There is limited insight into the mechanisms, progression, and related comorbidities of obesity through simple modeling tools such as linear regression. Keeping in mind the words of the late George E. P. Box that “all models are wrong, some are useful,” this symposium presented 4 useful mathematical models or methodologic refinements. Presenters placed specific emphasis on how these novel models and methodologies can be applied to further our knowledge of the etiology of obesity.
Energy intake (EI) and physical activity energy expenditure (PAEE) are key modifiable determinants of energy balance, traditionally assessed by self-report despite its repeated demonstration of considerable inaccuracies. We argue here that it is time to move from the common view that self-reports of EI and PAEE are imperfect, but nevertheless deserving of use, to a view commensurate with the evidence that self-reports of EI and PAEE are so poor that they are wholly unacceptable for scientific research on EI and PAEE. While new strategies for objectively determining energy balance are in their infancy, it is unacceptable to use decidedly inaccurate instruments, which may misguide health care policies, future research, and clinical judgment. The scientific and medical communities should discontinue reliance on self-reported EI and PAEE. Researchers and sponsors should develop objective measures of energy balance.
The objective of this study was to examine the role of body mass and subcutaneous fat in injury severity and pattern sustained by overweight drivers. Finite element models were created to represent the geometry and properties of subcutaneous adipose tissue in the torso with data obtained from reconstructed magnetic resonance imaging datasets. The torso adipose tissue models were then integrated into the standard multibody dummy models together with increased inertial parameters and sizes of the limbs to represent overweight occupants. Frontal crash simulations were performed considering a variety of occupant restraint systems and regional body injuries were measured. The results revealed that differences in body mass and fat distribution have an impact on injury severity and pattern. Even though the torso adipose tissue of overweight subjects contributed to reduce abdominal injury, the momentum effect of a greater body mass of overweight subjects was more dominant over the cushion effect of the adipose tissue, increasing risk of other regional body injuries except abdomen. Through statistical analysis of the results, strong correlations (p < 0.01) were found between body mass index and regional body injuries except neck injury. The analysis also revealed that a greater momentum of overweight males leads to greater forward torso and pelvic excursions that account for higher risks (p < 0.001) of head, thorax, and lower extremity injury than observed in non-overweight males. The findings have important implications for improving the vehicle and occupant safety systems designed for the increasing global obese population.
Overweight; Crash injury; Modeling; Cushion effect; Momentum effect
Excess adiposity is the main phenotypic feature that defines human obesity and that plays a pathophysiological role in most chronic diseases. Measuring the amount of fat mass present is thus a central aspect of studying obesity at the individual and population levels. Nevertheless, a consensus is lacking among investigators on a single accepted “reference” approach for quantifying fat mass in vivo. While the research community generally relies on the multicomponent body-volume class of “reference” models for quantifying fat mass, no definable guide discerns among different applied equations for partitioning the four (fat, water, protein, and mineral mass) or more quantified components, standardizes “adjustment” or measurement system approaches for model-required labeled water dilution volumes and bone mineral mass estimates, or firmly establishes the body temperature at which model physical properties are assumed. The resulting differing reference strategies for quantifying body composition in vivo leads to small but under some circumstances important differences in the amount of measured body fat. Recent technological advances highlight opportunities to expand model applications to new subject groups and measured components such as total body protein. The current report reviews the historical evolution of multicomponent body volume-based methods in the context of prevailing uncertainties and future potential.
Nutritional Assessment; Underwater Weighing; Dual-Energy X-Ray Absorptiometry; Isotope Dilution; Obesity; Total Body Fat
Obesity; Diet; Mathematical Model; Body Composition; Weight Loss; Energy Balance
Childhood obesity remains a substantial health concern for our population and thoughtful attempts to develop and evaluate the utility of programs to reduce childhood obesity levels are needed. Unfortunately, we believe the conclusion by Burke et al. that the HealthMPowers program produces positive change in body composition is incorrect because the results obtained are likely due to regression to the mean (RTM), a well-known threat to the validity of studies that is often overlooked. Using empirical data, we demonstrate that RTM is likely to be the cause for the changes reported. A more reasonable conclusion than the one of effectiveness the authors offered would be that the results did not support the effectiveness of the intervention. Public health officials, parents, school leaders, community leaders, and regulators need and deserve valid evidence free from spin on which they can base decisions.
