutamine infusion, plasma glutamine concentration doubled (673 +/- 66 vs. 1,184 +/- 37 microM, P < 0.05), whereas RaLeu did not change (122 +/- 9 vs. 122 +/- 7 mumol. kg-1.h-1), OxLeu decreased (19 +/- 2 vs. 11 +/- 1 mumol.kg-1.h-1, P < 0.01), and NOLD increased (103 +/- 8 vs. 111 +/- 6 mumol. kg-1.h-1, P < 0.01). During glycine infusion, plasma glycine increased 14-fold (268 +/- 62 vs. 3,806 +/- 546 microM, P < 0.01), but, in contrast to glutamine, RaLeu (124 +/- 6 vs. 110 +/- 4 mumol. kg-1.h-1, P = 0.02), OxLeu (17 +/- 1 vs. 14 +/- 1 mumol.kg-1.h-1, P = 0.03), and NOLD (106 +/- 5 vs. 96 +/- 3 mumol.kg-1.h-1, P < 0.05) all decreased. We conclude that glutamine enteral infusion may exert its protein anabolic effect by increasing protein synthesis, whereas an isonitrogenous amount of glycine merely decreases protein turnover with only a small anabolic effect resulting from a greater decrease in proteolysis than protein synthesis.

Adult↗

PubMed1996

Sex steroids, growth hormone, insulin-like growth factor-1: neuroendocrine and metabolic regulation in puberty.

UNLABELLED: The control of the onset of puberty involves the complex interaction of pituitary and gonadal hormones. At a preprogrammed time in a child's life there is an increase in the amplitude of GnRH pulses which triggers a cascade of events including increases in the amplitude of FSH and LH pulses, followed by marked increases in gonadal sex steroidal output, which in turn increases growth hormone (GH) and insulin-like growth factor-1 (IGF-1) production. Evidence suggests that there is an integral interaction between the endogenous opiate system and the hypothalamic-pituitary-gonadal axis, at least in the later stages of puberty in the male. Both androgenic and estrogenic hormones markedly increase GH production rates as measured by deconvolution models in the prepubertal human, and compelling data strongly suggest that it is indeed the estrogen which controls the feedback amplification of GH production during puberty even in the male. It appears that the prepubertal gonad is actively producing sex hormones which might be important in the control of GH production since early childhood. The translation of these neuroendocrine rhythms into distal metabolic actions is also reviewed. Utilizing isotopic tracer infusions of the essential amino acid leucine, studies clearly show a selective stimulation of whole body protein synthesis by both GH and IGF-1. GH, IGF-1 and androgenic hormones all increase in puberty, stimulating whole body protein anabolism during that period. However, we observed no protein-anabolic effect in the hypogonadal female given increasing doses of estrogen. The latter suggests that at least as it pertains to whole body protein effects, the action of androgens is probably mediated via the androgen and not the estrogen receptor, in clear distinction from the estrogen-mediated effects of androgens on the neuroendocrine axis. Calcium absorption and retention are also positively affected by the androgens as shown by significant increases in calcium absorption and retention after the administration of testosterone to the prepubertal male. This suggests an important role of sex steroidal hormones in the mineralization of the skeleton. IN CONCLUSION: GH, IGF-1 and sex steroids all markedly increase during puberty and their actions are amplified mutually as they control growth, increase muscle mass and affect the mineralization of the skeleton. The dichotomy of androgen and estrogen effects in the male and female may regulate the differential timing of the onset of puberty and final height in the two sexes. The synergistic actions of these anabolic hormones appear to be most significant during the finite years of puberty.

Adolescent↗

PubMed1996

The rationale for the use of recombinant human growth hormone and insulin-like growth factor-I for catabolic conditions in humans.

Patients with a variety of catabolic illnesses or conditions are subjected to protein catabolic losses which we attempt to address with traditional enteral or parenteral nutritional support. Accelerated protein catabolism and energy requirements together with inadequate intake or assimilation of exogenous amino acids are all contributing causes. Circulating glucocortico-steroids may play a significant contributing role in the redistribution and loss of body protein in acute, and possibly chronic, catabolic illnesses but such complex metabolic conditions are not easily studied. Short-term, high-dose glucocorticosteroid administration, a model for such protein catabolic condition, increases rates of whole-body proteolysis, increases amino acid oxidation, and decrease the effectiveness insulin in suppressing proteolysis. Recombinant human growth hormone (rhGH) administration alone in humans decreases amino acid oxidation and increases the estimated rate of whole body protein synthesis. The exact proteins affected by rhGH and the nutritional implications of this, remain to be determined. rhGH when given in combination with high-dose glucocorticosteroids offsets the protein catabolic effects of steroids alone. Thus, rhGH might provide a means to manipulate protein homeostasis in acute and possibly chronic catabolic conditions. Current data with the use of IGF-I is less clear and will require further investigation to clarify its potential role in such conditions. Finally, clear clinical utility of adjunctive rhGH and/or rhIGF-I therapy must be demonstrated to justify its wide applicability in specific clinical settings as a standard care.

