Intra-pancreatic fat is associated with high circulating glucagon and GLP-1 concentrations following whey protein ingestion in overweight women with impaired fasting glucose: A randomised controlled trial.

AIM: Intra-pancreatic fat deposition (IPFD) while hypothesised to impair beta-cell function, its impact on alpha-cells remains unclear. We evaluated the association between IPFD and markers of pancreatic cells function using whey protein. METHODS: Twenty overweight women with impaired fasting glucose (IFG) and low or high IPFD (<4.66% vs ≥4.66%) consumed 3 beverage treatments: 0 g (water control), 12.5 g (low-dose) and 50.0 g (high-dose) whey protein, after an overnight fast, in randomised order. Blood glucose, insulin, C-peptide, glucagon, gastric-inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and amylin were analysed postprandially over 4 h. Incremental area-under-the-curve (iAUC), incremental maximum concentration (iCmax), and time to maximum concentration (Tmax) for these were compared between IPFD groups using repeated measures linear mixed models, also controlled for age (pcov). RESULTS: iAUC and iCmax glucose and insulin while similar between the two IPFD groups, high IPFD and ageing contributed to higher postprandial glucagon (iAUC: p = 0.012; pcov = 0.004; iCmax: p = 0.069; pcov = 0.021) and GLP-1 (iAUC: p = 0.006; pcov = 0.064; iCmax: p = 0.011; pcov = 0.122) concentrations. CONCLUSION: In our cohort, there was no evidence that IPFD impaired protein-induced insulin secretion. Conversely, IPFD may be associated with increased protein-induced glucagon secretion, a novel observation which warrants further investigation into its relevance in the pathogenesis of dysglycaemia and type-2 diabetes.

No Evidence That Circulating GLP-1 or PYY Are Associated with Increased Satiety during Low Energy Diet-Induced Weight Loss: Modelling Biomarkers of Appetite.

Bariatric surgery and pharmacology treatments increase circulating glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), in turn promoting satiety and body weight (BW) loss. However, the utility of GLP-1 and PYY in predicting appetite response during dietary interventions remains unsubstantiated. This study investigated whether the decrease in hunger observed following low energy diet (LED)-induced weight loss was associated with increased circulating 'satiety peptides', and/or associated changes in glucose, glucoregulatory peptides or amino acids (AAs). In total, 121 women with obesity underwent an 8-week LED intervention, of which 32 completed an appetite assessment via a preload challenge at both Week 0 and Week 8, and are reported here. Visual analogue scales (VAS) were administered to assess appetite-related responses, and blood samples were collected over 210 min post-preload. The area under the curve (AUC0-210), incremental AUC (iAUC0-210), and change from Week 0 to Week 8 (∆) were calculated. Multiple linear regression was used to test the association between VAS-appetite responses and blood biomarkers. Mean (±SEM) BW loss was 8.4 ± 0.5 kg (-8%). Unexpectedly, the decrease in ∆AUC0-210 hunger was best associated with decreased ∆AUC0-210 GLP-1, GIP, and valine (p < 0.05, all), and increased ∆AUC0-210 glycine and proline (p < 0.05, both). The majority of associations remained significant after adjusting for BW and fat-free mass loss. There was no evidence that changes in circulating GLP-1 or PYY were predictive of changes in appetite-related responses. The modelling suggested that other putative blood biomarkers of appetite, such as AAs, should be further investigated in future larger longitudinal dietary studies.

Effect of Cocoa Beverage and Dark Chocolate Consumption on Blood Pressure in Those with Normal and Elevated Blood Pressure: A Systematic Review and Meta-Analysis.

