Effects on cardiovascular risk factors of a low- vs high-glycemic index Mediterranean diet in high cardiometabolic risk individuals: the MEDGI-Carb study.

BACKGROUND: The role of dietary Glycemic Index (GI), independently of fiber intake, in modulating cardiovascular disease (CVD) risk among non-diabetic individuals has not been fully elucidated. OBJECTIVE: To evaluate the effects of a low- versus a high-GI diet, based on a Mediterranean dietary pattern, on cardiometabolic risk factors in individuals at high CVD risk, participating in the MEDGI-Carb intervention study. SUBJECTS AND METHODS: 160 individuals, aged 30-69 years, BMI 25-37 kg/m2, with a waist circumference >102 cm (males) or >88 cm (females) and one feature of the metabolic syndrome, participated in a multi-national (Italy, Sweden, USA) randomized controlled parallel group trial. Participants were assigned to a low GI (< 55) or high-GI MedDiet ( > 70) for 12 weeks. The diets were isoenergetic and similar for available carbohydrate (270 g/d) and fiber (35 g/d) content. Fasting metabolic parameters were evaluated in the whole cohort, while an 8-h triglyceride profile (after standard breakfast and lunch) was evaluated only in the Italian cohort. RESULTS: Blood pressure and most fasting metabolic parameters improved at the end of the dietary intervention (time effect, p < 0.05 for all); however, no differences were observed between the low- and the high-GI MedDiet groups (time x group effect; p > 0.05 for all). Conversely, the low-GI diet, compared with high-GI diet, significantly reduced the 8-h triglyceride profile (p < 0.017, time*group effect) that was measured only in the Italian cohort. However, it induced a reduction of plasma triglycerides after lunch (tAUC) that was of only borderline statistically significance (p = 0.065). CONCLUSIONS: Consuming a low-GI in comparison with a high-GI MedDiet does not differentially affect the major cardiometabolic risk factors at fasting in individuals at increased cardiometabolic risk. Conversely, it could reduce postprandial plasma triglycerides. CLINICAL TRIAL REGISTRY NUMBER: NCT03410719, ( https://clinicaltrials.gov ).

Whey Protein Supplementation and Type 2 Diabetes Mellitus Risk Factors: An Umbrella Systematic Review of Randomized Controlled Trials.

Emerging research suggests whey protein (WP) supplementation may modify type 2 diabetes mellitus (T2DM) risk factors, including glucose control. As systematic reviews and/or meta-analyses of randomized controlled trials (RCTs) gain importance in nutrition literature, we conducted an umbrella systematic review to chronicle published systematic reviews and/or meta-analyses of RCTs pertinent to WP supplementation and T2DM modifiable risk factors. This review was conducted in accordance with Preferred Reporting Items for Overviews of Reviews standards. Potentially eligible articles were identified via a systematic search of 5 electronic health research databases (PubMed, Cochrane Library, CINAHL [EBSCO], Scopus, and SPORTDiscus [EBSCO]). Included articles were assessed for quality using the "A MeaSurement Tool to Assess systematic Reviews 2" critical appraisal tool. Thirteen articles, representing 109 unique RCTs, of the 2205 identified articles met the inclusion criteria. Nine articles (69%) were deemed high quality, 2 (15%) moderate quality, and 2 (15%) low quality. Findings from this umbrella review of 13 systematic reviews, including 12 meta-analyses, suggest WP may lower hemoglobin A1c, homeostasis model assessment of insulin resistance, and fasting insulin in groups classified as overweight/obese or at risk for or with metabolic syndrome; blood triglycerides in groups classified as overweight/obese or at risk for or with metabolic syndrome; and blood pressure in groups classified as overweight/obese. WP did not differentially affect C-reactive protein, body weight, body mass index, or waist circumference, nor did it adversely affect any T2DM risk factors. Insufficient evidence precluded assessing the influence of WP on glucose control-related outcomes in groups classified at lower risk for T2DM. Information regarding WP dose, duration, or types was insufficient to draw conclusions. Collectively, evidence suggests WP supplementation may improve multiple clinical indicators of glucose control, along with triglycerides and blood pressure, in groups of adults at increased risk of developing T2DM.

