The precariousness of living with, and caring for people with, dementia: Insights from the IDEAL programme.

This paper uses precarity as a framework to understand the vulnerabilities experienced by those living with or caring for someone living with dementia. Drawing on qualitative interview data from the Improving the Experience of Dementia and Enhancing Active Life (IDEAL) programme, we attend to our participants' reflections on how they manage the condition and the wider circumstances in which this occurs. To interrogate the utility of precarity, we focus on our participants' descriptions of needs and challenges and set these alongside both the wider contexts in which they seek or offer care (formal and informal) and the sets of values attributed to different ways of living with dementia. Building on the work of Portacolone, our analysis identified four interconnected themes: uncertainty; experiences of support and services; independence and personhood; and cumulative pressures and concerns. We develop this analysis by reviewing how our themes reflect, extend, or depart from previously identified markers of precarity and consider the specific ways in which these markers shape the lives of those living with dementia.

Endocrine profiles in 693 elite athletes in the postcompetition setting.

OBJECTIVE: To measure a profile of hormones in a group of elite athletes. Increasing awareness of the widespread use of hormones as performance-enhancing agents focusses attention on what may be considered as normal in this unusual group. DESIGN: Blood samples were obtained from 813 volunteer elite athletes from a cross-section of 15 sporting categories. An endocrine profile was measured on a subset of 693. PARTICIPANTS: Volunteer elite athletes. Samples were drawn within two hours of an event at a major national or international competition. MEASUREMENTS: Demographics and hormone profiles were obtained on 454 male and 239 female elite athletes. RESULTS: Hormone profiles showed significant differences in 19 of the 24 measured variables between sexes and between all of the 15 sporting disciplines in men and 11 out of 24 in women. 16.5% of men had low testosterone levels, whereas 13.7% of women had high levels with complete overlap between the sexes. Women had a lean body mass 85% that of men - sufficient to account for sex differences in performance. There were highly significant correlations between many of the measured hormones. CONCLUSIONS: Hormone profiles from elite athletes differ from usual reference ranges. Individual results are dependent on a number of factors including age, gender and physique. Differences in profiles between sports suggest that an individual's profile may contribute to his/her proficiency in a particular sport. The IOC definition of a woman as one who has a 'normal' testosterone level is untenable.

Understanding exercise uptake and adherence for people with chronic conditions: a new model demonstrating the importance of exercise identity, benefits of attending and support.

Understanding the factors influencing uptake and adherence to exercise for people with chronic conditions from different ages, genders and ethnicities is important for planning exercise services. This paper presents evidence supporting a new model of exercise uptake and adherence applicable to people with chronic conditions from diverse socio-demographic backgrounds. The study is based on 130 semi-structured interviews with people with chronic conditions, including both those who did and those who did not attend exercise services, and supporters of those who attended. Analysis followed the guidelines of 'framework analysis'. Results show that three factors were particularly important in influencing adherence behavior: (i) exercise identity, (ii) support and (iii) perceived benefits of attending. Social and cultural identities impacted on willingness to exercise, importance of exercise and perceived appropriateness of exercising. Having at least one supporter providing different types of support was associated with high levels of attendance. Those people who valued the social and psychological benefits of attending were more likely to be high attenders. The new model illustrates interaction between these three factors and discusses how these can be taken into account when planning exercise services for people with chronic conditions drawn from diverse socio-demographic groups.

Elevation of anions in exercise-induced acidosis: a study by ion-exchange chromatography/mass spectrometry.

Acidosis is a major factor that determines the upper limit of exercise endurance. We have previously shown that anions usually associated with intermediary metabolism are elevated in critically ill patients with metabolic acidosis and contribute significantly to acidosis generation. This study was to determine whether volunteers with normal metabolism would exhibit similar elevations in anions associated with intermediate metabolism when exposed to a short-term physiological stress leading to a brief lactic acidosis. Physiological stress was induced on five healthy male subjects by means of a ramped exercise protocol. Blood was obtained immediately prior to and post-exercise, plasma ultrafiltrate was prepared and analysed immediately both by enzyme assay and liquid chromatography coupled to electrospray-mass spectrometry (LC/ESI-MS). Metabolic acidosis concomitant with a significant increase in blood lactate occurred in each subject, but in addition, anions normally associated with intermediate metabolism were significantly elevated after exercise. The contribution of these anions to generating an acidosis, and thus potentially limiting the extent of exercise, has never been acknowledged.

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism.

