Effect of raloxifene after recombinant teriparatide [hPTH(1-34)] treatment in postmenopausal women with osteoporosis.

UNLABELLED: Loss of bone mineral density occurs after discontinuation of teriparatide, if no subsequent treatment is given. Sequential raloxifene prevented rapid bone loss at lumbar spine and further increased bone mineral density (BMD) at femoral neck, whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. INTRODUCTION: We compared the sequential effects of raloxifene treatment with a placebo on teriparatide-induced increases in bone mineral density (BMD). A year of open-label raloxifene extended the study to assess the response with and without delay after discontinuation of teriparatide. METHODS: Following a year of open-label teriparatide 20 mug/day treatment, postmenopausal women with osteoporosis were randomly assigned to raloxifene 60 mg/day (n = 157) or a placebo (n = 172) for year 2, followed by a year of open-label raloxifene. BMD was measured by dual energy x-ray absorptiometry. RESULTS: The raloxifene and placebo groups showed a decrease in lumbar spine (LS) BMD in year 2 for raloxifene and placebo groups (-1.0 +/- 0.3%, P = 0.004; and -4.0 +/- 0.3%, P < 0.001, respectively); the decrease was less with raloxifene (P < 0.001). Open-label raloxifene treatment reversed the LS BMD decrease with a placebo, resulting in similar decreases 2 years after randomization (-2.6 +/- 0.4% (raloxifene-raloxifene) and -2.7 +/- 0.4% (placebo-placebo). At study end, LS and femoral neck (FN) BMD were higher than pre-teriparatide levels, with no significant differences between the raloxifene-raloxifene and placebo-raloxifene groups, respectively (LS: 6.1 +/- 0.5% vs. 5.1 +/- 0.5%; FN: 3.4 +/- 0.6% vs. 3.0 +/- 0.5%). CONCLUSION: Sequential raloxifene prevented rapid bone loss at the LS and increased FN BMD whether raloxifene was started immediately or after a one-year delay following teriparatide treatment.

Severity of vertebral fracture reflects deterioration of bone microarchitecture.

INTRODUCTION: Bone microarchitecture, a component of bone strength, is generally measured on transiliac bone biopsy samples. The objective of this study was to determine whether assessment of four grades of vertebral fracture severity could serve as a noninvasive surrogate marker for trabecular bone volume and microarchitecture. METHODS: Baseline vertebral fracture severity was determined by semiquantitative assessment of spine radiographs from 190 postmenopausal women with osteoporosis. Bone-structure indices were obtained by 2D histomorphometry and 3D microcomputed tomography (CT) analyses. Significance of differences was determined after adjusting for age, height, and lumbar spine bone mineral density. RESULTS: There were significant (P < 0.05) trends in decreasing bone volume, trabecular number, and connectivity, and increasing trabecular separation with greater vertebral fracture severity. Histomorphometric bone volume was 25 and 36% lower (P < 0.05) in women with moderate and severe fractures than in women with no fractures, respectively. Compared with women without fractures, women with mild, moderate, and severe fractures had lower (P < 0.05) microCT bone volume (23, 30, and 51%, respectively). CONCLUSIONS: Microarchitectural deterioration was progressively worse in women with increasing severity of vertebral fractures. We conclude that assessment of vertebral fracture severity is an important clinical tool to evaluate the severity of postmenopausal osteoporosis.

Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy.

Teriparatide (rhPTH[1-34]), a bone-forming agent for the treatment of osteoporosis, increases bone mineral density in men and women, and reduces the risk of fractures in women with osteoporosis. However, fracture efficacy has not yet been confirmed in men. Further, there is limited information on the effect of withdrawal of teriparatide. The purpose of this manuscript is to report on bone mineral density and vertebral fracture incidence during a 42-month observation period, from the baseline of the previously reported treatment study in men [1] through 30 months of posttreatment follow-up. Three hundred fifty-five men who were treated with once-daily self-injections of either placebo or 20 or 40 microg of teriparatide participated in the follow-up study. Bone mineral density gradually decreased following discontinuation of teriparatide therapy. However, the lumbar spine and total hip values remained significantly higher than baseline after 30 months of follow-up (p< or =0.001). Antiresorptive treatment prevented the decline and tended to further increase bone mineral density. Lateral thoracic lumbar radiographs obtained at baseline and 18 months after discontinuation of teriparatide were available for 279 men. Of these men, 11.7% assigned to placebo, 5.4% treated with teriparatide 20 microg, and 6.0% treated with teriparatide 40 microg had an incident vertebral fracture. In the combined teriparatide treated groups vs placebo, the risk of vertebral fracture was reduced 51% (nonsignificant, p=0.07). The incidence of moderate or severe fractures was significantly reduced by 83% (p=0.01). In conclusion, men who received teriparatide and who may have received follow-up antiresorptive therapy had a decreased risk of moderate and severe vertebral fractures.

