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

2001 ◽  
Vol 281 (1) ◽  
pp. E113-E121 ◽  
Author(s):  
Michael J. Toth ◽  
Cynthia K. Sites ◽  
William T. Cefalu ◽  
Dwight E. Matthews ◽  
Eric T. Poehlman
Keyword(s):  
Physical Activity ◽  
Maximal Oxygen Consumption ◽  
Premenopausal Women ◽  
Abdominal Fat ◽  
Fat Free Mass ◽  
Thigh Muscle ◽  
Whole Body ◽  
Glucose Disposal ◽  
Statistical Control ◽  
Regional Adiposity

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

Glucose tolerance and insulin action in healthy centenarians

1996 ◽  
Vol 270 (5) ◽  
pp. E890-E894 ◽  
Author(s):  
G. Paolisso ◽  
A. Gambardella ◽  
S. Ammendola ◽  
A. D'Amore ◽  
V. Balbi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Insulin Action ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Aged Subjects

Advancing age has been found to be associated with a decline in insulin action. Nevertheless, no study has been conducted in healthy centenarians. Our study investigates glucose tolerance and insulin action in centenarians. Fifty-two subjects were enrolled. The subjects were divided in three groups as follows: 1) adults (< 50 yr; n = 20);2) aged subjects (> 75 yr; n = 22); and 3) centenarians (> 100 yr; n = 14). Body composition was studied by bioimpedance analysis. In all subjects, an oral glucose tolerance test and euglycemic glucose clamp were performed. Centenarians have a lower fat-free mass (FFM) than aged subjects and adults, whereas fasting plasma glucose, triglycerides, free fatty acids, urea, and creatinine were not different in the groups studies. Centenarians had a 2-h plasma glucose concentration (6.0 +/- 0.2 mmol/l) that was lower than that in aged subjects (6.6 +/- 0.5 mmol/l, P < 0.05) but not different from adults [6.4 +/- 0.4 mmol/l, P = not significant (NS)]. During the clamp, plasma glucose and insulin concentrations were similar in the three groups. In these conditions, centenarians had a whole body glucose disposal (34.1 +/- 0.6 mumol.kg FFM-1.min 1) that was greater than that in aged subjects (23.3 +/- 0.5 mumol.kg FFM-1.min-1 P < 0.01) but not different from adults (34.6 +/- 0.5 mumol/kg x min, P = NS). In conclusion, our study demonstrates that centenarians compared with aged subjects had a preserved glucose tolerance and insulin action.

Racial differences in lipid metabolism in women with abdominal obesity

2000 ◽  
Vol 279 (3) ◽  
pp. R944-R950 ◽  
Author(s):  
Susan B. Racette ◽  
Jeffrey F. Horowitz ◽  
Bettina Mittendorfer ◽  
Samuel Klein
Keyword(s):  
Fatty Acid ◽  
Black Women ◽  
Racial Differences ◽  
Abdominal Obesity ◽  
Plasma Insulin ◽  
White Women ◽  
Abdominal Fat ◽  
Fat Free Mass ◽  
Whole Body ◽  
Epinephrine Infusion

We evaluated palmitate rate of appearance (Ra) in plasma during basal conditions and during a four-stage epinephrine infusion plus pancreatic hormonal clamp in nine white and nine black women with abdominal obesity, who were matched on fat-free mass, total and percent body fat, and waist-to-hip circumference ratio. On the basis of single-slice magnetic resonance imaging analysis, black women had the same amount of subcutaneous abdominal fat but less intra-abdominal fat than white women (68 ± 9 vs. 170 ± 14 cm2, P < 0.05). Basal palmitate Rawas lower in black than in white women (1.95 ± 0.26 vs. 2.88 ± 0.23 μmol · kg fat-free mass−1 · min−1, P < 0.005), even though plasma insulin and catecholamine concentrations were the same in both groups. Palmitate Ra across a physiological range of plasma epinephrine concentrations remained lower in black women, because the increase in palmitate Ra during epinephrine infusion was the same in both groups. We conclude that basal and epinephrine-stimulated palmitate Ra is lower in black than in white women with abdominal obesity. The differences in basal palmitate kinetics are not caused by alterations in plasma insulin or catecholamine concentrations or lipolytic sensitivity to epinephrine. The lower rate of whole body fatty acid flux and smaller intra-abdominal fat mass may have clinical benefits because of the relationship between excessive fatty acid availability and metabolic diseases.

