Interaction of PPARG Pro12Ala with dietary fat influences plasma lipids in subjects at cardiometabolic risk

The PPARγ2 gene SNP Pro12Ala has shown variable association with metabolic syndrome traits in healthy subjects. We investigated the effect of interaction between genotype and the ratio of polyunsaturated:saturated (P:S) fatty acid intake on plasma lipids in 367 White subjects aged 30-70 y at increased cardiometabolic risk, in the RISCK study. Interaction was determined after habitual diet at recruitment, at baseline after a 4-week high-SFA (HS) diet and after 24-week reference (HS), high-MUFA (HM) and low-fat (LF) diets. At recruitment, there were no significant associations between genotype and plasma lipids, however, P:S x genotype interaction influenced plasma total cholesterol (TC) (P=0.02), LDL-cholesterol (LDL-C) (P=0.002) and triglyceride (TG) (P=0.02) concentrations. At P:S ratio ≤0.33, mean TC and LDL-C concentrations in Ala12 allele carriers were significantly higher than in non-carriers (respectively P=0.003; P=0.0001). Significant trends in reduction of plasma TC (P=0.02) and TG (P=0.002) concentrations occurred with increasing P:S (respectively ≤0.33 to >0.65 and 0.34 to >0.65) in Ala12 allele carriers. There were no significant differences between carriers and non-carriers after the 4-week HS diet or 24-week interventions. Plasma TC and TG concentrations in PPARG Ala12 allele carriers decrease as P:S increases, but are not dependent on a reduction in SFA intake.

Obesity and body fat classification in the metabolic syndrome: impact on cardiometabolic risk metabotype

Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by body mass index (BMI) and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study). Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules and haemostatic factors were determined at baseline and after 12 weeks of 4 dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA) and 2 low fat high complex carbohydrate (LFHCC) diets, 1 supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs)). 39% and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (± 30 kg/m2) and BF% (± 25% (men) and ± 35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as non-obese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more pro-inflammatory (higher C reactive protein (CRP) and leptin), pro-thrombotic (higher plasminogen activator inhibitor-1 (PAI-1)), pro-atherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA-IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumour necrosis factor alpha (TNF-α) concentrations were lower post-intervention in NOO individuals compared to OO subjects (P < 0.001). In conclusion, assessing BF% and BMI as part of a metabotype may help identify individuals at greater cardiometabolic risk than BMI alone.

Role of dietary fats in modulating cardiometabolic risk during moderate weight gain : a randomized double-blind overfeeding trial (LIPOGAIN study)

BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study. METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001). CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA. CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.

A comparison of subjective and objective measures of physical activity and fitness in identifying associations with cardiometabolic risk factors

Purpose
To compare the ability of alternative measures of physical activity and fitness to quantify associations with health outcomes.

Methods
Associations between a range of subjective and objective physical activity and fitness measures and cardiometabolic risk factors were examined using data from 1,631 Australians aged 26–36 years. Anthropometry, fitness, blood pressure, and fasting blood glucose, insulin, and lipids were measured at study clinics. Participants completed the International Physical Activity Questionnaire (IPAQ) and 7-day pedometer diaries; they also reported sedentary behavior (sitting, television viewing).

Results
In men and women, associations were strongest for fitness, with those in the highest (vs. lowest) fitness quarter having a 75% to 80% lower prevalence of two or more primary risk factors (waist circumference, high-density lipoprotein cholesterol, and insulin resistance). In men, a 60% to 70% reduced prevalence of two or more risk factors was observed across extreme quarters of IPAQ leisure, IPAQ vigorous, sitting duration, and pedometer measures. Similar reductions in prevalence were observed only across extreme quarters of pedometer activity and television viewing in women.

Conclusions
Associations between alternative measures and cardiometabolic risk were relatively independent, suggesting that a range of physical activity and fitness measures may be needed to most accurately quantify associations between physical activity and health.

Deleterious associations of sitting time and television viewing time with cardiometabolic risk biomarkers

We examined the associations of sitting time and television (TV) viewing time with continuously measured biomarkers of cardio-metabolic risk in Australian adults. Waist circumference, BMI, resting blood pressure, triglycerides, HDL cholesterol, fasting and 2-h postload plasma glucose, and fasting insulin were measured in 2,761 women and 2,103 men aged ≥30 years (mean age 54 years) without clinically diagnosed diabetes from the 2004-2005 Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Multivariate linear regression analyses examined associations of self-reported sitting time and TV viewing time (hours per day) with these biomarkers, adjusting for potential confounding variables. For both women and men, sitting time was detrimentally associated with waist circumference, BMI, systolic blood pressure, fasting triglycerides, HDL cholesterol, 2-h postload plasma glucose, and fasting insulin (all P < 0.05), but not with fasting plasma glucose and diastolic blood pressure (men only). With the exception of HDL cholesterol and systolic blood pressure in women, the associations remained significant after further adjustment for waist circumference. TV viewing time was detrimentally associated with all metabolic measures in women and all except HDL cholesterol and blood pressure in men. Only fasting insulin and glucose (men only) remained deleteriously associated with TV viewing time after adjustment for waist circumference. In women and men, sitting time and TV viewing time were deleteriously associated with cardio-metabolic risk biomarkers, with sitting time having more consistent associations in both sexes and being independent of central adiposity. Preventive initiatives aimed at reducing sitting time should focus on both nonleisure and leisure-time domains.