Dual-energy X-ray absorptiometry of birds: an examination of excised skeletal specimens.

The ability of dual-energy X-ray absorptiometry (DXA) to measure bone mineral content and density of bird bones has received little attention. This paper represents the first comprehensive study of the methods, precision, and reproducibility of DXA (GE-Lunar DPX-L) for the uniquely shaped, thin and pneumatic bones of birds. Skeletal elements and portions represented by 26 regions of interest (ROIs) are presented and evaluated for the gallinaceous bird species, wild turkey (Meleagris gallopavo), ruffed grouse (Bonasa umbellus) and bobwhite quail (Colinus virginianus). Using Lunar small animal software and the methods described in this paper, photodensitometry of bird bones is possible and opens new opportunities for using birds in clinical models in veterinarian science, osteoporosis studies, space biology, and even archaeological and paleontological research.

Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis.

Treatment with teriparatide (rDNA origin) injection [teriparatide, recombinant human parathyroid hormone (1-34) [rhPTH(1-34)]] reduces the risk of vertebral and nonvertebral fragility fractures and increases cancellous bone mineral density in postmenopausal women with osteoporosis, but its effects on cortical bone are less well established. This cross-sectional study assessed parameters of cortical bone quality by peripheral quantitative computed tomography (pQCT) in the nondominant distal radius of 101 postmenopausal women with osteoporosis who were randomly allocated to once-daily, self-administered subcutaneous injections of placebo (n = 35) or teriparatide 20 microg (n = 38) or 40 microg (n = 28). We obtained measurements of moments of inertia, bone circumferences, bone mineral content, and bone area after a median of 18 months of treatment. The results were adjusted for age, height, and weight. Compared with placebo, patients treated with teriparatide 40 microg had significantly higher total bone mineral content, total and cortical bone areas, periosteal and endocortical circumferences, and axial and polar cross-sectional moments of inertia. Total bone mineral content, total and cortical bone areas, periosteal circumference, and polar cross-sectional moment of inertia were also significantly higher in the patients treated with teriparatide 20 microg compared with placebo. There were no differences in total bone mineral density, cortical thickness, cortical bone mineral density, or cortical bone mineral content among groups. In summary, once-daily administration of teriparatide induced beneficial changes in the structural architecture of the distal radial diaphysis consistent with increased mechanical strength without adverse effects on total bone mineral density or cortical bone mineral content.

Bone mineral density of competitive male mountain and road cyclists.

The purpose of this study was to compare the bone mineral density (BMD) of two types of trained male cyclists (n = 30) with recreationally active men (n = 15), aged 20-40 years. Sixteen of the cyclists regularly trained for, and competed in, cross-country mountain bike races. The other 14 cyclists trained and raced on the road. The cyclists had trained an average of 11 +/- 3 hours per week for 8 +/- 4 years. Fifteen recreationally active men volunteered as controls. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD of the proximal femur, lumbar spine, and total body. Anthropometric, muscle strength and power, aerobic fitness, and sex hormone data assessments were conducted on all participants. Mountain cyclists were younger and weighed less than road cyclists and controls. BMD at all sites was comparable among the three groups (p > 0.05). When adjusted for body weight and controlled for age, BMD was significantly higher at all sites in the mountain cyclists compared with the road cyclists and controls. Some anthropometric, physical fitness, and sex steroid variables were predictive of BMD, but of these variables, only total body weight, total body fat, and aerobic fitness were different between the groups. In conclusion, endurance road cycling does not appear to be any more beneficial to bone health than recreational activity in apparently healthy men of normal bone mass. Higher BMD in the mountain cyclists suggests that mountain cycling may provide an osteogenic stimulus that is not inherent to road cycling.

Comparison of accelerometers with oxygen consumption in older adults during exercise.

