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Biomedical subjects

R R Wolfe

Publications and source records attributed to R R Wolfe.

At least 235 records · Page 13Linked to original sources
PubMed1988

On the measurement of lactate turnover in humans.

It has been shown in studies of turnover in vivo of lactate and several amino acids that the specific activity in blood depends on the site of tracer administration and of sampling. Theoretical and experimental studies have established that to obtain valid estimation of turnover in vivo for these compounds, tracers should be administered into the left heart, ideally the ventricle, and blood sampled from the right heart, ideally the pulmonary artery. Alternately, tracer may be infused into the pulmonary artery and blood sampled from the right ventricle. The insertion of such in-dwelling catheters for turnover studies is difficult in small animals and not justified on ethical grounds in humans. We describe here a method to calculate valid turnover rates when the tracer is administered in a peripheral vein and blood sampled from any peripheral artery. In humans, infusion into a hand vein and sampling from the contralateral heated hand vein can be used. The true turnover rate can then be calculated if the cardiac output is determined. Several noninvasive methods for the determination of cardiac output are available. Thus a correct estimate, avoiding major catheterization, for turnover for many blood-borne compounds is possible.

Alanine↗
PubMed1988

Effect of elevated free fatty acids on glucose oxidation in normal humans.

In vitro studies indicating an inverse relationship between free fatty acid (FFA) availability and glucose oxidation led to proposal of the glucose-fatty acid cycle. In vivo studies have yielded conflicting results regarding the effect of FFA on glucose oxidation. In the present study the effect of FFA on glucose oxidation was determined in six normal volunteer subjects. The rate of glucose uptake was fixed by using a constant glucose infusion to suppress endogenous glucose production. Glucose was infused continuously overnight and during the four hour study at 8 mg/kg X min to ensure use of glucose as an energy substrate by virtually all tissues. Following a two-hour baseline glucose infusion, infusion of 20% IV fat emulsion at 1.0 mL/min plus heparin was added to the constant glucose infusion for two additional hours. Total carbohydrate oxidation was determined by indirect calorimetry, and the direct oxidation of the infused (plasma) glucose was measured by the use of U-13C-glucose. Glycogen oxidation was calculated as the difference between total carbohydrate oxidation and the oxidation of plasma glucose. Glucose uptake was calculated from the infusion rate, corrected for any changes in plasma and/or urine glucose concentration. Glucose uptake closely approximated the rate of IV glucose infusion and was unchanged by fat infusion. The percent of CO2 production from U-13C-glucose oxidation (74.5 +/- 12.3, mean +/- SD) was not affected by FFA, nor was the percent of glucose uptake oxidized (37.5 +/- 4.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Dynamics of the protein metabolic response to burn injury.

The protein metabolic response to burn injury was assessed in 17 children aged 7.1 +/- 1.1 years (mean +/- SEM) and a mean burn size of 65 +/- 7% total body surface area (TBSA) during the acute, flow, convalescent, and recovery phases. Stable isotopes of leucine, valine, lysine, and urea were infused in postabsorptive patients in order to measure protein kinetics. The absolute rate of protein breakdown was assessed from the plasma flux of the essential amino acids (EAA), and the rate of urea production (Ra urea) was used as an index of net protein catabolism. Compared to values obtained in recovered patients, the plasma fluxes of all three EAAs were significantly increased (P less than .05), indicating an increased protein breakdown, during the acute, flow, and convalescent phases of injury. Ra urea, however, was only significantly increased during the flow phase (P less than .01), suggesting that protein breakdown was adequately counteracted in the acute and convalescent phases by elevations in protein synthesis but not in the flow phase. The protein kinetic response did not correlate with changes in the metabolic rate since resting energy expenditure (REE) was significantly increased above predicted levels during the acute and flow phases (by 40% and 50%, respectively), and returned to normal in convalescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Essential↗
PubMed1988

Normal aerobic and anaerobic exercise data for North American school-age children.

