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D E Matthews

Publications and source records attributed to D E Matthews.

At least 37 records · Page 2Linked to original sources
PubMed1999

Measurement of homocysteine concentrations and stable isotope tracer enrichments in human plasma.

Elevated levels of plasma homocysteine have been established as an independent risk factor for cardiovascular disease. Homocysteine is in low concentration in plasma (5-15 microM) and is bound to other thiols (e.g., cysteine in plasma proteins) via disulfide bonds. Existing methods for measuring homocysteine have difficulty in reducing and maintaining the reduction of homocysteine for measurement. We describe a GC/MS method that first reduces the disulfides in the physiological sample matrix and then immediately alkylates the free thiols with 4-vinylpyridine to prevent the reformation of the disulfide bonds. We use a deuterated internal standard, [3,3,3',3',4,4,4',4'-2H8]homocystine to account for losses associated with the isolation, derivatization, and measurement of the natural homocysteine. The amino acids are separated and derivatized to form the tert-butyldimethylsilyl derivatives. This method requires only 50 microL of plasma to measure homocysteine concentrations to 5 microM. Total homocysteine concentrations in plasma can be measured routinely from 0.5-mL samples with relative intra- and interday precisions of 1.3 and 4.0%, respectively. This method is sensitive enough to determine tracer enrichments of [1-13C]homocysteine with a detection limit of < 0.3 mol% excess and an average tracer precision of 0.6%.

Algorithms↗
PubMed1999

Splanchnic utilization of enteral alanine in humans.

The splanchnic bed extracts the majority of the enteral nonessential amino acids glutamine and glutamate, while extracting a much smaller proportion of essential amino acids such as leucine and phenylalanine. Alanine is an abundant nonessential amino acid that plays an important role in hepatic gluconeogenesis and ureagenesis. However, its enteral fate has not been studied. Twelve normal healthy postabsorptive adults received a 7-hour infusion of [1-13C]alanine, 3.5 hours intravenously (IV) and 3.5 hours via a nasogastric tube (NG). The order of infusion was randomized among subjects. Alanine kinetics were calculated from the enrichments of plasma alanine 13C and expired 13CO2. The alanine appearance rate (Ra), measured during the IV tracer infusion, was 279+/-17 micromol/kg/h; 92%+/-2% of the IV-infused and 86%+/-2% of the NG-infused [1-13C]alanine tracer was recovered as 13CO2. From the difference in plasma alanine 13C enrichment between IV-infused and NG-infused tracers, we determined that the splanchnic bed extracted 69%+/-1% of the enterally delivered alanine tracer on the first pass during absorption. Only one third of the enteral alanine passed intact through the splanchnic bed and was made available to systemic tissues. Of the enteral alanine extracted, 83%+/-3% of the carboxyl-carbon label was recovered as CO2, leaving only 17% of the sequestered alanine available for use in splanchnic protein synthesis. Thus, the splanchnic bed, presumably the liver, extracts and metabolizes most of the enterally delivered alanine.

Adult↗
PubMed1999

Splanchnic bed utilization of enteral alpha-ketoisocaproate in humans.