Differential Responders to a Mixed Meal Tolerance Test Associated with Type 2 Diabetes Risk Factors and Gut Microbiota-Data from the MEDGI-Carb Randomized Controlled Trial.

The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades, and the identification of differential glycemic responders can aid tailored treatment for the prevention of prediabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers the potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among participants with elevated T2DM risk to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary intervention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females and 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distinguish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.

Perspective: A Research Roadmap about Ultra-Processed Foods and Human Health for the United States Food System: Proceedings from an Interdisciplinary, Multi-Stakeholder Workshop.

Our objective was to convene interdisciplinary experts from government, academia, and industry to develop a Research Roadmap to identify research priorities about processed food intake and risk for obesity and cardiometabolic diseases (CMD) among United States populations. We convened attendees at various career stages with diverse viewpoints in the field. We held a "Food Processing Primer" to build foundational knowledge of how and why foods are processed, followed by presentations about how processed foods may affect energy intake, obesity, and CMD risk. Breakout groups discussed potential mechanistic and confounding explanations for associations between processed foods and obesity and CMD risk. Facilitators created research questions (RQs) based on key themes from discussions. Different breakout groups convened to discuss what is known and unknown for each RQ and to develop sub-RQs to address gaps. Workshop attendees focused on ultra-processed foods (UPFs; Nova Group 4) because the preponderance of evidence is based on this classification system. Yet, heterogeneity and subjectivity in UPF classification was a challenge for RQ development. The 6 RQs were: 1) What objective methods or measures could further categorize UPFs, considering food processing, formulation, and the interaction of the two? 2) How can exposure assessment of UPF intake be improved? 3) Does UPF intake influence risk for obesity or CMDs, independent of diet quality? 4) What, if any, attributes of UPFs influence ingestive behavior and contribute to excess energy intake? 5) What, if any, attributes of UPFs contribute to clinically meaningful metabolic responses? 6) What, if any, external environmental factors lead people to consume high amounts of UPFs? Uncertainty and complexity around UPF intake warrant further complementary and interdisciplinary causal, mechanistic, and methodological research related to obesity and CMD risk to understand the utility of applying classification by degree of processing to foods in the United States.

The effects of Mediterranean diets with low or high glycemic index on plasma glucose and insulin profiles are different in adult men and women: Data from MEDGI-Carb randomized clinical trial.

BACKGROUND & AIMS: Recent evidence suggests that the ability to regulate glucose and insulin homeostasis is different in men and women. Against this background, it has been hypothesized that the impact on daily plasma glucose and insulin profiles of the glycemic index (GI) of the habitual diet may differ according to sex. The aim of this study is to evaluate whether 8-h average plasma glucose and insulin profiles during a low- or a high-GI diet in individuals at high risk of developing type 2 diabetes are influenced by sex. METHODS: We conducted a randomized, controlled, parallel group dietary intervention, comparing high-versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of 156 adults at risk for type 2 diabetes. For 12 weeks, 82 vs 74 participants consumed either a low-GI or high-GI Mediterranean diet, respectively. The two experimental diets contained the same quantity of available carbohydrate (270 g/d) and fiber (35 g/d) and the same foods and beverages, except for the major sources of starch that was specific to the low-GI and high-GI groups (pasta, brown rice, flatbread, all bran, and wheat bread plus rye and seeds, vs jasmine rice, potato, couscous, wholegrain bread, and rusks). At baseline and after the intervention plasma glucose and insulin profiles were evaluated for 8 h in the two intervention groups - separately for men and women - with both breakfast and lunch resembling food choices of the assigned diet. RESULTS: One hundred fifty-six adults (82 women, 74 men) with at least two traits of the metabolic syndrome completed the intervention. In women, the high-GI induced significantly higher (23%, p < 0.05) 8-h average plasma glucose concentrations in comparison to the low-GI diet already on the first day of the intervention; the difference increased up to 37% (p < 0.05) after 12 weeks of diet. Conversely, there were no significant differences between the two diets in men. These results were confirmed by the two-way analysis of variance showing a statistically significant interaction between the effects of sex and diet on the glucose profile after breakfast and lunch (F = 7.887, p = 0.006). CONCLUSION: The results of our intervention show that women, compared to men, are more sensitive to the metabolic effects of the dietary GI. This has a strong clinical and scientific relevance and, if confirmed in further studies, it might have important implications for dietary strategies for diabetes and cardiovascular disease prevention in the context of personalized nutrition. REGISTRATION NUMBER OF CLINICAL TRIAL: Clinicaltrials.gov n. NCT03410719.

