Effects of tempol on endothelial and vascular dysfunctions and insulin resistance induced by a high-fat high-sucrose diet in the rat.

We investigated the effects of treatment with tempol (an antioxidant) on vascular and metabolic dysfunction induced by a high-fat high-sucrose (HFHS) diet. Rats were randomized to receive an HFHS or chow diet with or without tempol treatment (1.5 mmol·(kg body mass)(-1)·day(-1)) for 4 weeks. Blood pressure, heart rate, and blood flow were measured in the rats by using intravascular catheters and Doppler flow probes. Insulin sensitivity and vascular responses to insulin were assessed during a euglycemic-hyperinsulinemic clamp. In-vitro studies were performed to evaluate vascular reactivity and endothelial and inducible nitric oxide synthase (eNOS; iNOS) expression in vascular and muscle tissues. Endothelin, nitrotyrosine, and NAD(P)H oxidase expressions were determined in vascular tissues, and glucose transport activity and glucose transporter 4 (GLUT4) expression were examined in muscles. Tempol treatment was found to prevent alterations in insulin sensitivity, glucose transport activity, GLUT4 expression, and vascular reactivity, and to prevent increases in plasma insulin, blood pressure, and heart rate noted in the untreated HFHS-fed rats. These were associated with increased levels of eNOS expression in vascular and muscle tissues, but reductions in nitrotyrosine, endothelin, NAD(P)H oxidase, and iNOS expressions. Therefore, oxidative stress induced by a relatively short-term HFHS diet could contribute to the early development of vascular and metabolic abnormalities in rats.

Discordances among different tools used to estimate cardiovascular risk in postmenopausal women.

BACKGROUND: New cardiovascular disease (CVD) risk factors are being recognized and suggested to be included in CVD risk stratification. High-sensitivity C-reactive protein (hs-CRP) and the metabolic syndrome (MetS) are among these risk factors. However, CVD risk classification may be divergent when using different approaches. OBJECTIVES: To compare differences in CVD risk estimation using the Framingham risk score (FRS), hs-CRP and the presence of the MetS in a group of 109 postmenopausal women in primary CVD prevention. METHODS: The FRS and presence of the MetS were determined. CVD risk was evaluated with a cardiovascular point scoring system based on Framingham covariables and hs-CRP values (Women's Health Study [WHS] model). The estimated CVD risks based on hs-CRP levels and the WHS model were compared with the FRS. RESULTS: Using the FRS, 99% of women (n=108) were determined to have a low CVD risk. The MetS was identified in 39.4% (n=43) of the women. When hs-CRP was used alone to estimate CVD risk, 37.6% (n=41) of women were classified as being at low, 33.9% (n=37) at moderate and 28.4% (n=31) at high CVD risk. With the WHS model, 83.5% (n=91), 14.7% (n=16) and 1.8 % (n=2) of women were classified as being at low, moderate and high CVD risk, respectively. CONCLUSIONS: A substantial number of postmenopausal women showing evidence of the MetS were not identified by the FRS, even though women with the MetS are at higher risk of CVD. Estimation of risk by hs-CRP is significantly divergent when using conventional hs-CRP cutoff values compared with an integrated use in the WHS model.

Regional body fat distribution and metabolic profile in postmenopausal women.

