Bioimpedance analysis: a useful technique for assessing appendicular lean soft tissue mass and distribution.

The present study was aimed at evaluating the feasibility and reliability of lower limb skeletal muscle (SM) mass estimates obtained by bioimpedance analysis (BIA). BIA estimates were compared with the estimates obtained by dual-energy X-ray absorptiometry (DXA). Ten normal weight and 10 obese women had BIA and DXA evaluations. Lower limb SM mass was then derived from DXA appendicular lean soft tissue estimates. Lower limb SM mass and SM distribution were also estimated from BIA modeling that fits measured resistance values along the leg. SM mass (mean +/- SD) was 5.8 +/- 1.0 kg by BIA vs. 5.8 +/- 1.1 kg by DXA in normal weight subjects and 7.2 +/- 1.4 kg by BIA vs. 7.2 +/- 1.2 kg by DXA in obese subjects. Mean +/- SD of the absolute value of the relative error was 7.0 +/- 3.4 and 5.9 +/- 3.4% in the two groups, respectively. Similar results were obtained by using five resistance values for the analysis. In conclusion, the proposed BIA model provides an adequate means of evaluating appendicular SM mass.     

Estimation of human body composition by electrical impedance methods: a comparative study

This study 1) further validated the relationship between total body electrical conductivity (TOBEC) and densitometrically determined lean body mass (LBMd) and 2) compared with existing body composition techniques (densitometry, total body water, total body potassium, and anthropometry) two new electrical methods for the estimation of LBM: TOBEC, a uniform current induction method, and bioelectrical impedance analysis (BIA), a localized current injection method. In a sample of 75 male and female subjects ranging from 4.9 to 54.9% body fat the correlation between LBMd and LBM predicted from TOBEC by use of a previously developed regression equation was extremely strong (r = 0.962), thus confirming the validity of the TOBEC method. LBM predicted from BIA by use of prediction equations provided with the instrument also correlated with LBMd (r = 0.912) but overestimated LBM compared with LBMd in obese subjects. However, no such systematic error was apparent when new prediction equations derived from this heterogeneous sample of subjects were applied. Thus the TOBEC and BIA methods, which are based on the differing electrical properties of lean tissue and fat and which are convenient, rapid, and safe, correlate well with more cumbersome human body composition techniques.     

Validity of estimating limb muscle volume by bioelectrical impedance.

The present study aimed to investigate the validity of estimating muscle volume by bioelectrical impedance analysis. Bioelectrical impedance and series cross-sectional images of the forearm, upper arm, lower leg, and thigh on the right side were determined in 22 healthy young adult men using a specially designed bioelectrical impedance acquisition system and magnetic resonance imaging (MRI) method, respectively. The impedance index (L(2)/Z) for every segment, calculated as the ratio of segment length squared to the impedance, was significantly correlated to the muscle volume measured by MRI, with r = 0.902-0.976 (P < 0.05). In these relationships, the SE of estimation was 38.4 cm(3) for the forearm, 40.9 cm(3) for the upper arm, 107.2 cm(3) for the lower leg, and 362.3 cm(3) for the thigh. Moreover, isometric torque developed in elbow flexion or extension and knee flexion or extension was significantly correlated to the L(2)/Z values of the upper arm and thigh, respectively, with correlation coefficients of 0.770-0.937 (P < 0.05), which differed insignificantly from those (0.799-0.958; P < 0.05) in the corresponding relationships with the muscle volume measured by MRI of elbow flexors or extensors and knee flexors or extensors. Thus the present study indicates that bioelectrical impedance analysis may be useful to predict the muscle volume and to investigate possible relations between muscle size and strength capability in a limited segment of the upper and lower limbs.     

Estimation of segmental muscle volume by bioelectrical impedance spectroscopy.

