Non-exercise equations to estimate fitness in white European and South Asian men

Cardiorespiratory fitness is a strong, independent predictor of health, whether it is measured in an exercise test or estimated in an equation. The purpose of this study was to develop and validate equations to estimate fitness in middle-aged white European and South Asian men.Multiple linear regression models (n=168, including 83 white European and 85 South Asian men) were created using variables that are thought to be important in predicting fitness (VO2 max, mL⋅kg⋅min): age (years); BMI (kg·m); resting heart rate (beats⋅min); smoking status (0=never smoked, 1=ex or current smoker); physical activity expressed as quintiles (0=quintile 1, 1=quintile 2, 2=quintile 3, 3=quintile 4, 4=quintile 5), categories of moderate- to vigorous-intensity physical activity (0=<75 min⋅wk, 1=75-150 min⋅wk, 2=>150-225 min⋅wk, 3=>225-300 min⋅wk, 4=>300 min⋅wk), or minutes of moderate- to vigorous-intensity physical activity (min⋅wk); and, ethnicity (0=South Asian, 1=white). The leave-one-out-cross-validation procedure was used to assess the generalizability and the bootstrap and jackknife resampling techniques were used to estimate the variance and bias of the models.Around 70% of the variance in fitness was explained in models with an ethnicity variable, such as: VO2 max = 77.409 - (age*0.374) - (BMI*0.906) - (ex or current smoker*1.976) + (physical activity quintile coefficient) - (resting heart rate*0.066) + (white ethnicity*8.032), where physical activity quintile 1 is 1, 2 is 1.127, 3 is 1.869, 4 is 3.793, and 5 is 3.029. Only around 50% of the variance was explained in models without an ethnicity variable. All models with an ethnicity variable were generalizable and had low variance and bias.These data demonstrate the importance of incorporating ethnicity in non-exercise equations to estimate cardiorespiratory fitness in multi-ethnic populations

Associations of objectively measured moderate-to-vigorous-intensity physical activity and sedentary time with all-cause mortality in a population of adults at high risk of type 2 diabetes mellitus

The relationships of physical activity and sedentary time with all-cause mortality in those at high risk of type 2 diabetes mellitus (T2DM) are unexplored. To address this gap in knowledge,we examined the associations of objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time with all-cause mortality in a population of adults at high risk of T2DM. In 2010–2011, 712 adults (Leicestershire, U.K.), identified as being at high risk of T2DM, consented to be followed up for mortality.MVPA and sedentary time were assessed by accelerometer; those with valid data (≥10 hours of wear-time/day with ≥4 days of data) were included. Cox proportional hazards regression models, adjusted for potential confounders, were used to investigate the independent associations of MVPA and sedentary time with all-cause mortality. 683 participants (250 females (36.6%)) were included and during a mean follow-up period of 5.7 years, 26 deaths were registered. Every 10% increase in MVPA time/day was associated with a 5% lower risk of all-cause mortality [Hazard Ratio (HR): 0.95 (95% Confidence Interval (95% CI): 0.91, 0.98); p=0.004]; indicating that for the average adult in this cohort undertaking approximately 27.5 minutes of MVPA/day, this benefit would be associated with only 2.75 additional minutes of MVPA/day. Conversely, sedentary time showed no association with all-cause mortality [HR (every 10-minute increase in sedentary time/day): 0.99 (95% CI: 0.95, 1.03); p=0.589]. These data support the importance of MVPA in adults at high risk of T2DM. The association between sedentary time and mortality in this population needs further investigation