Cocoa is a major dietary source of polyphenols, including flavanols, which have been associated with reduced blood pressure (BP). While earlier systematic reviews and meta-analyses have shown significant effects of cocoa consumption on systolic BP, limitations include small sample sizes and study heterogeneity. Questions regarding food matrix and dose of polyphenols, flavanols, or epicatechins remain. This systematic review and meta-analysis aimed to investigate the effects of ≥2 weeks of cocoa consumption as a beverage or dark chocolate in those with normal or elevated (< or ≥130 mmHg) systolic BP measured in the fasted state or over 24-h. A systematic search conducted on PubMed and Cochrane Library databases up to 26 February 2022 yielded 31 suitable articles. Independent of baseline BP, cocoa consumption for ≥2 weeks was associated with reductions in systolic and diastolic BP (p < 0.05, all). Compared with cocoa, chocolate lowered the weighted mean of resting systolic BP (−3.94 mmHg, 95% CI [−5.71, −2.18]) more than cocoa beverage (−1.54 mmHg, 95% CI [−3.08, 0.01]). When the daily dose of flavanols was ≥900 mg or of epicatechin ≥100 mg, the effect was greater. Future, adequately powered studies are required to determine the optimal dose for a clinically significant effect.

Does a Higher Protein Diet Promote Satiety and Weight Loss Independent of Carbohydrate Content? An 8-Week Low-Energy Diet (LED) Intervention.

Both higher protein (HP) and lower carbohydrate (LC) diets may promote satiety and enhance body weight (BW) loss. This study investigated whether HP can promote these outcomes independent of carbohydrate (CHO) content. 121 women with obesity (BW: 95.1 ± 13.0 kg, BMI: 35.4 ± 3.9 kg/m2) were randomised to either HP (1.2 g/kg BW) or normal protein (NP, 0.8 g/kg BW) diets, in combination with either LC (28 en%) or normal CHO (NC, 40 en%) diets. A low-energy diet partial diet replacement (LEDpdr) regime was used for 8 weeks, where participants consumed fixed-energy meal replacements plus one ad libitum meal daily. Four-day dietary records showed that daily energy intake (EI) was similar between groups (p = 0.744), but the difference in protein and CHO between groups was lower than expected. Following multiple imputation (completion rate 77%), decrease in mean BW, fat mass (FM) and fat-free mass (FFM) at Week 8 in all was 7.5 ± 0.7 kg (p < 0.001), 5.7 ± 0.5 kg (p < 0.001), and 1.4 ± 0.7 kg (p = 0.054) respectively, but with no significant difference between diet groups. LC (CHO×Week, p < 0.05), but not HP, significantly promoted postprandial satiety during a preload challenge. Improvements in blood biomarkers were unrelated to LEDpdr macronutrient composition. In conclusion, HP did not promote satiety and BW loss compared to NP LEDpdr, irrespective of CHO content.

The impact of ethnicity and intra-pancreatic fat on the postprandial metabolome response to whey protein in overweight Asian Chinese and European Caucasian women with prediabetes.

The "Thin on the Outside Fat on the Inside" TOFI_Asia study found Asian Chinese to be more susceptible to Type 2 Diabetes (T2D) compared to European Caucasians matched for gender and body mass index (BMI). This was influenced by degree of visceral adipose deposition and ectopic fat accumulation in key organs, including liver and pancreas, leading to altered fasting plasma glucose, insulin resistance, and differences in plasma lipid and metabolite profiles. It remains unclear how intra-pancreatic fat deposition (IPFD) impacts TOFI phenotype-related T2D risk factors associated with Asian Chinese. Cow's milk whey protein isolate (WPI) is an insulin secretagogue which can suppress hyperglycemia in prediabetes. In this dietary intervention, we used untargeted metabolomics to characterize the postprandial WPI response in 24 overweight women with prediabetes. Participants were classified by ethnicity (Asian Chinese, n=12; European Caucasian, n=12) and IPFD (low IPFD < 4.66%, n=10; high IPFD ≥ 4.66%, n=10). Using a cross-over design participants were randomized to consume three WPI beverages on separate occasions; 0 g (water control), 12.5 g (low protein, LP) and 50 g (high protein, HP), consumed when fasted. An exclusion pipeline for isolating metabolites with temporal (T0-240mins) WPI responses was implemented, and a support vector machine-recursive feature elimination (SVM-RFE) algorithm was used to model relevant metabolites by ethnicity and IPFD classes. Metabolic network analysis identified glycine as a central hub in both ethnicity and IPFD WPI response networks. A depletion of glycine relative to WPI concentration was detected in Chinese and high IPFD participants independent of BMI. Urea cycle metabolites were highly represented among the ethnicity WPI metabolome model, implicating a dysregulation in ammonia and nitrogen metabolism among Chinese participants. Uric acid and purine synthesis pathways were enriched within the high IPFD cohort's WPI metabolome response, implicating adipogenesis and insulin resistance pathways. In conclusion, the discrimination of ethnicity from WPI metabolome profiles was a stronger prediction model than IPFD in overweight women with prediabetes. Each models' discriminatory metabolites enriched different metabolic pathways that help to further characterize prediabetes in Asian Chinese women and women with increased IPFD, independently.

