33 resultados para Insulin Resistance


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In summary, these results imply that the relationship of adiponectin with lipoproteins is more complex than previously predicted using other methods of lipoprotein fractionation. Higher correlation of adiponectin was shown with large lipoprotein particle size, independent of the apolipoprotein content. Given the small population studied, we could not assess the influence of mild risk factors for venous thrombosis, such as obesity, on the analysis of the results. Thus, we can only state that adiponectin levels appear not to be a strong risk factor for VTE. It is possible that adiponectin deficiency may contribute indirectly to the etiology of VTE by enhancing the inflammatory state. © 2006 International Society on Thrombosis and Haemostasis.

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Aims: This study investigated the association between the basal (rest) insulin-signaling proteins, Akt, and the Akt substrate AS160, metabolic risk factors, inflammatory markers and aerobic fitness, in middle-aged women with varying numbers of metabolic risk factors for type 2 diabetes. Methods: Sixteen women (n = 16) aged 51.3+/-5.1 (mean +/-SD) years provided muscle biopsies and blood samples at rest. In addition, anthropometric characteristics and aerobic power were assessed and the number of metabolic risk factors for each participant was determined (IDF criteria). Results: The mean number of metabolic risk factors was 1.6+/-1.2. Total Akt was negatively correlated with IL-1 beta (r = -0.45, p = 0.046), IL-6 (r = -0.44, p = 0.052) and TNF-alpha (r = -0.51, p = 0.025). Phosphorylated AS160 was positively correlated with HDL (r = 0.58, p = 0.024) and aerobic fitness (r = 0.51, p = 0.047). Furthermore, a multiple regression analysis revealed that both HDL (t = 2.5, p = 0.032) and VO(2peak) (t = 2.4, p = 0.037) were better predictors for phosphorylated AS160 than TNF-alpha or IL-6 (p>0.05). Conclusions: Elevated inflammatory markers and increased metabolic risk factors may inhibit insulin-signaling protein phosphorylation in middle-aged women, thereby increasing insulin resistance under basal conditions. Furthermore, higher HDL and fitness levels are associated with an increased AS160 phosphorylation, which may in turn reduce insulin resistance.

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Reasons for performing study: Many domestic horses and ponies are sedentary and obese due to confinement to small paddocks and stables and a diet of infrequent, high-energy rations. Severe health consequences can be associated with this altered lifestyle. Objectives: The aims of this study were to investigate the ability of horses to learn to use a dynamic feeder system and determine the movement and behavioural responses of horses to the novel system. Methods: A dynamic feed station was developed to encourage horses to exercise in order to access ad libitum hay. Five pairs of horses (n = 10) were studied using a randomised crossover design with each pair studied in a control paddock containing a standard hay feeder and an experimental paddock containing the novel hay feeder. Horse movement was monitored by a global positioning system (GPS) and horses observed and their ability to learn to use the system and the behavioural responses to its use assessed. Results: With initial human intervention all horses used the novel feeder within 1 h. Some aggressive behaviour was observed between horses not well matched in dominance behaviour. The median distance walked by the horses was less (P = 0.002) during a 4 h period (117 [57–185] m) in the control paddock than in the experimental paddock (630 [509–719] m). Conclusions: The use of an automated feeding system promotes increased activity levels in horses housed in small paddocks, compared with a stationary feeder.

