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Biomedical subjects

D S Hardin

Publications and source records attributed to D S Hardin.

At least 19 recordsLinked to original sources
PubMed2002

Growth hormone treatment in children with cystic fibrosis.

Children with cystic fibrosis (CF) have problems with poor linear growth and inadequate weight gain. Nutritional augmentation has been the mainstay of therapy for improving both weight and height in CF; however inadequate growth continues to be a problem. Furthermore, protein catabolism has been documented even in non-acutely ill adults and children with CF, and could adversely affect longitudinal growth. Human recombinant growth hormone (GH) has positive effects on nitrogen balance, and multiple studies have demonstrated improved height and weight in children treated with GH. The purpose of this article is to summarize studies evaluating GH use in children with CF.

Adolescent↗
PubMed2001

Growth hormone improves clinical status in prepubertal children with cystic fibrosis: results of a randomized controlled trial.

OBJECTIVES: We conducted a 1-year randomized controlled trial to test the hypothesis that growth hormone (GH) improves the clinical status of children with cystic fibrosis. STUDY DESIGN: Nineteen prepubertal children were randomized to control (NonTX, n = 9) or to daily injections of GH (0.3 mg/kg/wk) (GHTX, n = 10) for 1 year. Every 3 months height, weight, and lean tissue mass were measured. Caloric intake, resting energy expenditure, pulmonary function, and respiratory muscle strength were measured every 6 months, as were total number of hospitalizations and courses of outpatient intravenous antibiotics. RESULTS: The GHTX group had significantly greater height, height velocity (NonTX = 3.8 +/- 1.4 cm/y, GHTX = 8.1 +/- 2.4 cm/y; P =.002), weight, weight velocity (NonTX = 2.1 +/- 0.9 kg/y, GHTX = 4.5 +/- 1.1 kg/y; P =.004), and change in lean tissue mass (NonTX = 2.1 +/- 1.6 kg, GHTX = 4.7 +/- 1.7 kg; P =.01) analyzed by the Student t test. The GHTX group had significant improvement in delta forced vital capacity compared with the year before study, and respiratory muscle strength improved. The number of hospitalizations and outpatient intravenous antibiotic courses significantly decreased in the GHTX group but did not change in the NonTX group. No subject had development of cystic fibrosis-related diabetes. CONCLUSIONS: Results of the first randomized controlled trial of GH treatment in cystic fibrosis indicate that GH improves growth and clinical status.

Body Composition↗
PubMed2001

Ingested IFN-alpha preserves residual beta cell function in type 1 diabetes.

Type 1 diabetes mellitus is a chronic disorder that presumably results from an autoimmune destruction of the insulin-producing pancreatic beta cells. The therapeutic potential of interventions aimed at preventing type 1 diabetes can be assessed in newly diagnosed patients. Because there is a historical experience of a low incidence of spontaneous remission in type 1 diabetes mellitus, interventions preserving beta cell function have been used to identify positive therapeutic outcomes. We treated 10 newly diagnosed type 1 diabetes patients with 30,000 IU ingested interferon-alpha (IFN-alpha) within 1 month of diagnosis and examined the difference between baseline and Sustacal-induced (Mead Johnson Nutritionals, Evansville, IN) C-peptide responses, respectively, at 0, 3, 6, 9, and 12 months. Eight of the ten patients showed preserved beta cell function, with at least a 30% increase in stimulated C-peptide levels at 0, 3, 6, 9, and 12 months after initiation of treatment. There was no discernible chemical or clinical toxicity associated with ingested IFN-alpha. Our results support the potential of ingested IFN-alpha to preserve residual beta cell function in recent onset type 1 diabetes mellitus and the testing of IFN-alpha in a placebo-controlled trial.

Administration, Oral↗
PubMed2001

Normal bone mineral density in cystic fibrosis.