The aim of the study was to examine how body fat distribution variables were associated with metabolic parameters in a sample of 113 postmenopausal women not receiving hormone therapy (56.9 +/- 4.4 years, 28.4 +/- 5.1 kg/m(2)). Body fat distribution variables (visceral adipose tissue [AT], subcutaneous AT, and total midthigh AT) were measured using computed tomography; body fat mass was assessed by hydrostatic weighing; insulin sensitivity was determined with the euglycemic-hyperinsulinemic clamp; fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) concentrations were measured by a 75-g oral glucose load; and (high-sensitivity) C-reactive protein (hs-CRP) was measured using a highly sensitive assay. After controlling for fat mass, visceral AT was positively associated with plasma triglyceride, hs-CRP, FPG, and 2hPG, and negatively associated with high-density lipoprotein cholesterol (HDL-C) and insulin sensitivity. Total midthigh AT was negatively associated with apolipoprotein B, FPG, and 2hPG, and positively associated with insulin sensitivity. Stepwise multiple regression analyses including abdominal visceral AT, subcutaneous AT and total midthigh AT as independent variables showed that abdominal visceral AT best predicted the variance in plasma triglyceride, HDL-C, low-density lipoprotein peak particle size, hs-CRP, FPG, 2hPG, and insulin sensitivity. Abdominal subcutaneous AT was a significant predictor of only insulin sensitivity, whereas total midthigh AT predicted HDL-C, low-density lipoprotein peak particle size, and apolipoprotein B. These multivariate analyses also indicated that total midthigh AT was favorably related to these outcomes, whereas abdominal visceral AT and subcutaneous AT were unfavorably related. These results confirmed that abdominal visceral fat is a critical correlate of metabolic parameters in postmenopausal women. In addition, a higher proportion of AT located in the total midthigh depot is associated with a favorable metabolic profile.

Endothelial and vascular dysfunctions and insulin resistance in rats fed a high-fat, high-sucrose diet.

This study was designed to examine the effects of a high-fat, high-sucrose (HFHS) diet on vascular and metabolic actions of insulin. Male rats were randomized to receive an HFHS or regular chow diet for 4 wk. In a first series of experiments, the rats had pulsed Doppler flow probes and intravascular catheters implanted to measure blood pressure, heart rate, and regional blood flows. Insulin sensitivity and vascular responses to insulin were assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine skeletal muscle glucose transport activity and to determine in vitro vascular reactivity, endothelial nitric oxide synthase (eNOS) protein expression in muscle and vascular tissues and endothelin content, nitrotyrosine formation, and NAD(P)H oxidase protein expression in vascular tissues. The HFHS-fed rats displayed insulin resistance, hyperinsulinemia, hypertriglyceridemia, hyperlipidemia, elevated blood pressure, and impaired insulin-mediated renal and skeletal muscle vasodilator responses. A reduction in endothelium-dependent vasorelaxation, accompanied by a decreased eNOS protein expression in muscles and blood vessel endothelium, and increased vascular endothelin-1 protein content were also noted in HFHS-fed rats compared with control rats. Furthermore, the HFHS diet induced a reduced insulin-stimulated glucose transport activity in muscles and increased levels of NAD(P)H oxidase protein and nitrotyrosine formation in vascular tissues. These findings support the importance of eNOS protein in linking metabolic and vascular disease and indicate the ability of a Westernized diet to induce endothelial dysfunction and to alter metabolic and vascular homeostasis.

Relationship between eating behaviours and food and drink consumption in healthy postmenopausal women in a real-life context.

Associations between eating behaviours and dietary variables have not been thoroughly investigated in healthy postmenopausal women in a real life uncontrolled context. To investigate how eating behaviours (cognitive dietary restraint, disinhibition and susceptibility to hunger) were associated with food and drink consumption, energy density and meal pattern in 112 healthy postmenopausal women (age 56.8 (SD 4.4) years) not on.hormonal therapy. Women completed a 3 d weighed food record and filled out the Three-Factor Eating Questionnaire. The sample was divided according to the median of the distribution of cognitive dietary restraint and disinhibition (9 and 6 respectively). Both subgroups of women with high restraint level (presenting either high or low disinhibition) consumed a diet with a lower energy density than subgroups of women with lower restraint level. Women with high restraint-low disinhibition had a lower consumption of red meat and processed meat and a lower consumption of diet soft drinks than women with low restraint-high disinhibition. They were also characterised by a higher intake of whole grains than women with high restraint-high disinhibition and than women with lower restraint level (with either high or low disinhibition). Women with high restraint-high disinhibition levels showed differences in dietary variables when compared with subgroups of women with lower restraint level, namely for refined grains and diet soft drinks. We conclude that in healthy postmenopausal women, dietary consumption of specific food and drink may be related to particular eating behaviours. Women with high restraint and low disinhibition levels generally showed the most healthy dietary pattern.

