The 2010 Dietary Guidelines for Americans (DGA) recommend nutrient needs be met by increasing fruit, vegetable, and whole-grain intake with the use of low-fat or fat-free dairy products and by ...reducing sodium, solid fats, and added sugars. However, the DGA, as a dietary pattern, have not been tested in an intervention trial.
The aim of this study was to evaluate the impact of a DGA-based diet compared with a representative typical American diet (TAD) on glucose homeostasis and fasting lipids in individuals at risk of cardiometabolic disease.
A randomized, double-blind, controlled 8-wk intervention was conducted in overweight and obese women selected according to indexes of insulin resistance or dyslipidemia. Women were randomly assigned to the DGA or TAD group (n = 28 DGA and 24 TAD). The TAD diet was based on average adult intake from the NHANES 2009–2010. The DGA and TAD diets had respective Healthy Eating Index scores of 98 and 62. All foods and beverages were provided during the intervention. Oral-glucose tolerance and fasting lipids were evaluated at 0, 2, and 8 wk of the intervention. Insulin resistance and sensitivity were estimated with the use of surrogates (e.g., homeostasis model assessment of insulin resistance).
By design, volunteers maintained their weight during the intervention. Fasting insulin, glucose, triglycerides, oral-glucose tolerance, and indexes of insulin resistance were not affected by either of the diets. Systolic blood pressure decreased in the DGA group (∼−9 mm Hg; P < 0.05). Total and HDL cholesterol also decreased in both groups (P < 0.05). Exploratory analysis comparing volunteers entering the study with insulin resistance and dyslipidemia with those with only dyslipidemia did not show an effect of pre-existing conditions on glucose tolerance or fasting lipid outcomes.
The consumption of a DGA dietary pattern for 8 wk without weight loss reduced systolic blood pressure. There were no differences between the DGA and TAD diets in fasting insulin, glucose, indexes of insulin resistance, or fasting lipids. This trial was registered at www.clinicaltrials.gov as NCT02298725.
To identify associations between circulating endocannabinoids and craving during the luteal phase of the menstrual cycle. This report is a secondary analysis of a trial registered in ...clinicaltrials.gov as NCT01407692.
Seventeen premenopausal women were studied during the follicular and luteal phases of their menstrual cycle. Previously we had reported fasting plasma estradiol, progesterone, leptin associations with luteal phase cravings for carbohydrate, fat, sweet-rich foods, and eating behavior. Here, we measured fasting plasma endocannabinoids (ECs) endocannabinoid-like substances (ECLs), and postprandial metabolic responses to a mixed meal challenge. Structural equation modeling was used to evaluate relationships between measured variables and cravings.
Oleoylethanolamide (OEA) and postprandial lipids were inversely associated with craving sweet-rich foods, while progesterone was positively associated (RMSEA = 0.041, χ2 p: 0.416 i.e. hypothetical and physiological models not different). OEA, progesterone and disinhibition were positively associated with craving carbohydrates (RMSEA: <0.001, χ2 p: 0.919). ECs and ECLs combined were stronger predictors of craving than clinical metabolic parameters, ECs only, satiety hormones or gonadocorticoids.
Our theoretical model suggests that ECs and ECLs influence craving. Since these metabolites can be modulated via dietary fat intake, they could be potential targets to alter menstrual cycle cravings.
Clinical Trial Registration Number: NCT01407692
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•Women experience craving and consume carbohydrate, fat and sweet-rich foods during luteal phase of the menstrual cycle•This can lead to weight gain over time, and thus far, ovarian hormones have been associated with cravings•In this study, endocannabinoids (AEA) and endocannabinoid like chemicals (OEA) were stronger predictors of craving than ovarian hormones•Our theoretical model suggests altering dietary fatty acid intake to help relieve cravings.
Risk stratification in Barrett's esophagus (BE) is challenging. We evaluated the ability of a panel of genetic markers to predict progression to high-grade dysplasia (HGD) or esophageal ...adenocarcinoma (EAC).