BACKGROUND: Osteoporosis has been reported as a complication of cystic fibrosis (CF). AIMS: To measure bone mineral density (BMD) in non-acutely ill adults and bone mineral content (BMC) in children with CF. METHODS: We analysed data from 28 adults and 13 children with CF. Corticosteroid use was minimal for the year prior to study in both groups. Dual x ray absorptiometry was used to measure total body and regional bone mineral density in adults. In children, whole body BMC was measured. Lean tissue mass (LTM) was also measured in all subjects. There were two control groups: A (matched for LTM and height, in addition to age and gender); and B (matched for age and gender only). RESULTS: There was no difference in whole body or regional BMD density between adult CF patients and control A subjects. Both whole body and regional BMD were significantly lower in adult CF patients than in control B subjects. Total body BMD was correlated with body mass index, LTM, and percent fat in both CF and control subjects. There was no significant correlation between total body BMD or regional BMD and either NIH clinical status scores, or pulmonary function tests in adults. There was no difference in total body BMC between CF children and control A subjects. Total body BMC was significantly lower in CF children than in control B subjects. There was no correlation between pulmonary function results and BMC in children. CONCLUSION: Osteopenia and osteoporosis in CF may be caused more by malnutrition and chronic use of intravenous or oral corticosteroids than by a CF related inherent defect in BMD. Appropriate "normal" data should be selected when determining whether or not osteoporosis is present in a CF patient.

Absorptiometry, Photon↗
PubMed2001

Mechanisms of insulin resistance in cystic fibrosis.

Cystic fibrosis (CF) is associated with a high incidence of diabetes. Studies evaluating causes of CF-related diabetes (CFRD) have consistently documented decreased insulin secretion. In patients with CFRD, insulin sensitivity has been documented to be decreased, but controversy exists in patients with normal or impaired glucose tolerance (IGT). We undertook this study 1) to reexplore insulin sensitivity in patients with IGT and 2) to evaluate potential mechanisms of insulin resistance in CF, including GLUT-4 translocation, elevation of serum cytokines, and free fatty acid (FFA) levels. We recruited nine CF subjects with impaired glucose tolerance (IGTCF) and nine age-, gender-, and body mass index-matched control volunteers. Each underwent a hyperinsulinemic euglycemic clamp (200 mU. m(-2). min(-1)) to measure insulin sensitivity. A muscle biopsy was obtained at maximal insulin stimulation for measure of GLUT-4 translocation with sucrose gradients. An oral glucose tolerance test and National Institutes of Health (NIH) clinical status scores were measured in all volunteers. We also measured tumor necrosis factor (TNF)-alpha levels and FFA in all subjects. Additionally, we report the results of TNF-alpha and FFA in 32 CF patients previously studied by our group. Results were that glucose disposal rate (GDR) was significantly lower in the CFIGT subjects than in controls, indicative of impaired insulin action. GLUT-4 translocation was impaired in CF and correlated with GDR. TNF-alpha levels were higher in all CF subjects than in controls and correlated with GDR. There was no difference in FFA between CF and control subjects. Modified NIH clinical status scores were inversely correlated with GDR and TNF-alpha levels. We conclude that IGTCF patients have decreased peripheral insulin sensitivity. Mechanisms include elevation of TNF-alpha and impaired translocation of GLUT-4.

Adult↗
PubMed2001

Growth hormone decreases protein catabolism in children with cystic fibrosis.

Despite aggressive nutritional therapy, low body weight and protein catabolism are common problems in children with cystic fibrosis. Previous studies by our group and others have demonstrated improvement in both height and weight in children with cystic fibrosis who were treated with human recombinant GH, and our group has recently documented improved clinical status and lean tissue mass as well. The purpose of this report is to summarize our findings of the effect of GH on whole body protein kinetics in cystic fibrosis and to relate these findings to changes in TNF-alpha levels. We conducted a 1-yr study of 19 prepubertal children with cystic fibrosis (age 7-12 yr, all <94% of ideal body weight). Ten children were randomly assigned to take daily injections of GH (0.3 mg/kg.wk), and nine were randomly assigned to be controls. Baseline results from the subjects with cystic fibrosis were compared with results obtained from nine age- and gender-matched healthy children. Whole body protein turnover was measured at baseline and every 6 months using the stable isotope [1-(13)C]leucine and mass spectrometric analysis. Leucine rate of appearance, a measure of protein catabolism, was similar in both cystic fibrosis subgroups at baseline and was significantly higher than in the control children without cystic fibrosis. Treatment with GH resulted in a significantly lower leucine rate of appearance, as well as significantly lower leucine oxidation. The rate of protein synthesis, as calculated from these numbers, actually decreased in the cystic fibrosis subgroup. TNF-alpha levels were higher in both cystic fibrosis subgroups than in controls and correlated with leucine rate of appearance. The results of this study suggest that one reason GH improves body weight and lean tissue mass is due to improved whole body protein catabolism and improved efficiency of whole body protein kinetics.

