Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education

OBJECTIVE: To investigate whether the changes in vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before and after weight reduction in Japanese overweight men are associated with changes in body mass index (BMI), visceral, subcutaneous fat, VO(2) and work rate (WR) at ventilatory threshold (VT). DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: In total, 30 Japanese overweight men (BMI, 29.0+/-2.2 kg/m(2)) and 31 normal-weight men (BMI, 22.5+/-1.6 kg/m(2)) at baseline were enrolled: 30 overweight men (BMI, 29.0+/-2.2 kg/m(2)) were further enrolled into a 6-month exercise program. MEASUREMENTS: Fat distribution evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, angiogenic peptides including VEGF and bFGF, exercise tests at baseline and after 6 months. RESULTS: In normal-weight and overweight subjects at baseline, VEGF positively correlated with S area (r=0.350, P=0.007) but not with V area. In contrast, bFGF negatively correlated with BMI (r=-0.619, P<0.001), S (r=-0.457, P<0.001) and V areas (r=-0.466, P<0.001). By intervention with exercise education, 30 overweight subjects showed reduction in BMI (29.0+/-2.2 to 28.0+/-2.0, P<0.001), V and S areas, increase in VO(2) and WR at VT, increase in bFGF (9.21+/-5.82-21.2+/-7.04 ng/ml, P<0.001), and no change in VEGF (1.45+/-0.72-1.88+/-0.52 ng/ml, P=0.016). The stepwise multiple regression analysis revealed that DeltaBMI (beta=-6.052) and DeltaVO(2) (beta=2.806) were independently related to DeltabFGF (P<0.001) and all other variables including DeltaS area, and DeltaV area, and DeltaWR did not enter the equation at significant levels. CONCLUSION: The present study indicated a negative correlation between serum bFGF levels and BMI at baseline as well as an association of DeltaBMI and DeltaVO(2) with DeltabFGF after exercise intervention. The exercise-induced elevation of bFGF may be beneficial in the prevention of the atherosclerosis in overweight subjects.     

Changes in serum leptin concentrations in overweight Japanese men after exercise

AIM: To investigate the link between serum leptin concentrations and exercise. DESIGN: Cross-sectional and longitudinal studies of an exercise intervention. SUBJECTS: 110 Japanese overweight men aged 32-59 years were recruited. At baseline, the average body mass index (BMI) was 28.5 +/- 2.5 kg/m2. From this group, we used data of 36 overweight men (BMI, 28.9 +/- 2.3) for a 1-year exercise programme. MEASUREMENTS: Leptin was measured at baseline and after 1 year. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical levels. Anthropometric parameters, aerobic exercise level, muscle strength and flexibility were also investigated at baseline and after 1 year. RESULTS: In the first analysis, using cross-sectional data, leptin was significantly correlated with total body fat (r = 0.760, p < 0.01), V (r = 0.383, p < 0.01) and S (r = 0.617, p < 0.01) areas. In the second analysis, using longitudinal data, leptin was significantly reduced after 1 year (pre 6.7 +/- 4.0 ng/ml vs. post 5.1 +/- 3.1 ng/ml, p < 0.01). Results showed that steps per day were increased, and aerobic exercise level, weight-bearing index (WBI) and insulin resistance were significantly improved. Although, there was a positive correlation between Delta leptin(positive changes in leptin after 1 year) and anthropometric measurements such as Delta body weight, Delta BMI and Delta body fat, leptin/body weight, leptin/BMI and leptin/body fat ratios were significantly reduced during exercise intervention. CONCLUSION: The present study indicated exercise significantly lowers serum leptin concentrations, and thus it may improve the leptin resistance observed in overweight Japanese men.     

Daily exercise lowers blood pressure and reduces visceral adipose tissue areas in overweight Japanese men

OBJECTIVE: To investigate the link between a reduction in blood pressure (BP) and daily exercise. DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: 43 overweight Japanese men aged 32-59 years (BMI, 29.0+/-2.3 kg/m2) at baseline. Among the participants, a randomly selected 23 overweight men (BMI, 28.5+/-1.7) were further enrolled into the 10 months exercise program. MEASUREMENTS: BP was measured every week and steps per day were also recorded every day throughout the observation period. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical level, at before, 5 months and after intervention. Anthropometric parameters were also measured at same point. Aerobic exercise level, muscle strength, flexibility and calorie intake and insulin resistance (HOMA index) were investigated at before and after the study. RESULTS: In a cross sectional analysis, systolic BP (SBP) and diastolic BP (DBP) were significantly correlated with body composition. In a second longitudinal analysis, SBP was significantly reduced at 2 months and DBP was also reduced at 3 months, and almost maintained until the end of the observation period. Increasing daily walking was observed in 3 months and maintained until 10 months. Body composition, aerobic exercise level, muscle strength, flexibility and insulin resistance were significantly improved. There was positive correlation between DeltaDBP and Deltavisceral fat area (1-5, 5-10, 1-10 months). By stepwise multiple regression analysis, only Deltavisceral fat area was independently related to DeltaDBP at a significant level (1-10 months: DeltaDBP=-0.608+0.105Deltavisceral fat area, r2=0.227, P=0.0334). CONCLUSION: The present study indicated daily exercise lowers BP and visceral fat area is the critical factor for BP change.     

