Mediterranean diet as a strategy for preserving kidney function in patients with coronary heart disease with type 2 diabetes and obesity: a secondary analysis of CORDIOPREV randomized controlled trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function. METHODS: 1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2, were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, < 50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, > 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention. RESULTS: Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p < 0.05). After dietary intervention, the Mediterranean diet induced a lower eGFR decline in patients with Obesity/T2DM, compared to a low-fat diet but not in the other groups (p = 0.014). The Mediterranean diet, but not the low-fat diet, also reduced uACR only in patients with Obesity/T2DM (p = 0.024). CONCLUSIONS: Obesity provided an additive effect to T2DM resulting in a more pronounced decline in kidney function compared to T2DM alone when compared to non-diabetics. In patients with concomitant presence of T2DM and obesity, with more metabolic complications, consumption of a Mediterranean diet seemed more beneficial than a low-fat diet in terms of preserving kidney function. These findings provide valuable insights for tailoring personalized lifestyle modifications in secondary prevention of cardiovascular disease. TRIAL REGISTRATION: URL, http://www.cordioprev.es/index.php/en . CLINICALTRIALS: gov number, NCT00924937.

Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial.

BACKGROUND: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years. METHODS: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements. FINDINGS: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group. CONCLUSION: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease. TRIAL REGISTRATION: Clinicaltrials.gov number NCT00924937.

Telomere Maintenance Is Associated with Type 2 Diabetes Remission in Response to a Long-Term Dietary Intervention without Non-Weight Loss in Patients with Coronary Heart Disease: From the CORDIOPREV Randomized Controlled Trial.

In order to evaluate whether telomere maintenance is associated with type 2 diabetes remission, newly diagnosed type 2 diabetes patients without glucose-lowering treatment (183 out of 1002) from the CORDIOPREV study (NCT00924937) were randomized to consume a Mediterranean or low-fat diet. Patients were classified as Responders, those who reverted from type 2 diabetes during the 5 years of dietary intervention (n = 69), and Non-Responders, who did not achieve diabetes remission by the end of the follow-up period (n = 104). We found no differences in diabetes remission between the two diets, and we determined telomere length (TL) by measuring qPCR, telomerase activity using the TRAP assay, and direct redox balance based on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) via colorimetric assay. Responders exhibited higher baseline TL in comparison with Non-Responders (p = 0.040), and a higher TL at baseline significantly predicted a higher probability of type 2 diabetes remission (OR 2.13; 95% CI, 1.03 to 4.41). After the dietary intervention, Non-Responders showed significant telomere shortening (-0.19, 95% CI -0.32 to 0.57; p = 0.005). Telomere shortening was significantly pronounced in type 2 diabetes patients with a worse profile of insulin resistance and/or beta-cell functionality: high hepatic insulin resistance fasting, a high disposition index (-0.35; 95% CI, -0.54 to -0.16; p < 0.001), and a low disposition index (-0.25; 95% CI, -0.47 to -0.01; p = 0.037). In addition, changes in TL were correlated to the GSH/GSSG ratio. Responders also showed increased telomerase activity compared with baseline (p = 0.048), from 0.16 (95% CI, 0.08 to 0.23) to 0.28 (95% CI, 0.15 to 0.40), with a more marked increase after the dietary intervention compared with Non-Responders (+0.07; 95% CI, -0.06-0.20; p = 0.049). To conclude, telomere maintenance may play a key role in the molecular mechanisms underlying type 2 diabetes remission in newly diagnosed patients. However, further larger-scale prospective studies are necessary to corroborate our findings.

Association between telomere length and intima-media thickness of both common carotid arteries in patients with coronary heart disease: From the CORDIOPREV randomized controlled trial.