PURPOSE: The purpose of this study was to compare two commercially available accelerometers with indirect calorimetry in a group of older adults (x +/- SD; 70.6+/-3.7 yr; N = 86, 44 males and 42 females). METHODS: The accelerometers (Caltrac and Tritrac, Hemokinetics, Madison, WI) were worn while performing three submaximal, discontinuous (5 min exercise, 2 min recovery), progressive levels of treadmill walking and bench stepping. The treadmill exercise averaged 3.4 mph, at 0.4% grade, 3.0% grade, and 5.1% grade, while the stepping work rates (24 steps x min(-1)) were performed on 15.2-, 20.3-, and 25.4-cm steps. Estimated energy expenditure (EE) from the two accelerometers was compared with EE as measured by indirect calorimetry. RESULTS: The Caltrac significantly (P < 0.05) overestimated EE at the three treadmill work rates (10-52% difference) and underestimated EE at the three stepping work rates (-19% to -28% difference). When comparing the changes in EE between work rates one, two and three, the Caltrac was not sensitive to the changes (increase in EE) that occurred during graded treadmill walking but did detect some changes in the stepping exercise. The Tritrac significantly (P < 0.05) underestimated EE for the three work rates of both the treadmill and stepping exercise when compared with indirect calorimetry but did detect differences in EE among work rates during stepping exercise (P < 0.05). CONCLUSIONS: These data indicate that the magnitude of the differences between measured and estimated EE is affected by exercise mode and intensity and that caution is warranted when using the accelerometers in an attempt to quantify EE in older adults.

Calciotropic hormones and bone markers in the elderly.

There is a lack of substantial data on changes in calciotropic hormones and bone markers in elderly subjects living in North America. Parathyroid hormone (PTH), serum 25-hydroxyvitamin D (25(OH)D) and bone markers (serum osteocalcin and urine N-telopeptide), were measured in 735 Caucasian subjects (235 men and 500 women) aged 65-87 years. There was a significant increase in serum osteocalcin and urine N-telopeptide with age in men, and a significant increase in serum osteocalcin with age in women. Serum PTH and 25(OH)D showed no significant change with age in men or women. After adjusting for age, calcium intake, serum creatinine, season, and weight, mean serum PTH (p = 0.01), serum osteocalcin (p = 0.0001) and 24 h urine N-telopeptide (p = 0.0001) were higher in women than men, and mean serum 25(OH)D (p = 0.0001) and 24 h urine calcium (p = 0.0001) were higher in men than women. Serum PTH was correlated with serum osteocalcin in men and women, r = 0.24, r = 0.17, p < 0.001, but not with urine N-telopeptide. Serum PTH was inversely correlated with serum 25(OH)D (r = -0.25, r = -034,p < 0.001), and positively correlated with serum creatinine (r = 0.14, r = 0.17,p < 0.01) in men and women. The prevalence of serum 25(OH)D levels below 12 ng/ml was only 33% in females and 0.4% in men. Thus vitamin D deficiency was very uncommon in the U.S.A. compared with Europe. Although mean serum PTH was increased in the elderly, only 4-6% had PTH levels above the normal range. In summary, the increase in serum PTH in the elderly can be explained more by changes in vitamin D status than by declining renal function. These data also show significantly higher (p = 0.001) bone remodeling markers in women.

Economy of mobility in older adults.

A decline in economy of mobility indicates that more physical work is required for a task (ie., walking) and may suggest an abnormal gait pattern. A normal gait pattern is essential for maintaining independence in older adults. The purpose of this study was to compare economy of mobility between sedentary older men and women. The subjects were 47 men (mean +/- SD; age = 71 +/- 4 years, weight = 83 +/- 8 kg, height = 175 +/- 7 cm) and 51 women (70 +/- 3 years, 65 +/- 8 kg, 161 +/- 5 cm). Men were significantly (p < 0.05) older, heavier, and taller than women. Maximal oxygen uptake (VO2max) was collected while subjects walked on a treadmill until volitional exhaustion. On a separate day, a submaximal test was performed at one speed requiring approximately 60% of VO2max on a level treadmill for 5 minutes. Men had significantly greater absolute and relative VO2max than women. Men walked at a significantly faster speed (92 +/- 8 vs. 86 +/- 7 m/min) than women during the submaximal test. Economy of mobility was the same for older men and women (0.17 +/- 0.02 ml/kg/m) with differences in walking speed controlled. The results indicate that there is not a gender-specific decrement in economy of mobility with aging.

Normalizing strength for body size differences in older adults.

