New Incretin Combination Treatments under Investigation in Obesity and Metabolism: A Systematic Review.

The worldwide upward trend in obesity in adults and the increased incidence of overweight children suggests that the future risk of obesity-related illnesses will be increased. The existing anti-obesity drugs act either in the central nervous system (CNS) or in the peripheral tissues, controlling the appetite and metabolism. However, weight regain is a common homeostatic response; current anti-obesity medications show limited effectiveness in achieving long-term weight loss maintenance; in addition to being linked to various side effects. Combined anti-obesity medications (per os or injectable) target more than one of the molecular pathways involved in weight regulation, as well as structures in the CNS. In this systematic review, we conducted a search of PubMed and The ClinicalTrials.gov up to February 2021. We summarized the Food and Drug Administration (FDA)-approved medications, and we focused on the combined pharmacological treatments, related to the incretin hormones, currently in a clinical trial phase. We also assessed the mechanism of action and therapeutic utility of these novel hybrid peptides and potential interactions with other regulatory hormones that may have beneficial effects on obesity. As we improve our understanding of the pathophysiology of obesity, we hope to identify more novel treatment strategies.

The relationship between behavioral factors, weight status and a dietary pattern in primary school aged children: The GRECO study.

BACKGROUND & AIMS: Numerous factors have been associated with the increase in childhood overweight and obesity, including environmental, dietary and behavioral. The latter have been associated with unhealthy eating behaviors but studies of their relation to dietary patterns are limited. Dietary patterns serve as a better means to evaluate children's diet and risk of obesity and therefore the aim of the study was to examine the relationship of behavioral factors with a specific dietary pattern developed for children (child derived Food Index (cdFI)), and to assess how behavioral and diet are related to children's weight status when addressed together in a model. METHODS: Study included school-aged children (n = 4434) from the Greek Childhood Obesity study (GRECO), a cross-sectional survey. Participants self-reported behavioral habits and dietary intake, using a semi-quantitative food-frequency questionnaire (FFQ). A high dietary pattern-cdFI is related to a healthier dietary pattern. Anthropometric data were measured. Multiple linear and logistic regressions were performed, adjusting for age and gender. RESULTS: The dietary pattern was positively associated with sleep, family meals and study hours, and was inversely associated with total screen time, frequency of eating out and eating while on some screen. Overweight and obese children were more likely to have a lower cdFI score (2%), sleep less (8%) and report more study hours (6%). CONCLUSION: In order to reduce and prevent child overweight and obesity, interventions probably need to address specific behavioral and dietary patterns together.

Maternal smoking and risk of obesity in school children: Investigating early life theory from the GRECO study.

Based on the Early Life Theory, maternal smoking may be a factor affecting child weight status, adiposity level and blood pressure later in life. The purpose of this study was primarily to examine the risk of maternal smoking during pregnancy with overweight and obesity, central and total adiposity in school children. Secondarily, to assess the effect of maternal smoking, with children's blood pressure (BP). Data from the Greek Childhood Obesity cross sectional study (GRECO), conducted from October 2008 to May 2009, were used. A total of 2400 questionnaires gathered from children and their parents were analysed. Maternal and gestational data were gathered by a self-administered questionnaire. Women were categorized as non-smokers or smokers if they smoked ≥ 1 cigarettes/day during pregnancy. Children's body weight, height, waist circumference and BP were measured. Multiple logistic and linear regression analysis was conducted, adjusting for covariates. Four models were used in the process. The study found that children of maternal-smokers were more likely to be overweight or obese (OR: 1.6 to 1.82) and to have a larger waist circumference (OR: 1.73 to 1.85), compared to children of non-smokers in all models used. Total fat percentage was not significantly associated with maternal smoking when adjusted. Systolic and diastolic BP was not associated with maternal smoking. Results of this study strengthen the need for smoking cessation during pregnancy in order to possibly reduce the childhood obesity epidemic. Creating public health awareness of the potential risk of maternal-smoking on children's weight status later in life is warranted.

Short-term effects of a low glycemic index carob-containing snack on energy intake, satiety, and glycemic response in normal-weight, healthy adults: Results from two randomized trials.