AIMS/HYPOTHESIS: It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables. SUBJECTS AND METHODS: We randomised 17 sedentary overweight male subjects (age 50 +/- 2.6 years, BMI 27.6 +/- 0.5 kg/m(2)) to a 6-week exercise programme (n = 10) or control group (n = 7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic-euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg(-1) min(-1)]. In the exercise group subjects were studied >72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning. RESULTS: After 6 weeks, fasting glycerol, palmitic acid Ra (p = 0.003, p = 0.042) and NEFA concentration (p = 0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p = 0.026; p = 0.007 and p = 0.04). There was no change in muscle triacylglycerol and liver fat in either group. CONCLUSIONS/INTERPRETATION: Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise.

Effects of high-dose growth hormone on glucose and glycerol metabolism at rest and during exercise in endurance-trained athletes.

CONTEXT: Recombinant human-GH (r-hGH), in supraphysiological doses, is self-administered by athletes in the belief that it is performance enhancing. OBJECTIVE: The objective of this study was to determine whether r-hGH alters whole-body glucose and glycerol metabolism in endurance-trained athletes at rest and during and after exercise. DESIGN: This was a 4-wk double-blind placebo-controlled trial. SETTING: This study was conducted at St. Thomas Hospital (London, UK). PARTICIPANTS: Twelve endurance-trained male athletes were recruited and randomized to r-hGH (0.2 U/kg.d) (n = 6) or identical placebo (n = 6) for 4 wk. One (placebo group) withdrew after randomization. INTERVENTION: Intervention was conducted by randomization to r-hGH (0.2 U/kg x d) or identical placebo for 4 wk. MAIN OUTCOME MEASURES: Whole-body rates of appearance (Ra) of glucose and glycerol (an index of lipolysis) and rate of disappearance of glucose were measured using infusions of d-[6-6-2H2]glucose and 2H5-glycerol. RESULTS: Plasma levels of glycerol and free fatty acids and glycerol Ra at rest and during and after exercise increased during r-hGH treatment (P < 0.05 vs. placebo). Glucose Ra and glucose rate of disappearance were greater after exercise during r-hGH treatment (P < 0.05 vs. placebo). Resting energy expenditure and fat oxidation were greater under resting conditions during r-hGH treatment (P < 0.05 vs. placebo). CONCLUSIONS: r-hGH in endurance-trained athletes increased lipolysis and fatty acid availability at rest and during and after exercise. r-hGH increased glucose production and uptake rates after exercise. The relevance of these effects for athletic performance is not known.

Gender differences in growth hormone response to exercise before and after rhGH administration and the effect of rhGH on the hormone profile of fit normal adults.

OBJECTIVES: Exercise is a potent physiological stimulus of GH secretion. We hypothesized that exogenous recombinant human growth hormone (rhGH) administration through an increase in GH and IGF-I levels would blunt the GH response to exercise. The aim of the study was to examine and compare the impact of rhGH on the exercise-induced GH response in healthy normal men and women. DESIGN AND MEASUREMENTS: Sixty-nine subjects (36 men, 33 women) were randomized to receive low-dose rhGH (0.1 U/kg/day), high dose rhGH (0.2 U/kg/day), or placebo. Subjects were matched for age (24 +/- 3.1), and body mass index (BMI). rhGH was given as a single subcutaneous (s.c.) injection for the first 28 days. All subjects exercised to exhaustion (maximal oxygen consumption--VO2max) before rhGH treatment (Test 1), and on day 28 (Test 2). GH was measured before exercise (time 0), immediately after exercise (time 0') and at 15, 30, 60, 90 and 120 min postexercise. Baseline IGF-I levels were measured before exercise on days 0 and 28. RESULTS: Baseline IGF-I levels showed no gender differences (42.3 women vs. 38.8 nmol/l men) but basal GH values were higher in women (9.9 vs. 1.8 mU/l, P < 0.001). The areas under the GH response curve, for Test 1 were similar in men and women. Peak GH values were higher in women than men (37.9 vs. 23.5 mU/l, but this did not quite reach statistical significance (P = 0.055). In men, administration of rhGH resulted in a significant increase in IGF-I levels over the basal state in both the LD and HD groups (P < 0.0001). In women, the increase in lGF-I levels reached significance only in the HD group (P < 0.0001). On day 28, GH secretion in response to exercise was calculated from the areas under the GH response curve correcting for an exogenous rhGH component (delta AUC). In men, the delta AUC, for Test 2 were similar in all three groups. In women, the delta AUC was higher in the placebo group, than in the HD group (P < 0.02). Free T4 levels decreased significantly in men, and free T3 increased in both men and women, in HD group after the rhGH administration. TSH levels were suppressed only in women. No changes in sex hormones were found in men or women in any of the treatment groups. Conclusions In terms of IGF-I, men are more responsive to rhGH treatment than women. In addition, as men, but not women, were able to overcome the negative feedback control of the elevated IGF-I levels, it seems that exercise may be a more robust stimulus to GH release in men compared to women.