Safety and magnitude of changes in blood glucose levels following exercise performed in the fasted and the postprandial state in men with type 2 diabetes.

BACKGROUND: Information on the extent to which acute exercise reduces blood glucose levels (BGL) in type 2 diabetes is lacking. For this reason, the effects of exercise initiated at different preexercise BGL were assessed in men with type 2 diabetes both in the fasted (FS) and the postprandial states (PS). DESIGN AND METHODS: Forty-three men with type 2 diabetes, 12 on diet alone and 31 on hypoglycaemic agents, completed a total of 1555 exercise sessions performed in the FS and 0-1, 1-2, 2-3, 3-4, 4-5, and 5-8 h in the PS. Capillary BGL were measured before and immediately after a 1h standardized aerobic exercise session on an ergocycle at 60% of VO2 peak. RESULTS: In the FS, there was an increase in postexercise BGL of 27+/-21% (mean+/-SD; P<0.001) when preexercise BGL was < or =6 mmol/l, no change when preexercise BGL were between 6 and 8 mmol/l, and a significant decrease of 12+/-13% when preexercise BGL were >8 mmol/l (P<0.001). In the PS, most exercise sessions were associated with significant decreases in BGL ranging between 18+/-17 and 50+/-12% (P<0.001), depending on the time interval between meals and the onset of exercise. Regarding the metabolic PS, the decline in BGL was most pronounced with high preexercise BGL. CONCLUSIONS: Our observations not only demonstrate that it was safe for middle-aged obese men with type 2 diabetes to exercise in the FS, but also show that the decrease in BGL during aerobic exercise was largely dependent on preexercise BGL.

Measuring insulin sensitivity in postmenopausal women covering a range of glucose tolerance: comparison of indices derived from the oral glucose tolerance test with the euglycemic-hyperinsulinemic clamp.

This study compares indices of insulin sensitivity derived from fasting and oral glucose tolerance test (OGTT) glucose and insulin measurements, with respect to the reference measure (M/I), obtained from the euglycemic-hyperinsulinemic clamp, in postmenopausal women with varying glucose tolerance status. Fasting plasma insulin index, homeostasis model assessment index, and OGTT-derived indices (insulin 120-minute, Matsuda, metabolic clearance rate [MCR] of glucose, insulin sensitivity [ISI], and Cederholm indices) were calculated and compared with the M/I value in 112 postmenopausal women. All indices examined were significantly correlated with M/I (0.28 < or = r(2) < or = 0.56). Association studies revealed that on average, 48% of women were grouped in the same tertile of insulin sensitivity when using M/I and fasting plasma insulin index, and 54% when using M/I and insulin 120-minute index. However, concordance with M/I tertiles were 57%, 58%, 64%, 64%, and 68% for homeostasis model assessment, Matsuda, MCR, ISI, and Cederholm indices, respectively. Finally, correlation coefficients between M/I and insulin sensitivity indices were generally lower in women with normal glucose tolerance compared with women with impaired glucose tolerance or type 2 diabetes mellitus. These results suggest that in postmenopausal women, surrogate indices of insulin sensitivity obtained from OGTT data and incorporating a measurement of body weight or body mass index) (Cederholm, ISI, and MCR indices) appear to be superior to those without OGTT data or body weight-body mass index measurements and, therefore, could offer a better estimate of insulin sensitivity, allowing an improved clinical evaluation of this population at higher risk of cardiovascular disease and type 2 diabetes mellitus.

Circulating oxidized LDL is associated with parameters of the metabolic syndrome in postmenopausal women.