This study validated bioelectrical impedance spectroscopy (BIS) with Cole-Cole modeled measurements of calf and arm segmental water volume and volume changes during 72 h of simulated microgravity and caloric restriction by using magnetic resonance imaging (MRI) muscle volume as a criterion method. MRI and BIS measurements of calf and upper arm segments were made in 18 healthy men and women [age, 29 +/- 8 (SD) yr; height, 171 +/- 11 cm; mass, 71 +/- 16 kg] before and after the intervention. Muscle volume of arm and leg segments by MRI was on average 15 +/- 10 and 14 +/- 8% lower, respectively, than the estimated total water volume by BIS (P < 0.01), but their correlations were excellent (r = 0.96 and r = 0.93, respectively). MRI- vs. BIS-predicted volume changes were a decrease of 49 +/- 68 vs. 41 +/- 62 ml in the calf and a decrease of 18 +/- 23 vs. 11 +/- 24 ml in the arm, respectively (P > 0.05 for both). BIS detected the extracellular water shifts in the calf resulting from the head-down tilt treatment, but the underfeeding protocol was not of sufficient duration or intensity to produce limb intracellular water changes detectable by BIS. BIS was highly correlated with segmental muscle volume and tracked changes associated with head-down tilt. Further research, however, is needed to determine whether BIS can accurately access separate changes in intracellular and extracellular volume.     

Reliability and validity of body composition measures in female athletes.

The purpose of this investigation was to determine the reliability and validity of bioelectrical impedance (BIA) and near-infrared interactance (NIR) for estimating body composition in female athletes. Dual-energy X-ray absorptiometry was used as the criterion measure for fat-free mass (FFM). Studies were performed in 132 athletes [age = 20.4 +/- 1.5 (SD) yr]. Intraclass reliabilities (repeat and single trial) were 0.987-0.997 for BIA (resistance and reactance) and 0.957-0.980 for NIR (optical densities). Validity of BIA and NIR was assessed by double cross-validation. Because correlations were high (r = 0.969-0.983) and prediction errors low, a single equation was developed by using all 132 subjects for both BIA and NIR. Also, an equation was developed for all subjects by using height and weight only. Results from dual-energy X-ray absorptiometry analysis showed FFM = 49.5 +/- 6.0 kg, which corresponded to %body fat (%BF) of 20.4 +/- 3.1%. BIA predicted FFM at 49.4 +/- 5.9 kg (r = 0.981, SEE = 1.1), and NIR prediction was 49. 5 +/- 5.8 kg (r = 0.975, SEE = 1.2). Height and weight alone predicted FFM at 49.4 +/- 5.7 kg (r = 0.961, SEE = 1.6). When converted to %BF, prediction errors were approximately 1.8% for BIA and NIR and 2.9% for height and weight. Results showed BIA and NIR to be extremely reliable and valid techniques for estimating body composition in college-age female athletes.     

Sex and limb-specific ischemic reperfusion and vascular reactivity

With little known regarding sex and limb heterogeneity, we investigated vascular reactivity and ischemic reperfusion (IR) in the upper and lower extremities of 15 healthy men (26 +/- 2 yr) and women (23 +/- 1 yr). Doppler ultrasound was used to evaluate IR and flow-mediated dilation (FMD) after suprasystolic cuff occlusion in both the arm [brachial artery (BA)] and the leg [popliteal artery (PA)]. Cumulative IR [area under the curve (AUC)], normalized for muscle mass, revealed no sex-related differences in either limb (forearm: men 38 +/- 3 and women 44 +/- 4 ml/100 g; lower leg: men 12 +/- 2 and women 14 +/- 2 ml/100 g), while both groups revealed a greater IR per unit of arm muscle mass (AUC) compared with the lower leg (P < 0.05). The BA and PA were smaller in women (BA 0.31 +/- 0.1, PA 0.47 +/- 0.1 cm) than in men (BA 0.41 +/- 0.1, PA 0.6 +/- 0.2 cm). Absolute FMD/shear rate revealed attenuated vascular function in the PA of the women [women 3.3 +/- 0.6, men 5.0 +/- 0.8 (all x10(-6)) cm/s(-1).s] and no sex difference in the BA [women 1.2 +/- 0.2, men 1.6 +/- 0.1 (all x10(-6)) cm/s(-1).s]. In both sexes the PA demonstrated greater vascular reactivity than the BA. Thus vascular reactivity in healthy young people is greater in the legs, regardless of sex, and women have vascular function similar to men in the upper extremities but appear to have poorer vascular function normalized for shear rate in the lower extremities.     

