Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage

The aim of this study was to estimate the heritability of and environmental contributions to skeletal muscle phenotypes (appendicular lean mass and calf muscle cross-sectional area) in subjects of African descent and to determine whether heritability estimates are impacted by sex or age. Body composition was measured by dual-energy X-ray absorptiometry and computed tomography in 444 men and women aged 18 yr and older (mean: 43 yr) from eight large, multigenerational Afro-Caribbean families (family size range: 21-112). Using quantitative genetic methods, we estimated heritability and the association of anthropometric, lifestyle, and medical variables with skeletal muscle phenotypes. In the overall group, we estimated the heritability of lean mass and calf muscle cross-sectional area (h(2) = 0.18-0.23, P < 0.01) and contribution of environmental factors to these phenotypes (r(2) = 0.27-0.55, P < 0.05). In our age-specific analysis, the heritability of leg lean mass was lower in older vs. younger individuals (h(2) = 0.05 vs. 0.23, respectively, P = 0.1). Sex was a significant covariate in our models (P < 0.001), although sex-specific differences in heritability varied depending on the lean mass phenotype analyzed. High genetic correlations (rho(G) = 0.69-0.81; P < 0.01) between different lean mass measures suggest these traits share a large proportion of genetic components. Our results demonstrate the heritability of skeletal muscle traits in individuals of African heritage and that heritability may differ as a function of sex and age. As the loss of skeletal muscle mass is related to metabolic abnormalities, disability, and mortality in older individuals, further research is warranted to identify specific genetic loci that contribute to these traits in general and in a sex- and age-specific manner.

Blood pressure in Jamaican children: relationship to body size and composition

Blood pressure levels in adults and children are related to body size and composition, but some of these relationships are unclear and they have been incompletely described in the Jamaican population. In a cross-sectional survey of 2,332 school children (6-16 years old; 1,046 boys, 1,286 girls), we measured systolic and diastolic blood pressure and pulse rate, and explored their relationship to weight, height, and waist, hip and mid-upper arm circumferences. The effect of these and other derived measures of body composition on blood pressure was explored in univariate and multivariate analysis. Blood pressure increased with age in both boys and girls, although the increase was greater for systolic than for diastolic blood pressure. The increase of systolic blood pressure among boys continued after age 11 years, but that for girls levelled off. Height and weight were the major predictors of blood pressure, but were highly correlated with each other and with all measures of body composition. Age, height and height-sex interaction explained 11.4 percent of systolic blood pressure variation, and the largest incremental contribution to this model was provided by the addition of body mass index or hip circumference, each explaining an additional 2.6 percent of the variance. Lean body mass made a larger contribution to blood pressure than percent fatness. Blood pressure in Jamaican children rises with age and this rise may be steeper in boys than girls. Blood pressure variation is significantly related to several measures of body composition including measures of fatness and fat free masses.(AU)

Association of waist circumference with risk of hypertension and type 2 diabetes in Nigerians, Jamaicans, and African-Americans

OBJECTIVE: Prior studies have supported that waist circumference correlates better with visceral adipose tissue and is a better predictor of cardiovascular disease than are BMI and waist-to-hip ratio. In this study, we reexamine the role of waist size on the risk of hypertension and type 2 diabetes in African-origin populations from three contrasting environments. RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted of 5,042 men and women 25-74 years of age from Nigeria, Jamaica, and the U.S. The relationship between waist, blood pressure, and fasting blood glucose was assessed using multiple linear regression analyses. Logistic regression analyses using sex-specific empirical waist cut-points were used to determine the risks of hypertension and type 2 diabetes. RESULTS: Waist circumference was positively correlated with blood pressure and fasting blood glucose (P < 0.05). Increasing waist quartiles were significantly associated with higher risks of hypertension in the three populations, as estimated from age-adjusted odds ratios obtained from sex-specific logistic regression models. A highly elevated risk of type 2 diabetes-10-fold for Jamaican men and 23-fold for African-American women - was observed in the comparison of lowest to highest quartiles of waist circumference. CONCLUSIONS: Substantial reduction in hypertension and diabetes in men and women is achievable if the waist size is decreased in these populations. Intervention programs designed to reduce waist circumference through lifestyle modification, including exercise and diet, may have significant public health significance in reducing the incidence of hypertension and adult-onset diabetes in these populations (Au)

