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Biomedical subjects

S C Kalhan

Publications and source records attributed to S C Kalhan.

At least 55 records · Page 3Linked to original sources
PubMed1995

Beta-adrenergic blockade heightens the exercise-induced increase in leucine oxidation.

The purpose of this study was to assess the interaction between beta-blockade and exercise on amino acid kinetics. This was a three-way crossover experiment using beta 1-blockade, beta 1,beta 2-blockade, and a placebo control. Three 6-h L-[1-13C]leucine and L-[alpha-15N]lysine infusions were performed. The first 3 h established an isotopic steady state, and 1 h of exercise (approximately 50% of maximal O2 consumption) and 2 h of recovery followed. Plasma glucose decreased with exercise during all trials (P < 0.0001). During beta 1- and beta 1,beta 2-blockade, plasma free fatty acids were reduced during rest and exercise (P < 0.001). Leucine and lysine rates of appearance were unaffected by beta-blockade during rest but were decreased with placebo exercise. Leucine oxidation increased with beta-blockade (P < 0.01) and exercise (P < 0.001). There was a statistical interaction between both treatments (P < 0.004). In conclusion, leucine oxidation increased with exercise, further increased with beta 1-blockade, and was additionally heightened with beta 1,beta 2-blockade. This cumulative response indicates that leucine oxidation was regulated through beta 1- and beta 2-receptors.

Adrenergic beta-Antagonists↗
PubMed1995

A limitation in the use of mass isotopomer distributions to measure gluconeogenesis in fasting humans.

The use of distributions of mass isotopomers in glucose from [U-13C]glycerol to estimate fractional rates of gluconeogenesis was examined. [U-13C]glycerol was infused into normal subjects who ingested acetaminophen and fasted for 60 h. Isotopomer distributions were measured by mass spectrometry in blood glucose and in glucuronic acid from urinary acetaminophen glucuronide. The distributions are incompatible with glucose production solely via gluconeogenesis from a single pool of triose phosphates. Rather, with the assumption of a single enriched triose phosphate pool, the distributions indicate, despite the 60 h of fasting, about as much glucose formation from an unlabeled glucose source as from that pool. Therefore the data indicate cellular heterogeneity in glycerol's metabolism, so that two or more pools with significantly different enrichments were the source of the glucose and glucuronic acid. This heterogeneity is related to much greater concentrations of glycerol in periportal than in pericentral zones of the liver lobule. Beyond evidence for heterogeneity, the findings emphasize a limitation in applying analyses of mass isotopomer distributions to measure polymer biosynthesis in the presence of heterogeneity in the precursor pool.

Acetaminophen↗
PubMed1995

Persistence of metabolic consequences in the progeny of rats fed a HC formula in their early postnatal life.

First-generation (1-) male and female rat pups were either reared artificially on a high-carbohydrate (HC) or a high-fat (HF) formula or nursed by mother (MF) from day 4 and weaned onto a stock diet on day 24. 1-HC rats compared with sex-matched control rats (1-HF and 1-MF) were hyperinsulinemic and mildly obese by day 60. We investigated the effect of maternal hyperinsulinemia on the second generation (2-) by intragroup breeding. The 2-HC male and female rats were hyperinsulinemic on day 45, had significantly increased growth rate from approximately day 60 onward, and became obese as evidenced by increased adipose tissue mass due to hypertrophy on day 100. The lipogenic capacity of liver and adipose tissues was significantly higher in the 2-HC than in control rats. Thus the metabolic changes that occurred in the first-generation rats fed a HC formula during early postnatal life not only persisted into their adult life but were also passed on to the next generation.

Adipose Tissue↗
PubMed1995

Use of 2H2O for estimating rates of gluconeogenesis. Application to the fasted state.

