Increased Body Fat Percentage Research Articles

248: Does modality of treatment affect percentage body fat in neonates of women with gestational diabetes?

Good glycemic control of women with gestational diabetes (GDM) is associated with a decreased risk of excessive fetal growth. Medical therapy with glyburide or insulin is added when diet alone fails to achieve goals of glycemic control. The purpose of this study was to test the hypothesis that requiring medical therapy (vs. diet alone) for control of GDM is associated with increased percentage body fat (%fat) in the neonate.

Effect of Obesity and Renal Insufficiency On Toxicity of High-Dose Melphalan for Multiple Myeloma.

Abstract 1177Poster Board I-199 BACKGROUND:High dose melphalan followed by an autologous peripheral blood stem cell transplant (ASCT) is standard initial therapy for multiple myeloma (MM). However, toxicity and efficacy of this treatment are variable, with the sources of variability being poorly understood. We hypothesized that obesity and renal insufficiency modulate the pharmacokinetics of melphalan and therefore impact treatment toxicity. METHODS:We evaluated 39 patients with MM undergoing high-dose melphalan followed by ASCT. Patients received melphalan on day -2 at a dose of 200 mg/m2 (one patient with poor renal function received 180 mg/m2) and ASCT on day 0. We assessed body composition using dual energy x-ray absorptiometry (DEXA) and renal function using 24 hour urine creatinine clearance. We assessed toxicity on day +7 using the Oral Mucositis Assessment Scale (OMAS), a physician evaluated measurement of erythema and ulceration (on a scale of 0-5, with higher scores indicating worse mucositis). We also assessed patient reported symptom scores for mouth and throat soreness using the Mucositis Daily Questionnaire (MDQ) periodically during the first month (on a scale of 0-10, with higher scores indicating worse soreness). RESULTS:The median age was 55 years (range 37-70). 59% were male. The median weight was 83 kg (48-128), with median percentage body fat as measured by DEXA of 31% (range 15–53), and the median glomerular filtration rate (GFR) was 105 ml/min (range 28-194). Results from univariate and multivariate analyses are shown in the table below. In univariate analyses, we observed a weak and statistically insignificant direct correlation between percent body fat and toxicity (as measured by OMAS score or peak soreness), and a weak and statistically significant indirect correlation between GFR and OMAS score. In a multi-variable linear regression model including percent body fat, weight, GFR, and actual melphalan dose, we observed a correlation between OMAS score and percent body fat, with an increase in body fat percentage of 0.10 associated with a 0.65 unit increase in OMAS score (p=0.01). In a similar multi-variable model, we observed a correlation between MDQ soreness score and percent body fat, with an increase in body fat percentage of 0.10 associated with a 2.07 increase in MDQ soreness score (p=0.05).Univariable modelMultivariable modelChange in OMAS scorepChange in OMAS scorep% body fat (per 10 percentage points)0.230.130.650.01GFR (per 10 ml/min)−0.080.02−0.060.09Weight (per 10 kg)−0.010.14−0.030.02Melphalan Actual Dose (per 10 mg)−0.060.100.010.08Change in peak soreness scorepChange in peak soreness scorep% body fat (per 10 percentage points)0.760.262.070.05GFR (per 10 ml/min)−0.030.860.030.89Weight (per 10 kg)−0.130.68−1.100.10Melphalan Actual Dose (per 10 mg)−0.050.750.380.19 CONCLUSION:More obese patients, as measured by percent body fat, have more severe oral mucositis after high dose melphalan, independent of melphalan dose, weight, and renal function. We are measuring melphalan pharmacokinetics in this group of patients, and further research should help guide rational chemotherapy dosing for this highly effective treatment. Disclosures:No relevant conflicts of interest to declare.

Predictors of the early introduction of solid foods in infants: results of a cohort study.