OBJECTIVES: The potential positive health effects of carob-containing snacks are largely unknown. Therefore, the aims of these studies were to determine the glycemic index (GI) of a carob snack compared with chocolate cookie containing equal amounts of available carbohydrates and to compare the effects of a carob versus chocolate cookie preload consumed as snack before a meal on (a) short-term satiety response measured by subsequent ad libitum meal intake, (b) subjective satiety as assessed by visual analog scales and (c) postprandial glycemic response. METHODS: Ten healthy, normal-weight volunteers participated in GI investigation. Then, 50 healthy, normal-weight individuals consumed, crossover, in random order, the preloads as snack, with 1-wk washout period. Ad libitum meal (lunch and dessert) was offered. Capillary blood glucose samples were collected at baseline, 2 h after breakfast, just before preload consumption, 2 h after preload, 3 h after preload, just before meal (lunch and dessert), 1 h after meal, and 2 h after meal consumption. RESULTS: The carob snack was a low GI food, whereas the chocolate cookie was a high GI food (40 versus 78, respectively, on glucose scale). Consumption of the carob preload decreased the glycemic response to a following meal and to the individual's feelings of hunger, desire to eat, preoccupation with food, and thirst between snack and meal, as assessed with the use of visual analog scales. Subsequently, participants consumed less amounts of food (g) and had lower total energy intake at mealtimes. CONCLUSIONS: The carob snack led to increased satiety, lower energy intake at meal, and decreased postmeal glycemic response possibly due to its low GI value. Identifying foods that promote satiety and decrease glycemic response without increasing the overall energy intake may offer advantages to body weight and glycemic control.

Short-term effects of Mediterranean-type diet intervention on soluble cellular adhesion molecules in subjects with abdominal obesity.

BACKGROUND & AIMS: Abdominal obesity (AO) is associated with increased risk for cardiovascular disease and with increased production of adhesion molecules. The present work examined the effect of a Mediterranean-style diet on soluble cellular adhesion molecules in individuals with AO. METHODS: Ninety subjects with AO without cardiovascular disease or diabetes mellitus were randomly allocated to the intervention or control group and were instructed to follow a Mediterranean-style diet for two months. Intervention group followed a specific relevant food plan with close dietetic supervision and provision of basic foods. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), sP and sE-selectin, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. RESULTS: Subjects in the intervention group increased their intake of total fat, monounsaturated fatty acids, dietary fiber, vitamin C, and alcohol compared to controls, while decreased their intake of saturated fat. Although there was a significant decrease in CRP, sP-selectin and in sE-selectin in the intervention group, and an increase in sVCAM-1 in the control group, between-group analysis showed no statistically significant differences. There were also no significant changes in sICAM-1, and IL-6 levels after intervention. CONCLUSIONS: Mediterranean-type diet for two months combined with close dietetic supervision showed a beneficial tendency towards the down-regulation of some markers of vascular inflammation, although the comparison between groups after the intervention did not reach statistical significance. A longer period of dietary intervention may be required to further support these changes.

Food sources of free sugars in children's diet and identification of lifestyle patterns associated with free sugars intake: the GRECO (Greek Childhood Obesity) study.

OBJECTIVE: Excessive free sugars consumption has a possible role in health issues, diet quality and obesity development. The present cross-sectional study aimed to identify the major food sources of free sugars in Greek children's diet and investigate possible associations of dietary patterns with free sugars intake. DESIGN: Anthropometric measurements and information on dietary and physical activity habits were obtained. Energy and free sugars intake coming from foods were estimated and principal components analysis was applied to identify dietary patterns. SETTING: The GRECO (Greek Childhood Obesity) study. SUBJECTS: Nationwide sample of 3089 children (aged 10-12 years). RESULTS: Adopting WHO criteria, 44·2 % of participants were categorized as having free sugars intake above 10 % of total energy intake. Mean contribution of free sugars to energy intake was 11·2 %, and the major food sources of free sugars differed from those of other childhood populations. Free sugars intake was not associated with overweight/obesity. Multiple linear regression analysis revealed that two lifestyle and dietary patterns, characterized by higher consumption of sweets, fast foods, fries, sugared drinks, frequently ordering/eating outside home and having meals in front of a screen (pattern 1) and higher consumption of whole fruits, 100 % fruit juices, vegetables, legumes and honey/jam (pattern 2), were positively associated with free sugars intake. CONCLUSIONS: A large proportion of children exceeded the recommended cut-off and free sugars intake was associated with lifestyle patterns rather than single foods. Public health programmes aiming to reduce free sugars consumption should be tailored on promoting the correct dietary habits of specific childhood populations.