A method is introduced for estimating the contribution of gluconeogenesis to glucose production. 2H2O is administered orally to achieve 0.5% deuterium enrichment in body water. Enrichments are determined in the hydrogens bound to carbons 2 and 6 of blood glucose and in urinary water. Enrichment at carbon 6 of glucose is assayed in hexamethylenetetramine, formed from formaldehyde produced by periodate oxidation of the glucose. Enrichment at carbon 2 is assayed in lactate formed by enzymatic transfer of the hydrogen from glucose via sorbitol to pyruvate. The fraction gluconeogenesis contributes to glucose production equals the ratio of the enrichment at carbon 6 to that at carbon 2 or in urinary water. Applying the method, the contribution of gluconeogenesis in healthy subjects was 23-42% after fasting 14 h, increasing to 59-84% after fasting 42 h. Enrichment at carbon 2 to that in urinary water was 1.12 +/- 0.13. Therefore, the assumption that hydrogen equilibrated during hexose-6-P isomerization was fulfilled. The 3H/14C ratio in glucose formed from [3-3H,3-14C]lactate given to healthy subjects was 0.1 to 0.2 of that in the lactate. Therefore equilibration during gluconeogenesis of the hydrogen bound to carbon 6 with that in body water was 80-90% complete, so that gluconeogenesis is underestimated by 10-20%. Glycerol's contribution to gluconeogenesis is not included in these estimates. The method is applicable to studies in humans of gluconeogenesis at safe doses of 2H2O.

Adult↗
PubMed1994

Rigorous management of insulin-dependent diabetes mellitus during pregnancy.

The effect of rigorous management of insulin-dependent diabetes mellitus (IDDM) during pregnancy on the perinatal outcome was assessed by comparing 78 prepartum gravid patients with IDDM managed prospectively with 78 matched controls. The diabetic women were treated with insulin by either infusion pump or split-dose therapy, with the goal of normalization of the fasting blood sugars and hemoglobin Hb A1c values. Differences in the perinatal outcome were evaluated by either chi-square or analysis of variance. Of the women with IDDM, 14% where White class B, 43% class C, 26% class D, 17% classes R and F. The mean Hb A1c value in the first half of pregnancy was 8.49% +/- 2.30%, and 7.34% +/- 1.79% in the second half. Women with IDDM had higher rates of premature delivery (31% vs. 10%, P = 0.003), pre-eclampsia (15% vs. 5%, P = 0.035), and cesarean section (55% vs. 27%, P = 0.002). Complications of infants born to diabetic mothers included large size for gestational age (41% vs. 16%, P = 0.0002), hypoglycemia (14% vs. 1%, P = 0.0025), hyperbilirubinemia (46% vs. 23%, P = 0.0002), and respiratory distress (12% vs. 1%, P = 0.008). The Apgar scores and mortality were similar. Congenital malformations occurred in 7.7% of infants of diabetic mothers and 1.3% of controls (P = 0.05). The maternal Hb A1c level did not correlate with the infant size for gestation. Although the improved medical management of IDDM has decreased neonatal mortality, significant perinatal complications persist.

Adolescent↗
PubMed1994

Leucine kinetics during a brief fast in diabetes in pregnancy.

The effect of diabetes in pregnancy on leucine turnover and oxidation was examined in 12 insulin-dependent diabetic (IDDM) subjects and 12 gestationally diabetic (GDM) subjects during the third trimester of pregnancy. The data were compared with those in normal pregnant women studied during the same time period and reported previously. Eight of the IDDM subjects were on continuous subcutaneous insulin infusion (insulin pump), and four were on conventional twice-daily insulin treatment. Of the GDM group, seven were on insulin therapy and five were on dietary management. Leucine kinetics were quantified using [1-13C]leucine tracer in combination with respiratory calorimetry and measurement of lean body mass using the H2[18O] dilution method. In addition, glucose kinetics were measured in insulin-treated subjects using [6,6(2)H2]glucose tracer. Despite rigorous metabolic control, fasting plasma glucose (IDDM 5.5 +/- 1.9 mmol/L [P < .05], GDM 4.7 +/- 1.3 [P < .01], controls 3.6 +/- .6, mean +/- SD) and hemoglobin A1 ([HbA1] IDDM 7.9 +/- 1.9%, GDM 7.5% +/- 2.1%) levels were higher in diabetic subjects. Although total insulin levels were higher in insulin-treated diabetic subjects, free-insulin concentrations were similar in all groups. Rates of excretion of urinary urea nitrogen and respiratory quotients were also similar. The rate of glucose turnover was lower in insulin-treated subjects compared with normals. Leucine flux, a measure of the rate of protein breakdown, and leucine oxidation were higher in IDDM and insulin-treated GDM subjects. The rate of leucine oxidation was increased in conventionally managed IDDM and insulin-treated GDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Roles of insulin resistance and beta-cell dysfunction in the pathogenesis of glucose intolerance in cystic fibrosis.