UNLABELLED: Oxidized low-density lipoproteins (ox-LDL) play a significant role in the development of atherosclerosis. OBJECTIVE: To investigate the relation between circulating ox-LDL and components of the metabolic syndrome (MS) in a sample of 124 postmenopausal women with varying glucose tolerance status. METHODS: This cross-sectional study included postmenopausal women not using hormone therapy. Ox-LDL concentrations were measured in plasma by a monoclonal antibody (mAb-4E6) based competition ELISA. LDL peak particle diameter (LDL-PPD) was measured by non-denaturating polyacrylamide gradient gel electrophoresis (PAGGE). Presence of the MS was determined according to the definition of the NCEP-ATPIII. RESULTS: Circulating ox-LDL concentrations were significantly associated with some factors of the MS such as triglyceride (r=0.48; p<0.0001), high-density lipoprotein cholesterol (r=-0.34; p=0.0001) and fasting plasma glucose concentrations (r=0.21; p=0.02). Ox-LDL concentrations were also associated with LDL cholesterol (r=0.54; p<0.0001), total cholesterol (r=0.48; p<0.0001), LDL apolipoprotein B (r=0.62; p<0.0001) and LDL-PPD (r=-0.18; p<0.05). Moreover, women with the MS had significantly higher ox-LDL concentrations (79.5+/-28.3 U/l) compared to women without the MS (64.2+/-19.9 U/l) (p<0.05). CONCLUSION: Ox-LDL concentrations are associated with individual components of the MS and are significantly higher in postmenopausal women with MS compared to healthy postmenopausal women.

Physical training reverses the increased activity of the hepatic ketone body synthesis pathway in chronically diabetic rats.

This study was designed to examine whether the training-induced improvement in the plasma concentration of ketone bodies in experimental diabetes mellitus could be explained by changes in the activity of the hepatic ketone body synthesis pathway and/or the plasma free fatty acid levels. Diabetes mellitus was induced by an intravenous injection of streptozotocin (50 mg/kg), and training was carried out on a treadmill. The plasma concentration of beta-hydroxybutyric acid was increased (P < 0.001) in sedentary diabetic rats, and this was partly reversed by training (P < 0.001). The plasma concentration of free fatty acids was increased (P < 0.001) in sedentary diabetic rats, and this was reversed to normal by training (P < 0.001). Diabetes was also associated with an increased activity of the hepatic ketone body synthesis pathway. When the data are expressed as per total liver, physical training decreased the activity of the hepatic ketone body synthesis pathway by 18% in nondiabetic rats (P < 0.05) and by 22% in diabetic rats (P < 0.01), the activity present in trained diabetic rats being not statistically different from that of sedentary control rats. These data suggest that the beneficial effects of physical training on the plasma beta-hydroxybutyric acid levels in the diabetic state are probably explained in part by a decrease in the activity of the hepatic ketone body synthesis pathway and in part by a decrease in plasma free fatty acid levels.

Effects of high-sucrose feeding on insulin resistance and hemodynamic responses to insulin in spontaneously hypertensive rats.

This study was designed to investigate the effects of a sucrose diet on vascular and metabolic actions of insulin in spontaneously hypertensive rats (SHR). Male SHR were randomized to receive a sucrose or regular chow diet for 4 wk. Age-matched, chow-fed Wistar-Kyoto (WKY) rats were used as normotensive control. In a first series of experiments, the three groups of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and blood flows. Insulin sensitivity was assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine glucose transport activity in isolated muscles and to determine endothelial nitric oxide synthase (eNOS) protein expression in muscles and endothelin content in vascular tissues. Sucrose feeding was shown to markedly enhance the pressor response to insulin and its hindquarter vasoconstrictor effect when compared with chow-fed SHR. A reduction in eNOS protein content in muscle, but no change in vascular endothelin-1 protein, was noted in sucrose-fed SHR when compared with WKY rats, but these changes were not different from those noted in chow-fed SHR. Similar reductions in insulin-stimulated glucose transport were observed in soleus muscles from both groups of SHR when compared with WKY rats. In extensor digitorum longus muscles, a significant reduction in insulin-stimulated glucose transport was only seen in sucrose-fed rats when compared with the other two groups. Environmental factors, that is, high intake of simple sugars, could possibly potentiate the genetic predisposition in SHR to endothelial dysfunction and insulin resistance.

Cholinergic involvement in vascular and glucoregulatory actions of insulin in rats.