BACKGROUND AND AIMS: A critical telomere length (TL) is associated with cardiovascular mortality. Dietary habits have been demonstrated to affect cardiovascular risk. However, it remains unclear how exactly TL determines the response to specific dietary approaches in the reduction of arterial injury. We aimed to evaluate whether TL was associated with the progression of arterial injury (assessed by intima-media thickness of both common carotid arteries: IMT-CC), after long-term consumption of two healthy dietary models in patients with coronary heart disease (CHD). METHODS: From the 1002 CHD patients of the CORDIOPREV study, 903 completed IMT-CC and TL evaluation at baseline and were randomized to follow a Mediterranean diet or a low-fat diet for 5 years. RESULTS: Patients at risk of short TL (TL < 20th percentile) presented an elevated IMT-CC, (0.79 ± 0.17 vs patients at non-risk 0.74 ± 0.17 p < 0.001). TL and IMT-CC showed an inverse association (ß = -0.035, p = 0.002). Patients who consumed a Mediterranean diet, regardless of the risk of short TL, showed a significant decrease in IMT-CC, with a higher reduction in those patients with risk of short TL (-0.03 ± 0.11, p = 0.036). TL (ß = 0.019, p = 0.024), age (ß = -0.001, p = 0.031), energy intake (ß = -0.000, p = 0.036), use of statins (ß = -0.027, p = 0.028) and allocation into the Mediterranean diet (vs low-fat diet) (ß = -0.024, p = 0.003) were significant contributors to changes in IMT-CC. CONCLUSIONS: Patients who had a reduced TL exhibited a greater decrease in IMT-CC after consuming a Mediterranean diet.

Changes in objectively measured sleep after a multidisciplinary lifestyle intervention in children with abdominal obesity: A randomized trial.

BACKGROUND/OBJECTIVE: childhood obesity and sleep disorders have a well-established cross-sectional association, but lifestyle interventions' effects on sleep quality remain under-researched. This study aimed to evaluate the sleep quality of 122 participants (7-16 years) with abdominal obesity after a 2-year necessary lifestyle intervention. PATIENTS/METHODS: participants were assigned to either the intervention group (moderate hypocaloric Mediterranean Diet) or the usual care group (standard recommendations on a healthy diet). Sleep was objectively assessed using triaxial accelerometry, and sleep parameters analyzed included latency, efficiency, wake after sleep onset, total time in bed, total sleep time, number of awakenings, and awakening duration. RESULTS AND CONCLUSIONS: the results showed that the intervention group significantly improved sleep latency at 12 and 24 months and improved sleep efficiency at 2 and 12 months, compared to the usual care group. Wake after sleep onset and the number of awakenings were significantly reduced at 24 months in the intervention group. Wake after sleep onset and leptin levels were positively associated in all participants. Total time in bed was inversely associated with triglycerides and metabolic score, and total sleep time was inversely associated with leptin, triglycerides, and metabolic score after the 2-month intervention. Triglyceride levels were inversely associated with total time in bed and total sleep time at one year, while the metabolic score was directly associated with wake after sleep onset and the number of awakenings and inversely associated with efficiency. In conclusion, the multidisciplinary intervention in children and adolescents with abdominal obesity reduced anthropometric parameters and improved sleep habits.

Circulating miRNAs in girls with abdominal obesity: miR-221-3p as a biomarker of response to weight loss interventions.

BACKGROUND: Recent studies have associated several microRNAs (miRNAs) with childhood obesity and energy homeostasis, suggesting that an individual miRNA profile could be used as an early predictor to estimate the response to weight loss interventions in the design of precision nutrition. OBJECTIVE: To investigate associations between the expression of circulating adiposity-related miRNAs and the response to a weight loss intervention. METHODS: A total of 51 Spanish girls (age 7-16 years) with abdominal obesity underwent 8 weeks of a multidisciplinary intervention for weight loss. Participants were stratified into two groups in accordance with changes in body mass index (BMI) standard deviation score: low-responders (LR) and high-responders (HR). The expression of 39 circulating miRNAs (c-miRNAs) was evaluated in plasma of all subjects before the intervention. RESULTS: Six miRNAs were differentially expressed between LR and HR. However, after adjustment for Tanner stage, the association was maintained only for miR-126-3p and miR-221-3p with a higher expression in HR group compared to LR group. After the intervention, miR-221-3p expression decreased in all subjects with a significant difference in the change within groups. However, changes in miR-126-3p levels were not significant. The expression of miR-221-3p was positively correlated with body weight, BMI and waist circumference, and negatively correlated with quantitative insulin sensitivity check index. CONCLUSIONS: Bioinformatic analysis evidenced that miR-221-3p participates in several obesity-related pathways, and more interestingly, this miRNA targets several candidate genes to childhood obesity according to DisGeNet database. Thus, miR-221-3p could be used for predicting the response to a multidisciplinary intervention for weight loss in young girls.