Algorithms↗
PubMed2001

Z score prediction model for assessment of bone mineral content in pediatric diseases.

The objective of this study was to develop an anthropometry-based prediction model for the assessment of bone mineral content (BMC) in children. Dual-energy X-ray absorptiometry (DXA) was used to measure whole-body BMC in a heterogeneous cohort of 982 healthy children, aged 5-18 years, from three ethnic groups (407 European- American [EA], 285 black, and 290 Mexican-American [MA]). The best model was based on log transformations of BMC and height, adjusted for age, gender, and ethnicity. The mean +/- SD for the measured/predicted in ratio was 1.000 +/- 0.017 for the calibration population. The model was verified in a second independent group of 588 healthy children (measured/predicted In ratio = 1.000 +/- 0.018). For clinical use, the ratio values were converted to a standardized Z score scale. The whole-body BMC status of 106 children with various diseases (42 cystic fibrosis [CF], 29 juvenile dermatomyositis [JDM], 15 liver disease [LD], 6 Rett syndrome [RS], and 14 human immunodeficiency virus [HIV]) was evaluated. Thirty-nine patients had Z scores less than -1.5, which suggest low bone mineral mass. Furthermore, 22 of these patients had severe abnormalities as indicated by Z scores less than -2.5. These preliminary findings indicate that the prediction model should prove useful in determining potential bone mineral deficits in individual pediatric patients.

Absorptiometry, Photon↗
PubMed1999

Diabetes mellitus in cystic fibrosis.

Glucose intolerance and diabetes are common complications of cystic fibrosis (CF), affecting up to 75% of the adult population. This article discusses the prevalence and pathophysiology of glucose tolerance abnormalities in CF, and reviews recent recommendations for diagnosis, screening, and management of CF-related diabetes (CFRD).

Adolescent↗
PubMed1999

Hepatic insulin resistance and defects in substrate utilization in cystic fibrosis.

Patients with cystic fibrosis (CF)-related diabetes (CFRD) have clinical features of both type 1 and type 2 diabetes. Past studies have documented peripheral insulin resistance in CF, and some studies have noted high hepatic glucose production (HGP) in CF patients. We hypothesized that patients with CF, similar to patients with type 2 diabetes, have hepatic insulin resistance. Cystic fibrosis is a catabolic condition, yet the etiology of catabolism is poorly understood. De novo lipogenesis is energy wasteful and precludes ketogenesis. Patients with CFRD rarely develop ketogenesis, despite insulin deficiency. We speculated that CF patients have de novo lipogenesis, and therefore evaluated substrate utilization in CF. Using [6,6-2H2]glucose and a three-step hyperinsulinemic-euglycemic clamp, we measured HGP in 29 adult CF subjects and 18 control volunteers. Using indirect calorimetry, we measured lipid oxidation, oxidative glucose metabolism, and resting energy expenditure at baseline and at high levels of insulin. All subjects were characterized by oral glucose tolerance testing (OGTT) and National Diabetes Data Group criteria. The CF subjects had increased HGP when compared with control subjects (CF, 3.5+/-0.6; control, 2.5+/-0.5 mg x kg(-1) x h(-1); P = 0.002). Baseline HGP correlated with glucose levels obtained 2 h after a glucose load given for OGTT (r = 0.69, P = 0.001). Suppression of HGP by insulin was significantly less in all CF subgroups than in control subjects at peripheral insulin levels of 16 and 29 microU/ml. At peripheral insulin levels of 100 microU/ml and 198 microU/ml, there was no difference in insulin suppression of HGP between CF and control subjects. At baseline, there was no significant difference between control and CF subjects for glucose or lipid oxidation. During maximum insulin stimulation, there was a greater tendency for nonoxidative glucose metabolism in all CF subjects. The CF subjects with abnormal glucose tolerance also had de novo lipogenesis. Our results indicate that CF patients have several defects in substrate utilization, including de novo lipogenesis. Furthermore, these results suggest that high hepatic glucose production and hepatic insulin resistance contribute to the high incidence of abnormal glucose tolerance in CF.