Effect of resistance exercise (body building) training on serum leptin levels in young men. Implications for relationship between body mass index and serum leptin

Available data about the influence of exercise on leptin level are controversial, and there are no studies concerning leptin levels in trained men with low fat mass plus large increase of muscle. 65 healthy young male matched for age were separated in three groups. 1) 25 non-professional body builders; 2) 21 mild overweight sedentary subjects; 3) 19 normal weight sedentary controls. Body composition was determined by bioelectrical impedance. Serum leptin was measured in duplicate by RIA. Statistics: Student's t and Pearson's test. Athletes showed similar BMI than overweight subjects: 26.98+/-0.49 vs 27.12+/-0.41 but lower fat mass: 12.53+/-0.96 vs 16.16+/-1.01 % (p=0.0064) and lower leptin: 4.66+/-0.51 vs 7.31+/-0.76 microg/l (p=0.014). Athletes showed higher BMI than controls: 26.98+/-0.49 vs 23.08+/-0.30 (p<0.0001) but similar fat mass: 12.53+/-0.96 vs 12.48+/-0.73% and leptin: 4.66+/-0.51 vs 4.79+0.58 microg/l. Overweight subjects showed higher BMI than controls: 27.12+/-0.41 vs 23.08+/-0.30 (p<0.0001), higher fat mass: 16.16+/-1.01 vs 12.48+/-0.73% (p=0.0064) and higher leptin: 7.31+/-0.76 vs 4.79+/-0.589 microg/l (p=0.014). When leptin was calculated by fat mass no differences were observed between the three groups. There was a significant correlation between leptin and fat mass in all groups. Leptin correlated with BMI in overweight subjects (r=0.438, p=0.0463), but this correlation was not observed either in athletes or in controls. In conclusion 1) regardless of the high BMI characteristic of body builders, no correlation was observed with leptin; 2) trained state induced by resistance exercise does not influence leptin production independently of variations in body composition.     

Exercise training-induced triglyceride lowering negatively correlates with DHEA levels in men with type 2 diabetes

OBJECTIVE: To investigate the effect of an exercise training program on lipid profile in correlation with DHEA level and body weight and body composition in type 2 diabetic men. DESIGN: Longitudinal, controlled clinical intervention study with exercise training consisting of an 8 week supervised program of aerobic exercise (75% VO(2) peak, 45 min), twice a week and intermittent exercise, once a week, on a bicycle ergometer. SUBJECTS: Sixteen men (age 45.4+/-7.2 y (mean+/-s.d.), HbA1c 8.15+/-1.7%, body mass index (BMI) 29.6+/-4.6 kg/m(2)) were randomly divided into two groups: trained group (n=8) and control group (n=8). MEASUREMENTS: Lipid, apo- and lipoprotein and DHEA concentrations. Cross-sectional areas of subcutaneous and visceral adipose tissue and mid-thigh muscle by magnetic resonance imaging. RESULTS: Training decreased visceral (153.25+/-38.55 vs 84.20+/-21.30 cm(2), P<0.001), subcutaneous (241.55+/-49.55 vs 198.00+/-39.99 cm(2), P<0.001) adipose tissue area and triglyceride levels (2.59+/-1.90 vs 1.79+/-1.08 nmol/l, P<0.05) and increased mid-thigh muscle cross-sectional area (148.30+/-36.10 vs 184.35+/-35.85 cm(2), P<0.001), and DHEA levels (11.00+/-3.10 vs 14.25+/-4.10 nmol/l, P<0.05) with no modification in body weight. Changes in triglycerides were negatively correlated with changes in DHEA (r=-0.81, P=0.03). This correlation was independent of changes in abdominal fat distribution. CONCLUSION: Training decreases abdominal fat depots, improves muscular mass and affects favourably triglyceride and DHEA levels. Changes in triglycerides and DHEA were inversely related.     