The branched-chain ketoacids (BCKAs) are used as dietary supplements to spare essential amino acid nitrogen, yet little is known about their absorption and utilization in the body. To study the fate of enterally delivered alpha-ketoisocaproate (KIC), seven healthy adults were infused in the postabsorptive state with [1-(13)C]KIC and [phenyl-2H5]phenylalanine intravenously (NGI) and with [5,5,5-2H3]KIC by nasogastric tube (NG). After 3.5 hours, the routes of tracer infusion were switched for an additional 3.5 hours. Each subject received a second infusion study on a different day with the order of tracer infusion reversed. KIC and phenylalanine kinetics and first-pass uptake and disposal of the enteral tracer by the splanchnic bed were calculated from the tracer enrichments measured in plasma KIC, leucine, and phenylalanine and breath CO2. Phenylalanine flux was 39.5 +/- 1.2 micromol/kg/h during the i.v. infusion periods. KIC flux was 33.1 +/- 1.8 and 30.4 +/- 1.4 micromol/kg/h measured with 13C- and 2H3-KIC, respectively, and these values were significantly different. The fraction of enterally delivered tracer sequestered by the splanchnic bed on the first pass was 30.9% +/- 2.0%, 30.0% +/- 1.4%, and 30.7% +/- 2.7% for 13C-KIC, 2H3-KIC, and 2H5-phenylalanine, respectively. The fraction of infused 13C-KIC tracer recovered as 13CO2 was 27.1% +/- 1.2% and 24.0% +/- 0.9% during i.v. and NG infusion, respectively. From these data, the fraction of ng KIC tracer extracted and oxidized on the first pass was calculated to be 5.1% +/- 1.1%. This fraction was greater than that previously reported for leucine extraction and oxidation (2%), but it was still only a small fraction of the overall extraction (5/30 = 16%). Because the only two fates of the KIC tracer extracted by the splanchnic bed are oxidation or transamination to leucine, the majority (84%) of the KIC tracer was extracted and converted to leucine. These results demonstrate that KIC delivered enterally to postabsorptive humans is rapidly extracted and predominantly converted to leucine by the splanchnic bed. This leucine appears to be available for use by both the splanchnic bed and the whole body.

Adult↗
PubMed1999

The role of glucose, long-chain triglycerides and amino acids for promotion of amino acid balance across peripheral tissues in man.

The role of amino acids, glucose and lipids in improving amino acid balance in peripheral tissues was evaluated. Primed constant infusion of L-[ring-2H5]phenylalanine in combination with flux measurements of glucose, free fatty acids (FFA) and amino acids across arm and leg tissues were applied in male volunteers after an overnight fast with subsequent primed constant infusions of amino acids (0.2 g N kg-1 body weight day-1), long-chain triglycerides (0.98-1.079 g kg-1 day-1) and glucose (3.13-3.62 g kg-1 day-1). Amino acids and phenylalanine tracer infusion continued for 6 h; the lipid infusion was provided during 2-6 h from the start, and glucose infusion was provided between 4 and 6 h. Flux measurements were performed at steady state before the next infusion started. Arterial concentrations of infused substrates increased during provision, but remained constant thereafter. Plasma insulin increased when glucose was provided, whereas insulin-like growth factor (IGF) I was unchanged during all infusions. Blood flow was unchanged in arm tissue during all infusions, while leg blood flow increased during fat and glucose infusion. FFA and glucose balance were unchanged during amino acid infusion but improved during lipid and glucose infusions. Amino acid balance was negative across arm and leg tissues in the fasted state, but reached balance during amino acid infusion. This effect was equally dependent on protein synthesis and protein degradation without any contribution from lipids and glucose. 3-Methylhistidine release from tissues was not influenced by any substrate. Our results suggest that extracellular amino acid concentrations determine amino acid balance across peripheral tissues independently of non-protein calories, insulin and IGF-I.

Adult↗
PubMed1999

Systemic resistance to the antilipolytic effect of insulin in black and white women with visceral obesity.

This study was designed to determine the role of visceral adipose tissue (VAT) accumulation in systemic fat metabolism and to compare this in black and white women who differ in their manifestations of upper body obesity. Systemic glycerol and free fatty acid (FFA) turnover rates (rates of appearance, Ra) were measured in the basal state and during a pancreatic euglycemic clamp in nondiabetic, premenopausal, obese black and white women with a wide range of VAT accumulation. The slopes of the regression equations predicting basal and insulin-suppressed RaGlycerol and RaFFA from VAT area, age, and fat mass or fat-free mass did not significantly differ between black and white women. VAT area was the best predictor of the %-suppressed RaGlycerol and RaFFA during the pancreatic clamp (partial r = 0.76, P < 0.0001 and partial r = 0.60, P < 0.05, respectively). Basal R(a)Glycerol, but not RaFFA, was lower in black than in white women (P < 0.05). During the clamp, black women showed greater insulin suppression of RaGlycerol than of RaFFA (P < 0.0001) and greater insulin suppression of RaGlycerol (P < 0. 05) but similar suppression of RaFFA compared with white women. These differences were independent of age, fat mass, or fat-free mass and were partly explained by a lower VAT in black women. Thus, in both races, VAT accumulation was associated with systemic resistance to the antilipolytic effect of insulin and, in obese black women, systemic lipolysis measured as glycerol turnover rate was more responsive to insulin suppression than were systemic FFA turnover rates.