In this case-control study, we assessed a measure of genetic instability, the mutational load (ML), in predicting progression to HGD or EAC. Cases had nondysplastic BE or low-grade dysplasia (LGD) at baseline and developed HGD/EAC ≥1 year later. Controls were matched 2:1, had nondysplastic BE or LGD, and no progression at follow-up. Formalin-fixed, paraffin-embedded tissue was microdissected for the epithelium. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were assessed. ML was calculated from derangements in 10 genomic loci. High-clonality LOH mutations were assigned a value of 1, low-clonality mutations were assigned a value of 0.5, and MSI 0.75 at the first loci, and 0.5 for additional loci. These values were summed to the ML. Receiver operator characteristic (ROC) curves were created.
There were 69 patients (46 controls and 23 cases). Groups were similar in age, follow-up time, baseline histology, and the number of microdissected targets. Mean ML in pre-progression biopsies was higher in cases (2.21) than in controls (0.42; P<0.0001). Sensitivity was 100% at ML ≥0.5 and specificity was 96% at ML ≥1.5. Accuracy was highest at 89.9% for ML ≥1. ROC curves for ML ≥1 demonstrated an area under the curve (AUC) of 0.95.
ML in pre-progression BE tissue predicts progression to HGD or EAC. Although further validation is necessary, ML may have utility as a biomarker in endoscopic surveillance of BE.
The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its ...deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time.
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•Live quantification of RhoA activity during development and disease progression•Real-time visualization of RhoA signaling in normal skin, osteocytes, and neutrophils•Monitoring deregulation of RhoA activity in invasive mammary and pancreatic cancers•Longitudinal in vivo imaging of RhoA inhibition using optical windows
Nobis et al. generated a RhoA-FRET biosensor mouse to characterize and quantify the spatiotemporal distribution of RhoA activity in native mammalian tissues in vivo during development and disease progression. They show that RhoA activity is tightly regulated during various normal biological processes and is co-opted in disease settings, such as invasive breast and pancreatic cancers.
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Objective
Food craving and intake are affected by steroid hormones during the menstrual cycle, especially in the luteal phase, when craving for certain foods has been reported to ...increase. However, satiety hormones such as leptin have also been shown to affect taste sensitivity, and therefore food choices. While in vitro studies have reported that estradiol can stimulate leptin release, some human studies have shown that leptin is inversely associated with estradiol. On the contrary, progesterone has been positively associated with leptin, and therefore may play a significant role in food intake regulation. Our objective was to characterize the associations between sex steroid hormones, leptin and food intake behavior.
Methods
Seventeen healthy, women with regular menstrual cycles, 23.2 ± 4.8 y, and BMI 22.4 ±1.9 kg/m
2
were studied during their late follicular and luteal phases. Estradiol, progesterone, DHEAS, SHBG, leptin and insulin were measured in fasting samples. In addition, volunteers were asked to answer validated “Food Craving inventory” (FCI) and “Carbohydrate Rich Food intake” (CRFI) questionnaires at the start of the study. The FCI captured information regarding the types of foods volunteers were craving – rich in fat, carbohydrate or sweet taste, followed by beverages and fast foods over a three month period prior to starting the study. The CFRI captured information with regard to consumption of these same foods. We used Pearson's correlation coefficients to identify positive or inverse associations between hormones and subjective food intake and craving scores.
Results
Estradiol, progesterone and leptin were not associated with each other. However, women with higher estradiol during the luteal phase reported consuming more carbohydrate‐rich foods in the past three months (r = 0.5174; p = 0.034), while also reporting increased craving for sweet foods (r = 0.4922; p = 0.045). Higher progesterone in the luteal phase was weakly associated with higher craving for sweetened beverages (
r = 0.4723, p = 0.056
). As expected, leptin was inversely associated with reported consumption of sweet tasting foods (r = −0.5071; p = 0.038), while also being inversely associated with craving fat rich foods (r = −0.4851; p = 0.048).