The roles of insulin deficiency and insulin resistance in the pathogenesis of glucose intolerance in cystic fibrosis (CF) were evaluated in eight patients (aged 16.5 +/- 1.9 yr), four with normal glucose tolerance (NGT) and four with impaired glucose tolerance (IGT), and in seven healthy control (CN) subjects. First and second phase insulin secretions were evaluated during a hyperglycemic clamp. Hepatic glucose production (HGP) and insulin-stimulated glucose disposal were measured using [6,6-2H2]glucose and a stepwise hyperinsulinemic-euglycemic clamp. First and second phase insulin levels were significantly lower in both groups of CF patients compared with control values. There was an inverse relationship between glycohemoglobin level and first phase insulin (r = -0.81; P = 0.015) and second phase insulin (r = -0.97; P < 0.001). During the hyperglycemic clamp, the insulin sensitivity index was lower in CF-IGT, but not CF-NGT, compared with control values (6.66 +/- 1.79, 12.82 +/- 1.61, and 13.02 +/- 1.78 mumol/kg.min/pmol.L, respectively; P < 0.05). Basal HGP and fasting plasma glucose were higher in CF vs. CN [24.8 +/- 2.9 vs. 16.9 +/- 1.4 mumol/kg.min (P = 0.036) and 5.8 +/- 0.2 vs. 5.4 +/- 0.1 mmol/L (P = 0.035), respectively]. During the hyperinsulinemic euglycemic clamp, insulin-stimulated glucose disposal was significantly lower in CF-IGT (45.68 +/- 4.87 mumol/kg.min) vs. CF-NGT (78.99 +/- 1.34 mumol/kg.min) and CN (71.74 +/- 6.88 mumol/kg.min). Insulin sensitivity was lower in CF-IGT vs. CF-NGT (7.04 +/- 0.86 and 14.38 +/- 0.84 mumol/kg.min/pmol.L; P < 0.05). We conclude that 1) glycohemoglobin is a strong correlate of insulin deficiency in CF; and 2) glucose intolerance in this group of CF patients occurred as a consequence of concomitant insulin deficiency and insulin resistance.

Adolescent↗
PubMed1994

Correlations between fatty acid and glucose metabolism. Potential explanation of insulin resistance of puberty.

In vivo resistance to the action of insulin on glucose uptake has been documented during puberty. To test the hypothesis that the glucose-fatty acid cycle, as proposed by Randle et al. (Randle PJ, Garland PB, Hales CN, Newsholme EA: The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785-789, 1963), may be responsible for this phenomenon, we studied nine prepubertal (Tanner I), nine pubertal (Tanner II-IV), and five young adult healthy subjects. The rate of lipolysis was measured with [d-5]glycerol tracer during basal state and during a stepwise hyperinsulinemic (10 and 40 mU.m-2.min-1)-euglycemic clamp. The rates of insulin-stimulated glucose disposal (Rd) were measured during the clamp, whereas glucose and fat oxidation were measured by using indirect respiratory calorimetry. Basal glycerol rate of appearance (Ra; lipolysis) and fat oxidation were similar between prepubertal and pubertal subjects but higher than adults when the data were expressed per kilogram body weight or per kilogram fat-free mass (FFM; glycerol Ra: 2.5 +/- 0.2, 2.6 +/- 0.2 vs. 1.6 +/- 0.2 mumol.min-1.kg FFM-1, P < 0.05; fat oxidation: 4.4 +/- 0.6, 4.8 +/- 0.3 vs. 3.2 +/- 0.6 mumol.min-1.kg FFM-1, P < 0.05). However, when expressed for total body, glycerol Ra and fat oxidation were higher in pubertal versus prepubertal and adult subjects. Insulin-like growth factor I (IGF-I) levels correlated with total-body lipolysis (r = 0.52, P = 0.006) and with total lipid oxidation (r = 0.44, P = 0.016) at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Glucose metabolism in a term infant with transient hyperinsulinism and high carbohydrate intake.