The purpose of this study was to establish normative data for untrained, healthy North American children by means of the James protocol for bicycle ergometry. Data were obtained on 151 of 185 children (70 girls and 81 boys). Their ages ranged from 7 years 6 months to 12 years 9 months. All subjects were divided into groups by gender and body surface area (BSA). Maximum heart rates were greater in girls. The mean difference between maximum and recovery heart rates differed significantly by gender, girls taking longer to recover than boys. Maximum oxygen consumption (measured in cubic centimeters per minute per kilogram body weight) did not differ in boys and girls. Ventilatory anaerobic threshold (VAT) occurred when there was an isolated increase in the slope for ventilatory equivalent for oxygen consumption (VE/VO2) with no change in the slope for ventilatory equivalent for carbon dioxide production (VE/VCO2) when both were plotted against time. Absolute oxygen consumption (VO2) at VAT increased with BSA in both sexes, and, when normalized to body size and expressed as a percent of VO2 maximum, no significant difference was observed between the sexes. These data may be used in the fitness evaluations of preadolescent children from North America.

Aerobiosis↗
PubMed1988

Low-dose bradykinin infusion reduces endogenous glucose production in surgical patients.

The systemic effect of low-dose bradykinin infusion on total body glucose production and arterial substrate concentrations was examined during D5W infusion (1.0 mg/kg/min) in five normal-weight postsurgical subjects and compared to the response in four saline infused control patients, well matched for age, weight, and degree of postoperative stress. The primed-constant infusion of 6,6-d2-glucose was used to determine the rate of endogenous glucose production. After a basal period of 90 minutes, subjects in the study group were infused with bradykinin at increasing rates of 2.0 and 4.0 micrograms/kg/h, each infusion rate lasting for 90 minutes, whereas in controls corresponding amounts of saline were given. After 75 minutes of bradykinin, endogenous glucose production was significantly reduced as compared to basal values (1.63 +/- 0.21 mg/kg/min, P less than .0125 v 2.20 +/- 0.35 basal). This was accompanied by a significant reduction in arterial concentrations of glucose, lactate, pyruvate, and alanine. Corresponding concentrations of insulin, glucagon, glycerol, free fatty acids, and ketone bodies, as well as mean arterial blood pressure and heart rate was not affected by bradykinin. In the control group no significant changes in substrate and hormone concentrations, or the rate of glucose production were observed. The higher bradykinin infusion rate did not further affect substrate metabolism or systemic hemodynamics. These results demonstrate the inhibitory effect of low-dose bradykinin on glucose production in surgically stressed patients. The stimulation of hepatic prostaglandin synthesis by bradykinin may explain the results since prostaglandins are known to exert an inhibitory effect on hormone stimulated gluconeogenesis and glycogenolysis in liver tissue.

Adult↗
PubMed1988

The impact of body composition on the regulation of lipolysis during short-term fasting.

Lipolytic rates were determined in normal-weight young adult (low body fat), normal-weight elderly (moderate body fat), and obese young adult (high body fat) subjects after an overnight (12-15 hr) and short-term (60-87 hr) fasting period. A simultaneous infusion of [1-13C] palmitate acid and [2H5]glycerol was used to measure the inflow of palmitate and glycerol into the bloodstream, and H2 18O dilution was used to measure body composition. The amount of body fat differed between the young adult (11 kg), elderly (23 kg) and obese (49 kg) subjects. Total lean body mass was similar in the normal-weight young adult (60 kg) and obese (63 kg) groups, but was lower in the elderly (46 kg). Lipolytic rates per unit of fat mass decreased in each group relative to the increase in the amount of body fat. Lipolytic rates, expressed as a function of lean body mass, however, were the same in all three groups. These results suggest that body composition contributes to the regulation of lipolysis during fasting. The decreased rate of lipolysis in subjects who have excess body fat may reflect the decreased need, per unit fat mass, for lipolysis to meet the energy requirements of the lean body mass.

Adipose Tissue↗
PubMed1988

Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes.

We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4 +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC. Beta-adrenergic stimulation with salbutamol resulted in a significant increase in glucose turnover from 12.1 +/- 1.1 mumol/kg/min to 13.4 +/- 0.9 mumol/kg/min (p less than 0.02), and the rates of appearance (Ra) of both alanine and free fatty acids (FFAs) also increased. Alanine Ra increased from 11.7 +/- 2.5 mumol/kg/min to 12.8 +/- 3.0 mumol/kg/min, and the corresponding values for FFA turnover were 7.6 +/- 1.1 mumol/kg/min and 10.3 +/- 2.1 mumol/kg/min (p less than 0.03), respectively. Salbutamol infusion did not result in any significant change in the rate of NPC.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1988

Energy and protein metabolism in sarcoma patients.