Insulin-like growth factor-I response to a single bolus of growth hormone is increased in obesity

Reduced GH levels are found in obesity; despite which IGF-I levels are reported as low normal or normal. Previously peripheral responsiveness to GH has been investigated and reported to be increased in obese men and premenopausal women; however, the use of weight-based GH doses in these studies made data interpretation difficult. GH binding protein (GHBP) measurement constitutes an indirect estimate of GH receptor number. GHBP has been reported to be elevated in obesity; however, results from a recent study implied that this was only in men and premenopausal but not postmenopausal women. Therefore, we pursued this question further by challenging a cohort of healthy normal-weight and obese subjects with a non-weight-based dose of GH and examined the relationship of GHBP with the IGF-I response in the context of their body composition. Ninety-eight (40 male) healthy subjects with a wide range of ages and body mass index (BMI) were studied. Ninety-one (34 male) of these subjects were divided into groups of similar age: men and women with a BMI less than 30 [normal-weight men (NM), BMI 26 (22-29) kg/m(2) (n = 19) and women (NW), BMI 24 (19-29) kg/m(2) (n = 23) and with a BMI > 30 (obese men (OM), 41 (30-72) kg/m(2) (n = 15) and women (OW), 43 (30-68) kg/m(2) (n = 34)]. Fat mass and percentage fat were measured by a bioelectrical impedance analyzer. An IGF-I generation test, which involved a sc injection of 21 IU (7 mg) GH, was performed. At baseline serum samples were assayed for GHBP; serum IGF-I and IGFBP3 levels were measured both at baseline and 24 h after GH administration. There was a higher increment IGF-I in obese men and women, compared with the equivalent normal-weight subjects [NM vs. OM: 245 (33-342) vs. 291 (192-427) ng/ml (P < 0.05); NW vs. OW: 220 (103-435) vs. 315 (144-450) ng/ml (P < 0.0005)]. Increment IGF-I was negatively correlated with baseline IGF-I (F = 12.1) and positively correlated with GHBP (F = 18.2) (R(2) = 0.29). GHBP levels were significantly higher in OM and OW (pre- and postmenopausal) than in the equivalent normal-weight groups [NM vs. OM: 2175 (995-4190) vs. 3030 (1540-5470) pmol/liter (P < 0.05); NW vs. OW: 2131 (1010-5040) vs. 3585 (1540-5740) pmol/liter (P < 0.0005)]. GHBP levels correlated highly with BMI, percentage fat, and fat mass (R > 0.6, P < 0.0001). Baseline IGF-I was not affected by body composition. In conclusion, in obese compared with normal-weight healthy subjects, there is a larger increment IGF-I to a single bolus of GH in men, and irrespective of menopausal status, women. Increment IGF-I is associated positively with GHBP level, which in turn is associated with markers of increasing obesity in men and women. GH responsiveness is increased in obesity.     

A novel method of measuring intra-abdominal fat volume using helical computed tomography

OBJECTIVES: :We present a novel method of scanning for intra-abdominal fat volume by helical computed tomography (CT), and describe the clinical significance of measuring the volumes of intra-abdominal visceral fat (V(vol)) and subcutaneous fat (S(vol)) vs these respective areas determined by conventional slice-by-slice CT at the umbilical level. METHOD: Subjects with obesity or hyperlipidemia (79 men, 74 women) were recruited for this study. We obtained helical CT scans with a tube current of 150 mA, voltage of 120 kV and 2:1 pitch (table speed in relation to slice thickness), starting at the upper edge of the liver and continuing until the pelvis. The intra-abdominal visceral fat volume was measured by drawing a line within the muscle wall surrounding the abdominal cavity. The abdominal subcutaneous fat volume was calculated by subtracting the visceral fat volume from the total abdominal fat volume. By comparison, the intra-abdominal visceral and subcutaneous fat areas were determined at the umbilical level by the established slice-by-slice CT scanning technique. RESULTS: V(vol) was correlated positively with visceral fat area (V(area)) measured by conventional CT in both genders (in men (n=79) V(vol) vs V(area), r=0.81 P<0.0001; in women (n=74) V(vol) vs V(area), r=0.85, P<0.0001). S(vol) also showed a positive correlation with subcutaneous fat area (S(area)) in both genders (in men (n=78) S(vol) vs S(area), r=0.95, P<0.0001; in women (n=74) S(vol) vs S(area), r=0.92, P<0.0001). CONCLUSION: We have reported a novel method for measuring intra-abdominal fat volume by the use of helical CT.     