Leptin and body composition of Nigerians, Jamaicans, and US blacks

The role of leptin in humans remains controversial. Leptin concentrations are highly correlated with body fat stores. We tested whether or not this relation was consistent across the range of body composition encompassing the lean as well as the obese. Individuals participating in community-based comparative research in Nigeria (n = 363), Jamaica (n = 372), and the United States (Maywood, IL; n = 699) had their plasma leptin concentrations and body compositions (with bioelectrical impedance analysis) measured. All participants identified themselves as being black. Body mass index (in KG/m2) ranged from across populations for both men and women in Nigeria, Jamaica, and the United States, respectively (men: 2.8, 3.9, and 6.8 microg/L; women: 10.3, 18.6, and 27.7 microg/L). An exponential function fit the relation between percentage body fat or total fat mass and leptin for men and women at each site. For women and men the exponential function with either percentage body fat or total fat mass was of the same shape, but increased by a constant in women, yielding higher leptin concentrations than in men at every level of body fat. On the basis of this broad distribution of body composition, the data suggest an exponential response of leptin to increase in body fat stores, consistent with the development of leptin resistance in individuals developing obesity. These findings likewise confirm that men and women exhibit different set points in terms of leptin production(AU)

Leptin concentration in women is influenced by regional distribution of adipose tissue

Leptin concentration in humans are increase with obesity, and women have higher leptin concentration than men. This sex difference reflects the greater fat mass of women. However, there is evidence that factors other than the size of the adipose tissue mass contribute to serum leptin concentrations. This study was undertaken to determine whether anthropometric factors influenced leptin concentrations in our population. Leptin concentrations were measured in 375 persons from a population study of hypertension and diabetes for whom body-composition data (bioelectrical impedance analysis and anthropometry) were available. Serum leptin concentrations were more than four times higher in women than in men (18.5 ñ 13.9 compared with 3.8 ñ 3.5 ng/L, P < 0.0001). In individuals with comparable body mass indexes, these differences persisted after adjustment for either percentage fat (P < 0.05) or fat mas (P < 0.0001) by multivariate-regression analysis. After fat mass was adjusted for, the serum leptin concentration in both men and women was independent of waist circumference but in women was associated with hip circumference. Hip circumference is a proxy measure of peripheral fat and these results suggest that the larger hips of women may contribute to the sex difference in serum leptin concentration.(AU)

Relation between body mass index and body fat in black population samples from Nigeria, Jamaica, and the United States

Body mass index (BMI) is the most commonly used measure of obesity. Recently, some investigators have advocated direct measurement of adiposity rather than use of the BMI. This study was undertaken to determine the ability of BMI to predict body fat levels in three populations of West Africa heritage living in different environments. A total of 1,054 black men and women were examined in Nigeria, Jamaica, and the United States during 1994 and 1995. A standardized protocol was used to measure height, weight, waist and hip circumferences, and blood pressure at all sites; percentage of body fat was estimated using bioelectrical impedance analysis. Percentage of body fat and BMI were highly correlated within site- and sex-specific groups, and the resulting r2 ranged from 0.61 to 0.85. The relation was quadratic in all groups except Nigerian men, in whom it was linear. The regression coefficients were similar across sites, yet the mean body fat levels differed significantly (p < 0.001) as estimated by the intercept, making intersite comparison difficult. Compared with BMI, percentage of body fat was not a better predictor of blood pressure or waist or hip circumference.(AU)

Urea kinetics varies in Jamaican women and men in relation to adiposity, lean body mass and protein intake

