No evidence of compensatory changes in energy balance, despite reductions in body weight and liver fat, during dapagliflozin treatment in type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled, cross-over trial (ENERGIZE).

AIM: This study assessed the impact of dapagliflozin on food intake, eating behaviour, energy expenditure, magnetic resonance imaging (MRI)-determined brain response to food cues and body composition in patients with type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: Patients were given dapagliflozin 10 mg once daily in a randomized, double-blind, placebo-controlled trial with short-term (1 week) and long-term (12 weeks) cross-over periods. The primary outcome was the difference in test meal food intake between long-term dapagliflozin and placebo treatment. Secondary outcomes included short-term differences in test meal food intake, short- and long-term differences in appetite and eating rate, energy expenditure and functional MRI brain activity in relation to food images. We determined differences in glycated haemoglobin, weight, liver fat (by 1 H magnetic resonance spectroscopy) and subcutaneous/visceral adipose tissue volumes (by MRI). RESULTS: In total, 52 patients (43% were women) were randomized; with the analysis of 49 patients: median age 58 years, weight 99.1 kg, body mass index 35 kg/m2 , glycated haemoglobin 49 mmol/mol. Dapagliflozin reduced glycated haemoglobin by 9.7 mmol/mol [95% confidence interval (CI) 3.91-16.27, p = .004], and body weight (-2.84 vs. -0.87 kg) versus placebo. There was no short- or long-term difference in test meal food intake between dapagliflozin and placebo [mean difference 5.7 g (95% CI -127.9 to 139.3, p = .933); 15.8 g (95% CI -147.7 to 116.1, p = .813), respectively] nor in the rate of eating, energy expenditure, appetite, or brain responses to food cues. Liver fat (median reduction -4.7 vs. 1.95%), but not subcutaneous/visceral adipose tissue, decreased significantly with 12 weeks of dapagliflozin. CONCLUSIONS: The reduction in body weight and liver fat with dapagliflozin was not associated with compensatory adaptations in food intake or energy expenditure.

Guilt, shame, and postpartum infant feeding outcomes: A systematic review.

Negative maternal affect (e.g., depression and anxiety) has been associated with shorter breastfeeding duration and poorer breastfeeding intention, initiation, and exclusivity. Other affective states, including guilt and shame, have been linked with formula feeding practice, though existing literature has yet to be synthesised. A narrative synthesis of quantitative data and a framework synthesis of qualitative and quantitative data were conducted to explore guilt and/or shame in relation to infant feeding outcomes. Searches were conducted on the DISCOVER database between December 2017 and March 2018. The search strategy was rerun in February 2020, together yielding 467 studies. The study selection process identified 20 articles, published between 1997 and 2017. Quantitative results demonstrated formula feeders experienced guilt more commonly than breastfeeding mothers. Formula feeders experienced external guilt most commonly associated with healthcare professionals, whereas breastfeeding mothers experienced guilt most commonly associated with peers and family. No quantitative literature examined shame in relation to infant feeding outcomes, warranting future research. The framework synthesis generated four distinct themes which explored guilt and/or shame in relation to infant feeding outcomes: 'underprepared and ineffectively supported', 'morality and perceived judgement' (breastfeeding), 'frustration with infant feeding care' and 'failures, fears and forbidden practice' (formula feeding). Both guilt and shame were associated with self-perception as a bad mother and poorer maternal mental health. Guilt and shame experiences were qualitatively different in terms of sources and outcomes, dependent on infant feeding method. Suggestions for tailored care to minimise guilt and shame, while supporting breastfeeding, are provided.

Nondigestible Carbohydrates Affect Metabolic Health and Gut Microbiota in Overweight Adults after Weight Loss.