Adipose Tissue↗
PubMed1999

Assessment of physical activity in older individuals: a doubly labeled water study.

We compared the accuracy of two physical activity recall questionnaires and a motion detector in 45- to 84-yr-old women (n = 35) and men (n = 32), using doubly labeled water (DLW) in conjunction with indirect calorimetry as the criterion measure. Subjects were administered the Yale Physical Activity Survey (YPAS) and Minnesota Leisure Time Physical Activity Questionnaire (LTA). Physical activity energy expenditure was determined over a 10-day period by using a Caltrac uniaxial accelerometer and DLW in conjunction with indirect calorimetry. In older women, Minnesota LTA (386 +/- 228 kcal/day) and Caltrac (379 +/- 162 kcal/day) underestimated physical activity by approximately 55% compared with DLW (873 +/- 244 kcal/day). No difference was observed between daily physical activity measured by the YPAS (863 +/- 447 kcal/day) and DLW in older women. In older men, Minnesota LTA (459 +/- 288 kcal/day) and Caltrac (554 +/- 242 kcal/day) underestimated daily physical activity by approximately 50-60% compared with DLW (1,211 +/- 429 kcal/day). No difference was found between physical activity measured by the YPAS (1,107 +/- 612 kcal/day) and DLW in older men. Despite no difference in mean physical activity levels between YPAS and DLW in women and men, Bland and Altman (Lancet 1: 307-310, 1986) analyses demonstrated poor concordance between DLW and YPAS (i.e., limits of agreement = -1,310-1,518 kcal/day). Our data suggest that the Minnesota LTA recall and Caltrac uniaxial accelerometer may significantly underestimate free-living daily physical activity energy expenditure in older women and men. Although the YPAS compares favorably with DLW on a group basis, its use as a proxy measure of individual daily physical activity energy expenditure may be limited in older women and men.

Aged↗
PubMed1999

Obesity-related phenotypes and the beta3-adrenoceptor gene variant in postmenopausal women.

We examined the hypothesis that postmenopausal women with the beta3-adrenoceptor gene variant (Trp64Arg) have reduced total daily energy expenditure (TEE), altered free fatty acid kinetics, and increased intra-abdominal fat. A secondary objective was to examine whether the obese state masks the effect of the variant on resting metabolic rate (RMR). There were 23 obese heterozygous women with the genetic variant (age 58 +/- 6 years; BMI 36 +/- 7 kg/m2) who were compared with 19 homozygous obese women with the normal allele (age 56 +/- 4 years; BMI 36 +/- 3 kg/m2). Daily energy expenditure was determined from doubly labeled water and indirect calorimetry, lipolysis from infusion of [1-13C]palmitate, and body fat distribution from computed tomography. No significant differences were found in TEE, RMR, energy expenditure of physical activity, the thermic effect of a meal, fat oxidation as estimated by fasting and postprandial respiratory quotients (RQs), or rate of lipolysis. Similarly, no difference was found in visceral adipose tissue and abdominal subcutaneous fat areas. When RMR was compared between obese (n = 23) and never-obese women with the Trp64Arg variant (n = 16), we found a 317 kcal/day lower RMR in never-obese women after controlling for fat mass, fat-free mass, and age (P < 0.0017). These results do not support the hypothesis that already obese women with the Trp64Arg polymorphism of the beta3-adrenergic receptor gene have lower daily energy expenditure, altered lipolysis, and increased abdominal obesity. On the other hand, the lower RMR in never-obese women suggests that the obese state may mask a moderate effect of the Trp64Arg variant on energy expenditure. Although these results need to be confirmed in other populations, the obese state may have been a confounding factor in previous studies of the beta3-adrenoceptor Trp64Arg variant and energy expenditure.