OBJECTIVE: We have measured urea kinetics in normal adult men and women of different body composition to determine whether adiposity is associated with differences in the rate of urea production or endogenous urea hydrolysis. DESIGN: Urea kinetics were determined from the excretion of [15N15N] urea in urine over a period of 48 h following a single oral dose of [15N15N] urea, in nine lean and nine obese women and in seven light and seven heavy males while they were consuming their habitual diets. Urinary 5-L-oxoproline was measured as an index of glycine metabolic status. SETTING: The studies were carried out in the research ward of the Tropical Metabolism Research Unit, University of the West Indies. RESULTS: Successful studies were completed in eight obese and five lean women and in six heavy and five light men. When compared with lean women, in obese women the rate of urea production and hydrolysis was significantly greater and this difference could not be accounted for by the greater fat-free mass alone, and was in part associated directly with the increase in fat mass. The rate of urea production and hydrolysis was greater in heavy men than in light men, a difference which was attributed to an increase in dietary protein. In obese women and heavy men there was a significantly higher rate of excretion of 5-Loxoproline in urine when compared with lean women and lean men respectively. CONCLUSION: This paper highlights the difficulty in identifying an appropriate reference with which to express results in people of different body composition. In obese women urea production and the hydrolysis of urea are increased, in part related to the increase fat-free mass, but also related to the increased fat mass itself. In obese women and men on high protein diets the greater rate of hydrolysis urea may be a reflection of an increased demand for the sythesis of non-essential amino acids, especially glycine.(AU)

Obesity in the Caribbean

People of African origin who lived in the Caribbean share a common genetic heritage but live in socioeconomic environments that diverge widely. A cross-cultural study of males and females from Jamaica, St. Lucia and Barbados investigated the prevalence of hypertension and its environmental determinants. Standardized measurement techniques allowed comparable measurements of weight, height, waist and hip circumferences, and blood pressure. The population values for body mass index (BMI), per cent overweight (males BMI > or = 27.8 kg/m2; females BMI > or 27.3 kg/m2) and per cent obese (males BMI > or = 31.1 kg/m2; females BMI > or = 32.3 kg/m2) are presented. Prevalence of hypertension is based on the age-adjusted total population. The gradient in per capita gross national product in Jamaica, St. Lucia and Barbados parallels the gradient in the proportions of population in those countries who are obese. BMI explained 26 percent of the variance in blood pressure in females and 13 percent in males. Obesity is a significant problem in the Caribbean, as it is in many other developing countries, and it is associated with a high prevalence of hypertension, particularly in women.(AU)

Resting metabolic rate and body composition in stunted and non-stunted children - abstract

There is little information supporting the common assumption that stunted children have reduced energy requirements. Previously we found that stunted Jamaican children, aged 9-24 months, have higher energy intakes per kilogram body weight than non-stunted children. We hypothesized that this may be related to differences in basal metabolism and body composition, particularly in lean body mass (LBM) which is the major determinant of resting energy expenditure (RMR). We therefore compared the RMR (using indirect calorimetry) and body composition (using anthropometry amd impedance) in 34 stunted children (S) aged 7-8 years, with two groups of non-stunted controls matched for either age and sex (A), or height and sex (H). The RMR per kilogram body weight of S (58.9ñ6.9 kcal/kg) was significantly higher than A (52.5ñ6.0 kcal/kg; p <0.001), yet lower than the height controls (64.1ñ8.kcal/kg; p <0.01). However, after controlling for sex and weight or LBM in a multiple regression analysis, the RMRs of S and A were no longer significantly different, while the younger H continued to have significantly higher RMRs (p <0.001). No significant group differences were found in the proportions of body fat and LBM to total body weight. In conclusion, the LBM of stunted and non-stunted children of the same age and sex is proportionately and functionally the same, differences in their RMRs being accounted for by size. The lower RMR of stunted children compared to younger non-stunted children of the same size and body composition may be due to age-related changes in the composition of the LBM (AU)

Bioelectrical-impedence analysis as a measure of body composition in a West Indian population

Percent body fat (percent BF) was estimated in 50 males and 50 females aged 8-21 y by using hydrodensitometry (percent BF) and a bioelectrical-impedance analyzer (percent BF-BIA). The sample population was racially heterogenous, though predominantly of African origin. Percent body fat was computed from density by using an equation derived specifically for blacks. The BIA predicted percent BF with r2 = 0.77 (SEE = 3.7 percent BF), underestimating by a mean of 1.7 percent BF. Residuals ( percent BFd - percent BF-BIA) were normally distributed but were significantly correlated with age (P less than 0.01), although this effect was small. The theoretical bases for impedance analysis and for hydrodensitometry would appear for different reasons to impair applicability of these techniques to the present population and age group. However, for our population sample the BIA estimated percent BF as precisely as other simple techniques applied to other populations. (AU)

