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1.  The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness 
European Heart Journal  2012;34(5):389-397.
Current knowledge on the prognosis of metabolically healthy but obese phenotype is limited due to the exclusive use of the body mass index to define obesity and the lack of information on cardiorespiratory fitness. We aimed to test the following hypotheses: (i) metabolically healthy but obese individuals have a higher fitness level than their metabolically abnormal and obese peers; (ii) after accounting for fitness, metabolically healthy but obese phenotype is a benign condition, in terms of cardiovascular disease and mortality.
Methods and results
Fitness was assessed by a maximal exercise test on a treadmill and body fat per cent (BF%) by hydrostatic weighing or skinfolds (obesity = BF% ≥25 or ≥30%, men or women, respectively) in 43 265 adults (24.3% women). Metabolically healthy was considered if meeting 0 or 1 of the criteria for metabolic syndrome. Metabolically healthy but obese participants (46% of the obese subsample) had a better fitness than metabolically abnormal obese participants (P < 0.001). When adjusting for fitness and other confounders, metabolically healthy but obese individuals had lower risk (30–50%, estimated by hazard ratios) of all-cause mortality, non-fatal and fatal cardiovascular disease, and cancer mortality than their metabolically unhealthy obese peers; while no significant differences were observed between metabolically healthy but obese and metabolically healthy normal-fat participants.
(i) Higher fitness should be considered a characteristic of metabolically healthy but obese phenotype. (ii) Once fitness is accounted for, the metabolically healthy but obese phenotype is a benign condition, with a better prognosis for mortality and morbidity than metabolically abnormal obese individuals.
PMCID: PMC3561613  PMID: 22947612
Cardiovascular diseases; Heart diseases; Metabolic syndrome; Mortality; Obesity; Physical fitness
2.  The Influence of Sex, Stroke and Distance on the Lactate Characteristics in High Performance Swimming 
PLoS ONE  2013;8(10):e77185.
In order to achieve world-class performances, regular performance diagnostics is required as an essential prerequisite for guiding high performance sport. In high performance swimming, the lactate performance diagnostic is an important instrument in testing the sport specific endurance capacity. Although the role of lactate as a signaling molecule, fuel and a gluconeogenic substrate is accepted, lactate parameters are discussed concerning stability, explanatory power and interpretability.
We calculated the individual anaerobic threshold (IAT) of Bunc using the swimming-specific lactate threshold test by Pansold.
The cross-sectional analysis (ANOVA) of n = 398 high performance swimmers showed significant effects for sex, stroke and distance on the IAT, the percentage of personal best time on the IAT (% of PB on IAT) and maximal lactate values (max. bLA). For the freestyle events the IAT decreased, % of PB on IAT and max. bLA increased from 100 to 400 m significantly in men and women. Women showed significantly higher % of PB on IAT with descriptive lower IAT in 7 of 8 analyzed events. Men showed significantly higher max. bLA in 5 of 8 events. In the second step, the analysis of 1902 data sets of these 398 athletes with a multi-level analysis (MLA) showed also significant effects for sex, swimming distance and stroke. For initial status and development over time, the effect sizes for the variables distance and sex were medium to large, whereas for stroke there were no or small effect sizes.
These significant results suggest that lactate tests in swimming specifically have to consider the lactate affecting factors sex and distance under consideration of the time period between measurements. Anthropometrical factors and the physiology of women are possible explanations for the relative better performance for lower lactate concentrations compared to men.
PMCID: PMC3805569  PMID: 24167563
3.  Are centenarians genetically predisposed to lower disease risk? 
Age  2011;34(5):1269-1283.