Associations of objectively measured moderate-to-vigorous-intensity physical activity and sedentary time with all-cause mortality in a population of adults at high risk of type 2 diabetes mellitus

a b s t r a c t a r t i c l e i n f o The relationships of physical activity and sedentary time with all-cause mortality in those at high risk of type 2 diabetes mellitus (T2DM) are unexplored. To address this gap in knowledge, we examined the associations of objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time with all-cause mortality in a population of adults at high risk of T2DM. In 2010-2011, 712 adults (Leicestershire, U.K.), identified as being at high risk of T2DM, consented to be followed up for mortality. MVPA and sedentary time were assessed by accelerometer; those with valid data (≥10 hours of wear-time/day with ≥4 days of data) were included. Cox proportional hazards regression models, adjusted for potential confounders, were used to investigate the independent associations of MVPA and sedentary time with all-cause mortality. 683 participants (250 females (36.6%)) were included and during a mean follow-up period of 5.7 years, 26 deaths were registered. Every 10% increase in MVPA time/day was associated with a 5% lower risk of all-cause mortality [Hazard Ratio (HR): 0.95 (95% Confidence Interval (95% CI): 0.91, 0.98); p = 0.004]; indicating that for the average adult in this cohort undertaking approximately 27.5 minutes of MVPA/day, this benefit would be associated with only 2.75 additional minutes of MVPA/day. Conversely, sedentary time showed no association with all-cause mortality [HR (every 10-minute increase in sedentary time/day): 0.99 (95% CI: 0.95, 1.03); p = 0.589]. These data support the importance of MVPA in adults at high risk of T2DM. The association between sedentary time and mortality in this population needs further investigation

Non-exercise equations to estimate fitness in white European and South Asian men

© 2015 American College of Sports Medicine PURPOSE: Cardiorespiratory fitness is a strong, independent predictor of health, whether it is measured in an exercise test or estimated in an equation. The purpose of this study was to develop and validate equations to estimate fitness in middle-aged white European and South Asian men. METHODS: Multiple linear regression models (n=168, including 83 white European and 85 South Asian men) were created using variables that are thought to be important in predicting fitness (VO2 max, mL⋅kg⋅min): age (years); BMI (kg·m); resting heart rate (beats⋅min); smoking status (0=never smoked, 1=ex or current smoker); physical activity expressed as quintiles (0=quintile 1, 1=quintile 2, 2=quintile 3, 3=quintile 4, 4=quintile 5), categories of moderate- to vigorous-intensity physical activity (0=150-225 min⋅wk, 3=>225-300 min⋅wk, 4=>300 min⋅wk), or minutes of moderate- to vigorous-intensity physical activity (min⋅wk); and, ethnicity (0=South Asian, 1=white). The leave-one-out-cross-validation procedure was used to assess the generalizability and the bootstrap and jackknife resampling techniques were used to estimate the variance and bias of the models. RESULTS: Around 70% of the variance in fitness was explained in models with an ethnicity variable, such as: VO2 max = 77.409 - (age*0.374) – (BMI*0.906) – (ex or current smoker*1.976) + (physical activity quintile coefficient) – (resting heart rate*0.066) + (white ethnicity*8.032), where physical activity quintile 1 is 1, 2 is 1.127, 3 is 1.869, 4 is 3.793, and 5 is 3.029. Only around 50% of the variance was explained in models without an ethnicity variable. All models with an ethnicity variable were generalizable and had low variance and bias. CONCLUSION: These data demonstrate the importance of incorporating ethnicity in non-exercise equations to estimate cardiorespiratory fitness in multi-ethnic populations

Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice

Epidemiology of Sedentary Behaviour: Novel Findings in Health and Measurement

The overall aim of this PhD was to further examine the associations between physical activity, sedentary behaviour and health (cardiometabolic health, all‐cause mortality, cognitive function), and explore novel approaches for analysing physical activity and sedentary behaviour data. Key Findings: •In a national survey sample of adults (Health Survey for England), being physically active was associated with better cardiometabolic health, even in those with high sedentary time. •In a regional sample of high risk of T2DM adults (Walking Away from Type 2 Diabetes), MVPA time was associated with a lower risk of mortality. Conversely, sedentary time showed no association with mortality. •In a large sample of UK adults (UK Biobank), TV viewing and driving time were inversely associated with cognition. Conversely, computer use time was positively associated with cognition. Further analyses demonstrated that fitness did not modify these associations, and that the number of healthy lifestyle factors was positively associated with cognition. •Sedentary behaviours can be separated from light activities (except standing still) using intensity‐based thresholds derived on experimental raw acceleration data. In conclusion, this project has helped fill several epidemiological gaps in knowledge via exploiting multifaceted databases, and evaluated innovative measurement techniques. The observational analyses demonstrated the importance of physical activity as a determinant of cardiometabolic health and mortality, but found the role of sedentary behaviour to be relatively equivocal. Additional work with cognitive outcomes showed that some sedentary behaviours, but not all, are associated with poor cognition. These results provide robust data supporting public health policies designed to reduce TV viewing and driving time in adults, and increase healthy behaviours for cognitive wellbeing. Intervention studies are required to confirm these findings. The experimental analyses showed that researchers can accurately separate sedentary behaviours from light activities using thresholds on raw acceleration data; thus, providing a useful resource for future studies

Associations between sedentary behaviours and cognitive function: cross-sectional and prospective findings from the UK Biobank

We investigated the cross-sectional and prospective associations between different sedentary behaviors and cognitive function in a large sample of adults with data stored in the UK Biobank. Baseline data were available for 502,643 participants (2006–2010, United Kingdom). Cognitive tests included prospective memory (baseline only: n = 171,585), visual-spatial memory (round 1: n = 483,832; round 2: n = 482,762), fluid intelligence (n = 165,492), and short-term numeric memory (n = 50,370). After a mean period of 5.3 years, participants (numbering from 12,091 to 114,373, depending on the test) also provided follow-up cognitive data. Sedentary behaviors (television viewing, driving, and nonoccupational computer-use time) were measured at baseline. At baseline, both television viewing and driving time were inversely associated with cognitive function across all outcomes (e.g., for each additional hour spent watching television, the total number of correct answers in the fluid intelligence test was 0.15 (99% confidence interval: 0.14, 0.16) lower. Computer-use time was positively associated with cognitive function across all outcomes. Both television viewing and driving time at baseline were positively associated with the odds of having cognitive decline at follow-up across most outcomes. Conversely, computer-use time at baseline was inversely associated with the odds of having cognitive decline at follow-up across most outcomes. This study supports health policies designed to reduce television viewing and driving in adults

Reaction time, cardiorespiratory fitness and mortality in UK Biobank: An observational study

Intelligence has previously been associated with mortality, although it is unclear whether the inverse association is independent of other related cognitive factors, such as information processing, or of measures related to physical health, such as cardiorespiratory fitness. We investigate whether fluid intelligence, reaction time and cardiorespiratory fitness are independently associated with mortality within the general population. UK Biobank recruited adults across England, Scotland and Wales, between March 2006 and July 2010: 54,019 participants (women 52%) with complete data were included in the analysis. Those who died in the first year of follow-up (n = 58) were excluded. Fluid intelligence was measured as the number of correct answers during a two minute logic/reasoning-test, reaction time was measured as average time taken to respond to matching symbols on a computer screen and cardiorespiratory fitness was measured through a sub-maximal exercise test. Associations with mortality were assessed by Cox-proportional hazard models adjusted for age, sex, ethnicity, social deprivation, cancer and non-cancer illnesses, medications, employment, education, smoking, BMI, diet, sleep, and physical activity. Over 5.8 years of follow-up, there were 779 deaths. Higher intelligence (hazard ratio [HR] per SD = 0.91; 95% CI 0.84, 0.99), faster reaction time (HR per SD = 0.92; 0.85, 0.98) and higher fitness (HR per SD = 0.85; 0.78, 0.93) were associated with a lower risk of mortality after adjustment for each other and other covariates. No interaction was observed between fluid intelligence and reaction time (p = 0.147) or between fluid intelligence and cardiorespiratory fitness (p = 0.238). In conclusion, fluid intelligence, reaction time and cardiorespiratory fitness were independently associated with mortality