Influence of human body composition on serum peak thyrotropin (TSH) after recombinant human TSH administration in patients with differentiated thyroid carcinoma

OBJECTIVES: In this study, we evaluated the influence of height, weight, body mass index (BMI), body surface area, and body composition [total lean body mass (LBM) and fat body mass] on serum peak TSH levels obtained after recombinant human (rh)TSH. Furthermore, to verify whether the serum peak TSH influenced the efficacy of radioiodine ((131)I), we compared the rate of thyroid remnant ablation according to the patients' BMI. PATIENTS: We studied 105 patients with differentiated thyroid carcinoma who underwent rhTSH stimulation test. Serum TSH measurements were performed before and 24, 48, and 72 h after rhTSH administration. We also compared the rate of thyroid remnant ablation among 70 differentiated thyroid carcinoma patients with different BMI. RESULTS: The serum peak TSH after rhTSH was significantly lower in overweight and obese subjects compared with normal-weight subjects (92.1 +/- 41.8, 82.4 +/- 24.2, and 112.7 +/- 46.3 microU/ml, respectively; P = 0.01) and in males compared with females (74.6 +/- 22.3 and 105.0 +/- 43.0 microU/ml, respectively; P = 0.0002). By univariate analysis, serum peak TSH was negatively related to weight, height, body surface area, BMI, LBM, and fat body mass, but only LBM was independently associated with serum peak TSH levels. Although it was confirmed that overweight and obese patients had a lower serum peak TSH, the rate of ablation did not differ among normal-weight, overweight, and obese patients. CONCLUSIONS: With this study we demonstrated that LBM is the only parameter independently associated with serum peak TSH after rhTSH administration. However, the serum peak TSH does not influence the rate of (131)I remnant ablation.     

Relationship between visceral fat accumulation and physical fitness in Japanese women

OBJECTIVE: To investigate the link between visceral fat (V) accumulation and physical fitness. DESIGN: Cross-sectional clinical investigation study. SUBJECTS: Twenty-eight overweight Japanese women with abdominal obesity (abdominal obesity) (body mass index, BMI>or=25, visceral fat area>or=100 cm2) aged 38-65 years (BMI 29.5+/-3.3 kg/m2) were enrolled in this study. They were compared with age and sex matched 28 normal weight subjects (BMI<25, visceral fat area<100 cm2) and 28 overweight subjects without abdominal obesity (overweight) (BMI>or=25, visceral fat area<100 cm2). Measurements: Fat distribution was evaluated by visceral fat and subcutaneous fat (S) areas measured by computed tomography (CT) scanning at umbilical level. Anthropometric parameters, aerobic exercise level, muscle strength, flexibility and blood examination were also investigated. RESULTS: Anthropometric and body composition parameters were significantly higher in abdominal obesity subjects than those in normal weight subjects. BMI, waist circumference, waist hip ratio and visceral fat (V) area were also significantly higher than those in overweight subjects. Reduced oxygen uptake at ventilatory threshold (VT), lowering weight bearing index (WBI), and elevation of blood enzymes were noted in abdominal obesity subjects. There were significant relationships between oxygen uptake at VT and visceral fat area, and also between oxygen uptake at VT and WBI. CONCLUSION: Reduced aerobic exercise level and WBI are characteristic and visceral fat may play an important role for the etiology in Japanese women with abdominal obesity.     

Plasma levels of agouti-related protein are increased in obese men

To investigate the relationship between peripheral blood levels of agouti-related protein (AGRP) and various parameters of obesity, we measured the plasma level of AGRP in 15 obese and 15 nonobese men and evaluated its relationship with body mass index (BMI), body fat weight, and visceral, sc, and total fat areas measured by computed tomography, fasting insulin levels, glucose infusion rate during an euglycemic hyperinsulinemic clamp study, serum leptin, and plasma alpha-MSH. Obese men had significantly higher plasma concentrations of AGRP than nonobese men (P < 0.01). Univariate analysis showed that the plasma levels of AGRP are proportionally correlated with BMI, body fat weight, and sc fat area in obese men (BMI: r = 0.732, P < 0.01; body fat weight: r = 0.603, P < 0.02; sc fat area: r = 0.668, P < 0.01) and in all men (BMI: r = 0.839, P < 0.0001; body fat weight: r = 0.818, P < 0.0001; sc fat area: r = 0.728, P < 0.0001). In all men, the plasma levels of AGRP were significantly correlated with the visceral fat area (r = 0.478, P < 0.01), total fat area (r = 0.655, P < 0.0001), fasting insulin level (r = 0.488, P < 0.01), glucose infusion rate (r = -0.564, P < 0.01), serum level of leptin (r = 0.661, P < 0.0001), and the plasma level of alpha-MSH (r = 0.556, P < 0.01). In all subjects, multiple regression analysis showed that the plasma levels of AGRP are significantly (F = 15.522, r = 0.801, P < 0.03) correlated with the plasma levels of alpha-MSH, independently from the total fat area. However, the correlation between plasma levels of AGRP and serum levels of leptin was found to be dependent on the total fat area. In brief, these findings showed that the circulating levels of AGRP are increased in obese men and that they are correlated with various parameters of obesity. Although correlation does not prove causation, the results of this study suggest that peripheral AGRP may play a role in the pathogenesis of obesity.     

Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans

OBJECTIVE: Leptin plays a major role in the regulation of body weight. It circulates in both free and bound form. One of the leptin receptor isoforms exists in a circulating soluble form that can bind leptin. In the present study, we measured the soluble leptin receptor (SLR) levels in lean and obese humans. We investigated the relationship between plasma SLR levels, plasma leptin levels and the degree of obesity. We also examined whether SLR concentrations could be modulated by fat mass loss induced by a 3 month weight-reducing diet. SUBJECTS: A total of 112 obese (age 18-50 y; body mass index (BMI) 30-44 kg/m2; 23 men and 89 women), 38 overweight (age 19-48 y; BMI 25-29 kg/m2; 10 men and 28 women) and 63 lean (age 18-50 y; BMI 17-24 kg/m2; 16 men and 47 women) humans. MEASUREMENTS: A direct double monoclonal sandwich enzyme-linked immunosorbent assay (ELISA) was used for the quantitative measurement of the soluble human leptin receptor. Leptin was measured by radioimmunoassay (RIA). Body composition was assessed by biphotonic absorptiometry DEXA (dual energy X-ray absorptiometry). RESULTS: We observed that the SLR is present in human plasma (range 10-100 ng/ml). SLR levels were lower in obese and overweight than lean subjects (28.7+/-8.8, 40.2+/-14.9, 51.2+/-12.5 ng/ml, respectively) and were inversely correlated to leptin and percentage of body fat (r=-0.74 and r=-0.76; respectively; P<0.0001). The ratio of circulating leptin to SLR was strongly related to the percentage of body fat (r=0.91; P<0.0001). Interestingly a gender difference was observed in SLR levels, which were higher in obese and overweight men than in obese and overweight women. In obese subjects after a 3 month low-calorie diet, SLR levels increased in proportion to the decrease in fat mass. In the gel filtration profile, SLR coeluted exactly with the bound leptin fractions. CONCLUSION: Obesity, in humans is associated with decreasing levels of the circulating soluble leptin receptor (SLR). The relationship of SLR with the degree of adiposity suggests that high SLR levels may enhance leptin action in lean subjects more than in obese subjects.     

Serum leptin level as an indicator to predict the clinical efficacy of troglitazone in patients with type 2 diabetes mellitus

Troglitazone is effective in approximately 50% in patients with type 2 diabetes (NIDDM). In this study, we investigated the relations between serum leptin levels and clinical efficacy of troglitazone. Forty-five type 2 diabetic patients (23 men and 22 women) from our outpatient clinic were treated with troglitazone 400 mg daily for 12 weeks. Fasting plasma glucose (FPG), HbA1c, body weight, serum insulin and leptin concentrations were measured before and after troglitazone treatment. After 12 weeks of troglitazone treatment, FPG (before versus after, 179+/-33 vs. 138+/-26 mg/dl, mean+/-SD), HbA1c (7.8+/-1.3 vs. 6.9+/-1.0%), IRI (8.3+/-4.3 vs. 6.3+/-3.4 microU/ml) and HOMA-R index (homeostasis model assessment of insulin resistance) (3.8+/-2.4 vs. 2.2+/-1.3) decreased significantly, while body mass index (BMI) slightly increased (26.3+/-3.5 vs. 26.6+/- 3.6 kg/m(2)), and serum leptin remained unchanged (8.5+/-7.2 vs. 9.1+/-8.7 ng/ml). Reduction in FPG (DeltaFPG) after troglitazone treatment were correlated with reduction in HOMA-R (DeltaHOMA-R) (r=0.721, P<0.0001). DeltaFPG was correlated with serum leptin (r=0.441, P<0.01), HOMA-R (r=0.460, P<0.01) and FPG (r=-0.781, P<0.0001) at baseline, but not with BMI and serum IRI at baseline. Furthermore, serum leptin at baseline was significantly correlated with DeltaHOMA-R (r=0.634, P<0.01). Leptin concentration before treatment therefore, can be used as an predictor for clinical efficacy of troglitazone in patients with type 2 diabetes.     