Our study purpose was to compare a disease-related polygenic profile that combined a total of 62 genetic variants among (i) people reaching exceptional longevity, i.e., centenarians (n = 54, 100–108 years, 48 women) and (ii) ethnically matched healthy controls (n = 87, 19–43 years, 47 women). We computed a ‘global’ genotype score (GS) for 62 genetic variants (mutations/polymorphisms) related to cardiometabolic diseases, cancer or exceptional longevity, and also specific GS for main disease categories (cardiometabolic risk and cancer risk, including 36 and 24 genetic variations, respectively) and for exceptional longevity (7 genetic variants). The ‘global’ GS was similar among groups (centenarians: 31.0 ± 0.6; controls 32.0 ± 0.5, P = 0.263). We observed that the GS for hypertension, cancer (global risk), and other types of cancer was lower in the centenarians group compared with the control group (all P < 0.05), yet the difference became non significant after adjusting for sex. We observed significant between-group differences in the frequency of GSTT1 and GSTM1 (presence/absence) genotypes after adjusting for multiple comparisons. The likelihood of having the GSTT1 low-risk (functional) allele was higher in centenarians (odds ratio [OR] 5.005; 95% confidence interval [CI], 1.810–13.839), whereas the likelihood of having the GSTMI low-risk (functional) allele was similar in both groups (OR 1.295; 95% CI, 0.868 –1.931). In conclusion, we found preliminary evidence that Spanish centenarians have a lower genetic predisposition for cancer risk. The wild-type (i.e., functional) genotype of GSTT1, which is associated with lower cancer risk, might be associated with exceptional longevity, yet further studies with larger sample sizes must confirm these findings.
PMCID: PMC3448993  PMID: 21894447
Centenarians; Genetics; Exceptional longevity; Ageing
4.  Nonreplication of an Association of Apolipoprotein E2 With Sinistrality 
Laterality  2012;18(2):251-261.
A recent report found that left-handed adolescents were over three-fold more likely to have an Apolipoprotein (APOE) ε2 allele. This study was unable to replicate this association in young-adults (N=166). A meta-analysis of nine other datasets (N = 360 to 7,559, Power > 0.999) including that of National Alzheimer’s Coordinating Center also failed to find an over-representation of ε2 among left-handers indicating that this earlier outcome was most likely a statistical artifact.
PMCID: PMC3770935  PMID: 22721421
APOE; handedness; right
5.  Muscular strength and adiposity as predictors of adulthood cancer mortality in men 
We examined the associations between muscular strength, markers of overall and central adiposity and cancer mortality in men.
Prospective cohort study including 8,677 men aged 20-82 years followed from 1980 to 2003. Participants were enrolled in The Aerobics Centre Longitudinal Study, the Cooper Clinic in Dallas, Texas, U.S. Muscular strength was quantified by combining 1-repetition maximal measures for leg and bench presses. Adiposity was assessed by body mass index (BMI), percent body fat, and waist circumference.
Cancer death rates per 10,000 person-years adjusted for age and examination year were: 17.5, 11.0, and 10.3 across incremental thirds of muscular strength (P=0.001); 10.9, 13.4, and 20.1 across BMI groups of 18.5-24.9, 25.0-29.9, and ≥30kg/m2, respectively (P=0.008); 11.6 and 17.5 for normal (<25%) and high percent body fat (≥25%), respectively (P=0.006); and 12.2 and 16.7 for normal (≤102 cm) and high waist circumference (>102 cm), respectively (P=0.06). After adjusting for additional potential confounders, hazard ratios (95% confidence intervals) were 1.00 (referent), 0.65 (0.47-0.90), and 0.61 (0.44-0.85) across incremental thirds of muscular strength, respectively (P=0.003 for linear trend). Further adjustment for BMI, percent body fat, waist circumference, or cardiorespiratory fitness had little effect on the association. The associations of BMI, percent body fat, or waist circumference with cancer mortality did not persist after further adjusting for muscular strength (all P≥0.1).
Higher levels of muscular strength are associated with lower cancer mortality risk in men, independent of clinically established measures of overall and central adiposity, and other potential confounders.
PMCID: PMC3762582  PMID: 19366909
Muscular strength; obesity; cancer; cardiorespiratory fitness; resistance exercise
6.  Objectively measured sedentary time and physical activity in women with fibromyalgia: a cross-sectional study 
BMJ Open  2013;3(6):e002722.
To characterise levels of objectively measured sedentary time and physical activity in women with fibromyalgia.
Cross-sectional study.
Local Association of Fibromyalgia (Granada, Spain).
The study comprised 94 women with diagnosed fibromyalgia who did not have other severe somatic or psychiatric disorders, or other diseases that prevent physical loading, able to ambulate and to communicate and capable and willing to provide informed consent.
Primary outcome measures
Sedentary time and physical activity were measured by accelerometry and expressed as time spent in sedentary behaviours, average physical activity intensity (counts/minute) and amount of time (minutes/day) spent in moderate intensity and in moderate-to-vigorous-intensity physical activity (MVPA).