Associations of reallocating sitting time into standing or stepping with glucose, insulin and insulin sensitivity: a cross-sectional analysis of adults at risk of type 2 diabetes

OBJECTIVE: To quantify associations between sitting time and glucose, insulin and insulin sensitivity by considering reallocation of time into standing or stepping. DESIGN: Cross-sectional. SETTING: Leicestershire, UK, 2013. PARTICIPANTS: Adults aged 30-75 years at high risk of impaired glucose regulation (IGR) or type 2 diabetes. 435 adults (age 66.8±7.4 years; 61.7% male; 89.2% white European) were included. METHODS: Participants wore an activPAL3 monitor 24 hours/day for 7 days to capture time spent sitting, standing and stepping. Fasting and 2-hour postchallenge glucose and insulin were assessed; insulin sensitivity was calculated by Homeostasis Model Assessment of Insulin Secretion (HOMA-IS) and Matsuda-Insulin Sensitivity Index (Matsuda-ISI). Isotemporal substitution regression modelling was used to quantify associations of substituting 30 min of waking sitting time (accumulated in prolonged (≥30 min) or short (<30 min) bouts) for standing or stepping on glucose regulation and insulin sensitivity. Interaction terms were fitted to assess whether the associations with measures of glucose regulation and insulin sensitivity was modified by sex or IGR status. RESULTS: After adjustment for confounders, including waist circumference, reallocation of prolonged sitting to short sitting time and to standing was associated with 4% lower fasting insulin and 4% higher HOMA-IS; reallocation of prolonged sitting to standing was also associated with a 5% higher Matsuda-ISI. Reallocation to stepping was associated with 5% lower 2-hour glucose, 7% lower fasting insulin, 13% lower 2-hour insulin and a 9% and 16% higher HOMA-IS and Matsuda-ISI, respectively. Reallocation of short sitting time to stepping was associated with 5% and 10% lower 2-hour glucose and 2-hour insulin and 12% higher Matsuda-ISI. Results were not modified by IGR status or sex. CONCLUSIONS: Reallocating a small amount of short or prolonged sitting time with standing or stepping may improve 2-hour glucose, fasting and 2-hour insulin and insulin sensitivity. Findings should be confirmed through prospective and intervention research. TRIAL REGISTRATION NUMBER: ISRCTN31392913, Post-results

Association of walking pace and handgrip strength with all-cause, cardiovascular, and cancer mortality : a UK Biobank observational study

To quantify the association of self-reported walking pace and handgrip strength with all-cause, cardiovascular, and cancer mortality. A total of 230 670 women and 190 057 men free from prevalent cancer and cardiovascular disease were included from UK Biobank. Usual walking pace was self-defined as slow, steady/average or brisk. Handgrip strength was assessed by dynamometer. Cox-proportional hazard models were adjusted for social deprivation, ethnicity, employment, medications, alcohol use, diet, physical activity, and television viewing time. Interaction terms investigated whether age, body mass index (BMI), and smoking status modified associations. Over 6.3 years, there were 8598 deaths, 1654 from cardiovascular disease and 4850 from cancer. Associations of walking pace with mortality were modified by BMI. In women, the hazard ratio (HR) for all-cause mortality in slow compared with fast walkers were 2.16 [95% confidence interval (CI): 1.68-2.77] and 1.31 (1.08-1.60) in the bottom and top BMI tertiles, respectively; corresponding HRs for men were 2.01 (1.68-2.41) and 1.41 (1.20-1.66). Hazard ratios for cardiovascular mortality remained above 1.7 across all categories of BMI in men and women, with modest heterogeneity in men. Handgrip strength was associated with cardiovascular mortality in men only (HR tertile 1 vs. tertile 3 = 1.38; 1.18-1.62), without differences across BMI categories, while associations with all-cause mortality were only seen in men with low BMI. Associations for walking pace and handgrip strength with cancer mortality were less consistent. A simple self-reported measure of slow walking pace could aid risk stratification for all-cause and cardiovascular mortality within the general population