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This study aimed to evaluate the effect of pioglitazone on brown adipose tissue function and hypothalamic gliosis in humans. Brown adipose tissue and the hypothalamus are regarded as important potential pharmacological targets to metabolic diseases, and defining the impact of current therapies on their structure and/or function could provide therapeutic advance in this field. Six patients with type 2 diabetes were treated for 24 weeks with pioglitazone 30 mg/day as an add-on therapy. Brown adipose tissue glucose uptake and volume were determined using 18F-FDG PET/CT scans; hypothalamic gliosis was determined using MRI scans; blood was collected for hormone and biochemistry measurements. All tests were performed at inclusion and six months after pioglitazone introduction. Pioglitazone treatment led to a significant 3% body mass increase. There were neither changes in cold-induced brown adipose tissue glucose uptake and volume nor changes in hypothalamic gliosis. This is a proof-of-concept study that provides clinical evidence for a lack of action of a thiazolidinedione, pioglitazone, to promote homogeneous and measurable changes in brown adipose tissue volume and also in hypothalamic gliosis after 6 months of treatment.

Background The brown adipose tissue (BAT) is a potential target for the treatment of obesity and metabolic disorders. Its activation by cold exposure or adrenergic drugs can increase systemic insulin sensitivity and improve lipid metabolism; however, little is known about the effects of specific dietary components on BAT activity. Objectives We asked if a short-term (4 weeks) dietary intervention with olive oil could modify BAT activity in lean and overweight/obese volunteers. Design This was a 4-week open clinical trial in which all participants underwent a dietary intervention with extra-virgin olive oil supplementation. As the initial intake of olive oil was controlled all the participants were controls of themselves. Results The intervention resulted in significant increase in blood monounsaturated fatty acid levels, which was accompanied by increased BAT activity in lean but not in overweight/obese volunteers. In the lean group, an increase in leptin was detected after the intervention, and low leptin values at the beginning of the study were predictive of greater BAT activity after intervention. In addition, increase in leptin concentration was associated with increased BAT activity. Three known endogenous mediators of BAT activity, secretin, fibroblast growth factor 21 (FGF21), and 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) were increased by intervention in lean, whereas only secretin and FGF21 were increased in subjects with excessive weight. Conclusion This study provides clinical evidence for the impact of monounsaturated fatty acids on BAT activity and an advance in the understanding of the beneficial health effects of olive oil.

Inflammation plays a key role in the development of insulin resistance and atherosclerosis. Fatty acids and fiber intake can selectively alter gene expression by modifying inflammation. We compared the postprandial expression of inflammatory genes after 2 distinct high-fat breakfast meals, before and after 1-month dietary interventions. This crossover clinical trial included 18 individuals at low-to-moderate cardiometabolic risk participating in evaluations before and after two 4-week breakfast interventions—one rich in saturated fatty acids (SFA) and the other in unsaturated fatty acids (unSFA) and fiber. Participants underwent meal tests with similar compositions to the breakfasts. Variables were compared by Student t test. The expression of inflammatory genes in leukocytes was analyzed using RT-PCR. Before and after the intervention with the SFA-enriched breakfast, this meal test induced a higher relative postprandial IL-1β expression compared to the responses to the unSFA and fiber-enriched meal (p = 0.02). On the other hand, following the intervention with the unSFA-fiber-enriched breakfast, postprandial IL-6 expression showed a reduction tendency comparing to the pre-intervention value (p = 0.08). Although fasting IL-1β, IL-6, MCP-1 and IFN-γ expressions had not changed after interventions, their circulating levels increased after the SFA-enriched meal test but not after the unSFA meal (p value between changes

Objectives Western dietary pattern predisposes to weight gain, insulin resistance and cardiometabolic diseases. Promoting satiety via modifications in diet composition could be useful to fight weight gain. Mediterranean diet which is recognized to be cardioprotective contains high fiber and unsaturated fat contents. We compared the effects of distinct breakfast patterns on satiety of individuals at cardiometabolic risk, and examined the correlation of satiety level after each breakfast intervention period with glucose parameters. Materials and methods In this 10-week cross-over clinical trial, 54 individuals with weight excess were submitted to 2 types of 4-week isocaloric breakfasts (2-week washout), one typically Brazilian and a modified one, differing concerning fiber and types of fatty acids contents. Clinical data were collected before and after each breakfast. A satiety scale was applied at fasting and 10, 30 and 120’ after breakfast consumption. Repeated measures ANOVA, Student t test or non-parametric correspondents were used; correlations were tested by Pearson or Spearman coefficients. Results Anthropometric variations after breakfasts were not significant. Only after the modified breakfast, reduction in blood pressure levels was observed. The satiety level did not show significant variation across each period or between the breakfasts. Non-significant correlation between satiety and glucose, insulin and HOMA-IR values after each intervention period was observed. Conclusion We conclude that different breakfast compositions do not alter satiety level, which is not correlated to glucose parameters in overweight individuals. Stronger modifications of daily meals might be necessary to differentiate satiety levels under distinct dietary patterns.