Adolescent↗
PubMed1999

Increased leucine turnover and insulin resistance in men with advanced HIV infection.

BACKGROUND: The purpose of this study was to determine if patients with advanced HIV infection exhibit increased rates of leucine turnover and to determine dose effects of insulin on suppression of leucine turnover. We also wished to evaluate hepatic glucose production and re-examine peripheral insulin sensitivity in HIV infected adults. METHODS: Results from 9 males with advanced HIV disease (96-121% ideal body weight, NW-AIDS) and 3 males (80-88% ideal body weight, UW-AIDS) were compared to age and weight matched normal volunteers (NW-C and UW-C). Each subject underwent basal leucine turnover studies followed by insulin dose response studies using a step-up hyperinsulinemic euglycemic clamp (insulin dose: 10, 20 and 120 mU/m2/min) and the stable isotope [1-13C]leucine. Hepatic glucose production was measured using the stable isotope d-6,6(2)H2-glucose. Resting energy expenditure (REE) was measured by indirect calorimetry and a 24-hour food recall was obtained. Viral load, Karnofsky score, and CD4 counts were measured in AIDS subjects. RESULTS: All subjects with AIDS had higher rates of leucine appearance (leucine Ra) than controls. Although both AIDS and Controls demonstrated suppression of leucine Ra with insulin, suppression was less in AIDS subjects. There was a strong relationship between leucine Ra and viral load (r = 0.87, P = 0.02). The AIDS subjects exhibited peripheral insulin resistance when compared to controls. CONCLUSIONS: Our results suggest that patients with HIV have both peripheral insulin resistance and resistance to the anticatabolic effects of insulin.

Adult↗
PubMed1998

Growth hormone improves weight velocity and height velocity in prepubertal children with cystic fibrosis.

We undertook this study to determine if growth hormone treatment of prepubertal children with cystic fibrosis could improve their height and weight. Nine prepubertal children with cystic fibrosis were treated with human recombinant growth hormone for one year. Results obtained during this year were compared to similar measurements made for each patient for the one year prior to the treatment year. Anthropometric data including: height, height velocity, weight, weight velocity and skin fold thickness were measured at three month intervals. Pulmonary function and skeletal muscle strength were measured at three month intervals. Glucose tolerance was evaluated by HbAlc and by fasting blood glucose and insulin levels every three months. Our results demonstrate that growth hormone treatment resulted in significant improvement in height velocity and height Z scores. Weight increased in all subjects, with a significant increase in weight velocity (year prior to treatment = 1.7+/-1.0 kg/yr, treatment year = 3.8+/-1.6 kg/yr; p=0.03). Measurements of skin fold thickness suggests that lean body mass improved with growth hormone treatment. Pulmonary function improved in all but two patients, whose pulmonary function remained the same and muscle strength improved in all subjects. These results suggest that growth hormone used in prepubertal children with cystic fibrosis can improve height and weight and may improve lean body mass.

Autoantibodies↗
PubMed1998

Serum leptin and IGF-I levels in cystic fibrosis.