Arginine↗
PubMed1998

Insulin resistance in cirrhosis: prolonged reduction of hyperinsulinemia normalizes insulin sensitivity.

Insulin resistance is present in nearly all patients with cirrhosis, but its etiology remains unknown. Chronic hyperinsulinemia has been suspected as a potential candidate, and we therefore tested the hypothesis that, in cirrhosis, prolonged reduction of the hyperinsulinemia restores insulin sensitivity. Whole-body insulin sensitivity (euglycemic insulin-clamp technique), glucose turnover (6,6-2H2-glucose isotope dilution), glucose oxidation (indirect calorimetry), non-oxidative glucose disposal, and fractional glycogen synthase activity in muscle (biopsies) were measured in eight clinically stable patients with cirrhosis before and at the end of a 4-day continuous subcutaneous infusion of the somatostatin-analogue octreotide (200 microg/24 h) designed to continuously reduce plasma insulin levels. Baseline data were compared with results obtained in healthy individuals matched for sex, age, and weight (n = 8). During the baseline (pre-octreotide) study, patients demonstrated a significant decrease in insulin-mediated glucose uptake compared with controls (5.75 +/- 0.21 vs. 7.98 +/- 0.84 mg/kg/min; P < .03), which was entirely accounted for by an impairment in non-oxidative glucose disposal (P < .04). Four-day infusion of octreotide to cirrhotic patients: 1) reduced postabsorptive and meal-stimulated plasma insulin levels by approximately 35% to 45% without significantly affecting glucose tolerance; 2) did not significantly alter plasma free fatty acids (FFA), growth hormone, and glucagon levels in the postabsorptive state and during the meal test; 3) normalized insulin-mediated whole-body glucose disposal (7.63 +/- 0.72 mg/kg/min post-octreotide; P = not significant vs. control). Restoration of insulin-mediated glucose utilization was entirely caused by normalization of non-oxidative glucose disposal; 4) was associated with a considerably more pronounced stimulation by insulin of the fractional glycogen synthase in muscle compared with pre-octreotide results (increment above baseline pre: 0.035 +/- 0.010 vs. post: 0.060 +/- 0.023 nmol/min/mg protein; P < .04). Fractional glycogen activity significantly correlated with non-oxidative glucose disposal during insulin infusion (r = .69; P < .03). Prolonged reduction of hyperinsulinemia for 96 hours in cirrhotic patients normalizes insulin-mediated glucose uptake and glycogen synthesis in muscle. We conclude that chronic hyperinsulinemia causes insulin resistance in cirrhosis.

Eating↗
PubMed1998

Literacy and body fatness are associated with underreporting of energy intake in US low-income women using the multiple-pass 24-hour recall: a doubly labeled water study.

