Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women

Lean body mass (LBM) and muscle mass remains difficult to quantify in large epidemiological studies due to non-availability of inexpensive methods. We therefore developed anthropometric prediction equations to estimate the LBM and appendicular lean soft tissue (ALST) using dual energy X-ray absorptiometry (DXA) as a reference method. Healthy volunteers (n= 2220; 36% females; age 18-79 y) representing a wide range of body mass index (14-44 kg/m2) participated in this study. Their LBM including ALST was assessed by DXA along with anthropometric measurements. The sample was divided into prediction (60%) and validation (40%) sets. In the prediction set, a number of prediction models were constructed using DXA measured LBM and ALST estimates as dependent variables and a combination of anthropometric indices as independent variables. These equations were cross-validated in the validation set. Simple equations using age, height and weight explained > 90% variation in the LBM and ALST in both men and women. Additional variables (hip and limb circumferences and sum of SFTs) increased the explained variation by 5-8% in the fully adjusted models predicting LBM and ALST. More complex equations using all the above anthropometric variables could predict the DXA measured LBM and ALST accurately as indicated by low standard error of the estimate (LBM: 1.47 kg and 1.63 kg for men and women, respectively) as well as good agreement by Bland Altman analyses. These equations could be a valuable tool in large epidemiological studies assessing these body compartments in Indians and other population groups with similar body composition.

The association of early life supplemental nutrition with lean body mass and grip strength in adulthood : evidence from APCAPS

In the present study, we examined the associations of early nutrition with adult lean body mass (LBM) and muscle strength in a birth cohort that was established to assess the long-term impact of a nutrition program. Participants (n = 1,446, 32% female) were born near Hyderabad, India, in 29 villages from 1987 to 1990, during which time only intervention villages (n = 15) had a government program that offered balanced protein-calorie supplementation to pregnant women and children. Participants’ LBM and appendicular skeletal muscle mass were measured using dual energy x-ray absorptiometry; grip strength and information on lifestyle indicators, including diet and physical activity level, were also obtained. Ages (mean = 20.3 years) and body mass indexes (weight (kg)/height (m)2; mean = 19.5) of participants in 2 groups were similar. Current dietary energy intake was higher in the intervention group. Unadjusted LBM and grip strength were similar in 2 groups. After adjustment for potential confounders, the intervention group had lower LBM (β = −0.75; P = 0.03), appendicular skeletal muscle mass, and grip strength than did controls, but these differences were small in magnitude (<0.1 standard deviation). Multivariable regression analyses showed that current socioeconomic position, energy intake, and physical activity level had a positive association with adult LBM and muscle strength. This study could not detect a “programming” effect of early nutrition supplementation on adult LBM and muscle strength.

Nutritional influences over the life course on lean body mass of individuals in developing countries

The double burden of childhood undernutrition and adult-onset adiposity in transitioning societies poses a significant public health challenge. The development of suboptimal lean body mass (LBM) could partly explain the link between these two forms of malnutrition. This review examines the evidence on both the role of nutrition in “developmental programming” of LBM and the nutritional influences that affect LBM throughout the life course. Studies from developing countries assessing the relationship of early nutrition with later LBM provide important insights. Overall, the evidence is consistent in suggesting a positive association of early nutritional status (indicated by birth weight and growth during first 2 years) with LBM in later life. Evidence on the impact of maternal nutritional supplementation during pregnancy on later LBM is inconsistent. In addition, the role of nutrients (protein, zinc, calcium, vitamin D) that can affect LBM throughout the life course is described. Promoting optimal intakes of these important nutrients throughout the life course is important for reducing childhood undernutrition as well as for improving the LBM of adults.

Determinants and measurement of lean body mass in Indian adults

Indians tend to have lower lean body mass than other ethnic groups which increases the risk of chronic diseases. Three complementary studies included in this thesis advanced knowledge on determinants of lean body mass in Indians and the techniques to measure it. The first study examined the determinants of lean body mass in young Indian adults and highlighted the importance of diet and physical activity for development of lean body mass. This study has important implications for policy on prevention of chronic diseases in India. The other two studies helped refinement of the techniques of lean body mass measurement and are expected to facilitate future research in this area. The thesis is presented in the form of publications in high ranking journals.