Dietary Exposure to Polychlorinated Biphenyls and Dioxins and Its Relationship to Telomere Length in Subjects Older Than 55 Years from the SUN Project.

Exposure to persistent organic pollutants (POPs) may influence telomere length (TL), which is considered as a marker of biological age associated with the risk of chronic disease. We hypothesized that dietary exposure to polychlorinated biphenyls (PCBs) and dioxins could affect TL. Our aim was to evaluate the association of dietary exposure to PCBs and dioxins with TL. In this cross-sectional study of 886 subjects older than 55 y (mean age: 67.7; standard deviation (SD): 6.1; 27% women) from the "Seguimiento Universidad de Navarra" (SUN) project. TL was determined by real-time quantitative polymerase chain reaction and dietary PCBs and dioxins exposure was collected using a validated 136-item Food Frequency Questionnaire. Multivariable linear regression models were used to control for potential confounding factors. Shorter TL was associated with dietary total PCBs (SD of T/S ratio/(ng/day) = -0.30 × 10-7; 95% CI, -0.55 × 10-7 to -0.06 × 10-7), dioxin-like PCBs (DL-PCBs) (SD of T/S ratio/(pg WHO TEQ (Toxic Equivalents)/day) = -6.17 × 10-7; 95% CI, -11.30 × 10-7 to -1.03 × 10-7), and total TEQ exposure (SD of T/S ratio/(pg WHO TEQ/day) = -5.02 × 10-7; 95% CI, -9.44 × 10-7 to -0.61 × 10-7), but not with dioxins (SD of T/S ratio/(pg WHO TEQ/day) = -13.90 × 10-7; 95% CI, -37.70 × 10-7 to 9.79 × 10-7). In this sample of middle-aged and older Spanish adults, dietary exposure to total PCBs and DL-PCBs alone and together with dioxins was associated with shorter TL. Further longitudinal studies, preferably with POPs measured in biological samples, are needed to confirm this finding.

Association between ideal cardiovascular health and telomere length in participants older than 55 years old from the SUN cohort.

INTRODUCTION AND OBJECTIVES: Telomeres are noncoding regions located at the end of chromosomes and their shortening has been associated with risk factors and cardiovascular disease. The aim of this study was to evaluate the association between ideal cardiovascular health (Life's simple 7) and the odds of having short telomeres in a subsample of participants older than 55 years from the Seguimiento Universidad de Navarra (SUN) study. METHODS: We included 886 participants older than 55 years (645 men and 241 women). Telomere length was measured using a real-time quantitative polymerase chain reaction. Cardiovascular health score was defined by the American Heart Association as a composite score of 7 key risk factors (smoking status, physical activity, diet, body mass index, blood pressure, total cholesterol, and fasting blood glucose) with 0 to 2 points for each factor. We categorized this score in tertiles as poor (0-9 points), intermediate (10-11 points) and ideal (12-14 points). The odds of having short telomeres was defined as telomere length below the 20th percentile. RESULTS: Individuals with higher ideal cardiovascular health had a lower prevalence of having short telomeres (adjusted OR, 0.60; 95%CI, 0.34-1.05; P trend=.052). This association was statistically significant in men (adjusted OR, 0.37; 95%CI, 0.17-0.83; P trend=.025) but not in women. CONCLUSIONS: An inverse association between cardiovascular health score and short telomeres was found especially for men older than 55 years in the SUN population. The SUN project was registered at ClinicalTrials.gov (Identifier: NCT02669602).

Higher Lipopolysaccharide Binding Protein and Chemerin Concentrations Were Associated with Metabolic Syndrome Features in Pediatric Subjects with Abdominal Obesity during a Lifestyle Intervention.

Elevated circulating plasma levels of both lipopolysaccharide-binding protein (LBP) and chemerin are reported in patients with obesity, but few studies are available on lifestyle intervention programs. We investigated the association of both LBP and chemerin plasma levels with metabolic syndrome (MetS) outcomes in a lifestyle intervention in children and adolescents with abdominal obesity Methods: Twenty-nine patients enrolled in a randomized controlled trial were selected. The lifestyle intervention with a 2-month intensive phase and a subsequent 10-month follow-up consisted of a moderate calorie-restricted diet, recommendations to increase physical activity levels, and nutritional education. Results: Weight loss was accompanied by a significant reduction in MetS prevalence (-43%; p = 0.009). Chemerin (p = 0.029) and LBP (p = 0.033) plasma levels were significantly reduced at 2 months and 12 months, respectively. At the end of intervention, MetS components were associated with both LBP (p = 0.017) and chemerin (p < 0.001) plasma levels. Conclusions: We describe for the first time a reduction in both LBP and chemerin plasma levels and its association with MetS risk factors after a lifestyle intervention program in children and adolescents with abdominal obesity. Therefore, LBP and chemerin plasma levels could be used as biomarkers for the progression of cardiovascular risk in pediatric populations.