Anthropometric, lifestyle and parental characteristics associated with the prevalence of energy intake misreporting in children: the GRECO (Greek Childhood Obesity) study.

The objectives of the present study were to identify childhood energy misreporting, and evaluate characteristics that are associated with its prevalence in a nationwide cross-sectional sample of Greek schoolchildren. Under the context of the GRECO (Greek Childhood Obesity) study, data from a total of 4547 children aged 10-12 years and 2318 parents were included in the analysis. Anthropometric, lifestyle and parental characteristics plus psychological concerns were investigated in relation to the prevalence of energy misreporting. Of the included children, 36 % were classified as energy under-reporters and 16 % as over-reporters. Multinomial logistic regression analysis revealed that the most important predictors of energy under-reporting (URP) were children's BMI (OR 1·11, 95 % CI 1·09, 1·14) and weight satisfaction (OR 0·87, 95 % CI 0·78, 0·97). In the case of energy over-reporting (ORP), children's BMI (OR 0·87, 95 % CI 0·84, 0·90), meal and snack consumption frequency (OR 1·52, 95 % CI 1·32, 1·75), female sex (OR 0·65, 95 % CI 0·45, 0·90), and maternal education (OR 0·95, 95 % CI 0·91, 0·99) remained as significant predictors. Additionally, parental perception that the body weight of their children was normal reduced the odds of URP (OR 0·69, 95 % CI 0·48, 0·99) and ORP (OR 0·53, 95 % CI 0·31, 0·93). In conclusion, the present study confirms that the issue of URP and ORP in childhood populations is evident and quite serious. Although there are no definite guidelines on how to use data obtained from misreporters in an epidemiological dataset, validity of reported energy intake seems to be influenced by children's BMI and weight satisfaction, as well as by parental perceptions regarding their children's weight.

Dietary and lifestyle patterns in relation to high blood pressure in children: the GRECO study.

OBJECTIVE: The objective of the present study was to investigate possible associations of dietary patterns with high blood pressure (BP) in a nationwide cross-sectional sample of 10-12 years old Greek schoolchildren. METHODS: Anthropometric measurements and information on dietary (by a semi-quantitative food frequency questionnaire) and physical activity habits were obtained from the children. BPs was measured in a single occasion using a standard protocol. Data from 2024 normal energy reporting children were included in the analysis. Principal component analysis was applied to identify dietary patterns. RESULTS: Seven dietary components (patterns) were extracted explaining 55% of the total variation in intake. Multiple logistic regression analysis revealed that predictors of high BP (75th percentile of SBP and/or DBP) were a pattern mainly characterized by the high consumption of cheese and red processed meat [odds ratio (OR) 1.15; 95% confidence intervals (CI) 1.03-1.30], being overweight (OR 2.10; 95% CI 1.61-2.73) or obese (OR 3.84; 95% CI 2.44-6.06) and breakfast frequency (OR 0.95; 95% CI 0.90-0.99). After controlling for sodium intake levels, the dietary pattern did not remain a significant predictor of high BP, indicating the potential mediating effect of sodium in the association. CONCLUSION: A dietary pattern that is characterized by high cheese and red processed meat consumption increases the likelihood of having high BP in children, probably through increasing dietary sodium intake. These findings could guide future interventions or public health initiatives to prevent the increasing rates of childhood elevated BP levels.

Socio-economic and demographic determinants of childhood obesity prevalence in Greece: the GRECO (Greek Childhood Obesity) study.