Transient hyperinsulinaemia is a well-known cause of hypoglycaemia in newborn infants. The hypoglycaemia may be caused by a decreased glucose production and/or an increased glucose uptake. Whether the increased uptake is caused by increased glucose oxidation or increased non-oxidative disposal is not known. The aim of this study was to investigate the fate of the large amount of glucose infused in a term infant who developed hypoglycaemia due to transient hyperinsulinaemia shortly after birth and was treated with high glucose infusions. On day 6 an indirect calorimetry study was performed, together with a glucose turnover study. Carbohydrate intake was 13.6 mg/kg per minute (19.6 g/kg per day). Both studies were repeated on day 11, when carbohydrate intake was normalised to 7.8 mg/kg per minute (11.2 g/kg per day). Glucose oxidation was 28% higher and non-oxidative glucose disposal was 257% higher on day 6 as compared to day 11. Our results indicate that hypoglycaemia during hyperinsulinism is the result of increased non-oxidative disposal of glucose and not increased glucose oxidation. The results indicate a remarkable capacity of the newborn for lipogenesis during high carbohydrate intake.

Adipose Tissue↗
PubMed1993

Vasoactive intestinal polypeptide causes relaxation of the pyloric sphincter in the rabbit.

Vasoactive intestinal peptide (VIP), which causes relaxation of gastrointestinal smooth muscle, has been found in high concentrations in the pylorus in many animal species, suggesting a prominent role for VIP in the control of pyloric sphincter function. We infused VIP into the gastric artery of 6 rabbits at rates from 12 to 1,200 ng/min and measured the intensity, duration, and frequency of spontaneous pyloric contractions with an intraluminal balloon and electromyography. VIP produced a dose-dependent reduction in the intensity (55% +/- 15% of baseline, P < .001) and the duration (29% +/- 25%, P < .001) of pyloric contraction. Maximal inhibition was observed at an infusion rate of 240 ng/min. The frequency of contractions did not decrease significantly in response to VIP infusion. Neostigmine infusion increased the intensity of pyloric contraction in a dose-dependent manner in doses of 0.10, 0.15, and 0.25 mg (140% +/- 78%, 273% +/- 76%, and 357% +/- 26% of baseline, respectively; P < .001). VIP infusion at 12 ng/min and 480 ng/min completely inhibited the increased intensity of contraction at neostigmine doses of 0.10 and 0.15 mg, respectively. Our results show that VIP decreases the intensity and the duration of pyloric contraction in a dose-dependent manner. As pyloric spasm may contribute to the pathogenesis of hypertrophic pyloric stenosis, we can postulate a role for reduced VIP-induced relaxation in the pathophysiology of hypertrophic pyloric stenosis.

Animals↗
PubMed1993

Hepatic insulin action in adolescents with insulin-dependent diabetes mellitus: relationship with long-term glycemic control.

The relationship between hepatic insulin action and long-term glycemic control was assessed in 20 adolescents with insulin-dependent diabetes mellitus (IDDM) and five healthy matched controls using a two-step (0.8 and 1.6 mU/kg/min) hyperinsulinemic-euglycemic clamp and [6,6-2H2]glucose. The night before the study, diabetic patients received variable-rate intravenous insulin in an attempt to normalize fasting plasma glucose concentrations. In the postabsorptive state, hepatic glucose production (HGP) was similar in IDDM patients and controls (593 +/- 40 v 518 +/- 27 mumol/m2/min); however, plasma glucose and free insulin concentrations were higher in IDDM patients than in controls (6.5 +/- 0.4 v 5.4 +/- 0.1 mmol/L [P = .01], and 207 +/- 21 v 104 +/- 10 pmol/L [P < .001], respectively). There was a positive correlation (r = .62 P = .002) between basal HGP and glycohemoglobin level (HbA1). Separation of the patients at the median HbA1 (group no. 1 < and group no. 2. > 11.4% HbA1) revealed two distinct patient populations with regard to hepatic and peripheral insulin action and plasma free fatty acid (FFA) suppression. During hyperinsulinemia, the percent suppression of HGP was lower in group no. 2 compared with group no. 1 (65.7% +/- 9.8% v 94.4% +/- 3.8%; P = .018). Rates of glucose disposal were lower in group no. 2 compared with controls and with group no. 1. Postabsorptive FFA levels were similar between group no. 2 and group no. 1 (0.45 +/- 0.03 and 0.43 +/- 0.04 mmol/L) despite higher free-insulin concentrations in group no. 2 (260 +/- 30 v 171 +/- 25 pmol/L; P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Long-term effects on pancreatic function of feeding a HC formula to rats during the preweaning period.