Skipping breakfast : longitudinal associations with cardiometabolic risk factors in the childhood determinants of adult health study

Background: The long-term effects of skipping breakfast on cardiometabolic health are not well understood.

Objective: The objective was to examine longitudinal associations of breakfast skipping in childhood and adulthood with cardiometabolic risk factors in adulthood.

Design: In 1985, a national sample of 9–15-y-old Australian children reported whether they usually ate breakfast before school. During follow-up in 2004–2006, 2184 participants (26–36 y of age) completed a meal-frequency chart for the previous day. Skipping breakfast was defined as not eating between 0600 and 0900. Participants were classified into 4 groups: skipped breakfast in neither childhood nor adulthood (n = 1359), skipped breakfast only in childhood (n = 224), skipped breakfast only in adulthood (n = 515), and skipped breakfast in both childhood and adulthood (n = 86). Diet quality was assessed, waist circumference was measured, and blood samples were taken after a 12-h fast (n = 1730). Differences in mean waist circumference and blood glucose, insulin, and lipid concentrations were calculated by linear regression.

Results: After adjustment for age, sex, and sociodemographic and lifestyle factors, participants who skipped breakfast in both childhood and adulthood had a larger waist circumference (mean difference: 4.63 cm; 95% CI: 1.72, 7.53 cm) and higher fasting insulin (mean difference: 2.02 mU/L; 95% CI: 0.75, 3.29 mU/L), total cholesterol (mean difference: 0.40 mmol/L; 95% CI: 0.13, 0.68 mmol/L), and LDL cholesterol (mean difference: 0.40 mmol/L; 95% CI: 0.16, 0.64 mmol/L) concentrations than did those who ate breakfast at both time points. Additional adjustments for diet quality and waist circumference attenuated the associations with cardiometabolic variables, but the differences remained significant.

Conclusions: Skipping breakfast over a long period may have detrimental effects on cardiometabolic health. Promoting the benefits of eating breakfast could be a simple and important public health message.

Increased cardiometabolic risk is associated with increased TV viewing time

Purpose: Television viewing time, independent of leisure time physical activity, has cross-sectional relationships with the metabolic syndrome and its individual components. We examined whether baseline and 5-yr changes in self-reported television viewing time are associated with changes in continuous biomarkers of cardiometabolic risk (waist circumference, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure, fasting plasma glucose, and a clustered cardiometabolic risk score) in Australian adults.


Methods: The Australian Diabetes, Obesity and Lifestyle Study (AusDiab) is a prospective, population-based cohort study with biological, behavioral, and demographic measures collected in 1999-2000 and 2004-2005. Noninstitutionalized adults aged >=25 yr were measured at baseline (11,247; 55% of those completing an initial household interview); 6400 took part in the 5-yr follow-up biomedical examination, and 3846 met the inclusion criteria for this analysis. Multiple linear regression analysis was used, and unstandardized B coefficients (95% confidence intervals (CI)) are provided.


Results: Baseline television viewing time (10 h·wk-1 unit) was not significantly associated with change in any of the biomarkers of cardiometabolic risk. Increases in television viewing time over 5 yr (10 h·wk-1 unit) were associated with increases in waist circumference (men: 0.43 cm, 95% CI = 0.08-0.78 cm, P = 0.02; women: 0.68 cm, 95% CI = 0.30-1.05, P < 0.001), diastolic blood pressure (women: 0.47 mm Hg, 95% CI = 0.02-0.92 mm Hg, P = 0.04), and the clustered cardiometabolic risk score (women: 0.03, 95% CI = 0.01-0.05, P = 0.007). These associations were independent of baseline television viewing time and baseline and change in physical activity and other potential confounders.


Conclusions: These findings indicate that an increase in television viewing time is associated with adverse cardiometabolic biomarker changes. Further prospective studies using objective measures of several sedentary behaviors are required to confirm causality of the associations found.

Daily eating frequency and cardiometabolic risk factors in young Australian adults : cross-sectional analyses

Eating frequency may be important in the development of overweight and obesity and other cardiometabolic risk factors; however, the evidence is inconsistent. The aim of the present study was to examine the associations between the number of eating occasions and cardiometabolic risk factors in a national population-based sample of young adults. A cohort of 1273 men and 1502 women, aged 26–36 years, completed a meal pattern chart to record when they had eaten during the previous day (in hourly intervals). The total number of eating occasions was calculated. Diet quality was assessed, waist circumference was measured and a fasting blood sample was taken. Dietary intake was compared with the Australian Guide to Healthy Eating. The associations between the number of eating occasions and cardiometabolic risk factors were calculated using linear regression. Analyses were adjusted for age, education and physical activity. Most men ate three to five times per d and most women ate four to six times. The proportion of participants meeting dietary recommendations increased with the number of eating occasions. For men, an additional eating occasion was associated with reductions in mean values for waist circumference ( − 0·75 cm), fasting glucose ( − 0·02 mmol/l), fasting insulin ( − 0·34 mU/l; 2·04 pmol/l), TAG ( − 0·03 mmol/l), total cholesterol ( − 0·08 mmol/l) and LDL-cholesterol ( − 0·06 mmol/l). Adjustment for waist circumference attenuated the results. Significant trends were not observed for women. In conclusion, a higher number of eating occasions were associated with reduced cardiometabolic risk factors in men. Many associations were mediated by waist circumference.

