The influence of obesity and consequent insulin resistance on coronary risk factors in medically treated patients with coronary disease.

OBJECTIVE: Obesity promotes the development and progression of coronary heart disease (CHD), in part, through its association with hyperlipidemia, hypertension, clotting abnormalities and insulin resistance. We assessed whether these relationships persist in patients with established CHD treated with evidence-based preventive pharmacologic therapies. DESIGN AND SUBJECTS: We performed a cross-sectional study of 74 adults with CHD and a body mass index (BMI) of >27 kg m(-2) (mean 32+/-4). The mean age of subjects was 64+/-9 years (range 44-84 years). MEASUREMENTS: Obesity measures included weight, BMI, waist, fat mass, intra-abdominal fat and subcutaneous fat. Risk factor measures included insulin sensitivity, fasting insulin level, lipid profiles, blood pressure, C-reactive protein (hs-CRP), plasminogen activator inhibitor (PAI-1) and platelet reactivity. Medication use included aspirin (99%), statin (84%), beta-blocker (71%), ACE inhibitor or blocker (37%) and clopidogrel (28%). RESULTS: There was no direct relationship between obesity parameters and risk factor measures of lipid concentrations, blood pressure, clotting abnormalities or platelet reactivity except for a modest relationship between visceral fat and hs-CRP (r=0.30, P=0.02). However, increased BMI, waist circumference, fat mass, total abdominal fat and abdominal subcutaneous fat all correlated with insulin sensitivity (r-values -0.30 to -0.45, P-values 0.01 to <0.001) and insulin concentrations. Insulin sensitivity, in turn, was the best predictor of PAI-1, triglycerides, high-density lipoprotein (HDL) levels, cholesterol/HDL levels (all P<0.01) and platelet reactivity (R=0.34, P=0.02). CONCLUSIONS: Use of preventive pharmacologic therapies obviated the expected relationship between adiposity and CHD risk factors. However, a residual effect of insulin resistance is left untreated. Total adiposity and central adiposity were strong predictors of insulin sensitivity, which in turn predicted cardiac risk factors such as lipid concentrations, PAI-1 and platelet reactivity. Thus, while evidence-based pharmacologic treatments may diminish the statistical relationship between obesity and many cardiac risk factors, adiposity negatively impacts CHD risk by reducing tissue insulin sensitivity.

Comparing energy expenditure data among individuals differing in body size and composition: statistical and physiological considerations.

Acute and chronic diseases are frequently characterized by alterations in energy metabolism that influence nutritional requirements and clinical care. Knowledge of the effect of disease on daily energy expenditure and its components is fundamental to understanding the impact of the disease process on energy balance. To obtain this information, energy expenditure data are often compared between healthy and diseased individuals. This review focuses on the statistical and physiological issues related to comparing energy expenditure data among individuals who differ in body size and composition.

Recovery of (13)CO(2) from infused [1-(13)C]leucine and [1,2-(13)C(2)]leucine in healthy humans.

Carbon (C) in the 1-position of leucine is released as CO(2) with the decarboxylation of alpha-ketoisocaproate (KIC). Carbon in the 2-position of leucine undergoes several additional metabolic steps before entering the tricarboxylic acid (TCA) cycle in the 1-position of acetyl-CoA, where it can be released as CO(2) or be incorporated into other compounds. This study examined the metabolic fate of C in the 2-position of leucine. We infused 11 healthy subjects with [1-(13)C]leucine and [1,2-(13)C(2)]leucine for 3.5--4 h to measure leucine kinetics and the oxidation of the tracers from enrichments of (13)C in blood and expired CO(2). The fraction of leucine infused that was oxidized (f(ox)) was used to define the degree of recovery of the (13)C label(s) for each tracer. As expected, leucine appearance (means +/- SE) did not differ between tracers ((13)C(1): 92.1 +/- 3.1 vs. (13)C(2): 89.2 +/- 3.2 micromol x kg(-1) x h(-1)) when calculated using plasma leucine enrichments as an index of intracellular enrichment. A small (3%) but significant (P = 0.048) difference between tracers was found when KIC was used to calculate leucine appearance ((13)C(1): 118.0 +/- 4.1 vs. (13)C(2): 114.4 +/- 4.5 micromol x kg(-1) x h(-1)). The value of f(ox) was 14 +/- 1% for [1,2-(13)C(2)]leucine and was lower than the f(ox) for [1-(13)C]leucine (19 +/- 1%). From the f(ox) data, we calculated that the recovery of the 2-(13)C label in breath CO(2) was 58 +/- 6% relative to the 1-(13)C label. These findings show that, although a majority of the 2-(13)C label of leucine is recovered in breath CO(2), a significant percentage (approximately 42%) is retained in the body, presumably by transfer to other compounds, via TCA exchange reactions.