OBJECTIVE: The accuracy of the multiple-pass 24-hour recall method for estimating energy intake in low-income women in the United States was ascertained by comparing the method with measurements of total energy expenditure. The multiple-pass 24-hour recall is designed to provide respondents with multiple cues and opportunities to report their food intake. It consists of 3 distinct passes: the quick list, detailed description, and review. Predictors of energy intake misreporting (energy intake--total energy expenditure) in the sample were determined. DESIGN: Four multiple-pass 24-hour recalls (2 in person, 2 by telephone) were obtained over a 14-day period to estimate energy intake. Total energy expenditure was measured over the same 14-day period using the doubly labeled water method. Body composition was measured using dual energy x-ray absorptiometry, and literacy was measured by the Wide Range Achievement Test (WRAT) for reading and spelling. SUBJECTS/SETTINGS: Thirty-five low-income women between the ages of 19 and 46 years were tested at the General Clinical Research Center at the University of Vermont, Burlington. Low income was defined as a household income at or below 130% of the federal poverty level. STATISTICAL ANALYSIS: Pearson product moment correlation coefficients, t tests, paired t tests, and stepwise multiple regression analysis were used to test the relationships among study variables. RESULTS: Mean energy intake was significantly lower than mean total energy expenditure (2,197 +/- 607 vs 2,644 +/- 503 kcal, P = .001) and the correlation between the 2 measures was poor (r = .22, P = .20). Percentage body fat and the combined age-adjusted reading and spelling WRAT scores were the best predictors of misreporting of energy intake (R = .52, P = .006). CONCLUSIONS: The multiple-pass 24-hour recall did not generate a group measure of energy intake that was accurate or unbiased in this sample. Underreporting was strongly associated with increased body fatness. The ability to read and spell as measured by the WRAT improved the accuracy of the women's recall of their food intake. APPLICATIONS: Dietetics professionals should take into consideration the problem of underreporting whenever conclusions are made about associations between diet and health and/or when evaluating the impact of food assistance programs on dietary intake.

Adipose Tissue↗
PubMed1998

Glucagon increases glutamine uptake without affecting glutamine release in humans.

Glucagon causes transient hyperglycemia and persistent hypoaminoacidemia, but the mechanisms of this action are unclear. To address this question, the present study measured the effects of glucagon on glucose, leucine, phenylalanine, and glutamine kinetics. Seven healthy subjects each underwent three pancreatic clamp studies (octreotide 30 ng/kg/min, insulin 0.15 mU/kg/min, and glucagon 1.4 ng/kg/min) lasting 7 hours. During the last 3.5 hours of the studies, glucagon infusion was either unchanged (study 0) or increased to 4 and 7 ng/kg/min (studies 1 and 2). The higher glucagon infusion rates increased the glucagon concentration by 50% and 100%, respectively. [6,6-(2)H2]glucose, [2-(15)N]glutamine, 2H5-phenylalanine, and 2H3-leucine were infused to quantify the respective fluxes. Glucagon transiently increased glucose concentrations by stimulating glucose production, which peaked in 15 minutes to 3.82 +/- 0.36 and 4.21 +/- 0.33 mg/kg/min in studies 1 and 2 and then returned to the postabsorptive levels. Glucagon decreased the glutamine concentration (-10% +/- 2% and -22% +/- 2% in studies 1 and 2 v study 0, P < .05), because glutamine uptake became greater than glutamine release (balance from -1.9 +/- 0.9 in study 0 to -8.1 +/- 1.1 and -13.6 +/- 1.0 micromol/kg/h in studies 1 and 2, P < .01). Glucagon decreased the leucine concentration (-11% +/- 3% in study 2 v study 0, P < .02) and caused a small increment in proteolysis (+6% in study 2 v study 0, P < .01) that was related to the decrement in glutamine concentrations. Phenylalanine kinetics were not significantly affected. These results show that glucagon promotes the uptake of gluconeogenic substrates but does not increase their release, suggesting that glucagon-induced hyperglycemia is short-lived because glucagon fails to provide more fuel for gluconeogenesis. The small increase in proteolysis and the depletion of circulating glutamine prove that physiologic hyperglucagonemia can contribute to protein catabolism.

Adult↗
PubMed1998

Metabolism of parenterally administered fat emulsions in the rat: studies of fatty acid oxidation with 1-13C- and 8-13C-labelled triolein.