This study was designed to test the glucose metabolic and vasodilator actions of insulin in rats and its relation to cholinergic system-dependent mechanisms. The first group of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique carried out in the absence or presence of atropine. The second group of rats was used to determine the cholinergic contribution to in vivo insulin-mediated glucose utilization in individual muscles. Glucose uptake was examined by using [(3)H]2-deoxy-D-glucose. Muscarinic cholinergic blockade was found to significantly (P = 0.002) reduce insulin sensitivity and to completely abrogate the renal (P = 0.008) and hindquarter (P = 0.02) vasodilator responses to euglycemic infusion of insulin. A significant reduction in insulin-stimulated in vivo glucose uptake was also noted in soleus (P = 0.006), quadriceps (P = 0.03), gastrocnemius (P = 0.02), and extensor digitorum longus (EDL) (P = 0.001) muscles, when insulin was infused at a rate of 4 mU . kg(-1) . min(-1), whereas at the rate of 16 mU . kg(-1) . min(-1), a significant reduction in glucose uptake was only observed in EDL (P = 0.03) and quadriceps (P = 0.01) muscles. Together, these results demonstrate a potential role for cholinergic involvement with physiological insulin actions in glucose clearance and blood flow regulation in rats.

The WHO and NCEP/ATPIII Definitions of the Metabolic Syndrome in Postmenopausal Women: Are They So Different?

BACKGROUND: The aim of this study was to examine the metabolic risk profile in postmenopausal women characterized by either the metabolic syndrome (MS) as defined by the World Health Organization (WHO) or the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). METHODS: One hundred and eight postmenopausal women (56.9 +/- 4.2 years; 28.5 +/- 5.9 kg/m(2)) were examined. Each underwent an oral glucose tolerance test, an euglycemic-hyperinsulinemic clamp, an assessment of body fat distribution by computed tomography, a complete plasma lipid-lipoprotein profile, and standard measurements of inflammatory markers. RESULTS: The prevalence of the MS-WHO was 29.6% in our women. Type 2 diabetes was found in 28.1% of women with the MS-WHO. Thirty-one percent of women had the MS-ATP, from which 36.4% had type 2 diabetes. Among the 32 women identified as having MS-WHO, 25 (78.1 %) were also identified as having the MS-ATP. On the other hand, among the 34 women identified as having MS-ATP, 24 (70.0 %) also had MS-WHO (kappa = 0.60). When we subdivided our sample of women as having either isolated MS-WHO, isolated MS-ATP, or combined MS-WHO and MS-ATP, we observed a more deteriorated metabolic risk profile (higher values for visceral adipose tissue, 2-h plasma glucose, and lower HDL-cholesterol concentrations) in women characterized by isolated MS-ATP compared to women with isolated MS-WHO. CONCLUSIONS: These results suggest that, in postmenopausal women, the concordance in the identification of subjects with the MS using each of the proposed definitions is only moderate.

Relation of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and fibrinogen to abdominal adipose tissue, blood pressure, and cholesterol and triglyceride levels in healthy postmenopausal women.

The associations of inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], tumor necrosis factor-alpha, and fibrinogen) with anthropometric and metabolic variables were examined in a sample of 112 postmenopausal women not receiving hormone therapy. Body fat distribution was measured by computed tomography, and insulin sensitivity was determined by an euglycemic-hyperinsulinemic clamp. hs-CRP (0.10 < or = r(2) < or =0.37) and IL-6 (0.06 < or = r(2) < or =0.31) were significantly associated with anthropometric and metabolic variables, including visceral and subcutaneous adipose tissue, systolic and diastolic blood pressure, triglycerides, high-density lipoprotein (HDL) cholesterol, and insulin sensitivity (p <0.05). Women with greater hs-CRP concentrations showed deterioration in their metabolic risk profiles, including abdominal obesity, greater triglyceride and lower HDL cholesterol concentrations, and lower insulin sensitivity compared with women with lower hs-CRP levels. Fifty-nine percent of women with high hs-CRP concentrations had the metabolic syndrome as recently defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. After adjustment for visceral adipose tissue, most of the differences in the plasma lipid-lipoprotein profile were eliminated between women with high hs-CRP levels and women with low hs-CRP levels, whereas some differences in blood pressure variables, insulin sensitivity, and inflammatory markers (IL-6 and fibrinogen) remained significant. In conclusion, these results suggest that increased visceral adipose tissue levels appear to be a determinant covariable of the association between high hs-CRP concentrations and alteration in the metabolic profile.

