Adjustment For Percent Body Fat Research Articles

Mechanical efficiency: associations with body composition and glycemic profile in healthy adults.

The aim of this study was to assess the association between net mechanical efficiency (NME) and body composition and glycemic profile, in middle-aged (38.3 ± 14.3years) participants from the Quebec Family Study (QFS). Analyses were completed on a sample of 605 participants (271 males and 334 females) who performed a submaximal exercise test on an ergometer consisting of three consecutive 6-min workloads at increasing intensity during which respiratory gas exchange was assessed. The calculation of NME [power output/ (vO2-vO2seated before exercise)] was based on the values of the last 3min of the first workload at a targeted power output of 30W. Correlations between NME and dependent variables were computed separately in males and females. Associations between NME and body composition and glucose-insulin variables were assessed by comparing groups of subjects categorized in sex-specific tertiles of NME after adjustments for age. Significant negative correlations were observed between NME and body composition and glycemic profile in both sexes. Comparison across tertiles showed that individuals with high NME displayed more favorable adiposity and glycemic profiles. These differences remained significant after further adjustments for participation in vigorous physical activity, cardiorespiratory fitness, and mean exercise respiratory exchange ratio whereas most differences in glucose-insulin variables became non-significant after further adjustment for percent body fat. QFS familial data indicate that the heritability of NME reaches about 30%. In conclusion, the results of this study show that beyond aerobic fitness and physical activity-participation, mechanical efficiency is an additional activity-related variable that is independently associated with variations in body composition and glycemic profile.

Plasma 25-Hydroxyvitamin D Concentrations and Serum and Salivary C-Reactive Protein in the Osteoporosis and Periodontal Disease Study.

Vitamin D has been hypothesized to play an important role in preventing the development and progression of periodontal disease, but the underlying immune modulatory mechanisms remain understudied. We examined the cross-sectional association between biomarkers of vitamin D status and C-reactive protein (CRP) among postmenopausal women aged 53–81 years. Linear regression was used to examine the association between plasma 25-hydroxyvitamin D (25[OH]D) concentrations, a biomarker of vitamin D status, and both salivary and serum CRP concentrations in 567 women from the Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) Study (1997–2000). CRP concentrations were measured with multiplex arrays and transformed for normality using the natural log. Concentrations above and below the limit of detection were included in analysis as right- and left-censored observations. An inverse association was observed between 25(OH)D and salivary CRP in a model adjusted for age, smoking status, frequency of tooth brushing and flossing, and hormone therapy use (−7.56% difference in salivary CRP concentrations per 10 nmol/L increase in 25(OH)D, 95% CI: −12.78 to −2.03). Further adjustment for percent body fat attenuated this association (−2.48%, 95% CI: −7.88 to 3.24). No significant associations were found between 25(OH)D and serum CRP. Plasma vitamin D concentrations were not associated with salivary or serum CRP concentrations in this cohort of postmenopausal women.

Associations among osteocalcin, leptin and metabolic health in children ages 9\u201313 years in the United States

BackgroundThis study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9–13 years.MethodsThis was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9–13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed.ResultsApproximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-β after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = −0.16; p = 0.04) and glucose (partial r = −0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-β after adjusting for age, sex and percent body fat (all p < 0.001).ConclusionsThese data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported.Clinical trial registration numberNCT00931580.

Parity and Components of the Metabolic Syndrome Among US Hispanic/Latina Women: Results From the Hispanic Community Health Study/Study of Latinos.