We have performed a series of isotopic infusions both in normal volunteers (N = 16) and in sarcoma patients (N = 7). Using the primed-constant infusion of stable or radioisotopes we have determined the rates of glucose turnover, glucose oxidation, glucose recycling, and net protein catabolism (NPC). In addition, we have measured VO2 and VCO2. The values for VCO2 and VO2 were higher in the patients than in the volunteers (mean VO2 values in volunteers and patients: 107 +/- 13 and 158 +/- 13 mumol/kg/min, respectively). The basal rate of glucose appearance in the sarcoma patients was twice the value seen in the volunteers (28.3 +/- 3.5 vs. 13.9 +/- 0.3 mumol/kg/min). Glucose infusion in the volunteers resulted in virtually total suppression of endogenous glucose production, while in the patients glucose infusion induced only a 30% suppression of endogenous glucose production (p less than 0.01). The rate of glucose clearance in the patients was approximately twice the value seen in the volunteers [5.4 +/- 1.0 vs. 2.7 +/- 0.1 mL/kg/min (p less than 0.01)]. The per cent of glucose uptake oxidized in the patients was significantly less than in the volunteers [22% vs. 36% (p less than 0.05)], and the per cent of glucose uptake that was recycled was significantly higher in the patients [55% vs. 10% (p less than 0.01)]. In addition, the basal rate of net protein loss was increased twofold in the patients [3.2 +/- 0.5 vs. 1.4 +/- 0.4 g (protein)/kg/d (p less than 0.01)], and in contrast to the situation in the volunteers there was no suppression in the rate of net protein loss when the patients were infused with glucose. The basal insulin concentration and the insulin response to glucose infusion in the patients were similar to that of the volunteers, but the plasma cortisol level was similar in volunteers and in the patients (p less than 0.05). We conclude from these studies the following: (1) Sarcoma patients have significantly elevated rates of glucose production and glucose clearance, but they have an impaired capacity to directly oxidize either endogenous or infused glucose, coupled with an increased rate of glucose recycling. (2) Sarcoma patients have an elevated metabolic rate and are catabolic. In addition, in contrast with normal volunteers, glucose infusion does not result in a suppression of protein loss.

Adolescent↗
PubMed1988

Effect of propranolol administration on hemodynamic and metabolic responses of burned pediatric patients.

Hypermetabolism, increased heart rate, and lipolysis are responses to high catecholamine levels associated with burn injury. This study tests the hypothesis that adrenergic beta blockade in burns could reduce myocardial work, lipolysis, and negative nitrogen balance without adversely affecting cardiac or metabolic function. Eighteen patients with burns of 70 +/- 3% total burn surface area (TBSA) (Mean +/- SEM), were studied after a 5-day infusion of 2 mg/Kg of intravenous (I.V.) propranolol infusion every 24 hours without their cardiac output or resting energy expenditure being adversely reduced. Heart rate, left ventricular work, and rate pressure product were significantly reduced by 20, 22, and 36%, respectively (P less than 0.05). Plasma glucose, free fatty acids, triglycerides, and insulin levels remained unchanged. The rate of urea production, however, was significantly increased by 54 +/- 12% in fasted patients, and to a much lesser 12 +/- 2% in fed patients. The marked decrease in myocardial work afforded by propranolol administration may be of clinical benefit in the treatment of large burns. Variations in drug dosage and feeding regimens will, however, need to be perfected to limit catabolic effects.

Adolescent↗
PubMed1988

Calculation of substrate flux using stable isotopes.