Pediatricians are encountering body composition information more frequently, with percentage of body fat (%BF) measurement receiving particular attention as a result of the obesity epidemic. One confounding issue is that different methods may yield different %BF results in the same person. The objective of this study was to compare dual-energy X-ray absorptiometry (DXA) with the criterion 4-compartment model (4-CM) for measurement of %BF in a large pediatric cohort and to assist pediatricians in appropriate interpretation of body composition information by recognizing differences between techniques.
Height, weight, anthropometrics, body density by underwater weighing, total body water by deuterium dilution, and bone mineral content and %BF by DXA (Lunar DPX/DPX-L) were measured in 411 healthy subjects, aged 6 to 18 years. Values for %BF by 4-CM and DXA were compared using regression analysis.
The mean ± standard deviation values for %BF by DXA (22.73% ± 11.23%) and by 4-CM (21.72% ± 9.42%) were different, but there was a strong relationship between the 2 methods (R2 = 0.85). DXA underestimated %BF in subjects with lower %BF and overestimated it in those with higher %BF. The relationship between the 2 methods was not affected by gender, age, ethnicity, pubertal stage, height, weight, or body mass index. The standard error of the estimate was 3.66%.
This analysis demonstrates a predictable relationship between DXA and 4-CM for %BF measurement. Because of its ease of use, consistent relationship with 4-CM, and availability, we propose that DXA has the capacity for clinical application including prediction of metabolic abnormalities associated with excess %BF in pediatrics.
body composition; percentage of body fat; obesity; pediatrics; children; adolescents; 4-compartment model; DXA
Depression has been found to predict the incidence of hypertension and other adverse cardiovascular events in prospective studies. Insomnia and short sleep duration, which are typical symptoms of depression, have also been shown to increase the risk for hypertension incidence. Insomnia is associated with increased activation of the hypothalamic–pituitary–adrenal axis, and short sleep duration raises average 24-h blood pressure, which over time could lead to structural adaptations that gradually reset the entire cardiovascular system to operate at an elevated pressure equilibrium. No previous published population studies have examined whether insomnia and sleep duration mediate the relationship between depression and hypertension incidence.
We conducted multivariate longitudinal (1982–1992) analyses stratified by age of the First National Health and Nutrition Examination Survey (NHANES I) (n = 4,913) using Cox proportional hazards models.
Middle-aged subjects who suffered from depression at baseline were 44% more likely to be diagnosed with hypertension over the follow-up period after controlling for covariates (hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.15–1.80). Both short sleep duration and insomnia were also significantly associated with hypertension incidence. Consistent with insomnia and sleep duration acting as mediators of the relationship between depression and hypertension incidence, the inclusion of these variables in the multivariate models appreciably attenuated the association (HR = 1.27, 95% CI 1.00–1.61). Depression, sleep duration, and insomnia were not significantly associated with hypertension incidence in elderly subjects.
These results suggest the hypothesis that treatment of sleep problems in middle-aged individuals suffering from depression could reduce their risk for developing hypertension, and its vascular and cardiac complications.
blood pressure; depression; essential hypertension; hypertension; insomnia; sleep
Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI.