We have investigated pancreatic changes associated with hyperinsulinemia and an insulin secretory response to an oral glucose load in a new rat model for obesity. Male Sprague-Dawley pups were reared on a high-carbohydrate (HC) or high-fat (HF) formula by gastrostomy during the suckling period and were weaned onto a stock diet. These animals remained either nutritionally unchallenged or challenged with a high-sucrose diet during the postweaning period. The HC formula-fed animals showed increased insulin concentrations in the plasma and pancreas and also showed impaired insulin secretory response compared with mother-fed control or HF animals in adult life. Immunocytochemical and morphometric studies revealed that hyperinsulinemia in the HC animals during the preweaning period and also in adult life was associated with hypertrophy of beta-cells in the pancreas. The results show that consumption of a HC formula during the suckling period influences pancreatic islet morphology resulting in hyperinsulinemia which eventually leads to the development of obesity later in adult life.

Animals↗
PubMed1993

Catecholamine response at birth in preterm newborns.

We compared the extrauterine adaptation of preterm with term newborn infants, by sequentially measuring plasma catecholamine (CAT) levels at birth and during the first 24 h of life. Twenty-seven preterm appropriate-for-gestational-age (AGA) infants, less than 35 weeks gestation, were compared with 26 healthy near-term AGA infants. Modes of delivery and umbilical arterial pH (mean 7.28) did not differ. Infants with asphyxia, presumed sepsis or hypoglycemia were excluded. CAT (norepinephrine, epinephrine, dopamine) levels were measured by radioenzymatic assay in blood samples from maternal vein, cord vein, cord artery and blood samples obtained at 1, 2 and 24 h of postnatal age. At birth, the cord arterial CAT levels were significantly higher than maternal venous CAT levels in both groups of neonates. Plasma epinephrine levels (mean +/- SD) at 1 and 2 h of postnatal age were significantly higher in preterm than in near-term newborns (0.98 +/- 0.82 nmol/l vs. 0.30 +/- 0.21 nmol/l at 1 h; 0.98 +/- 0.68 nmol/l vs. 0.28 +/- 0.29 nmol/l at 2 h; p < 0.05). The norepinephrine and dopamine measurements did not differ between the two groups studied at birth, 1, 2 and 24 h of postnatal age. These data indicate that the preterm infants (25-35 weeks gestation) are capable of mounting a catecholamine response at birth similar to near-term newborns. The persistent elevation of epinephrine in preterm infants at 1 and 2 h of life may be attributed to either slower clearance of epinephrine or continued stimulation during clinical care in the NICU.

Delivery, Obstetric↗
PubMed1993

Maternal-fetal substrate relationships in the third trimester in human pregnancy.

The maternal-fetal relationship of metabolic substrates was examined in 12 mothers undergoing cordocentesis for clinical reasons between 23 and 36 weeks' gestation. Twenty cordocentesis procedures were performed. Blood glucose, insulin, beta-hydroxybutyrate, glycerol and lactate were measured in simultaneously obtained maternal and fetal samples. There was a linear correlation between fetal and maternal concentration of glucose (y = 0.687x + 0.756, R2 = 0.65 and p = 0.001), and beta-hydroxybutyrate (y = 0.443x + 0.16, R2 = 0.938 and p = 0.0001). No relation between fetal insulin and glucose concentration was observed. No correlation was seen between maternal and fetal lactate concentration. The data on glycerol could be divided into two groups. When the fetal glycerol levels were below 100 mumol/l, the fetal glycerol concentration was always less than the simultaneously obtained maternal level. However, when the fetal glycerol levels were greater than 100 mumol/l, the corresponding maternal levels were lower than that in the fetus. The exact mechanism or significance of higher fetal glycerol levels remains unknown. These data demonstrate the usefulness of cordocentesis in the understanding of fetal metabolism. In correlation with isotopic tracer, cordocentesis could provide detailed insight into human fetus in the future.

3-Hydroxybutyric Acid↗
PubMed1993

Decreased glucose oxidation in preterm infants fed a formula containing medium-chain triglycerides.