scholarly journals Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat

2006 ◽  
Vol 100 (5) ◽  
pp. 1584-1589 ◽  
Author(s):  
Valerie B. O’Leary ◽  
Christine M. Marchetti ◽  
Raj K. Krishnan ◽  
Bradley P. Stetzer ◽  
Frank Gonzalez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Oxygen Consumption ◽  
Glucose Metabolism ◽  
Exercise Training ◽  
Visceral Fat ◽  
Maximal Oxygen Consumption ◽  
Subcutaneous Fat ◽  
Abdominal Fat ◽  
Fat Free Mass ◽  
Men And Women

Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 ± 1 yr, body mass index = 33.2 ± 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 ± 0.8 vs. 24.3 ± 1.0 ml·kg−1·min−1, P < 0.0001), decreased body weight ( P < 0.0001) and fat mass ( P < 0.001), while fat-free mass was not altered ( P > 0.05). VF (176 ± 20 vs. 136 ± 17 cm2, P < 0.0001), subcutaneous fat (351 ± 34 vs. 305 ± 28 cm2, P < 0.03), and total abdominal fat (525 ± 40 vs. 443 ± 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower ( P < 0.003) after training, but total adiponectin and tumor necrosis factor-α remained unchanged. Insulin resistance was reversed by exercise (40.1 ± 7.7 vs. 27.6 ± 5.6 units, P < 0.01) and correlated with changes in VF ( r = 0.66, P < 0.01) and maximal oxygen consumption ( r = −0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.

scholarly journals Metabolically-Unhealthy Obesity Is Associated With Increased Adipose Tissue Inflammatory Gene Expression and 24-Hour Plasma Concentrations of PAI-1, but Not Other Inflammatory Cytokines

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A21-A22
Author(s):  
Max C Petersen ◽  
Gordon I Smith ◽  
Mihoko Yoshino ◽  
Vincenza Cifarelli ◽  
Jun Yoshino ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Plasma Concentrations ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Insulin Resistant ◽  
Markers Of Inflammation ◽  
Metabolically Healthy ◽  
Metabolically Unhealthy Obesity ◽  
Pai 1

Abstract Insulin resistant glucose metabolism is the most common metabolic complication associated with obesity; however, a subset of people with obesity have normal insulin sensitivity and are considered to be metabolically healthy. In rodent models of obesity, adipose tissue (AT) inflammation contributes to whole-body insulin resistance mediated, at least in part, by production of proinflammatory cytokines that are secreted into the systemic circulation. We therefore hypothesized that AT markers of inflammation and plasma concentrations of inflammatory cytokines would be greater in people with metabolically-unhealthy obesity (MUO) and insulin-resistant glucose metabolism than in insulin-sensitive people with metabolically-healthy obesity (MHO). We measured AT expression of genes that encode for proinflammatory proteins by using RNA sequencing and plasma cytokine concentrations assessed serially over 24 hours by using multiplex assays in: i) 28 people with MHO (defined as normal glucose tolerance and normal insulin-stimulated glucose disposal assessed using the hyperinsulinemic-euglycemic clamp procedure [48 ± 2 µmol/kg fat-free mass/min]); and ii) 28 people with MUO (defined as prediabetes and impaired insulin-stimulated glucose disposal [28 ± 1 µmol/kg fat-free mass/min]). AT markers of inflammation (expression of SERPINE1, CCL3, CCL5, CD68, CD74, MRC1, and CXCL16) were greater in the MUO than in the MHO group (all P &lt; 0.05). However, the 24-hour plasma concentration areas-under-the curve (AUC) for TNFα, MCP-1, IL-6, RANTES, IL-1β, IL-17, and IFN-γ were not different between MHO and MUO groups. In contrast, 24-hour plasma plasminogen activator inhibitor 1 (PAI-1) AUC was greater in the MUO (1,759 ± 169 ng/mL x h) group than in the MHO (716 ± 85 ng/mL x h) group (P &lt; 0.001) and plasma PAI-1 was inversely correlated with whole-body insulin sensitivity (r= -0.57; P &lt; 0.001). We conclude that, with the exception of PAI-1, AT inflammation does not contribute to whole-body insulin resistance by increasing systemic circulating inflammatory cytokine levels. However, increased AT production of PAI-1 is associated with whole-body insulin resistance in people with MUO.