The role of leptin in states of negative energy balance such as cystic fibrosis (CF) has not been explored. We hypothesized that leptin levels in patients with CF would be low due to correlation with body weight. Despite the importance of IGF-I in normal growth and anabolism, there are few data on IGF-I in CF. We studied 27 CF patients (25+/-5 yrs, 57+/-9 kg, 10M/17F) and 12 control subjects (25+/-4 yrs, 57+/-9 kg, 6M/6F). Each subject underwent analysis of lean body mass (LBM) and percent body fat by dual-energy x-ray absorptiometry (DEXA). Serum leptin and IGF-I levels were measured by radioimmunoassay. Serum leptin levels were similar both in CF and in controls (CF=5.3+/-4.1 ng/ml, C=4.4+/-3.6ng/ml; p=0.3), and there was no difference in percent body fat between the two groups (CF=26+/-13%, C=21+/-7%; p=0.3). Leptin levels were significantly lower in CF males than females corresponding to lower fat levels in males in both CF and controls. Leptin levels were positively correlated with percent body fat both in CF and controls (CF: r=0.8; p=0.01, CONTROL: r=0.8; p =0.2). Serum IGF-I levels were significantly lower in CF patients than in controls (CF=1.13+/-0.41 ng/ml, C=6.72+/-3.62 ng/ml; p=<0.01). We conclude that the physiological regulation of leptin is maintained in relation to body fat even in chronic illness and that the negative energy balance in CF is not caused by high leptin levels.

Adult↗
PubMed1998

Proteolysis associated with insulin resistance in cystic fibrosis.

OBJECTIVE: We hypothesized that patients with cystic fibrosis (CF) have higher rates of protein breakdown than normal volunteers and that the infusion of insulin would result in less suppression of proteolysis. Methods. Using [1-C]leucine and a three-step hyperinsulinemic euglycemic clamp, we measured rates of leucine appearance in 29 adult CF patients and 18 matched-control volunteers. The CF patients were characterized by oral glucose tolerance testing and clinical status scoring. RESULTS: The CF patients had significantly increased proteolysis when compared with that of controls (CF, 123 +/- 28 micromol/kg/h; controls, 71 +/- 15 micromol/kg/h) and rates of proteolysis were significantly different between CF patients with impaired glucose tolerance and diabetes and those CF patients with normal glucose tolerance. Suppression of proteolysis by insulin was less in all CF subgroups than in the controls at peripheral insulin levels of 16 and 29 microU/mL. At peripheral insulin levels of 100 microU/mL, there was no difference in insulin suppression of proteolysis between CF patients and controls. Importantly, basal rates of proteolysis had an inverse relationship with clinical status in CF patients (r = -.76). CONCLUSIONS: Our findings indicate that proteolysis is higher in adult CF patients than in controls and that CF patients exhibit resistance to the anabolic effects of insulin on proteolysis. Most significantly, our findings indicate that basal rates of proteolysis inversely correlate with clinical status in CF.

Adolescent↗
PubMed1997

Effects of growth hormone treatment in children with cystic fibrosis: the National Cooperative Growth Study experience.

Poor longitudinal growth and low body weight affect many persons with cystic fibrosis (CF). The Cystic Fibrosis Foundation reports that 28% of all persons with CF are below the 10th percentile for height and that 34% are below the 10th percentile for weight. Intensive nutritional supplementation has not resulted in sustained improvement in the poor linear growth and low weight in CF. Because of the significant impact of nutrition in CF, the anabolic effects of growth hormone (GH) may make the agent useful as adjunctive treatment for malnutrition and poor linear growth. To date, 24 patients with CF (16 boys; 87% Tanner stage 1) have been enrolled in the National Cooperative Growth Study. The average age at enrollment was 10.3 years, and there was significant delay in height in all patients (mean height age, 7.1 years). Bone age was also significantly delayed (mean delay, 3.0 years). The mean maximum stimulated GH level was 12.3 micrograms/L and the mean GH dose given was 0.291 +/- 0.038 mg/kg per week. After 1 and 2 years of treatment with GH the growth rate increased in all patients with available growth rate data. The growth rates in these children were slightly lower than in children who were treated with GH for idiopathic GH deficiency. The weight-for-height standard deviation scores improved significantly after 2 years of GH treatment. There were adverse reactions (glucose intolerance) to GH in only two patients; treatment was suspended in one of these patients but was continued in the other. National Cooperative Growth Study data indicate that treatment with GH increases linear growth and weight in prepubertal patients with CF. These data suggest that GH may be useful for treating malnutrition in CF.