Physical training reverses defect in 3-ketoacid CoA-transferase activity in skeletal muscle of diabetic rats.

To investigate one potential mechanism whereby physical training improves the plasma concentration of ketone bodies in experimental diabetes mellitus, we measured the activity of 3-ketoacid CoA-transferase, the key enzyme in the peripheral utilization of ketone bodies. Diabetes was induced with streptozotocin (50 mg/kg) and training carried out on a treadmill with a progressive 10-wk program. Diabetes resulted in an increase (P < 0.001) in plasma concentration of beta-hydroxybutyric acid in sedentary rats, which was partly reversed by training (P < 0.001). Diabetes was also associated with a decreased activity of 3-ketoacid CoA-transferase in gastrocnemius muscle. When expressed per total gastrocnemius, training increased the activity of 3-ketoacid CoA-transferase by 66% in nondiabetic rats (P < 0.001) and by 150% in diabetic rats (P < 0.001), the decrease present in diabetic rats being fully reversed by training. Simple linear regression between the log of 3-ketoacid CoA-transferase activity and the log of plasma beta-hydroxybutyric acid levels showed a statistically significant (r = 0.563, P < 0.001) negative correlation. The beneficial effects of training on plasma ketone bodies in diabetic rats are probably explained, at least in part, by an increase in ketone body utilization, mediated by an increase in skeletal muscle 3-ketoacid CoA-transferase activity.

Contribution of abdominal visceral obesity and insulin resistance to the cardiovascular risk profile of postmenopausal women.

The aim of this study was to determine the respective contribution of abdominal visceral adipose tissue (AT) accumulation and insulin resistance (IR) to the determination of a comprehensive cardiovascular metabolic risk profile in 108 postmenopausal women not receiving hormone therapy. Insulin sensitivity (M/I) was determined by a hyperinsulinemic-euglycemic clamp, and visceral AT area was measured by computed tomography. Median values of visceral AT (133.9 cm(2)) and insulin sensitivity (0.010189 mg . kg(-1) . min(-1) . pmol(-1)) were used to form four subgroups: 1) low visceral AT-low IR (n = 35), 2) low visceral AT-high IR (n = 19), 3) high visceral AT-low IR (n = 19), and 4) high visceral AT-high IR (n = 35). Women with isolated IR (low visceral AT and high IR) were characterized by significantly higher fasting and 2-h glycemia and higher fibrinogen, triglyceride, and VLDL-apolipoprotein (apo)B concentrations than women with low visceral AT and low IR (P < 0.05). The plasma lipid-lipoprotein profile and inflammatory markers were not significantly different between women with high visceral AT and low IR and women with low visceral AT and low IR. Women with high visceral AT and high IR had higher fasting and 2-h glycemia, triglyceride, and VLDL-apoB levels; lower apoAI and HDL(2) cholesterol levels; as well as higher C-reactive protein and interleukin-6 concentrations than women with low visceral AT and low IR (P < 0.05). In addition, 15 of the 35 women (42.9%) in the high visceral AT and high IR group were newly diagnosed with type 2 diabetes, whereas no women were diagnosed with type 2 diabetes in the group of women with low visceral AT and low IR. These results show that although the presence of high IR in its isolated form is associated with some metabolic alterations, it is the combination of both high visceral AT and high IR that is the most detrimental for the metabolic health in postmenopausal women.

Energy expenditure from physical activity and the metabolic risk profile at menopause.