Evaluation and optimization of ion-current ratio measurements by selected-ion-monitoring mass spectrometry.

Stable isotopically labeled compounds are regularly used as internal standards in quantitation and as tracers of in vivo metabolism. In both applications, the ratio of unlabeled to labeled analogues is determined from an ion-current ratio measured by a mass spectrometer. The precision of the ion-current ratio measurement defines the detection limit for quantitation and for tracer enrichment measurement. We have used standard models of noise to develop a method that evaluates ion-current ratio noise (i) that varies with the signal intensity and (ii) that is signal independent. This model produces a simple equation that defines the ion-current ratio precision using constants that can be evaluated empirically from the measurement of two ion-current ratios from a single standard measured multiple times. We demonstrate that our approach can predict the effect of signal intensity, ion-current ratio magnitude, and internal standard or tracer choice on the measurement precision. The standard deviations predicted by our method are shown to equal standard deviations of samples measured experimentally. This method allows a simple evaluation of a mass spectrometry system and can define the precision of new quantitation and tracer methods.

Determinants of insulin-stimulated glucose disposal in middle-aged, premenopausal women.

Controversy exists regarding the relative importance of adiposity, physical fitness, and physical activity in the regulation of insulin-stimulated glucose disposal. To address this issue, we measured insulin-stimulated glucose disposal [mg. kg fat-free mass (FFM)(-1). min(-1); oxidative and nonoxidative components] in 45 nondiabetic, nonobese, premenopausal women (mean +/- SD; 47 +/- 3 yr) by use of hyperinsulinemic euglycemic clamp (40 mU. m(-2). min(-1)) and [6,6-2H2]glucose dilution techniques. We also measured body composition, abdominal fat distribution, thigh muscle fat content, maximal oxygen consumption (VO2 max), and physical activity energy expenditure ((2)H(2)(18)O kinetics) as possible correlates of glucose disposal. VO2 max was the strongest correlate of glucose disposal (r = 0.63, P < 0.01), whereas whole body and abdominal adiposity showed modest associations (range of r values from -0.32 to -0.46, P < 0.05 to P < 0.01). A similar pattern of correlations was observed for nonoxidative glucose disposal. None of the variables measured correlated with oxidative glucose disposal. The relationship of VO2 max to glucose disposal persisted after statistical control for FFM, percent body fat, and intra-abdominal fat (r = 0.40, P < 0.01). In contrast, correlations of total and regional adiposity measures to insulin sensitivity were no longer significant after statistical adjustment for VO2 max. VO2 max was the only variable to enter stepwise regression models as a significant predictor of total and nonoxidative glucose disposal. Our results highlight the importance of VO2 max as a determinant of glucose disposal and suggest that it may be a stronger determinant of variation in glucose disposal than total and regional adiposity in nonobese, nondiabetic, premenopausal women.

Identification of SCAN dimerization domains in four gene families.

Zinc-finger transcription factors are often accompanied by modular sequence motifs such as the Kruppel-associated box (KRAB) and the SCAN domain. The KRAB domain mediates transcriptional repression while the SCAN domain mediates selective protein dimerization. The hypoalphalipoproteinemia susceptibility gene ZNF202 encodes a SCAN box and a KRAB domain followed by eight Cys2-His2 zinc-finger motifs. In order to identify the existence of genes which encode proteins of structural homology to ZNF202, a mouse lambda library was screened with a human ZNF202 cDNA probe. The isolated cDNA clones represented three SCAN-domain-encoding gene families. We purified three novel cDNAs that encode a SCAN-KRAB-(Cys2-His2)x domain alignment and one cDNA that encodes a SCAN-(Cys2-His2)x domain alignment. In addition, we identified one cDNA sequence with a predicted protein sequence containing a KRAB-SCAN-KRAB-(Cys2-His2)x domain alignment. Therefore, when combined with the recently discovered family of isolated SCAN-domain-encoding genes, four SCAN domain gene families can be distinguished. The consensus sequences for the murine SCAN and KRAB domains are highly conserved within the mammalian phylogenetic tree which may be useful in elucidating the biological function of these protein modules and the crucial residues responsible for their binding specificity.

Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women.

OBJECTIVE: We examined the hypothesis that an age-related increase in the compartments of visceral fat would account, in part, for the deleterious changes in insulin sensitivity and blood lipid profile in nonobese women. RESEARCH DESIGN AND METHODS: We directly assessed visceral and subcutaneous abdominal adipose tissue areas (computed tomography), glucose disposal (hyperinsulinemic-euglycemic clamp), body composition (dual energy X-ray absorptiometry), blood-lipid profile, and aerobic fitness (VO2max) in 178 nonobese women categorized into four age groups: group 1, 28 +/- 4 years, n = 88; group 2, 46 +/- 2 years, n = 38; group 3, 53 +/- 2 years, n = 31; and group 4. 67 +/- 6 years, n = 21. RESULTS: Visceral abdominal adipose tissue area increased with age (2.36 cm2 per year, P < 0.0001). We noted an age-related increase in total cholesterol (P < 0.0003), triglycerides (P < 0.0009), LDL cholesterol (P < 0.027), and the ratio of total cholesterol to HDL cholesterol (P < 0.042). However, age-related changes in insulin sensitivity exhibited a different age-related pattern. That is, insulin sensitivity, expressed on an absolute basis or indexed per kilogram of fat-free mass, was lowest in group 4 but was not significantly different among groups 1, 2, and 3. After statistical control for visceral fat, lower insulin sensitivity persisted in group 4, although differences were diminished relative to other groups. However, the effect of visceral fat on age-related changes in the blood-lipid profile was stronger. That is, differences in visceral and deep subcutaneous adipose tissue area abolished age-related differences in total cholesterol, triglycerides, and LDL cholesterol. No independent effects of VO2max or leisure-time physical activity on age-related changes in insulin sensitivity or on the blood-lipid profile were noted. CONCLUSIONS: We conclude that 1) visceral fat shows an increase with advancing age, whereas a decrease in insulin sensitivity was noted only in older women; 2) age-related differences in visceral fat explain only a modest part of the decline in insulin sensitivity in nonobese women; and 3) unfavorable changes in plasma lipids were strongly associated with the age-related increase in visceral abdominal adipose tissue.

Effects of estradiol and progesterone on body composition, protein synthesis, and lipoprotein lipase in rats.

Prior studies suggest that estradiol and progesterone regulate body composition in growing female rats. Because these studies did not consider the confounding effect of changes in food intake, it remains unclear whether ovarian hormones regulate body composition independently of their effects on food intake. We utilized a pair-feeding paradigm to examine the effects of these hormones on body composition. In addition, skeletal muscle protein fractional synthesis rate and adipose tissue lipoprotein lipase activity were measured to examine pathways of substrate deposition into fat and fat-free tissue. Female Sprague-Dawley rats [pubertal: 7-8 wk old; 190 +/- 0.5 (SE) g] were separated into four groups: 1) sham-operated (S; n = 8), 2) ovariectomized plus placebo (OVX; n = 8), 3) ovariectomized plus estradiol (OVX+E; n = 8), and 4) ovariectomized plus progesterone (OVX+P; n = 8). All ovariectomized groups were pair-fed to the S group. Body composition was measured using total body electrical conductivity. The relative increase in fat-free mass was greater (P < 0.01) in the OVX group (31 +/- 2%) than in the S (17 +/- 2%), OVX+E (18 +/- 2%), and OVX+P (22 +/- 2%) groups. The fractional synthetic rates of gastrocnemius muscle protein paralleled changes in fat-free mass: OVX had a higher (P < 0.05) synthesis rate (21 +/- 3%/day) than S (12 +/- 2%/day), OVX+E (11 +/- 2%/day), and OVX+P (8 +/- 1%/day) groups. Body fat increased in the S group (31 +/- 7%; P < 0.01), whereas the OVX groups lost fat (OVX: -10 +/- 7%; OVX+E: -15 +/- 7%; OVX+P: -13 +/- 7%). No differences in lipoprotein lipase were found. Our results suggest that estradiol and progesterone may regulate the growth of fat and fat-free tissues in female rats. Moreover, ovarian hormones may influence skeletal muscle growth through their effects on skeletal muscle protein synthesis.