Association between favourable changes in objectively measured physical activity and telomere length after a lifestyle intervention in pediatric patients with abdominal obesity.

The purpose of this study was to assess the effect of physical activity (PA) changes, measured by accelerometry, on telomere length (TL) in pediatric patients with abdominal obesity after a lifestyle intervention. One hundred and twenty-one children (7-16 years old) with abdominal obesity were randomized to the intervention (a moderately hypocaloric Mediterranean diet) or the usual care group (standard pediatric recommendations) for 22 months (a 2 month intensive phase and a subsequent 20 month follow-up). Both groups were encouraged to accumulate an extra 200 min/week of PA. TL was measured by MMqPCR. Data were analyzed in 102 subjects after 2 months and 64 subjects at the first 10 months of follow-up. Light PA level decreased in both groups after 12 months of intervention. At month 2, moderate to vigorous PA (MVPA) increased in the intervention group (+5.4 min/day, p = 0.035) and so did sedentary time in the usual care group (+49.7 min/day, p = 0.010). TL changes were positively associated (p < 0.050) with metabolic equivalents (METs), MVPA level, and number of steps, and were inversely associated with sedentary and light PA levels in the intervention group after the intensive phase. In conclusion, favourable changes in PA levels in the intensive phase of a lifestyle intervention could contribute to TL maintenance in a pediatric population with abdominal obesity. Novelty Changes in physical activity levels had a direct effect on telomere length, a biomarker of cellular aging and oxidative stress. PA advice based on The American College of Sports Medicine included in this intervention is easy to implement in primary care.

Higher adherence to an empirically derived Mediterranean dietary pattern is positively associated with telomere length: the Seguimiento Universidad de Navarra (SUN) project.

Telomere integrity is influenced by oxidative stress. Also, inflammation-related factors, including nutritional factors, could modulate telomere integrity. The relationship between a posteriori-derived dietary patterns and telomere length (TL) has been scarcely investigated. Thus, our objective was to examine the association between empirically derived dietary patterns ascertained through principal component analysis (PCA) and TL in an older adult Spanish population. A total of 886 older adults (>55 years old; 645 males and 241 females) from the Seguimiento Universidad de Navarra (SUN) cohort were included in the study. TL was measured by monochrome multiplex real-time quantitative PCR. Age-adjusted TL was used for all analyses. Dietary patterns were identified by PCA based on thirty predefined candidate food groups collected from a validated 136-food items frequency questionnaire. Generalised linear models were fitted to obtain ß-coefficients and their 95 % CI evaluating differences in TL between each of the four upper quintiles of adherence to dietary patterns and the lowest quintile. Sensitivity analyses by rerunning all multiple linear models under different stratifications were performed to evaluate the robustness of our results. Two major dietary patterns were empirically identified, Western dietary pattern (WDP) and Mediterranean dietary pattern (MDP). After adjustment for potential confounders, longer TL was found among subjects in the highest quintile of MDP (ß = 0·064; 95 % CI 0·004, 0·123). The WDP showed no significant association with TL. In conclusion, higher adherence to a posteriori-derived MDP was independently associated with longer telomeres in an older adult Spanish population of the SUN project.

Associations of telomere length with two dietary quality indices after a lifestyle intervention in children with abdominal obesity: a randomized controlled trial.