Bioelectrical impedence, anthropometry and body composition in stunted and non-stunted children

Bioelectrical impedance (BIA) and anthropometric measurements were taken of 129 stunted and 32 non-stunted children aged 9-24 months in Kingston, Jamaica. The reliability of BIA in such young children was examined and the relationships between impedance and anthropometry were determined. The stunted children had significantly lower body mass index (BMI) and smaller triceps skinfolds than the non-stunted children, suggesting differences in body composition between the groups. Resistance was significantly higher in the stunted children than the non-stunted children and nutritional group (stunted or non-stunted) contributed significantly to the variance in resistance after controlling for length, weight, mid-upper arm circumference, triceps and subscapular skinfolds, age and sex. This suggests that there were differences in body composition and/or body shape between the groups beyond that measured by the anthropometric indices used. Total body water (TBW) was estimated using an equation for Jamaican children of comparable age. As a percentage of body weight the TBW estimates were the same for the two groups, a finding which is inconsistent with the anthropometric data.(AU)

Evaluation of a diet for use in the rehabilitation of severely malnourished children

The recovery diet used at the Tropical Metabolism Research Unit, although correcting some of the abnormalities associated with malnutrition, has for several years been known to be unsuitable for this purpose. The standard regime is deficient in several vitamins, minerals, trace elements and even water; rehabilitation on this diet results in some abnormalities in blood biochemistry and an inadequate rate of lean tissue deposition with an excessive accumulation of adipose tissue. In addition, the preparation and dispensation of the feeds is difficult as several additions have to be made. The need was therefore seen for a diet which would contain the nutrients lacking in the standard regimen, promote rapid growth of normal composition, and which could be easily prepared and dispensed. The test diet proposed for this purpose was fed to eight severely malnourished children throughout recovery, and the data collected were compared with that on several children previously recovered on the standard regimen. The results showed that although the test diet, MGM, was of a lower energy density than the standard diet, the energy intake was similar on both diets. The test children therefore compensated for the reduced energy density by increasing their volume of intake. Blood biochemistry of the children on the test diet was found to improve. They experienced no additional oxidant stress and their antioxidant status improved. Plasma concentrations of the trace elements zinc, copper and selenium increased during the period of rehabilitation. Recovery on the test diet resulted in a weight and height gain, cost of growth and rate of weight gain similar to that on the standard diet. The diet was found to be well absorbed, and the biochemistry of the blood improved. Other advantages are: the feeds are easily prepared, as all nutrients, vitamins and minerals are contained in the milk powder, and it is necessary only to add water. The risk of errors which are sometimes introduced due to weighing is therefore minimized. Energy content of the feed is 100 kcal/100g, thus providing for ease in calculation of prescribed intake, and energy content of feed taken. The test diet was found to be an improvement over the existing ward regimen, and with its easy preparation and dispensation was found to be suitable for use in hospitals, rehabilitation centres, and for rehabilitation in the home (AU)

Body composition and hormonal studies during protein energy malnutrition and subsequent re-feeding on different diets

Weanling rats were used as experimental models to determine the changes in body composition, insulin output and rate of weight gain during P.E.M. and recovery from P.E.M. on different diets. The treatments were 1) ad libitum food intake to obtain "normal" growth, 2) restricted food intake to produce malnutrition, and 3) restricted food intake followed by any five experimental diets fed in ad libitum quantities. The malnourished rat model showed an increase in total body water percent, total body protein percent and decreased total body fat percent. Fasting plasma insulin levels were low and rate of weight gain was negligible. Recovery from P.E.M. occured in two stages: 1) an early spate of rapid growth associated with increased insulin output and increased synthesis of lean tissue and 2) a later spate of slow growth associated with decreased insulin output and increased deposition of fat tissue. Rapid recovery was achieved on only two of the diets. The rats which recovered on the diet which supported "normal" growth in control rats demonstrated "normal" body composition. "Abnormal" body composition was observed in rats recovering on a high protein, high energy diet which had a high percentage of fat. They had increased total body fat percent after recovery. Rats failed to recover on diets which were low in protein although adequate in energy. They demonstrated increased total body fat percent and decreased total body protein percent. Fasting plasma insulin levels and rates of weight gain were low. Rats failed to recover on a high energy, high protein diet which had a high percentage of sucrose. There was a high mortality on this diet. Total body protein percent was increased and low plasma insulin levels were obtained (AU)