OBJECTIVE: Given the rapid increase in the prevalence of childhood obesity, identifying the sociodemographic influences on obesity status is important for planning and implementing effective prevention initiatives. However, this type of data is limited for Greek children. Therefore the aim of the present study was to identify possible sociodemographic factors associated with childhood obesity at the national level. DESIGN: Cross-sectional, population-based survey, carried out from October to May 2009. Setting Under the context of the GRECO (Greek Childhood Obesity) study, a nationwide sample of 2315 primary-school children. SUBJECTS: Children aged 10-12 years and their parents were voluntarily enrolled. Direct anthropometric measurements of the children were obtained and information on sociodemographic characteristics of the parents, as well as their self-reported values of body weight and height, were collected. RESULTS: Overweight and obesity prevalence was 29·5 % and 13·1 %, respectively, among boys; 29·5 % and 9·0 %, respectively, among girls. Multiple logistic regression analysis revealed that the most important sociodemographic predictors of childhood obesity were mother's age, parental BMI classification and father's type of occupation. More specifically, increased mother's age and normal BMI status of the parents seemed to have a protective effect on the likelihood of having an overweight/obese child. Additionally, the odds of a female child of being overweight/obese were reduced when the father's type of occupation tended to be less manual. CONCLUSIONS: Anti-obesity health policy interventions have to address to the parents and promote their active involvement, to effectively confront the alarming magnitude of the paediatric obesity problem in Greece.

Perinatal and family factors associated with preadolescence overweight/obesity in Greece: the GRECO study.

OBJECTIVE: To explore associations of perinatal and family factors with preadolescence overweight and obesity in a sample of Greek schoolchildren. METHODS: A nationwide cross-sectional study among 2093 students (10.9 ± 0.72 years, 44.9% boys) and their parents were conducted. Anthropometric (e.g., height, weight, mother's body mass index (BMI) at the time of the study and at conception), socio-demographic (e.g., age, education, socio-economic status), diet and other major lifestyle characteristics (e.g., smoking, alcohol intake, physical activity and inactivity) and perinatal factors (e.g., breast- and formula-feeding) were collected with validated questionnaires. Height and weight of students were measured. Overweight/obesity was classified using IOTF cut-offs. Multivariable logistic and linear regression analyses were used to identify major independent factors of overweight/obesity among preadolescents and factors related with the percentage change of mother's BMI, respectively. RESULTS: Increased age at pregnancy [odds ratios (OR)=0.95, 95% Confidence Interval (CI): 0.93-0.97], higher BMI at conception (OR=1.17, 95% CI: 1.12-1.22) and heavy smoking (OR = 2.02, 95% CI: 1.23-3.33) were positively associated with child's overweight/obesity status. Moreover, mother's age and TV viewing, indicating inactivity, were the strongest factors of the percentage increase in mother's BMI (b ± se = 0.23 ± 0.07, p = 0.002; b ± se=0.32 ± 0.10, p = 0.002, respectively). CONCLUSIONS: Preadolescent obesity is associated with mother's pre-pregnancy weight, age and heavy smoking at conception and mother's BMI change after gestation.

Very high childhood obesity prevalence and low adherence rates to the Mediterranean diet in Greek children: the GRECO study.

OBJECTIVE: In order to provide estimates of overweight and obesity among Greek schoolchildren, and the adherence rates to the Mediterranean diet (MD), a nationwide survey was performed among fifth and sixth grade students aged 10-12 years old. METHODS: A stratified sampling in 10 regions of the country was applied to voluntarily enroll a representative sample of 4786 children. Children were weighed and measured and completed a semi-quantitative food frequency questionnaire with a supplementary section for the assessment of dietary aspects and physical activity levels. Additionally, the KIDMED index was used to evaluate the degree of adherence to the MD. RESULTS: According to the IOTF cut-offs, overweight (OW) and obesity (OB) prevalence among boys was 29.9% and 12.9%, while in girls 29.2% and 10.6%, respectively. Only 4.3% of the children had an optimal KIDMED score. KIDMED score did not differ between boys and girls and no differences were detected between normal weight and OW and OB children. However, children from semi-urban or rural regions had higher score. Furthermore, children with higher KIDMED score reported following a healthier diet and having higher physical activity levels. CONCLUSION: The prevalence of childhood obesity in Greece is the highest ever reported together with low adherence rates to the dietary patterns of the MD. Current findings suggest an increased risk for even higher rates of obesity in adolescence and adulthood in the near future. Taking into account that children are also abandoning the traditional cardio-protective MD, the increased risk for future adverse health consequences seems evident.