The intestinal fatty acid binding protein is not essential for dietary fat absorption in mice.

The intestinal fatty acid binding protein (I-FABP) belongs to a family of 15 kDa clamshell-like proteins that are found in many different tissues. So far, nine types have been identified. Their primary structures are highly conserved between species but somewhat less so among the different types. The function of these proteins, many of which are highly expressed, is not well understood. Their ability to bind lipid ligands suggests a role in lipid metabolism, but direct evidence for this idea is still lacking. We tested the hypothesis that I-FABP serves an essential role in the assimilation of dietary fatty acids by disrupting its gene (Fabpi) in the mouse. We discovered that Fabpi-/- mice are viable, but they display alterations in body weight and are hyperinsulinemic. Male Fabpi-/- mice had elevated plasma triacylglycerols and weighed more regardless of the dietary fat content. In contrast, female Fabpi-/- mice gained less weight in response to a high-fat diet. The results clearly demonstrate that I-FABP is not essential for dietary fat absorption. We propose that I-FABP functions as a lipid-sensing component of energy homeostasis that alters body weight gain in a gender-specific fashion.

Lipid metabolism in the elderly.

Adiposity increases with age. The size of the adipose tissue mass is determined by the balance between the recruitment of lipid substrates (ie free fatty acids) from adipose tissue and their subsequent oxidation by respiring tissues. Thus, change in the liberation of free fatty acids from adipocytes, the capacity of respiring tissue to oxidize free fatty acids or a combination of both may contribute to the age-related increase in body fat. This review focuses on studies that have examined the effect of age on free fatty acid release and the capacity of respiring tissues to oxidize fat. In vitro studies have shown that hormonal and pharmacological stimulation of lipolysis diminished with age. Despite this cellular defect, however, in vivo studies suggest that fatty acids are recruited from adipose tissue in excess of the energy demands of the body in older individuals. The capacity of respiring tissues, in particular skeletal muscle, to oxidize fat declines with age. The age-related decrease in fat oxidation is related to a reduction in both the quantity and oxidative capacity of respiring tissue. Taken together, these results suggest that an age-related decrease in the capacity of respiring tissues to oxidize fat, rather than decreased free fatty acid release, is a more likely determinant of lipid imbalance and the age-related increase in adiposity. Interventions designed to increase the mass or oxidative capacity of respiring tissue, therefore, may be effective in counteracting the age-related reduction in fat oxidation.

Menopause-related changes in body fat distribution.

Menopause-related changes in body fat distribution may partially explain the greater risk of cardiovascular and metabolic disease during the postmenopausal years. To date, however, the effect of the menopause transition on body fat distribution remains unclear. Cross-sectional and longitudinal studies using waist circumference or the waist-to-hip ratio show no effect of menopause on body fat distribution. By contrast, studies using dual-energy X-ray absorptiometry showed increased trunk fat in postmenopausal women. Moreover, studies using computed tomography (CT) and magnetic resonance imaging (MRI) show that postmenopausal women have greater amounts of intra-abdominal fat compared to premenopausal women. Collectively, these studies suggest that the menopause transition is associated with an accumulation of central fat and, in particular, intra-abdominal fat. Whether menopause-related differences in trunk or intra-abdominal fat are independent of age and/or adiposity, however, is unclear. Thus, we recently examined the effect of menopausal status on body composition and abdominal fat distribution in 53 middle-aged, premenopausal women (47 +/- 3 years) and 28 early postmenopausal women (51 +/- 4 years). Postmenopausal women had 36% more trunk fat (p < 0.01), 49% greater intra-abdominal fat area (p < 0.01), and 22% greater subcutaneous abdominal fat area (p < 0.05) than premenopausal women. The menopause-related difference in intra-abdominal fat persisted (p < 0.05) after statistical adjustment for age and fat mass, whereas no differences were noted in trunk or abdominal subcutaneous fat. A similar pattern of differences in trunk, subcutaneous, and intra-abdominal fat was observed in subsamples of pre- and postmenopausal women matched for age or fat mass. Our data and that of others suggest that early postmenopausal status is associated with a preferential increase in intra-abdominal fat that is independent of age and total adiposity. Thus, CT and MRI should be used when examining menopause-related changes in body fat distribution.