The use of stable isotope tracers to calculate substrate kinetics in humans is favored over the use of radioactive isotopes because of their greater safety and versatility. However, potential complications not met when dealing with radioactive tracers are caused by 1) the natural occurrence of the stable isotope used as a tracer and 2) the necessity to administer the tracer in an amount that cannot be treated as "massless." We therefore found it desirable to derive a theoretically valid equation for calculating the rate of appearance, Ra, of a substrate under steady-state conditions using a stable isotope tracer. This theoretically valid equation yields results that differ from those of the equations conventionally used to calculate (endogenous) Ra in steady state. Quantitative determination of the error in one of these equations revealed that for tracers commonly used in metabolic studies the error is negligible, whereas the error made in the other equation is likely to be quite high in commonly encountered situations. Finally, to allow for proper use of different definitions of isotopic enrichment that have arisen from practical considerations, we use the results derived above to determine valid equations for Ra appropriate to the two prevalent definitions.

Humans↗
PubMed1988

Evaluation of the isotopic equilibration between lactate and pyruvate.

When an isotopic tracer is infused for the purpose of determining the rate of turnover or oxidation of a substrate, it is assumed that the resulting isotopic enrichment by the tracer will reflect the kinetics of only the pool of interest. However, this may not be the case when carbon-labeled lactate is infused, since rapid isotopic exchange with the intracellular pyruvate and alanine pools could potentially occur. Therefore we have determined the extent of isotopic exchange occurring during the infusion of [3-13C]lactate into six anesthetized dogs. In the steady state, pyruvate enrichment was 91 +/- 2.2% (means +/- SE) of the lactate enrichment, and alanine enrichment was 81 +/- 3.3% of the pyruvate enrichment and 72 +/- 2.6% of the lactate enrichment. In contrast, when [3-13C]alanine was infused (n = 2), pyruvate (and lactate) enrichment was 9.9% of the alanine enrichment. We therefore conclude that there is rapid isotopic equilibration between lactate and pyruvate but that interaction with alanine reflects the true metabolic flux rates, rather than isotopic exchange. Consequently, lactate kinetics, as traditionally determined, more accurately reflect whole body pyruvate kinetics.

Animals↗
PubMed1988

Insulin responsiveness of protein metabolism in vivo following bedrest in humans.

To test the influence of bedrest on insulin regulation of leucine metabolism, six normal young men were subjected to a five-step hyperinsulinemic euglycemic clamp before and after 7 days of strict bedrest. A primed-constant infusion of [1-13C]leucine at 0.12 +/- 0.02 mumol.kg-1.min-1 was used. Before bedrest, the basal rate of appearance (Ra) of intracellular leucine and leucine oxidation were 2.79 +/- 0.17 and 0.613 +/- 0.070 mumol.kg-1.min-1, respectively. Insulin caused a dose-dependent reduction of the intracellular leucine Ra and leucine oxidation to a minimum of 1.64 +/- 0.08 and 0.322 +/- 0.039 mumol.kg-1.min-1, respectively, in nonbedrested subjects (P less than 0.001). Insulin also caused a dose-dependent reduction of plasma leucine concentration from 95 +/- 4 to 38 +/- 2 mumol/l (P less than 0.001). After bedrest, subjects exhibited decreased glucose tolerance and increased endogenous insulin secretion, but basal and insulin-suppressed intracellular leucine Ra and leucine oxidation rates were not different from control. Magnetic resonance imaging of the back and lower extremities revealed a 1-4% decrease in muscle volume and a 2-5% increase in fat volume secondary to bedrest. Bedrest also resulted in a negative nitrogen balance as compared with the control period, with an average cumulative loss of 6.3 g of nitrogen after 6 days. Urinary 3-methyl-L-histidine excretion was unchanged by bed rest. Thus because negative nitrogen balance and skeletal muscle atrophy occurred in six rested subjects in the absence of changes in the two indices of protein breakdown used in this study (3-methyl-L-histidine release and leucine release), it seems likely that muscle protein synthesis was inhibited.

Adipose Tissue↗
PubMed1988

Effect of isotope infusion and sampling sites on glucose kinetics during a euglycemic clamp.