Conjugated Linoleic Acid Combined with Physical Activity Reduces Body Fat Accumulation But Does Not Modify Lean Body Mass in Male and Female Wistar Rats

Several biological and clinical studies have suggested that conjugated linoleic acid (CLA) prevents body fat accumulation and increases lean body mass. CLA is available as a concentrated dietary supplement and is purported to provide the aforementioned benefits for people who perform physical activity. This study was conducted to evaluate the effect of a CLA-supplemented diet combined with physical activity on the body composition of Wistar rats. Two groups of Wistar rats of both sexes, between 45 and 60 days old, were fed a diet containing 5.5% soybean oil (control group) or a CLA-supplemented diet (0.5% CLA and 5.0% soybean oil) (test group). Half the rats in both groups were assigned to exercise by running on a treadmill. The biochemical and anatomical body compositions were analyzed. In both groups, CLA had no effect on the dietary consumption or the weight of the liver, heart, and lungs. However, it did influence the overall weight gain of exercised male rats and the chemical and anatomical body composition in exercised and sedentary rats of both sexes. The results confirm that a CLA-supplemented diet with and without physical activity reduced body fat accumulation in rats of both sexes. However, there is no evidence of an increase in the lean body mass of the exercised rats.

Change in lean body mass Is a major determinant of change in areal bone mineral density of the proximal femur: A 12-year observational study

Our objective was to assess the contribution of lean body mass (LBM) and fat body mass (FBM) to areal bone mineral density (aBMD) in women during the years surrounding menopause. We used a 12-year observational design. Participants included 75 Caucasian women who were premenopausal, 53 of whom were available for follow-up. There were two measurement periods: baseline and 12-year follow-up. At both measurement periods, bone mineral content and aBMD of the proximal femur, posterior-anterior lumbar spine, and total body was assessed using dual-energy X-ray absorptiometry (DXA). LBM and FBM were derived from the total-body scans. General health, including current menopausal status, hormone replace therapy use, medication use, and physical activity, was assessed by questionnaires. At the end of the study, 44% of the women were postmenopausal. After controlling for baseline aBMD, current menopausal status, and current hormone replacement therapy, we found that change in LBM was independently associated with change in aBMD of the proximal femur (P = 0.001). The cross-sectional analyses also indicated that LBM was a significant determinant of aBMD of all three DXA-scanned sites at both baseline and follow-up. These novel longitudinal data highlight the important contribution of LBM to the maintenance of proximal femur bone mass at a key time in women's life span, the years surrounding menopause.

Associations of body mass index and waist circumference with: energy intake and percentage energy from macronutrients, in a cohort of Australian children

Background It is evident from previous research that the role of dietary composition in relation to the development of childhood obesity remains inconclusive. Several studies investigating the relationship between body mass index (BMI), waist circumference (WC) and/or skin fold measurements with energy intake have suggested that the macronutrient composition of the diet (protein, carbohydrate, fat) may play an important contributing role to obesity in childhood as it does in adults. This study investigated the possible relationship between BMI and WC with energy intake and percentage energy intake from macronutrients in Australian children and adolescents. Methods Height, weight and WC measurements, along with 24 h food and drink records (FDR) intake data were collected from 2460 boys and girls aged 5-17 years living in the state of Queensland, Australia. Results Statistically significant, yet weak correlations between BMI z-score and WC with total energy intake were observed in grades 1, 5 and 10, with only 55% of subjects having a physiologically plausible 24 hr FDR. Using Pearson correlations to examine the relationship between BMI and WC with energy intake and percentage macronutrient intake, no significant correlations were observed between BMI z-score or WC and percentage energy intake from protein, carbohydrate or fat. One way ANOVAs showed that although those with a higher BMI z-score or WC consumed significantly more energy than their lean counterparts. Conclusion No evidence of an association between percentage macronutrient intake and BMI or WC was found. Evidently, more robust longitudinal studies are needed to elucidate the relationship linking obesity and dietary intake.

Prospective ten-month exercise intervention in premenarcheal girls: Positive effects on bone and lean mass

Enhancement of bone mineral acquisition during growth may be a useful preventive strategy against osteoporosis. The aim of this study was to explore the lean mass, strength, and bone mineral response to a 10-month, high-impact, strength-building exercise program in 71 premenarcheal girls, aged 9–10 years. Lean body mass, total body (TB), lumbar spine (LS), proximal femur (PF), and femoral neck (FN) bone mineral were measured using the Hologic QDR 2000+ bone densitometer. Strength was assessed using a grip dynamometer and the Cybex isokinetic dynamometer (Cybex II). At baseline, no significant difference in body composition, pubertal development, calcium intake, physical activity, strength, or bone mineral existed between groups. At completion, there were again no differences in height, total body mass, pubertal development, calcium intake, or external physical activity. In contrast, the exercise group gained significantly more lean mass, less body fat content, greater shoulder, knee and grip strength, and greater TB, LS, PF, and FN BMD (exercise: TB 3.5%, LS 4.8%, PF 4.5%, and FN 12.0%) compared with the controls (controls: TB 1.2%, LS 1.2%, PF 1.3%, and FN 1.7%). TB bone mineral content (BMC), LS BMC, PF BMC, FN BMC, LS bone mineral apparent density (BMAD), and FN bone area also increased at a significantly greater rate in the exercise group compared with the controls. In multiple regression analysis, change in lean mass was the primary determinant of TB, FN, PF, and LS BMD accrual. Although a large proportion of bone mineral accrual in the premenarcheal skeleton was related to growth, an osteogenic effect was associated with exercise. These results suggest that high-impact, strength building exercise is beneficial for premenarcheal strength, lean mass gains, and bone mineral acquisition.

