G. E. Butterfield

Evaluation of exercise and training on muscle lipid metabolism

To evaluate the hypothesis that endurance training increases intramuscular triglyceride (IMTG) oxidation, we studied leg net free fatty acid (FFA) and glycerol exchange during 1 h of cycle ergometry at two intensities before training [45 and 65% of peak rate of oxygen consumption (V˙o 2 peak)] and after training [65% pretrainingV˙o 2 peak, same absolute workload (ABT), and 65% posttrainingV˙o 2 peak, same relative intensity (RLT)]. Nine male subjects (178.1 ± 2.5 cm, 81.8 ± 3.3 kg, 27.4 ± 2.0 yr) were tested before and after 9 wk of cycle ergometer training, five times per week at 75%V˙o 2 peak. The power output that elicited 66.1 ± 1.1% ofV˙o 2 peak before training elicited 54.0 ± 1.7% after training due to a 14.6 ± 3.1% increase inV˙o 2 peak. Training significantly ( P < 0.05) decreased pulmonary respiratory exchange ratio (RER) values at ABT (0.96 ± 0.01 at 65% pre- vs. 0.93 ± 0.01 posttraining) but not RLT (0.95 ± 0.01). After training, leg respiratory quotient (RQ) was not significantly different at either ABT (0.98 ± 0.02 pre- vs. 0.98 ± 0.03 posttraining) or RLT (1.01 ± 0.02). Net FFA uptake was increased at RLT but not ABT after training. FFA fractional extraction was not significantly different after training or at any exercise intensity. Net glycerol release, and therefore IMTG lipolysis calculated from three times net glycerol release, did not change from rest to exercise or at ABT but decreased at the same RLT after training. Muscle biopsies revealed minor muscle triglyceride changes during exercise. Simultaneous measurements of leg RQ, net FFA uptake, and glycerol release by working legs indicated no change in leg FFA oxidation, FFA uptake, or IMTG lipolysis during leg cycling exercise that elicits 65% pre- and 54% posttrainingV˙o 2 peak. Training increases working muscle FFA uptake at 65%V˙o 2 peak, but high RER and RQ values at all work intensities indicate that FFA and IMTG are of secondary importance as fuels in moderate and greater-intensity exercise.

Muscle net glucose uptake and glucose kinetics after endurance training in men.

We evaluated the hypotheses that alterations in glucose disposal rate (Rd) due to endurance training are the result of changed net glucose uptake by active muscle and that blood glucose is shunted to working muscle during exercise requiring high relative power output. We studied leg net glucose uptake during 1 h of cycle ergometry at two intensities before training [45 and 65% of peak rate of oxygen consumption (V˙o 2 peak)] and after training [65% pretrainingV˙o 2 peak, same absolute workload (ABT), and 65% posttrainingV˙o 2 peak, same relative workload (RLT)]. Nine male subjects (178.1 ± 2.5 cm, 81.8 ± 3.3 kg, 27.4 ± 2.0 yr) were tested before and after 9 wk of cycle ergometer training, five times a week at 75%V˙o 2 peak. The power output that elicited 66.0 ± 1.1% ofV˙o 2 peak before training elicited 54.0 ± 1.7% after training. Whole body glucose Rd decreased posttraining at ABT (5.45 ± 0.31 mg ⋅ kg-1 ⋅ min-1at 65% pretraining to 4.36 ± 0.44 mg ⋅ kg-1 ⋅ min-1) but not at RLT (5.94 ± 0.47 mg ⋅ kg-1 ⋅ min-1). Net glucose uptake was attenuated posttraining at ABT (1.87 ± 0.42 mmol/min at 65% pretraining and 0.54 ± 0.33 mmol/min) but not at RLT (2.25 ± 0.81 mmol/min). The decrease in leg net glucose uptake at ABT was of similar magnitude as the drop in glucose Rd and thus could explain dampened glucose flux after training. Glycogen degradation also decreased posttraining at ABT but not RLT. Leg net glucose uptake accounted for 61% of blood glucose flux before training and 81% after training at the same relative (65%V˙o 2 peak) workload and only 38% after training at ABT. We conclude that 1) alterations in active muscle glucose uptake with training determine changes in whole body glucose kinetics; 2) muscle glucose uptake decreases for a given, moderate intensity task after training; and 3) hard exercise (65%V˙o 2 peak) promotes a glucose shunt from inactive tissues to active muscle.

Effect of sustained resistance training on basal metabolic rate in older women.

OBJECTIVE: To determine if basal metabolic rate (BMR) could be elevated in older women undertaking a program of progressive resistance exercise of up to 52‐weeks duration.

Accuracy of equations to predict basal metabolic rate in older women.