Effect of menopausal status on insulin-stimulated glucose disposal: comparison of middle-aged premenopausal and early postmenopausal women.

OBJECTIVE: Studies in animal models suggest that ovarian hormone deficiency is associated with the development of insulin resistance. In women, ovarian hormone levels are dramatically reduced after the menopause transition. However, the effect of the menopause transition on insulin sensitivity is unclear. Thus, we examined the effect of menopausal status on insulin sensitivity. RESEARCH DESIGN AND METHODS: Insulin-stimulated glucose disposal was measured in 43 middle-aged premenopausal women (47 +/- 3 years of age) during the luteal phase of the menstrual cycle and 40 early postmenopausal women (51 +/- 4 years; time since menopause, 21 +/- 13 months) using the hyperinsulinemic-euglycemic clamp technique. Body composition was measured by dual-energy X-ray absorptiometry and abdominal fat distribution by computed tomography RESULTS: No difference in fat-free mass (FFM) was found between groups. Total body (P < 0.01), subcutaneous abdominal (P < 0.05), and intra-abdominal (P < 0.01) adiposity were greater in postmenopausal women compared with premenopausal women. No differences in insulin-stimulated glucose disposal were found between premenopausal and postmenopausal women on an absolute basis (pre, 436 +/- 130 vs. post, 446 +/- 120 mg/min), when expressed relative to FFM (pre, 10.7 +/- 3.0 vs. post, 11.5 +/- 3.6 mg x kg(-1) FFM x min(-1)) or when statistically adjusted for FFM (pre, 436 +/- 125 vs. post, 445 +/- 126 mg/min). CONCLUSIONS: These results suggest that menopausal status does not affect insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique.

Energetic adaptation to chronic disease in the elderly.

Several chronic diseases occur with increased prevalence in the elderly. Body weight loss is a common feature of many chronic diseases. Weight loss increases the risk for morbidity and mortality and contributes to decreased functional independence and poor quality of life. Thus, an understanding of the effect of chronic disease on energy balance has important implications for nutritional supplementation and clinical outcome. This brief review will consider recent studies that have examined the effect of several chronic diseases (i.e., Alzheimer's disease, Parkinson's disease, and congestive heart failure) on daily energy expenditure in elderly individuals. Additionally, we put forth a model to explain the energetic adaptation to chronic disease in the elderly that is based on measurements of daily energy expenditure and its components. Studies suggest that chronic disease decreases daily energy expenditure in elderly individuals due to a marked reduction in physical activity energy expenditure. Moreover, these changes in daily energy expenditure often occur in the presence of increased resting energy expenditure. Thus, the net effect of chronic disease is to decrease daily energy expenditure. These results do not favor the hypothesis that increased energy expenditure contributes to disease-related weight loss. Instead, reduced energy intake appears to be a more likely mediator of the negative energy imbalance and weight loss that frequently accompany chronic disease in the elderly.

Regulation of protein metabolism in middle-aged, premenopausal women: roles of adiposity and estradiol.

The age-related loss of fat-free mass (FFM) is accelerated in women during the middle-age years and continues at an increased rate throughout the postmenopausal period. Because protein is the primary structural component of fat-free tissue, changes in FFM are largely due to alterations in protein metabolism. Knowledge of the hormonal and physiological correlates of protein metabolism in middle-aged women, therefore, has important implications for understanding the mechanisms underlying changes in FFM. We measured leucine kinetics (expressed relative to FFM: micromol/kg FFM/h) in 46 middle-aged, premenopausal women (mean +/- SD, 47 +/- 3 yr) after an overnight fast (i.e. basal) and during euglycemic hyperinsulinemia (40 mU/m2/min) using a 5.5-h infusion of [1-13C]leucine. Additionally, we measured insulin-stimulated glucose disposal by euglycemic hyperinsulinemic clamp, body composition by dual energy x-ray absorptiometry, abdominal fat distribution by computed tomography, and hormone levels by RIA as possible correlates of protein metabolism. Under basal conditions, stepwise regression analysis showed that leucine appearance (i.e. protein breakdown) was related to percent body fat and serum estradiol (r2 = 40%; P < 0.01), and leucine oxidation was related to serum estradiol and percent body fat (r2 = 26%; P < 0.05). Under euglycemic hyperinsulinemic conditions, no variables correlated with the percent change in leucine appearance. The percent change in leucine oxidation was related to intraabdominal adipose tissue area and glucose disposal rate (r2 = 48%; P < 0.01). Correlates and r2 values for nonoxidative leucine disposal (i.e. protein synthesis) under basal and euglycemic hyperinsulinemic conditions were similar to those observed for leucine appearance. From these results, we conclude that adiposity and/or serum estradiol may contribute to the regulation of protein metabolism and FFM in middle-aged, premenopausal women.