Lean and Fat Mass Loss in Obese Patients Before and After Roux-en-Y Gastric Bypass: A New Application for Ultrasound Technique

This study aims to evaluate the thickness of the femoral quadriceps and biceps brachii and brachialis muscles bilaterally and the adjacent subcutaneous fat in patients undergoing gastric bypass Roux-en-Y before and after surgery, using ultrasound as the diagnostic method of choice. We studied 12 patients undergoing this surgical method preoperatively and during the first, third, and sixth postoperative months. During these periods, patients were evaluated by ultrasound to determine the thickness of subcutaneous adipose tissue and muscle of the upper and lower limbs. Postoperatively, these patients showed a reduction in the thickness of the upper and lower extremities muscle and adipose tissue as compared to their preoperative values. There was a significant difference in the loss of muscle thickness in all postoperative months and in the thickness of fatty tissue in the sixth month after surgery, compared to the preoperative muscle and fatty tissue thickness. Ultrasound can be considered as the diagnostic method of choice when assessment of the fat and lean body mass is required in morbidly obese patients before and after bariatric surgery.

Effects of excess body mass on strength and fatigability of quadriceps in postmenopausal women

Objective: Obesity is a major public health problem leading to, among other things, reduced functional capacity. Moreover, obesity-related declines in functional capacity may be compounded by the detrimental consequences of menopause. The aim of this study was to understand the potential effects of excess body mass on measures of functional capacity in postmenopausal women. Methods: Forty-five postmenopausal women aged 50 to 60 years were divided into two groups according to body mass index (BMI): obese (BMI, >= 30 kg/m(2); n = 19) and nonobese (BMI, 18.5-29.9 kg/m(2); n = 26). To determine clinical characteristics, body composition, bone mineral density, and maximal exercise testing was performed, and a 3-day dietary record was estimated. To assess quadriceps function, isokinetic exercise testing at 60 degrees per second (quadriceps strength) and at 300 degrees per second (quadriceps fatigue) was performed. Results: The absolute value of the peak torque was not significantly different between the groups; however, when the data were normalized by body mass and lean mass, significantly lower values were observed for obese women compared with those in the nonobese group (128% +/- 25% vs 155% +/- 24% and 224% +/- 38% vs 257% +/- 47%, P < 0.05). The fatigue index did not show any significant difference for either group; however, when the data were normalized by the body mass and lean mass, significantly lower values were observed for obese women (69% +/- 16% vs 93% +/- 18% and 120% +/- 25% vs. 135% +/- 23%, P < 0.01). Conclusions: Our results show that despite reduced muscle force, the combination of obesity and postmenopause may be associated with greater resistance to muscle fatigue.

Androgen receptor gene polymorphisms lean mass and performance in young men

[EN] The exon-1 of the androgen receptor (AR) gene contains two repeat length polymorphisms which modify either the amount of AR protein inside the cell (GGN(n), polyglycine) or its transcriptional activity (CAG(n), polyglutamine). Shorter CAG and/or GGN repeats provide stronger androgen signalling and vice versa. To test the hypothesis that CAG and GGN repeat AR polymorphisms affect muscle mass and various variables of muscular strength phenotype traits, the length of CAG and GGN repeats was determined by PCR and fragment analysis and confirmed by DNA sequencing of selected samples in 282 men (28.6 +/- 7.6 years). Individuals were grouped as CAG short (CAG(S)) if harbouring repeat lengths of 21. GGN was considered short (GGN(S)) or long (GGN(L)) if GGN 23, respectively. No significant differences in lean body mass or fitness were observed between the CAG(S) and CAG(L) groups, or between GGN(S) and GGN(L) groups, but a trend for a correlation was found for the GGN repeat and lean mass of the extremities (r=-0.11, p=0.06). In summary, the lengths of CAG and GGN repeat of the AR gene do not appear to influence lean mass or fitness in young men.