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The increasing prevalence of obesity in society has been associated with a number of atherogenic risk factors such as insulin resistance. Aerobic training is often recommended as a strategy to induce weight loss, with a greater impact of high-intensity levels on cardiovascular function and insulin sensitivity, and a greater impact of moderate-intensity levels on fat oxidation. Anaerobic high-intensity (supramaximal) interval training has been advocated to improve cardiovascular function, insulin sensitivity and fat oxidation. However, obese individuals tend to have a lower tolerance of high-intensity exercise due to discomfort. Furthermore, some obese individuals may compensate for the increased energy expenditure by eating more and/or becoming less active. Recently, both moderate- and high-intensity aerobic interval training have been advocated as alternative approaches. However, it is still uncertain as to which approach is more effective in terms of increasing fat oxidation given the issues with levels of fitness and motivation, and compensatory behaviours. Accordingly, the objectives of this thesis were to compare the influence of moderate- and high-intensity interval training on fat oxidation and eating behaviour in overweight/obese men. Two exercise interventions were undertaken by 10-12 overweight/obese men to compare their responses to study variables, including fat oxidation and eating behaviour during moderate- and high-intensity interval training (MIIT and HIIT). The acute training intervention was a methodological study designed to examine the validity of using exercise intensity from the graded exercise test (GXT) - which measured the intensity that elicits maximal fat oxidation (FATmax) - to prescribe interval training during 30-min MIIT. The 30-min MIIT session involved 5-min repetitions of workloads 20% below and 20% above the FATmax. The acute intervention was extended to involve HIIT in a cross-over design to compare the influence of MIIT and HIIT on eating behaviour using subjective appetite sensation and food preference through the liking and wanting test. The HIIT consisted of 15-sec interval training at 85 %VO2peak interspersed by 15-sec unloaded recovery, with a total mechanical work equal to MIIT. The medium term training intervention was a cross-over 4-week (12 sessions) MIIT and HIIT exercise training with a 6-week detraining washout period. The MIIT sessions consisted of 5-min cycling stages at ±20% of mechanical work at 45 %VO2peak, and the HIIT sessions consisted of repetitive 30-sec work at 90 %VO2peak and 30-sec interval rests, during identical exercise sessions of between 30 and 45 mins. Assessments included a constant-load test (45 %VO2peak for 45 mins) followed by 60-min recovery at baseline and the end of 4-week training, to determine fat oxidation rate. Participants’ responses to exercise were measured using blood lactate (BLa), heart rate (HR) and rating of perceived exertion (RPE) and were measured during the constant-load test and in the first intervention training session of every week during training. Eating behaviour responses were assessed by measuring subjective appetite sensations, liking and wanting and ad libitum energy intake. Results of the acute intervention showed that FATmax is a valid method to estimate VO2 and BLa, but is not valid to estimate HR and RPE in the MIIT session. While the average rate of fat oxidation during 30-min MIIT was comparable with the rate of fat oxidation at FATmax (0.16 ±0.09 and 0.14 ±0.08 g/min, respectively), fat oxidation was significantly higher at minute 25 of MIIT (P≤0.01). In addition, there was no significant difference between MIIT and HIIT in the rate of appetite sensations after exercise, but there was a tendency towards a lower rate of hunger after HIIT. Different intensities of interval exercise also did not affect explicit liking or implicit wanting. Results of the medium-term intervention indicated that current interval training levels did not affect body composition, fasting insulin and fasting glucose. Maximal aerobic capacity significantly increased (P≤0.01) (2.8 and 7.0% after MIIT and HIIT respectively) during GXT, and fat oxidation significantly increased (P≤0.01) (96 and 43% after MIIT and HIIT respectively) during the acute constant-load exercise test. RPE significantly decreased after HIIT greater than MIIT (P≤0.05), and the decrease in BLa was greater during the constant-load test after HIIT than MIIT, but this difference did not reach statistical significance (P=0.09). In addition, following constant-load exercise, exercise-induced hunger and desire to eat decreased after HIIT greater than MIIT but were not significant (p value for desire to eat was 0.07). Exercise-induced liking of high-fat sweet (HFSW) and high-fat non-sweet (HFNS) foods increased after MIIT and decreased after HIIT (p value for HFNS was 0.09). The intervention explained 12.4% of the change in fat intake (p = 0.07). This research is significant in that it confirmed two points in the acute study. While the rate of fat oxidation increased during MIIT, the average rate of fat oxidation during 30-min MIIT was comparable with the rate of fat oxidation at FATmax. In addition, manipulating the intensity of acute interval exercise did not affect appetite sensations and liking and wanting. In the medium-term intervention, constant-load exercise-induced fat oxidation significantly increased after interval training, independent of exercise intensity. In addition, desire to eat, explicit liking for HFNS and fat intake collectively confirmed that MIIT is accompanied by a greater compensation of eating behaviour than HIIT. Findings from this research will assist in developing exercise strategies to provide obese men with various training options. In addition, the finding that overweight/obese men expressed a lower RPE and decreased BLa after HIIT compared with MIIT is contrary to the view that obese individuals may not tolerate high-intensity interval training. Therefore, high-intensity interval training can be advocated among the obese adult male population. Future studies may extend this work by using a longer-term intervention.