BackgroundThe early introduction of solid foods before 4 months of age has been associated with an increased risk of diarrhoea in infancy and a greater risk of wheeze and increased percentage body fat and weight in childhood. The purpose of this study was to identify the level of compliance with national recommendations related to the timing of the introduction of solid foods and to describe the maternal and infant characteristics associated with the timing of the introduction of solids.MethodsSubjects were 519 participants in the second longitudinal Perth Infant Feeding Study (PIFS II) recruited from two maternity hospitals in Perth, Western Australia in 2002/3. Data collected prior to, or shortly after discharge from hospital, and at 4, 10, 16, 22, 32, 40 and 52 weeks postpartum included timing of the introduction of solid foods and a variety of maternal and infant characteristics associated with the introduction of solid foods. Multivariate logistic regression was used to identify those factors associated with the risk of introducing solid foods early, which for the purposes of this study was defined as being before 17 weeks.ResultsThe median age of introduction of solid foods was 17.6 weeks. In total, 44% of infants had received solids before 17 weeks and 93% of infants had received their first solids before 26 weeks of age. The strongest independent predictors of the early introduction of solids were young maternal age, mother smoking prior to pregnancy and not fully breastfeeding at 4 weeks postpartum. In general, mothers introduced solids earlier than recommended because they perceived their baby to either need them or be ready for them.ConclusionThis study showed a high level of non-compliance among Australian mothers with the infant feeding recommendation related to the timing of solids that was current at the time. In order to improve compliance health professionals need to be aware of those groups least likely to comply with recommendations and their reasons for non-compliance. Infant feeding recommendations need to be evidence-based, uniformly supported by professionals and widely, clearly and consistently articulated if higher rates of compliance are to be achieved in the future.

The association of adiposity with parathyroid hormone in healthy older adults.

Elevated parathyroid hormone (PTH) is a risk factor for increased morbidity and mortality. PTH levels increase with adiposity in older adults but the basis for this association is unclear. The objective of this study was to examine the association of percent body fat (%Fat) with serum PTH in 307 older men and women and to determine the extent to which it may be explained by vitamin D status, bone turnover, calcium metabolism, and glucose homeostasis. The data are from the baseline visit of a clinical trial of calcium and vitamin D to prevent bone loss. %Fat was measured by dual-energy X-ray absorptiometry and fasting blood and urine samples were collected. Serum PTH levels increased by about 0.4 pmol/l per 10 unit increase in percent body fat (P = 0.003). The variables that we examined, including plasma 25-hydroxyvitamin D and serum osteocalcin, calcium, phosphorus, and insulin explained only a small proportion of this association (18%). Further work is needed to identify the mediators of the higher PTH levels in subjects with greater adiposity. This is important in view of worldwide increases in overweight and obesity and the potential contribution of elevated PTH to morbidity and mortality.

Diet-induced obesity is associated with hyperleptinemia, hyperinsulinemia, hepatic steatosis, and glomerulopathy in C57Bl/6J mice

Obesity and obesity-related illnesses are global epidemics impacting the health of adults and children. The purpose of the present work is to evaluate a genetically intact obese mouse model that more accurately reflects the impact of aging on diet-induced obesity and type 2 diabetes in humans. Male C57Bl/6J mice consumed either a control diet or one in which 60% kcal were due to lard beginning at 5-6 weeks of age. Body weight and fat measurements were obtained and necropsy performed at 15, 20, 30, and 40 weeks of age. Serum chemistry, histopathology, gene expression of the liver, and renal and hepatic function were also evaluated. In concert with significant increases in percent body fat and weight, mice fed the high-fat versus control diet had significantly increased levels of serum cholesterol. At ages 20 and 30 weeks, serum glucose was significantly higher in obese versus controls, while serum insulin levels were >/=4-fold higher in obese mice at ages 30 and 40 weeks. The effect of age exacerbated the effects of consuming a high-fat diet. In addition to being hyperinsulinemic and leptin resistant, older obese mice exhibited elevated hepatic PAI-1 and downregulation of GLUT4, G6PC, IGFBP-1, and leptin receptor mRNA in the liver, steatosis with subsequent inflammation, glomerular mesangial proliferation, elevated serum ALT, AST, and BUN, and increased numbers of pancreatic islets.

Effects of Body Size and Body Fatness on Left Ventricular Mass in Children and Adolescents: Project HeartBeat!

