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The double burden of malnutrition in individuals: Identifying key challenges and re-thinking research focus.
Kiosia, A, Dagbasi, A, Berkley, JA, Wilding, JPH, Prendergast, AJ, Li, JV, Swann, J, Mathers, JC, Kerac, M, Morrison, D, et al
Nutrition bulletin. 2024
Abstract
The 'double burden of malnutrition' is a global health challenge that increasingly affects populations in both low- and middle-income countries (LMICs). This phenomenon refers to the coexistence of undernutrition and overweight or obesity, as well as other diet-related non-communicable diseases, in the same population, household or even individual. While noteworthy progress has been made in reducing undernutrition in some parts of the world, in many of these areas, the prevalence of overweight and obesity is increasing, particularly in urban areas, resulting in greater numbers of people who were undernourished in childhood and have overweight or obesity in adulthood. This creates a complex and challenging situation for research experts and policymakers who must simultaneously address the public health burdens of undernutrition and overweight/obesity. This review identifies key challenges and limitations in the current research on the double burden of malnutrition in individuals, including the need for a more comprehensive and nuanced understanding of the drivers of malnutrition, the importance of context-specific interventions and the need for greater attention to the food environment and food systems. We advocate for the re-evaluation of research strategies and focus, with a greater emphasis on multidisciplinary and systems approaches and greater attention to the synergistic relationship between the biological, environmental, commercial and socio-economic determinants of malnutrition. Addressing these key challenges can enable us to better comprehend and tackle the multifaceted and dynamic issues of the double burden of malnutrition, particularly in individuals and work towards more effective and sustainable solutions.
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Effect of inulin on breath hydrogen, postprandial glycemia, gut hormone release, and appetite perception in RYGB patients: a prospective, randomized, cross-over pilot study.
Steinert, RE, Mueller, M, Serra, M, Lehner-Sigrist, S, Frost, G, Gero, D, Gerber, PA, Bueter, M
Nutrition & diabetes. 2024;(1):9
Abstract
BACKGROUND AND OBJECTIVE Large intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients. METHOD Eight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales. RESULTS Surgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3-5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations. CONCLUSION RYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin.
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Improvements in Sperm Motility Following Low- or High-Intensity Dietary Interventions in Men With Obesity.
Sharma, A, Papanikolaou, N, Abou Sherif, S, Dimakopolou, A, Thaventhiran, T, Go, C, Holtermann Entwistle, O, Brown, A, Luo, R, Jha, R, et al
The Journal of clinical endocrinology and metabolism. 2024;(2):449-460
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Abstract
INTRODUCTION Obesity increases risks of male infertility, but bariatric surgery does not improve semen quality. Recent uncontrolled studies suggest that a low-energy diet (LED) improves semen quality. Further evaluation within a randomized, controlled setting is warranted. METHODS Men with obesity (18-60 years) with normal sperm concentration (normal count) (n = 24) or oligozoospermia (n = 43) were randomized 1:1 to either 800 kcal/day LED for 16 weeks or control, brief dietary intervention (BDI) with 16 weeks' observation. Semen parameters were compared at baseline and 16 weeks. RESULTS Mean age of men with normal count was 39.4 ± 6.4 in BDI and 40.2 ± 9.6 years in the LED group. Mean age of men with oligozoospermia was 39.5 ± 7.5 in BDI and 37.7 ± 6.6 years in the LED group. LED caused more weight loss than BDI in men with normal count (14.4 vs 6.3 kg; P < .001) and men with oligozoospermia (17.6 vs 1.8 kg; P < .001). Compared with baseline, in men with normal count total motility (TM) increased 48 ± 17% to 60 ± 10% (P < .05) after LED, and 52 ± 8% to 61 ± 6% (P < .0001) after BDI; progressive motility (PM) increased 41 ± 16% to 53 ± 10% (P < .05) after LED, and 45 ± 8% to 54 ± 65% (P < .001) after BDI. In men with oligozoospermia compared with baseline, TM increased 35% [26] to 52% [16] (P < .05) after LED, and 43% [28] to 50% [23] (P = .0587) after BDI; PM increased 29% [23] to 46% [18] (P < .05) after LED, and 33% [25] to 44% [25] (P < .05) after BDI. No differences in postintervention TM or PM were observed between LED and BDI groups in men with normal count or oligozoospermia. CONCLUSION LED or BDI may be sufficient to improve sperm motility in men with obesity. The effects of paternal dietary intervention on fertility outcomes requires investigation.
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Author Correction: Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.
Allesøe, RL, Lundgaard, AT, Hernández Medina, R, Aguayo-Orozco, A, Johansen, J, Nissen, JN, Brorsson, C, Mazzoni, G, Niu, L, Biel, JH, et al
Nature biotechnology. 2023;(7):1026
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A comparison of the effects of resistant starch types on glycemic response in individuals with type 2 diabetes or prediabetes: A systematic review and meta-analysis.
Pugh, JE, Cai, M, Altieri, N, Frost, G
Frontiers in nutrition. 2023;:1118229
Abstract
BACKGROUND Type 2 diabetes (T2D) diagnoses are predicted to reach 643 million by 2030, increasing incidences of cardiovascular disease and other comorbidities. Rapidly digestible starch elevates postprandial glycemia and impinges glycemic homeostasis, elevating the risk of developing T2D. Starch can escape digestion by endogenous enzymes in the small intestine when protected by intact plant cell walls (resistant starch type 1), when there is a high concentration of amylose (resistant starch type 2) and when the molecule undergoes retrogradation (resistant starch type 3) or chemical modification (resistant starch type 4). Dietary interventions using resistant starch may improve glucose metabolism and insulin sensitivity. However, few studies have explored the differential effects of resistant starch type. This systematic review and meta-analysis aims to compare the effects of the resistant starch from intact plant cell structures (resistant starch type 1) and resistant starch from modified starch molecules (resistant starch types 2-5) on fasting and postprandial glycemia in subjects with T2D and prediabetes. METHODS Databases (PubMed, SCOPUS, Ovid MEDLINE, Cochrane, and Web of Science) were systematically searched for randomized controlled trials. Standard mean difference (SMD) with 95% confidence intervals (CI) were determined using random-effects models. Sub-group analyses were conducted between subjects with T2D versus prediabetes and types of resistant starch. RESULTS The search identified 36 randomized controlled trials (n = 982), 31 of which could be included in the meta-analysis. Resistant starch type 1 and type 2 lowered acute postprandial blood glucose [SMD (95% CI) = -0.54 (-1.0, -0.07)] and [-0.96 (-1.61, -0.31)]. Resistant starch type 2 improved acute postprandial insulin response [-0.71 (-1.31, -0.11)]. In chronic studies, resistant starch type 1 and 2 lowered postprandial glucose [-0.38 (-0.73, -0.02), -0.29 (-0.53, -0.04), respectively] and resistant starch type 2 intake improved fasting glucose [-0.39 (-0.66, -0.13)] and insulin [-0.40 (-0.60, -0.21)]. CONCLUSION Resistant starch types 1 and 2 may influence glucose homeostasis via discrete mechanisms, as they appear to influence glycemia differently. Further research into resistant starch types 3, 4, and 5 is required to elucidate their effect on glucose metabolism. The addition of resistant starch as a dietary intervention for those with T2D or prediabetes may prevent further deterioration of glycemic control.
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The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study.
Frampton, J, Serrano-Contreras, JI, Garcia-Perez, I, Franco-Becker, G, Penhaligan, J, Tan, ASY, de Oliveira, ACC, Milner, AJ, Murphy, KG, Frost, G, et al
The Journal of physiology. 2023;(16):3461-3480
Abstract
An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.
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The effect of mycoprotein intake on biomarkers of human health: a systematic review and meta-analysis.
