The protective effect of dietary folate intake on gastric cancer is modified by alcohol consumption: A pooled analysis of the StoP Consortium.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 µg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85-1.56), and the OR100 µg/day = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.

Dietary intake of copper and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Evidence on the potential association between dietary copper intake and gastric cancer (GC) is lacking. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project-an international consortium of epidemiological studies on GC. METHODS: Data from five case-control studies within the StoP Project were included (2448 cases, 4350 controls). We estimated adjusted odds ratios (ORs) and 95% CIs for the association between dietary copper intake and GC using multivariable mixed-effects logistic regression models. We also modelled the dose-response relationship between copper intake and GC using a logistic mixed-effects model with fractional polynomial. RESULTS: The OR for the highest quartile of copper intake compared with the lowest one was 0.78 (95% CI: 0.63-0.95; P for trend = 0.013). Results were similar for non-cardia-type (OR: 0.72; 95% CI: 0.57-0.91), intestinal-type (OR: 0.75; 95% CI: 0.56-0.99) and other histological-type GC (OR: 0.65; 95% CI: 0.44-0.96). The dose-response analysis showed a steep decrease in ORs for modest intakes (<1 mg/day), which were subsequently steady for ≤3 mg/day (OR: 0.09; 95% CI: 0.02-0.41) and slowly increased for higher intakes. CONCLUSIONS: The findings of our large study suggest that copper intake might be inversely associated with GC, although their confirmation by prospective studies is required.

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS: Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS: Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS: The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

The metabolic load-capacity model and cardiometabolic health in children and youth with obesity.

BACKGROUND: The metabolic load-capacity index (LCI), which represents the ratio of adipose to skeletal muscle tissue-containing compartments, is potentially associated with cardiometabolic diseases. OBJECTIVES: To examine the associations between the LCI and cardiometabolic risk factors in children and youth with obesity. METHODS: This is a cross-sectional study including 10-18 years-old participants with a BMI of ≥95th . LCI by air-displacement plethysmography (ADP) was calculated as fat mass divided by fat-free mass, and LCI by ultrasound (US) as subcutaneous adipose tissue divided by skeletal muscle thickness. Sex-specific medians stratified participants into high versus low LCI. Single (inflammation, insulin resistance, dyslipidemia and hypertension) and clustered cardiometabolic risk factors were evaluated. Linear and logistic regression models tested the associations between these variables, adjusted for sexual maturation. RESULTS: Thirty-nine participants (43.6% males; 59% mid-late puberty) aged 12.5 (IQR: 11.1-13.5) years were included. LCI by ADP was positively associated with markers of inflammation and dyslipidemia; having a higher LCI predicted dyslipidemia in logistic regression. Similarly, LCI by US was positively associated with markers of dyslipidemia and blood pressure. In mid-late pubertal participants, LCI by US was positively associated with markers of insulin resistance and inflammation. CONCLUSIONS: Participants with unfavourable cardiometabolic profile had higher LCI, suggesting its potential use for predicting and monitoring cardiometabolic health in clinical settings.

Revisiting the Calculation for a Novel Measure of Average Lifespan Shortened: Real-World Examples From Cervical and Ovarian Cancers in Alberta, Canada, 2000 - 2020.

In this technical note, we primarily demonstrate the computation of confidence limits for a novel measure of average lifespan shortened (ALSS). We identified women who had died from cervical and ovarian cancer between 2000 and 2020 from the Alberta cancer registry. Years of life lost (YLL) was calculated using the national life tables of Canada. We estimated the ALSS as a ratio of YLL in relation to the expected lifespan. We computed the confidence limits of the measure using various approaches, including the normal distribution, gamma distribution, and bootstrap method. The new ALSS measure shows a modest gain in lifespan of women, particularly women with ovarian cancer, over the study period.

Symptom severity and trajectories among adolescent and young adult patients with cancer.