The importance of the location of isotope infusion and blood sampling on calculating glucose kinetics was studied in five mongrel dogs in the basal state and when glucose turnover was increased during a hyperinsulinemic euglycemic clamp. [U-14C]glucose was infused into the pulmonary artery, unlabeled glucose was infused into a femoral vein to maintain euglycemia, and blood was sampled from the right atrium (AV mode) and the femoral artery (VA mode). In the basal state there was no difference between the AV or VA mode in plateau specific activity; hence, the calculated rate of appearance of glucose was the same with either mode. During the euglycemic clamp procedure, plateau specific activity of the AV mode was significantly lower than that of the VA mode (P less than 0.05). The rate of appearance of glucose calculated from the VA mode was almost identical to the rate of infusion of unlabeled glucose (13.0 +/- 1.4 vs. 12.6 +/- 1.4 mg.kg-1.min-1, respectively), but the rate of appearance of glucose calculated from the AV mode was 12% greater. This study demonstrates that the calculation of glucose kinetics is sensitive to differences in sampling site when the turnover rate is high relative to the mass flow rate (cardiac output times substrate concentration).

Animals↗
PubMed1988

Hormonal control of substrate cycling in humans.

Recent studies have established the existence of substrate cycles in humans, but factors regulating the rate of cycling have not been identified. We have therefore investigated the acute response of glucose/glucose-6P-glucose (glucose) and triglyceride/fatty acid (TG/FA) substrate cycling to the infusion of epinephrine (0.03 microgram/kg.min) and glucagon. The response to a high dose glucagon infusion (2 micrograms/kg.min) was tested, as well as the response to a low dose infusion (5 ng/kg.min), with and without the simultaneous infusion of somatostatin (0.1 microgram/kg.min) and insulin (0.1 mU/kg.min). Additionally, the response to chronic prednisone (50 mg/d) was evaluated, both alone and during glucagon (low dose) and epinephrine infusion. Finally, the response to hyperglycemia, with insulin and glucagon held constant by somatostatin infusion and constant replacement of glucagon and insulin at basal rates, was investigated. Glucose cycling was calculated as the difference between the rate of appearance (Ra) of glucose as determined using 2-d1- and 6,6-d2-glucose as tracers. TG/FA cycling was calculated by first determining the Ra glycerol with d5-glycerol and the Ra FFA with [1-13C]palmitate, then subtracting Ra FFA from three times Ra glycerol. The results indicate that glucagon stimulates glucose cycling, and this stimulatory effect is augmented when the insulin response to glucagon infusion is blocked. Glucagon had minimal effect on TG/FA cycling. In contrast, epinephrine stimulated TG/FA cycling, but affected glucose cycling minimally. Prednisone had no direct effect on either glucose or TG/FA cycling, but blunted the stimulatory effect of glucagon on glucose cycling. Hyperglycemia, per se, had no direct effect on glucose or TG/FA cycling. Calculations revealed that stimulation of TG/FA cycling theoretically amplified the sensitivity of control of fatty acid flux, but no such amplification was evident as a result of the stimulation of glucose cycling by glucagon.

Adult↗
PubMed1988

Increased rate of Cori cycle in obese subjects with NIDDM and effect of weight reduction.

To determine the contribution of the rate of glucose recycling via the Cori cycle (glucose----3-carbon compounds----glucose) to the higher rate of endogenous glucose production (EGPR) in subjects with non-insulin-dependent diabetes mellitus (NIDDM), we studied eight obese, weight-stabilized diabetic Pima Indians before [93.1 +/- 5.4 kg, 38 +/- 2% body fat, fasting plasma glucose (FPG) 254 +/- 11 mg/dl] and after (87.7 +/- 4.7 kg, 36 +/- 2% body fat, FPG 153 +/- 17 mg/dl) a 5-wk weight-loss diet and eight obese Indians (95.0 +/- 4.2 kg, 36 +/- 2% body fat, FPG 97 +/- 1 mg/dl) with normal glucose tolerance. EGPR and glucose recycling rate were measured during a 4-h primed continuous tracer infusion of [1-13C]glucose, and the rate of reincorporation of 1-13C of glucose into C2-6 positions in glucose was quantified by gas chromatography mass spectrometry. Substrate utilization rates were measured by simultaneous indirect calorimetry. EGPR (corrected for measured rate of recycling) decreased in the diabetic subjects from 3.80 to 2.74 mg.min-1.kg-1 fat-free mass (FFM) (P less than .01) after weight loss, approaching the rate observed in nondiabetic subjects (2.09 mg.min-1.kg-1 FFM).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗
PubMed1988

Whole-body protein kinetics in patients with early and advanced gastrointestinal cancer: the response to glucose infusion and total parenteral nutrition.