A cross-sectional study on body composition and energy expenditure in women athletes during aging

1996 ◽  
Vol 271 (5) ◽  
pp. E916-E921 ◽  
Author(s):  
A. S. Ryan ◽  
B. J. Nicklas ◽  
D. Elahi
Keyword(s):  
Body Composition ◽  
Women Athletes ◽  
Resting Metabolic Rate ◽  
Maximal Oxygen Consumption ◽  
Abdominal Fat ◽  
Fat Free Mass ◽  
Young Athletes ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Regional Body Composition

The relationships between total and regional body composition, intra-abdominal adipose tissue (IAAT), resting metabolic rate (RMR), and substrate oxidation were examined in 43 highly trained women athletes and 14 sedentary women aged 18-69 yr. Athletes were divided into four groups (18-29, 30-39, 40-49, and 50-69 yr) and controls into two groups (18-29 and 40-50 yr). Maximal oxygen consumption declined with age (r = -0.52, P < 0.0005) in the athletes and was higher in all groups of athletes than in controls (P < 0.0001). No differences in percent fat and fat-free mass (FFM) were found between the youngest and oldest athletes. Although body mass index was < 25 kg/m2 in all subjects, percent body fat and total fat mass were higher in controls than in athletes for both young and older women (all P < 0.05). FFM was higher in young athletes than in young controls (P < 0.0001). Despite similar percent fat among athletes, IAAT increased with age (r = 0.75, P < 0.0001), but subcutaneous abdominal fat and sagittal diameter did not. IAAT and subcutaneous abdominal fat were also higher in young controls than in young athletes and in older controls than in older athletes (all P < 0.005). Age and FFM were independent predictors of the decline in RMR in the athletes. Fat oxidation (g/day) was highest in the youngest athletes and declined with age (r = -0.47, P < 0.005). We conclude that intense chronic exercise in women athletes prevented the decline in FFM with age. Endurance-trained women have low IAAT stores, which may potentially reduce subsequent risk associated with the metabolic syndrome.

Comparison of leucine kinetics in endurance-trained and sedentary humans

1999 ◽  
Vol 86 (1) ◽  
pp. 320-325 ◽  
Author(s):  
Linda S. Lamont ◽  
Arthur J. McCullough ◽  
Satish C. Kalhan
Keyword(s):  
Body Weight ◽  
Oxygen Consumption ◽  
Maximal Oxygen Consumption ◽  
Kinetic Studies ◽  
Fat Free Mass ◽  
Whole Body ◽  
Tissue Mass ◽  
Cross Sectional ◽  
Leucine Oxidation ◽  
Leucine Kinetics

Whole body leucine kinetics was compared in endurance-trained athletes and sedentary controls matched for age, gender, and body weight. Kinetic studies were performed during 3 h of rest, 1 h of exercise (50% maximal oxygen consumption), and 2 h of recovery. When leucine kinetics were expressed both per unit of body weight and per unit of fat-free mass, both groups demonstrated an increase in leucine oxidation during exercise ( P < 0.01). Trained athletes had a greater leucine rate of appearance during exercise and recovery compared with their sedentary counterparts ( P < 0.05) and an increased leucine oxidation at all times on the basis of body weight ( P < 0.05). However, all of these between-group differences were eliminated when leucine kinetics were corrected for fat-free tissue mass. Therefore, correction of leucine kinetics for fat-free mass may be important when cross-sectional investigations on humans are performed. Furthermore, leucine oxidation, when expressed relative to whole-body oxygen consumption during exercise, was similar between groups. It is concluded that there was no difference between endurance-trained and sedentary humans in whole body leucine kinetics during rest, exercise, or recovery when expressed per unit of fat-free tissue mass.