Left ventricular mass (LVM) is a strong predictor of cardiovascular disease in adults. Available study findings on effects of body fatness on LVM in children are inconsistent. Understanding the impact of body fat on LVM in children may help prevent excessive LVM through measures to reduce overweight and obesity. Healthy children (n=678) aged 8, 11, and 14 years at baseline were examined at 4-month intervals for up to 4 years (1991-1995); 4608 valid measurements of LVM were obtained with M-mode echocardiography. A multilevel linear model was used for analysis. The impact of body size was examined by adding separately nine body-size indicators to a basic LVM-gender-age model. The impact of body fatness was tested by introducing four body-fatness indicators into the nine models, yielding 36 models. All body-size indicators showed strong, positive effects on LVM. In models containing weight or body surface area (measuring both fat-free and fat contributions to body size), additional effects of body fatness were negative; in models containing fat-free mass (FFM) or height (both measuring body size independent of body fat), increased body fatness was related to a significant increase in LVM. For example, in models with FFM as a body-size indicator, a 1-SD increase in percent body fat or fat mass was related to a 5.4- or 7.2-g increase in LVM, respectively. Effects of body size on LVM attributable to fat-free body mass can be distinguished from those attributable to fat body mass; both are independent, positive predictors, but the former is the stronger determinant. When a body-size indicator not independent of body fat is used as a predictor, effects of fat-free body mass and fat body mass are forced to relate to the same indicator; because their magnitudes are estimated to be equal, the effect of fat body mass is overestimated. Thus, when an additional body-fatness indicator is included in the prediction of LVM, the additional estimated effect related to the indicator appears to be negative.

Eliminating leptin signals to somatotropes reduces GH and fertility and causes obesity in adults

Leptin restores growth hormone (GH) in leptin‐deficient animals, suggesting a role in somatotrope maintenance. To determine leptin's importance to somatotropes, we ablated the leptin receptor (LEPR) selectively using targeted Cre‐recombinase in somatotropes of mice bearing two floxed alleles of LEPR exon 17, thereby removing the JAK binding site of LEPR‐b. We detected no early or extrapituitary expression of Cre‐Recombinase and 3 generations showed >95% viability. In adult males or females, the mutation reduced serum GH by 50‐84% and reduced % of pituitary cells bearing LEPR‐b or GH. For example, pituitary cells with LEPR‐b in males declined from 37 ± 1% (controls) to 20 ± 2% (heterozygotes) and 11 ± 1% (homozygotes) and GH cells in males were reduced from 26 ± 2% (controls) to 12 ± 1% or 7 ± 1% in F2 or F3 generation homozygotes, respectively. In spite of reduced GH, mutant mice grew normally. However, a 70% reduction in corpora lutea in F2 homozygotes correlated with a significant reduction in litter size. By 3‐4.5 months of age, homozygote males showed significant weight gains (30% over controls) and a 1.8‐fold increase in percent body fat by DEXA analysis. Females showed these changes by 6 months. Direct leptin signaling to somatotropes is thus important especially in functions related to maintaining GH, fertility and body composition. Supported by DK26687 (SC), and core facilities funded by P20 RR020146 and P30 NS047546.

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

Maternal obesity is thought to increase the offspring's risk of juvenile obesity and metabolic diseases; however, the mechanism(s) whereby excess maternal nutrition affects fetal development remain poorly understood. Here, we investigated in nonhuman primates the effect of chronic high-fat diet (HFD) on the development of fetal metabolic systems. We found that fetal offspring from both lean and obese mothers chronically consuming a HFD had a 3-fold increase in liver triglycerides (TGs). In addition, fetal offspring from HFD-fed mothers (O-HFD) showed increased evidence of hepatic oxidative stress early in the third trimester, consistent with the development of nonalcoholic fatty liver disease (NAFLD). O-HFD animals also exhibited elevated hepatic expression of gluconeogenic enzymes and transcription factors. Furthermore, fetal glycerol levels were 2-fold higher in O-HFD animals than in control fetal offspring and correlated with maternal levels. The increased fetal hepatic TG levels persisted at P180, concurrent with a 2-fold increase in percent body fat. Importantly, reversing the maternal HFD to a low-fat diet during a subsequent pregnancy improved fetal hepatic TG levels and partially normalized gluconeogenic enzyme expression, without changing maternal body weight. These results suggest that a developing fetus is highly vulnerable to excess lipids, independent of maternal diabetes and/or obesity, and that exposure to this may increase the risk of pediatric NAFLD.