Several formulas for preterm infants contain medium-chain triglycerides (MCT) to enhance fat absorption. Although fat absorption with MCT was slightly higher in several studies in preterm infants, a beneficial effect on growth has only been reported in one publication. We hypothesized that when part of the fat blend of preterm formula is substituted by MCT oil, this might lead to a different metabolic pattern in which, due to the preferential oxidation of MCT, an increase in lipogenesis from glucose could lead to an increase in metabolic rate. To study the impact of MCT on glucose metabolism, 18 preterm infants were randomized to receive either an MCT or an LCT formula containing 38- and 6%-by-weight medium-chain fatty acids, respectively, in their fat blend. At 4 wk of age, the metabolic rate, substrate utilization, glucose kinetics, and oxidation were measured by indirect respiratory calorimetry in combination with a constant-rate oral infusion of [U-13C]glucose. The "true" rate of appearance of glucose (Ra "true") was measured from the dilution of the uniformly labeled (m + 6) species of infused tracer, whereas "apparent" rate of appearance of glucose (Ra "apparent") was measured from the dilution of infused tracer C (carbon). The latter was measured by an on-line combustion method using a gas chromatograph-isotope ratio mass spectrometer. At a carbohydrate intake of 8.4 mg.kg-1.min-1, total utilization of carbohydrate was equal in both groups at 7.6 mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary Carbohydrates↗
PubMed1993

Rates of urea synthesis in the human newborn: effect of maternal diabetes and small size for gestational age.

The rates of urea synthesis and glucose turnover were quantified during fasting using [15N2]urea and [6,62H2]glucose tracers with the prime constant rate infusion technique in 33 infants: 19 normal infants, 10 infants of diabetic mothers (IDM), and four small for gestational age (SGA) infants born at term gestation. All infants were studied during fasting 4 h after their last feed. Eleven normal infants and six IDM were studied soon after birth before any feeding. The rate of urea synthesis in normal infants was 5.84 +/- 2.0 mg of nitrogen (N)/kg.h-1 or 3.5 mumol of urea/kg.min-1. The rate was slightly higher in IDM (7.09 +/- 3.0 mg N/kg.h-1) and lower in SGA infants (4.59 +/- 1.22 mg N/kg.h-1); however, the differences were not statistically significant. No differences in urea synthesis were observed between infants studied soon after birth and those studied after initiation of feeding. The rate of appearance of glucose was lower in IDM infants studied during the first 6 h after birth (IDM 19.62 +/- 2.14 mumol/kg.min-1, normal infants 24.03 +/- 4.05 mumol/kg.min-1, p = 0.01). However, rate of appearance of glucose in IDM infants studied between 17 and 20 h after birth was similar to that in normal infants. Rate of appearance of glucose was lower (not significantly) in SGA infants (17.7 +/- 3.3 mumol/kg.min-1) as compared with normal infants. No correlation between rates of urea synthesis and glucose turnover was observed. These data show that newborn infants during fasting have an obligatory rate of protein oxidation of approximately 0.87 g/kg.d-1 and that maternal diabetes has no effect on it.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗
PubMed1992

In vivo differences between the turnover rates of leucine and leucine's ketoacid in stable cirrhosis.

Based on urinary nitrogen excretion, previous studies have indicated increased protein breakdown rates in cirrhosis. However, studies using [1-13C]-leucine infusion methodology have found normal protein breakdown rates. Because abnormal partitioning between extracellular and intracellular leucine exists in cirrhosis, plasma enrichment of leucine's keto acid (KIC), a marker of intracellular leucine, may more accurately reflect protein metabolism than plasma [1-13C]leucine enrichment. Therefore, protein breakdown and oxidation were calculated using both [1-13C]leucine and [1-13C]KIC and compared with urinary nitrogen excretion in seven cirrhotics and seven matched controls after an overnight fast. The ratio of KIC and leucine plasma enrichment was decreased (P less than 0.001) in cirrhosis because of lower KIC enrichment (P less than 0.006). Cirrhotics had increased rates of protein breakdown (P less than 0.006) and protein oxidation (P less than 0.05) based on KIC (P less than 0.006) but not leucine enrichment. In controls, protein oxidation calculated from urinary nitrogen excretion did not differ from KIC results (0.88 +/- 0.08 vs. 0.83 +/- 0.06) but was higher than the leucine method (0.88 +/- 0.08 vs. 0.73 +/- 0.05; P less than 0.01). However, in cirrhotics protein oxidation based on urinary nitrogen was lower than the KIC methodology (P less than 0.01). Therefore, cirrhotics have accelerated rates of protein breakdown and oxidation associated with increased extrarenal nitrogen loss. Furthermore, these results suggest abnormal leucine transport across cell membranes.

Adult↗