The proportion of women meeting the physical activity recommendations of 30 min/day of MVPA on 5 or more days a week was 60.6%. Women spent, on average, 71% of their waking time (approximately 10 h/day) in sedentary behaviours. Both sedentary behaviour and physical activity levels were similar across age groups, waist circumference and percentage body fat categories, years since clinical diagnosis, marital status, educational level and occupational status, regardless of the severity of the disease (all p>0.1). Time spent on moderate-intensity physical activity and MVPA was, however, lower in those with greater body mass index (BMI) (−6.6 min and −7 min, respectively, per BMI category increase, <25, 25–30, >30 kg/m2; p values for trend were 0.056 and 0.051, respectively). Women spent, on average, 10 min less on MVPA (p<0.001) and 22 min less on sedentary behaviours during weekends compared with weekdays (p=0.051).
These data provide an objective measure of the amount of time spent on sedentary activities and on physical activity in women with fibromyalgia.
PMCID: PMC3686217  PMID: 23794573
Epidemiology; Preventive Medicine; Public Health; Rheumatology
8.  Objectively Measured Physical Activity and Sedentary Time during Childhood, Adolescence and Young Adulthood: A Cohort Study 
PLoS ONE  2013;8(4):e60871.
To know how moderate-to-vigorous physical activity (MVPA) and sedentary time change across lifespan periods is needed for designing successful lifestyle interventions. We aimed to study changes in objectively measured (accelerometry) MVPA and sedentary time from childhood to adolescence and from adolescence to young adulthood.
Estonian and Swedish participants from the European Youth Heart Study aged 9 and 15 years at baseline (N = 2312) were asked to participate in a second examination 6 (Sweden) to 9/10 (Estonia) years later. 1800 participants with valid accelerometer data were analyzed.
MVPA decreased from childhood to adolescence (−1 to −2.5 min/d per year of follow-up, P = 0.01 and <0.001, for girls and boys respectively) and also from adolescence to young adulthood (−0.8 to −2.2 min/d per year, P = 0.02 and <0.001 for girls and boys, respectively). Sedentary time increased from childhood to adolescence (+15 and +20 min/d per year, for girls and boys respectively, P<0.001), with no substantial change from adolescence to young adulthood. Changes in both MVPA and sedentary time were greater in Swedish than in Estonian participants and in boys than in girls. The magnitude of the change observed in sedentary time was 3–6 time larger than the change observed in MVPA.
The decline in MVPA (overall change = 30 min/d) and increase sedentary time (overall change = 2∶45 h/d) observed from childhood to adolescence are of concern and might increase the risk of developing obesity and other chronic diseases later in life. These findings substantially contribute to understand how key health-related behaviors (physical activity and sedentary) change across important periods of life.
PMCID: PMC3634054  PMID: 23637772
9.  Are mitochondrial haplogroups associated with extreme longevity? A study on a Spanish cohort 
Age  2011;34(1):227-233.
Mitochondrial haplogroups could influence individual susceptibility to mitochondrial DNA (mtDNA) damage, and human longevity, as indicated by previous studies with Caucasian (European) or Asian cohorts. Here, we compared the frequency of mtDNA haplogroups in a group of Spanish (Caucasian) centenarians (n = 65, aged 100–108 years, 58 women, most from the central part of Spain) and a group of healthy young adults (n = 138, 62 women, aged 20–40 years) of the same ethnic origin. We did not find significant differences between centenarians and the control group (P > 0.2). Only two centenarians (both women) had the haplogroup J, which hampered comparison with the control group (n = 15, five women). Our data confirm that the potential effects of mitochondrial haplogroups on human longevity might be population/geographic specific, with important differences between studies (notably, with regard to the previously reported potential benefit brought about by the haplogroup J) arising from the different living environment and ethnic background of the study cohorts.
PMCID: PMC3260354  PMID: 21274636
Genetics; Mitochondria; Centenarians
10.  Physical Activity Attenuates the Effect of Low Birth Weight on Insulin Resistance in Adolescents 
Diabetes  2011;60(9):2295-2299.
To examine whether physical activity influences the association between birth weight and insulin resistance in adolescents.