BACKGROUND: Patients with cancer experience significant symptom burden. We investigated symptom severity in adolescents and young adults (18- to 39-year-olds) during the year following a cancer diagnosis and made comparisons with older adult (those older than 40 years of age) patients with cancer. METHODS: All Albertan residents diagnosed with a first primary neoplasm at 18 years of age or older between April 1, 2018, and December 31, 2019, and who completed at least 1 electronic patient-reported outcome questionnaire were included. Symptom severity was assessed using the Edmonton Symptom Assessment System-revised. Descriptive statistics, multivariable logistic modeling, and mixed logistic regression modeling were used to describe symptom severity, identify risk factors, and assess symptom trajectories, respectively. RESULTS: In total, 473 and 322 adolescents and young adults completed a patient-reported outcomes questionnaire at diagnosis and 1 year after diagnosis, respectively. Adolescent and young adult patients with cancer reported high levels of tiredness, poor well-being, and anxiety. Important risk factors included metastatic disease, female sex, treatment types received, and age at diagnosis. Symptom severity varied by clinical tumor group, with those diagnosed with sarcoma having the worst scores for all symptoms at diagnosis and patients with intrathoracic or endocrine tumors having the worst scores for all symptoms at 1 year after diagnosis. Statistically significant differences in symptom severity over the 1-year period were observed between adolescents and young adults and older adults-specifically, the odds of having moderate to severe symptoms were statistically significantly greater among adolescents and young adults with respect to pain, tiredness, nausea, depression, anxiety, and poor well-being (all P < .01). CONCLUSIONS: A substantial proportion of adolescents and young adults experience moderate to severe symptoms during the year following diagnosis. Modifying existing supportive services and developing interventions based on the needs of adolescent and young adult patients with cancer could aid symptom control.

Dairy product consumption and risk of non-alcoholic fatty liver disease: A systematic review and meta-analysis of observational studies.

BACKGROUND AND AIMS: It is unclear whether regular consumption of dairy products is associated with the risk of developing non-alcoholic fatty liver disease (NAFLD). Thus, we conducted a systematic review followed by a meta-analysis of studies reporting on the association of dairy consumption with NAFLD risk. METHODS AND RESULTS: We comprehensively searched PubMed, Web of Science, and Scopus for observational studies that evaluated the association between dairy intake and NAFLD likelihood that were published before September 1, 2022. The reported odds ratios (ORs) of fully adjusted models and their 95% confidence intervals (CIs) were pooled using a random-effects model for the meta-analysis. Out of 1206 articles retrieved, 11 observational studies, including 43,649 participants and 11,020 cases, were included. Pooled OR indicated a significant association between dairy intake and NAFLD (OR = 0.90; 95% CI: 0.83, 0.98; I2 = 67.8%, n = 11). Pooled ORs revealed that milk (OR: 0.86; 95% CI: 0.78, 0.95; I2 = 65.7%, n = 6), yogurt (OR: 0.88; 95% CI: 0.82; I2 = 0.0%, n = 4), and high-fat dairy (OR: 0.38; 95% CI: 0.19, 0.75; I2 = 0.0%, n = 5) consumption was inversely associated with NAFLD while cheese was not linked to NAFLD risk. CONCLUSION: We observed that consumption of dairy products is linked to a reduced risk of developing NAFLD. Overall, the data in the source articles is of low to moderate quality; therefore, further observational studies are required to support the current findings (PROSPERO Reg. number: CRD42022319028).

Adult height and risk of gastric cancer: a pooled analysis within the Stomach cancer Pooling Project.