Muscle mass and composition in malnourished infants and children and changes seen after recovery

A method of measuring muscle mass in children with [15N]creatinine has been used to study changes in muscle after recovery from protein-energy malnutrition. Creatinine pool size, muscle mass, total muscle cell number, muscle cell size, and total body water have been measured in seven malnourished and eight recovered children. After recovery there was a significant reduction in the muscle concentration (micrograms mg[-1] wet wt muscle) of creatine (4.21 to 3.12), and a trend towards reduction in noncollagen protein (155 to 136) and DNA (2.13 to 1.34). The fractional turnover rate of creatine did not change but the creatine pool size increased significantly (4.2 to 5.6 g). Average muscle mass almost doubled (1.00 to 1.91 kg) and made up a greater percentage of body weight (16 to 22 percent). When muscle mass was expressed as a percentage of the expected muscle mass for a normal child of the same height the increase with recovery was from 49 percent to 92 percent. Total muscle noncollagen protein (NCP) increased after recovery (153 to 265 g) and accounted for a greater percentage of total body solids (6.6 to 8.5 percent). The average total muscle DNA was 2.049 g in the malnourished and 2.380 g in the recovered children and the ratio of NCP:DNA increased from 92 to 110 on recovery. Total body water as a percentage of body weight was not significantly different after recovery. Values for muscle mass in recovered children were similar to those reported for normal children of the same weight, height, and age. (Summary)

The energy cost of repleting tissue deficits during recovery from protein-energy malnutrition

Five children with protein-energy malnutrition were treated with a high calorie, high protein diet and the energy cost of growth in body weight and muscle mass were calculated. Energy expenditures correlated statistically with increases in muscle mass, estimated by [15N] creatine kinetics, but not with gains in body weight.(AU)

A comparison of the response of thirteen muscles in the rat to dietary restriction

Information derived from a sample of a particular muscle or the entire muscle is often assumed to be characteristic of skeletal muscle in general. There has been little experimental work designed to validate this assumption which has important implications in clinical situations such as severe protein-energy malnutrition in which gross muscle wasting is a characteristic feature. This project was designed to gain information on the changes that take place in a number of muscles in the rat exhibiting severe muscle wasting following dietary deprivation. Eight male albino rats aged 5 weeks and weighing 100g were starved for 33 days and then fed a 1 percent protein diet for 20-22 days. Control animals were albino male rats of the same initial age and body weight. The 13 muscles examined were those of the trunk (rectus abdominis, diaphragm and psoas), thigh (gluteus), hind-limb (quadriceps, tibialis anterior, gastrocnemius and soleus), and fore-limb (Triceps, biceps, brachialis, Flexor carpi radialis and Extensor carpi ulnaris). Estimations on the whole muscle were made of wet weight, dry weight, fat free dry weight, cellular protein, extracellular protein, DNA and RNA. The results showed that the muscles of the experimental animals underwent similar compositional changes in response to the dietary restriction. The changes of four small fore-limb muscle were not characteristic at times. Overall the muscles lost 19 percent wet weight, 17 percent dry weight and 18 percent fat free dry weight. The total water content decreased by approximately 2 percent, cellular protein by 20 percent and total muscle RNA by 44 percent. Extracellular protein increased by 35 percent. There was no significant difference in the total DNA and fat content of nearly all the muscles of control and experimental animals. Although the muscles responded similarly to the dietary treatment the extent of change varied. Caution must be exercised when extrapolating these changes to the entire musculature (Summary)