To reassess the hypothesis that fatty acid catabolism occurs to completion via beta-oxidation, male Sprague-Dawley rats receiving continuous total parenteral nutrition (TPN) including 43% energy as fat were infused with [1-(13)C]- or [8-(13)C]triolein. Expired CO2 was collected continuously for 4 h and its 13C:12C ratio determined by isotope-ratio mass spectrometry. Bicarbonate retention was also assessed over 4 h by infusion of NaH14CO3 and measurement of the expired 14CO2. A possible loss of label from [8-(13)C]oleic acid from the citric acid cycle via labelled acetyl-CoA without oxidation to CO2 was assessed by infusing further animals with acetate labelled with 14C either at C atoms 1 or 2 and determination of its conversion to expired 14CO2. At isotopic steady state, 63.2 (SE 1.6)% (n 8) of the infused [1-(14)C]acetate and 46.0 (SE 1.2)% (n 8) of [2-(14)C]acetate was recovered as expired 14CO2. After correction for bicarbonate retention and non-oxidative isotope loss, 37.3 (SE 1.2)% (n 20) of the [1-(13)C]triolein was found to have been oxidized, whereas 32.6 (SE 1.0)% (n 20) of the [8-(13)C]triolein was oxidized (P < or = 0.01). The lower oxidation of the C atom at position 8 of oleic acid than that at position 1 indicates incomplete oxidative breakdown of the fatty acid after entering beta-oxidation.

Acetates↗
PubMed1998

Epinephrine produces a prolonged elevation in metabolic rate in humans.

BACKGROUND: Epinephrine increases the metabolic rate and contributes to the hypermetabolic state in severe illness. OBJECTIVE: We sought to determine the effect of prolonged elevation of epinephrine on resting energy expenditure (REE). DESIGN: Thirteen healthy men were placed on a well-defined diet for 5 d. Beginning on the morning of the second diet day, the subjects were infused for 24 h with saline, then for 23 h with epinephrine (0.18 nmol x kg(-1) x min(-1)) to increase plasma epinephrine concentrations into the high physiologic range (4720 +/- 340 pmol/L). REE and the respiratory quotient (RQ) were measured by indirect calorimetry in the postabsorptive state at the same time every morning. RESULTS: Infusion of epinephrine significantly increased heart rate and systolic blood pressure, but the response was transient (values after 23 h of epinephrine infusion were not significantly different from those on the day saline was infused). Infusion of epinephrine significantly increased REE by 12% and increased the RQ. These changes were apparent at the end of the 23-h infusion (REE: 97.5 +/- 2.3 kJ x kg(-1) x d(-1) with saline infusion and 108.9 +/- 2.3 kJ x kg(-1) x d(-1) with epinephrine infusion; RQ: 0.832 +/- 0.012 with saline infusion and 0.879 +/- 0.013 with epinephrine infusion). REE returned to baseline by 24 h after the epinephrine infusion ended, but the postabsorptive RQ remained modestly elevated. Infusion of epinephrine also produced a transient increase in urine flow and in urinary nitrogen excretion. This diuresis was compensated for by a drop in urine volume and nitrogen excretion after the epinephrine infusion was stopped. CONCLUSIONS: Epinephrine produced a prolonged increase in REE in healthy subjects. The fuel for this increase in REE, determined by the RQ, was from increased carbohydrate oxidation, not from that of fat or protein.

Adult↗
PubMed1998

Energy requirements and physical activity in free-living older women and men: a doubly labeled water study.

Determinants of daily energy needs and physical activity are unknown in free-living elderly. This study examined determinants of daily total energy expenditure (TEE) and free-living physical activity in older women (n = 51; age = 67 +/- 6 yr) and men (n = 48; age = 70 +/- 7 yr) by using doubly labeled water and indirect calorimetry. Using multiple-regression analyses, we predicted TEE by using anthropometric, physiological, and physical activity indexes. Data were collected on resting metabolic rate (RMR), body composition, peak oxygen consumption (VO2 peak), leisure time activity, and plasma thyroid hormone. Data adjusted for body composition were not different between older women and men, respectively (in kcal/day): TEE, 2,306 +/- 647 vs. 2,456 +/- 666; RMR, 1,463 +/- 244 vs. 1,378 +/- 249; and physical activity energy expenditure, 612 +/- 570 vs. 832 +/- 581. In a subgroup of 70 women and men, RMR and VO2 peak explained approximately two-thirds of the variance in TEE (R2 = 0.62; standard error of the estimate = +/-348 kcal/day). Crossvalidation of this equation in the remaining 29 women and men was successful, with no difference between predicted and measured TEE (2,364 +/- 398 and 2,406 +/- 571 kcal/day, respectively). The strongest predictors of physical activity energy expenditure (P < 0.05) for women and men were VO2 peak (r = 0.43), fat-free mass (r = 0.39), and body mass (r = 0.34). In summary, RMR and VO2 peak are important independent predictors of energy requirements in the elderly. Furthermore, cardiovascular fitness and fat-free mass are moderate predictors of physical activity in free-living elderly.