Adolescent↗
PubMed1997

Insulin resistance is associated with decreased clinical status in cystic fibrosis.

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patients was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m2 per minute). Results from the 120 mU/m2 per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 +/- 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 +/- 1.1, patients with CF = 10.2 +/- 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance (r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes.

Adult↗
PubMed1997

Treatment of childhood syndrome X.

OBJECTIVE: Hyperinsulinemia, hyperlipidemia, hypertension, and coronary artery disease comprise a quartet known as Syndrome X. This syndrome was first described in adults, but has recently been described in children and adolescents. The purpose of our study was to determine if diet or exercise is able to change the clinical profile of Syndrome X in children. STUDY DESIGN: We recruited 36 obese (% ideal body weight = 170.3 +/- 31.1), children (9 to 12 yrs old) known to have high fasting cholesterol levels (177.5 +/- 33.5 mg/dL). Each participated in a 6-week protocol in one of three groups: control (C), diet (D), or exercise (E). Twenty-five of the patients completed the study with full compliance. At the beginning and end of the study, we measured weight, height, blood pressure, serum insulin, and a lipid profile including: cholesterol, low density lipoprotein, high density lipoprotein (HDL), triglycerides, and apolipoprotein A (ApoA). All subject groups were similar before the study. The D group had the greatest attrition (40%) and all of the E group completed the study. RESULTS: After the 6-week study period, there was no significant weight loss or change in body mass index for any group. There was no significant change in blood pressure and there was no significant decline of fasting cholesterol or low density lipoprotein levels in any of the groups. HDL levels were low in all groups and did not significantly change with treatment. There was a significant decline in the triglyceride levels in both the diet and exercise groups after the study (preD = 150 +/- 60; postD = 122 +/- 50; preE = 165 +/- 50; postE = 116 +/- 39). Both the D and E groups also demonstrated a significant decrease in ApoA levels (preD = 174 +/- 33; postD = 142 +/- 24; preE = 200 +/- 50; postE = 161 +/- 23). Most impressively, fasting insulin levels significantly decreased with both diet and exercise, but did not change in controls during the 6 weeks (preC = 52 +/- 19; postC = 53 +/- 21; preD = 54 +/- 23; postD = 15 +/- 8; preE = 48 +/- 21; postE = 9). CONCLUSIONS: The findings of this study are consistent with previous studies describing the presence of Syndrome X in childhood. Both diet and exercise were effective in lowering triglyceride, ApoA levels, and insulin levels. However, due to the large rate of noncompliance in the diet group, exercise seems to be the best treatment for improvement in Syndrome X in children.

Child↗
PubMed1996

Spectrophometric assay for measuring branched-chain amino acid concentrations: application for measuring the sensitivity of protein metabolism to insulin.

Plasma amino acid concentrations fall during insulin infusion. Amino acid concentrations can be maintained using an infusion of amino acids if their plasma concentration can be determined within a few minutes. We developed a spectrophometric assay which determines the total concentration of all three branched-chain amino acids in plasma within 1 min. The enzyme leucine dehydrogenase oxidatively deaminates leucine, isoleucine, and valine, with stoichiometric reduction of NAD that is measured using a spectrophotometer. The assay was developed in both a kinetic and end-point format. For the kinetic assay the buffer conditions were formulated to obtain equivalent rates with all three amino acids so that it could be used in samples containing unknown mixtures. For the end-point assay additional enzyme was added so that an end-point could be reached within 1 min. The application of the kinetic assay for "clamping" the branched-chain amino acids during hyperinsulinemic euglycemic clamps in humans is demonstrated.

Amino Acid Oxidoreductases↗