Evaluation of effects of cassis (Ribes nigrum L.) juice on human vascular function and gene expression using a microarray system

Objective: Vascular function testing and microarray analysis were performed to evaluate the physical effects of cassis (Ribes nigrum L.) juice in women.Methods: In healthy women (Study I: n=21, age 53.6±3.6 years, BMI 24.2±3.9; Study II: n=40, age 47.4±8.8 years, BMI 22.4±3.9) assigned to one of four cassis groups (polysaccharide (PS) content: 0, 50, 125, and 250 mg) or a water control group (duration of intake: 2 to 8 weeks), the following parameters were assessed: for vascular function, blood pressure, thermographically measured body surface temperature, CAVI (cardio-ankle vascular index), ABI (ankle-brachial pressure index), accelerated plethysmography, and FMD (flow-mediated dilation) were determined. In the PS 250 mg (n=3) and water (n=4) groups, total RNA was extracted from blood collected before and 2 weeks after the study to perform gene expression analysis using Human Whole Genome 4 × 44K kit (Agilent).Results: Cassis juice (PS content: 125 to 250 mg) (n=16) increased body fat percentage (+2.5%, p=0.011), decreased systolic (121.3±15.8 mmHg at baseline, −4.8%, p=0.001) and diastolic blood pressure (76.9±11.2 mmHg at baseline, −5.9%, p=0.001), and increased FMD blood flow (p=0.004), upper limb temperature (+0.23±0.47ºC, p=0.011), and lower limb temperature (+0.55±0.50ºC, p‹0.001). The percentage increase in lower limb temperature was dependent on PS (p‹0.05) and polyphenol (p‹0.01) contents. In gene analysis, inhibition of expression of α-adrenoceptor ADRA1D and thromboxane A2 receptor TBXA2R was prominent. Pathway analysis revealed significant accumulation of less frequently expressed genes (CACNA1B, GJB3, etc.) in the “Ca regulation in the cardiac cell” pathway (p=0.006). No serious adverse events occurred during the study.Conclusion: Cassis juice induced limb peripheral vasodilatation, increase in blood flow, and decrease in blood pressure. The microarray analysis showed inhibited expression of genes of α-adrenoceptor, thromboxane A2 receptor and Ca channel, and an inhibited pathway of Ca influx into vascular smooth muscle. Couppled with the fact that vascular endothelium plays a role in vasodilatation associated with various mRNA expressions, it is suggested that cassis juice may improve the function of endothelial cells.

Comparison of Body Mass Index (BMI) Categories Based on Asian and Universal Standards and Language Spoken at Home among Asian American University Students

Background: The World Health Organization released lower Body Mass Index (BMI) cutoff points for Asian individuals to account for increased body fat percentage (BF%) and risk of obesity-related conditions at a lower body mass index. Purpose: This preliminary study: (1) explores the impact of utilizing Asian BMI standards (compared to universal standards) on the overweight/obese categorization of Asian females and males; and (2) determines whether age, gender, acculturation, and living arrangements are associated with BMI and BF%. Methods: Data on demographic variables, height and weight, BF%, living situation, and language spoken at home were collected from 170 Asian students enrolled in a health course at a public university in California. Results: When Asian BMI cutoffs were applied, categorization of Asian males and females as normal weight decreased significantly. Language spoken at home was not significantly associated with BMI; however, acculturated females tended to have higher BMIs than non-acculturated females, while acculturated males tended to have lower BMIs than non-acculturated males. Discussion: Utilization of Asian-specific BMI cutoffs will significantly increase the reported prevalence of overweight and obesity among Asians. Acculturation to the United States may be a risk factor for overweight/obesity especially among Asian females. Translation to Health Education Practice: Asian-specific BMI cutoffs may be appropriate in clinical settings, given that overweight-obesity related conditions occur at relatively lower rates of BMI and BF% among Asians.

Abstract 3558: Time of Day: A Vital Determinant in Diet-Induced Cardiometabolic Syndrome Development

Excess caloric intake is strongly associated with the development of obesity, type 2 diabetes mellitus, and cardiovascular disease (CVD). Research efforts have focused attention primarily on the quality (i.e., nutritional content) and/or quantity of calories as potential causes for diet-induced pathology. Little is known regarding how the timing of nutrient ingestion influences CVD development, despite growing acceptance that biological rhythms strongly affect cardiovascular physiology and pathophysiology. We therefore hypothesized that the time of day at which dietary fat is consumed profoundly influences the development of the cardiometabolic syndrome. Mice were initially fed either control or high fat diets (10% and 45% calories from fat, respectively) in an ad libitum fashion. As expected, 16 weeks ad libitum high fat feeding resulted in increased body weight gain (13%), increased percent body fat (23%), increased ventricular weight (11%), and myocardial contractile dysfunction (33% decrease in cardiac power, as assessed in ex vivo working mouse heart perfusions), relative to control mice (p<0.05). A separate set of mice were next fed only during the 12hr active/awake/dark phase, and were divided into early fat (EF) and late fat (LF) groups (access to high fat diet only during the first 4 hours versus the last 4 hours of the active phase, respectively; mice were allowed access to control diet for remaining active phase hours). LF feeding resulted in increased body weight gain, increased percent body fat, decreased glucose tolerance, decreased skeletal muscle oxidative capacity, induction of myocardial anf expression, and decreased cardiac power, relative to EF feeding, despite virtually identical quantity and quality of calories consumed (see Table ). These data reveal that the consumption of dietary lipids during the end of the active phase (i.e., dinner for humans) significantly contributes to diet-induced cardiometabolic syndrome development.