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A small rural Aboriginal community in northern Australia was surveyed for diabetes, impaired glucose tolerance (IGT), hyperinsulinemia, and lipid levels. Of the 122 adults >17 yr of age who participated (95% response rate), 11.5% had diabetes, 7.4% had IGT, and the remaining 81.1% had normal glucose tolerance. Both diabetes and IGT were strongly age related. This high frequency of diabetes occurred, despite the population being relatively lean. Although the body mass index (BMI) increased with age in both men and women, only 25% of the population overall had BMI >25 kg/m2. There were wide ranges of insulin responses to glucose, with the upper fertile of 2-h insulin levels being more than seven times higher than the lower fertile (144 ± 13 vs. 19 ± 1 mLI/L). Hyperinsulinemia was associated with IGT, elevated triglycerides, and lower high-density lipoprotein cholesterol levels. Lipid abnormalities were much more frequent among men than women. Cholesterol levels were an average of 0.55 mM higher and triglycerides an average of 1.05 mM higher in men than in women, and both increased with age. In conclusion, this small isolated Aboriginal population from northern Australia had an unexpectedly high frequency of diabetes (in view of their relative leanness) in association with a high frequency of metabolic abnormalities indicative of insulin resistance (hyperinsulinemia, IGT, hypertriglyceridemia).

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Objectives To evaluate the feasibility, acceptability and effects of a Tai Chi and Qigong exercise programme in adults with elevated blood glucose. Design, Setting, and Participants A single group pre–post feasibility trial with 11 participants (3 male and 8 female; aged 42–65 years) with elevated blood glucose. Intervention Participants attended Tai Chi and Qigong exercise training for 1 to 1.5 h, 3 times per week for 12 weeks, and were encouraged to practise the exercises at home. Main Outcome Measures Indicators of metabolic syndrome (body mass index (BMI), waist circumference, blood pressure, fasting blood glucose, triglycerides, HDL-cholesterol); glucose control (HbA1c, fasting insulin and insulin resistance (HOMA)); health-related quality of life; stress and depressive symptoms. Results There was good adherence and high acceptability. There were significant improvements in four of the seven indicators of metabolic syndrome including BMI (mean difference −1.05, p<0.001), waist circumference (−2.80 cm, p<0.05), and systolic (−11.64 mm Hg, p<0.01) and diastolic blood pressure (−9.73 mm Hg, p<0.001), as well as in HbA1c (−0.32%, p<0.01), insulin resistance (−0.53, p<0.05), stress (−2.27, p<0.05), depressive symptoms (−3.60, p<0.05), and the SF-36 mental health summary score (5.13, p<0.05) and subscales for general health (19.00, p<0.01), mental health (10.55, p<0.01) and vitality (23.18, p<0.05). Conclusions The programme was feasible and acceptable and participants showed improvements in metabolic and psychological variables. A larger controlled trial is now needed to confirm these promising preliminary results.

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Objective: This review focuses on laminitis that develops as a result of metabolic dysfunction and aims to provide a concise assessment of the current state of knowledge on this form of the disease. Outline: The most prevalent form of laminitis is associated with metabolic or endocrinopathic diseases, such as Equine Metabolic Syndrome and pituitary pars intermedia dysfunction, and the feeding of high-energy diets, particularly those rich in non-structural carbohydrates. Insulin dysregulation is the key hormonal imbalance implicated in causing this form of laminitis and hyperinsulinaemia is an important risk factor for the disease. Hyperinsulinaemia can occur in association with insulin resistance, obesity, regionalised adiposity, dysregulated cortisol metabolism and may also be related to other factors, such as breed and genetic predisposition. Recognition of hyperinsulinaemia is best achieved by using a dynamic oral glucose test that can be performed relatively easily under field conditions. Insulin produces a unique pathological lesion in the lamellae and the features of this lesion have informed investigations on the pathogenesis of the disease. Research into the mechanism of disease is continuing so that more targeted therapies than are currently available can be developed. However, dietary restriction and exercise remain effective management strategies for metabolic disease. Conclusions: Although the pathogenic mechanism/s of metabolic and endocrinopathic forms of laminitis remain the subject of intense research, ample data on risk factors for the disease are available. Efforts focussed on preventing the disease should aim to identify metabolic disease and reduce obesity and insulin resistance in at-risk individuals.

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The aim of this study was to use lipidomics to determine if the lipid composition of apolipoprotein-B-containing lipoproteins is modified by dyslipidaemia in type 2 diabetes and if any of the identified changes potentially have biological relevance in the pathophysiology of type 2 diabetes. VLDL and LDL from normolipidaemic and dyslipidaemic type 2 diabetic women and controls were isolated and quantified with HPLC and mass spectrometry. A detailed molecular characterisation of VLDL triacylglycerols (TAG) was also performed using the novel ozone-induced dissociation method, which allowed us to distinguish vaccenic acid (C18:1 n-7) from oleic acid (C18:1 n-9) in specific TAG species. Lipid class composition was very similar in VLDL and LDL from normolipidaemic type 2 diabetic and control participants. By contrast, dyslipidaemia was associated with significant changes in both lipid classes (e.g. increased diacylglycerols) and lipid species (e.g. increased C16:1 and C20:3 in phosphatidylcholine and cholesteryl ester and increased C16:0 [palmitic acid] and vaccenic acid in TAG). Levels of palmitic acid in VLDL and LDL TAG correlated with insulin resistance, and VLDL TAG enriched in palmitic acid promoted increased secretion of proinflammatory mediators from human smooth muscle cells. We showed that dyslipidaemia is associated with major changes in both lipid class and lipid species composition in VLDL and LDL from women with type 2 diabetes. In addition, we identified specific molecular lipid species that both correlate with clinical variables and are proinflammatory. Our study thus shows the potential of advanced lipidomic methods to further understand the pathophysiology of type 2 diabetes.

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Objective To explore the feasibility of conducting a 10-week home-based physical activity (PA) programme and evaluate the changes in insulin sensitivity (S I) commensurate with the programme in obese young people. Design Open-labelled intervention. Setting Home-based intervention with clinical assessments at a tertiary paediatric hospital. Subjects 18 obese (body mass index (BMI)>International Obesity Task Force age and sex-specifi c cut-offs) children and adolescents (8-18 years, 11 girls/7 boys) were recruited. 15 participants (nine girls/six boys, mean±SE age 11.8±0.6 years, BMI-SD scores (BMI-SDS) 3.5±0.1, six prepubertal/nine pubertal) completed the intervention. Intervention The programme comprised biweekly home visits over 10 weeks with personalised plans implemented aiming to increase moderate-intensity PA. Pedometers and PA diaries were used as self-monitoring tools. The goals were to (1) teach participants behavioural skills related to adopting and maintaining an active lifestyle and (2) increase daily participation in PA. Outcome measures Mean steps/day were assessed. SI assessed by the frequently sampled intravenous glucose tolerance test and other components of the insulin resistance syndrome were measured. Results Mean steps/day increased significantly from 10 363±927 (baseline) to 13 013±1131 (week 10) (p<0.05). S I was also significantly increased, despite no change in BMI-SDS, and remained so after an additional 10-week follow-up. Conclusions The results suggest that such a homebased PA programme is feasible. S I improved without changes in BMI-SDS. More rigorous evaluations of such programmes are warranted.