Physiological adaptations occurring across successive pregnancies may increase the risk of adverse cardiovascular health outcomes in later life. The association between parity and metabolic syndrome was examined among 7467 Hispanic/Latina women of diverse backgrounds, aged 18 to 74 years, who participated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2008 to 2011. Metabolic syndrome components were defined according to American Heart Association/National Heart, Lung, and Blood Institute criteria and included abdominal obesity, elevated triglycerides, low high-density lipoprotein cholesterol, high blood pressure, and elevated fasting glucose. Logistic regression models estimated odds ratios (ORs) adjusting for sociodemographic, behavioral, and reproductive characteristics. At HCHS/SOL baseline, women reported none (21.1%), 1 (19.9%), 2 (25.7%), 3 (18.6%), 4 (8.8%), and ≥ 5 (5.9%) live births. When compared with women with 1 birth, those with 4 births had the highest odds of abdominal obesity (OR, 2.0; 95% confidence interval, 1.5-2.8) and overall metabolic syndrome (OR, 1.4; 95% confidence interval, 1.0-2.0) and those with ≥ 5 births had the highest odds of low high-density lipoprotein cholesterol (OR, 1.5; 95% confidence interval, 1.2-2.0) and elevated fasting glucose (OR, 1.6; 95% confidence interval, 1.1-2.4), after adjusting for age, background, education, marital status, income, nativity, smoking, physical activity, menopause, oral contraceptive use, hormone therapy, and field center. Further adjustment for percent body fat attenuated these associations. No associations were observed between parity and elevated triglycerides or high blood pressure. Higher parity is associated with an increased prevalence of selected components of the metabolic syndrome among Hispanic/Latina women in the US. High parity among Hispanics/Latinas with a high prevalence of abdominal obesity suggests high risk for metabolic dysregulation.

Sensitivity of blood lipids to changes in adiposity, exercise, and diet in children.

This study aims to determine whether blood lipids in healthy preadolescent children are sensitive to normally occurring changes in percent body fat, physical activity (PA), cardiorespiratory fitness (CRF), and macronutrient intake. Repeated measurements of fasting serum LDL cholesterol, HDL cholesterol, and triglycerides (TG); percent body fat (dual-energy x-ray absorptiometry); PA (pedometers); CRF (multistage run); and carbohydrate, sugar, and fat intake (dietary recall and record) were carried out in 469 children (51% girls) age 8, 10, and 12 yr. Longitudinal relationships in boys showed that, for every one-unit increase in percent body fat, there was a 1.3% (95% CI, 0.9-1.8; P < 0.001) increase in LDL cholesterol; among girls, the increase was 0.8% (95% CI, 0.3-1.2; P = 0.003). In addition, we found a positive longitudinal relationship between TG and percent body fat (P < 0.001) in girls, and a negative longitudinal relationship between HDL cholesterol and percent body fat (P = 0.03) in boys. There were also longitudinal relationships between TG and CRF in both sexes (P < 0.05), but these were not sustained upon adjustment for percent body fat. Although cross-sectional relationships occurred in girls for both HDL cholesterol and TG with PA (P < 0.05), we found no evidence of any relationships between lipids and fat or sugar intake. By age 12 yr, LDL cholesterol was elevated (>3.36 mmol·L) in 16% and 20% of girls and boys, respectively. Blood lipids in preadolescent children appear sensitive to normal changes occurring in their percent body fat and, thus, fitness. Our data support early attention to body composition in community strategies designed to prevent cardiovascular disease in later life.

Higher daily physical activity is associated with higher osteocalcin levels in adolescents

BackgroundExercise stimulates bone remodeling and improves insulin sensitivity (Si), even without associated weight loss. Osteocalcin (OCN), a bone-derived protein, is associated with improved Si. PurposeWe examined how daily physical activity is associated with OCN and Si. MethodsPhysical activity was measured through questionnaires completed in Minneapolis from 2010 to 2012. A physical activity score (PAQsum) was calculated to quantify physical activity (range 1–5). OCN and bone specific alkaline phosphatase (BAP) were measured by ELISA. Si was measured by the insulin modified frequently sampled IV glucose tolerance test. ResultsThe mean PAQsum value was 2.4±0.8 in 47 participants (12–17.9years old). PAQsum was positively associated with OCN (p=0.006). Participants with PAQsum <2 had significantly lower OCN levels compared to participants with PAQsum >2 (p<0.02). Obesity did not modify the association between PAQsum and OCN. There was no statistically significant association between PAQsum and Si or between OCN and Si, even after adjustment for percent body fat. ConclusionsOCN is higher in more physically active individuals. More research is needed to clarify the relationship between OCN, physical activity and Si.

Sex-related differences in the association between waist circumference and bone mineral density in a Korean population.