The association between sleep duration and obesity in older adults

BackgroundReduced sleep has been reported to predict obesity in children and young adults. However, studies based on self-report have been unable to identify an association in older populations. In this study, the cross-sectional associations between sleep duration measured objectively and measures of weight and body composition were assessed in two cohorts of older adults.MethodsWrist actigraphy was performed for a mean (SD) of 5.2 (0.9) nights in 3055 men (age: 67–96 years) participating in the Osteoporotic Fractures in Men Study (MrOS) and 4.1 (0.8) nights in 3052 women (age: 70–99 years) participating in the Study of Osteoporotic Fractures (SOF). A subgroup of 2862 men and 455 women also underwent polysomnography to measure sleep apnea severity.ResultsCompared to those sleeping an average of 7–8 hours per night, and after adjusting for multiple risk factors and medical conditions, a sleep duration of less than 5 hours was associated with a body mass index (BMI) that was on average 2.5 kg/m2 (95% CI: 2.0–2.9) greater in men and 1.8 kg/m2 (95%CI: 1.1–2.4) greater in women. The odds of obesity (BMI ≥ 30 kg/m2) was 3.7-fold greater (95% CI: 2.7–5.0) in men and 2.3-fold greater in women (95% CI: 1.6–3.1) who slept less than 5 hours. Short sleep was also associated with central body fat distribution and increased percent body fat. These associations persisted after adjusting for sleep apnea, insomnia, and daytime sleepiness.ConclusionsIn older men and women, actigraphy-ascertained reduced sleep durations are strongly associated with greater adiposity.

Longitudinal Changes in Insulin Sensitivity and Body Composition of Small-For-Gestational-Age Adolescents after Cessation of Growth Hormone Treatment

GH treatment reduces insulin sensitivity (Si). For small-for-gestational-age (SGA) subjects, who might have an increased risk to develop cardiovascular disease and type 2 diabetes, it is still uncertain how Si, beta-cell function, and body composition change over time after stopping GH treatment. Our objective was to investigate longitudinal changes in Si, beta-cell function, and body composition after cessation of long-term GH treatment. We conducted a longitudinal study that included 48 SGA adolescents studied at adult height, while still on GH, and 6 months after GH stop and compared them with 38 appropriate-for-gestational-age (AGA) controls at both time points. We took paired measurements of Si and beta-cell function, assessed by frequently sampled iv glucose tolerance tests with tolbutamide, and body composition, measured by dual-energy x-ray absorptiometry. After stopping GH, Si (P = 0.006), glucose effectiveness (Sg; P = 0.009) and beta-cell function (disposition index; P = 0.024) increased, whereas insulin secretion (acute insulin response; not significant) decreased. Fat percentage increased (P < 0.0005), and lean body mass decreased (P < 0.0005), but fat distribution remained unaltered, and body composition remained within the normal range. Compared with AGA controls, Si was lower during GH and became similar after GH stop, acute insulin response was higher at both time points, and glucose effectiveness and disposition index became higher. The GH-induced lower Si in SGA adolescents increases after stopping long-term GH treatment and becomes similar to that of AGA controls. Discontinuation of GH treatment is, however, also associated with an increase in percent body fat and with a decrease in lean body mass, without changes in fat distribution.