MRI; Growth effects; Androstenedione; 4-Androsdiol; Bolandiol; 19-Noradrostenedione
Maximizing fat loss while preserving lean tissue mass and function is a central goal of modern obesity treatments. A widely cited rule guiding expected loss of lean tissue as fat-free mass (FFM) states that approximately one-fourth of weight loss will be FFM (i.e., ΔFFM/ΔWeight = ~0.25) with the remaining three-fourths fat mass. This review examines the dynamic relations between FFM, fat mass, and weight changes that follow induction of negative energy balance with hypocaloric dieting and/or exercise. Historical developments in the field are traced with the “Quarter FFM Rule” used as a framework to examine evolving concepts on obesity tissue, excess weight, and what is often cited as “Forbes’ Rule”. Temporal effects in the fractional contribution of FFM to changes in body weight are examined as are lean tissue moderating effects such as aging, inactivity, and exercise that frequently accompany structured low-calorie diet weight loss protocols. Losses of lean tissue with dieting typically tend to be small, raising questions about study design, power, and applied measurement method reliability. Our review elicits important questions related to the fractional loss of lean tissues with dieting and provides a foundation for future research on this topic.
Body Composition; Obesity; Mathematical Model; Energy Expenditure; Exercise
Body composition refers to the amount of fat and lean tissues in our body; it is a science that looks beyond a unit of body weight, accounting for the proportion of different tissues and its relationship to health. Although body weight and body mass index are well-known indexes of health status, most researchers agree that they are rather inaccurate measures, especially for elderly individuals and those patients with specific clinical conditions. The emerging use of imaging techniques such as dual energy x-ray absorptiometry, computerized tomography, magnetic resonance imaging, and ultrasound imaging in the clinical setting have highlighted the importance of lean soft tissue (LST) as an independent predictor of morbidity and mortality. It is clear from emerging studies that body composition health will be vital in treatment decisions, prognostic outcomes, and quality of life in several nonclinical and clinical states. This review explores the methodologies and the emerging value of imaging techniques in the assessment of body composition, focusing on the value of LST to predict nutrition status.
body composition; lean body mass; lean soft tissue; imaging; nutrition status; DXA; CT; MRI; ultrasound; sarcopenia; sarcopenic obesity; osteosarcopenic obesity
Despite theoretical evidence that the model commonly referred to as the 3500 kcal rule grossly overestimates actual weight loss, widespread application of the 3500 kcal formula continues to appear in textbooks, on respected government and health related websites, and scientific research publications. Here we demonstrate the risk of applying the 3500 kcal rule even as a convenient estimate by comparing predicted against actual weight loss in seven weight loss experiments conducted in confinement under total supervision or objectively measured energy intake. We offer three newly developed, downloadable applications housed in Microsoft® Excel and Java which simulates a rigorously validated, dynamic model of weight change. The first two tools available at www.pbrc.edu/sswcp, provide a convenient alternative method for providing patients with projected weight loss/gain estimates in response to changes in dietary intake. The second tool which can be downloaded from the URL, www.pbrc.edu/mswcp, projects estimated weight loss simultaneously for multiple subjects. This tool was developed to inform weight change experimental design and analysis. While complex dynamic models may not be directly tractable, the newly developed tools offer the opportunity to deliver dynamic model predictions as a convenient and significantly more accurate alternative to the 3500 kcal rule.
3500 kcal Rule; Wishnofsky’s Rule; Dynamic Model; Energy Balance; First Law of Thermodynamics
Diabetes confers a very high risk of lower-extremity amputation (LEA); however, few studies have assessed whether blood glucose control can reduce LEA risk among patients with diabetes, especially in practice settings where low-income patients predominate.
RESEARCH DESIGN AND METHODS
We performed a prospective cohort study (2000–2009) on patients with diabetes that included 19,808 African Americans and 15,560 whites. The cohort was followed though 31 May 2012. Cox proportional hazards regression models were used to estimate the association of HbA1c with LEA risk.