Misreporting of total energy intake in older African Americans.

OBJECTIVES: (1) To examine misreporting of total energy intake in older African-American men and women using the double-labeled water procedure; and (2) to identify significant physiological and demographic determinants of total energy intake misreporting in older African Americans. DESIGN: Cross-sectional study examining gender differences and determinants of misreporting of total energy intake in older African-American men and women. SUBJECTS: Sixty-four, older African-American men (n=28) and women (n=36); 52-84 y old; body mass index of 20.5-45.1 kg/m2. MEASUREMENTS: Misreporting of total energy intake (difference between reported intakes and measured energy expenditure by doubly labeled water procedure), peak VO2, resting metabolic rate (by indirect calorimetry), indices of body fat and fat distribution (by dual-energy X-ray absorptiometry and anthropometry), income, living arrangement and education (by interview). RESULTS: Older African-American men and women under-reported total energy intake to a modest degree and there were no gender differences in the magnitude of the misreporting. Peak VO2 (a determinant of daily energy requirements) and percentage intakes of fat and protein were significant correlates of misreporting of total energy intake in older African Americans. When these correlates were entered in a multiple regression model, only percentage dietary fat and protein intakes independently predicted misreporting of total energy intake. CONCLUSIONS: Cultural differences in attitudes regarding food and weight have significant effects on misreporting of total energy intake in older African Americans. In addition, individuals who misreported their total energy intake to a greater extent reported consuming less fat and more protein. Misreporting of total energy intake may occur less frequently in older African Americans as compared to other racial groups, since they may be less preoccupied with body size and image. International Journal of Obesity (2000)24, 20-26

Effect of menopausal status on body composition and abdominal fat distribution.

OBJECTIVE: Preliminary studies suggest that the menopause transition is associated with deleterious changes in body composition and abdominal fat distribution. Limitations of the methodology used in these studies, however, render their conclusions controversial. Thus, the present study used radiologic imaging techniques to examine the effect of menopausal status on body composition and abdominal fat distribution. DESIGN: Cross-sectional. SUBJECTS: Fifty-three healthy, middle-aged, premenopausal women (mean+/-SD; 47+/-3 y) and 28 early-postmenopausal women (51+/-4 y). MEASUREMENTS: Total and regional body composition by dual energy X-ray absorptiometry and abdominal fat distribution by computed tomography. RESULTS: No differences in total body fat-free mass or appendicular skeletal muscle mass were noted between groups. In contrast, total body fat mass was 28% higher (23+/-7 vs 18+/-7 kg) and percentage fat 17% higher (35+/-6 vs 30+/-9%; both P<0.01) in postmenopausal women compared with premenopausal women. Postmenopausal women had a 49% greater intra-abdominal (88+/-32 vs 59+/-32 cm2; P<0.01) and a 22% greater abdominal subcutaneous fat area (277+/-93 vs 227+/-108 cm2; P<0.05) compared to premenopausal women. The menopause-related difference in intra-abdominal fat persisted (P<0.05) after statistical adjustment for age and total body fat mass, whereas no difference in abdominal subcutaneous fat was noted. A similar pattern of differences in total and abdominal adiposity was noted in sub-samples of pre- and postmenopausal women matched for age or fat mass. CONCLUSION: Our data suggest that early-postmenopausal status is associated with a preferential increase in intra-abdominal fat that is independent of age and total body fat mass. International Journal of Obesity (2000) 24, 226-231

Physical activity and the progressive change in body composition with aging: current evidence and research issues.