Measurement of visceral adipose tissue by DXA combined with anthropometry in obese humans

OBJECTIVE: To get accurate measurements of visceral adipose tissue (VAT) using dual energy X-ray absorptiometry (DXA). DESIGN: DXA and anthropometric data and their combinations were compared to the VAT area calculated from a computed tomography (CT) single scan. SUBJECTS: 71 overweight subjects (44 women, 27 men), age: 16-70 y, BMI: 27-52 kg/m2. MEASUREMENTS: Total body and segmental tissue composition, and new parameters obtained from DXA, in addition to waist and hip circumferences and abdominal sagittal diameter measurements. RESULTS: The ratio measured at the umbilical level (sagittal diameter - subcutaneous fat width) x (transverse internal diameter)/(height) was closely related to VAT (r=0.94 for women and 0.88 for men). It gave the most predictive equation for VAT: y = 79.6x (s.e. 3.9) - 149 cm2 for the whole population (r2=0.86, P<0.0001, root mean square error=38.2 cm2. An independent relationship between lean mass or its index (r=0.52 and 0.72, P<0.001) and VAT was also found in women. CONCLUSION: This study demonstrates the potential usefulness of DXA to supply accurate measurements of VAT in addition to total body composition determination in obese subjects.     

Quantitative insulin sensitivity check index is a useful indicator of insulin resistance in Japanese metabolically obese, normal-weight subjects with normal glucose tolerance

To clarify whether quantitative insulin sensitivity check index (QUICKI) is useful as an indicator of insulin resistance in Japanese metabolically obese, normal-weight (MONW, body mass index (BMI) <25 and visceral fat area (VFA) > or = 100 cm2 by abdominal computed tomography scanning) subjects with normal glucose tolerance (NGT). Insulin resistance was measured by QUICKI and euglycemic hyperinsulinemic clamp study (clamp IR) in 27 MONW and 27 normal subjects (BMI <25 and visceral fat area <100 cm2). QUICKI (P<0.01) and clamp IR (p<0.01) were significantly decreased in MONW subjects compared with normal subjects. QUICKI was significantly associated with VFA [MONW subjects: r = -0.459, p<0.02; all (MONW and normal) subjects: r = -0.506, p<0.0001] and with the serum levels of triglycerides (MONW subjects: r = -0.386, p<0.05; all subjects: r = -0.505, p<0.001) in MONW and all subjects. There were significant correlations between clamp IR and VFA (MONW subjects: r = -0.562, p<0.01; all subjects: r = -0.575, p<0.0001), fasting serum levels of insulin (MONW subjects: r = -0.673, p<0.001; all subjects: r = -0.619, p<0.0001) or serum levels of triglycerides (MONW subjects: r = -0.485, p<0.02; all subjects: r = -0.565, p<0.0001) in MONW and all subjects. QUICKI was significantly correlated with clamp IR in MONW (r = 0.754, p<0.0001) and in all subjects (r = 0.568, p<0.0001). QUICKI may be an useful method for assessing insulin resistance in Japanese MONW subjects with NGT.     

Elevated plasma levels of alpha-melanocyte stimulating hormone (alpha-MSH) are correlated with insulin resistance in obese men

OBJECTIVE: The role of alpha-melanocyte stimulating hormone (MSH) in obesity has been well-documented. However, circulating alpha-MSH concentrations in obese men and their relationship with clinical indicators of obesity and glucose metabolism have not as yet been evaluated. METHODS: We measured the plasma concentrations of alpha-MSH in 15 obese and 15 non-obese male subjects. The relationship of the plasma concentrations of alpha-MSH with body mass index (BMI), body fat mass (measured by bioelectric impedance), body fat distribution (measured by computed tomography), insulin levels, insulin resistance (assessed by the glucose infusion rate (GIR) during an euglycemic hyperinsulinemic clamp study) and with the serum concentrations of leptin and TNF-alpha were also evaluated. RESULTS: In obese men, the plasma alpha-MSH concentrations were significantly increased compared with those in non-obese men (P< 0.02). The plasma levels of alpha-MSH were positively correlated with BMI (r= 0.560, P< 0.05), fasting insulin levels (r=0.528, P< 0.05) and with visceral fat area (r=0.716, P<0.01), but negatively correlated with GIR (r= -0.625, P< 0.02) in obese male subjects. There were significant correlations between plasma concentrations of alpha-MSH and visceral fat area (r=0.631, P< 0.02), and GIR (r = -0.549, P< 0.05) in non-obese male subjects. Circulating concentrations of alpha-MSH were not significantly correlated with the serum concentrations of leptin and TNF-alpha in both obese and non-obese men. CONCLUSION: Circulating concentrations of alpha-MSH are significantly increased and correlated with insulin resistance in obese men.     

GH-binding protein in obese men with varying glucose tolerance: relationship to body fat distribution, insulin secretion and the GH-IGF-I axis

Bioelectrical impedance for measurement of total body fat and computed tomography for visceral and subcutaneous fat at umbilicus levels were performed in 34 obese and 10 lean men. Insulin secretion in response to an oral glucose tolerance test (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP) and IGF-I were measured. Obese subjects were divided into three groups according to the OGTT. The obese type II diabetes mellitus group had the highest GHBP levels and the most visceral fat. GHBP levels were most strongly correlated with the ratio of visceral fat area to body weight (VWR) above any other parameters (r = 0.725, P<0.001). The insulin and free fatty acid (FFA) areas under curves (AUC) during the OGTT, and the IGF-I level, were also positively correlated with GHBP levels (r = 0.474, P<0.005; r = 0.572, P<0.005; r = 0.453. P<0.005). GH-AUC to the L-dopa stimulation test was negatively correlated with GHBP levels (r = -0.432. P<0.005). Stepwise multiple linear regression analysis showed that VWR, FFA-AUC and insulin-AUC significantly contributed to the variability of GHBP (r2 = 0.58). In conclusion, we demonstrated that: (i) visceral fat amount mainly determined GHBP levels in obese men with varying glucose tolerance: (ii) hyperglycemia per se did not influence the GHBP level, whereas insulin and FFA could play a role in regulation of GHBP: and (iii) although GH was not the main regulator of GHBP, the unchanged IGF-I level despite GH hyposecretion suggests that increased GHBP levels reflect GH hypersensitivity in order to compensate for decreased GH secretion in obesity.     

Metabolic correlates of eating behavior in severe obesity.

BACKGROUND: The benefit of spreading energy intake over many small meals ('nibbling') rather than few large ones ('gorging') for control of blood glucose, serum lipids and body fat accretion has been known for 60 y, but the mechanisms are poorly understood. Men exhibit more of a gorging eating pattern than women and are also more prone to the metabolic complications of obesity, as are women with a 'male', central distribution of adipose tissue. We have shown correlations between central fat distribution, and other components of the metabolic 'Syndrome X' and fatty infiltration of the liver. Here we study relationships between eating rate and fat distribution and test the hypothesis that gorging might be associated with fatty liver. SUBJECTS AND METHODS: In 30 non-alcoholic, non-diabetic, severely obese women (body mass index, BMI=47+/-1 kg/m(2); mean+/-s.e.m.) with a mean age of 36+/-1 y and 16 men (BMI: 52+/-3) age 38+/-2 y, who were candidates for anti-obesity surgery, we measured eating rate using an eating monitor, and fat distribution by the waist-hip circumference ratio (WHR). In addition in the 17 women and 11 men who had surgery, serum lipids were analyzed and routine liver biopsies were evaluated for steatosis by a pathologist blinded to the conditions of the study. RESULTS: Men ate significantly faster than women (188+/-28 vs 123+/-9 g/min; P<0.01), and had more liver fat (score: 2.7+/-03 vs 1.5+/-0.3; P<0.01), with no statistically significant sex differences in s-cholesterol or s-triglycerides. Eating rate correlated with WHR (r=0.46; P<0.01, n=46), liver fat (r=0.55; P<0.01), and s-triglycerides (r=0.42; P<0.05) adjusting for sex. Liver fat correlated with WHR (r=0.50; P<0.05), s-triglycerides (r=0.70; P<0.01) and s-cholesterol (r=0.50; P<0.05), while there were no significant correlations with BMI or body weight. In multivariate analysis eating rate (32%), meal size (8%) and WHR (6%) contributed 46% of the variance in liver fat. CONCLUSION: We showed increased eating rates in severely obese men and women with central fat distribution. Furthermore, increased eating rates were associated with fatty liver and elevated serum lipids. Eating rate in severely obese women and men may be a determinant of the metabolic syndrome.     