The study comprised adolescents who participated in two cross-sectional studies: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study (n = 520, mean age = 14.6 years) and the Swedish part of the European Youth Heart Study (EYHS) (n = 269, mean age = 15.6 years). Participants had valid data on birth weight (parental recall), BMI, sexual maturation, maternal education, breastfeeding, physical activity (accelerometry, counts/minute), fasting glucose, and insulin. Insulin resistance was assessed by homeostasis model assessment–insulin resistance (HOMA-IR). Maternal education level and breastfeeding duration were reported by the mothers.
There was a significant interaction of physical activity in the association between birth weight and HOMA-IR (logarithmically transformed) in both the HELENA study and the EYHS (P = 0.05 and P = 0.03, respectively), after adjusting for sex, age, sexual maturation, BMI, maternal education level, and breastfeeding duration. Stratified analyses by physical activity levels (below/above median) showed a borderline inverse association between birth weight and HOMA-IR in the low-active group (standardized β = −0.094, P = 0.09, and standardized β = −0.156, P = 0.06, for HELENA and EYHS, respectively), whereas no evidence of association was found in the high-active group (standardized β = −0.031, P = 0.62, and standardized β = 0.053, P = 0.55, for HELENA and EYHS, respectively).
Higher levels of physical activity may attenuate the adverse effects of low birth weight on insulin sensitivity in adolescents. More observational data, from larger and more powerful studies, are required to test these findings.
PMCID: PMC3161315  PMID: 21752955
11.  The ACTN3 R577X Polymorphism across Three Groups of Elite Male European Athletes 
PLoS ONE  2012;7(8):e43132.
The ACTN3 R577X polymorphism (rs1815739) is a strong candidate to influence elite athletic performance. Yet, controversy exists in the literature owing to between-studies differences in the ethnic background and sample size of the cohorts, the latter being usually low, which makes comparisons difficult. In this case:control genetic study we determined the association between elite athletic status and the ACTN3 R577X polymorphism within three cohorts of European Caucasian men, i.e. Spanish, Polish and Russian [633 cases (278 elite endurance and 355 power athletes), and 808 non-athletic controls]. The odds ratio (OR) of a power athlete harbouring the XX versus the RR genotype compared with sedentary controls was 0.54 [95% confidence interval (CI): 0.34–0.48; P = 0.006]. We also observed that the OR of an endurance athlete having the XX versus the RR genotype compared with power athletes was 1.88 (95%CI: 1.07–3.31; P = 0.028). In endurance athletes, the OR of a “world-class” competitor having the XX genotype versus the RR+RX genotype was 3.74 (95%CI: 1.08–12.94; P = 0.038) compared with those of a lower (“national”) competition level. No association (P>0.1) was noted between the ACTN3 R577X polymorphism and competition level (world-class versus national-level) in power athletes. Our data provide comprehensive support for the influence of the ACTN3 R577X polymorphism on elite athletic performance.
PMCID: PMC3420864  PMID: 22916217
12.  Effectiveness of a Tai-Chi Training and Detraining on Functional Capacity, Symptomatology and Psychological Outcomes in Women with Fibromyalgia 
Background. The purpose was to analyze the effects of Tai-Chi training in women with fibromyalgia (FM). Methods. Thirty-two women with FM (mean age, 51.4 ± 6.8 years) attended to Tai-Chi intervention 3 sessions weekly for 28 weeks. The outcome measures were: tenderness, body composition, functional capacity and psychological outcomes (Fibromyalgia impact questionnaire (FIQ), Short Form Health Survey 36 (SF-36)). Results. Patients showed improvements on pain threshold, total number of tender points and algometer score (all P < 0.001). The intervention was effective on 6-min walk (P = 0.006), back scratch (P = 0.002), handgrip strength (P = 0.006), chair stand, chair sit & reach, 8 feet up & go and blind flamingo tests (all P < 0.001). Tai-Chi group improved the FIQ total score (P < 0.001) and six subscales: stiffness (P = 0.005), pain, fatigue, morning tiredness, anxiety, and depression (all P < 0.001). The intervention was also effective in six SF-36 subscales: bodily pain (P = 0.003), vitality (P = 0.018), physical functioning, physical role, general health, and mental health (all P < 0.001). Conclusions. A 28-week Tai-Chi intervention showed improvements on pain, functional capacity, symptomatology and psychological outcomes in female FM patients.