Objectives Associations of leisure-time physical activity (LTPA), commuting and total physical activity with inflammatory markers, insulin resistance and metabolic profile in individuals at high cardiometabolic risk were investigated. Design This was a cross-sectional study. Methods A total of 193 prediabetic adults were compared according to physical activity levels measured by the international physical activity questionnaire; p for trend and logistic regression was employed. Results The most active subset showed lower BMI and abdominal circumference, reaching significance only for LTPA (p for trend = 0.02). Lipid profile improved with increased physical activity levels. Interleukin-6 decreased with increased total physical activity and LTPA (p for trend = 0.02 and 0.03, respectively), while adiponectin increased in more active subsets for LTPA (p for trend = 0.03). Elevation in adjusted OR for hypercholesterolemia was significant for lower LTPA durations (p for trend = 0.04). High apolipoprotein B/apolipoprotein A ratio was inversely associated with LTPA, commuting and total physical activity. Increase in adjusted OR for insulin resistance was found from the highest to the lowest category of LTPA (p for trend = 0.04) but significance disappeared after adjustments for BMI and energy intake. No association of increased C-reactive protein with physical activity domains was observed. Conclusions In general, the associations of LTPA, but not commuting or total physical activity, with markers of cardiometabolic risk reinforces the importance of initiatives to increase this domain in programs for the prevention of lifestyle-related diseases.

OBJETIVO: Este estudo comparou parâmetros antropométricos e de resistência à insulina de indivíduos sem e com síndrome metabólica (SM), subestratificados pela presença de anormalidades glicêmicas. SUJEITOS E MÉTODOS: Foram incluídos 454 indivíduos (66% mulheres, 54% brancos), sendo 155 alocados para o grupo 1 (sem SM, sem anormalidade glicêmica), 32 para o grupo 2 (sem SM, com anormalidade glicêmica), 104 no grupo 3 (com SM, sem anormalidade glicêmica) e 163 no grupo 4 (com SM e anormalidade glicêmica). Os grupos foram comparados por ANOVA. RESULTADOS: Os grupos com SM (3 e 4) apresentaram os piores perfis antropométrico e lipídico; no grupo 2, apesar de glicemias significantemente mais elevadas, as médias das variáveis antropométricas e lipídicas não diferiram do grupo 1. Os maiores valores médios de HOMA-IR foram encontrados nos grupos com SM, enquanto o grupo 2 apresentou o menor HOMA-β. A trigliceridemia foi a variável metabólica com coeficientes de correlação mais elevados com a antropometria. Porém, as correlações mais fortes foram da circunferência da cintura (r = 0,503) e da razão cintura-altura (r = 0,513) com o HOMA-IR (p < 0,01). CONCLUSÃO: Nossos achados revelam que, em amostra da população brasileira, qualquer das medidas antropométricas identifica indivíduos com SM, mas não parece capaz de diferenciar aqueles com distúrbio glicêmico. Reforçamos a relação mais forte das medidas de adiposidade central com resistência à insulina, sugerindo utilidade da razão cintura-altura. É possível que componente autoimune contribua para o comprometimento do metabolismo glicídico dos indivíduos do grupo 2.

Objective This study aimed to compare the effects of two lifestyle intervention programs for type 2 diabetes mellitus (T2DM) prevention – traditional or interdisciplinary psychoeducation-based intervention – in daily habits and cardiometabolic risk factors and investigate the role of the psychoeducational approach for the retention of individuals in the program. Subjects and methods Between 2008 and 2010, in a public health service, 183 pre-diabetic individuals were allocated to two 18-month interventions involving diet and physical activity. Physical activity, diet, quality of life (QOL) and depression and biochemical measurements were obtained. Linear mixed-effect models were used to assess the effect of the interventions. A student t test was used to compare dropouts versus non-dropouts. Results Improvements in energy intake and physical activity were greater in the interdisciplinary than the traditional intervention. A decrease in fat mass and blood pressure was more pronounced with interdisciplinary intervention. Dropouts from the traditional intervention only had higher BMI and lower fiber intake and QOL than non-dropouts. Conclusion The interdisciplinary psychoeducation-based intervention revealed useful for reducing cardiometabolic risk and retaining individuals with worse health profiles. This approach represents a feasible strategy for motivating high-risk individuals to adopt a long-term healthy lifestyle.