BackgroundLarge waist circumference is linked to poor health. Investigations of the relationship between waist circumference, as an index of abdominal fat, and bone mineral density (BMD) have yielded inconsistent results. We investigated the association between abdominal obesity measured using waist circumference and BMD in a large-scale population-based study.MethodsWe enrolled 8981 Korean (3592 males and 5389 females) community-dwelling individuals aged ≥50 years from 2007 to 2010. BMD was measured using dual-energy X-ray absorptiometry at lumbar spine and femoral neck skeletal sites. A multiple linear regression analysis was used to evaluate the relationship between waist circumference quartiles and BMD after adjusting for age, height, weight, and regular exercise.ResultsThe adjustment for age, height, weight, and regular exercise revealed a negative linear association between quartile of waist circumference and BMD at the femoral neck and lumbar spine sites in males and females. Waist circumference was more strongly correlated with BMD in males than in females. Although the correlations were slightly attenuated following further adjustment for percent body fat, they remained statistically significant.ConclusionsOur results revealed that waist circumference is independently and inversely associated with BMD after adjusting for age, weight, height, regular exercise and percent body fat, suggesting that waist circumference is a potential predictor of osteoporosis in middle-aged and older Korean males and females.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-326) contains supplementary material, which is available to authorized users.

Lung function and plasma fibrinogen concentrations in the Newcastle Thousand Families birth cohort between age 49 and 51 years

A number of studies have suggested inverse associations between lung function and inflammatory markers, including fibrinogen. In this study, we used data from the Newcastle Thousand Families birth cohort to assess the association between contemporaneous markers of lung function and fibrinogen while adjusting for potential confounding factors throughout life. At age 49-51 years, complete data on lung function and plasma fibrinogen were available for 380 study members. These data were analysed in relation to each other, adjusted for sex and height, with further adjustment for potential confounders within linear regression models using robust estimates. Forced expiratory volume in 1 s was significantly inversely associated with plasma fibrinogen concentration after initial adjustments for sex and height (beta = -0.12, P = 0.011) and remained so after further adjustments for pack-years of cigarettes smoked and current smoking status. On further adjustment for standardized birthweight and duration breast-fed, the association approached statistical significance (P = 0.051). Adjusting for body mass index (BMI) resulted in a loss of significance (P = 0.09), but an unchanged regression coefficient, while, after adjustment for percent body fat, rather than BMI, the association was no longer significant (P = 0.20) and the coefficient reduced. The association between lung function and fibrinogen remains after adjustment for potential early-life confounders and smoking. However, it is not independent of contemporaneous measures of adiposity, with evidence of confounding by percent body fat. Further studies, with measures of adiposity, are required to confirm whether associations between markers of inflammation and lung function are due to residual confounding by adiposity.

Common Variants Near Melanocortin 4 Receptor Are Associated with General and Visceral Adiposity in European- and African-American Youth

Recent genome-wide association studies found common variants near the melanocortin 4 receptor gene associated with obesity. This study aimed to assess the influence of the identified single nucleotide polymorphisms rs17782313 and rs17700633 on general and visceral adiposity in European- and African-American youth. In 1890 youth (49.1% European-American, 45.6% male, mean age 16.7 years), we examined the associations of the rs17782313 and rs17700633 with anthropometry, percent body fat, visceral adipose tissue, and subcutaneous abdominal adipose tissue. Interaction of the single nucleotide polymorphisms with ethnicity or sex was investigated and haplotype analyses conducted. Rs17782313 was significantly associated with weight (P = .02) and waist circumference (P = .03) in all subjects and with body mass index (P = .002) in females. In females rs17700633 was significantly associated with percent body fat (P = .001), visceral adipose tissue (P < .001), and subcutaneous abdominal adipose tissue (P < .001). Rs17700633 was significantly associated with fasting insulin and homeostasis model assessment, but the significance attenuated after adjustment for percent body fat. These findings were confirmed by haplotype analysis. No significant interactions of the variants with ethnicity were found for any of these phenotypes. The relatively large effect of these common variants near melanocortin 4 receptor on general and visceral adiposity in childhood, especially in girls, could prove helpful in elucidating the molecular mechanisms underlying the development of obesity in early life.

Macrophage Content in Subcutaneous Adipose Tissue

OBJECTIVE— In severely obese individuals and patients with diabetes, accumulation and activation of macrophages in adipose tissue has been implicated in the development of obesity-associated complications, including insulin resistance. We sought to determine whether in a healthy population, adiposity, sex, age, or insulin action is associated with adipose tissue macrophage content (ATMc) and/or markers of macrophage activation.RESEARCH DESIGN AND METHODS— Subcutaneous ATMc from young adult Pima Indians with a wide range of adiposity (13–46% body fat, by whole-body dual-energy X-ray absorptiometry) and insulin action (glucose disposal rate 1.6–9 mg/kg estimated metabolic body size/min, by glucose clamp) were measured. We also measured expression in adipose tissue of factors implicated in macrophage recruitment and activation to determine any association with ATMc and insulin action.RESULTS— ATMc, as assessed by immunohistochemistry (Mphi) and by macrophage-specific gene expression (CD68, CD11b, and CSF1R), were correlated with percent body fat, age, and female sex. Gene expression of CD68, CD11b, and CSF1R but not Mphi was correlated negatively with glucose disposal rate but not after adjustment for percent body fat, age, and sex. However, adipose tissue expression of plasminogen activator inhibitor type-1 (PAI-1) and CD11 antigen-like family member C (CD11c), markers produced by macrophages, were negatively correlated with adjusted glucose disposal rate (r = −0.28, P = 0.05 and r = −0.31, P = 0.03).CONCLUSIONS— ATMc is correlated with age and adiposity but not with insulin action independent of adiposity in healthy human subjects. However, PAI-1 and CD11c expression are independent predictors of insulin action, indicating a possible role for adipose tissue macrophage activation.

Leptin Levels among Prepubertal Children with Down Syndrome Compared with Their Siblings

To compare levels of leptin and other obesity-related hormones in prepubertal children with Down syndrome (DS), a population at high obesity risk, and those in unaffected siblings to better understand the pathophysiology of obesity in children with DS. This was a cross-sectional study of 35 children with DS and 33 control siblings, ages 4 to 10 years, with a fasting blood sample and anthropometric measurements to estimate body composition. Generalized estimating equations were used to account for the lack of independence between siblings. In addition to having higher body mass index and percent body fat, children with DS had higher leptin levels than unaffected siblings, even after adjustment for age, sex, race, and ethnicity (difference, 5.8 ng/mL; 95% CI, 2.4-9.3; P = .001) and further adjustment for percent body fat (difference, 2.7 ng/mL; 95% CI, 0.08-5.40, P = .04). Leptin and percent body fat were positively associated in both groups (P < .0001), but with a significantly greater positive association in the DS group, suggesting a significant effect modification (P < .0001). This group of children with DS had increased leptin levels for percent body fat than their unaffected siblings. This difference may contribute to the increased risk for obesity in children with DS.

AMPD1 gene polymorphism and the vasodilatory response to ischemia

Peripheral vasculature resistance can play an important role in affecting blood pressure and the development of cardiovascular disease. A better understanding of the genes that encode vasodilators, such as adenosine, will provide insight into the mechanisms underlying cardiovascular disease. We tested whether the adenosine monophosphate deaminase-1 ( AMPD1) C34T gene polymorphism was associated with the vasodilatory response to ischemia in Caucasian females aged 18–35 years. Blood samples ( n = 58) were analyzed for the C34T variant and resulted in the following genotype groups: CC ( n = 45) and CT ( n = 13). Mean blood pressure (MBP), heart rate, and forearm blood flow (FBF) measured by venous occlusion plethysmography were measured at baseline and at 1 (peak FBF), 2 and 3 min of vasodilation during reactive hyperemia following 5 min of arm ischemia. To control for interindividual variability in baseline FBF and forearm vascular resistance (FVR) the percent change in FBF and FVR were calculated for each min. The percent decrease in FVR was significantly greater in the CT compared to the CC genotype group (− 40 ± 4% vs. − 24 ± 3%, P = 0.01) during the 2nd min of reactive hyperemia. The percent increase in FBF tended to be greater in the CT compared to the CC genotype group (+ 69 ± 9% vs. + 42 ± 9%, P = 0.07) during the 2nd min of reactive hyperemia after adjustment for percent body fat. Consistent with previous findings of increased production of adenosine during exercise in individuals carrying a T allele, our findings suggest that the AMPD1 C34T polymorphism is associated with vasodilatory response to ischemia in the peripheral vasculature because individuals with the T allele had a greater vasodilatory response to ischemia.

Life course determinants of insulin secretion and sensitivity at age 50 years: the Newcastle thousand families study

Suboptimal nutrition during fetal life and infancy is suggested to increase insulin resistance in adulthood. This study investigated the proportion of variance in insulin secretion and resistance accounted for by factors operating at different stages of life using a cohort of all 1142 births in the city of Newcastle, UK in May and June 1947. Detailed information was collected prospectively during childhood, including birth weight, growth and socio-economic circumstances. At age 50, 412 study members attended for clinical examination. Fasting and 30-min plasma insulin and glucose levels were determined and HOMA-IR and insulin secretion derived. Birth weight was not a significant predictor of HOMA-IR after adjustment for percent body-fat and waist-hip ratio. Duration of breastfeeding was significantly negatively associated with HOMA-IR in men. For both genders, fetal life explained directly little variation in either HOMA-IR or insulin secretion (0.1-5.6%). Compared to early life, adult lifestyle and body composition directly explained larger proportions of the variances for insulin secretion and HOMA-IR for men (11 and 22% respectively) and women (5.9 and 34%). Insulin secretion is largely unexplained by these data. For insulin resistance, the evidence suggests a limited impact of early life and a larger impact of adult factors.

Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans.

Adiponectin, the most abundant adipose-specific protein, has been found to be negatively associated with degree of adiposity and positively associated with insulin sensitivity in Pima Indians and other populations. Moreover, adiponectin administration to rodents has been shown to increase insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and also increase whole-body insulin sensitivity. To further characterize the relationship between plasma adiponectin concentration and insulin sensitivity in humans, we examined 1) the cross-sectional association between plasma adiponectin concentration and skeletal muscle IR tyrosine phosphorylation and 2) the prospective effect of plasma adiponectin concentration at baseline on change in insulin sensitivity. Fasting plasma adiponectin concentration, body composition (hydrodensitometry or dual energy X-ray absorptiometry), insulin sensitivity (insulin-stimulated glucose disposal, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) were measured in 55 Pima Indians (47 men and 8 women, aged 31 +/- 8 years, body fat 29 +/- 8% [mean +/- SD]; 50 with normal glucose tolerance, 3 with impaired glucose tolerance, and 2 with diabetes). Group 1 (19 subjects) underwent skeletal muscle biopsies for the measurement of basal and insulin-stimulated tyrosine phosphorylation of the IR (stimulated by 100 nmol/l insulin). The fold increase after insulin stimulation was calculated as the ratio between maximal and basal phosphorylation. Group 2 (38 subjects) had follow-up measurements of insulin-stimulated glucose disposal. Cross-sectionally, plasma adiponectin concentration was positively associated with insulin-stimulated glucose disposal (r = 0.58, P < 0.0001) and negatively associated with percent body fat (r = -0.62, P < 0.0001) in the whole group. In group 1 plasma adiponectin was negatively associated with the basal (r = -0.65, P = 0.003) and positively associated with the fold increase in IR tyrosine phosphorylation (r = 0.69, P = 0.001) before and after the adjustment for percent body fat (r = -0.58, P = 0.01 and r = 0.54, P = 0.02, respectively). Longitudinally, after adjustment for age, sex, and percent body fat, low plasma adiponectin concentration at baseline was associated with a decrease in insulin sensitivity (P = 0.04). In conclusion, our cross-sectional data suggest a role of physiological concentration of fasting plasma adiponectin in the regulation of skeletal muscle IR tyrosine phosphorylation. Prospectively, low plasma adiponectin concentration at baseline precedes a decrease in insulin sensitivity. Our data indicate that adiponectin plays an important role in regulation of insulin sensitivity in humans.

Insulin action and insulinemia are closely related to the fasting complement C3, but not acylation stimulating protein concentration.

An elevated C3 concentration has been reported in people with obesity, type 2 diabetes, hypertension, and dyslipidemia, and has been proposed to play a role in the development of atherosclerosis. We hypothesized that an elevated C3 concentration might be linked to insulin resistance and/or hyperinsulinemia, abnormalities commonly observed in association with the above conditions. Fasting concentrations of C3 and acylation stimulating protein (ASP, C3adesarg), a cleavage product of C3 recently found to stimulate glucose uptake in vitro, were measured in 33 healthy nondiabetic Pima Indians (14 women and 19 men; age 27 +/- 1 and body fat 33 +/- 1%, means +/- SEM). Subjects were characterized for body composition dual-energy X-ray absorptiometry, insulin action (insulin-stimulated glucose disposal [M], hyperinsulinemic glucose clamp), and glucose tolerance (75-g oral glucose tolerance test). Fasting C3 and ASP concentrations were positively correlated (r = 0.43, P < 0.05). Fasting C3 concentration was closely related to percent body fat (r = 0.77), M (r = -0.75), and fasting insulin concentration (r = 0.72) (all P < 0.0001). Fasting C3 concentrations remained significantly related to M and fasting insulin after adjusting for percent body fat (partial r = -0.53 and 0.33, both P < 0.05). In subjects with impaired glucose tolerance, fasting C3 concentrations were higher than in those with normal glucose tolerance--a difference that remained after adjustment for percent body fat and M. We found that fasting ASP concentrations were significantly related to percent body fat (r = 0.37, P < 0.05), but not to M or fasting insulin. In Pima Indians, fasting C3 concentration is closely related to adiposity, insulin action, and fasting insulin levels and may thus be a mediator for the postulated link between obesity, insulin resistance, hyperinsulinemia, and possibly atherosclerosis.

Hypothalamic-pituitary-adrenal axis and sympathetic nervous system activities in Pima Indians and Caucasians

It has been proposed that both hypercortisolism and low sympathetic nervous system (SNS) activity contribute to obesity. Because glucocorticoids inhibit SNS activity, we hypothesized that hypercortisolism and low SNS activity may be found in association in Pima Indians, a population with a high prevalence of obesity. We therefore measured indices of hypothalamic-pituitary-adrenal (HPA) axis and SNS activities in 39 nondiabetic men, 20 Pimas (age, 30 ± 5 years; weight, 94 ± 26 kg; 35% ± 8% body fat [mean ± SD]) and 19 Caucasians (33 ± 9 years, 91 ± 23 kg, 28% ± 11% body fat). HPA axis activity was assessed by measurements of morning fasting plasma corticotropin (ACTH) and cortisol concentrations and 24-hour urinary free cortisol (UFC) excretion. SNS activity was assessed as muscle sympathetic nerve activity (MSNA) by microneurography and by measurement of catecholamines (fasting plasma concentration and 24-hour urinary excretion). Plasma ACTH and cortisol and UFC were similar in Pimas and Caucasians. MSNA was positively correlated with percent body fat ( r = .49, P = .002) and was lower in Pimas compared with Caucasians after adjustment for percent body fat (24 ± 9 v 31 ± 10 bursts/min, P = .04). We conclude that Pima Indians, a population with a high prevalence of obesity, have lower SNS activity but normal HPA axis activity compared with Caucasians.

Plasma leptin concentrations in Pima Indians living in drastically different environments.

Plasma leptin, an important signal for the regulation of energy stores, is known to be influenced by many hormonal factors, but may also be affected by behavioral and environmental factors. The purpose of this study was to investigate the impact of lifestyle (diet composition, level of physical activity) on plasma leptin concentrations among Pima Indians living in drastically different environments. We studied 224 Mexican Pima Indians (115 women, 109 men) living a traditional lifestyle in a remote, mountainous area of northwest Mexico and 418 U.S. Pima Indians (281 women, 137 men) living a North American lifestyle on the Gila River Indian Reservation in Arizona. We hypothesized that the absolute value of leptin would be lower in Mexican Pima Indians because of their lower percent body fat, but could be further influenced by their lifestyle, independent of body composition. Leptin concentration (enzyme-linked immunosorbent assay [ELISA]) was strongly correlated with percent fat (bioimpedance) in Mexican Pima Indians (r = 0.83, P < 0.0001) and U.S. Pima Indians (r = 0.86, P < 0.0001). Among U.S. Pima Indians, independent of percent fat, subjects with type 2 diabetes had lower leptin than nondiabetic subjects (difference = 6.9 +/- 1.0 ng/ml, P < 0.002). Among nondiabetic subjects, Mexican Pima Indians had lower absolute leptin concentrations than U.S. Pima Indians, but higher after adjustment for percent body fat, waist circumference, age, and sex. In a subset of 70 pairs of subjects matched for sex and percent body fat, leptin concentration was 4.4 +/- 1.0 ng/ml (P < 0.0001) higher in Mexican Pima Indians versus U.S. Pima Indians. These results suggest that independent of body composition, leptin concentration may be increased by environmental factors, such as a high-carbohydrate diet and a high level of physical activity.