Body composition studies in children admitted to hospital with protein-energy malnutrition

Thirteen children who were suffering from protein energy malnutrition were studied in an effort to determine their body composition on admission to hospital, while they were rapidly growing and when they had fully recovered. A review of the available methods for measuring body composition, the methods which are applicable to malnourished children, those used in this project, the results obtained and the difficulties encountered from the body of this report. The main aims of this study were (i) to validate the use of simple anthropometric measurements in body composition studies, and (ii) to see whether the children who recovered from malnutrition were depositing tissue in normal proportions when fed on the high calorie dietary regime. The results are encouraging and have opened up new areas for future reseach. The main findings can be summerised as follows:- (1) the values for total body fat calculated from anthropometric measurements are not significantly different from those calculated from total body water measurement. In the malnourished phase total body fat (TBF) was found to be 14.3 percent and 10.2 percent of body weight from TBW and skinfold measurements respectively. While values for the rapidly growing stage were 16.7 percent and 15.9 percent and in the recovered stage these values were 22.8 percent and 22.5 percent. (2) The measurement of 24 hour urinary creatinine excretions is not a reliable indicator of muscle mass in malnourished children. (3) The serial measurements of TWB should carried out at carefully timed intervals which relate to the energy intake on admission, during rapid growth and at recovery. (4) The faecal energy losses of the 5 children studied on nitrogen balance were variable. In the malnourished stage these values were 5.1 percent, 37.4 percent and 45.3 percent of the energy intake. In the rapidly growing phase the values ranged from 8.1 percent - 58.9 percent of the intake. In the recovered stage there was less variation but the values were higher than those reported in the literature(39.1 percent - 43.1 percent of the intake). (5) Simple anthropometric measurements (arm circumference, triceps skinfold) can be used to estimate the nutritional status of children, and as a measure of recovery from malnutrition (Summary)

The measurement of muscle mass in children using [15N] creatinine

In eight infants and children who had recovered from protein-energy malnutrition (PEM), muscle mass was estimated by measuring creatine turnover by an isotope dilution technique using [15N] creatine, creatine concentration, and urinary creatinine output. Creatine turnover varied from 1.5 to 2.6 percent of the muscle creatine pool per day and muscle creatine concentration ranged from 1.7 to 3.9æg/æg muscle DNA. Muscle mass was between 15 percent and 37percent of total body weight. The results indicate that daily creatinine output is not reliable indicator of muscle mass in children who have recently recovered from severe PEM.(AU)

Resting metabolic rate in malnourished babies in relation to total body potassium

Fasting metabolic rate was investigated in 53 malnourished children and 17 controls of similar age. Total body potassium (TBK) was also measured in 18 of the malnourished children and in all the controls, so that metabolic rates could be compared in relation to a measure of metabolically active tissue. In newly admitted malnourished children specific potassium depletion was corrected orally while they were given a maintenance diet. Resting metabolism correlated better with TBK than with weight, height or surface area in control and recovered children, but metabolic rate per unit TBK decline with increasing body-weight (r=-0.51). This negative correlation became insignificant if metabolic rate was expressed in terms of TBK3/4. In the malnourished children resting metabolic rate was reduced compared with control and recovered values, when expressed in terms of weight, height or surface area. The results were confirmed by a comparison of metabolic rates per unit TBK3/4, which showed a reduction of about 27 percent in the malnourished children. No significant difference was found between children with marasmus and those with oedematous malnutrition. During rapid growth fasting metabolism was increased. We conclude that oxygen consumption in metabolically active tissues is reduced in all forms of untreated infantile malnutrition. (AU)

Techniques for the measurement of human body composition

In many disorders of nutrition, and of water and electrolyte balance, body weight may be an unreliable index of the clinical state, since it may fail to reflect the change in body composition which is physiologically more important. Some techniques by which body composition can be measured in the living subject have been briefly reviewed: recent developments in the field have included some methods of great expense and complexity, and some which are very cheap and simple. An attempt has been made to suggest which methods are most appropriate for specific applications, and to indicate the assumptions which are implicit in these methods (AU)