Shahid, M, Gaines, A, Coyle, D, Alessandrini, R, Finnigan, T, Frost, G, Marklund, M, Neal, B
The American journal of clinical nutrition. 2023;(1):141-150
Abstract
BACKGROUND Mycoprotein is a fungal source of protein that is increasingly consumed as an ingredient in meat analogs. OBJECTIVES This study aimed to systematically review and meta-analyze the effects of mycoprotein intake on selected biomarkers of human health. METHODS This study was registered in PROSPERO (CRD42022308980). We searched the PubMed, Scopus, and Embase databases to identify randomized control trials in any language until 16 August, 2022. Trials were included if they administered a mycoprotein intervention against a nonmycoprotein control arm and if reported outcomes included blood lipids, blood glucose, insulin, blood pressure, or body weight. Eligible trials were assessed for risk of bias using the Cochrane risk-of-bias tool for randomized trials. An inverse-variance-weighted, random-effects meta-analysis model was used to assess the effects of intake across each biomarker. RESULTS Nine trials that included 178 participants with a mean follow-up of 13 d were included, with 4 reporting on blood lipids and 5 reporting on postprandial blood glucose or insulin. The overall reduction of total cholesterol was -0.55 mmol/L (95% CI: -0.85 to -0.26; P < 0.001) in the mycoprotein group compared to control, but no clear effects on HDL cholesterol, LDL cholesterol, or TGs were found (all P > 0.05). There were no reductions in postprandial blood glucose concentrations at 30, 60, 90 or 120 min. Postprandial blood insulin concentration was reduced by -76.51 pmol/L (95% CI: -150.75 to -2.28; P = 0.043) at 30 min, with no detectable effects at 60, 90, or 120 min. CONCLUSIONS Mycoprotein intake may have important effects on blood lipids, but the evidence base is limited by the small sample sizes and short intervention periods of the contributing trials. The protocol for this systematic review has been registered in PROSPERO as CRD42022308980.
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Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits.
Brown, AA, Fernandez-Tajes, JJ, Hong, MG, Brorsson, CA, Koivula, RW, Davtian, D, Dupuis, T, Sartori, A, Michalettou, TD, Forgie, IM, et al
Nature communications. 2023;(1):5062
Abstract
We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.
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Diet-induced Weight Loss and Phenotypic Flexibility Among Healthy Overweight Adults: A Randomized Trial.
Rundle, M, Fiamoncini, J, Thomas, EL, Wopereis, S, Afman, LA, Brennan, L, Drevon, CA, Gundersen, TE, Daniel, H, Perez, IG, et al
The American journal of clinical nutrition. 2023;(3):591-604
Abstract
BACKGROUND The capacity of an individual to respond to changes in food intake so that postprandial metabolic perturbations are resolved, and metabolism returns to its pre-prandial state, is called phenotypic flexibility. This ability may be a more important indicator of current health status than metabolic markers in a fasting state. AIM: In this parallel randomized controlled trial study, an energy-restricted healthy diet and 2 dietary challenges were used to assess the effect of weight loss on phenotypic flexibility. METHODS Seventy-two volunteers with overweight and obesity underwent a 12-wk dietary intervention. The participants were randomized to a weight loss group (WLG) with 20% less energy intake or a weight-maintenance group (WMG). At weeks 1 and 12, participants were assessed for body composition by MRI. Concurrently, markers of metabolism and insulin sensitivity were obtained from the analysis of plasma metabolome during 2 different dietary challenges-an oral glucose tolerance test (OGTT) and a mixed-meal tolerance test. RESULTS Intended weight loss was achieved in the WLG (-5.6 kg, P < 0.0001) and induced a significant reduction in total and regional adipose tissue as well as ectopic fat in the liver. Amino acid-based markers of insulin action and resistance such as leucine and glutamate were reduced in the postprandial phase of the OGTT in the WLG by 11.5% and 28%, respectively, after body weight reduction. Weight loss correlated with the magnitude of changes in metabolic responses to dietary challenges. Large interindividual variation in metabolic responses to weight loss was observed. CONCLUSION Application of dietary challenges increased sensitivity to detect metabolic response to weight loss intervention. Large interindividual variation was observed across a wide range of measurements allowing the identification of distinct responses to the weight loss intervention and mechanistic insight into the metabolic response to weight loss.
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Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.
Allesøe, RL, Lundgaard, AT, Hernández Medina, R, Aguayo-Orozco, A, Johansen, J, Nissen, JN, Brorsson, C, Mazzoni, G, Niu, L, Biel, JH, et al
Nature biotechnology. 2023;(3):399-408
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Abstract
The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.