Effects of slow- v. fast-digested protein supplementation combined with mixed power training on muscle function and functional capacities in older men.

Ageing leads to a progressive loss of muscle function (MF) and quality (MQ: muscle strength (MS)/lean muscle mass (LM)). Power training and protein (PROT) supplementation have been proposed as efficient interventions to improve MF and MQ. Discrepancies between results appear to be mainly related to the type and/or dose of proteins used. The present study aimed at determining whether or not mixed power training (MPT) combined with fast-digested PROT (F-PROT) leads to greater improvements in MF and MQ in elderly men than MPT combined with slow-digested PROT (S-PROT) or MPT alone. Sixty elderly men (age 69 (sd 7) years; BMI 18-30 kg/m2) were randomised into three groups: (1) placebo + MPT (PLA; n 19); (2) F-PROT + MPT (n 21) and (3) S-PROT + MPT (n 20) completed the intervention. LM, handgrip and knee extensor MS and MQ, functional capacity, serum metabolic markers, skeletal muscle characteristics, dietary intake and total energy expenditure were measured. The interventions consisted in 12 weeks of MPT (3 times/week; 1 h/session) combined with a supplement (30 g:10 g per meal) of F-PROT (whey) or S-PROT (casein) or a placebo. No difference was observed among groups for age, BMI, number of steps and dietary intake pre- and post-intervention. All groups improved significantly their LM, lower limb MS/MQ, functional capacity, muscle characteristics and serum parameters following the MPT. Importantly, no difference between groups was observed following the MPT. Altogether, adding 30 g PROT/d to MPT, regardless of the type, does not provide additional benefits to MPT alone in older men ingesting an adequate (i.e. above RDA) amount of protein per d.

Muscle adaptation in response to a high-intensity interval training in obese older adults: effect of daily protein intake distribution.

BACKGROUND: Aging is associated with declines in muscle mass, strength and quality, leading to physical impairments. An even protein distribution in daily meals has recently been proposed along with adequate total protein intake as important modulators of muscle mass. In addition, due to its short duration, high-intensity interval training (HIIT) has been highlighted as a promising intervention to prevent physical deterioration. However, the interaction between daily protein intake distribution and HIIT intervention in elderlies remain unknown. OBJECTIVE: To investigate muscle adaptation following HIIT in older adults according to daily protein intake distribution. METHODS: Thirty sedentary obese subjects who completed a 12-week elliptical HIIT program were matched [criteria: age (± 2 years), sex, BMI (± 2 kg/m2)] and divided a posteriori into 2 groups according to the amount of protein ingested at each meal: < 20 g in at least one meal (P20-, n = 15, 66.8 ± 3.7 years) and ≥ 20 g in each meal (P20+, n = 15, 68.1 ± 4.1 years). Body composition, functional capacity, muscle strength, muscle power, physical activity level, and nutritional intakes were measured pre- and post-intervention. A two way repeated ANOVA was used to determine the effect of the intervention (HIIT) and protein distribution (P20- vs P20+, p < 0.05). RESULTS: No difference was observed at baseline between groups. Following the HIIT intervention, we observed a significant decrease in waist and hip circumferences and improvements in functional capacities in both P20- and P20 + group (p < 0.05). However, no protein distribution effect was observed. CONCLUSION: A 12-week HIIT program is achievable and efficient to improve functional capacities as well as body composition in obese older adults. However, consuming at least 20 g of proteins in every meal does not further enhance muscle performance in response to a 12-week HIIT intervention.

[The Confusion Assessment Method: Transcultural adaptation of a French version]. / Adaptation transculturelle francophone de la Confusion Assessment Method.

INTRODUCTION: The Confusion Assessment Method (CAM) is a validated key tool in clinical practice and research programs to diagnose delirium and assess its severity. There is no validated French version of the CAM training manual and coding guide (Inouye SK). The aim of this study was to establish a consensual French version of the CAM and its manual. METHODS: Cross-cultural adaptation to achieve equivalence between the original version and a French adapted version of the CAM manual. RESULTS: A rigorous process was conducted including control of cultural adequacy of the tool's components, double forward and back translations, reconciliation, expert committee review (including bilingual translators with different nationalities, a linguist, highly qualified clinicians, methodologists) and pretesting. A consensual French version of the CAM was achieved. CONCLUSION: Implementation of the CAM French version in daily clinical practice will enable optimal diagnosis of delirium diagnosis and enhance communication between health professionals in French speaking countries. Validity and psychometric properties are being tested in a French multicenter cohort, opening up new perspectives for improved quality of care and research programs in French speaking countries.