PMCID: PMC3357550  PMID: 22649476
13.  A Prospective Study of Muscular Strength and All-cause Mortality in Men with Hypertension 
To assess the impact of muscular strength on mortality in men with hypertension.
Muscular strength is inversely associated with mortality in healthy men, but this association has not been examined in men with hypertension.
We followed 1506 hypertensive men aged ≥ 40 years enrolled in the Aerobics Center Longitudinal Study from 1980 to 2003. Participants received an extensive medical examination at baseline. Muscular strength was quantified by combining one repetition maximum (1-RM) measures for leg and bench press, and cardiorespiratory fitness (CRF) assessed by maximum exercise test on a treadmill.
During an average follow-up of 18.3 years, 183 deaths occurred. Age adjusted death rates per 10 000 man-years across incremental thirds of muscular strength were 81.8, 65.5 and 52.0 (P<0.05 for linear trend). Multivariable Cox regression hazard ratios were 1.0 (reference), 0.81 (95% confidence interval, 0.57 to 1.14), and 0.59 (0.40 to 0.86) across incremental thirds of muscular strength. After further adjustment for CRF, those participants in the upper third of muscular strength still had a lower risk of death (0.66; 0.45 to 0.98). In the muscular strength and CRF combined analysis, men simultaneously in the upper third of muscular strength and high fitness group had the lowest mortality risk among all combination groups (0.49; 0.30 to 0.82), with men in the lower third of muscular strength and low fitness group as reference.
High levels of muscular strength appear to protect hypertensive men against all-cause mortality, and this is in addition to the benefit provided by CRF.
PMCID: PMC3098120  PMID: 21527158
Hypertension; muscular strength; cardiorespiratory fitness; mortality
14.  Land- and water-based exercise intervention in women with fibromyalgia: the al-andalus physical activity randomised controlled trial 
The al-Andalus physical activity intervention study is a randomised control trial to investigate the effectiveness of a land- and water-based exercise intervention for reducing the overall impact of fibromyalgia (primary outcome), and for improving tenderness and pain-related measures, body composition, functional capacity, physical activity and sedentary behaviour, fatigue, sleep quality, health-related quality of life, and cognitive function (secondary outcomes) in women with fibromyalgia.
One hundred eighty women with fibromyalgia (age range: 35-65 years) will be recruited from local associations of fibromyalgia patients in Andalucía (Southern Spain). Patients will be randomly assigned to a usual care (control) group (n = 60), a water-based exercise intervention group (n = 60) or a land-based exercise intervention group (n = 60). Participants in the usual care group will receive general physical activity guidelines and participants allocated in the intervention groups will attend three non-consecutive training sessions (60 min each) per week during 24 weeks. Both exercise interventions will consist of aerobic, muscular strength and flexibility exercises. We will also study the effect of a detraining period (i.e., 12 weeks with no exercise intervention) on the studied variables.
Our study attempts to reduce the impact of fibromyalgia and improve patients' health status by implementing two types of exercise interventions. Results from this study will help to assess the efficacy of exercise interventions for the treatment of fibromyalgia. If the interventions would be effective, this study will provide low-cost and feasible alternatives for health professionals in the management of fibromyalgia. Results from the al-Andalus physical activity intervention will help to better understand the potential of regular physical activity for improving the well-being of women with fibromyalgia.
Trial registration ID: NCT01490281
PMCID: PMC3350451  PMID: 22336292
15.  Health-related quality of life of Spanish children with cystic fibrosis 
Quality of Life Research  2012;21(10):1837-1845.
To investigate (1) the contributions of sex, age, nutritional status- and physical-fitness-related variables on health-related quality of life (HRQOL) in Spanish children with cystic fibrosis, and (2) the agreement on HRQOL between children and their parents.
In 28 children aged 6–17 years, body mass index percentile, percentage body fat, physical activity, pulmonary function, cardiorespiratory fitness, functional mobility, and dynamic muscle strength were determined using objective measures. HRQOL was measured using the revised version of the cystic fibrosis questionnaire. Simple and multiple linear regression analyses were performed to determine the variables associated with HRQOL. To assess the agreement on HRQOL between children and parents, intra-class correlation coefficients (ICCs) were calculated.
Girls reported worse emotional functioning, a higher treatment burden, and more respiratory problems than boys. Greater functional mobility appeared associated with a less favourable body image and more eating disturbances. Agreement on HRQOL between children and parents was good to excellent, except for the domain of treatment burden.