Conclusions
Estradiol is associated with increased carbohydrate rich food intake, while progesterone with craving sweetened beverage intake. Leptin, while being associated with reduced craving for fat‐rich food, and reduced sweet food intake, however, appears to not be associated with estradiol and progesterone, thereby suggesting that the female sex steroid hormones may be independent influences on food intake behaviors. Understanding the changes of estradiol, progesterone and leptin in women could clinically aid in advocating food choices during the pre‐menstrual phase.
Support or Funding Information
USDA projects #2032‐51530‐022 and #5306‐51530‐019
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BMI is a widely used anthropometric measure for identifying CVD and metabolic syndrome (MetS) risk. Two new anthropometric indices are A Body Shape Index (ABSI) and Body Roundness Index ...(BRI) that may provide better correlations to features of MetS.
Methods
Subject data were obtained from 91 overweight or obese (BMI 31.8 kg/m2 ± 3.7) women who screened for participation in a dietary pattern intervention study (NCT02298725). The screening consisted of collecting anthropometric, blood biomarker, and blood pressure measures. The screening measures were performed to identify participants who have metabolic syndrome.
Results
Ninety one participants were successfully screened for symptoms of metabolic syndrome. Three anthropometric indices, BMI, ABSI, and BRI, were used to find correlations with clinical measures of MetS. Fasting OGTT Glucose (FG), Two Hour OGTT Glucose (Gluc‐2Hr), Hemoglobin A1c (HbA1C), and Quantitative Insulin Sensitivity Check Index (QUICKI) did not significantly correlate with any of these indices. All of these indices had a significant correlation with Triglyceride (TG) and log HOMA (Homeostatic Model Assessment). BRI and BMI had high correlations with several blood measures that are indicative of MetS.
Out of the anthropometric indices studied, BRI was significantly correlated with TG (r=0.362), HDL (r=−0.418) and HOMA (r=0.303). BMI was significantly correlated with HOMA (r=0.400), log HOMA (r=0.405), and the Matsuda Index (r=−0.255). Although demonstrating significant correlations with several measures, ABSI had weaker correlations than both BRI and BMI in all cases.
It is also of note that there is significant difference between the mean ABSI of participants who had one or less, two, or three or more primary parameters of MetS (p=0.0008). Similarly, the mean BRI of participants in these MetS groups were also different (p<0.001).
Conclusion
In general, BRI showed a stronger relationship to dyslipidemic measures while BMI showed a stronger relationship to glucose intolerance. Both ABSI and BRI showed significant differences between participants who had ≤1 feature of MetS and those who had ≥3 features of MetS, suggesting a potential role of ABSI and BRI as anthropometric indices for predicting MetS. With our next 100 screened participants we will be using these indices to validate these relationships.
Support or Funding Information
National Dairy Council and USDA project #2032‐51530‐022.
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Objective
To evaluate the impact of circulating endocannabinoids on food craving, food intake behaviors, and satiety hormones across the menstrual cycle.
Methods
We studied 17 ...premenopausal women with regular menstrual cycles (23.2 ± 4.8 y, and BMI 22.4 ±1.9 kg/m
2
) during their late follicular and luteal phases. We measured fasting plasma estradiol, progesterone and leptin using electrochemiluminescence, and serum endocannabinoids using targeted LC‐MS/MS methods. Measured endocannabinoids and endocannabinoid‐like compounds included monoacylglycerol derivatives of arachidonate, linoleate and oleate (1‐ and 2‐AG, LG and OG, respectively), and acylethanolamides anandamide (AEA), stearoylethanolamide (SEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and docosatetraenoylethanolamide (DEA). We used a food craving inventory during the luteal phase to record cravings for sweet‐tasting and fat‐rich foods. We used the same construct to evaluate habitual intake in the three‐month period prior to the study. Three‐factor eating questionnaire was used once during the study to evaluate cognitive restraint, disinhibition, and hunger in these women. Spearman's correlation analyses were used to identify associations between ovarian hormones, endocannabinoids, leptin and eating behaviors. Wilcoxon's rank tests were used to evaluate differences between the phases of the menstrual cycle.