BACKGROUND: The association between height and risk of gastric cancer has been studied in several epidemiological studies with contrasting results. The aim of this study is to examine the association between adult height and gastric cancer within a large pooled analysis of case-control studies members of the Stomach cancer Pooling (StoP) Project consortium. METHODS: Data from 18 studies members of the StoP consortium were collected and analyzed. A multivariable logistic regression model was used to estimate the study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between 10-cm increase in height and risk of gastric cancer. Age, sex, tobacco smoking, alcohol consumption, social class, geographical area and Helicobacter pylori (H. pylori ) status were included in the regression model. Resulting estimates were then pooled with random-effect model. Analyses were conducted overall and in strata of selected variables. RESULTS: A total of 7562 cases and 19 033 controls were included in the analysis. The pooled OR was 0.96 (95% CI 0.87-1.05). A sensitivity analysis was performed restricting the results to the studies with information on H. pylori status, resulting in an OR of 0.97 (95% CI 0.79-1.20). CONCLUSION: Our study does not support a strong and consistent association between adult height and gastric cancer.

Association of dairy consumption patterns with the incidence of type 2 diabetes: Findings from Alberta's Tomorrow Project.

BACKGROUND AND AIMS: We aimed to extract dairy consumption patterns of men and women from a population-based cohort and then assess the association of each consumption pattern with incident T2D risk. METHODS AND RESULTS: This prospective study was conducted within the framework of Alberta's Tomorrow Project (ATP), in which 8615 men and 15,016 women provided information on dietary intake by completing a food-frequency questionnaire at baseline, and then were followed up over time to determine the incidence of T2D via questionnaires. Principal Component Analysis (PCA) was used to extract dairy consumption patterns (DCPs). The association between each extracted pattern and T2D incidence was estimated using multivariable logistic regression models.The incidence of T2D among men and women was 3.8 and 3.2%, respectively, and the mean duration of follow-up was 5.2 years. Three major DCPs were identified. After controlling for potential confounders, the OR for risk of T2D in men in the highest compared with those in the lowest quartile of the DCP3 (whole milk, regular cheese, and non-fat milk as a beverage and in cereal) was 0.64 (95%CI: 0.47 to 0.88, P-trend=0.001), whereas it was not significant for women. DCP1 and DCP2 were not associated with incident T2D in men or women. CONCLUSION: Adherence to a DCP characterized by higher consumption of whole milk, regular cheese, and non-fat milk was associated with decreased risk of incident T2D only in men. Our results support current evidence that a combination of different dairy products, regardless of their fat content, might be favorable for health maintenance, at least in men.

Inverse Association between Dietary Iron Intake and Gastric Cancer: A Pooled Analysis of Case-Control Studies of the Stop Consortium.

Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 case-control studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83-0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77-0.94) and non-cardia GC (OR = 0.87, 95% CI = 0.81-0.94), and for diffuse (OR = 0.79, 95% CI = 0.69-0.89) and intestinal type (OR = 0.88, 95% CI = 0.79-0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis.

Salt intake and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

PURPOSE: Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project. METHODS: Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI). RESULTS: Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25-2.03), always using table salt (aOR 1.33, 95% CI 1.16-1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01-1.51) vs. the lowest tertile. No significant association was observed for the highest vs. the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82-1.43). The results obtained were consistent across anatomic sites, strata of Helicobacter pylori infection, and sociodemographic, lifestyle and study characteristics. CONCLUSION: Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake.

Allium vegetables intake and the risk of gastric cancer in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: The role of allium vegetables on gastric cancer (GC) risk remains unclear. METHODS: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. RESULTS: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I2 > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata. CONCLUSIONS: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.

Demographic and Clinicopathologic Distribution of Oral Cavity and Oropharyngeal Cancer in Alberta, Canada: A Comparative Analysis.