Sex and age were stronger predictors of HRQOL than nutritional status- or physical-fitness-related variables. Children reported a lower treatment burden than their parents perceived them to have.
PMCID: PMC3496548  PMID: 22219170
Cystic fibrosis; Quality of life; Children; Parents; Physical fitness; Nutritional status
16.  Psychological Well-Being, Cardiorespiratory Fitness, and Long-Term Survival 
Psychological well-being is associated with mortality/survival. Although cardiorespiratory fitness (CRF) is one of the strongest predictors of mortality, studies examining the relationship between well-being and survival seldom account for the possible effects of CRF.
This study examined the independent associations of psychological well-being components (low level of negative emotion and high level of positive emotion) and CRF, as well as their combined effects, with survival.
Participants (N=4888) were examined in 1988–1997 and followed up for a median period of ~15 years (212 deaths, 4.3%). CRF was assessed by a maximal exercise test on a treadmill. Low-level negative emotion was defined as the minimum score of the negative emotion subscale of the CES-D scale, and high-level positive emotion as the maximum score of positive emotion subscale. Results are presented as hazard ratios (95% CIs). Data were analyzed in 2009.
After adjustment for a set of established risk factors, men and women with low levels of negative emotion had lower risk of death than those with higher levels of negative emotion, 0.66 (0.50, 0.87). The association persisted after additional adjustment for CRF and positive emotion. High level of positive emotion was not associated with survival. A high level of CRF independently predicted lower risk of death, 0.54 (0.37, 0.79), compared to a low level of CRF. The risk of death in participants with both a low level of negative emotion and a high level of CRF was 0.37 (0.22, 0.63), compared to their peers with higher levels of negative emotion/low levels of CRF.
Low levels of negative emotion and high levels of CRF are independent predictors of long-term survival in men and women. A strong combined effect was observed, as individuals with both a low level of negative emotion and a high level of CRF had a 63% lower risk of death than those with higher levels of negative emotion and a low level of CRF.
PMCID: PMC2962920  PMID: 20965381
17.  Stability of the factorial structure of metabolic syndrome from childhood to adolescence: a 6-year follow-up study 
Metabolic syndrome (MS) is a clustering of cardiometabolic risk factors that is considered a predictor of cardiovascular disease, type 2 diabetes and mortality. There is no consistent evidence on whether the MS construct works in the same way in different populations and at different stages in life.
We used confirmatory factor analysis to examine if a single-factor-model including waist circumference, triglycerides/HDL-c, insulin and mean arterial pressure underlies metabolic syndrome from the childhood to adolescence in a 6-years follow-up study in 174 Swedish and 460 Estonian children aged 9 years at baseline. Indeed, we analyze the tracking of a previously validated MS index over this 6-years period.
The estimates of goodness-of-fit for the single-factor-model underlying MS were acceptable both in children and adolescents. The construct stability of a new model including the differences from baseline to the end of the follow-up in the components of the proposed model displayed good fit indexes for the change, supporting the hypothesis of a single factor underlying MS component trends.
A single-factor-model underlying MS is stable across the puberty in both Estonian and Swedish young people. The MS index tracks acceptably from childhood to adolescence.
PMCID: PMC3193025  PMID: 21933439
Tracking; Metabolic syndrome; Confirmatory factor analysis
18.  Validity of Resting Energy Expenditure Predictive Equations before and after an Energy-Restricted Diet Intervention in Obese Women 
PLoS ONE  2011;6(9):e23759.
We investigated the validity of REE predictive equations before and after 12-week energy-restricted diet intervention in Spanish obese (30 kg/m2>BMI<40 kg/m2) women.
We measured REE (indirect calorimetry), body weight, height, and fat mass (FM) and fat free mass (FFM, dual X-ray absorptiometry) in 86 obese Caucasian premenopausal women aged 36.7±7.2 y, before and after (n = 78 women) the intervention. We investigated the accuracy of ten REE predictive equations using weight, height, age, FFM and FM.
At baseline, the most accurate equation was the Mifflin et al. (Am J Clin Nutr 1990; 51: 241–247) when using weight (bias:−0.2%, P = 0.982), 74% of accurate predictions. This level of accuracy was not reached after the diet intervention (24% accurate prediction). After the intervention, the lowest bias was found with the Owen et al. (Am J Clin Nutr 1986; 44: 1–19) equation when using weight (bias:−1.7%, P = 0.044), 81% accurate prediction, yet it provided 53% accurate predictions at baseline.