Results
Serum endocannabinoids were not different between the two phases of the menstrual cycle (eg: 2‐AG: p = 0.38). Irrespective of phase, several endocannabinoids were inversely associated with estradiol (Eg: 2‐OG: r = −0.39, p = 0.02; 2‐AG: r = −0.30, p = 0.09). Also, disinhibition was inversely associated with leptin (r = −0.54, p <0.01), and positively associated with habitual intake of sweet‐rich foods (r = 0.45, p <0.01). While evaluating only the luteal phase, OEA was positively associated with craving fat‐rich foods (r=0.61, p=0.01). Endocannabinoids were inversely associated with leptin (1‐OG: r =−0.56, p=0.02; 1‐LG: r=−0.50, p=0.04; 2‐AG: r= −0.44, p= 0.07), and cognitive restraint (2‐AG: r =−0.49, p=0.04; AEA: r=−0.57, p=0.02), while cognitive restraint was positively associated with craving sweet‐rich foods (r=0.49, p=0.05). Both SEA and PEA were positively associated with circulating progesterone (r=0.60, p=0.01; r=0.52, p =0.03 respectively), while AEA and 2‐AG showed a positive trend with progesterone/estradiol ratio (r=0.45, p=0.07; r=0.42, p=0.09 respectively). These associations were not present in the follicular phase.
Conclusions
The association of endocannabinoids with leptin, progesterone and increased fat‐rich food craving during the luteal phase warrants further study into what role they play in food intake regulation during the menstrual cycle.
Support or Funding Information
USDA‐ARS‐CRIS Project 2032‐51530‐022‐00D
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Objective
To devise a dietary adherence monitoring tool for use in controlled human feeding trials involving free‐living study participants.
Methods
A scoring tool was devised to ...measure and track dietary adherence for an 8‐wk randomized trial evaluating the effects of two different dietary patterns on metabolic health outcomes. One dietary pattern is based on the 2010 Dietary Guidelines for Americans; and the other using recent dietary intake data from the What We Eat In America (WWEIA) National survey. In our trial, all foods and beverages are provided to the study participants. The scoring system is a modified version of that used in the
Dietary Approaches to Stop Hypertension (DASH)
feeding study. Study volunteers maintain detailed daily food logs that are used to score their adherence in these categories. These scores are then adjusted using weigh‐backs of foods not consumed, when a discrepancy between self‐report and weigh backs arise. Adherence scores are assigned on a daily basis to four categories: 1) adherence to the provided study foods (SF), 2) intake of non‐study foods (NSF), 3) intake of coffee or tea that was not provided (C/T), and 4) addition of salt, pepper, herbs or other spices (S/P/S). A score of 0 indicates complete adherence in all categories. For the study and non‐study food categories, scores of 1, 2 or 3 represent deviations of <1, 1–2.9, or ≥ 3 servings/d. In the C/T or S/P/S categories, scores of 1 indicate that these items were added by the participant. A Wilcoxon's signed‐rank test was used to compare the difference in adherence between SF and NSF.
Results
Scores for the first ten participants suggest that deviations from adhering to eating all of the study foods (0.6 ± 1.0) were greater than deviations from eating non‐study foods (0.1 ± 0.5) (p=0.002). There were only a total of 10 reported instances of C/T deviations and 4 of S/P/S deviations during the full 8‐wk study for these ten participants.
Conclusions
The scoring tool enables us to closely follow free‐living participants on a daily basis in controlled feeding trials and has the potential to improve adherence while the volunteer is actively enrolled in the study. In our study, this scoring tool will be paired with additional objective checks of adherence, including measurements of body weight and urinary nitrogen, sodium and potassium to more fully characterize dietary adherence.
Support or Funding Information
Supported by National Dairy Council, Campbell Soup Company, and the USDA project number #2032‐51530‐022
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