Fatty acid transport protein-1 mRNA expression in skeletal muscle and in adipose tissue in humans

Fatty acid transporter protein (FATP)-1 mRNA expression was investigated in skeletal muscle and in subcutaneous abdominal adipose tissue of 17 healthy lean, 13 nondiabetic obese, and 16 obese type 2 diabetic subjects. In muscle, FATP-1 mRNA levels were higher in lean women than in lean men (2.2 +/- 0.1 vs. 0.6 +/- 0.2 amol/microg total RNA, P < 0.01). FATP-1 mRNA expression was decreased in skeletal muscle in obese women both in nondiabetic and in type 2 diabetic patients (P < 0.02 vs. lean women in both groups), and in all women there was a negative correlation with basal FATP-1 mRNA level and body mass index (r = -0.74, P < 0.02). In men, FATP-1 mRNA was expressed at similar levels in the three groups both in skeletal muscle (0.6 +/- 0.2, 0.6 +/- 0.2, and 0.8 +/- 0.2 amol/microg total RNA in lean, obese, and type 2 diabetic male subjects) and in adipose tissue (0.9 +/- 0.2 amol/microg total RNA in the 3 groups). Insulin infusion (3 h) reduced FATP-1 mRNA levels in muscle in lean women but not in lean men. Insulin did not affect FATP-1 mRNA expression in skeletal muscle in obese nondiabetic or in type 2 diabetic subjects nor in subcutaneous adipose tissue in any of the three groups. These data show a gender-related difference in the expression of the fatty acid transporter FATP-1 in skeletal muscle of lean individuals and suggest that changes in FATP-1 expression may not contribute to a large extent to the alterations in fatty acid uptake in obesity and/or type 2 diabetes.     

Lower limb skeletal muscle mass: development of dual-energy X-ray absorptiometry prediction model.

Although magnetic resonance imaging (MRI) can accurately measure lower limb skeletal muscle (SM) mass, this method is complex and costly. A potential practical alternative is to estimate lower limb SM with dual-energy X-ray absorptiometry (DXA). The aim of the present study was to develop and validate DXA-SM prediction equations. Identical landmarks (i.e., inferior border of the ischial tuberosity) were selected for separating lower limb from trunk. Lower limb SM was measured by MRI, and lower limb fat-free soft tissue was measured by DXA. A total of 207 adults (104 men and 103 women) were evaluated [age 43 +/- 16 (SD) yr, body mass index (BMI) 24.6 +/- 3.7 kg/m(2)]. Strong correlations were observed between lower limb SM and lower limb fat-free soft tissue (R(2) = 0.89, P < 0.001); age and BMI were small but significant SM predictor variables. In the cross-validation sample, the differences between MRI-measured and DXA-predicted SM mass were small (-0.006 +/- 1.07 and -0.016 +/- 1.05 kg) for two different proposed prediction equations, one with fat-free soft tissue and the other with added age and BMI as predictor variables. DXA-measured lower limb fat-free soft tissue, along with other easily acquired measures, can be used to reliably predict lower limb skeletal muscle mass.     

Percentage of total body fat as estimated by three automatic bioelectrical impedance analyzers

The present study aimed to compare the accuracy of estimating the percentage of total body fat (%TBF) among three bioelectrical impedance analysis (BIA) devices: a single-frequency BIA with four tactile electrodes (SF-BIA4), a single-frequency BIA with eight tactile electrodes (SF-BIA8) and a multi-frequency BIA with eight tactile electrodes (MF-BIA8). Dual-energy x-ray absorptiometry (DXA) and hydrostatic weighing (HW) were used as references for the measured values. Forty-five healthy college student volunteers (21 males: 172.9 +/- 5.5 cm and 65.8 +/- 9.1 kg and 24 females: 160.7 +/- 6.6 cm, 52.6 +/- 6.2 kg) were the subjects. Correlation coefficients between the BIA measurements and the references were calculated. The standard error of estimation (SEE) was calculated by regression analysis when estimating the reference measures (DXA and HW) from the predictor (SF-BIA4, SF-BIA8 and MF-BIA8). The differences in %TBF between the reference and the predictor, calculated by the reference minus the predictor, were plotted against the %TBF measured by the references. The MF-BIA 8 here showed the highest correspondence to the reference and the least estimation error compared with the other BIA methods. It is considered that there is a limit to directly estimate FFM from a regression equation using impedance, weight, height and age as independent variables, and that %TBF can be more accurately estimated by measuring segmental impedances using eight electrodes and multi-frequency electric currents and then estimating total body water from these impedances.     

Regional changes in muscle mass following 17 weeks of bed rest.