Handgrip strength predicts survival and is associated with markers of clinical and functional outcomes in advanced cancer patients.

PURPOSE: Handgrip strength (HGS) has been shown to predict survival and is associated with changes in body composition, nutritional status, inflammation, and functional ability in several chronic disease conditions. Whether similar relationships exist between HGS and clinical outcomes in patients with advanced cancer are currently unknown. We evaluated the association between HGS and survival as well as several key markers of body composition (e.g., sarcopenia), subjective performance measures (e.g., quality of life), and muscle strength (e.g., isokinetic torque of the quadriceps) in patients with advanced forms of non-small cell lung and gastrointestinal cancers. METHODS: A consecutive cohort of 203 patients with advanced cancer was enrolled and categorized into three HGS percentiles (e.g., ≥50th, 25th, and ≤10th) according to published normative values. Multivariate regression analyses were used to test for independent associations between HGS and survival, sarcopenia, quality of life (QoL), and lower extremity muscle strength as well as key biological markers (e.g., hemoglobin, albumin, and C-reactive protein) while controlling for age, gender, cancer diagnosis, treatment (chemotherapy/radiotherapy), medications, and time from diagnosis to assessment. RESULTS: When compared to HGS ≥50th, patients in the HGS ≤10th percentile had lower BMI (B, -2.5 kg/m(2); 95% CI, -4.5 to -0.45), shorter survival (hazard ratio, 3.2; 2.0-5.1), lower hemoglobin (-19.70 g/L; -27.28 to -12.13) and albumin (-4.99 g/L; -7.85 to -2.13), greater occurrence of sarcopenia (odds ratio, 9.53; 1.95-46.55), lower isokinetic torque of the quadriceps at both 60°/s (-30.6 Nm; -57.9 to -3.3) and 120°/s (-25.1 Nm; -46.4 to -3.7), lower QoL (-1.6 on McGill Quality of Life Questionnaire scale; -2.5 to -0.6), higher levels of fatigue (18.8 on Brief Fatigue Inventory scale; 4.7 -32.9), poorer performance status (0.75 on Eastern Cooperative Oncology Group Performance Status scale; 0.34-1.15), lower fat mass (-7.4 kg; -14.4 to -0.5), and lower lean body mass (-6.5 kg; -10.3 to -2.8). CONCLUSIONS: HGS is independently associated with survival and important biological, functional, and quality of life characteristics in advanced cancer patients. Patients presenting with very low percentiles with respect to their handgrip assessment may require timely referral to supportive and/or palliative care services.

Postprandial hyperaminoacidaemia overcomes insulin resistance of protein anabolism in men with type 2 diabetes.

AIMS/HYPOTHESIS: Although protein is usually ignored when considering insulin resistance, we have shown resistance of protein concurrent with glucose metabolism in men with type 2 diabetes during a hyperinsulinaemic clamp at euglycaemia and fasting aminoacidaemia. We hypothesised that this resistance is even worse during conditions that simulate the postprandial state, when anabolism should be maximal. METHODS: Eight overweight and obese men with type 2 diabetes underwent a hyperinsulinaemic-hyperglycaemic (8 mmol/l) clamp, first with plasma amino acids at postabsorptive (Hyper-2) then at postprandial concentrations (Hyper-3). Whole-body protein kinetics were assessed using L-: [1-(13)C]leucine. Hyper-2 results were compared with those of diabetic men whose plasma glucose was lowered to 5.5 mmol/l and fasting aminoacidaemia maintained during the hyperinsulinaemic clamp (Hyper-1). RESULTS: In Hyper-2 vs Hyper-1 clamps, leucine flux (2.99 ± 0.16 vs 2.62 ± 0.06 µmol kg [fat-free mass (FFM)](-1) min(-1)), rates of synthesis (2.31 ± 0.15 vs 1.98 ± 0.06) and breakdown (2.38 ± 0.16 vs 2.00 ± 0.07) were higher (p < 0.05), but leucine oxidation and net balance did not differ. In Hyper-3 vs Hyper-2 clamps, leucine flux and synthesis and oxidation rates increased markedly as did net balance (0.84 ± 0.09 vs -0.07 ± 0.04 µmol [kg FFM](-1) min(-1), p < 0.0001). CONCLUSIONS/INTERPRETATION: In type 2 diabetic men, insulin resistance of protein metabolism is of the same magnitude at 8 vs 5.5 mmol/l, but turnover rates are higher with hyperglycaemia. Contrary to our hypothesis, sustained postprandial-level hyperaminoacidaemia stimulated positive net protein balance comparable with that previously found in lean non-diabetic men. This was sufficient to overcome the insulin resistance of protein anabolism.