High sodium intake of children through 'hidden' food sources and its association with the Mediterranean diet: the GRECO study.

OBJECTIVES: Sodium is the mineral that has been, mainly, linked to hypertension and cardiovascular disease. It is found naturally in many foods, but is also used in the food industry and manufacturing. Identification of total sodium intake, as well as 'hidden' sodium intake from food sources early in life is necessary. METHODS: Four thousand, five hundred and eighty children aged 10-12 years were enrolled, in a cross-sectional, population-based survey. Among other measurements, dietary data were obtained by a semi-quantitative food frequency questionnaire, and sodium intake was calculated. High sodium consumption was considered an intake over 2200 mg/day. Adherence to the Mediterranean dietary pattern was evaluated using the Mediterranean Diet Quality Index for children and adolescent score (KIDMED score). RESULTS: Twenty-three percent of Greek children had sodium intake which exceeded the 2200 mg/day recommendation, excluding salt added at table and during cooking. Sodium intake was found elevated in children with moderate and high adherence to the Mediterranean Diet. Additionally, 1 unit increase in KIDMED score (i.e. higher adherence) was associated with 10% [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.07-1.13] increased likelihood of consuming sodium above the median intake (i.e. >1500 mg/day). Thirty-four percent of sodium intake from 'hidden' sources came from bread, processed cereals and white cheese. CONCLUSIONS: Greek children have an elevated sodium intake from 'hidden' sources and main contributors are foods which are recommended to be consumed on a daily basis according to the Mediterranean Diet Pyramid. These findings should induce manufacturers to reduce the amount of sodium added during processing of 'healthy' foods, especially bread and cheese.

Short-term effects of a snack including dried prunes on energy intake and satiety in normal-weight individuals.

The purpose of this study was to test the hypothesis that a preload including dried prunes consumed as a snack before a meal, compared to an isoenergetic and equal weighed bread product preload would: (a) have greater short-term effect on satiety measured by subsequent ad libitum meal intake, (b) induce greater satiety as assessed by visual analogue scales (VAS), and (c) reduce appetite for dessert offered shortly after lunch. Forty-five healthy, normal-weight subjects participated in this randomised within-subject crossover study. Statistical analysis of the results showed that when subjects consumed the preload that included dried prunes, also consumed less amount of dessert and had lower total energy intake at meal. Additionally, subjects' feeling of hunger, desire and motivation to eat, as assessed with the use of VAS, were lower at all time points between snack and meal. Since macronutrients content of both preloads were similar, the satiating power of prunes could be due to their relatively high fiber content. Identifying meal patterns and foods that promote satiety without increasing considerably the overall energy intake is very important. The addition of dried prunes to a snack seems to promote satiety besides providing valuable nutrients.

Obesity indices in relation to cardiovascular disease risk factors among young adult female students.

The objective of the present study was to compare the percentage of body fat (%BF), BMI, and central fat distribution anthropometric measures as indices of obesity and to assess the respective associations with cardiovascular risk factors in young female students. Subjects were 220 healthy Greek female students. Dual-energy X-ray absorptiometry was used to estimate %BF, anthropometric measurements were obtained and blood samples were analysed for CVD risk factors. Results showed that 48.6 % of students had increased adiposity, while a considerable proportion was characterised by central fat distribution irrespective of the anthropometric index used. The proportion of subjects with at least one metabolic risk factor present was 60.4 %. Although %BF was not associated with any of the CVD risk factors, waist circumference, waist:hip ratio and waist:height ratio were all associated with CVD risk factors. Higher levels of these anthropometric variables demonstrated higher prevalence of CVD risk factors. The lack of association between %BF and CVD risk factors could be attributed to the fact that females with undesirable adiposity had a tendency for the gynaecoid type of obesity. In contrast, the present results suggest that central body fat distribution in young women may reflect increased risk due to high visceral and particularly intra-abdominal fat levels. Recent epidemiological data from Greece show a high prevalence of overweight and obesity in young adults. Therefore, assessing the risk for the presence of CVD risk factors is of particular importance. Central obesity anthropometric indices seem to be valuable screening tools for young women.