This work reports on the muscle loss and recovery after 17 wk of continuous bed rest and 8 wk of reambulation in eight normal male volunteers. Muscle changes were assessed by urinary levels of 3-methylhistidine (3-MeH), nitrogen balance, dual-photon absorptiometry (DPA), magnetic resonance imaging (MRI), and isokinetic muscle performance. The total body lean tissue loss during bed rest calculated from nitrogen balance was 3.9 +/- 2.1 (SD) kg (P < 0.05). Although the total loss is minimal, DPA scans showed that nearly all of the lean tissue loss occurred in the lower limbs. Similarly, MRI muscle volume measurements showed greater percent loss in the limbs relative to the back muscles. MRI, DPA, and nitrogen balance suggest that muscle atrophy continued throughout bed rest with rapid recovery after reambulation. Isokinetic muscle strength decreased significantly (P < 0.05) in the thigh and calf with no loss in the arms and with rapid recovery during reambulation. We conclude that there is great variability in the degree and location of muscle loss in bed rest and that the lower limb muscles are primarily affected.     

The influence of posture change on measurements of relative body fat in the bioimpedance analysis method

The purpose of this study was to clarify the influence of posture change on relative body fat in the bioelectrical impedance analysis (BIA) method. The subjects were 30 Japanese healthy young adult males (age: 19.8 +/- 1.4 years, height: 172.3 +/- 5.8 cm, weight: 67.1 +/- 8.2 kg). We used devices with different body segment inductions, between the hand and foot (H-F BIA) and between hands (H-H BIA), and set four measurement conditions differing in posture (supine or sitting), during rest and measurement. The reliabilities of %BF in the H-H and H-F BIA methods were very high (r = 0.995, 0.966), and the relationship in %BF between the UW method and each BIA method was mid-range (r = 0.767, 0.709). Although there were no differences in %BF among different measurement postures in the H-F BIA method, %BF in the H-H BIA method increased significantly when the posture was changed just before measurement. This indicated that it is necessary to pay attention to the posture change just before measurement in the H-H BIA method.     

Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength

The effect of recombinant DNA human growth hormone (rhGH) treatment in adults with growth hormone (GH) deficiency was studied in 24 patients in a double-blind placebo-controlled trial. The dose was 0.07 U/kg body wt daily. After 6 mo of treatment, significant increases were noted in the rhGH group for total cross-sectional area of thigh muscle (+11.2 +/- 3.1 vs. -0.5 +/- 3.0 cm2; P = 0.015 vs. placebo) and quadriceps muscle (+4.1 +/- 0.8 vs. +0.4 +/- 1.2 cm2; P = 0.031) measured by computerized tomography. Strong correlations were noted between lean body mass (measured as total body potassium) and total thigh muscle area in normal and GH-deficient adults both before and after rhGH treatment. Strength of hip flexors (+1.25 +/- 0.27 vs. +0.25 +/- 0.12 z-scores; P = 0.004) and limb girdle muscles increased (P = 0.02) in the rhGH group. We conclude that 1) rhGH increases lean tissue and skeletal muscle mass in adults with human GH deficiency, 2) this suggests a role for GH in the regulation of body composition of adult humans, 3) the increase in strength of limb girdle muscles after rhGH treatment suggests that adults with GH deficiency may have a proximal myopathy, and 4) the failure to demonstrate an increase in strength in other muscle groups may require the study of larger numbers of patients.     

Comparison of responses to strenuous eccentric exercise of the elbow flexors between resistance-trained and untrained men

This study compared resistance-trained and untrained men for changes in commonly used indirect markers of muscle damage after maximal voluntary eccentric exercise of the elbow flexors. Fifteen trained men (28.2 +/- 1.9 years, 175.0 +/- 1.6 cm, and 77.6 +/- 1.9 kg) who had resistance trained for at least 3 sessions per week incorporating exercises involving the elbow flexor musculature for an average of 7.7 +/- 1.4 years, and 15 untrained men (30.0 +/- 1.5 years, 169.8 +/- 7.4 cm, and 79.9 +/- 4.4 kg) who had not performed any resistance training for at least 1 year, were recruited for this study. All subjects performed 10 sets of 6 maximal voluntary eccentric actions of the elbow flexors of one arm against the lever arm of an isokinetic dynamometer moving at a constant velocity of 90 degrees .s. Changes in maximal voluntary isometric and isokinetic torque, range of motion, upper arm circumference, plasma creatine kinase activity, and muscle soreness before, immediately after, and for 5 days after exercise were compared between groups. The trained group showed significantly (P < 0.05) smaller changes in all of the measures except for muscle soreness and faster recovery of muscle function compared with the untrained group. For example, muscle strength of the trained group recovered to the baseline by 3 days after exercise, where the untrained group showed approximately 40% lower strength than baseline. These results suggest that resistance-trained men are less susceptible to muscle damage induced by maximal eccentric exercise than untrained subjects.     