Hyperaminoacidaemia at postprandial levels does not modulate glucose metabolism in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Hyperaminoacidaemia attenuates glucose disposal during hyperinsulinaemic clamps in healthy lean individuals, an effect thought to be mediated by negative feedback on insulin signalling, downstream of the mammalian target of rapamycin (mTOR) signalling pathway. This has been interpreted as amino acids causing insulin resistance in healthy people, and contributing to it in type 2 diabetes. However, the effect of hyperaminoacidaemia on glucose disposal in type 2 diabetic individuals remains to be determined. METHODS: Eight obese men with type 2 diabetes underwent a two-step hyperinsulinaemic-hyperglycaemic (8 mmol/l) clamp, first with amino acids at postabsorptive concentrations, followed by postprandial concentrations. Whole-body glucose turnover was assessed using D: -[3-(3)H]glucose. Vastus lateralis biopsies were obtained at baseline and during each step of the clamp to determine the phosphorylation states of AKT, mTOR, ribosomal protein (rp) S6, and insulin receptor substrate (IRS)-1. RESULTS: Rates of glucose infusion (1.30 ± 0.19 vs 1.15 ± 0.13 mmol/min), endogenous glucose production (0.48 ± 0.06 vs 0.53 ± 0.05 mmol/min) and disposal (1.24 ± 0.17 vs 1.17 ± 0.14 mmol/min) did not differ between postabsorptive and postprandial amino acid concentrations (p > 0.05). Whereas phosphorylation of AKT(Ser473), AKT(Thr308) mTOR(Ser2448) and rpS6(Ser235/236) increased (p < 0.05) with elevated amino acids, that of IRS-1(Ser636/639) and IRS-1(Ser1101) did not change. CONCLUSIONS/INTERPRETATION: Postprandial circulating amino acid concentrations do not worsen the already attenuated glucose disposal in hyperglycaemic type 2 diabetic men, and cell-signalling events are consistent with this. Our results do not support recommendations to restrict dietary protein in type 2 diabetes.

Antihyperglycaemic medication modifies factors of postprandial satiety in type 2 diabetes.

AIM: Type 2 diabetes is characterized by hyperglycaemia, delayed gastric emptying and a blunted response of gut hormones during feeding that may modulate satiety. We hypothesized that it is associated with more hunger when treated by medication. METHODS: We studied nine type 2 diabetic men (A1C: 6.7+/-0.3%, waist circumference: 104+/-4 cm) after an overnight fast, during 5 h in response to a 2.88 MJ breakfast, twice, in a crossover design, with or without antihyperglycaemic agents. Satiety ratings, thermic effect of meal, gastric emptying, plasma concentrations of gut peptides, leptin, insulin and substrates and intake from a subsequent buffet were determined. RESULTS: With medication, fasting and postprandial plasma glucose levels were lower but area under the curve (AUC) did not vary vs. without medication. Gastric emptying was shortened, branched chain amino acids (BCAA) AUC and thermic effect were lower, and postprandial glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY3-36) were maintained at higher levels beyond 4 h. Correlations were significant between duration of diabetes and fasting ghrelin (r=0.779, p=0.013) and peak insulin (r=-0.769, p=0.016), 5-h postmeal ghrelin and peak glucose (r=0.822, p=0.007), 5-h glucose and GLP-1 (r=-0.788, p=0.012), and 5-h hunger scores and energy intake at buffet (r=0.828, p=0.006). Without medication, fullness scores correlated with BCAA levels. Visual analogue scale scores, ghrelin and leptin levels did not differ between studies. CONCLUSIONS: The decrease in factors associated with postprandial satiety with treatment is counterbalanced by higher GLP-1 and PYY3-36. Medication may normalize the link between perception of hunger and subsequent food intake.

Putting the best foot forward: Relationships between indicators of step quality and cadence in three gait vulnerable populations.