Adolescent↗
PubMed1998

Trp64Arg variant of the beta3-adrenoceptor and insulin resistance in obese postmenopausal women.

There is controversy regarding the role of the Trp64Arg variant of the beta3-adrenergic receptor (beta3AR) gene in the pathogenesis of insulin resistance. The modest effect of the variant as well as differences in study design, gender, age, and genetic background may contribute to divergent results among investigations. Insulin sensitivity (euglycemic clamp and tracers) was measured in 13 obese women (57 +/- 6 yr old) heterozygous for the beta3AR variant and in 14 women (57 +/- 4 yr old) homozygous for the normal gene. Groups were matched for age, body composition, intraabdominal fat, sc abdominal fat, physical activity level, and aerobic capacity. Exogenous glucose infusion during the clamp was significantly lower (P = 0.03) in beta3AR heterozygotes (241 +/- 135 mg/min) vs. normal homozygotes (379 +/- 172 mg/min). Basal endogenous glucose production was not different (P = 0.20) between heterozygotes (175 +/- 27 mg/min) and normal homozygotes (164 +/- 14 mg/min). Endogenous glucose production during hyperinsulinemia was also not different (P = 0.22) between heterozygotes (77 +/- 57 mg/min) and normal homozygotes (56 +/- 16 mg/min). Total glucose disposal adjusted for residual endogenous glucose production was lower (P = 0.049) for heterozygotes (320 +/- 111 mg/min) than for normal homozygotes (441 +/- 183 mg/min). Our results suggest that obese postmenopausal women who are heterozygous for the Trp64Arg variant in the beta3AR gene have greater insulin resistance than age-, body composition-, and physical activity-matched women homozygous for the normal gene.

Aged↗
PubMed1998

Energy requirements and physical activity of older free-living African-Americans: a doubly labeled water study.

We examined daily energy requirements and determinants of physical activity in older, free-living African-American women (n = 37; age, 64 +/- 8 yr) and men (n = 28; age, 64 +/- 7 yr). Total daily energy expenditure and its components [i.e. resting metabolic rate (RMR) and physical activity energy expenditure] were determined using doubly labeled water and indirect calorimetry. Body composition from dual energy x-ray absorptiometry, maximal oxygen consumption from a graded treadmill test, and leisure time physical activity from a structured interview were determined. Total daily energy expenditure adjusted for body composition was lower (P < 0.05) for women (2198 +/- 621 kcal/d) than for men (2633 +/- 669 kcal/d) due to a lower RMR (1431 +/- 240 vs. 1576 +/- 259 kcal/d; P = 0.07) and physical activity energy expenditure (548 +/- 559 vs. 794 +/- 603 kcal/d; P = 0.19), respectively. The physical activity level ratio (i.e. total daily energy expenditure/RMR) was not different from Food and Agriculture Organization/World Health Organization/United Nations University recommendations (i.e. 1.51) for women (1.51 +/- 0.25), but was higher for men (1.71 +/- 0.32). The strongest correlates with physical activity energy expenditure were age for women (r = -0.44; P < 0.01) and maximal oxygen consumption for men (r = 0.39; P < 0.05). These data show that daily energy requirements are significantly lower in African-American women compared to men, primarily due to lower levels of physical activity energy expenditure. Furthermore, lower levels of cardiovascular fitness in men and advancing age in women are associated with lower physical activity energy expenditure.