Visceral adipose tissue is not increased in Pima Indians compared with equally obese Caucasians and is not related to insulin action or secretion

Pima Indians are insulin resistant and hyperinsulinaemic compared with Caucasians. We investigated whether abdominal fat distribution was different between Pimas and Caucasians and whether differences in the amount of visceral fat explained metabolic differences between the groups. Total body fat (absorptiometry) and abdominal fat distribution at L4-L5 (magnetic resonance imaging) were compared in 20 Pima Indians (10 men/10 women) and 20 age-, sex- and BMI-matched Caucasians. Insulin action was measured as glucose disposal during a two-step hyperinsulinaemic-euglycaemic glucose clamp and insulin secretion was assessed in response to oral and intravenous glucose tolerance tests. By design, percent body fat was similar in Pimas and Caucasians. Abdominal visceral and subcutaneous adipose tissue areas were also similar in the two groups (151+/-16 vs 139+/-15 cm2 and 489+/-61 vs 441+/-7 cm2 respectively). Plasma insulin concentrations were higher in Pimas than Caucasians in the fasting state (27+/-6 vs 11+/-2 mU/ml; p < 0.01) and after a 75-g oral glucose load (area under the curve 19975+/-2626 vs 9293+/-1847 mU x l(-1) x 180 min(-1); p < 0.005). Glucose disposal was lower in Pimas than Caucasians during both steps of the clamp and negatively correlated (after adjustment for percent body fat and sex) with visceral adipose tissue in Caucasians (partial r = -0.51, p = 0.03), but not in Pima Indians (r = -0.03, p = 0.92). Insulin secretion was not related to visceral fat independently of percent body fat in either group. We conclude that a relative increase in visceral fat does not explain insulin resistance and hyperinsulinaemia in Pima Indians.

No effect of Trp64Arg β 3-adrenoceptor polymorphism on the plasma leptin concentration in Pima Indians

In rodents, administration of leptin promotes β 3-adrenergic stimulation of thermogenesis in brown adipose tissue. Conversely, administration of a β 3-adrenoceptor (β 3-AR) agonist decreases leptin mRNA expression and secretion, suggesting that leptin and sympathetic nervous system activity mediated through the β3-AR comprise a negative-feedback loop. It has recently been proposed that a defect in the β 3-AR in humans may contribute to a resistance to the sympathetically mediated effects of leptin on thermogenesis and lipolysis, thus leading to obesity and type 2 diabetes mellitus. We thus hypothesized that the Trp64Arg variant in the human β3-AR would be associated with elevated plasma leptin concentrations. We studied 101 healthy nondiabetic Pima Indians: 11 Arg64 homozygotes, 35 Trp64 homozygotes, and 55 heterozygotes. The fasting plasma leptin concentration as an absolute value or after adjustment for percent body fat and sex was not associated with the β3-AR genotype. Thus, the data do not support an influence of the Trp64Arg variant on the plasma leptin concentration.

The Impact of Physical Activity on Lipids, Lipoproteins, and Blood Pressure in Preadolescent Girls

Inconsistent findings reported for the effect of physical activity on lipids, lipoproteins, and blood pressure in children may be due to errors inherent in the methods used to measure physical activity, lack of control for other cardiovascular risk factors, or both. The purpose of this study was to evaluate the association between physical activity assessed using direct measures of energy expenditure and cardiovascular risk factors, controlling for dietary intake and percent body fat. Nonresting energy expenditure was determined in 49 8- to 11-year-old girls from measurements of daily energy expenditure (using doubly-labeled water, 2H2(18)O) and resting metabolic rate (using indirect calorimetry). Self-reported recall of the hours of participation in physical activities of at least moderate intensity (energy expenditure at least four times the resting metabolic rate, METS > or = 4) during the previous year was also obtained. Percent body fat was estimated from the measurement of total body water with H2(18)O. Concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), apo A-I, lipoprotein (a), insulin, and estradiol, as well as the waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, and dietary intake from 7-day food records were measured. Data were analyzed using Pearson product-moment correlation and stepwise multiple regression. Self-reported hours of participation in activities with METS (metabolic equivalents) of 4 or greater significantly predicted LDL-C and apo B concentrations, even after adjustment for percent body fat and percentage of dietary energy from saturated fat. Nonresting energy expenditure adjusted for weight, a measure of the energy spent on physical activity, did not predict LDL-C or high-density lipoprotein cholesterol concentrations. Body mass index and insulin concentration predicted systolic and diastolic blood pressure, respectively. These findings suggest that the intensity of physical activity may be a more important determinant of LDL-C in children than the energy spent on physical activity.