Fasting inhibits insulin-mediated glycolysis and anaplerosis in human skeletal muscle

1991 ◽  
Vol 261 (5) ◽  
pp. E598-E605 ◽  
Author(s):  
C. E. Castillo ◽  
A. Katz ◽  
M. K. Spencer ◽  
Z. Yan ◽  
B. L. Nyomba
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Glycogen Synthase ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Glycolytic Flux ◽  
Quadriceps Femoris Muscle ◽  
Before And After ◽  
Femoris Muscle

uglycemic (approximately 5.5 mM) hyperinsulinemic (60 mU.m-2.min-1) clamps were performed for 2 h after a 10-h fast and after a prolonged (72-h) fast. Biopsies were obtained from the quadriceps femoris muscle before and after each clamp. The rate of whole body glucose disposal was approximately 50% lower during the clamp after the 72-h fast (P less than or equal to 0.001). The increase in carbohydrate (CHO) oxidation (which is proportional to glycolysis) during the clamp after the 10-h fast (to 13.8 +/- 1.5 mumol.kg fat free mass-1.min-1) was completely abolished during the clamp after the 72-h fast (1.7 +/- 0.6; P less than or equal to 0.001). During the clamp after the 10-h fast, postphosphofructokinase (PFK) intermediates and malate in muscle increased, whereas glutamate decreased (P less than or equal to 0.05-0.001 vs. basal) and citrate did not change. During the clamp after the 72-h fast, there were no significant changes in post-PFK intermediates or glutamate (P greater than 0.05 vs. basal), but there was a decrease in citrate (P less than or equal to 0.01 vs. basal). Euglycemic hyperinsulinemia increased glycogen synthase fractional activity in muscle under both conditions but to a greater extent after the 72-h fast (P less than or equal to 0.01). It is concluded that insulin (after 10-h fast) increases glycolytic flux and the content of malate in muscle, which is probably due to increased anaplerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatty acid oxidation in African-American and Caucasian women during physical activity

2001 ◽  
Vol 90 (6) ◽  
pp. 2319-2324 ◽  
Author(s):  
R. C. Hickner ◽  
J. Privette ◽  
K. McIver ◽  
H. Barakat
Keyword(s):  
Physical Activity ◽  
African American ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Premenopausal Women ◽  
Fat Oxidation ◽  
Fat Free Mass ◽  
Analysis Of Covariance ◽  
Exercise Session ◽  
Acid Oxidation

The goal of this study was to determine whether differences in physical activity-related fat oxidation exist between lean and obese African-American (LAA and OAA) and lean and obese Caucasian (LC and OC) premenopausal women. Lean AA (28.4 ± 2.8 yr, n = 7), LC (24.7 ± 1.8 yr, n = 9), OAA (30.9 ± 2.2 yr, n = 11), and OC (34.1 ± 2.5 yr, n = 9) women underwent preliminary assessment of peak aerobic capacity (V˙o 2 peak). On a subsequent testing day, participants exercised after an 8-h fast on a cycle ergometer at 15 W (∼40% V˙o 2 peak) for 10 min and then for 10 min at ∼65% V˙o 2 peak. Fatty acid oxidation was determined using the average respiratory exchange ratio and O2 consumption during minutes 5–9of the exercise session. Percent body fat and fat-free mass were lower ( P < 0.05) in LAA (25.8 ± 2.8% and 48.3 kg) and LC (26.4 ± 2.0% and 45.8 ± 1.7 kg) than in OAA (41.2 ± 1.3% and 58.8 ± 3.3 kg) and OC (39.3 ± 2.7% and 58.6 kg) women. Fat oxidation among the groups was analyzed statistically using analysis of covariance with fat-free mass andV˙o 2 peak as covariates. During exercise at 15 W, fat oxidation was as low in LAA (0.134 ± 0.024 g/min) as in OAA (0.144 ± 0.026 g/min) and OC (0.156 ± 0.020 g/min) women: all these rates of fat oxidation were lower than in LC women (0.200 ± 0.021 g/min, P < 0.05, LC vs. all other groups). Fatty acid oxidation during higher-intensity exercise (65%V˙o 2 peak) was higher in LC than in OC women but was not statistically different between African-American and Caucasian groups. Fatty acid oxidation was therefore lower during low-intensity physical activity in OAA, LAA, and OC than in LC women.