Effects of deflazacort versus prednisone on bone mass, body composition, and lipid profile: a randomized, double blind study in kidney transplant patients

To compare the effects of deflazacort (DEFLA) vs. prednisone (PRED) on bone mineral density (BMD), body composition, and lipids, 24 patients with end-stage renal disease were randomized in a double blind design and followed 78 weeks after kidney transplantation. BMD and body composition were assessed using dual energy x-ray absorptiometry. Seventeen patients completed the study. Glucocorticosteroid doses, cyclosporine levels, rejection episodes, and drop-out rates were similar in both groups. Lumbar BMD decreased more in PRED than in DEFLA (P < 0.05), the difference being particularly marked after 24 weeks (9.1 +/- 1.8% vs. 3.0 +/- 2.4%, respectively). Hip BMD decreased from baseline in both groups (P < 0.01), without intergroup differences. Whole body BMD decreased from baseline in PRED (P < 0.001), but not in DEFLA. Lean body mass decreased by approximately 2.5 kg in both groups after 6-12 weeks (P < 0.001), then remained stable. Fat mass increased more (P < 0.01) in PRED than in DEFLA (7.1 +/- 1.8 vs. 3.5 +/- 1.4 kg). Larger increases in total cholesterol (P < 0.03), low density lipoprotein cholesterol (P < 0.01), lipoprotein B2 (P < 0.03), and triglycerides (P = 0.054) were observed in PRED than in DEFLA. In conclusion, using DEFLA instead of PRED in kidney transplant patients is associated with decreased loss of total skeleton and lumbar spine BMD, but does not alter bone loss at the upper femur. DEFLA also helps to prevent fat accumulation and worsening of the lipid profile.

Does cigarette smoking modify the association between change in body mass index during young adulthood and risk of coronary mortality during middle-age in men? Twenty-five year follow-up results from the Chicago Western Electric Study

Many persons in the U.S. gain weight during young adulthood, and the prevalence of obesity has been increasing among young adults. Although obesity and physical inactivity are generally recognized as risk factors for coronary heart disease (CHD), the magnitude of their effect on risk may have been seriously underestimated due to failure to adequately handle the problem of cigarette smoking. Since cigarette smoking causes weight loss, physically inactive cigarette smokers may remain relatively lean because they smoke cigarettes. We hypothesize cigarette smoking modifies the association between weight gain during young adulthood and risk of coronary heart disease during middle age, and that the true effect of weight gain during young adulthood on risk of CHD can be assessed only in persons who have not smoked cigarettes. Specifically, we hypothesize that weight gain during young adulthood is positively associated with risk of CHD during middle-age in nonsmokers but that the association is much smaller or absent entirely among cigarette smokers. The purpose of this study was to test this hypothesis. The population for analysis was comprised of 1,934 middle-aged, employed men whose average age at the baseline examination was 48.7 years. Information collected at the baseline examinations in 1958 and 1959 included recalled weight at age 20, present weight, height, smoking status, and other CHD risk factors. To decrease the effect of intraindividual variation, the mean values of the 1958 and 1959 baseline examinations were used in analyses. Change in body mass index ($\Delta$BMI) during young adulthood was the primary exposure variable and was measured as BMI at baseline (kg/m$\sp2)$ minus BMI at age 20 (kg/m$\sp2).$ Proportional hazards regression analysis was used to generate relative risks of CHD mortality by category of $\Delta$BMI and cigarette smoking status after adjustment for age, family history of CVD, major organ system disease, BMI at age 20, and number of cigarettes smoked per day. Adjustment was not performed for systolic blood pressure or total serum cholesterol as these were regarded as intervening variables. Vital status was known for all men on the 25th anniversary of their baseline examinations. 705 deaths (including 319 CHD deaths) occurred over 40,136 person-years of experience. $\Delta$BMI was positively associated with risk of CHD mortality in never-smokers, but not in ever-smokers (p for interaction = 0.067). For never-smokers with $\Delta$BMI of stable, low gain, moderate gain, and high gain, adjusted relative risks were 1.00, 1.62, 1.61, and 2.78, respectively (p for trend = 0.010). For ever-smokers, with $\Delta$BMI of stable, low gain, moderate gain, and high gain, adjusted relative risks were 1.00, 0.74, 1.07, and 1.06, respectively (p for trend = 0.422). These results support the research hypothesis that cigarette smoking modifies the association between weight gain and CHD mortality. Current estimates of the magnitude of effect of obesity and physical inactivity on risk of coronary mortality may have been seriously underestimated due to inadequate handling of cigarette smoking. ^

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10(-5), Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10(-06)/Pfemales: 3.45 × 10(-07)/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation.