Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women

Older obese postmenopausal women have an increased risk for type 2 diabetes and cardiovascular disease. Increased abdominal obesity may contribute to these comorbidities. There is considerable controversy, however, regarding the effects of visceral adipose tissue as a singular predictor of insulin resistance compared to the other constituents of adiposity. To address this issue, we examined the independent association of regional adiposity and total fat mass with glucose disposal in obese older postmenopausal women. A secondary objective examined the association between glucose disposal with markers of skeletal muscle fat content (muscle attenuation) and physical activity levels. We studied 44 healthy obese postmenopausal women between 50 and 71 yr of age (mean +/- SD, 56.5 +/- 5.3 yr). The rate of glucose disposal was measured using the euglycemic/hyperinsulinemic clamp technique. Visceral and sc adipose tissue areas and midthigh muscle attenuation were measured from computed tomography. Fat mass and lean body mass were estimated from dual energy x-ray absorptiometry. Peak VO2 was measured from a treadmill test to volitional fatigue. Physical activity energy expenditure was measured from indirect calorimetry and doubly labeled water. Pearson correlations indicated that glucose disposal was inversely related to visceral adipose tissue area (r = -0.40; P < 0.01), but not to sc adipose tissue area (r = 0.17), total fat mass (r = 0.05), midthigh muscle attenuation (r = 0.01), peak VO2 (r = -0.22), or physical activity energy expenditure (r = -0.01). The significant association persisted after adjusting visceral adipose tissue for fat mass and abdominal sc adipose tissue levels (r = -0.45; P < 0.005; in both cases). Additional analyses matched two groups of women for fat mass, but with different visceral adipose tissue levels. Results showed that obese women with high visceral adipose tissue levels (283 +/- 59 vs. 137 +/- 24 cm2; P < 0.0001) had a lower glucose disposal per kg lean body mass compared to those with low visceral adipose tissue levels (0.44 +/- 0.14 vs. 0.66 +/- 0.28 mmol/kg x min; P < 0.05). Visceral adipose tissue is an important and independent predictor of glucose disposal, whereas markers of skeletal muscle fat content or physical activity exhibit little association in obese postmenopausal women.     

What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean +/- SD, 58.0 +/- 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 +/- 2.6 mg/min.kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 +/- 1.1 mg/min.kg lean body mass). Despite comparable total body fatness between groups (45.2 +/- 5.3% vs. 44.8 +/- 6.6%; P: = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 +/- 53 vs. 211 +/- 85 cm(2); P: < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); P: = NS), total fat mass (38.1 +/- 10.6 vs. 40.0 +/- 11.8 kg), muscle attenuation (42.2 +/- 2.6 vs. 43.6 +/- 4.8 Houndsfield units), and physical activity energy expenditure (1060 +/- 323 vs. 1045 +/- 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P: values ranging between 0.01-0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P: < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (<20 yr old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.     

Leptin in postmenopausal women: influence of hormone therapy, insulin, and fat distribution

Whether use of hormone-replacement therapy (HRT) influences menopause-related changes in body weight is unclear. HRT may affect energy balance by influencing synthesis of the adipocyte-derived hormone leptin. The objectives of this study were to: 1) identify factors influencing circulating leptin in postmenopausal women; 2) determine whether HRT influences serum leptin after adjusting for confounding factors; and, 3) identify potential independent effects of HRT or leptin on resting energy expenditure (REE). Subjects were 54 postmenopausal women, 45-55 yr old, 35 of whom used HRT (estrogen plus progestin). Total and regional body composition and fat distribution were determined by dual-energy x-ray absorptiometry and computed tomography; fasting serum leptin and insulin, by RIA; and REE, by indirect calorimetry. Stepwise multiple linear regression analysis indicated that serum leptin could best be predicted from total fat mass, fasting serum insulin, and total lean mass [log leptin = 1.08 x log fat mass) + (0.46 x log insulin) + (-1.25 x log lean mass) + 1.88; model R2 = 0.78, P < 0.001]. Multiple linear regression analysis indicated that visceral fat was independently related to leptin (parameter estimate = 0.23, P < 0.05), after adjusting for s.c. abdominal fat and leg fat, as well as lean mass and insulin. After adjusting for total fat mass, total lean mass, and fasting insulin, serum leptin did not differ between users and nonusers of HRT (21.7 +/- 1.0 vs. 20.2 +/- 1.3 ng/mL, P = 0.369, adjusted mean +/- SE, respectively). Serum estradiol was inversely correlated with (adjusted) leptin in non-HRT users (r = -0.50), suggesting that ovarian senescence may lead to an increase in leptin. Multiple linear regression analysis indicated that REE (adjusted for fat mass, fat-free mass, and ethnicity) was not associated with leptin (P = 0.298) or hormone use status (P = 0.999; 1323 +/- 31 vs. 1316 +/- 42 kcal/day, adjusted mean +/- SE for users and nonusers, respectively). These results indicate that, in postmenopausal women: 1) total fat mass, lean mass, and fasting insulin, but not HRT, are significant determinants of serum leptin; 2) visceral and s.c. fat contribute to serum leptin; and, 3) neither HRT nor leptin is independently related to REE.     

Abdominal fat distribution in pre- and postmenopausal women: The impact of physical activity, age, and menopausal status

Age-related increases in total body fat have been reported, but the impact of menopause on abdominal fat distribution is still unclear. The purpose of this study was to determine the impact of menopausal status on abdominal fat distribution using magnetic resonance imaging (MRI). In addition, we investigated the influence of abdominal fat distribution on blood lipid profiles and leptin concentrations. Twenty-three premenopausal (PRE), 27 postmenopausal (POST), and 28 postmenopausal women on estrogen replacement therapy (ERT) had measurements of regional abdominal fat, blood lipids, and serum leptin concentrations. The women were matched for body mass index (BMI) and total body fat mass. Age and menopausal status were not found to be significant predictors of total abdominal fat, visceral fat, or subcutaneous fat, while physical activity was a significant predictor (P <.01) for total abdominal fat (R(2) =.16), visceral fat (R(2) =.32) and percent visceral fat (R(2) =.25). There was a trend for a greater visceral fat content in the POST women compared with the PRE women (2,495.0 +/- 228.4 v 1,770.4 +/- 240.8 cm(2), respectively, P =.06). The percent visceral abdominal fat was significantly lower (P <.05) in the premenopausal women than in either postmenopausal group (PRE, 23.2% +/- 1.7%; POST, 28.9% +/- 1.8%; ERT, 28.9% +/- 1.6%). Menopausal status and age did not influence any of the blood lipid values. Abdominal fat distribution was a significant predictor of cholesterol concentrations and the cholesterol/high-density lipoprotein-cholesterol (HDL-C) ratio, but only accounted for approximately 15% of the variability in these levels. Total body fat and physical activity accounted for 47% of the variability in leptin concentrations, while abdominal fat distribution, age, and menopausal status were not significant predictors. In conclusion, in early postmenopausal women, the level of physical activity accounts for the variability in abdominal fat distribution observed, while menopausal status and age do not play a significant role. ERT was not associated with additional benefits in abdominal fat distribution compared with postmenopausal women not on ERT or in the blood lipid profile in these women.     

Racial differences in subcutaneous and visceral fat distribution in postmenopausal black and white women

Most studies examining racial disparities in abdominal fat distribution have focused on premenopausal women. The purpose of this report was to determine if racial differences exist in the abdominal fat distribution in postmenopausal white and black women. Fifty-four women (33 white and 21 black) were scanned by magnetic resonance imaging (MRI) to determine abdominal fat distribution, were measured by hydrostatic weighing for percent body fat, and had their fasting blood lipids, glucose, and insulin levels measured. These women were matched for age (mean age, 53.5 +/- 0.9 years) and percent body fat (black: 39.6% +/- 2.3%, white: 37.3% +/- 1.2%). When adjusted for total body fat mass and hormone replacement therapy (HRT), total abdominal fat (white: 10,352.1 +/- 535.2, black: 11,220.4 +/- 670.1 cm(3)) was not statistically different between groups, but the visceral fat content was significantly higher in the white women (white: 2,943.5 +/- 220.4, black: 2,332.6 +/- 176.1 cm(3)). The percent visceral fat was also higher in these women (white: 30.5% +/- 1.3%, black: 22.1% +/- 1.6%, P <.01). Subcutaneous adipose tissue (SAT) was significantly higher in the black women (white: 7,408.6 +/- 450.2, black: 8,887 +/- 563.1 cm(3), P <.05). No significant differences were found in the insulin concentrations or the blood lipid profile of these women. Regardless of race, visceral fat was a significant predictor of log triglyceride, low-density lipoprotein-cholesterol (LDL-C), cholesterol/LDL-C, insulin levels, and insulin resistance. Race was only found to contribute to 8% of the variability of LDL-C. HRT use had no effect on abdominal fat distribution or the blood lipid profile in this cohort of women. In conclusion, disparities in abdominal fat distribution between black and white women continue to exist in the early postmenopausal years, and the regression results indicate that the absolute amount of visceral fat, and not the relative amounts of visceral fat, is the best predictor of the blood lipid profile and insulin sensitivity. HRT use did not result in differences in abdominal fat distribution in these women. Factors, such as genetics and lifestyle, must play a larger role in explaining the increased health risk in black women.     

Hormone replacement therapy affects body composition and leptin differently in obese and non-obese postmenopausal women.

Leptin and oestrogen are both involved in the regulation of adipose tissue deposition and feeding behaviour. We investigated whether 5 years of hormone replacement therapy (HRT) affected serum leptin and body composition differently in 89 postmenopausal women treated with HRT compared with 178 controls. At baseline, leptin was significantly correlated with oestradiol (r=0.13, P<0.05) and in multiple backward regression analysis including oestradiol and any estimate of body fat, oestradiol remained a significant determinant of leptin levels. In the control group, all estimates of body fat determined by dual energy X-ray absorptiometry (DEXA) or anthropometry were increased (3.6-16.9%) and leptin increased 31.3% (16.03+/-1.02 to 20.84+/-1.2 ng/ml (s.e.m.), P<0.001). In the HRT group all estimates of body composition also increased during the 5-year observation but to a lesser extent than observed in the control group (1.0-8.5%). Leptin was raised by 19.7% (17.81+/-1.32 to 20.57+/-1.65 ng/ml, P<0.001). However, the DEXA scans revealed that the control group gained 2.4-fold more fat during the 5-year observation (1.9+/-0.3 vs 0.8+/-0.4 kg, P<0.05), and especially the trunk fat increased (1.4+/-0.2 vs 0.7+/-0.3 kg, P<0.05). This was reflected in the increase in leptin levels, which were increased by 7.4% in the control group compared with the HRT group (4.81+/-0.60 vs 2.76+/-0.87 ng/ml, P<0.05). Adjusting for the difference in adipose tissue revealed that HRT had no independent effect on leptin levels. Comparisons between obese (body mass index>25 kg/m(2)) and non-obese (<25 kg/m(2)) subjects by stratifying for HRT treatment using multiple linear regression revealed that the change in fat mass was significantly less among treated subjects (P=0.038) and especially in the non-obese subjects (P=0.001). The change in trunk fat was similarly correlated with treatment status (P=0.029) and with the degree of obesity (P=0.006). In conclusion, 5 years of HRT treatment significantly reduced fat mass accumulation, especially in the trunk region. This effect of HRT was more pronounced in non-obese as compared with obese subjects. The HRT-induced reduction in fat mass seems not to be mediated by leptin.     

Effect of menopausal status on lipolysis: comparison of plasma glycerol levels in middle-aged, premenopausal and early, postmenopausal women

To determine whether menopausal status affects systemic lipolysis, we measured plasma glycerol concentrations following an overnight fast and during euglycemic hyperinsulinemic conditions (40 mU x m(-2) x min(-1)) in 43 middle-aged, premenopausal women (mean +/- SE; 47 +/- 0.4 years) and 26 early, postmenopausal (51 +/- 0.8 years) women. In addition, body composition was measured by dual-energy x-ray absorptiometry and abdominal fat distribution by computed tomography (CT). Postmenopausal women had greater amounts of whole body (fat mass, 22.8 +/- 1.4 v 17.4 +/- 1.2 kg; percent fat, 34.7 +/- 1.2 v 29.1 +/- 1.4; both P <.01) and intra-abdominal fat (89.0 +/- 6.5 v 55.9 +/- 4.4 cm2; P <.01) compared with premenopausal women. Despite greater adiposity, plasma glycerol concentrations were similar between pre- and postmenopausal women following an overnight fast (142.7 +/- 9.7 v 136.1 +/- 6.4 micromol/L) and at 30 minutes (112.7 +/- 5.5 v 108.4 +/- 4.5 micromol/L ) and 120 minutes (92.7 +/- 4.5 v 97.5 +/- 5.9 micromol/L ) into the euglycemic hyperinsulinemic clamp. Plasma glycerol levels remained similar after statistical adjustment for fat mass, percent fat, and intra-abdominal fat. Moreover, no differences in plasma glycerol were observed in pre- and postmenopausal women matched (+/- 5%) for fat mass (n = 22/group) or intra-abdominal fat (n = 15/group). In premenopausal women, plasma glycerol levels at 30 and 120 minutes of hyperinsulinemia were positively related to adiposity measures (range, r =.314 to r =.493; P <.05 to P <.01), although no relationships were found in postmenopausal women. Our results suggest no effect of menopausal status on plasma glycerol levels under postabsorptive or hyperinsulinemic conditions.     

Effects of lifestyle modifications on C-reactive protein: contribution of weight loss and improved aerobic capacity

High-sensitivity C-reactive protein (hs-CRP) is associated with an increased risk of cardiovascular disease and the development of type 2 diabetes mellitus. We analyzed the effects of lifestyle modifications including exercise training on hs-CRP in 47 overweight and obese adults. Subjects were divided into a lifestyle modification group (n=23) (exercise and diet instruction) and a control group (n=24) who did not participate in any lifestyle modification. After 3 months, body weight (80.8+/-11.5 to 73.5+/-10.7 kg, P<.01), total cholesterol (217+/-38.4 to 178.0+/-25.6 mg/dL, P<.01), low-density lipoprotein cholesterol (151.3+/-34.9 to 116.7+/-27.8 mg/dL, P<.01), Vo(2)peak (30.3+/-5.1 to 37.1+/-6.9 mL/[kg . min], P<.01), and log hs-CRP (0.75+/-0.4 to 0.56+/-0.3 mg/dL, P=.01) were significantly improved in the lifestyle modification group, but there was no significant improvement in the control group. Changes in log hs-CRP were associated with changes in Vo(2)peak (r=-0.41, P=.004) and changes in weight loss (r=0.42, P=.004). In stepwise multiple regression analysis, weight loss (P=.034) and improved Vo(2)peak (P=.039) were independent predictors of the changes in hs-CRP. When grouped into quartiles according to decreasing weight and increasing Vo(2)peak, levels of changes in log hs-CRP improved across quartiles of weight loss (P<.05) and improved Vo(2)peak (P<.01). Thus, lifestyle changes including regular exercise training in overweight and obese adults decreased hs-CRP, and this was associated with weight loss and improved Vo(2)peak.     

Changes in serum hypoxanthine levels by exercise in obese subjects

To study on effect of obesity on changes in serum hypoxanthine with exercise, exercise stress testing with treadmill was performed on 7 obese subjects (body mass index [BMI], 30.6 +/- 3.2 kg/m(2)) and 16 healthy volunteers (BMI, 21.5 +/- 2.10 kg/m(2)). Expiratory gas analysis during exercise showed that peak Vo(2) was significantly lower in the obese group than in the control group (28.1 +/- 4.0 v 37.1 +/- 4.7 mL/kg/min; P <.001). Furthermore, the obese group had lower anaerobic threshold (AT) values (P <.005), respiratory quotient at AT (P =.003), and exercise capacity reserve (P =.002) than the control group. Baseline serum hypoxanthine levels were significantly higher in the obese group than in the control group (3.46 +/- 3.70 v 1.23 +/- 1.16 micromol/L; P <.05). Exercise induced a pronounced increase in serum hypoxanthine level in the obese group compared with the control group (10.65 +/- 6.81 v 43.86 +/- 4.56 micromol/L; P <.01). Serum levels of uric acid before and after load were also higher in the obese group than in the control group (404 +/- 43 v 302 +/- 77 micromol/L; P <.005). A pronounced increase in hypoxanthine with exercise may result in organ damage caused by free radicals, and intermittent training from mild intensity may be less hazardous for exercise treatment of obesity.     

Obesity gene variant and elite endurance performance

beta2-adrenergic receptor (ADRB2) Gln27Glu genotype was determined in sedentary (n = 19), active (n = 20), and elite endurance athletic (n = 24) Caucasian postmenopausal women. Age was similar in all physical activity and ADRB2 genotype groups. ADRB2 genotypes were in Hardy-Weinberg equilibrium in sedentary and active women, but not in the athletes (chi(2) = 4.28, P <.05), due to the near absence of ADRB2 Glu27Glu homozygotes among the athletes. Weight tended to be higher in ADRB2 Glu27Glu women (63.5 +/- 1.8 v 57.7 +/- 1.7 and 60.0 +/- 1.8, P =.08), as did body mass index (BMI) (25.0 +/- 0.4 v 22.9 +/- 0.6 and 23.4 +/- 0.5 kg/m(2), P =.05), due to a higher fat mass in Glu27Glu women (24.1 +/- 1.0 v 18.1 +/- 1.4 and 20.1 +/- 1.4 kg, P <.05). Maximal O2 consumption was lower in ADRB2 Glu27Glu than in ADRB2 Glu27Gln and Gln27Gln genotype women (25.4 +/- 1.1 v 32.4 +/- 1.5 and 29.1 +/- 1.7 mL/kg/min, P <.05). We conclude that the Glu27Glu ADRB2 genotype may dissociate from and the Gln27Gln and Gln27Glu genotypes may associate with elite endurance performance in older women.     

The metabolic syndrome in obese postmenopausal women: relationship to body composition, visceral fat, and inflammation

The purpose of this study was to investigate whether aerobic fitness, body composition, body fat distribution, and inflammation are different in obese postmenopausal women with and without the metabolic syndrome (MS), and whether the severity of MS is associated with these characteristics. Fifty-eight women (age, 59 +/- 1 yr; body mass index, 33.0 +/- 0.6 kg/m2)completed testing of maximal aerobic capacity, body composition (fat mass, lean mass, and percent body fat), body fat distribution (sc and visceral fat areas, and regional adipocyte sizes), and inflammation (C-reactive protein, IL-6, and TNF-alpha,and their soluble receptors). Lean mass (44.4 +/- 0.9 vs. 41.2 +/- 0.9 kg; P < 0.05), visceral fat area (180 +/- 10 vs. 135 +/- 7 cm2; P <0.001), and plasma soluble TNF receptor 1 (sTNFR1; 860 +/- 25 vs. 765 +/- 42 pg/ml; P < 0.05) were higher in women with the MS(n = 27) than in those without the MS (n = 31). The number of MS components was directly related to weight, body mass index, fat mass, lean mass, visceral fat area, and plasma sT-NFR1. We conclude that obese older women with the MS are characterized by high lean mass, high visceral fat, and elevated sTNFR1, and the severity of the MS is associated with body composition, visceral adiposity, and inflammation.     

Differences in adipose tissue metabolism between postmenopausal and perimenopausal women

Changes in adipose tissue metabolism may contribute to the changes in body fat distribution seen during the menopause transition. We compared in vitro abdominal and gluteal sc adipose tissue metabolism [basal and stimulated lipolysis and activity of adipose tissue lipoprotein lipase (AT-LPL)] in postmenopausal and perimenopausal women (n = 12/group), matched for race, body mass index (29.5 +/- 3.8 kg/m(2); mean +/- SD), and percentage body fat (42 +/- 6%). The postmenopausal women were older (54 +/- 3 vs. 48 +/- 3 yr; P < 0.01) and had higher FSH (55.5 +/- 26.4 vs. 16.6 +/- 22.5 IU/ml; P < 0.01) and lower estradiol (33.8 +/- 14.9 vs. 97.4 +/- 61.7 pmol/liter; P < 0.05) concentrations than the perimenopausal women. Despite similar fat cell size and beta-adrenergic receptor and postreceptor (dibutyryl-cAMP)-stimulated lipolysis, basal lipolysis was 77% lower in gluteal adipose cells from postmenopausal compared with perimenopausal women (P < 0.05). Within each group, AT-LPL activity in the gluteal region was significantly higher than in the abdominal region (P < 0.05). In addition, AT-LPL activity was significantly higher in the postmenopausal compared with perimenopausal women in both gluteal (4.9 +/- 3.6 vs. 2.0 +/- 1.4 nmol free fatty acid/g.min; P < 0.05) and abdominal (3.2 +/- 2.6 vs. 1.3 +/- 0.9 nmol free fatty acid/g.min; P < 0.05) adipose cells. The results of this study suggest that menopause status is associated with differences in adipose tissue metabolism in both the abdominal and gluteal fat depots. The lower lipolysis and higher AT-LPL activity in postmenopausal women may predispose them to gain body fat after menopause.     

Exercise is required for visceral fat loss in postmenopausal women with type 2 diabetes

This study examined the effects of aerobic exercise without weight loss, a hypocaloric high monounsaturated fat diet, and diet plus exercise (D+E) on total abdominal and visceral fat loss in obese postmenopausal women with type 2 diabetes. Thirty-three postmenopausal women (body mass index, 34.6 +/- 1.9 kg/m(2)) were assigned to one of three interventions: a hypocaloric high monounsaturated fat diet alone, exercise alone (EX), and D+E for 14 wk. Aerobic capacity, body composition, abdominal fat distribution (magnetic resonance imaging), glucose tolerance, and insulin sensitivity were measured pre- and postintervention. Body weight ( approximately 4.5 kg) and percent body fat ( approximately 5%) were decreased (P < 0.05) with the D and D+E intervention, whereas only percent body fat ( approximately 2.3%) decreased with EX. Total abdominal fat and sc adipose tissue (SAT) were reduced with the D and D+E interventions (P < 0.05), whereas visceral adipose tissue (VAT) decreased with the D+E and EX intervention, but not with the D intervention. EX resulted in a reduction in total abdominal fat, VAT, and SAT (P < 0.05) despite the lack of weight loss. The reductions in total abdominal fat and SAT explained 32.7% and 9.7%, respectively, of the variability in the changes in fasting glucose levels, whereas the reductions in VAT explained 15.9% of the changes in fasting insulin levels (P < 0.05). In conclusion, modest weight loss, through either D or D+E, resulted in similar improvements in total abdominal fat, SAT, and glycemic status in postmenopausal women with type 2 diabetes; however, the addition of exercise to diet is necessary for VAT loss. These data demonstrate the importance of exercise in the treatment of women with type 2 diabetes.     

Postabsorptive resting metabolic rate and thermic effect of food in relation to body composition and adipose tissue distribution

One hundred thirty subjects were studied to investigate relationships between the body composition and fat distribution as evaluated by computed tomography and the resting metabolic rate (RMR) as evaluated by indirect calorimetry: 82 premenopausal women (age, 18 to 52 years; body mass index [BMI], 27 to 52 kg/m2), 27 postmenopausal women (46 to 71 years; 28 to 49 kg/m2), and 21 men (18 to 70 years; 31 to 43 kg/m2). The thermic effect of food (TEF) was evaluated in all men and in 2 subgroups of 55 and 19 women. The best-fitting equations for predicting RMR, obtained by multiple regression, included the following as covariates: fat-free mass and both subcutaneous and visceral adipose tissue in premenopausal women (R2 = .55, P = .0001), fat-free mass and visceral adipose tissue in postmenopausal women (R2 = .58, P = .001), and age, with minus sign, and visceral adipose tissue in men (R2 = .44, P = .0051). Fasting insulin and fat-free mass, with minus sign, and both visceral and subcutaneous adipose tissue were the predictors of the TEF (R2 = .25, P = .0055) in premenopausal women. This study demonstrates that visceral fat distribution is important in determining the RMR in postmenopausal women and men. In premenopausal women, total adipose tissue is a main determinant of both the RMR and TEF This last effect could be counterbalanced by insulin resistance.     

Regional abdominal fat distribution in lean and obese Thai type 2 diabetic women: relationships with insulin sensitivity and cardiovascular risk factors

To determine the relationships of body fat distribution and insulin sensitivity and cardiovascular risk factors in lean and obese Thai type 2 diabetic women, 9 lean and 11 obese subjects, with respective mean age 41.7 +/- 6.3 (SD) and 48.0 +/- 8.5 years, and mean body mass index (BMI) 23.5 +/- 1.8 and 30.3 +/- 3.7 kg/m2, were studied. The amount of total body fat (TBF) and total abdominal fat (AF) were measured by dual-energy x-ray absorptiometer, whereas subcutaneous (SAF) and visceral abdominal fat areas (VAF) were measured by computerized tomography (CT) of the abdomen at the L4-L5 level. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Cardiovascular risk factors, which included fasting and post-glucose challenged plasma glucose and insulin, systolic (SBP) and diastolic blood pressure (DBP), lipid profile, fibrinogen, and uric acid, were also determined. VAF was inversely correlated with insulin sensitivity as determined by glucose infusion rate (GIR) during the clamp, in both lean (r=-0.8821; P=.009) and obese subjects (r=-0.582; P=.078) independent of percent TBF. SAF and TBF were not correlated with GIR. With regards to cardiovascular risk factors, VAF was correlated with SBP (r=0.5279; P=.024) and DBP (r=0.6492; P=.004), fasting insulin (r=0.7256; P=.001) and uric acid (r=0.4963; P=.036) after adjustment for percent TBF. In contrast, TBF was correlated with fasting insulin (r=0.517; P=.023), area under the curve (AUC) of insulin (r=0.625; P=.004), triglyceride (TG) (r=0.668; P=.002), and uric acid (r=0.49; P=.033). GIR was not correlated with any of cardiovascular risk factors independent of VAF. In conclusion, VAF was a strong determinant of insulin sensitivity and several cardiovascular risk factors in both lean and obese Thai type 2 diabetic women.     

Decrease in visceral fat following diet-induced weight loss in upper body compared to lower body obese premenopausal women

BACKGROUND: Obesity is associated with numerous metabolic disturbances, such as insulin resistance, diabetes mellitus type 2, dyslipidemia, and hypertension. An excess of fat within the abdomen, so-called visceral adiposity, confers a greater and independent health risk of metabolic and cardiovascular complications than does adipose tissue accumulation elsewhere. The present study aimed to investigate a possible differential effect of diet-induced weight loss in visceral fat mass and metabolic parameters in obese individuals with the upper body (UBO) and lower body (LBO) obese phenotype. METHODS: The obese subjects were prescribed a liquid, very-low calorie diet to reduce 50% of their overweight (15% body weight loss). Specific body fat measurements (MRI, BIA), anthropometrics, and fasting metabolic parameters were obtained in control subjects and two groups of obese subjects (UBO and LBO) before and after weight loss. RESULTS: Weight loss was accompanied by significant decreases in total, subcutaneous, and visceral fat in both UBO and LBO women. The largest reduction in visceral fat mass was found in the UBO women (absolute decrease 223+/-32 cm(2) vs 122+/-91 cm(2) in LBO women; P=0.01), while the amount of visceral fat was reduced to normal levels in LBO women (155+/-25 cm(2) after weight loss vs 143+/-17 cm(2) in controls; P=NS). Furthermore, weight loss significantly lowered fasting glucose, total cholesterol, and LDL cholesterol concentrations in UBO women. CONCLUSION: The obese phenotype is preserved after body weight loss. UBO women have to lose a larger amount of overweight in order to bring the amount of fat in the visceral depot down to normal levels and to obtain normalization of their cardiovascular risk profile.     

Five weeks of insulin-like growth factor-I treatment does not alter glucose kinetics or insulin sensitivity during a hyperglycemic clamp in older women

Insulin sensitivity and the activity of the hypothalamic-growth hormone (GH)- insulin-like growth factor-I (IGF-I) axis both decline with age. Treatment with IGF-I increases insulin sensitivity in healthy young subjects. We hypothesized that increasing plasma IGF-I in postmenopausal women to levels characteristic of young women would enhance insulin sensitivity. To test the hypothesis, fasting glucose kinetics and insulin sensitivity were measured in 24 healthy, normoglycemic, postmenopausal women before and after 5 weeks of treatment with either recombinant human (rh)IGF-I (15 microg/kg body weight/d twice daily) or placebo in a double-blind study. Diet energy content and composition were rigidly controlled to maintain energy balance. A hyperglycemic clamp (8 mmol/L) coupled with stable isotope infusion ([6,6(2)H]glucose) was performed before and after treatment to assess whole-body insulin sensitivity; defined as the glucose rate of disappearance (Rd) or rate of infusion (GRIF) scaled to the steady-state insulin concentration (I). There were no differences in fasting glucose or insulin concentrations, glucose kinetics, or glucose oxidation after either treatment. During the clamps, steady-state insulin concentrations with placebo (pre = 151 +/- 28 pmol/L, post = 173 +/- 31 pmol/L) were slightly different than with IGF-I (pre = 182 +/- 37 pmol/L, post = 163 +/- 33 pmol/L), but the variations were not significant. No significant changes in whole-body insulin sensitivity were observed after treatment with IGF-I, calculated as Rd/I (pre = 17.7 +/- 2.6 microg/kg/min/pmol/L, post = 19.3 +/- 2.0 microg/kg/min/pmol/L for IGF-I v pre = 24.2 +/- 2.5 microg/kg/min/pmol/L, post = 22.8 +/- 3.4 microg/kg/min/pmol/L for placebo) or as GRIF/I (pre = 18.0 +/- 3.9 microg/kg/min/pmol/L, post = 22.3 +/- 3.5 microg/kg/min/pmol/L for IGF-I v pre = 26.4 +/- 6.2 microg/kg/min/pmol/L, post = 26.9 +/- 4.8 microg/kg/min/pmol/L for placebo). Baseline insulin sensitivity in women using hormone replacement therapy (HRT, n = 15) was similar to nonusers (n = 9), but HRT users derived a greater portion of energy expenditure from carbohydrate oxidation compared with nonusers. HRT use had no impact on the response to IGF-I. Overall, we observed subtle, but physiologically insignificant, variations after IGF-I treatment in the direction of enhanced insulin sensitivity. The data suggest that 5 weeks of low-dose rhIGF-I treatment has no material influence on whole-body insulin sensitivity in normoglycemic postmenopausal women.     

Effects of troglitazone on fat distribution in the treatment of male type 2 diabetes.

We investigated the efficacy of additional administration of 400 mg troglitazone (+T), which became available as a treatment for type 2 diabetes following the demonstration of its ability to reduce insulin resistance, in combination with diet (D + T) or sulfonylurea (S + T) therapy. Body fat area as determined by computed tomographic (CT) scanning at the umbilical level, as well as several clinical and biochemical parameters of glycemic control and lipid metabolism, were compared before and after 3 months of additional treatment with troglitazone. The body mass index (BMI) tended to increase in both groups (22.7 +/- 0.6 v 23.2 +/- 0.6 kg/m2 in D + T, nonsignificant [NS]; 22.2 +/- 0.5 v 22.3 +/- 0.5 kg/m2 in S + T, NS), while it tended to decrease in the control group (only diet therapy, 23.6 +/- 0.6 v 23.1 +/- 0.8 kg/m2, NS). Mean blood pressure ([BP] 96 +/- 3 v 89 +/- 4 mm Hg, P < .05) decreased significantly in the D + T group. Changes in the glycemic and lipid profile and leptin did not reach statistical significance. The D + T group showed a significant decline in immunoreactive insulin ([IRI] 12.4 +/- 1.2 v 8.0 +/- 1.0 microU/mL, P < .05), reflecting markedly reduced insulin resistance, as well as a significant increase in plasma insulin-like growth factor-1 ([IGF-1] 175.7 +/- 14.2 v 189.8 +/- 12.6 ng/mL, P < .05). A slight weight gain was associated with a tendency for subcutaneous fat to increase, while visceral fat decreased in both troglitazone-treated groups. The decrease in the visceral to subcutaneous fat ratio (V/S ratio) was statistically significant in the D + T group (1.09 +/- 0.11 v 0.94 +/- 0.09, P < .05), while the V/S ratio in the control group did not change. A notable finding of this study is the difference in the response to troglitazone between subcutaneous and visceral adipose tissue. It is suggested that troglitazone may exert beneficial effects by reducing visceral fat.     

Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation: the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study

Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P相似文献   

Effect of aerobic training on plasma levels and subcutaneous abdominal adipose tissue gene expression of adiponectin, leptin, interleukin 6, and tumor necrosis factor alpha in obese women

Adipocytokines secreted by adipose tissue are suggested to play a role in the development of obesity-related complications. Regular aerobic exercise has been shown to reduce the risk of metabolic complications in obese subjects. The aim of this study was to investigate the effect of aerobic training on gene expression in subcutaneous abdominal adipose tissue (SCAAT) and on plasma levels of several adipocytokines in obese women. Twenty-five obese sedentary premenopausal women (body mass index, 32.18 +/- 3.17 kg/m(2)) underwent a 12-week aerobic exercise program, with a frequency of 5 d/wk and intensity corresponding to 50% of individual maximal oxygen consumption (V(.-)(O(2)max)) consisting of 2 sessions per week of supervised aerobic exercise and 3 sessions per week of home-based exercise on a bicycle ergometer. Before and after the aerobic training, (V(.-)(O(2)max)) and body composition were measured and plasma and SCAAT biopsy samples (in a subgroup of 8 subjects) were obtained for determination of plasma and messenger RNA levels of adipocytokines (leptin, adiponectin, interleukin 6, tumor necrosis factor alpha). The aerobic training resulted in an increase of subjects' V o(2)max by 12.8% (24.6 +/- 3.9 vs 27.7 +/- 4.8 mL x min(-1) x kg(-1), P < .05). Body weight and fat mass were reduced by 5.9% (88.5 +/- 8.2 vs 83.3 +/- 7.7 kg, P < .001) and 6.4% (38.8 +/- 4.2% vs 36.3 +/- 4.6%, P < .001), respectively, and the revised QUantitative Insulin sensitivity ChecK Index (QUICKI) increased (0.43 +/- 0.06 vs 0.48 +/- 0.06, P < .05) during the aerobic training. No aerobic training-induced changes in messenger RNA levels of the investigated genes in SCAAT were observed. A decrease of plasma leptin (24.3 +/- 8.7 vs 18.1 +/- 8.3 ng/mL, P < .05) was detected, whereas plasma levels of other cytokines remained unchanged. In moderately obese females, 3 months' aerobic training did not promote changes in the adipose tissue gene expression or plasma levels of the adipocytokines (except for leptin) involved in a regulation of lipid and carbohydrate metabolism.