Basal and insulin-regulated free fatty acid and glucose metabolism in humans

2007 ◽  
Vol 292 (6) ◽  
pp. E1770-E1774 ◽  
Author(s):  
Samyah Shadid ◽  
Jill A. Kanaley ◽  
Michael T. Sheehan ◽  
Michael D. Jensen
Keyword(s):  
Glucose Metabolism ◽  
Body Fat ◽  
Premenopausal Women ◽  
Glucose Production ◽  
Normal Weight ◽  
Fat Free Mass ◽  
Glucose Disposal ◽  
Percent Body Fat ◽  
Class Iii ◽  
Glucose Flux

These studies were done to examine the effects of body composition, resting energy expenditure (REE), sex, and fitness on basal and insulin-regulated FFA and glucose metabolism. We performed 137 experiments in 101 nondiabetic, premenopausal women and men, ranging from low normal weight to class III obese (BMI 18.0–40.5 kg/m2). Glucose flux was measured using [6-2H2]glucose and FFA kinetics with [9,10-3H]oleate under either basal (74 experiments) or euglycemic hyperinsulinemic (1.0 mU·kg FFM−1·min−1) clamp conditions (63 experiments). Consistent with our previous findings, REE and sex independently predicted basal FFA flux, whereas fat-free mass was the best predictor of basal glucose flux; in addition, percent body fat was independently and positively associated with basal glucose flux (total r2 = 0.52, P < 0.0001). Insulin-suppressed lipolysis remained significantly associated with REE ( r = 0.25, P < 0.05), but percent body fat also contributed (total adjusted r2 = 0.36, P < 0.0001), whereas sex was not significantly related to insulin-suppressed FFA flux. Glucose disposal during hyperinsulinemia was independently associated with peak V̇o2, percent body fat, and FFA concentrations (total r2 = 0.63, P < 0.0001) but not with sex. We conclude that basal glucose production is independently related to both FFM and body fatness. In addition, hyperinsulinemia obscures the sex differences in FFA release relative to REE, but brings out the effects of fatness on lipolysis.

Effects of high-intensity exercise training on body composition, abdominal fat loss, and cardiorespiratory fitness in middle-aged Korean females

2012 ◽  
Vol 37 (6) ◽  
pp. 1019-1027 ◽  
Author(s):  
Man-Gyoon Lee ◽  
Kyung-Shin Park ◽  
Do-Ung Kim ◽  
Soon-Mi Choi ◽  
Hyoung-Jun Kim
Keyword(s):  
Oxygen Consumption ◽  
Exercise Training ◽  
High Intensity ◽  
Maximal Oxygen Consumption ◽  
Training Group ◽  
Abdominal Fat ◽  
High Intensity Exercise ◽  
Whole Body ◽  
Fat Loss ◽  
Intensity Training

The primary purpose of this study was to investigate the effects of high-intensity exercise training under relatively equal energy expenditure on whole body fat and abdominal fat loss, and cardiorespiratory fitness. Twenty-two untrained middle-aged Korean females were randomized into one of the following groups: control, low-intensity training group (LI), and high-intensity training group (HI). Subjects completed 14 weeks of training at 50% maximal oxygen consumption (LI) or 70% maximal oxygen consumption (HI) with the volume of exercise equated relative to kilograms of body weight. Weekly exercise volumes were 13.5 METs⋅h/week for the first 4 weeks, 18 METs⋅h/week for next 5 weeks, and 22.5 METs⋅h/week for the final 5 weeks. Data were analyzed using 2-way repeated measures ANOVA with post hoc test, using Bonferroni’s correction. HI showed significant reductions in fat mass (p < 0.05), total abdominal fat (p < 0.01), and subcutaneous abdominal fat (p < 0.01). LI reduced total abdominal fat (p < 0.05), but there were no other significant changes found in the control or LI groups. Maximal oxygen consumption was enhanced in both HI and LI with no significant group difference. High-density lipoprotein cholesterol increased significantly in HI (p < 0.05). IL-6, C-reactive protein, TNF-α, and other blood lipids were unaltered following training. Results indicate that high-intensity exercise training is more beneficial in whole body and abdominal fat loss; however, cardiorespiratory enhancement shows a dose–response relationship with weekly exercise volume. It is suggested that 14 weeks of aerobic exercise training at either high- or low-intensity is not sufficient enough to induce changes in levels of inflammatory proteins.

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