Upper limb muscle volumes in adult subjects

Muscle force-generating properties are often derived from cadaveric studies of muscle architecture. While the relative sizes of muscles at a single upper limb joint have been established in cadaveric specimens, the relative sizes of muscles across upper limb joints in living subjects remain unclear. We used magnetic resonance imaging to measure the volumes of the 32 upper limb muscles crossing the glenohumeral joint, elbow, forearm, and wrist in 10 young, healthy subjects, ranging from a 20th percentile female to a 97th percentile male, based on height. We measured the volume and volume fraction of these muscles. Muscles crossing the shoulder, elbow, and wrist comprised 52.5, 31.4, and 16.0% of the total muscle volume, respectively. The deltoid had the largest volume fraction (15.2%+/-1%) and the extensor indicis propius had the smallest (0.2%+/-0.05%). We determined that the distribution of muscle volume in the upper limb is highly conserved across these subjects with a three-fold variation in total muscle volumes (1427-4426cm(3)). When we predicted the volume of an individual muscle from the mean volume fraction, on average 85% of the variation among subjects was accounted for (average p=0.0008). This study provides normative data that forms the basis for investigating muscle volumes in other populations, and for scaling computer models to more accurately represent the muscle volume of a specific individual.     

Body composition assessment in extreme obesity and after massive weight loss induced by gastric bypass surgery

Body composition methods were examined in 20 women [body mass index (BMI) 48.7 +/- 8.8 kg/m(2)] before and after weight loss [-44.8 +/- 14.6 (SD) kg] after gastric bypass (GBP) surgery. The reference method, a three-compartment (3C) model using body density by air displacement plethysmography and total body water (TBW) by H(2)18O dilution (3C-H(2)18O), showed a decrease in percent body fat (%BF) from 51.4 to 34.6%. Fat-free mass hydration was significantly higher than the reference value (0.738) in extreme obesity (0.756; P < 0.001) but not after weight reduction (0.747; P = 0.16). %BF by H(2)18O dilution and air displacement plethysmography differed significantly from %BF by 3C-H(2)18O in extreme obesity (P < 0.05) and 3C models using (2)H(2)O or bioelectrical impedance analysis (BIA) to determine TBW improved mean %BF estimates over most other methods at both time points. BIA results varied with the equation used, but BIA better predicted %BF than did BMI at both time points. All methods except BIA using the Segal equation were comparable to the reference method for determining changes over time. A simple 3C model utilizing air displacement plethysmography and BIA is useful for clinical evaluation in this population.     

Metabolically active components of fat free mass and resting energy expenditure in nonobese adults

Resting energy expenditure (REE) and components of fat-free mass (FFM) were assessed in 26 healthy nonobese adults (13 males, 13 females). Detailed body composition analyses were performed by the combined use of dual-energy X-ray absorptiometry (DEXA), magnetic resonance imaging (MRI), bioelectrical impedance analysis (BIA), and anthropometrics. We found close correlations between REE and FFM(BIA) (r = 0.92), muscle mass(DEXA) (r = 0.89), and sum of internal organs(MRI) (r = 0.90). In a multiple stepwise regression analysis, FFM(BIA) alone explained 85% of the variance in REE (standard error of the estimate 423 kJ/day). Including the sum of internal organs(MRI) into the model increased the r(2) to 0.89 with a standard error of 381 kJ/day. With respect to individual organs, only skeletal muscle(DEXA) and liver mass(MRI) significantly contributed to REE. Prediction of REE based on 1) individual organ masses and 2) a constant metabolic rate per kilogram organ mass was very close to the measured REE, with a mean prediction error of 96 kJ/day. The very close agreement between measured and predicted REE argues against significant variations in specific REEs of individual organs. In conclusion, the mass of internal organs contributes significantly to the variance in REE.     

Estimation of skeletal muscle mass by bioelectrical impedance analysis.