PURPOSE: A sedentary lifestyle and visceral obesity are important risk factors for Type 2 diabetes and the development of cardiovascular disease, two conditions that are prevalent in women after menopause. The aim of this study was to assess the relationship between daily energy expenditure from moderate to intense physical activity and several metabolic parameters in postmenopausal women not receiving hormone therapy (HT) and to verify whether these associations are independent of the accumulation of visceral adipose tissue (AT). METHODS: Daily energy expenditure and frequency of participation in physical activity (kcal.kg(-1).15 min(-1)) were measured from a 3-d activity diary in 118 postmenopausal women (56 +/- 4 yr; 29 +/- 6 kg.m(-2)). Daily activities for each 15-min period during 24 h were categorized according to their intensity on a 1-9 scale. Category 1 indicated very low energy expenditure such as sleeping, and category 9 indicated very high energy expenditure such as running. Energy expenditure corresponding to categories 6-9 (EE6-9) was examined in relation to the metabolic risk profile. RESULTS: EE6-9 was negatively and significantly associated with body mass index (BMI) (r = -0.22, P < 0.05) and visceral AT accumulation (r = -0.18, P < 0.05). Partial correlation analyses adjusted for visceral AT showed that EE6-9 was significantly associated with systolic blood pressure (r = -0.22, P < 0.05), plasma concentrations of HDL-cholesterol (chol) (r = 0.23, P < 0.05), HDL2-chol (r = 0.22, P < 0.05), fasting glucose (r = -0.24, P < 0.05), and fasting C-peptide (r = -0.24, P = or <0.05). EE6-9 was also associated with insulin sensitivity as measured by the hyperinsulinemic-euglycemic clamp (r = 0.27, P < 0.01). CONCLUSIONS: Higher engagement in physical activity (EE6-9) is associated with a lower BMI and visceral AT accumulation and with a healthier metabolic profile in postmenopausal women. Furthermore, the associations between EE6-9 and some metabolic parameters appear to be independent of visceral AT accumulation.

Associations between the fatty acid content of triglyceride, visceral adipose tissue accumulation, and components of the insulin resistance syndrome.

Many factors are involved in the development of the insulin resistance syndrome, such as visceral obesity and the type of dietary fat. The main purpose of this study was to investigate the relationships between fatty acid content of triglyceride (TG), visceral adipose tissue (AT) accumulation, and metabolic components of the insulin resistance syndrome in a group of 97 Caucasian men with a mean age of 45.1 +/- 7.2 years (29 to 63 years). To reach these objectives, Spearman correlations, group comparisons, and stepwise multiple regression analyses were performed. The proportion of palmitic acid (16:0) in the TG fraction was positively associated with plasma fasting insulin (r =.25, P =.03), diastolic (r =.45, P <.001), and systolic (r =.29, P =.003) blood pressure. On the other hand, the proportion of alpha-linolenic acid (18:3n-3) was associated negatively with apolipoprotein (apo) B (r = -.29, P =.005) and positively with low-density lipoprotein (LDL) diameter (r =.29, P =.007), while the proportion of gamma-linolenic acid (18:3n-6) was associated negatively with plasma TG (r = -.33, P =.003), diastolic (r = -.29, P =.01), and systolic (r = -.35, P =.002) blood pressure and plasma fasting insulin (r = -.37, P =.0005) and positively with high-density lipoprotein (HDL)(2)-cholesterol (r =.27, P =.01) and LDL diameter (r =.25, P =.02). Stepwise multiple regression analyses were conducted to determine the contribution of visceral AT, body fat mass, and the fatty acid content of TG to the variance of metabolic variables studied. It was found that visceral AT contributed significantly to the variance in plasma TG (R(2) = 20.7%, P <.0001), apo B (R(2) = 9.0%, P =.007), HDL(2)-cholesterol (R(2) = 17.9%, P <.0001), LDL diameter (R(2) = 4.9%, P =.02), and area under the glucose curve (AUC-glucose) (R(2) = 8.2%, P =.006). On the other hand, body fat mass contributed significantly to the variance in fasting insulin (R(2) = 19.7%, P <.0001) and diastolic (R(2) = 6.8%, P =.007) and systolic (R(2) = 10.5%, P =.01) blood pressure. At least one fatty acid made a significant contribution to the variance of each metabolic variable studied. In fact, the proportion of 18:3n-6 contributed significantly to the variance in both TG (R(2) = 8.9%, P = 0.007) and HDL(2)-cholesterol (R(2) = 6.0%, P =.01). Moreover, 18:3n-3 contributed to the variance of apo B (R(2) = 7.0%, P =.02), while 18:3n-6 made the largest contribution to the variance of LDL diameter (R(2) = 7.6%, P =.02). Finally, 16:0 significantly contributed to the variance of AUC-glucose (R(2) = 11.4%, P =.0003), diastolic (R(2) = 25.2%, P <.0001), and systolic (R(2) = 6.8%, P =.002) blood pressure. In summary, results of this study suggest that the fatty acid content of TG is associated with many metabolic variables of the insulin resistance syndrome independently of body fat mass or visceral AT accumulation.