BACKGROUND: Aging and neurological conditions like Multiple Sclerosis (MS) and Parkinson's disease (PD) make people vulnerable for gait impairments, limit function, and restrict sustained walking needed for health promotion. Walking to meet physical activity guidelines requires adequate cadence which is difficult to achieve for gait vulnerable populations. OBJECTIVE: The objective of this study is to estimate, for seniors and people with MS or PD, the extent to which cadence is associated with heel-to-toe stepping pattern (good steps), angular velocity of ankle at heel-strike and its variability. METHODS: A cross-sectional regression analysis was performed on data collected during walking tests using the Heel2Toe sensor. RESULTS: Health condition (MS = 57, PD = 27, seniors = 56) had an association with cadence, independent of age and sex. Only angular velocity showed a significant relationship with cadence such that every - 50° difference in angular velocity (more negative is better) was associated with a difference of ≈3.5 steps per minute. CONCLUSION: Adequate angular velocity occurs with an optimal heel-to-toe movement. This heel-to-toe gait can easily be targeted during therapy but technology would be an asset to sustain the relearned movement during everyday activities, Technology that provides real-time feedback for steps with adequate angular velocity at heel strike could be a valuable therapeutic adjunct.

Differences in muscle adaptation to a 12-week mixed power training in elderly men, depending on usual protein intake.

INTRODUCTION: Normal aging is often associated with a decline of muscle mass (MM), strength (MS) and quality (MQ: MS/MM), leading to functional incapacities. This aging-related deterioration of muscles may involve a decreased protein intake. Mixed power training has been recently shown to induce positive effects on MM, MS and MQ. However, to our knowledge, no study has examined if muscle adaptations following mixed power training could be influenced by the daily amount of protein ingested in elderly men. METHODS: Twenty-one men completed the intervention and were divided into 2 groups based on their usual protein intake: PROT 1.1- (<1.1 g·kg-1·d-1 [n = 10; 73 ±â€¯3 years]) and PROT 1.2+ (>1.2 g·kg-1·d-1 [n = 11; 73 ±â€¯3 years]). Body composition (DXA: lean and fat masses), MS (1-maximal repetition on leg-press and handgrip strength), MQ (MS/body mass and MS/lower limb lean mass), functional capacities (Short Physical Performance Battery/Senior Fitness Test), dietary intake (3-day food record) and energy expenditure (accelerometer; 7 days) were measured. Mixed power training intervention consisted in power and functional exercises (12 weeks; 3 times/week; 1 h/session). RESULTS: Lower limb MS increase in the PROT 1.2+ group was greater from that of the PROT 1.1- group when normalized to lower limbs lean mass (p = 0.036). In addition, a trend for greater gain in lower limb MS normalized to body mass (p = 0.053) was observed in the PROT 1.2+. CONCLUSION: To optimize mixed power training effects on muscle function, healthy older men should ingest daily at least 1.2 g·kg-1·d-1 of protein. These beneficial effects of a higher usual protein intake were observed especially for MQ, which is one of the best predictors of functional capacities in older adults.

Protein turnover and requirements in the healthy and frail elderly.

There are as yet no definitive data that warrant the establishment of evidence-based dietary protein recommendations for the elderly. We reviewed the relevance of the new 2002 recommended protein intake of 0.80 g/kg body weight.d for adults to healthy and frail elderly persons. We found that data from published nitrogen balance studies indicate that, a higher protein intake of 1.0 - 1.3 g/k.d is required to maintain nitrogen balance in the healthy elderly, which may be explained by their lower energy intake and impaired insulin action during feeding compared with young persons. Although it needs to be confirmed, a decrease in efficiency of protein utilization with aging may also dictate a higher protein-intake recommendation. Measures of the dynamic aspects of protein metabolism done in the postabsorptive state have shown no change in whole body protein turnover per unit of active metabolic tissue with aging. However, the contribution of muscle protein to wholebody protein metabolism was significantly reduced in the elderly, and explained by their reduced muscle mass and lower rates of myofibrillar protein turnover. Consequently, the contribution of nonmuscle protein, especially that of visceral tissue whose rates of protein turnover are known to be more rapid was proportionally greater with aging. It is conceivable that higher protein consumption rates could compensate for the decrease in availability of muscle amino acids and spare the muscle mass. Despite a paucity of data on the frail elderly population, we present a rationale to justify a greater protein intake of at least equivalent to that of their healthy counterparts. We propose that higher protein intakes for the elderly, and especially the frail population, than those presently recommended may minimize the sarcopenia of aging and thereby protect against some of the health risks of aging.

Intakes of folate, vitamin B6 and B12 and risk of depression in community-dwelling older adults: the Quebec Longitudinal Study on Nutrition and Aging.