During a mean follow-up of 6.83 years, 578 LEA incident cases were identified. The multivariable-adjusted hazard ratios of LEA associated with different levels of HbA1c at baseline (<6.0% [reference group], 6.0–6.9, 7.0–7.9, 8.0–8.9, 9.0–9.9, and ≥10.0%) were 1.00, 1.73 (95% CI 1.07–2.80), 1.65 (0.99–2.77), 1.96 (1.14–3.36), 3.02 (1.81–5.04), and 3.30 (2.10–5.20) (P trend <0.001) for African American patients with diabetes and 1.00, 1.16 (0.66–2.02), 2.28 (1.35–3.85), 2.38 (1.36–4.18), 2.99 (1.71–5.22), and 3.25 (1.98–5.33) (P trend <0.001) for white patients with diabetes, respectively. The graded positive association of HbA1c during follow-up with LEA risk was observed among both African American and white patients with diabetes (all P trend <0.001). With stratification by sex, age, smoking status, blood pressure, LDL cholesterol, BMI, use of glucose-lowering agents, and income, this graded association of HbA1c with LEA was still present.
The current study conducted in a low-income population suggests a graded association between HbA1c and the risk of LEA among both African American and white patients with type 2 diabetes.
Albumin and prealbumin are associated with nutritional status and inflammatory status. Each has a residual effect on mortality outcomes when included in regression models that include the other. Prealbumin is increased in the obese mouse model as a consequence of stabilization of prealbumin by Retinol Binding Protein 4 (RTB4), secreted by adipocytes. We carried out this study to establish the contribution of adiposity to prealbumin levels in prevalent dialysis patients and the relationship of prealbumin to RTB4.
We determined whether prealbumin was associated with adiposity in hemodialysis (HD) patients, controlling for the effects of inflammation and nutrition.
Subjects and Methods
We evaluated body composition in 48 prevalent HD patients by magnetic resonance imaging (MRI), measuring total skeletal muscle mass (SM), visceral and subcutaneous adipose tissue (VAT and SAT), and serum albumin, prealbumin, RTB4, and interleukin-6 (IL-6). We used normalized protein catabolic rate (nPCR) to report nutrition and separately analyzed the determinants of albumin and then of prealbumin by multiple stepwise regression.
Thirty two subjects were women, 16 were diabetic, median age and body mass index 54.5 and 27.3 kg/m2, respectively; median TAT 24.3 kg and VAT and 3.25 kg, respectively. Prealbumin was positively associated with VAT, nPCR and RTB4, and negatively associated with IL-6; r2 for the model 0.64. By contrast albumin was positively associated with nPCR and negatively with IL-6 but not with any measure of adiposity (r2 for the model = 0.2).
Prealbumin, like albumin, is associated with markers of nutrition (nPCR) and inflammation, but unlike albumin, prealbumin levels are positively associated with visceral adiposity.
Prealbumin; Visceral Adipose Tissue; Retinol-Binding Protein 4; Interleukin-6; Inflammation; Hemodialysis
Blood pressure control can reduce the risk of coronary heart disease (CHD) among diabetic patients; however, it is not known whether the lowest risk of CHD is among diabetic patients with the lowest blood pressure level.
RESEARCH DESIGN AND METHODS
We performed a prospective cohort study (2000–2009) on diabetic patients including 17,536 African Americans and 12,618 whites. Cox proportional hazards regression models were used to estimate the association of blood pressure with CHD risk.
During a mean follow-up of 6.0 years, 7,260 CHD incident cases were identified. The multivariable-adjusted hazard ratios of CHD associated with different levels of systolic/diastolic blood pressure at baseline (<110/65, 110–119/65–69, 120–129/70–80, and 130–139/80–90 mmHg [reference group]; 140–159/90–100; and ≥160/100 mmHg) were 1.73, 1.16, 1.04, 1.00, 1.06, and 1.11 (P trend <0.001), respectively, for African American diabetic patients, and 1.60, 1.27, 1.08, 1.00, 0.95, and 0.99 (P trend<0.001) for white diabetic patients, respectively. A U-shaped association of isolated systolic and diastolic blood pressure at baseline as well as blood pressure during follow-up with CHD risk was observed among both African American and white diabetic patients (all Ptrend <0.001). The U-shaped association was present in the younger age-group (30–49 years), and this U-shaped association changed to an inverse association in the older age-group (≥60 years).