The Effect of Physical Activity on Weight Loss in College Students

Weight loss is possibly the major reason that most people begin an exercise program. It has been used in many populations to help with weight loss. PURPOSE: To examine the effects of two different physical training programs on weight loss, body composition, and oxygen consumption in overweight individuals. METHODS: Twenty sedentary, overweight college-age students (6 males, 14 females, 22.6 Ãâ~Ã'± 8.2 y, BMI = 27.76 Ãâ~Ã'± 6.03) volunteered to participate in this study. After signing an informed consent form, they were randomly assigned to either a cardiovascular (C) training group (n = 10) or a strength and cardiovascular (S) training group (n = 10). The C group was required to accumulate 60 minutes of brisk walking 4 days per week. The S group performed 30 minutes of brisk walking 4 days per week, plus two strength training sessions each week. Anthropometric measures (height, weight, BMI, circumference measures, percent body fat, and fat-free mass) and cardiorespiratory fitness were collected before and after the 12-week exercise intervention. RESULTS: The attrition rate was 10% of the S group and 40% of the C group, which equals 25% of the total number of subjects who began the study. The S group finishers (n = 9) gained 1.27 kg (gained 1.95 kg of fat, and lost 0.68 kg of lean body mass), while the C group finishers (n = 6) lost 0.75 kg (gained 0.44 kg of fat and lost 1.19 kg of lean body mass). These changes were not significantly different within or between groups. The S group significantly increased body fat percentage by 2.27 Ãâ~Ã'± 2.31% (p = .019), whereas the C group had no change in body fat percentage (0.78 Ãâ~Ã'±1.90 %). Finally, the S group increased their estimated VO2 max (0.90 Ãâ ~Ã'± 2.05 mLÃâ~Ã'·kg-1Ãâ ~Ã'·min-1), although it was not significant. The C group had relatively no change in estimated VO2 max (0.10 Ãâ~Ã'± 4.62 mLÃâ~Ã'·kg-1 Ãâ ~Ã'·min-1), despite walking twice as much as the S group. CONCLUSIONS: These results support previous research reporting that exercise interventions produce only minimal changes in body weight without a change in dietary intake. Therefore, additional research is needed with a larger sample size and possibly diet modification to determine if combining strength training with cardiovascular training is superior to cardiovascular training alone for weight loss.

Reducing Diabetes Risk in American Indian Women

American Indians experience high rates of type 2 diabetes. The impact of low-intensity interventions on diabetes risk among young American Indian women is unknown. Randomized controlled trial. Community-based; participants were 200 young urban American Indian women who were block-randomized on fasting blood glucose (FBG) into intervention and control groups. Inclusion criteria included self-reported identity, aged 18-40 years, not pregnant, willingness to stay in urban area for 2 years, and not having type 2 diabetes. Measures were taken at baseline, 6, 12, and 18 months. Data were gathered in 2002-2006 and analyzed in 2006-2007. Five discussion group sessions (one meeting per month for 5 months) were held focusing on healthful eating, physical activity, goal-setting, and social support. Primary outcomes included dietary fat and vegetable consumption and self-reported physical activity. Secondary outcomes included cardiorespiratory fitness, insulin sensitivity, blood pressure, lipid profiles, percent body fat, BMI, intake of fruit, total sugar and sweetened beverages, FBG, and television viewing. Mean vegetable and fruit intake increased significantly more in the intervention group than in the control group over time (group by visit interaction, p=0.02 and p=0.002, respectively). Both groups had significant increases in percent body fat and decreases in waist circumference, insulin sensitivity, blood cholesterol, LDL, television viewing, and total intakes of energy, saturated fat, sugar, and sweetened beverages. A culturally influenced, low-intensity lifestyle intervention can improve self-reported intakes of vegetables and fruit over 18 months in young, urban American Indian women.