BACKGROUND: The composition of diets consumed following weight loss (WL) can have a significant impact on satiety and metabolic health. OBJECTIVE: This study was designed to test the effects of including a nondigestible carbohydrate to achieve weight maintenance (WM) following a period of WL. METHODS: Nineteen volunteers [11 females and 8 males, aged 20-62 y; BMI (kg/m2): 27-42] consumed a 3-d maintenance diet (15%:30%:55%), followed by a 21-d WL diet (WL; 30%:30%:40%), followed by 2 randomized 10-d WM diets (20%:30%:50% of energy from protein:fat:carbohydrate) containing either resistant starch type 3 (RS-WM; 22 or 26 g/d for females and males, respectively) or no RS (C-WM) in a within-subject crossover design without washout periods. The primary outcome, WM after WL, was analyzed by body weight. Secondary outcomes of fecal microbiota composition and microbial metabolite concentrations and gut hormones were analyzed in fecal samples and blood plasma, respectively. All outcomes were assessed at the end of each dietary period. RESULTS: Body weight was similar after the RS-WM and C-WM diets (90.7 and 90.8 kg, respectively), with no difference in subjectively rated appetite. During the WL diet period plasma ghrelin increased by 36% (P < 0.001), glucose-dependent insulinotropic polypeptide (GIP) decreased by 33% (P < 0.001), and insulin decreased by 46% (P < 0.001), but no significant differences were observed during the RS-WM and C-WM diet periods. Fasting blood glucose was lower after the RS-WM diet (5.59 ± 0.31 mmol/L) than after the C-WM diet [5.75 ± 0.49 mmol/L; P = 0.015; standard error of the difference between the means (SED): 0.09]. Dietary treatments influenced the fecal microbiota composition (R2 = 0.054, P = 0.031) but not diversity. CONCLUSIONS: The metabolic benefits, for overweight adults, from WL were maintained through a subsequent WM diet with higher total carbohydrate intake. Inclusion of resistant starch in the WM diet altered gut microbiota composition positively and resulted in lower fasting glucose compared with the control, with no apparent change in appetite. This trial was registered at clinicaltrials.gov as NCT01724411.

Short-term decreased physical activity with increased sedentary behaviour causes metabolic derangements and altered body composition: effects in individuals with and without a first-degree relative with type 2 diabetes.

AIMS/HYPOTHESIS: Low physical activity levels and sedentary behaviour are associated with obesity, insulin resistance and type 2 diabetes. We investigated the effects of a short-term reduction in physical activity with increased sedentary behaviour on metabolic profiles and body composition, comparing the effects in individuals with first-degree relatives with type 2 diabetes (FDR+ve) vs those without (FDR-ve). METHODS: Forty-five habitually active participants (16 FDR+ve [10 female, 6 male] and 29 FDR-ve [18 female, 11 male]; age 36 ± 14 years) were assessed at baseline, after 14 days of step reduction and 14 days after resuming normal activity. We determined physical activity (using a SenseWear armband), cardiorespiratory fitness ([Formula: see text]), body composition (dual-energy x-ray absorptiometry/magnetic resonance spectroscopy) and multi-organ insulin sensitivity (OGTT) at each time point. Statistical analysis was performed using a two-factor between-groups ANCOVA, with data presented as mean ± SD or (95% CI). RESULTS: There were no significant between-group differences in physical activity either at baseline or following step reduction. During the step-reduction phase, average daily step count decreased by 10,285 steps (95% CI 9389, 11,182; p < 0.001), a reduction of 81 ± 8%, increasing sedentary time by 223 min/day (151, 295; p < 0.001). Pooling data from both groups, following step reduction there was a significant decrease in whole-body insulin sensitivity (Matsuda index) (p < 0.001), muscle insulin sensitivity index (p < 0.001), cardiorespiratory fitness (p = 0.002) and lower limb lean mass (p = 0.004). Further, there was a significant increase in total body fat (p < 0.001), liver fat (p = 0.001) and LDL-cholesterol (p = 0.013), with a borderline significant increase in NEFA AUC during the OGTT (p = 0.050). Four significant between-group differences were apparent: following step reduction, FDR+ve participants accumulated 1.5% more android fat (0.4, 2.6; p = 0.008) and increased triacylglycerol by 0.3 mmol/l (0.1, 0.6; p = 0.044). After resuming normal activity, FDR+ve participants engaged in lower amounts of vigorous activity (p = 0.006) and had lower muscle insulin sensitivity (p = 0.023). All other changes were reversed with no significant between-group differences. CONCLUSIONS/INTERPRETATION: A short-term reduction in physical activity with increased sedentary behaviour leads to a reversible reduction in multi-organ insulin sensitivity and cardiorespiratory fitness, with concomitant increases in central and liver fat and dyslipidaemia. The effects are broadly similar in FDR+ve and FDR-ve individuals. Public health recommendations promoting physical activity should incorporate advice to avoid periods of sedentary behaviour.

Dishware size and snack food intake in a between-subjects laboratory experiment.