Our study suggests that there is a U-shaped or inverse association between blood pressure and the risk of CHD, and aggressive blood pressure control (blood pressure <120/70 mmHg) is associated with an increased risk of CHD among both African American and white patients with diabetes.
Hyperphagia is a central feature of inherited disorders (e.g., Prader–Willi Syndrome) in which obesity is a primary phenotypic component. Hyperphagia may also contribute to obesity as observed in the general population, thus raising the potential importance of common underlying mechanisms and treatments. Substantial gaps in understanding the molecular basis of inherited hyperphagia syndromes are present as are a lack of mechanistic of mechanistic targets that can serve as a basis for pharmacologic and behavioral treatments.
Design and Methods
International conference with 28 experts, including scientists and caregivers, providing presentations, panel discussions, and debates.
The reviewed collective research and clinical experience provides a critical body of new and novel information on hyperphagia at levels ranging from molecular to population. Gaps in understanding and tools needed for additional research were identified.
This report documents the full scope of important topics reviewed at a comprehensive international meeting devoted to the topic of hyperphagia and identifies key areas for future funding and research.
The objective was to evaluate the effectiveness of belt-positioning booster seats, compared with no restraint use and with seat belt use only, during motor vehicle crashes among U.S. children.
This was a retrospective matched cohort study with data from the 1998 through 2009 National Automotive Sampling System (NASS) Crashworthiness Data System (CDS). The study sample consisted of children aged 0 to 10 years who were not seated in the front seat of the vehicle. We used Cox proportional hazards models to estimate the risk of overall, fatal, and regional body injury.
Children using seat belts in belt-positioning booster seats experienced less overall injury (Injury Severity Score [ISS] > 0, adjusted risk ratio [RR] = 0.73, 95% confidence interval [CI] = 0.55 to 0.96; Abbreviated Injury Scale [AIS] score of 2 or higher, adjusted RR = 0.30, 95% CI = 0.16 to 0.58; ISS > 8, adjusted RR = 0.19, 95% CI = 0.06 to 0.56), and less injury in most body regions except the neck (adjusted RR = 4.79, 95% CI = 1.43 to 16.00) than did children with no restraint use. Children using seat belts in belt-positioning booster seats had an equal risk of injury but higher risks of neck (adjusted RR = 1.86, 95% CI = 1.02 to 3.40) and thorax (adjusted RR = 2.86, 95% CI = 1.33 to 6.15) injury than did children restrained by seat belts only.
Children using belt-positioning booster seats appear to experience a higher risk of AIS > 0 injury to the neck and thorax than do children using seat belts only. Future research should examine whether the observed increase in neck and thorax injuries can be attributed to improper use of booster seats.
Obesity prevalence in the United States (US) appears to be leveling, but the reasons behind the plateau remain unknown. Mechanistic insights can be provided from a mathematical model. The objective of this study is to model known multiple population parameters associated with changes in body mass index (BMI) classes and to establish conditions under which obesity prevalence will plateau.
Design and Methods
A differential equation system was developed that predicts population-wide obesity prevalence trends. The model considers both social and non-social influences on weight gain, incorporates other known parameters affecting obesity trends, and allows for country specific population growth.
The dynamic model predicts that: obesity prevalence is a function of birth rate and the probability of being born in an obesogenic environment; obesity prevalence will plateau independent of current prevention strategies; and the US prevalence of obesity, overweight, and extreme obesity will plateau by about 2030 at 28%, 32%, and 9%, respectively.
The US prevalence of obesity is stabilizing and will plateau, independent of current preventative strategies. This trend has important implications in accurately evaluating the impact of various anti-obesity strategies aimed at reducing obesity prevalence.