Relationships between changes in abdominal fat distribution and insulin sensitivity during a very low calorie diet in abdominally obese men and women

BACKGROUND AND AIM: Little is known about the association between abdominal obesity and insulin sensitivity during rapid weight loss. We assessed the role of visceral and subcutaneous fat as determinants of insulin sensitivity during rapid weight loss in obese persons with the metabolic syndrome. METHODS AND RESULTS: Twenty abdominally obese individuals [11 women and 9 men, body mass index (BMI) 35.8+/-3.5 kg/m2] with the metabolic syndrome underwent a very-low-calorie diet (VLCD) for nine weeks. At baseline, the computed tomography (CT) measured area of total (r=-0.50, p=0.033) and visceral fat tissue (r=-0.48, p=0.043), but not that of subcutaneous fat tissue (r=-0.34, p=0.17), correlated with insulin sensitivity as assessed by the quantitative insulin sensitivity check index after adjusting for sex and age. The 18 subjects who completed the study lost 14.8 kg during the VLCD. Total, visceral and subcutaneous abdominal fat tissue decreased by 22%, 29% and 17%, respectively. The decrease in total (r=-0.51, p=0.035) and subcutaneous abdominal fat (r=-0.57, p=0.017), but not visceral fat (r=0.11, p=0.68), correlated with the increase in insulin sensitivity. Waist circumference did not offer any additional information concerning abdominal fat distribution or insulin sensitivity compared with that provided by BMI at baseline or after weight loss. The waist/hip ratio was not associated with the CT measures of abdominal fat distribution or insulin sensitivity. CONCLUSIONS: Total abdominal fat may be more important than its compartmentalisation in abdominally obese individuals with the metabolic syndrome. In this subgroup of individuals with obesity, the measurement of waist circumference and the waist/hip ratio offered little additional information over that provided by BMI at baseline or after weight loss.     

Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening

OBJECTIVE: We sought to study arterial endothelial function and carotid intima-media thickness (IMT), both early markers of atherosclerosis, in overweight compared to normal children. DESIGN: Case-control comparison. SUBJECTS: A total of 36 asymptomatic overweight children (body mass index (BMI)>23; mean 25+/-3) aged 9-12 y and 36 age- and gender-matched nonobese healthy children (BMI<21) from a school community. MEASUREMENTS: The key parameters were: BMI, arterial endothelial function (ultrasound-derived endothelium-dependent dilation) and carotid artery IMT. The secondary parameters measured included body fat content, waist-hip ratio (WHR), blood pressures, blood lipids, insulin and glucose. RESULTS: The two groups were well matched for blood pressures, cholesterol and glucose levels, but BMI (P<0.0001), body fat (P=0.001), WHR (P<0.05), fasting blood insulin (P=0.001) and triglyceride levels (P<0.05) were higher in obese children. Overweight was associated with impaired arterial endothelial function (6.6+/-2.3 vs 9.7+/-3.0%, P<0.0001) and increased carotid IMT (0.49+/-0.04 mm vs 0.45+/-0.04 mm, P=0.006). The degree of endothelial dysfunction correlated with BMI (P<0.003) on multivariate analysis. CONCLUSION: Obesity, even of mild-to-moderate degree, is independently associated with abnormal arterial function and structure in otherwise healthy young children.     

Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men

OBJECTIVE: To examine the association between baseline testosterone levels and changes in visceral adiposity in Japanese-American men. DESIGN: Prospective observational study. SUBJECTS: Second-generation Japanese-American males enrolled in a community-based population study. MEASUREMENTS: At baseline, 110 men received a 75g oral glucose tolerance test (OGTT), and an assessment of body mass index (BMI); visceral adiposity measured as intra-abdominal fat area (IAF) using computed tomography (CT); fasting insulin and C-peptide levels; and total testosterone levels. IAF was re-measured after 7.5 y. Subcutaneous fat areas were also measured by CT in the abdomen, thorax and thigh. The total fat (TF) was calculated as the sum of IAF and total subcutaneous fat areas (SCF). RESULTS: After 7.5y, IAF increased by a mean of 8.0 cm2 (95% CI: 0.8, 15.3). Baseline total testosterone was significantly correlated with change in IAF (r= -0.26, P= 0.006), but not to any appreciable degree with change in BMI, TF, or SCF. In a linear regression model with change in IAF as the dependent variable, baseline testosterone was significantly related to this outcome while adjusting for baseline IAF, SCF, BMI, age, diabetes mellitus status (OGTT by the WHO diagnostic criteria) and fasting C-peptide (regression coefficient for baseline testosterone [nmol/l] = -107.13, P = 0.003). CONCLUSIONS: In this Japanese-American male cohort, lower baseline total testosterone independently predicts an increase in IAF. This would suggest that by predisposing to an increase in visceral adiposity, low levels of testosterone may increase the risk of type 2 diabetes mellitus.