Insulin-like Growth Factor-I (rhIGF-I) Therapy of Short Stature

The United States Food and Drug Administration (FDA) approved the use of subcutaneously injected rhIGF-I in late 2005 for treatment of children with severe short stature from growth hormone (GH) insensitivity due to genetic defects in the GH receptor or postreceptor mechanisms or from the development of GH inactivating antibodies. The approval was based on 15 years experience treating these rare conditions with rhIGF-I. Because of the very small numbers of children with these conditions, there has been an effort to justify and promote broader use for rhIGF-I. Attempts to identify GH unresponsiveness in children with idiopathic short stature (ISS) have yielded only a handful of patients with rare genetic disorders. IGF-I treatment for unequivocal GH insensitivity improves but does not correct growth failure, in contrast to the typical experience with GH replacement of GH deficiency. This emphasizes the importance of direct effects of GH at the growth plate, including the stimulation of maturation of cartilage precursor cells and local production of IGF-I, effects that cannot be duplicated by exogenous administration of rhIGF-I. Adverse effects testify to the more than adequate delivery of administered rhIGF-I to other tissues; these include lymphoid hyperplasia, coarsening of the facies, and increased percentage body fat. The absence of convincing evidence of GH insensitivity in a substantial number of children with ISS, the limited ability of endocrine IGF-I to restore normal growth in those with unequivocal GH unresponsiveness, the suppression of endogenous GH (and thereby, local GH effects on growth) that occurs with IGF-I administration, the risk profile, and the absence of data on efficacy in other than proven severe GH insensitivity, led the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society to conclude that rhIGF-I use is only justified in conditions approved by the FDA and that other growth promotional use should only be investigational. Nonetheless, substantial numbers of children are being treated with rhIGF-I off-label, exuberant estimates of potentially eligible patients are projected, and several uncontrolled clinical trials have been undertaken which are not based on sound preliminary data or established growth principles, and a single four-arm study begun comparing monotherapy with rhGH to combination rhGH with three dosages of rhIGF-I as a single daily injection, a means of administration of rhIGF-I that has not been tested.

Adiposity and Reporting of Vasomotor Symptoms among Midlife Women: The Study of Women's Health Across the Nation

It has long been hypothesized that increased adiposity would be associated with decreased vasomotor symptoms during menopause because of conversion of androgens to estrogens in body fat. However, recent thermoregulatory models have postulated that increased adipose tissue would be associated with a greater likelihood of vasomotor symptoms. The authors evaluated these hypotheses in the Study of Women's Health Across the Nation, a multiethnic, community-based observational study of US women transitioning through menopause. The sample included 1,776 women aged 47-59 years with an intact uterus and at least one ovary who completed bioelectrical impedance analysis for assessment of body composition at the sixth annual study visit (2002-2004). Assessments also included reported vasomotor symptoms (hot flashes, night sweats) and serum levels of follicle-stimulating hormone, estradiol, and sex hormone-binding globulin-adjusted estradiol (free estradiol index). Results indicated that a higher percentage of body fat was associated with increased odds of reporting vasomotor symptoms (per standard deviation increase in percent body fat, odds ratio = 1.27, 95% confidence interval: 1.14, 1.42) in age- and site-adjusted models. Associations persisted in fully adjusted models and were not reduced when models included reproductive hormones. These findings support a thermoregulatory model of vasomotor symptoms.

Abstract 3555: Increased Fatness and Reduced Fitness are Associated with Aortic Stiffness in Persons with Type 2 Diabetes and Hypertension

Background: Large artery stiffness, thought to be a marker of cardiovascular disease, is accelerated in persons with diabetes and hypertension. While reduced fatness and increased fitness are associated with lower BP, we tested the hypothesis that increased fatness and reduced fitness are each independently associated with greater aortic stiffness. Methods: Sedentary subjects (M=60; F=29), mean (SD) age 57.1 (5.8) years, were examined at baseline as part of an exercise training study to reduce BP in persons with type 2 diabetes. Subjects were taking their usual medical therapy. For BP eligibility, subjects were required to have SBP between 120–159 and/or DBP between 80–99 mm Hg during 2 consecutive weekly visits. BP was the mean of the screening visits and a visit after qualification for the study. Aortic stiffness was assessed by carotid-to-femoral pulse wave velocity (PWV), using ultrasound probes simultaneously at each of these sites. General fatness was assessed by dual-energy x-ray absorptiometry (DEXA) and expressed as percent body fat. Abdominal fatness was assessed by magnetic resonance imaging at the level of the umbilicus and the areas for total, subcutaneous, and visceral fat were measured. Maximal oxygen uptake was obtained on a treadmill. The associations of PWV with BP, oxygen uptake, and abdominal fat were determined by stepwise regression analysis with adjustment for age and gender. Results: PWV was 922.9 (300.0) msec, SBP was 126.9 (13.2) mm Hg, DBP was 71.8 (8.8) mm Hg, pulse pressure (PP) was 55.0 (10.4) mm Hg, percent body fat was 35.0 (6.5) %, and maximal oxygen uptake was 21.7 (5.0) ml/kg/min. In the final model, the variance in PWV was accounted for by increased PP, 8.9%; increased abdominal visceral fat accounted for an additional 6.2%; increased percent body fat, an additional 3%; and decreased maximal oxygen uptake, an additional 5.6%. Conclusions: These data bring to light an independent relationship of aortic stiffness with increased fatness and reduced fitness. Though further work is needed to elucidate the mechanisms linking aortic stiffness, fatness, and fitness, these findings support the need for a therapeutic approach for reducing aortic stiffness that considers the potential benefits of weight reduction and exercise.