We have isotopically determined rates of whole-body protein synthesis and catabolism in a group of normal volunteers and in two groups of cancer patients: 20 patients with advanced weight-loss (AWL) upper gastrointestinal cancer and 7 patients with early non-weight-loss (ENWL) lower gastrointestinal cancer. In both patients and volunteers we determined protein kinetics in the basal state and during glucose infusion at 4 mg/kg/min. In addition, in the AWL patients the effect of total parenteral nutrition (TPN) on protein dynamics was also assessed. The rate of net protein breakdown was determined with the primed constant infusion of either 15N-urea or 14C-urea, the rate of whole-body protein catabolism was measured with the primed constant infusion of 15N-lysine, and the rate of whole-body protein synthesis was deduced from the above two values. The basal rates of net protein catabolism, whole-body protein catabolism, and whole-body protein synthesis were similar in the volunteers and ENWL cancer patients. The basal values for net protein catabolism in the volunteers and ENWL patients were 1.46 +/- 0.18 and 1.34 +/- 0.08 gm/kg/min, respectively. In both volunteers and ENWL patients glucose infusion resulted in a significant decrease in net protein catabolism. In the ENWL patients this decrease was due to a significant decrease in whole-body protein catabolism (p less than 0.05); the rate of whole-body protein synthesis did not change significantly. In the AWL cancer patients the rate of net protein catabolism was significantly higher than in either the volunteer or ENWL group (p less than 0.05), and glucose infusion did not result in a decrease in net protein catabolism. However, when the AWL group was studied during TPN there was a significant decrease in net protein catabolism from 2.24 +/- 0.30 to 0.17 +/- 0.09 gm/kg/day (p less than 0.01). This decrease was due to the combined effect of a significant decrease in whole-body protein catabolism coupled with an increase in whole-body protein synthesis. From these studies we conclude the following: (1) ENWL cancer patients and normal volunteers have similar protein dynamics, and in both groups glucose infusion resulted in a significant decrease in protein loss. (2) AWL cancer patients have an elevated rate of net protein catabolism, and this is not sensitive to glucose infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1988

Glucose, fat, and protein kinetics in patients with primary and secondary hyperparathyroidism.

We performed a series of isotopic studies in 16 normal volunteers, four patients with secondary hyperparathyroidism (SHPT), and in nine patients with primary hyperparathyroidism (PHPT). Using the primed constant infusion of stable and radioisotopes, we have determined glucose, glycerol, free fatty acids, and urea kinetics, as well as glucose oxidation. Measurements were performed both in the basal state and during glucose infusion (4 mg/kg body weight/min). Compared with normal volunteers, PHPT patients are intolerant of glucose because of a limited suppression of endogenous glucose turnover during glucose infusion (34% versus 96% suppression). In addition, the plasma cortisol level increased in the PHPT patients during glucose infusion. Glucose oxidation and fat kinetics in both PHPT patients and volunteers were similar, but the rate of net protein loss was significantly greater in the PHPT patients than in the volunteers (2.1 +/- 0.5 versus 1.4 +/- 0.2 gm/kg/day). Rates of VO2 in the PHPT patients and volunteers were similar, but the value in the SHPT patients was higher (120 +/- 9 versus 142 +/- 20 mumol/kg/min for PHPT and SHPT patients, respectively). The SHPT patients had significantly increased rates of glucose turnover, glucose clearance, and glycerol turnover, compared with the other two groups, as well as an increased reliance on glucose for energy. We conclude from these studies that (1) SHPT patients are catabolic and have increased rates of glucose and fat turnover; (2) PHPT patients have limited suppression of endogenous glucose turnover after glucose infusion compared with volunteers and higher rates of net protein loss; (3) fat metabolism and glucose utilization are unimpaired in PHPT patients; and (4) these alterations in metabolism and hormonal response to glucose infusion suggest that some of the symptoms seen in these patients may have a metabolic-hormonal basis.

Adult↗