Glucocorticoids↗

PubMed1996

Protein and energy metabolism in prepubertal children with sickle cell anemia.

We hypothesized that, in children with homozygous sickle cell anemia (HbSS), the shortened life-span of erythrocytes places an increased demand on protein stores, accelerates whole body protein turnover, and consequently, energy expenditure, as well as the rate of utilization of glutamine, a major fuel for reticulocytes. Eight (11.2 +/- 0.4 y old) children with HbSS who were free of infection of vaso-occlusive disease, and seven (11.3 +/- 0.4 y old) healthy black children were therefore studied in the postabsorptive state. Each received a continuous 4-h infusion of L-[1-(13)C]leucine to determine the rate of leucine oxidation, leucine rate of appearance, and nonoxidative leucine disposal, indicators of whole body protein breakdown and synthesis, respectively. Infusion of L-[2-(15)N]glutamine was used to assess rates of glutamine utilization. Resting energy expenditure and cardiac output were measured using indirect calorimetry and echocardiography, respectively. Compared with control subjects, HbSS children had a 58 and 65% higher leucine rate of appearance and nonxidative leucine disposal, respectively (both p < 0.001), 47% higher rates of whole body glutamine utilization (p < 0.01), 19% higher resting energy expenditure (p < 0.05), and 66% higher cardiac output (p < 0.01). In conclusion, children with HbSS show evidence of hypermetabolism with regard to protein, energy, and glutamine utilization. Both increased Hb synthesis and increased cardiac workload may contribute to excess protein and energy utilization. Whatever the mechanism of hypermetabolism, the data suggest that children with HbSS may have greater protein and energy requirements than the general population.

Amino Acids↗

PubMed1995

Use of [13C]bicarbonate infusion for measurement of CO2 production.

To determine whether infusion of 13C-labeled bicarbonate can be used to measure rates of CO2 production (VCO2), seven healthy adults received 6-h primed continuous intravenous infusions of NaH13CO3 and L-[1-14C]leucine in the post-absorptive state while VCO2 was measured by indirect calorimetry. Indirect calorimetry and the use of specific activity and rate of 14CO2 expired yielded identical values of VCO2: 8.97 +/- 0.82 and 8.80 +/- 0.83 mmol/min, respectively (P = NS). The concentration of NaH13CO3 in the infusates and the 13C enrichment in breath CO2 were determined using gas chromatography-isotope ratio mass spectrometry. The rate of appearance of CO2 measured using the NaH13CO3 infusion rate and the steady-state breath 13CO2 enrichments was 11.41 +/- 1.56 mmol/min, which was higher (P < 0.001) than that determined by either of the other two methods. When corrected for the recovery of labeled CO2 during the infusion of NaH13CO3 by use of published values, rate of appearance of CO2 was 9.24 +/- 0.78 mmol/min, which did not differ from VCO2 determined using the other two methods. We conclude that infusion of NaH13CO3 can be used to determine VCO2. This method should be useful to study the oxidation of substrates in populations such as ventilator-dependent neonates, in whom indirect calorimetry is laborious and inaccurate.

Adult↗

PubMed1994

Long-acting somatostatin analogue therapy and protein metabolism in patients with jejunostomies.

BACKGROUND/AIMS: Previous studies have shown that secretory losses in patients with end jejunostomy syndrome (EJS) on home parenteral nutrition (HPN) can be suppressed by the somatostatin analogue, octreotide, thus facilitating fluid balance. However, the hormone also has antianabolic actions that may interfere with the use of infused amino acids. METHODS: Amino acid metabolism, pancreatic enzyme synthesis and secretion, and mucosal protein turnover were measured by primed/continuous intravenous infusion of [1-14C] leucine tracer, duodenal aspiration, and endoscopic mucosal biopsy techniques during hormonal stimulation with pentagastrin and cholecystokinin 8. RESULTS: In comparison with normal healthy controls, baseline measurements of amino acid metabolism were normal in patients with EJS/HPN, but pancreatic enzyme synthesis and secretion were elevated. Octreotide therapy improved fluid balance but suppressed gut hormone (insulin, gastrin, glucagon, peptide YY) levels in blood and the uptake of amino acids into pancreatic enzyme and mucosal proteins, increasing oxidative losses. CONCLUSIONS: Octreotide improves fluid balance in patients who have undergone jejunostomy but reduces the use of amino acids for splanchnic protein synthesis. This may interfere with the physiological process of adaptation to intestinal resection.

Adult↗