The purpose of this study was to compare the normalization methods of ratio standards, allometry, and ANCOVA with knee extensor strength of older adults. The apparently healthy older volunteers were 71 men (mean +/- SD; age, 71 +/- 4 yr; body mass, 81 +/- 10 kg; height, 174 +/- 7 cm) and 77 women (71 +/- 4 yr, 65 +/- 8 kg, 160 +/- 5 cm. respectively). Strength was defined as peak torque (N.m-1) and measured with a Cybex II isokinetic dynamometer. Body composition was estimated with dual energy x-ray absorptiometry. With allometry, the body mass exponent (0.74) was not statistically different from theory (0.67). Body mass adjusted strengths were 34.7% (allometry), 32.0% (ANCOVA), and 29.4% (ratio standards) greater in older men than women. Allometry revealed that the bone-free lean tissue mass exponent was not different from ratio standard exponent of 1.0. After adjustment by bone-free lean tissue mass, strength in men remained 16.0% (allometry and ratio standards) higher than in women, but, strength differences between genders were eliminated with ANCOVA. The methods used to normalize strength yielded similar results with body mass but conflicting results with bone-free lean tissue mass.

Guidelines for diagnosing osteoporosis.

Women who are estrogen deficient have an increased risk of osteoporosis and future fractures. In recent years, improving technology and a consensus on the definition of osteoporosis have made it easier to measure bone density and assess the risk of osteoporosis. Density should be measured at two sites, the lumbar spine and the femoral neck. If only one measurement is possible, the site should be the lumbar spine in women younger than 65 and the femoral neck in women 65 and older. Treatment is recommended if a woman's bone density is more than one standard deviation below the young adult reference value.

Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise.

Plasma free fatty acid (FFA) levels tend to be lower and the plasma lipolytic hormone response to prolonged exercise of the same intensity is blunted after endurance exercise training. To determine whether training elicits a corresponding decrease in plasma FFA turnover and metabolism during prolonged exercise, we measured plasma [1-13C]palmitate kinetics and oxidation and respiratory gas exchange in 13 subjects during the latter portion of a 90- to 120-min bout of cycle ergometer work performed before and after 12 wk of alternate-day cycling and running. Training increased total fat oxidation during prolonged exercise by 41% (P < 0.005). However, for the final 30-60 min of the cycle ergometer protocol, the rate of 13CO2 production from [1-13C]palmitate oxidation was 27% lower (P < 0.05), the rate of palmitate turnover was 33% less (P < 0.05), and plasma FFA and glycerol concentrations were 32 and 20% lower (P < 0.05), respectively, than in the untrained state. Thus endurance exercise training results in decreased plasma FFA turnover and oxidation during a 90- to 120-min bout of submaximal exercise because of a slower rate of FFA release from adipose tissue.

Bone mineral density in elite junior Olympic weightlifters.

The purpose of this study was to examine the relationship of bone mineral density (BMD) to muscular strength in highly trained young male athletes in order to gain insights concerning the influence of heavy resistance training on BMD. Twenty-five elite junior weightlifters (age, 17.4 +/- 1.4 yr) and 11 age-matched controls (16.9 +/- 1.1 yr) volunteered for this investigation. Measurements of BMD (g.cm-2) utilizing dual energy x-ray absorptiometry were obtained for the lumbar spine (L2-4) and the proximal femur (neck; trochanter, Ward's triangle). The BMD values for the junior lifters were found to be significantly greater at all sites for the junior weightlifters compared with their age-matched control group. The BMD values of the spine and femoral neck of the junior weightlifters when compared with adult reference data (i.e., 20-39 yr old men) were found to be significantly greater. Both simple and multiple regression analyses demonstrated significant relationships of BMD with strength accounting for 30-65% of the variance. These data suggest that in elite junior weightlifters, muscle strength, highly specific to the sport of weightlifting, has a major influence on BMD due to the influence of the chronic overloads experienced in training.

Body composition of healthy sedentary and trained, young and older men and women.