High dose growth hormone exerts an anabolic effect at rest and during exercise in endurance-trained athletes.

The anabolic actions of GH in GH-deficient adults and children are well documented. Replacement with GH in such individuals promotes protein synthesis and reduces irreversible loss of protein through oxidation. Although GH is known to be self-administered by athletes, its protein metabolic effects in this context are unknown. This study was designed to determine whether 4 wk of high dose recombinant human GH (r-hGH) administration altered whole body leucine kinetics in endurance-trained athletes at rest and during and after 30 min of exercise at 60% of maximal oxygen uptake. Eleven endurance-trained male athletes were studied, six randomized to receive r-hGH (0.067 mg/kg.d), and five to receive placebo. Whole body leucine turnover was measured at rest and during and after exercise, using a 5-h primed constant infusion of 1-[(13)C]leucine, from which rates of leucine appearance (an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (an index of protein synthesis) were estimated. Under resting conditions, r-hGH administration increased rate of leucine appearance and nonoxidative leucine disposal, and reduced leucine oxidation (P < 0.01). This effect was apparent after 1 wk, and was accentuated after 4 wk, of r-hGH administration (P < 0.05). During and after exercise, GH attenuated the exercise-induced increase in leucine oxidation (P < 0.05). There were no changes observed in placebo-treated subjects compared with the baseline study. We conclude that GH administration to endurance-trained male athletes has a net anabolic effect on whole body protein metabolism at rest and during and after exercise.

Effect of growth hormone (GH) on glycerol and free fatty acid metabolism during exhaustive exercise in GH-deficient adults.

GH is an important regulator of fat metabolism at rest, but it is not known whether it regulates fat metabolism during exercise. To determine whether physiologic concentrations of GH influence fat metabolism during exercise, we randomized 16 GH-deficient adults, receiving long-term (mean duration, 5 yr) GH replacement, to either continue GH (n = 8) or receive identical placebo (n = 8) for a 3-month period. Metabolic studies, at rest, during and following exhaustive exercise were carried out at baseline and at the end of the 3 months. The rate of appearance of glycerol (glycerol Ra, an index of lipolysis) and free fatty acids (FFA, FFA Ra) and the rate of disappearance of FFA (FFA Rd) in the plasma were measured using infusions of (2)H(5)-glycerol and 1-(13)C-palmitic acid. Changes in body composition were assessed using dual-energy x-ray absorptiometry scanning and anthropometric measurements. In the baseline studies, exercise resulted in an increase in plasma glycerol and FFA concentrations, glycerol Ra, FFA Ra, and FFA Rd (P < 0.001). Three months of GH withdrawal resulted in reductions in plasma glycerol and FFA, glycerol Ra, FFA Ra, and FFA Rd at rest (P < 0.05 vs. baseline) and during exercise (P < 0.05 vs. baseline and vs. GH treated). Lean body mass decreased after 3 months of GH withdrawal, but total body fat, trunk fat, waist circumference, and the sum of skinfold thicknesses increased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). Fasting insulin and homeostasis model assessment of insulin resistance decreased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). In summary, GH withdrawal for 3 months resulted in reductions in release of glycerol and FFA into the circulation and uptake of FFA into the tissues during intense exercise. These changes were accompanied by reduced lean body mass and increased total body and trunk fat. Further studies are required to determine whether reduced mobilization of fat during exercise contributes to reduced exercise capacity and increased body fat in GH-deficient adults.

The growth hormone/insulin-like growth factor-I axis hormones and bone markers in elite athletes in response to a maximum exercise test.