OBJECTIVES: The aims of this study were to determine demographic profiles, tumour characteristics and treatment factors related to oral cavity and oropharyngeal cancer (OCC and OPC) and comparatively analyze these cancers in the adult population of Alberta, Canada, over 12 years. METHODS: Demographic, tumour characteristics and treatment data regarding OCC and OPC incidence in Alberta residents ≥18 years in 2005-2017 were extracted from the Alberta Cancer Registry database. Age-standardized incidence and mortality rates (ASIR and ASMR) were computed. RESULTS: Among 3448 OCC and OPC cases, mean (standard deviation) age at diagnosis was 63.9 (14.4) and 60.1 (10.2) years, respectively. There was a male predilection for both OCC (58.2%) and OPC (81.7%). With some fluctuations, ASIR remained the same for OCC but increased for OPC. ASMR increased for both. The most common site for OCC was tongue and for OPC tonsil. Squamous cell carcinoma was the most common diagnosis for OCC and OPC. Involvement of at least 1 lymph node was observed in 38.5% of OCC and 85.8% of OPC cases. For 45.2% of OCC and 82.3% of OPC cases, diagnosis occurred at stage IV. The most common initial treatments for OCC were surgery, alone or combined with radiation, whereas radiation with chemotherapy was the main treatment modality for OPC. CONCLUSION: The incidence of OPC in younger males was higher than that of OCC. Although incidence of OPC per 100 000 population increased over the 12-year study period, it remained largely unchanged for OCC. For both cancers, initial diagnoses were made at advanced stages, with almost twice as many stage IV OPC cases than OCC cases.

Identifying the Profile of Helicobacter pylori-Negative Gastric Cancers: A Case-Only Analysis within the Stomach Cancer Pooling (StoP) Project.

BACKGROUND: The prevalence of Helicobacter pylori-negative gastric cancer (HpNGC) can be as low as 1%, when infection is assessed using more sensitive tests or considering the presence of gastric atrophy. HpNGC may share a high-risk profile contributing to the occurrence of cancer in the absence of infection. We estimated the proportion of HpNGC, using different criteria to define infection status, and compared HpNGC and positive cases regarding gastric cancer risk factors. METHODS: Cases from 12 studies from the Stomach cancer Pooling (StoP) Project providing data on H. pylori infection status determined by serologic test were included. HpNGC was reclassified as positive (eight studies) when cases presented CagA markers (four studies), gastric atrophy (six studies), or advanced stage at diagnosis (three studies), and were compared with positive cases. A two-stage approach (random-effects models) was used to pool study-specific prevalence and adjusted odds ratios (OR). RESULTS: Among non-cardia cases, the pooled prevalence of HpNGC was 22.4% (n = 166/853) and decreased to 7.0% (n = 55) when considering CagA status; estimates for all criteria were 21.8% (n = 276/1,325) and 6.6% (n = 97), respectively. HpNGC had a family history of gastric cancer more often [OR = 2.18; 95% confidence interval (CI), 1.03-4.61] and were current smokers (OR = 2.16; 95% CI, 0.52-9.02). CONCLUSION: This study found a low prevalence of HpNGC, who are more likely to have a family history of gastric cancer in first-degree relatives. IMPACT: Our results support that H. pylori infection is present in most non-cardia gastric cancers, and suggest that HpNGC may have distinct patterns of exposure to other risk factors.

Family History and Gastric Cancer Risk: A Pooled Investigation in the Stomach Cancer Pooling (STOP) Project Consortium.

Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64-2.04; I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82; 95% CI: 1.59-2.05 for subjects with FH) than for cardia GC (OR = 1.38; 95% CI: 0.98-1.77), and for the intestinal (OR = 1.92; 95% CI: 1.62-2.23) than for the diffuse histotype (OR = 1.62; 95% CI: 1.28-1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.

Average lifespan shortened due to breast cancer in Australia, 1990-2015.

BACKGROUND: This short report aims to investigate changes in lifespan of Australian women with breast cancer using the novel average lifespan shortened (ALSS) measure METHODS: We obtained the mortality data of Australian women with breast cancer from the World Health Organization mortality database for the 1990-2015 period. We calculated the age-standardized rate (ASR) according to the World Standard Population. We estimated the ALSS as a ratio of years of life lost in relation to the expected lifespan to examine changes in lifespan of Australian women with breast cancer over the study period. RESULTS: Over a 25-year period, the ASR of breast cancer deaths decreased from 20.5 to 12.6 deaths per 100,000 women. We observed a decline in ALSS values from 24.0% of their lifespan in 1990 to 22.0% in 2015. CONCLUSION: The novel ALSS measure indicates an improvement of two percentage points in the lifespan of Australian women with breast cancer over the study.

Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial.

BACKGROUND: Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome. METHODS: This is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12-18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids. DISCUSSION: This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04578652 . Registered on 8 October 2020.

Dietary habits and the 10-year risk of overweight and obesity in urban adult population: A cohort study predicated on Yazd Healthy Heart Project.

BACKGROUND AND OBJECTIVE: Overweight and obesity are thought to be associated with increased risk of chronic disease in the Middle East. The present study aimed to determine the association between dietary habits and the incidence of overweight and obesity in urban adult population in the central part of Iran after a 10-year follow-up. METHODS: This cohort study was initiated with 2000 participation aged 20-74 years from Yazd city in Iran based on Yazd Healthy Heart Project (YHHP). The participants without overweight and obesity at the baseline of the study were followed up to 10 years. Demographic data, anthropometric measurements, behavioral and metabolic risk factors of cardiovascular diseases and dietary habits were assessed at baseline and phase II. RESULTS: After a 10-year follow up, 516 non-overweight and 1068 non-obese participants were included for the final analysis. Once adjustments were made for all potential confounders including age, sex, smoking, economic status, physical activity and education, it was identified that lack of weight control increased the risk of obesity (hazard ratio; 95% CI) in total population (1.9; 1.06, 3.4), as well as the risk of overweight (2.39; 1.07, 5.27) and obesity (2.65; 1.13, 6.25) in men. Moreover, consumption of mayonnaise increased the 10-year risk of overweight in women (6.09; 1.2, 30.99). CONCLUSIONS: As revealed by the present study, unhealthy dietary habits can increase the incidence of overweight and obesity in central part of Iran. Therefore, changing the lifestyle appears to be urgent in reducing the risk of overweight and obesity.

Dietary macronutrient regulation of acyl and desacyl ghrelin concentrations in children with Prader-Willi syndrome (PWS).

BACKGROUND: The effects of dietary macronutrients on orexigenic and anorexigenic hormones in children are poorly understood. OBJECTIVE: To explore effects of varying dietary macronutrients on appetite-regulating hormones [acyl ghrelin (AG) and desacyl ghrelin (DAG), glucagon-like peptide 1 (GLP-1), peptide tyrosine tyrosine (PYY) and insulin] in children with PWS and healthy children (HC). DESIGN: Randomized, cross-over experiments compared two test diets [high protein-low carbohydrate (HP-LC) and high protein-low fat (HP-LF)] to a STANDARD meal (55% carbohydrate, 30% fat, 15% protein). Experiment 1 included ten children with PWS (median age 6.63 years; BMI z 1.05); experiment 2 had seven HC (median age 12.54 years; BMI z 0.95). Blood samples were collected at baseline and at 60-minute intervals for 4 hours. Independent linear mixed models were adjusted for age, sex and BMI z-score. RESULTS: Fasting and post-prandial AG and DAG concentrations are elevated in PWS children; the ratio of AG/DAG is normal. Food consumption reduced AG and DAG concentrations in both PWS and HC. GLP-1 levels were higher in PWS after the HP-LC and HP-LF meals than the STANDARD meal (P = .02-0.04). The fasting proinsulin to insulin ratio (0.08 vs 0.05) was higher in children with PWS (P = .05) than in HC. Average appetite scores in HC declined after all three meals (P = .02) but were lower after the HP-LC and HP-LF meals than the STANDARD meal. CONCLUSION: Altered processing of proinsulin and increased GLP-1 secretion in children with PWS after a high protein meal intake might enhance satiety and reduce energy intake.