BACKGROUND/OBJECTIVES: Depression can decrease quality of life and affect health outcomes in older population. We investigated whether different intake levels of folate, vitamin B6 and B12 were associated with a 3-year depression incidence among generally healthy, community-dwelling older men and women. SUBJECTS/METHODS: Participants in the Québec Longitudinal Study on Nutrition and Aging (NuAge), free of depression (that is, 30-item Geriatric Depression Scale (GDS) <11) at baseline (N=1368; 74 ± 4 years old; 50.5% women), were screened annually for incident depression (GDS ⩾ 11) or antidepressant medication. Tertiles of intakes (food only and food+supplements) were obtained from the mean of three non-consecutive 24-h recalls at baseline. Sex-stratified multiple logistic regression models were adjusted for age, physical activity, physical functioning, stressful life events and total energy intake. RESULTS: Over 3 years, 170 participants were identified as depressed. Women in the highest tertile of B6 intake from food were 43% less likely to become depressed when adjusting for demographic and health factors (multivariate odds ratio (OR) 0.57, 95% confidence interval (CI) 0.39-0.96), but adjustment for energy intake attenuated the effect. Men in the highest tertile of dietary B12 intake had decreased risk of depression (energy-adjusted multivariate OR 0.42, 95% CI 0.20-0.90). No other association was observed. CONCLUSIONS: This study provides some evidence of decreased depression risk among women with higher intakes of vitamin B6 from food, which was dependent on total energy intake, and among men with higher intakes of B12 from food, independently of energy intake.

Muscle Mass Index and Animal Source of Dietary Protein Are Positively Associated with Insulin Resistance in Participants of the NuAge Study.

OBJECTIVES: Contribute evidence towards the complex interrelationships of body composition, insulin sensitivity and protein intake independently from adiposity in an older population. DESIGN: This is a cross-sectional analysis of an existing dataset in which a literature-supported model linking together the variables of interest is tested using path analysis. SETTING: The loss of muscle mass has been implicated in the development of insulin resistance. We propose to test associations of muscle mass with insulin sensitivity and their respective associations with animal and vegetable sources of protein intake, independently from adiposity. PARTICIPANTS: Non-diabetic participants aged 68-82 years from the NuAge study with all available measures (n=441) were included. MEASUREMENTS: A model considering age, sex, chronic diseases, physical activity; smoking and sources of protein intake influencing body composition components and insulin sensitivity was created and tested with Path Analysis for their independent associations. Muscle mass index (MMI; kg/height in m2) and % body fat were derived from DXA and BIA. Insulin resistance was estimated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score and physical activity by the Physical Activity Scale for the Elderly (PASE) questionnaire. Protein intakes were obtained from three non-consecutive 24h-diet recalls. RESULTS: In the final model, direct positive associations were observed between HOMA-IR score and MMI (ß=0.42; 95%CI: 0.24; 0.6) and % body fat (ß=0.094; 95%CI: 0.07; 0.11). There were no direct associations between animal protein intake and MMI or with HOMA-IR. There was a significant direct negative association between plant protein intake and MMI (ß= -0.068; 95%CI: -0.13; -0.003) and significant indirect associations mediated through MMI and % body fat between HOMA-IR and animal protein intake (ß=0.0321; 95%CI: 0.01; 0.05), as well as plant protein intake (ß= -0.07; 95%CI: -0.1; 0.0). CONCLUSIONS: Our final model indicated that MMI and HOMA score were significantly positively associated. Protein intake sources were related to HOMA-IR score differently through MMI and % body fat, respectively.

Developments in the rat adjuvant arthritis model and its use in therapeutic evaluation of novel non-invasive treatment by SOD in Transfersomes.