There is a wide variation in the accuracy of REE predictive equations before and after weight loss in non-morbid obese women. The results acquire especial relevance in the context of the challenging weight regain phenomenon for the overweight/obese population.
PMCID: PMC3167807  PMID: 21909404
19.  The K153R variant in the myostatin gene and sarcopenia at the end of the human lifespan 
Age  2010;32(3):405-409.
We studied the A55T, E164K, I225T, K153R and P198A variants in the myostatin (GDF8) gene, muscle strength and mass, and physical function during daily living in 41 nonagenarians [33 women, age range, 90, 97]. No participant carried a mutant allele of the aforementioned variants, except three participants (all women), who carried the R allele of the K153R polymorphism, with one of them (woman aged 96 years) being homozygous. Overall, in KR women muscle phenotype values (1RM leg press and estimated muscle mass) were low-to-normal compared to the whole group (∼25th–50th percentile), and their functional capacity (Barthel and Tinetti tests) was normal. In the woman bearing the RR genotype, values of muscle mass and functional capacity were below the 25th percentile. She is the first RR Caucasian whose phenotype has been characterised specifically. In summary, heterozygosity for the GDF8 K153R polymorphism does not seem to exert a negative influence on the muscle phenotypes of women who are at the end of the human lifespan, yet homozygosity might do so. More research on larger cohorts of nonagenarians is needed to corroborate the present findings.
PMCID: PMC2926851  PMID: 20640547
Activities of daily living; GDF-8; Muscle strength; Nonagenarians
20.  Intergenerational Cardiovascular Disease Risk Factors Involve Both Maternal and Paternal BMI 
Diabetes Care  2010;33(4):894-900.
To examine the association between parental BMI and offspring cardiovascular disease (CVD) risk factors.
The study comprised 940 children (9.5 ± 0.4 years) and 873 adolescents (15.5 ± 0.5 years). Parental weight and height were reported by the mother and the father, and BMI was calculated. CVD risk factors included total (sum of five skinfolds) and central (waist circumference) body fat, blood pressure, cardiorespiratory fitness, insulin sensitivity, total cholesterol, HDL cholesterol, triglycerides, and fibrinogen.
Maternal and paternal BMI were positively associated with total and central fatness in offspring (P < 0.001). BMIs of both parents were significantly related to fibrinogen levels (P < 0.02), but these associations disappeared when controlling for fatness. There was a positive relationship between maternal and paternal BMI and waist circumference in the offspring regardless of total adiposity and height (P < 0.001). Maternal BMI was negatively associated with offspring cardiorespiratory fitness independently of fatness (P < 0.02). These relationships persisted when overweight descendants were excluded from the analysis. There were no significant associations between parental BMI and the other CVD risk factors.
Both maternal and paternal BMI increase CVD risk factors of their offspring, characterized by total and central body fat, and higher maternal BMI was associated with poorer cardiorespiratory fitness. Our findings give further support to the concept that adiposity in parents transmits susceptibility to CVD risk to descendants, which is detectable even in the absence of overweight in offspring.
PMCID: PMC2845048  PMID: 20056951
21.  Are ‘Endurance’ Alleles ‘Survival’ Alleles? Insights from the ACTN3 R577X Polymorphism 
PLoS ONE  2011;6(3):e17558.
Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100–108 years), young healthy controls (n = 283, 67 females, 216 males; 21±2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (α-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain ‘survival’ advantage brought about by α-actinin-3 deficiency and the ‘endurance’/oxidative muscle phenotype that is commonly associated with this condition.
PMCID: PMC3048287  PMID: 21407828
22.  The K153R Polymorphism in the Myostatin Gene and Muscle Power Phenotypes in Young, Non-Athletic Men 
PLoS ONE  2011;6(1):e16323.
The Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A>G replacement) of the myostatin (MSTN) gene is a candidate to influence skeletal muscle phenotypes. We examined the association between the MSTN K153R polymorphism and ‘explosive’ leg power, assessed during sprint (30 m) and stationary jumping tests [squat (SJ) and counter-movement jumps (CMJ)] in non-athletic young adults (University students) [n = 281 (214 men); age: 21–32 years]. We also genotyped the MSTN exonic variants E164K (rs35781413), I225T, and P198A, yet no subject carried any of these variant MSTN alleles. As for the K153R polymorphism, we found only one woman with the KR genotype; thus, we presented the results only for men. The results of a one-way ANCOVA (with age, weight and height entered as covariates) showed that men with the KR genotype (n = 15) had a worse performance in vertical jumps compared with those with the KK genotype [SJ: vertical displacement of center of gravity (CG) of 35.17±1.42 vs. 39.06±0.39 cm, respectively, P = 0.009; CMJ: vertical displacement of CG of 36.44±1.50 vs. 40.63±0.41 cm, respectively, P = 0.008]. The results persisted after adjusting for multiple comparisons according to Bonferroni. Performance in 30 m sprint tests did however not differ by K153R genotypes. In summary, the MSTN K153R polymorphism is associated with the ability to produce ‘peak’ power during muscle contractions, as assessed with vertical jump tests, in young non-athletic men. Although more research is still needed, this genetic variation is among the numerous candidates to explain, alone or in combination with other polymorphisms, individual variations in muscle phenotypes.
PMCID: PMC3024427  PMID: 21283721
23.  Cardiorespiratory fitness, adiposity and incident asthma in adults 
Capsule summary
Our data support that excess fat increases the risk of incident asthma among adults, and this risk might be attenuated by higher fitness. Physical fitness enhancement in overfat people may reduce risk of incident asthma.
PMCID: PMC2836774  PMID: 20109755
Aerobic capacity; obesity; fatness; airways diseases; pulmonary function
24.  Early Life Programming of Abdominal Adiposity in Adolescents: The HELENA Study 
Diabetes Care  2009;32(11):2120-2122.
To examine the relationship between birth weight and abdominal adiposity in adolescents.
A total of 284 adolescents (49.3% of whom were female) aged 14.9 ± 1.2 years were included in the study. Birth weight and gestational age were obtained from parental records. Abdominal adiposity (in three regions: R1, R2, and R3) and trunk and total body fat mass were measured by dual-energy X-ray absorptiometry. Regional fat mass indexes (FMIs) were thereafter calculated as fat mass divided by the square of height (Trunk FMI and abdominal FMI R1, R2, and R3).
Birth weight was negatively associated with abdominal FMI R1, R2, and R3 independently of total fat mass, gestational age, sex, breast-feeding duration, pubertal stage, physical activity, and socioeconomic status (all P < 0.01).
Our study shows an inverse association between birth weight and abdominal adiposity in adolescents independently of total fat mass and other potential confounders. These findings suggest that fetal nutrition, as reflected by birth weight, may have a programming effect on abdominal adiposity later in life.
PMCID: PMC2768211  PMID: 19641158
25.  Opposite Associations of Trunk and Leg Fat Depots with Plasma Ferritin Levels in Middle-Aged and Older Chinese Men and Women 
PLoS ONE  2010;5(10):e13316.
Few data have been published on the associations of ferritin with trunk and leg fat depots. We aimed to investigate these associations in a Chinese population.
Trunk fat mass and leg fat mass were determined in a cross-sectional sample of 1,150 Chinese (479 men and 671 women) aged 50–70 years by dual-energy X-ray absorptiometry scan. Fasting plasma ferritin was measured.
Principal Findings
Plasma ferritin was positively correlated with waist circumference, waist-to-hip ratio, total body fat and trunk fat mass, but inversely correlated with leg fat mass in men (r = 0.16, 0.26, 0.19, 0.22 and −0.12, respectively, all P<0.05) and women (r = 0.16, 0.16, 0.08, 0.17 and −0.12, respectively, all P<0.05). Multivariate regression analysis showed that ferritin levels increased with larger trunk fat mass (β = 0.33 ± 0.08 for men and β = 0.21 ± 0.05 for women, both P<0.001) while decreased with larger leg fat mass (β = −0.12 ± 0.09, P = 0.15 for men; and β = −0.14 ± 0.05, P = 0.005 for women). Moreover, plasma ferritin levels decreased with increasing tertile of leg fat mass among each tertile of trunk fat mass.
This is the first study to report the opposite associations of trunk and leg fat depots with plasma ferritin levels.
PMCID: PMC2954152  PMID: 20967253

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