Postprandial glycine as a biomarker of satiety: A dose-rising randomised control trial of whey protein in overweight women.

This study aimed to identify biomarkers of appetite response, modelled using a dose-rising whey protein preload intervention. Female participants (n = 24) with body mass index (BMI) between 23 and 40 kg/m2 consumed preload beverages (0 g protein water control, WC; 12.5 g low-dose protein, LP; or 50.0 g high-dose protein, HP) after an overnight fast, in a randomised cross over design. Repeated venous blood samples were collected to measure plasma biomarkers of appetite response, including glucose, glucoregulatory peptides, gut peptides, and amino acids (AAs). Appetite was assessed using Visual Analogue Scales (VAS) and ad libitum energy intake (EI). Dose-rising protein beverage significantly changed the postprandial trajectory of almost all biomarkers (treatment*time, p < 0.05), but did not suppress postprandial appetite (treatment*time, p > 0.05) or EI (ANOVA, p = 0.799). Circulating glycine had the strongest association with appetite response. Higher area under the curve (AUC0-240) glycine was associated with lower EI (p = 0.026, trend). Furthermore, circulating glycine was associated with decreased Hunger in all treatment groups, whereas the associations of glucose, alanine and amylin with appetite were dependent on treatment groups. Multivariate models, incorporating multiple biomarkers, improved the estimation of appetite response (marginal R2, range: 0.13-0.43). In conclusion, whilst glycine, both alone and within a multivariate model, can estimate appetite response to both water and whey protein beverage consumption, a large proportion of variance in appetite response remains unexplained. Most biomarkers, when assessed in isolation, are poor predictors of appetite response, and likely of utility only in combination with VAS and EI.

How Satiating Are the 'Satiety' Peptides: A Problem of Pharmacology versus Physiology in the Development of Novel Foods for Regulation of Food Intake.

Developing novel foods to suppress energy intake and promote negative energy balance and weight loss has been a long-term but commonly unsuccessful challenge. Targeting regulation of appetite is of interest to public health researchers and industry in the quest to develop 'functional' foods, but poor understanding of the underpinning mechanisms regulating food intake has hampered progress. The gastrointestinal (GI) or 'satiety' peptides including cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) secreted following a meal, have long been purported as predictive biomarkers of appetite response, including food intake. Whilst peptide infusion drives a clear change in hunger/fullness and eating behaviour, inducing GI-peptide secretion through diet may not, possibly due to modest effects of single meals on peptide levels. We conducted a review of 70 dietary preload (DIET) and peptide infusion (INFUSION) studies in lean healthy adults that reported outcomes of CCK, GLP-1 and PYY. DIET studies were acute preload interventions. INFUSION studies showed that minimum increase required to suppress ad libitum energy intake for CCK, GLP-1 and PYY was 3.6-, 4.0- and 3.1-fold, respectively, achieved through DIET in only 29%, 0% and 8% of interventions. Whether circulating 'thresholds' of peptide concentration likely required for behavioural change can be achieved through diet is questionable. As yet, no individual or group of peptides can be measured in blood to reliably predict feelings of hunger and food intake. Developing foods that successfully target enhanced secretion of GI-origin 'satiety' peptides for weight loss remains a significant challenge.