The aim of this study was firstly to refine a rat model of arthritis, the adjuvant arthritis (AA) model, by studying the time course of the disease, introducing new evaluation methods such as haematological and biochemical parameters in order to identify the main stages of the disease. An optimisation of treatment schedule and evaluation criteria was developed. This refinement provided novel non-invasive anti-inflammatory treatment of the AA with SOD by using mixed lipid vesicles specially developed for transdermal delivery, Transfersomes (Tfs), this being the second major aim. The time course of AA includes a first stage: 1 day after the disease induction, the induced paw volume more than doubled and the paw circumference increased by approx. 50%. Two weeks later, another stage occurred where the disease shifted from the local arthritis form towards polyarthritis: an additional increase of volume and circumference of the induced and non-induced paws, occurred. The animals also started to loose weight around day 14 after the disease induction. Radiographic observable lesions increased correspondingly. Treatment of animals, started at day 1 after induction, by epicutaneous application of SOD-Tfs showed that 1 mg SOD/kg body weight is more efficient than 0.66 mg SOD /kg body weight. As a positive control, SOD liposomes intravenously injected were used for comparison and confirmed the biological efficiency of epicutaneously applied SOD in Tfs. SOD solution and empty Tfs epicutaneously applied exerted no effect. In addition, epicutaneous application of SOD-Tfs used prophylactically was able to suppress the induced rat paw oedema. Radiographic images showed less joint lesions in SOD-Tfs treated animals in comparison with control and placebo treated rats. It was shown for the first time that SOD incorporated into Tfs and applied onto a skin area not necessarily close to the inflamed tissue is able to promote non-invasive treatment of induced arthritis.

Effects of oral hypoglycemic agents and diet on protein metabolism in type 2 diabetes.

OBJECTIVE: We tested whether oral hypoglycemic agents (OHA), gliclazide with or without metformin, during an isoenergetic (ISO) and then a low-energy diet (LED) improve the altered kinetics of whole-body protein metabolism in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 13 type 2 diabetic patients (aged 51+/-2 years, weight 110+/-5 kg, BMI 41+/-1 kg/m2, fasting glucose [FSG] 11.5+/-0.9 mmol/l) (means+/-SEM) and 10 obese control subjects (48+/-3 years, 98+/-6 kg, 37+/-2 kg/m2, FSG 5.5+/-0.3 mmol/l) consumed an ISO, 1.5 g x kg(-1) x day(-1) protein for a body weight corresponding to a BMI of 25 (BMI25), a formula diet (7 days for obese control subjects, 15 days for diabetic patients), and then a 28-day LED with 50% of the energy of ISO but the same protein intake (101+/-2 g/day). OHAs were given during ISO (days 8-15) and LED. On days 6-8 (and 12-14 for diabetic subjects) of ISO and 26-28 of LED, the 60-h oral 15N-glycine method was used to obtain nitrogen flux (Q), synthesis (S), and breakdown (B). Muscle protein catabolism was estimated from N(tau)-methylhistidine (3MH) excretion. RESULTS: During ISO with hyperglycemia, Q, and B adjusted for fat-free mass, sex, and age were higher and nitrogen balance and net endogenous protein synthesis (S-B) lower than in control subjects (P<0.05). OHA decreased FSG (9+/-1 mmol/l) and 3MH and increased plasma insulin-to-glucose ratio, nitrogen retention, and S-B to levels in control subjects. The change in S-B correlated with that in FSG (r = -0.845, P = 0.001) and in fasting plasma C-peptide (r = 0.852, P = 0.0005). With LED and OHA, weight decreased 6.3 kg, glycemia reached near-normal levels, and nitrogen equilibrium was maintained; Q decreased by 7%, S and B by 11% (P<0.05) to values found in control subjects. CONCLUSIONS: OHA during ISO corrected protein turnover in relation to glycemia and plasma C-peptide. The LED maintained protein homeostasis in obese control subjects and, in diabetes patients with OHA, normalized protein metabolism. These findings have implications for diet and OHA prescription.

Effect of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women.

BACKGROUND: Plasma leptin in humans is subject to both long- and short-term regulation; it correlates with indexes of body fat that can only change slowly. However, short-term fasting causes large and rapid decreases. OBJECTIVE: We tested the interactions between energy intake and fat loss on plasma leptin during prolonged moderate and severe energy restriction, with a view to understanding mechanisms of control. DESIGN: Postabsorptive leptin was measured with an enzyme-linked immunosorbent assay specific for the human peptide in 21 obese women aged 41 +/- 3 y (weight: 102 +/- 4 kg; 48 +/- 1% body fat) after 1 wk of a weight-maintaining diet and then weekly for 4 wk during a total fast (group 1); a 1.9-MJ/d all-protein, very-low-energy diet (VLED) (group 2); or a low-energy, balanced-deficit diet (BDD) providing 50% of maintenance energy (group 3). In groups 1 and 2, leptin was also measured after 1 wk of refeeding with a diet equivalent to the BDD. RESULTS: Mean leptin decreased markedly by up to 66% (P < 0.001) at week 1 of energy restriction and then gradually thereafter. The change in leptin per kilogram fat mass correlated with that in glucose concentrations [r = 0.538 (P = 0.012) at week 1 and r = 0.447 (P = 0.042) at week 4] but not with that in fat mass. During refeeding postfasting, leptin increased (P = 0.008), despite an ongoing loss of fat mass and correlated positively with changes in resting energy expenditure. At times with comparable cumulative energy restriction and fat loss between diets, the percentage change in leptin paralleled that in glucose. CONCLUSIONS: In obesity, changes in energy intake over days to weeks are a primary modulator of plasma leptin concentrations that are related to the change in glycemia and are able to override the regulatory influence of fat mass.