OBJECTIVE: The use of smaller dishware as a way of reducing food consumption has intuitive appeal and is recommended to the general public. Recent experimental studies have failed to find an effect of plate size on food intake, although the methods used across studies have varied. The aim of the present study was to examine the effect that bowl size had on snack food consumption in a 'typical' snacking context (snacking while watching television). DESIGN: Between-subjects. SETTING: Laboratory experiment. SUBJECTS: Sixty-one adult participants served themselves and ate popcorn while watching television. Participants were randomly assigned to serve themselves with and eat from either a small or a large bowl. RESULTS: The use of a smaller bowl size did not reduce food consumption. Unexpectedly, participants in the small bowl condition tended to consume more popcorn (34·0 g) than participants in the large bowl condition (24·9 g; 37 % increase, d=0·5), although the statistical significance of this difference depended on whether analyses were adjusted to account for participant characteristics (e.g. gender) associated with food intake (P=0·02) or not (P=0·07). CONCLUSIONS: Counter to widely held belief, the use of a smaller bowl did not reduce snack food intake. Public health recommendations advising the use of smaller dishware to reduce food consumption are premature, as this strategy may not be effective.

Maternal guilt and shame in the postpartum infant feeding context: A concept analysis.

Background After birth, guilt and shame are differentially experienced by breastfeeding and formula feeding mothers. Despite this, currently utilized guilt and shame definitions lack context specificity, leaving concepts open to misinterpretation. Objective The current study aimed to develop infant feeding-specific definitions of postpartum guilt and shame. Methods Study selection involved a three-stage systematic screening process, outlined in Jackson et al. (2021). Walker and Avant's (2005, 2019) concept analysis framework was then applied to included articles to identify guilt-specific, shame-specific, and overlapping attributes, antecedents, and consequences. Results A guilt-specific, shame-specific, and overlapping definition were generated based on exclusive and overlapping antecedents, attributes, and consequences. Guilt and shame belonged to the empirical referent Moral Emotions, which may explain some of the overlapping antecedents, attributes, and consequences identified during analysis. Conclusions The overlapping definition provides a broad scope for shared characteristics, while specific definitions allow for more in-depth and focused investigations of guilt and shame experiences within an infant feeding context. Utilising context-specific definitions may serve to improve research homogeneity. Shame was found to be uniquely associated with postnatal depression. As such, suggestions are made for future research to further investigate the relationship between shame, infant feeding, and maternal wellbeing outcomes. Implications Identified antecedents may be used by healthcare professionals to provide additional support to mothers at risk of experiencing guilt and shame, to prevent the occurrence and consequences of these emotions.

Circulating Metabolites Associated with Postprandial Satiety in Overweight/Obese Participants: The SATIN Study.

Scope: To identify a metabolomic profile related to postprandial satiety sensations involved in appetite control would help for a better understanding of the regulation of food intake. Methods and Results: A cross-sectional analysis of plasma metabolites was conducted over 151 overweight/obese adults from the "Satiety Innovation"-SATIN study, a randomized clinical trial of a 12-week weight-loss maintenance period. Postprandial satiety sensations (3 h-iAUC) were assessed by visual analogue scale (VAS) at the beginning and at the end of the study. Fasting plasma metabolites were profiled using a targeted multiplatform metabolomics approach before each appetite test meal. Associations between 124 metabolites and iAUC-satiety were assessed using elastic net linear regression analyses. The accuracy of the multimetabolite weighted models for iAUC-VAS was evaluated using a 10-fold cross-validation (CV) approach and the Pearson's correlation coefficients were estimated. Five and three metabolites were selected in the first and the second assessments, respectively. Circulating glycine and linoleic acid concentrations were consistently and positively associated with higher iAUC-satiety in both visits. Sucrose and sphingomyelins (C32:2, C38:1) were negatively associated with iAUC-satiety in the first visit. The Pearson correlations coefficients between the metabolomic profiles and iAUC-satiety in the first and the second appetite assessments were 0.37 and 0.27, respectively. Conclusion: Higher glycine and linoleic acid were moderately but consistently associated with higher postprandial satiety in two different appetite assessments in overweight and obese subjects.

A rational review on the effects of sweeteners and sweetness enhancers on appetite, food reward and metabolic/adiposity outcomes in adults.