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Toll-like receptors (TLR) are key regulators of innate immune and inflammatory responses and their activation is linked to impaired glucose metabolism during metabolic disease. Determination of whether TLR4 signaling can be activated in the heart by insulin may shed light on the pathogenesis of diabetic cardiomyopathy, a process that is often complicated by obesity and insulin resistance. The aim of the current study was to determine if supraphysiological insulin concentrations alter the expression of TLR4, markers of TLR4 signaling and glucose transporters (GLUTs) in the heart. Firstly, the effect of insulin on TLR4 protein expression was investigated in vitro in isolated rat cardiac myocytes. Secondly, protein expression of TLR4, the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) suppressor of cytokine signaling 3 (SOCS3) and GLUTs (1, 4, 8, 12) were examined in the equine ventricular myocardium following a prolonged, euglycemic, hyperinsulinemic clamp. Down-regulation of TLR4 protein content in rat cardiac myocytes was observed after incubation with a supraphysiologic concentration of insulin as well as in the equine myocardium after prolonged insulin infusion. Further, cardiac TLR4 expression was negatively correlated with serum insulin concentration. Markers of cardiac TLR4 signaling and GLUT expression were not affected by hyperinsulinemia and concomitant TLR4 down-regulation. Since TLRs are major determinants of the inflammatory response, our findings suggest that insulin infusion exerts an anti-inflammatory effect in the hearts of non-obese individuals. Understanding the regulation of cardiac TLR4 signaling during metabolic dysfunction will facilitate improved management of cardiac sequela to metabolic syndrome and diabetes.

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REASONS FOR PERFORMING STUDY An increased incidence of metabolic disease in horses has led to heightened recognition of the pathological consequences of insulin resistance (IR). Laminitis, failure of the weight-bearing digital lamellae, is an important consequence. Altered trafficking of specialised glucose transporters (GLUTs) responsible for glucose uptake, are central to the dysregulation of glucose metabolism and may play a role in laminitis pathophysiology. OBJECTIVES We hypothesised that prolonged hyperinsulinaemia alters the regulation of glucose transport in insulin-sensitive tissue and digital lamellae. Our objectives were to compare the relative protein expression of major GLUT isoforms in striated muscle and digital lamellae in healthy horses and during hyperinsulinaemia. STUDY DESIGN Randomised, controlled study. METHODS Prolonged hyperinsulinaemia and lamellar damage were induced by a prolonged-euglycaemic hyperinsulinaemic clamp (p-EHC) or a prolonged-glucose infusion (p-GI) and results were compared to electrolyte-treated controls. GLUT protein expression was examined with immunoblotting. RESULTS Lamellar tissue contained more GLUT1 protein than skeletal muscle (p = 0.002) and less GLUT4 than the heart (p = 0.037). During marked hyperinsulinaemia and acute laminitis (induced by the p-EHC), GLUT1 protein expression was decreased in skeletal muscle (p = 0.029) but unchanged in the lamellae, while novel GLUTs (8; 12) were increased in the lamellae (p = 0.03), but not skeletal muscle. However, moderate hyperinsulinaemia and subclinical laminitis (induced by the p-GI) did not cause differential GLUT protein expression in the lamellae vs. control horses. CONCLUSIONS The results suggest that lamellar tissue functions independently of insulin and that IR may not be an essential component of laminitis aetiology. Marked differences in GLUT expression exist between insulin-sensitive and insulin-independent tissues during metabolic dysfunction in horses. The different expression profiles of novel GLUTs during acute and subclinical laminitis may be important to disease pathophysiology and require further investigation.

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OBJECTIVE The effects of free fatty acids (FFA), leptin, tumour necrosis factor (TNF) alpha and body fat distribution on in vivo oxidation of a glucose load were studied in two South African ethnic groups. DESIGN AND MEASUREMENTS Anthropometric and various metabolic indices were measured at fasting and during a 7h oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis and subcutaneous and visceral fat mass was assessed using a five- and two-level CT-scan respectively. Glucose oxidation was evaluated by measuring the ratio of (13)CO(2) to (12)CO(2) in breath following ingestion of 1-(13)C-labelled glucose. SUBJECTS Ten lean black women (LBW), ten obese black women (OBW), nine lean white women (LWW) and nine obese white women (OWW) were investigated after an overnight fast. RESULTS Visceral fat levels were significantly higher (P < 0.01) in obese white than black women, despite similar body mass indexes (BMIs). There were no ethnic differences in glucose oxidation however; in the lean subjects of both ethnic groups the area under the curve (AUC) was higher than in obese subjects (P < 0.05 for both) and was found to correlate negatively with weight (r = -0.69, P < 0.01) after correcting for age. Basal TNF alpha concentrations were similar in all groups. Percentage suppression of FFAs at 30 min of the OCTT was 24 +/- 12% in OWW and - 38 +/- 23% (P < 0.05) in OBW, ie the 30 min FFA level was higher than the fasting level in the latter group. AUC for FFAs during the late postprandial period (120 - 420 min) was significantly higher in OWW than OBW (P < 0.01) and LWW (P < 0.01) and correlated positively with visceral fat mass independent of age (r = 0.78, P < 0.05) in the OWW only. Leptin levels were higher (P < 0.01) both at fasting and during the course of the OCTT in obese women from both ethnic groups compared to the lean women. CONCLUSIONS Glucose oxidation is reduced in obese subjects of both ethnic groups; inter- and intra-ethnic differences were observed in visceral fat mass and FFA production and it is possible that such differences may play a role in the differing prevalences of obesity-related disorders that have been reported in these two populations.