The purpose of this study was to develop and cross-validate predictive equations for estimating skeletal muscle (SM) mass using bioelectrical impedance analysis (BIA). Whole body SM mass, determined by magnetic resonance imaging, was compared with BIA measurements in a multiethnic sample of 388 men and women, aged 18-86 yr, at two different laboratories. Within each laboratory, equations for predicting SM mass from BIA measurements were derived using the data of the Caucasian subjects. These equations were then applied to the Caucasian subjects from the other laboratory to cross-validate the BIA method. Because the equations cross-validated (i.e., were not different), the data from both laboratories were pooled to generate the final regression equation SM mass (kg) = [(Ht²/ R x 0.401) + (gender x 3.825) + (age x -0. 071)] + 5.102 where Ht is height in centimeters; R is BIA resistance in ohms; for gender, men = 1 and women = 0; and age is in years. The r(2) and SE of estimate of the regression equation were 0.86 and 2.7 kg (9%), respectively. The Caucasian-derived equation was applicable to Hispanics and African-Americans, but it underestimated SM mass in Asians. These results suggest that the BIA equation provides valid estimates of SM mass in healthy adults varying in age and adiposity.     

Validity of leg-to-leg bioelectrical impedance measurement in highly active women

The aim of this study was to compare the validity of the leg-to-leg bioelectrical impedance analysis (BIA) method with that of anthropometry using hydrostatic weighing (HW) as the criterion test. A secondary objective was to cross-validate previously developed anthropometric regression equations as well as to develop a new regression equation formula based on the anthropometric data collected in this study. Three methods for assessing body composition (HW, BIA, and anthropometric) were applied to 60 women university athletes. The means and standard deviations of age, weight, height, and body mass index (BMI) of athletes were as follows: age, 20.70 +/- 1.43; weight, 56.19 +/- 7.83 kg; height, 163.33 +/- 6.11 cm; BMI, 21.01 +/- 2.63 kg x m(-2). Leg-to-leg BIA (11.82 +/- 2.39) has shown no statistical difference between percentage body fat determined by HW (11.63 +/- 2.42%) in highly active women (p > 0.05). This result suggests that the leg-to-leg BIA and HW methods were somewhat interchangeable in highly active women (R = 0.667; standard error of estimate [SEE] = 1.81). As a result of all cross-validation analyses, anthropometric and BIA plus anthropometric results have generally produced lower regression coefficients and higher SEEs for highly active women between the ages of 18 and 25 years. The regression coefficients (0.903, 0.926) and SEE (1.08, 0.96) for the new regression formulas developed from this study were better than the all the other formulas used in this study.     

Effects of fasting on insulin action and glucose kinetics in lean and obese men and women

The development of insulin resistance in the obese individual could impair the ability to appropriately adjust metabolism to perturbations in energy balance. We investigated a 12- vs. 48-h fast on hepatic glucose production (R(a)), peripheral glucose uptake (R(d)), and skeletal muscle insulin signaling in lean and obese subjects. Healthy lean [n = 14; age = 28.0 +/- 1.4 yr; body mass index (BMI) = 22.8 +/- 0.42] and nondiabetic obese (n = 11; age = 34.6 +/- 2.3 yr; BMI = 36.1 +/- 1.5) subjects were studied following a 12- and 48-h fast during 2 h of rest and a 3-h 40 mUxm(-2)xmin(-1) hyperinsulinemic-euglycemic clamp (HEC). Basal glucose R(a) decreased significantly from the 12- to 48-h fast (lean 1.96 +/- 0.23 to 1.63 +/- 0.15; obese 1.23 +/- 0.07 to 1.07 +/- 0.07 mgxkg(-1)xmin(-1); P = 0.004) and was equally suppressed during the HEC after both fasts. The increase in glucose R(d) during the HEC after the 12-h fast was significantly decreased in lean and obese subjects after the 48-h fast (lean 9.03 +/- 1.17 to 4.16 +/- 0.34, obese 6.10 +/- 0.77 to 3.56 +/- 0.30 mgxkg FFM(-1)xmin(-1); P < 0.001). After the 12- but not the 48-h fast, insulin-stimulated AKT Ser(473) phosphorylation was greater in lean than obese subjects. We conclude that 1) 48 h of fasting produces a marked decline in peripheral insulin action, while suppression of hepatic glucose production is maintained in lean and obese men and women; and 2) the magnitude of this decline is greater in lean vs. obese subjects.