BACKGROUND: Dietary factors seem to influence telomere length. Moreover, associations between changes in adiposity indices and telomere length (TL) have been found in intervention studies. OBJECTIVE: We evaluated changes in two diet quality indices and their association with TL in children with abdominal obesity in a 12-month lifestyle intervention. METHODS: Eighty-seven participants (7-16 years old) were assigned to the intervention (moderate hypocaloric Mediterranean diet) or usual care group (standard paediatric recommendations) for a 2-month intensive phase and a subsequent 10-month follow-up. Diet quality was assessed using the Diet Quality Index for Adolescents (DQI-A) and the Healthy Lifestyle Diet Index (HLD-I). TL was measured by monochrome multiplex real-time quantitative PCR. The intra-class correlation coefficient for TL was 0.793 (95% CI 0.707, 0.857). RESULTS: After a 12-month lifestyle intervention, a significant reduction in BMI-SDS (-0.57 and -0.49 for the intervention and usual care groups, respectively) and fat mass was observed in all subjects without differences between groups. Changes in DQI-A (+12.36% vs +5.53%, P = .005) and HLD-I (+4.43 vs +1.09, P < .001) were higher in the intervention subjects compared with usual care subjects after 2 months. Interestingly, we observed a positive change in TL between 2 and 12 months (P = .025), which was associated with higher scores on the DQI-A (ß = 0.008, R2 = 0.088, P = .010) and HLD-I (ß = 0.022, R2 = 0.198, P = .015), in the intervention group after the 2-month intensive phase. CONCLUSION: Favourable changes in diet quality indices could contribute to telomere integrity in children with abdominal obesity enrolled in an intensive lifestyle intervention.

Ultra-processed food consumption and the risk of short telomeres in an elderly population of the Seguimiento Universidad de Navarra (SUN) Project.

BACKGROUND: Telomere length (TL) is a marker of biological age that may be affected by dietary factors through oxidation and inflammation mechanisms. In addition, ultra-processed food (UPF) consumption has increased worldwide and it has been associated with the risk of developing several diseases. OBJECTIVES: We aimed to evaluate the association between UPF consumption and the risk of having short telomeres in an elderly population of the Seguimiento Universidad de Navarra (SUN) Project. METHODS: This is a cross-sectional study of 886 participants (645 men and 241 women) aged 57-91 y recruited from the SUN Project (Spain, 1999-2018). TL was measured from saliva samples by real-time qPCR at baseline and UPF consumption was collected using a validated 136-item FFQ and classified according to the NOVA system. We evaluated the association between consumption of energy-adjusted UPF categorized into quartiles (low, medium-low, medium-high, and high consumption) and the risk of having short telomeres (<20th percentile) using logistic regression models. RESULTS: Those participants with the highest UPF consumption had almost twice the odds of having short telomeres compared with those with the lowest consumption (adjusted OR: 1.82; 95% CI: 1.05, 3.22; P-trend = 0.03). CONCLUSIONS: A higher consumption of UPF (>3 servings/d) was associated with higher risk of having shorter telomeres in an elderly Spanish population of the SUN Project.This trial was registered at clinicaltrials.gov as NCT02669602.

Associations of telomere length with anthropometric and glucose changes after a lifestyle intervention in abdominal obese children.

BACKGROUND AND AIMS: In lifestyle intervention studies, we demonstrated that changes in telomere length (TL) were associated with changes in anthropometric indices. Therefore, our new hypothesis is that TL could be a predictor of changes in anthropometric or metabolic measures in children with abdominal obesity. The aim of the study was to evaluate the association between anthropometric and biochemical measurements with TL before and after an 8-week lifestyle intervention in children with abdominal obesity (7-16 years old). METHODS AND RESULTS: We assessed anthropometric and biochemical outcomes at baseline and after 8-week lifestyle intervention in 106 children with abdominal obesity (11.30 ± 2.49 years old, 63% girls). TL was measured by monochrome multiplex real-time quantitative PCR. After the lifestyle intervention, anthropometric parameters and glucose metabolism indicators significantly improved in the participants. TL did not change after the intervention in participants. Significant negative correlations between baseline TL and anthropometric measures (BMI, body weight and waist circumference) were observed. Furthermore, baseline TL was a predictor for changes in blood glucose levels after the lifestyle intervention. CONCLUSIONS: An inverse correlation between TL and obesity traits was observed in children with abdominal obesity. Interestingly, we found that baseline TL could predict changes in blood glucose levels. CLINICAL TRIAL: NCT03147261. Registered 10 May 2017.

Association between diet quality indexes and the risk of short telomeres in an elderly population of the SUN project.