Mathematical model; differential equation; infectious disease model; obesity prevalence
Heritability estimates of human body fatness vary widely and the contribution of body composition methodology to this variability is unknown. The effect of body composition methodology on estimations of genetic and environmental contributions to body fatness variation was examined in 78 adult male and female monozygotic twin pairs reared apart or together. Body composition was assessed by six methods – body mass index (BMI), dual energy x-ray absorptiometry (DXA), underwater weighing (UWW), total body water (TBW), bioelectric impedance (BIA), and skinfold thickness. Body fatness was expressed as percent body fat, fat mass, and fat mass/height2 to assess the effect of body fatness expression on heritability estimates. Model-fitting multivariate analyses were used to assess the genetic and environmental components of variance. Mean BMI was 24.5 kg/m2 (range of 17.8–43.4 kg/m2). There was a significant effect of body composition methodology (p<0.001) on heritability estimates, with UWW giving the highest estimate (69%) and BIA giving the lowest estimate (47%) for fat mass/height2. Expression of body fatness as percent body fat resulted in significantly higher heritability estimates (on average 10.3% higher) compared to expression as fat mass/height2 (p=0.015). DXA and TBW methods expressing body fatness as fat mass/height2 gave the least biased heritability assessments, based on the small contribution of specific genetic factors to their genetic variance. A model combining DXA and TBW methods resulted in a relatively low FM/ht2 heritability estimate of 60%, and significant contributions of common and unique environmental factors (22% and 18%, respectively). The body fatness heritability estimate of 60% indicates a smaller contribution of genetic variance to total variance than many previous studies using less powerful research designs have indicated. The results also highlight the importance of environmental factors and possibly genotype by environmental interactions in the etiology of weight gain and the obesity epidemic.
body composition; adiposity; twins; heritability; genetics
Data suggest that a diet deficient in calcium is associated with higher body weight and that augmenting calcium intake may reduce weight and fat gain or enhance loss. Our aim was to determine whether calcium supplementation during a weight loss intervention affects body fat or weight loss. Data were combined from three separate 25-wk randomized, double blind, placebo-controlled trials of 1000 mg/d calcium supplementation in 100 premenopausal and postmenopausal women. The primary outcome measures were change in body weight and fat mass adjusted for baseline values.
There were no significant differences in body weight or fat mass change between the placebo and the calcium-supplemented groups in the pooled analysis (adjusted mean ± SE; body weight, placebo –6.2 ± 0.7 vs. Ca –7.0 ± 0.7 kg; fat mass, placebo –4.5 ± 0.6 vs. Ca –5.5 ± 0.6 kg), and no significant interactions of calcium supplementation with menopausal/diet status. Analysis as separate trials also found no significant differences between the placebo and the calcium groups. Calcium supplementation did not significantly affect amount of weight or fat lost by women counseled to follow a moderately restricted diet for 25 wk. Nevertheless, the magnitude and direction of the differences for group means are consistent with a hypothesized small effect.
Computed tomography and magnetic resonance imaging are currently used to measure abdominal visceral adipose tissue (VAT) in humans; however, more widely available and less costly dual-energy x-ray absorptiometry (DXA) also has the potential to measure VAT.
The purpose of this study was to determine reproducibility and clinical thresholds for DXA-derived VAT.
Design and Methods
The sample included 2317 white and African American adults 18–74 years of age. VAT areas (cm2) were measured using a Hologic DXA scanner equipped with APEX 4.0 software. Reproducibility was assessed using repeated measurements on 101 participants scanned 14 days apart. Receiver Operating Characteristic (ROC) curves were used to assess clinical utility and select thresholds that identified elevated cardiometabolic risk, defined as the presence of ≥2 risk factors.
Reproducibility of DXA-VAT was 8.1%. The areas under the ROC curves ranged from 0.754 in African American men to 0.807 in white women. The thresholds were higher in white men (154 cm2) and women (143 cm2) compared to African American men (101 cm2) and women (114 cm2).
The results demonstrate that DXA VAT is a useful clinical marker of cardiometabolic risk; however, further research is required to determine associations with health outcomes using longitudinal studies.
imaging; abdominal obesity; ethnicity; race differences; risk factors