Effects of intense and prolonged exercise on insulin sensitivity and glycogen metabolism in hypertensive subjects.

BACKGROUND: The information that insulin sensitivity and glycogen synthesis are reduced in hypertension arises primarily from studies using insulin infusions. Whether glycogen metabolism is actually altered in a physiological condition, such as during and after prolonged exercise, is currently unknown. METHODS AND RESULTS: To examine this issue, 9 hypertensive and 11 normotensive subjects were evaluated on a rest day and after intense and prolonged exercise on a separate day. Insulin sensitivity and hemodynamic variables were measured on both days. On the exercise day, whole-body substrate utilization was assessed and muscle biopsies were taken in the leg at baseline, immediately after exercise, and 2.5 and 4 hours after exercise. Insulin sensitivity at rest was lower in hypertensive than normotensive subjects (P<0.05) and increased after exercise in normotensive (P<0.01) but not in hypertensive (P=NS) subjects. Leg blood flow increased after exercise in both groups but to a lesser extent in hypertensive than normotensive subjects. Baseline glycogen content and maximal glycogen synthase activity were higher in hypertensive than normotensive subjects (P<0.001). Glycogen concentration decreased relatively less (-35 versus -66%) and returned to baseline levels faster in hypertensive subjects after exercise. Hypertensive subjects used approximately 40% less carbohydrates during exercise (P<0.001) at the expense of greater free fatty acid oxidation. CONCLUSIONS: It is concluded that increased intramuscular glycogen storage and resynthesis in hypertension are independent of blood flow and may represent compensatory mechanisms for the reduced insulin sensitivity and carbohydrate metabolism in this condition.

Effect of troglitazone on vascular and glucose metabolic actions of insulin in high-sucrose-fed rats.

In rats, diets high in simple sugar induce insulin resistance and alter vascular reactivity. The present study was designed to evaluate the effects of 5 weeks treatment with troglitazone on insulin sensitivity, regional hemodynamics, and vascular responses to insulin in chow-fed and high-sucrose-fed rats. Male rats were randomly divided in 4 groups to receive a regular chow diet in the absence (group 1) or presence of troglitazone (0.2% in food; group 2), or a sucrose-enriched diet in the absence (group 3) or presence of troglitazone (group 4) for 5 weeks. The rats were instrumented with Doppler flow probes and intravascular catheters to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Glucose transport activity was examined in isolated muscles. Sucrose feeding was found to induce insulin resistance and to impair the insulin-mediated skeletal muscle vasodilation. Treatment with troglitazone was found to increase whole-body insulin sensitivity in sucrose- and chow-fed rats, but had no effect on skeletal muscle glucose transport activity measured in isolated muscles from both dietary groups. Changes in regional hemodynamics were observed in both dietary cohorts treated with troglitazone, and the hindquarter vasoconstrictor response to insulin noted in sucrose-fed rats was abolished by the treatment. The vascular effects of troglitazone, and its insulin-related attenuating effects on contractile tone, could have contributed, in part, to improve insulin action on peripheral glucose disposal, presumably by improving blood flow distribution and glucose delivery.