BACKGROUND: Shorter telomeres are associated with several age-related diseases, and lifestyle factors could influence this relationship. The aim of this study was to examine associations between salivary telomere length (TL) and diet quality using 5 evidence-based dietary indexes in an elderly (>55 years old) Spanish population of the SUN project (n = 886). METHOD: TL was measured using the quantitative real-time polymerase chain reaction. Age-adjusted TL variable through residuals methods was used for all analysis. Diet quality was assessed by the Prime Diet Quality Score (PDQS), Fat Quality Index (FQI), Mediterranean Diet Adherence Screener (MEDAS), Dietary Approaches to Stop Hypertension (DASH) index and the Alternative Healthy Eating Index (AHEI-2010). RESULTS: TL did differ according to sex, smoking status, and dyslipidemia in elderly subjects of the SUN study. In addition, subjects with dyslipidemia (compared to absence of dyslipidemia) had a significantly higher risk (27% vs. 18%, p = 0.015) of short telomeres (

Melanocortin-4 Receptor and Lipocalin 2 Gene Variants in Spanish Children with Abdominal Obesity: Effects on BMI-SDS After a Lifestyle Intervention.

Mutations leading to a reduced function of the melanocortin-4 receptor (MC4R) exert a major gene effect on extreme obesity. Recently it was shown that the bone derived hormone lipocalin 2 (LCN2) binds to the MC4R and activates a MC4R dependent anorexigenic pathway. We identified mutations in both genes and screened the effects of MC4R and LCN2 mutations on eating behavior and weight change after a lifestyle intervention. One hundred and twelve children (11.24 ± 2.6 years, BMI-SDS 2.91 ± 1.07) with abdominal obesity participated in a lifestyle intervention. MC4R and LCN2 coding regions were screened by Sanger sequencing. Eating behavior was assessed at baseline with the Children Eating Behavior Questionnaire (CEBQ). We detected three previously described non-synonymous MC4R variants (Glu42Lys, Thr150Ile, and Arg305Gln) and one non-synonymous polymorphism (Ile251Leu). Regarding LCN2, one known non-synonymous variant (Thr124Met) was detected. Eating behavior was described in carriers of the MC4R and LCN2 mutation and in non-carriers. MC4R and LCN2 mutations were detected in 2.42% and 0.84%, respectively, of Spanish children with abdominal obesity. A number of subjects with functional mutation variants in MC4R and LCN2 were able to achieve a reduction in BMI-SDS after a lifestyle intervention.

Changes in objectively measured physical activity after a multidisciplinary lifestyle intervention in children with abdominal obesity: a randomized control trial.

BACKGROUND: Physical activity (PA) is associated with changes in body composition that affect insulin sensitivity and leptin levels. Few studies have assessed the effect of lifestyle interventions on changes in objectively measured PA levels in obese children. To evaluate the effects of a multidisciplinary lifestyle intervention on anthropometric indices, biochemical parameters and accelerometer measured PA in abdominal obese children. METHODS: A randomized control trial was performed in 106 children and adolescents with abdominal obesity. Participants were randomly assigned to usual or intensive care group for 8-week. PA was measured by accelerometry over four days including, at least, two weekdays in all participants. Both groups were encouraged to accumulate an extra time of 200 min per week in their PA. RESULTS: At baseline, 75% of subjects do not fulfill the WHO recommendation of being more than 60 min/day on moderate-to-vigorous PA (MVPA). The intensive care group achieved a significant reduction in anthropometric indexes compared to the usual care but no significant change was found in biochemical or PA parameters. Both groups achieved a significant reduction in light PA. Interestingly, intensive care participants significantly increased MVPA in 5.5 min/day. Moreover, an inverse association between changes in MVPA and leptin levels was found. CONCLUSION: The two lifestyle intervention reduced anthropometric indexes and lowered light PA in abdominal obese children. No significant differences were observed between intensive care and usual care in regard to PA. Intensive care participants significantly increase physical activity (MVPA) and, changes in MVPA were inversely associated with changes in leptin levels after the intervention. TRIAL REGISTRATION: ClinicalTrials.gov , Identifier: NCT03147261 . Registered 10 May 2017. Retrospectively registered.

Clustering of Multiple Energy Balance-Related Behaviors in School Children and its Association with Overweight and Obesity-WHO European Childhood Obesity Surveillance Initiative (COSI 2015⁻2017).