The aim of the GH-2000 project is to develop a method for detecting GH doping among athletes. Previous papers in the GH-2000 project have proposed that a forthcoming method to detect GH doping will need specific components from the GH/IGF-I axis and bone markers because these specific variables seem more sensitive to exogenous GH than to exercise. The present study examined the responses of the serum concentrations of these specific variables to a maximum exercise test in elite athletes from selected sports. A total of 117 elite athletes (84 males and 33 females; mean age, 25 yr; range, 18-53 yr) from Denmark, the United Kingdom, Italy, and Sweden participated in the study. The serum concentrations of total GH, GH22 kDa, IGF-I, IGF binding protein (IGFBP)-2, IGFBP-3, acid-labile subunit, procollagen type III (P-III-P), and the bone markers osteocalcin, carboxy-terminal cross-linked telopeptide of type I collagen (ICTP), and carboxy-terminal propeptide of type I procollagen were measured. The maximum exercise test showed, in both genders, a peak concentration of total GH (P < 0.001) and GH22 kDa (P < 0.001) by the time exercise ended compared with baseline, and a subsequent decrease to baseline levels within 30-60 min after exercise. The mean time to peak value for total GH and GH22 kDa was significantly shorter in males than females (P < 0.001). The components of the IGF-I axis showed a similar pattern, with a peak value after exercise compared with baseline for IGF-I (P < 0.001, males and females); IGFBP-3 (P < 0.001, males and females); acid-labile subunit [P < 0.001, males; not significant (NS), females], and IGFBP-2 (P < 0.05, females; NS, males). The serum concentrations of the bone markers ICTP (P < 0.001, males; P < 0.05, females) and P-III-P (P < 0.001, males and females) increased in both genders, with a peak value in the direct post-exercise phase and a subsequent decrease to baseline levels or below within 120 min. The osteocalcin and propeptide of type I procollagen values did not change during the exercise test. Specific reference ranges for each variable in the GH/IGF-I axis and bone markers at specific time points are presented. Most of the variables correlated negatively with age. In summary, the maximum exercise test showed a rather uniform pattern, with peak concentrations of the GH/IGF-I axis hormones and the bone markers ICTP and P-III-P immediately after exercise, followed by a subsequent decrease to baseline levels. The time to peak value for total GH and GH22 kDa was significantly shorter for females compared with males. This paper presents reference ranges for each marker in each gender at specific time points in connection to a maximum exercise test to be used in the development of a test for detection of GH abuse in sports.

Aging and physical fitness are more important than obesity in determining exercise-induced generation of GH.

Exercise is a potent stimulus for GH secretion. Aging and obesity are associated with a diminution of GH secretion. We wanted to determine whether age or fat mass is more important in regulating the GH response to exercise. Four groups of healthy men were studied: seven lean young men [age, <40 yr; body mass index (BMI), <25 kg/m(2)], six overweight young men (age, <40 yr; BMI, >27.5), seven lean older men (age, >60 yr; BMI, <25), and 6 overweight older men (age, 60 yr; BMI, >27.5). The men performed a maximal exercise test. GH secretion was higher in the younger men than in the older men. Peak GH was higher in the older lean men than in the older overweight men. There was no difference between the young groups. Fitness correlated negatively with age and positively with peak GH. In young men, there was no relation between BMI, bioimpedance, or leptin and GH secretion. In contrast, in older men there was an inverse correlation between measures of fat mass and GH secretion. Age and physical fitness are more important than body fat in regulating exercise-induced GH secretion. These findings have important clinical implications if we are to prevent the frailty and morbidity associated with aging.

Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group.

The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications of most markers, in particular procollagen type III and osteocalcin, persist after GH withdrawal, they may be suitable markers for detecting GH abuse.

Responses of the growth hormone (GH) and insulin-like growth factor axis to exercise, GH administration, and GH withdrawal in trained adult males: a potential test for GH abuse in sport.

GH abuse by elite athletes is currently undetectable. To define suitable markers of GH doping, we assessed the effects of acute exercise, GH administration, and GH withdrawal on the GH/insulin-like growth factor (IGF) axis in athletic adult males. Acute endurance-type exercise increased serum GH, GH-binding protein (GHBP), total IGF-I, IGF-binding protein (IGFBP)-3, and acid-labile subunit (ALS), each peaking at the end of exercise. IGFBP-1 increased after exercise was completed. Free IGF-I did not change with exercise. Recombinant human GH treatment (0.15 IU/kg x day) for 1 week increased serum total IGF-I, IGFBP-3, and ALS, exaggerating the responses to exercise. IGFBP-2 and IGFBP-1 were trivially suppressed. After GH withdrawal, the GH response to identical exercise was suppressed. Total IGF-I, IGFBP-3, and ALS returned to baseline over 3-4 days. In summary, 1) acute exercise transiently increased all components of the IGF-I ternary complex, possibly due to mobilization of preformed intact complexes; 2) GH pretreatment augmented the exercise-induced changes in ternary complexes; 3) postexercise IGFBP-1 increments may protect against delayed onset hypoglycemia; 4) serum total IGF-I, IGFBP-3, and ALS may be suitable markers of GH abuse; and 5) differences in disappearance times altered the sensitivity of each marker for detecting GH abuse.