OBJECTIVE To assess the accuracy of several published equations for predicting basal metabolic rate (BMR) in older women. DESIGN BMR was assessed in 116 healthy, older white women, aged 60 to 82 years, on three successive mornings by indirect calorimetry. Body composition was determined by dual energy X-ray absorptiometry or hydrostatic weighing. The measured BMRs were compared with values obtained from eight published prediction equations that used solely, or in various combinations, measures of height, weight, fat-free mass, age, and menopausal status. STATISTICAL ANALYSES PERFORMED The root mean squared prediction error (RMSPE) was used to determine how accurately predicted BMR matched actual BMR for each subject. In addition, regression analysis was used to evaluate accuracy of predicted BMR vs directly measured BMR. RESULTS Predicted mean BMR determined using all eight equations was significantly correlated to measured BMR (P = .0001), accounting for 30% to 52% of the variance of measured BMR. When analyzed by RMSPE, however, the equations of Owen et al (1986), Fredrix et al (1990), and Harris-Benedict (1919) predicted actual BMR for each subject within an average of 116 kcal/day, and the equation of Cunningham (1980) resulted in the largest prediction error at 208 kcal/day. APPLICATIONS/CONCLUSIONS The regression equations of Owen et al (1986), which used body weight, Fredrix et al (1990), which used body weight and age, and Harris-Benedict (1919), which used age, weight, and height as variables, were most accurate in predicting BMR in our sample of healthy older women.

Nutritional Intake in Patients with Senile Dementia of the Alzheimer Type

Summary:The dietary intake of 29 healthy controls was compared with that of 35 community-dwelling patients with probable or definite senile dementia of the Alzheimer type (SDAT), based on NINCDS-ADRDA criteria. The control subject or the caregiver of the SDAT patient completed a 3-day estimated-dietaryintake record. Foods offered to patients were chosen, for the most part, by caregivers, but SDAT patients were allowed to eat ad libitum from those choices, and food consumed was recorded. Dietary intake was evaluated against the 1989 Recommended Dietary Allowances (RDA). Dietary intakes did not differ significantly between control and SDAT patients for any of the 32 nutrients analyzed. The controls and SDAT patients met the RDA guidelines for intake of total energy, protein, and micronutrients, with the exception of female SDAT patients, who did not consume a minimum of two thirds of the RDA for vitamin D. All biochemical indices of nutritional status were within normal limits for the SDAT patients. In addition, cognitive function did not correlate with intake of any nutrient studied. We conclude that moderately impaired, community-dwelling patients with SDAT do not differ from healthy controls in nutritional status or nutrient intake. Neither general nor nutrient-specific malnutrition was present in this population. Based on this cross-sectional study, malnutrition does not appear to be a major contributor to the pathogenesis of Alzheimer disease. However, this investigation examined only a single point in time, when patients were being fed by caregivers, so that the role of malnutrition at the beginning of the disease was not addressed.

Functional consequences of the somatopause and its treatment

The decline in the function of the growth hormone-releasing hormone, growth hormone, insulin-like growth factor (GHRH-GH-IGF) axis has been termed the somatopause. Many of the catabolic sequelae seen in normal aging has been attributed to this decrease in circulating GH and IGF-I. In order to provide hormone replacement therapy for the somatopause, elderly subjects have been treated with GH, IGF-I, or both hormones together. Whereas numerous beneficial effects on body composition, strength, and quality of life have been reported in some studies, other studies have reported only marginal functional imporvements. Moreover, it is clear that both hormones can cause significant morbidity.

Influence of α-adrenergic blockade on the catecholamine response to exercise at 4,300 meters

Abstract This investigation examined the influence of α-adrenergic blockade on plasma and urinary catecholamine responses to both exercise and high-altitude exposure. Sixteen nonsmoking, eumenorrheic women (age 23.2 ± 1.4 years, 68.7 ± 1.0 kg) were studied at sea level and during 12 days of high-altitude exposure (4,300 m). Subjects received either α-blockade (prazosin 3 mg/d) or a placebo in a double-blinded, randomized fashion. Resting plasma and 24-hour urine samples were collected periodically throughout the duration of the study. Further, subjects participated in submaximal exercise tests (50 minutes at 50% sea level maximum oxygen consumption [Vo 2 max]) at Sea level and on days 1 and 12 at altitude. Urinary norepinephrine (NE) excretion rates increased significantly over time at altitude, with blocked subjects having greater values compared to controls. Plasma NE levels increased significantly with chronic altitude exposure compared to sea level and acute hypoxia both at rest and during exercise. NE levels at rest were greater for blocked compared to control subjects during all conditions. Urinary and plasma epinephrine (EPI) levels increased dramatically, with acute altitude exposure returning to sea level values by day 12 of altitude exposure. EPI levels were greater for blocked compared to placebo both at rest and during exercise for all conditions studied. Changes in α-adrenergic activity over time at altitude were associated with select metabolic and physiologic adjustments. The presence of α-blockade significantly affected these responses during chronic altitude exposure. It was concluded that: (1) α- adrenergic blockade elicited a potentiated sympathoadrenal response to the stress of both exercise as well as high-altitude exposure, and (2) the sympathetics, via α-adrenergic stimulation, contribute to a number of key adaptations associated with acclimatization to high altitude.