This study examined the effects of age and physical activity on body composition and fat distribution by comparing differences between young and older endurance trained men and women with differences between young and older sedentary people. Although indices of total body adiposity (fat mass, percent body fat) were higher in the older than in the young people in both the trained and the sedentary groups, the magnitude of the difference was markedly less in the trained group (P less than 0.01). The average differences in fat mass between young and old sedentary men and women were 10.1 kg and 12.2 kg, respectively, but only 4.3 kg and 5.5 kg in trained men and women. Skinfold thicknesses were approximately 24% and approximately 47% larger at all sites (triceps, thigh, subscapula, pectoralis, umbilicus, suprailiac) in the older than in the young trained men and women, respectively. Similar differences were found between young and older sedentary people except at central, upper body sites, where the relative differences in skinfold thicknesses between young and older sedentary people were 2- to 6-fold greater than in trained people. Thus, people who exercise regularly appear to accumulate less adipose tissue in upper, central body regions as they get older, potentially reducing the risk for the metabolic disorders associated with upper body obesity.

Insulin secretory capacity in endurance-trained and untrained young men.

Insulin secretion in response to glucose stimulation is reduced in endurance-trained humans. In this study, a modified hyperglycemic clamp, with a superimposed arginine infusion and fat meal, was performed on eight endurance-trained and nine untrained men to determine whether insulin secretory capacity is reduced by exercise training. Raising the plasma glucose concentration to approximately 450 mg/dl resulted in a plasma insulin response in the trained men that was approximately 64% lower than that of the untrained (peak values: 54 +/- 8 vs. 149 +/- 35 microU/ml; P less than 0.001). When a primed continuous infusion of arginine was superimposed on the hyperglycemia, the plasma insulin response was also markedly lower (66%) in the trained subjects, reaching peak values of 333 +/- 68 and 974 +/- 188 microU/ml for trained and untrained subjects, respectively (P less than 0.005). When insulin secretion was further stimulated during the arginine-infused hyperglycemia by the ingestion of a high-fat meal, peak insulin concentrations averaged 989 +/- 205 microU/ml in the trained compared with 2,232 +/- 455 microU/ml in the untrained subjects (P less than 0.01). The response of gastric inhibitory polypeptide (GIP) to the fat meal was delayed and blunted, suggesting that some enteric factor(s) other than GIP mediated the insulinotropic effect of the fat meal. The reduced plasma insulin response in trained people to the stimuli investigated suggests that regular exercise produces either several adaptations within the beta-cell or a single alteration of the beta-cell that results in an attenuation of the insulin secretory response to glucose, arginine, and fat ingestion.

Effect of exercise on bone: permissive influence of estrogen and calcium.

Estrogen deficiency in postmenopausal women is associated with low lumbar bone mineral density and an increased incidence of fractures of the vertebrae and proximal femur. Estrogen deficiency in premenopausal women with secondary amenorrhea related to athletic training or anorexia nervosa is also associated with decreased lumbar bone mineral density. The purpose of this review is to present four concepts related to the adaptations of bone to physical exercise, as a basis to explain the loss of bone mass in women with athletic amenorrhea. These concepts are based on Lanyon's theory of a Minimum Effective Strain-Related Stimulus. The bone remodeling response to estrogen deficiency is an increase in the rate of bone remodeling activity and in the rate of bone resorption relative to formation, resulting in a net loss of bone mass. In the presence of estrogen deficiency, the stimulus of physical activity is thought first to decrease the rate of turnover and secondly to increase bone formation. Endurance exercise training appears to be an insufficient stimulus to accomplish both tasks, which may explain why these athletes often have low lumbar bone mineral density.

The role of exercise in the prevention of osteoporosis.

The response of an individual's bone mass to exercise training will depend, in part, on their present level of functional activity and on the hormonal and nutritional milieus of bone tissue. For normally active, but not trained persons, an exercise training program may lead to a new bone mass as much as 5% to 10% above baseline. In an individual with a bone mass which is markedly reduced because of inactivity, poor nutrition, or hormonal deficiency (or excess, depending on the hormone), it is possible that exercise will result in even larger gains in bone mass. Training with weight-bearing exercises may serve as an osteogenic stimulus to both young and older individuals. If the training program is limited or restricted, however, older people may not show the same magnitude of change as do younger subjects. In women, low estrogen levels may reduce the apparent benefit from exercise training, as seen from the studies of amenorrheic athletes. Low bone mass may be related to an estrogen withdrawal effect as well as to the basic estrogen deficiency. Exercise training is likely to provide an osteogenic stimulus for the maintenance of bone mass when it is done in an environment of optimal hormonal levels and nutrition. Physical activity, however, may not be an effective substitute for estrogen therapy. Under optimal conditions, exercise training does provide an osteogenic stimulus to bone, resulting in an increase or maintenance of bone mass, when a loss might otherwise be expected. It is not realistic, however, to expect that exercise training will bring about a large increase in bone mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women.