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There is a higher prevalence of ischemic heart disease (IHD) in South African white than black women. The objective of this study was to determine biochemical explanations for this prevalence. The study group contained 15 obese black women (OBW) and 14 obese white women (OWW), ah premenopausal, who were examined after an overnight fast. Anthropometric measurements and blood concentrations of glucose, non-esterified fatty acids (NEFAs), catecholamines, plasminogen activator inhibitor-1, C-peptide, proinsulin, lipograms, cortisol, growth hormone, and post-heparin Lipoprotein Lipase activity were measured during an oral glucose tolerance test (OGTT), Body composition was measured using bioelectrical impedance analysis, and subcutaneous and visceral fat mass were assessed with CT-scans. Visceral fat area was higher in OWW (139.7 +/- 10.7 cm(2)) than in OBW (72.3 +/- 3.9 cm(2)) (P < 0.01), as were fasting and 3 h triglyceride concentrations (P < 0.05 for all). OWW also had higher NEFA levels than OBW at 3 and 4 h compared, with OBW (P < 0.05 for both). Fasting cortisol (266 +/- 24 vs. 197 +/- 19 nmol/l; P < 0.05) was higher in OWW than in OBW. These data demonstrate that OWW have higher visceral fat mass than OBW, which may lead to a more atherogenic fasting and postprandial Lipid profile. The higher cortisol levels of the OWW may promote visceral fat deposition. - Punyadeera, C., M-T. van der Merwe, N.J. Crowther, M. Toman, C. P. Schlaphoff, and I. P. Gray. Ethnic differences in lipid metabolism in two groups of obese South African women.

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Objective Lower lipid and insulin levels are found during a glucose-tolerance test in obese black than obese white South African women. Therefore, β-cell function and lipid metabolism were compared in these populations during a mixed meal. Research Methods and Procedures Blood concentrations of glucose, free fatty acids (FFAs), insulin, lipograms, and in vivo FFA oxidation were determined at fasting and for 7 hours after oral administration of a mixed emulsion containing glucose-casein-sucrose-lipid and [1-13C] palmitic acid in 8 lean black women (LBW), 10 obese black women (OBW), 9 lean white women (LWW), and 10 obese white women (OWW). Subcutaneous and visceral fat mass was assessed by computerized tomography. Results Visceral fat area was higher in OWW (152.7 ± 17.0 cm2) than OBW (80.0 ± 6.7 cm2; p < 0.01). In OBW, 30-minute insulin levels were higher (604.3 ± 117.6 pM) than OWW (311.0 ± 42.9 pM; p < 0.05). Total triglyceride was higher in OWW (706.7 ± 96.0 mM × 7 hours) than OBW (465.7 ± 48.2 mM × 7 hours; p < 0.05) and correlated with visceral fat area (β = 0.38, p = 0.05). Palmitate oxidation was higher in lean than obese women in both ethnic groups and correlated negatively with fat mass (β = −0.58, p < 0.005). Discussion The higher 30-minute insulin response in OBW may reflect a higher insulinotropic effect of FFAs or glucose. The elevated triglyceride level of OWW may be due to their higher visceral fat mass and possibly reduced clearance by adipose tissue.