Whole-body protein turnover in the healthy elderly.

We tested the hypothesis that aging affects whole-body protein turnover via altered fat-free mass (FFM). Whole-body protein kinetics were estimated by the 60-h oral [15N]glycine method. Results from 16 healthy, elderly subjects (8 men and 8 women with a mean age of 72.6 y) were compared for age and sex effects with those of 15 lean young subjects (8 men and 7 women with a mean age of 28.4 y) during isoenergetic formula diets. Per kilogram body weight, nitrogen flux was lower only as an effect of age (P = 0.006) whereas age and female sex significantly lowered synthesis and breakdown (P < or = 0.04). However, per kilogram FFM, no significant age or sex effects on rates of protein kinetics remained. Age and female sex contributed significantly to decreased muscle protein catabolism (based on 3-methylhistidine excretion), both in absolute terms and as a percentage of whole-body protein breakdown in the elderly compared with the young: 20.2% compared with 30.9% in women and 27.9% compared with 39.8% in men. No significant age or sex effects on rates of nonmuscle lean tissue protein breakdown were observed with or without correction for body composition. We conclude that the lower rates of flux, synthesis, and breakdown per kilogram body weight in elderly compared with young persons are due to changes in body composition with aging because rates are not different per kilogram FFM. However, there is a reduced contribution by muscle to whole-body protein catabolism in older persons. This has potential implications for the nutrition of both normal and sick elderly persons.

Glucoregulation during and after intense exercise: effects of alpha-adrenergic blockade.

In intense exercise (>80% maximal oxygen consumption [VO2 max]), the 7- to 8-fold increase in glucose production (Ra) is tightly correlated with the greater than 14-fold increase in plasma norepinephrine (NE) and epinephrine (EPI). To distinguish the relative roles of alpha- and beta-adrenergic receptors, the responses of 12 control (C) lean, healthy, fit young male subjects to 87% VO2 max cycle ergometer exercise were compared with those of 7 subjects (at 83% VO2max) receiving intravenous phentolamine (Ph). The Ph group received a 70-microg/kg bolus and then 7 microg/kg/min from -30 minutes, during exercise and for 60 minutes of recovery. The data were analyzed by comparing exercise responses to exhaustion in Ph subjects (11.4 +/- 0.6 min) with those at both 12 minutes and at exhaustion in C subjects (14.6 +/- 0.3 min) and during recovery. There were no significant differences between groups in the plasma glucose response during exercise, but values were higher in C versus Ph subjects during the first 40 minutes of postexercise "recovery." The Ra response during the first 12 minutes of exercise was not different by repeated-measures ANOVA, reaching 10.6 +/- 1.3 mg/kg/min in C and 9.6 +/- 1.5 in Ph subjects at 12 minutes. However, in C subjects, Ra increased significantly to 14.1 +/- 1.2 mg/kg/min by exhaustion, and remained higher versus Ph subjects until 15 minutes of recovery. The Rd during recovery was not different between groups; thus, the higher Ra in C subjects in early recovery was responsible for the greater hyperglycemia observed in C subjects. Ph subjects showed a more rapid, marked increment (P = .002) in both plasma NE (to 64 v38 nmol/L) and EPI at exhaustion, and catecholamine concentrations remained higher in Ph versus C subjects during recovery. Whereas plasma insulin (IRI) declined in the C group, it increased 3-fold (P = .001) in the Ph group during exercise and until 15 minutes of recovery. Ph had no effect on glucagon (IRG). Thus, the glucagon to insulin ratio decreased in Ph subjects from baseline levels during exercise and early recovery, but increased in C subjects. The increase in Ra among Ph subjects despite the decrease in the glucagon to insulin ratio supports our earlier evidence that these hormones are not principal regulators of the Ra in intense exercise. The shorter time to exhaustion and markedly higher catecholamine levels in Ph subjects limited our ability to isolate the effects of alpha-adrenergic receptors on the Ra.alpha-Adrenergic receptors appear to have little influence on the Rd.