STUDY OBJECTIVE: To assess the effect of weight-bearing exercise training and subsequent detraining on lumbar bone mineral content in postmenopausal women. DESIGN: Non-randomized, controlled, short-term (9 months) trial and long-term (22 months) exercise training and detraining (13 months). SETTING: Section of applied physiology at a university school of medicine. PATIENTS: Thirty-five healthy, sedentary postmenopausal women, 55 to 70 years old. All women completed the study. There was 90% compliance with exercise training. INTERVENTIONS: All women were given calcium, 1500 mg daily. The exercise group did weight-bearing exercise (walking, jogging, stair climbing) at 70% to 90% of maximal oxygen uptake capacity for 50 to 60 min, 3 times weekly. MEASUREMENTS AND MAIN RESULTS: Bone mineral content increased 5.2% (95% confidence interval [CI], 2.0% to 8.4%; P = 0.0037) above baseline after short-term training whereas there was no change (-1.4%) in the control group. After 22 months of exercise, bone mineral content was 6.1% (95% CI, 3.9% to 8.3% above baseline; P = 0.0001) in the long-term training group. After 13 months of decreased activity, bone mass was 1.1% above baseline in the detraining group. CONCLUSIONS: Weight-bearing exercise led to significant increases above baseline in bone mineral content which were maintained with continued training in older, postmenopausal women. With reduced weight-bearing exercise, bone mass reverted to baseline levels. Further studies are needed to determine the threshold exercise prescription that will produce significant increases in bone mass.

Glucagon, not insulin, may play a secondary role in defense against hypoglycemia during exercise.

The sympathochromaffin system, probably sympathetic neural norepinephrine, plays a primary role in the prevention of hypoglycemia during exercise in humans. Our previous data indicated that changes in pancreatic islet hormones are not normally critical but decrements in insulin, increments in glucagon, or both become critical when catecholamine actions are blocked pharmacologically. To distinguish between the role of insulin and that of glucagon in this secondary line of defense against hypoglycemia during exercise in humans, glucoregulation during moderate exercise (approximately 55% of maximum O2 consumption over 60 min) was studied in people who could not decrease insulin but could increase glucagon, i.e., patients with insulin-dependent diabetes mellitus (IDDM). While receiving constant intravenous infusions of regular insulin, in individualized doses shown to result in stable plasma glucose concentrations of approximately 95 mg/dl before exercise, patients with IDDM were studied under two conditions: 1) a control study (n = 13) and 2) an adrenergic blockade study (propranolol infusion, n = 8). In the control study, mean plasma glucose concentrations did not change (from 95 +/- 2 to 100 +/- 11 mg/dl) during exercise despite constant plasma free insulin levels. In the adrenergic blockade study plasma glucose declined (from 96 +/- 2 to 74 +/- 7 mg/dl, P less than 0.01) but stabilized; hypoglycemia did not occur. Exercise-associated increments in plasma glucagon were comparable in the two studies. These data confirm that decrements in insulin are not critical to the prevention of hypoglycemia during moderate exercise in humans and indicate that compensation for deficient catecholamine action does not require decrements in insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of exercise and lack of exercise on insulin sensitivity and responsiveness.

Insulin action is enhanced in people who exercise regularly and vigorously. In the present study, the hyperinsulinemic, euglycemic clamp procedure was used to determine whether this enhanced insulin action is due to an increased sensitivity and/or an increased responsiveness to insulin. To avoid the variability that exists between individuals and complicates cross-sectional studies, the same subjects were studied in the trained exercising state and again after 10 days of physical inactivity. When the plasma insulin concentration was maintained at approximately 78 microU.ml-1 (a submaximal level), glucose disposal rate averaged 8.7 +/- 0.5 mg.kg-1.min-1 before and 6.7 +/- 0.6 mg.kg-1.min-1 after 10 days of activity (P less than 0.001). When the plasma insulin concentration was maintained at approximately 2,000 microU.ml-1 (a maximally effective concentration), the rate of glucose disposal was not significantly different before (15.3 +/- 0.5 mg.kg-1.min-1) compared with after (14.5 +/- 0.4 mg.kg-1.min-1) 10 days without exercise. These results provide evidence that the reversal of enhanced insulin action that occurs within a few days when exercise-trained individuals stop exercising is due to a decrease in sensitivity to insulin, not to a decrease in insulin responsiveness.