Effect of Sun-Dried Raisins on Bile Acid Excretion, Intestinal Transit Time, and Fecal Weight: A Dose–Response Study

The effect of increasing doses of sun-dried raisins (SDR) on intestinal transit time (TT), fecal weight (FW), and fecal bile acids (FBA) was investigated in 16 healthy adults (6 men and 10 women). In three cycles of 2 weeks each, subjects consumed 84, 126, or 168 g/day of SDR. Four-day fecal collections were performed during the second week of each cycle, and TT, FW, and FBA were measured. FW (mean +/- SEM), increased from 168 +/- 14 g/day without raisins (cycle 1), with a TT of 54 +/- 6 hours, to 200 +/- 24 g/day with 168 g/day raisins (cycle 4), with a TT of 42 +/- 6 hours. Intermediate increases in FW and decreases in TT were observed for cycles 2 and 3. A physiologically meaningful decrease in TT (less than 2 days), to 44 +/- 6 hours, was reached at cycle 2 (not statistically significant). FBA, a possible indicator of colon cancer risk, showed a significant decrease, from 1.00 +/- 0.18 mg/g wet feces at baseline to 0.38 +/- 0.07 mg/g in cycle 2 (P <.005), and remained low in cycles 3 and 4. Major decreases were observed in cycle 2 for fecal lithocholic (P <.02), deoxycholic (P <.002), chenodeoxycholic, and cholic acids, and their concentrations remained low in cycles 3 and 4. Two servings of raisins per day (84 g/day), a relatively small change in diet, can cause beneficial changes in colon function and may decrease the risk for colon cancer.

Five weeks of insulin-like growth factor-I treatment does not alter glucose kinetics or insulin sensitivity during a hyperglycemic clamp in older women

Insulin sensitivity and the activity of the hypothalamic-growth hormone (GH)- insulin-like growth factor-I (IGF-I) axis both decline with age. Treatment with IGF-I increases insulin sensitivity in healthy young subjects. We hypothesized that increasing plasma IGF-I in postmenopausal women to levels characteristic of young women would enhance insulin sensitivity. To test the hypothesis, fasting glucose kinetics and insulin sensitivity were measured in 24 healthy, normoglycemic, postmenopausal women before and after 5 weeks of treatment with either recombinant human (rh)IGF-I (15 microg/kg body weight/d twice daily) or placebo in a double-blind study. Diet energy content and composition were rigidly controlled to maintain energy balance. A hyperglycemic clamp (8 mmol/L) coupled with stable isotope infusion ([6,6(2)H]glucose) was performed before and after treatment to assess whole-body insulin sensitivity; defined as the glucose rate of disappearance (Rd) or rate of infusion (GRIF) scaled to the steady-state insulin concentration (I). There were no differences in fasting glucose or insulin concentrations, glucose kinetics, or glucose oxidation after either treatment. During the clamps, steady-state insulin concentrations with placebo (pre = 151 +/- 28 pmol/L, post = 173 +/- 31 pmol/L) were slightly different than with IGF-I (pre = 182 +/- 37 pmol/L, post = 163 +/- 33 pmol/L), but the variations were not significant. No significant changes in whole-body insulin sensitivity were observed after treatment with IGF-I, calculated as Rd/I (pre = 17.7 +/- 2.6 microg/kg/min/pmol/L, post = 19.3 +/- 2.0 microg/kg/min/pmol/L for IGF-I v pre = 24.2 +/- 2.5 microg/kg/min/pmol/L, post = 22.8 +/- 3.4 microg/kg/min/pmol/L for placebo) or as GRIF/I (pre = 18.0 +/- 3.9 microg/kg/min/pmol/L, post = 22.3 +/- 3.5 microg/kg/min/pmol/L for IGF-I v pre = 26.4 +/- 6.2 microg/kg/min/pmol/L, post = 26.9 +/- 4.8 microg/kg/min/pmol/L for placebo). Baseline insulin sensitivity in women using hormone replacement therapy (HRT, n = 15) was similar to nonusers (n = 9), but HRT users derived a greater portion of energy expenditure from carbohydrate oxidation compared with nonusers. HRT use had no impact on the response to IGF-I. Overall, we observed subtle, but physiologically insignificant, variations after IGF-I treatment in the direction of enhanced insulin sensitivity. The data suggest that 5 weeks of low-dose rhIGF-I treatment has no material influence on whole-body insulin sensitivity in normoglycemic postmenopausal women.

Effects of Recombinant Human Insulin-Like Growth Factor I in Aging

While growth hormone (GH) is necessary for metabolic homeostasis in infants and for linear growth in children, the role of this pituitary hormone in adults has not yet been clarified. It has long been appreciated that normal aging is associated with a decline in the activity of the GH releasing hormone (GHRH)-GH-insulin-like growth factor I (IGF-I) axis, and it has recently been suggested that many of the degenerative changes seen in the elderly, such as muscle wasting and osteopenia, are in part caused by relative GH and/or IGF-I deficiency. It has been postulated that the age-related decline in the activity of the hypothalamic-somatotroph-IGF-I axis results in a catabolic diathesis that leads to falls, fractures, and frailty in the elderly, a syndrome complex that has been named the somatopause (1).