Glucose infusion partially attenuates glucose production and increases uptake during intense exercise.

Glucose infusion can prevent the increase in glucose production (Ra) and increase glucose uptake (Rd) during exercise of moderate intensity. We postulated that 1) because in postabsorptive intense exercise (>80% maximal O2 uptake) the eightfold increase in Ra may be mediated by catecholamines rather than by glucagon and insulin, exogenous glucose infusion would not prevent the Ra increment, and 2) such infusion would cause greater Rd. Fit young men were exercised at >85% maximal O2 uptake for 14 min in the postabsorptive state [controls (Con), n = 12] or at minute 210 of a 285-min glucose infusion. In seven subjects, the infusion was constant (CI; 4 mg . kg-1 . min-1), and in seven subjects it was varied (VI) to mimic the exercise Ra response in Con. Although glucose suppressed Ra to zero (with glycemia approximately 6 mM and insulin approximately 150 pM), an endogenous Ra response to exercise occurred, to peak increments two-thirds those in Con, in both CI and VI. Glucagon was unchanged, and very small increases in the glucagon-to-insulin ratio occurred in all three groups. Catecholamine responses were similar in all three groups, and correlation coefficients of Ra with plasma norepinephrine and epinephrine were significant in all. In all CI and VI, Rd at rest was 2x Con, increased earlier in exercise, and was higher for the 1 h of recovery with glucose infusion. Thus the Ra response was only partly attenuated, and the catecholamines are likely to be the regulators. This suggests that an acute endogenous Ra rise is possible even in the postprandial state. Furthermore, the fact that more circulating glucose is used by muscle during exercise and early recovery suggests that muscle glycogen is spared.

The effects of mandibular two-implant overdentures on nutrition in elderly edentulous individuals.

It is unclear whether mandibular implant overdentures improve the nutritional state of edentulous patients better than conventional dentures. In a randomized clinical trial, we tested for post-treatment differences in nutritional status between patients with mandibular two-implant retained overdentures and those with conventional complete dentures. Edentulous subjects (ages 65-75 yrs) received two-implant mandibular overdentures (IOD, n = 30) or conventional dentures (CD, n = 30). Measures of nutritional state were gathered before and 6 mos after treatment. Significant improvements in anthropometric parameters were detected in the IOD but not in the CD group, for percent body fat (p = 0.011) and skin-fold thickness at the biceps, subscapularis, and abdomen (p < 0.05), with significant decreases in waist circumference (p < 0.0001) and waist-hip ratio (p = 0.001). Significant increases were seen in concentrations of serum albumin (p = 0.015), hemoglobin (p = 0.01), and B12 (p = 0.01). No significant between-group differences were found. These results suggest that low-cost IOD treatment may improve the nutritional state of edentulous people.

Muscle strength and functional mobility in relation to lean body mass in free-living frail elderly women.

OBJECTIVES: (1) To describe body composition of the frail elderly, (2) To relate lean body mass to muscle strength and functional ability, and (3) To assess temporal stability of strength measures and index of functional ability. DESIGN: Cross-sectional study. SETTING: Community-dwelling. SUBJECTS: Thirty frail elderly women (81.5 +/- 7 y) recruited from residences or out-patient facilities. METHODS: Total body fat and fat-free mass (FFM) were determined using multi-frequency bioelectrical impedance analysis and predicted from anthropometry. Handgrip strength, biceps and quadriceps strength, functional capacities (Timed 'Up & Go') as well as self-perceived health and functional status were measured. Reliability was assessed using two separate observations made one week apart by the same examiner. RESULTS: Mean height, weight and body mass index were 1.52 +/- 0.04 m, 60.4 +/- 10.7 kg and 26.0 +/- 4.8 kg/m2 respectively. FFM (34.1 +/- 4.6 kg) was lower than previous reports for autonomous elderly females and associated with all measures of muscle strength (Pearson's r = 0.42-0.62, P < or = 0.02), but not with performance on the Timed 'Up & Go' or self-perceived health and functional status. Strength measures correlated significantly with different subscales of self-perceived functional capacities and were significantly lower among women with a low %FFM (n = 19) and those reporting pain (n = 11) as compared to other women. Excellent temporal stability for muscle and functional measures was observed (ICC = 0.80-0.90). CONCLUSIONS: Muscle strength was strongly related to FFM in free-living frail elderly women especially in the absence of pain.