Aged↗
PubMed1998

Absence of glutamine isotopic steady state: implications for the assessment of whole-body glutamine production rate.

1. During infusion of [5-15N]glutamine in patients with gastrointestinal cancer we unexpectedly observed a gradual decrease in time of the appearance rate (Ra) of glutamine in plasma. Here we investigate whether the failure to achieve a plateau isotopic enrichment in plasma is, among other factors, due to incomplete equilibration of the glutamine tracer with the large intramuscular free glutamine pool.2. Plasma and intramuscular glutamine enrichment were measured during 6-11 h infusions of L-[5-15N]glutamine and L-[1-13C]glutamine in post-absorptive patients admitted to hospital for elective abdominal surgery. L-[1-13C]Leucine and L-[ring-2H5]phenylalanine were infused to measure the proportion of glutamine appearing in plasma directly due to its release from protein.3. The glutamine tracer entered muscle, but the rise in intramuscular glutamine enrichment was small, presumably as a result of the enormous size of the intramuscular glutamine pool and the limited speed of entry of glutamine into muscle. In each patient the intramuscular glutamine enrichment was lower than that in plasma (P<0.001), and both increased with tracer infusion time (P<0.001), indicating incomplete equilibration of the glutamine tracer.4.A comparison of the results obtained by the two glutamine tracers indicated that recycling of the nitrogen label contributed to about 15% of the decrease in Ra.5. There was a gradual reduction in the glutamine release from proteolysis, which contributed to 16-21% of the decline in Ra.6. We conclude that slow equilibration of the glutamine tracer with the large muscle glutamine pool significantly contributes to the absence of isotopic steady state. Consequently, the appearance rate of glutamine in plasma measured during short tracer infusion periods (hours) considerably overestimates the whole-body glutamine flux.

Aged↗
PubMed1997

Effect of moderate exercise on insulin sensitivity and substrate metabolism during post-exercise recovery in cirrhosis.

We examined whether a single bout of moderate exercise has a beneficial effect on insulin sensitivity and fuel homeostasis in cirrhosis. Clinically stable cirrhotic patients and age-, sex-, and weight-matched controls participated in insulin clamp studies (either euglycemic hyperinsulinemic or hyperglycemic hyperinsulinemic) in combination with indirect calorimetry and [6,6-2H2]glucose. Three to seven days later, studies were repeated following a single bout of exercise (30 minutes of treadmill exercise at 60% of maximal aerobic capacity). After an overnight fast, following exercise, both cirrhotic and control individuals showed a shift in fuel utilization to enhanced lipid oxidation, decreased glucose oxidation, and increased nonoxidative glucose disposal rates (i.e., glycogen synthesis in muscle) when compared with pre-exercise rates but differences were statistically significant only in the patient group. During euglycemic hyperinsulinemia, insulin-mediated glucose disposal was significantly reduced in cirrhotic patients (3.43 +/- 0.26 vs. 7.36 +/- 0.48 mg/kg/min, P < .01). Following exercise, glucose uptake increased significantly in cirrhotic patients when compared with pre-exercise levels (P < .05) but remained unchanged in the control group. The increase in total body glucose disposal in cirrhotic patients was entirely accounted for by an increase in nonoxidative glucose disposal (0.81 +/- 0.20 vs. 0.51 +/- 0.15 mg/kg/min, P < .05). During combined hyperglycemia/hyperinsulinemia, however, insulin sensitivity was unaffected by exercise in both patients and control individuals. In summary, in cirrhotic patients, a single bout of moderate exercise 1) causes a shift in substrate utilization with an increase in lipid oxidation in the postexercise period that is significantly more pronounced than in controls, and 2) increases insulin sensitivity only during euglycemia but not during the more physiological condition of hyperglycemia. Single bouts of moderate exercise therefore may not have a beneficial effect on the metabolic status of patients with chronic liver disease.

Adult↗