We investigated whether diet quality was associated with leisure-time physical activity (LTPA) and television viewing and the associations of these variables with traditional cardiovascular risk factors and novel biomarkers in individuals at cardiometabolic risk.A total of 193 prediabetic adults (63.7% women, mean age 54.1 years), screened for a diabetes prevention program in Brazil, participated in this cross-sectional study. Clinical data and blood samples were collected for several determinations. Twenty-four-hour recalls were used to calculate the Healthy Eating Index (HEI) adapted to Brazilian dietary habits and the International Physical Activity Questionnaire to assess physical activity level. Analysis of covariance with adjustments for age and body mass index (BMI) was employed to test associations across categories of LTPA and television viewing.Stratifying according to LTPA categories, the most active subset (≥150 minutes/week) showed better HEI scores after adjustments (64.6 ± 11.0, 65.1 ± 10.3, and 68.6 ± 10.8, p = 0.02) and significant higher values of dark green and orange vegetables but not of whole grains (p = 0.06). Active individuals had lower BMI, waist circumference, inflammatory markers, and better insulin sensitivity (p0.05). Individuals at the highest category of television viewing had higher age-adjusted BMI (32.0 ± 6.2, 30.7 ± 6.0, and 28.8 ± 4.7 hours/week; p = 0.01) than the others. Time watching television was inversely associated with homeostasis model assessment (HOMA-IR) and C-reactive protein (CRP; p0.01) after adjustments but not with lipids and HEI score. Comparisons of individuals with healthy habits (better diet and higher physical activity [PA]), with those with unhealthy habits revealing better anthropometric and cardiometabolic profiles in the former group.Diet quality assessed by the HEI adapted for Brazilian eating habits attained significance in differentiating more active from inactive at-risk individuals during leisure time. Time watching television, as a surrogate of sedentary behavior, is not useful to detect unhealthy diet quality. LTPA is indicative of better cardiometabolic profile reflected by lipid and inflammatory markers and index of insulin resistance.

Background Dietary guidelines of 5 servings per day of fruits and vegetables (FV) offer a reasonable amount of vitamins to control organic processes, which may contribute to a favorable cardiometabolic profile. This study aimed at investigating whether the intake of the FV group as well as pro-vitamin A carotenoids and vitamins C and E were associated with circulating markers of oxidative stress, inflammation and insulin resistance in Brazilians individuals at cardiometabolic risk. Methods This cross-sectional study included 205 individuals screened for diabetes prevention program in a healthcare center from the School of Public Health, University of São Paulo, conducted in 2008. Possible associations of consumption of FV group, as well as pro-vitamin A carotenoids and vitamins C and E, with circulating markers of oxidative stress (superoxide dismutase – SOD and oxidized LDL – oxLDL), inflammation (C reactive protein, TNF-α and adiponectin) and insulin resistance (HOMA-IR) were investigated. Pearson correlation coefficient, ANOVA and multiple linear regression were employed. Results The sample (64.7% women) had a mean age of 54.1 ± 12.7 years and body mass index of 30.7 ± 5.7 kg/m2. Dietary, physical activity, anthropometric and laboratory data were obtained. Participants consumed a mean of 3.8 servings/day of FV; their FV intake was categorized into three groups: 5.0 servings/day. Significant trends for lower waist circumference (103.4 ± 13.6 vs. 100.1 ± 12.2 vs. 98.2 ± 12.7 cm, p-trend

Background/objectives Cardioprotective effects of Mediterranean-style diet have been shown. Instead of excluding foods, replacement or addition may facilitate compliance with impact on glucose metabolism of individuals at cardiometabolic risk. This study investigated the effect of changing selected nutrients intake on glucose metabolism during a lifestyle intervention tailored to living conditions of prediabetic Brazilians. Subjects/methods 183 prediabetic adults treated under the Brazilian public health system underwent an 18-month intervention on diet and physical activity. Dietary counseling focused on reducing saturated fat replaced by unsaturated fatty acids. Data were collected at baseline and after follow-up. ANOVA and multiple linear regression were used to test association of changes in nutrients intake with changes in plasma glucose. Results Changes in fasting and 2-h plasma glucose but not in weight, HOMA-IR or C-reactive protein decreased after intervention across tertiles of MUFA changes (p-trend 0.017 and 0.024, respectively). Regression models showed that increase in MUFA intake was independently associated with reduction in fasting (β -1.475, p = 0.008) and 2-h plasma glucose (β -3.321, p = 0.007). Moreover, increase in soluble fibers intake was associated with decrease in fasting plasma glucose (β -1.579, p = 0.038). Adjustment for anthropometric measurements did not change the results but did after including change in insulin in the models. Conclusions Increases of MUFA and soluble fibers intakes promote benefits on glucose metabolism, independently of adiposity, during a realistic lifestyle intervention in at-risk individuals. Mechanisms mediating these processes may include mainly insulin sensitivity improvement.