PURPOSE: The purpose was to review studies that have examined the effect of aerobic (AEX) or resistance exercise (REX) on body composition in older individuals (>55 yr). Our goal was to examine the effect of these two exercise paradigms on fat mass and fat-free mass and to consider those factors that may explain variability in findings among studies. METHODS: We conducted a literature search (Medline, 1984-1999) for intervention studies (at least 2 months in duration) that have examined the independent effect of either REX or AEX on body composition in older individuals. RESULTS: AEX decreased fat mass (range: -0.4 to -3.2 kg) but had little effect on fat-free mass. The change in fat mass with AEX was related to the duration of the exercise program (r = 0.51; P < 0.02) but not to body composition methodology. In contrast, REX reduced fat mass (range: -0.9 to -2.7 kg) and increased fat-free mass (range: 1.1 to 2.1 kg). Changes in body composition with REX were not related to body composition methodology or the duration of the exercise program. CONCLUSION: Both AEX and REX appear to be beneficial in reducing body fat. REX appears to have the additional benefit of increasing fat-free mass.

Sex hormone-binding globulin levels in middle-aged premenopausal women. Associations with visceral obesity and metabolic profile.

OBJECTIVE: Low sex hormone-binding globulin (SHBG) levels in women are associated not only with hyperinsulinemia, increased risk for cardiovascular disease, and type 2 diabetes but also with excess body fatness and abdominal obesity. We tested the hypothesis that an elevated total or intra-abdominal adipose tissue accumulation mediates the relationship between low SHBG levels and an altered metabolic profile. RESEARCH DESIGN AND METHODS: We measured body composition (dual-energy X-ray absorptiometry [DEXA]) and body fat distribution (computed tomography) in 52 middle-aged (46.7 +/- 0.4, mean +/- SEM) premenopausal women. Insulin and glucose responses to a 75-g oral glucose load and plasma lipid-lipoprotein levels were also measured. RESULTS: Low plasma SHBG concentrations were associated with increased total body fat mass (r = -0.41, P < 0.005) and subcutaneous abdominal (r = -0.39, P < 0.005) and intra-abdominal (r = -0.37, P < 0.008) adipose tissue area. Low SHBG was also associated with a greater insulin response to oral glucose (r = -0.40, P < 0.005), higher triglyceride levels (r = -0.29, P < 0.05), higher cholesterol/HDL cholesterol ratio (r = -0.51, P < 0.005), but lower HDL cholesterol concentrations (r = 0.65, P < 0.005). When matched for intra-abdominal fat or total fat mass, subjects with either low or high SHBG showed no difference in the insulin response to an oral glucose challenge. Statistical adjustment for differences in intra-abdominal adipose tissue accumulation or total body fat mass also eliminated the associations between SHBG levels and metabolic variables, with the exception of the association between SHBG and HDL cholesterol levels (r = 0.52, P < 0.005). CONCLUSIONS: Our results suggest that the previously reported relationship between low SHBG levels and increased metabolic disease risk in women is mediated, to a large extent, by concomitant variation in body fatness and intra-abdominal adipose tissue accumulation.

Hormonal and physiological correlates of energy expenditure and substrate oxidation in middle-aged, premenopausal women.

An understanding of the hormonal and physiological correlates of energy expenditure and substrate oxidation in middle-aged women will increase our knowledge of factors that promote changes in energy balance and adiposity. We measured resting and postprandial energy expenditure and substrate oxidation in 59 middle-aged, premenopausal women (mean+/-sD age, 47+/-2 yr) to examine the hormonal and physiological correlates of energy and substrate metabolism. Energy expenditure and substrate oxidation were measured at rest using indirect calorimetry and urinary nitrogen excretion and for 180 min after the ingestion of a liquid meal (10 kcal/kg fat-free mass; 410+/-44 Cal). Fasting hormone levels were measured by RIA, glucose tolerance was determined by a 75-g oral glucose tolerance test, body composition was measured by dual energy x-ray absorptiometry, and peak aerobic capacity was determined by a treadmill test. Using stepwise regression analysis, we found that resting energy expenditure was predicted by fat-free mass and serum leptin concentration (r2 = 66%; P < 0.01), fat oxidation was predicted by resting energy expenditure (r2 = 17%; P < 0.01), and carbohydrate oxidation was predicted by serum leptin and appendicular skeletal muscle mass (r2 = 21%;P < 0.01). Novariables were related to postprandial energy expenditure or substrate oxidation. We conclude that in middle-aged, premenopausal women, variation in resting energy expenditure and substrate oxidation is primarily explained by fat-free mass and serum leptin levels. Thus, changes in metabolically active tissue mass or leptin concentration may partially contribute to changes in resting energy expenditure or substrate oxidation in middle-aged women.