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized c

While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss.

Associations of the TNF-alpha-308 G/A, IL6-174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Background: Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention. Methods: This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-alpha -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype. Results: In the entire sample (66.7% women; mean age 56.5 +/- 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-alpha -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL-6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention. Conclusion: The TNF alpha -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.

Cardiometabolic risk reduction through lifestyle intervention programs in the Brazilian public health system

Public health strategies to reduce cardiovascular morbidity and mortality should focus on global cardiometabolic risk reduction. The efficacy of lifestyle changes to prevent type 2 diabetes have been demonstrated, but low-cost interventions to reduce cardiometabolic risk in Latin-America have been rarely reported. Our group developed 2 programs to promote health of high-risk individuals attending a primary care center in Brazil. This study compared the effects of two 9-month lifestyle interventions, one based on medical consultations (traditional) and another with 13 multi-professional group sessions in addition to the medical consultations (intensive) on cardiometabolic parameters. Adults were eligible if they had pre-diabetes (according to the American Diabetes Association) and/or metabolic syndrome (International Diabetes Federation criteria for Latin-America). Data were expressed as means and standard deviations or percentages and compared between groups or testing visits. A p-value < 0.05 was considered significant. Results: 180 individuals agreed to participate (35.0% men, mean age 54.7 ± 12.3 years, 86.1% overweight or obese). 83 were allocated to the traditional and 97 to the intensive program. Both interventions reduced body mass index, waist circumference and tumor necrosis factor-α. Only intensive program reduced 2-hour plasma glucose and blood pressure and increased adiponectin values, but HDL-cholesterol increased only in the traditional. Also, responses to programs were better in intensive compared to traditional program in terms of blood pressure and adiponectin improvements. No new case of diabetes in intensive but 3 cases and one myocardial infarction in traditional program were detected. Both programs induced metabolic improvement in the short-term, but if better results in the intensive are due to higher awareness about risk and self-motivation deserves further investigation. In conclusion, these low-cost interventions are able to minimize cardiometabolic risk factors involved in the progression to type 2 diabetes and/or cardiovascular disease.

Associations of the TNF-alpha -308 G/A, IL6 -174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Abstract Background Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention. Methods This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-α -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype. Results In the entire sample (66.7% women; mean age 56.5 ± 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-α -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention. Conclusion The TNFα -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.

A behavioral intervention in a cohort of Japanese-Brazilians at high cardiometabolic risk

OBJECTIVE: To assess the effect of a health promotion program on cardiometabolic risk profile in Japanese-Brazilians. METHODS: A total of 466 subjects from a study on diabetes prevalence conducted in the city of Bauru, southeastern Brazil, in 2000 completed a 1-year intervention program (2005-2006) based on healthy diet counseling and physical activity. Changes in blood pressure and metabolic parameters in the 2005-2006 period were compared with annual changes in these same variables in the 2000-2005 period. RESULTS: During the intervention, there were greater annual reductions in mean (SD) waist circumference [-0.5(3.8) vs. 1.2(1.2) cm per year, p<0.001], systolic blood pressure [-4.6(17.9) vs. 1.8(4.3) mmHg per year, p<0.001], 2-hour plasma glucose [-1.2(2.1) vs. -0.2(0.6) mmol/L per year, p<0.001], LDL-cholesterol [-0.3(0.9) vs. -0.1(0.2) mmol/L per year, p<0.001] and Framingham coronary heart disease risk score [-0.25(3.03) vs. 0.11(0.66) per year, p=0.02] but not in triglycerides [0.2(1.6) vs. 0.1(0.42) mmol/L per year, p<0.001], and fasting insulin level [1.2(5.8) vs. -0.7(2.2) IU/mL per year, p<0.001] compared with the pre-intervention period. Significant reductions in the prevalence of impaired fasting glucose/impaired glucose tolerance and diabetes were seen during the intervention (from 58.4% to 35.4%, p<0.001; and from 30.1% to 21.7%, p= 0.004, respectively). CONCLUSIONS: A one-year community-based health promotion program brings cardiometabolic benefits in a high-risk population of Japanese-Brazilians.

Regular physical activity moderates cardiometabolic risk in Alzheimer's caregivers

Dementia caregivers have an increased risk of cardiovascular disease, and it is possible that metabolic disturbances contribute to this risk. Regular physical exercise reduces cardiometabolic risk, but caregivers may have less opportunity to engage in such activity. We hypothesized that regular physical activity would moderate cardiometabolic risk in dementia caregivers.