Abstract 3591: Group X sPLA2 Deficiency Increases Adiposity and Adipose Tissue Inflammation in Mice

Introduction: Of the 10 secretory phospholipase A 2 (sPLA 2 ) enzymes expressed in humans, Group X (GX) sPLA 2 is the most potent in hydrolyzing phospholipids on cell membranes. In addition to its lipolytic activity, GX sPLA 2 is also a high affinity ligand for the M-type sPLA 2 receptor. Although numerous studies have implicated GX sPLA 2 in important biological processes in vitro , data from studies in vivo are lacking. To elucidate the physiological functions of this enzyme we recently developed C57BL/6 mice with targeted deletion of the GX sPLA 2 gene. Results : Analysis by real time RT-PCR showed that GX sPLA 2 mRNA is widely distributed in mouse tissues, with highest expression in intestine, testes, brain, thymus, spleen, fat, lung, and heart. Unlike some of the other members of the sPLA 2 family, tissue expression of GX sPLA 2 was not highly upregulated in mice injected with lipopolysaccharide. However, GX sPLA 2 was induced almost 5-fold in retroperitoneal fat of mice fed a high-fat (60 kcal%) diet for 17 weeks.Targeted disruption of GX sPLA 2 resulted in increased body weight in 1.5 year-old mice fed a normal laboratory diet (male GX sPLA 2 +/+ mice: 35.8±0.4 g; male GX sPLA 2 −/− mice: 45.033.2 g; p&lt;0.05). The increase in body weight was associated with significantly increased percent body fat (GX sPLA 2 +/+ mice: 16.0±1.0%; GX sPLA 2 −/− mice: 19.6±1%; p&lt;0.05), increased adipocyte size (GX sPLA 2 +/+ mice: 1300±26 um 2 GX sPLA 2 −/− mice: 2700±78 um 2 ; p&lt;0.001), and decreased fasting plasma triglyceride levels (GX sPLA 2 +/+ mice: 46.3±4.9 mg/dl; GX sPLA 2 −/− mice: 33.8±2.9 mg/dl; p&lt;0.05) at 3 months of age. Food consumption, fasting blood glucose, and plasma total cholesterol levels were not significantly different between GX sPLA 2 −/− and GX sPLA 2 +/+ mice. Compared to 3 month old GX sPLA 2 +/+ mice, the relative expression of IL-6 and F4/80 mRNAs in adipose tissue of age-matched GX sPLA 2 −/− mice was increased 9- and 4-fold, respectively, suggesting that the increased adiposity in GX sPLA 2 −/− mice was associated with an increase in the inflammatory profile of adipose tissue Conclusions: Our data points to a previously unrecognized role for Group X sPLA 2 in the development of obesity and associated adipose tissue inflammation.

Strength training and adiposity in premenopausal women: Strong, Healthy, and Empowered study

Background: American women aged 25–44 y gain 0.5–1 kg yearly, most of which is fat. Because few midlife women participate in strength training, this mode of activity may be a novel intervention for preventing age-associated fat increases in this population.Objectives: The primary aim was to assess the efficacy of twice-weekly strength training to avoid increases in percentage body fat and intraabdominal fat.Design: A randomized controlled trial was conducted in an ethnically diverse sample of 164 overweight and obese [body mass index (in kg/m2): 25–35] women aged 25–44 y. The treatment group did twice-weekly strength training for 2 y. The standard care comparison group was given brochures recommending aerobic exercise. Assessments at baseline, 1, and 2 y included intraabdominal fat by computed tomography scan and body fat and fat-free mass by dual-energy X-ray absorptiometry.Results: During 2 y, percentage body fat changes were −3.68 ± 0.99% for the treatment group and −0.14 ± 1.04% for the control group, P = 0.01. Two-year intraabdominal fat changes were 7.05 ± 5.07% for the treatment group and 21.36 ± 5.34% for the control group, P = 0.05.Conclusion: This study suggests that strength training is an efficacious intervention for preventing percentage body fat increases and attenuating intraabdominal fat increases in overweight and obese premenopausal women. This is relevant to public health efforts for obesity prevention because most weight gain can be assumed to be fat, including abdominal fat.