It is unclear how dietary, physical activity and sedentary behaviors co-occur in school-aged children. We investigated the clustering of energy balance-related behaviors and whether the identified clusters were associated with weight status. Participants were 6- to 9-year-old children (n = 63,215, 49.9% girls) from 19 countries participating in the fourth round (2015/2017) of the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative. Energy balance-related behaviors were parentally reported. Weight and height were objectively measured. We performed cluster analysis separately per group of countries (North Europe, East Europe, South Europe/Mediterranean countries and West-Central Asia). Seven clusters were identified in each group. Healthier clusters were common across groups. The pattern of distribution of healthy and unhealthy behaviors within each cluster was group specific. Associations between the clustering of energy balance-related behaviors and weight status varied per group. In South Europe/Mediterranean countries and East Europe, all or most of the cluster solutions were associated with higher risk of overweight/obesity when compared with the cluster 'Physically active and healthy diet'. Few or no associations were observed in North Europe and West-Central Asia, respectively. These findings support the hypothesis that unfavorable weight status is associated with a particular combination of energy balance-related behavior patterns, but only in some groups of countries.

Improved Diet Quality and Nutrient Adequacy in Children and Adolescents with Abdominal Obesity after a Lifestyle Intervention.

High rates of childhood obesity require integral treatment with lifestyle modifications that achieve weight loss. We evaluated a lifestyle intervention on nutrient adequacy and diet quality in children and adolescents with abdominal obesity. A randomized controlled trial was performed on 107 participants, assigned either to a usual care group or to an intensive care group that followed a moderate hypocaloric Mediterranean diet and received nutritional education. Intake adequacy was evaluated using Dietary Reference Intakes and diet quality through the Diet Quality Index for Adolescents (DQI-A), the Healthy Lifestyle Diet-Index (HLD-I) and the Mediterranean Diet Quality Index (KIDMED). Both groups achieved a significant reduction in BMI standard deviation score (BMI-SDS), glucose and total cholesterol levels. Intake of Calcium, Iodine and vitamin D were higher in the intensive care group, with enhanced compliance with recommendations. Higher dietary scores were associated with lower micronutrient inadequacy. DQI-A and HLD-I were significantly higher in the intensive care group vs. usual care group after the treatment. In conclusion, we observed that an intensive lifestyle intervention was able to reduce BMI-SDS in children with abdominal obesity. Furthermore, participants significantly improved dietary indices getting closer to the nutritional recommendations. Therefore, these diet quality indices could be a valid indicator to evaluate micronutrient adequacy.

Reduced serotonin levels after a lifestyle intervention in obese children: association with glucose and anthropometric measurements.

BACKGROUND: serotonin signaling participates in body weight regulation and glucose metabolism. However, little information is available on circulating serotonin levels in obese subjects after a weight loss program. We aimed to assess the effect of a lifestyle intervention on serotonin levels in obese children and possible associations with anthropometric and blood glucose measurements. METHODS: forty-four obese children were enrolled in a ten-week lifestyle intervention consisting of a moderate caloric restriction diet, nutritional education and familial involvement. They were distributed according to the weight loss response. Subjects who lost > 0.5 BMI-SDS were considered as high responders (HR; n = 22) and those who lost ≤ 0.5 BMI-SDS, as low responders (LR; n = 22). Anthropometric, biochemical parameters and plasma serotonin levels were measured as pre and post-intervention values. RESULTS: obese children (HR and LR groups) were able to reduce anthropometric indices and to improve glucose profile after the intervention. Interestingly, plasma serotonin levels were significantly (p ˂0.05) reduced in all subjects (-35.14 nmol/l HR group and -30.63 nmol/l LR group). Moreover, multiple-adjusted regression models showed a significant association between pre-intervention (R2 = 0.224, B = 0.047; p = 0.004) and post-intervention (R2 = 0.140; B = 0.055; p = 0.042) plasma serotonin and glucose levels. In addition, in HR subjects changes in plasma serotonin were associated with changes in glucose levels (R2 = 0.292; b = 0.04; p = 0.045). Interestingly, pre and post-intervention plasma serotonin levels were inversely associated (p ˂0.05) with anthropometric measures. CONCLUSIONS: serotonin levels were reduced after a lifestyle intervention independently of the program response. Moreover, plasma serotonin levels were associated with glucose and anthropometric measures in obese children.