Numerous strategies have been investigated to overcome the excessive weight gain that accompanies a chronic positive energy balance. Most approaches focus on a reduction of energy intake and the improvement of lifestyle habits. The use of high intensity artificial sweeteners, also known as non-caloric sweeteners (NCS), as sugar substitutes in foods and beverages, is rapidly developing. NCS are commonly defined as molecules with a sweetness profile of 30 times higher or more that of sucrose, scarcely contributing to the individual's net energy intake as they are hardly metabolized. The purpose of this review is first, to assess the impact of NCS on eating behaviour, including subjective appetite, food intake, food reward and sensory stimulation; and secondly, to assess the metabolic impact of NCS on body weight regulation, glucose homeostasis and gut health. The evidence reviewed suggests that while some sweeteners have the potential to increase subjective appetite, these effects do not translate in changes in food intake. This is supported by a large body of empirical evidence advocating that the use of NCS facilitates weight management when used alongside other weight management strategies. On the other hand, although NCS are very unlikely to impair insulin metabolism and glycaemic control, some studies suggest that NCS could have putatively undesirable effects, through various indirect mechanisms, on body weight, glycemia, adipogenesis and the gut microbiota; however there is insufficient evidence to determine the degree of such effects. Overall, the available data suggests that NCS can be used to facilitate a reduction in dietary energy content without significant negative effects on food intake behaviour or body metabolism, which would support their potential role in the prevention of obesity as a complementary strategy to other weight management approaches. More research is needed to determine the impact of NCS on metabolic health, in particular gut microbiota.

Plasma metabolites associated with homeostatic model assessment of insulin resistance: metabolite-model design and external validation.

Different plasma metabolites have been related to insulin resistance (IR). However, there is a lack of metabolite models predicting IR with external validation. The aim of this study is to identify a multi-metabolite model associated to the homeostatic model assessment (HOMA)-IR values. We performed a cross-sectional metabolomics analysis of samples collected from overweight and obese subjects from two independent studies. The training step was performed in 236 subjects from the SATIN study and validated in 102 subjects from the GLYNDIET study. Plasma metabolomics profile was analyzed using three different approaches: GC/quadrupole-TOF, LC/quadrupole-TOF, and nuclear magnetic resonance (NMR). Associations between metabolites and HOMA-IR were assessed using elastic net regression analysis with a leave-one-out cross validation (CV) and 100 CV runs. HOMA-IR was analyzed both as linear and categorical (median or lower versus higher than the median). Receiver operating characteristic curves were constructed based on metabolites' weighted models. A set of 30 metabolites discriminating extremes of HOMA-IR were consistently selected. These metabolites comprised some amino acids, lipid species and different organic acids. The area under the curve (AUC) for the discrimination between HOMA-IR extreme categories was 0.82 (95% CI: 0.74-0.90), based on the multi-metabolite model weighted with the regression coefficients of metabolites in the validation dataset. We identified a set of metabolites discriminating between extremes of HOMA-IR and able to predict HOMA-IR with high accuracy.

Compensatory changes in energy balance during dapagliflozin treatment in type 2 diabetes mellitus: a randomised double-blind, placebo-controlled, cross-over trial (ENERGIZE)-study protocol.

INTRODUCTION: Sodium glucose cotransporter 2 (SGLT2) inhibitors are effective blood-glucose-lowering medications with beneficial effects on body weight in patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is less than that predicted from quantified glycosuria, suggesting a compensatory increase in energy intake or a decrease in energy expenditure. Studies using dual-energy X-ray absorptiometry (DEXA) have suggested most body weight change is due to loss of adipose tissue, but organ-specific changes in fat content (eg, liver, skeletal muscle) have not been determined. In this randomised, double-blind, placebo-controlled crossover study, we aim to study the compensatory changes in energy intake, eating behaviour and energy expenditure accompanying use of the SGLT2 inhibitor, dapagliflozin. Additionally, we aim to quantify changes in fat distribution using MRI, in liver fat using proton magnetic resonance spectroscopy (1H-MRS) and in central nervous system (CNS) responses to food images using blood oxygen level dependent (BOLD) functional MRI (fMRI). METHODS AND ANALYSIS: This outpatient study will evaluate the effect of dapagliflozin (10 mg), compared with placebo, on food intake and energy expenditure at 7 days and 12 weeks. 52 patients with T2DM will be randomised to dapagliflozin or placebo for short-term and long-term trial interventions in a within participants, crossover design. The primary outcome is the difference in energy intake during a test meal between dapagliflozin and placebo. Intake data are collected automatically using a customised programme operating a universal eating monitor (UEM). Secondary outcomes include (1) measures of appetite regulation including rate of eating, satiety quotient, appetite ratings (between and within meals), changes in CNS responses to food images measured using BOLD-fMRI, (2) measures of energy expenditure and (3) changes in body composition including changes in liver fat and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). ETHICAL APPROVAL: This study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/0340) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice (GCP). TRIAL REGISTRATION NUMBER: ISRCTN14818531. EUDRACT number 2013-004264-60.