Effects of Consuming Ounce-Equivalent Portions of Animal- vs. Plant-Based Protein Foods, as Defined by the Dietary Guidelines for Americans on Essential Amino Acids Bioavailability in Young and Older Adults: Two Cross-Over Randomized Controlled Trials.

BACKGROUND: The Dietary Guidelines for Americans (DGA) recommends consuming a variety of "Protein Foods" based on "ounce-equivalent" (oz-eq) portions. No study has assessed the same oz-eq portions of animal- vs. plant-based protein foods on essential amino acid (EAA) bioavailability for protein anabolism in young and older adults. OBJECTIVES: We assessed the effects of consuming two oz-eq portions of pork, eggs, black beans, and almonds on postprandial EAA bioavailability in young and older adults. METHODS: We conducted two investigator-blinded, randomized crossover trials in young (n = 30; mean age ± SD: 26.0 ± 4.9 y) and older adults (n = 25; mean age ± SD: 64.2 ± 6.6 y). Participants completed four testing sessions where they consumed a standardized meal with two oz-eq of either unprocessed lean pork, whole eggs, black beans, or sliced almonds. Blood samples were taken at baseline and 30, 60, 120, 180, 240, and 300 min postprandially. Plasma EAA bioavailability was based on postprandial integrated positive areas under the curve. RESULTS: Participant age did not affect EAA bioavailability among the four protein foods tested. Two oz-eq portions of pork (7.36 g EAA) and eggs (5.38 g EAA) resulted in greater EAA bioavailability than black beans (3.02 g EAA) and almonds (1.85 g EAA) in young and older adults, separately or combined (p < 0.0001 for all). Pork resulted in greater EAA bioavailability than eggs in young adults (p < 0.0001), older adults (p = 0.0007), and combined (p < 0.0001). There were no differences in EAA bioavailability between black beans and almonds. CONCLUSIONS: The same "oz-eq" portions of animal- and plant-based protein foods do not provide equivalent EAA content and postprandial bioavailability for protein anabolism in young and older adults.

Structural and Thermal Characterization of Protein Isolates from Australian Lupin Varieties as Affected by Processing Conditions.

Proteins from the full and defatted flours of L. angustifolius cv Jurien and L. albus cv Murringo were prepared using alkaline extraction and iso-electric precipitation. Isolates were either freeze dried or spray dried or pasteurized at 75 ± 3 °C/5 min before freeze-drying. Various structural properties were investigated to elucidate the varietal and processing-induced effect on molecular and secondary structure. Irrespective of processing, isolated proteins had a similar molecular size, with α-conglutin (412 kDa) and ß-conglutin (210 kDa) being principal fractions for the albus and angustifolius variety, respectively. Smaller peptide fragments were observed for the pasteurized and spray dried samples, indicating some degree of processing-induced changes. Furthermore, secondary structure characterization by Fourier-transform-infrared and circular dichroism spectroscopy showed ß-sheet and α-helical structure being the dominant structure, respectively. Thermal characterization showed two denaturation peaks corresponding to ß-conglutin (Td = 85-89 °C) and α-conglutin (Td = 102-105 °C) fractions. However, the enthalpy values for α-conglutin denaturation were significantly higher for albus species, which corroborates well with higher amounts of heat stable α-conglutin present. Amino acid profile was similar for all samples with limiting sulphur amino acid. In summary, commercial processing conditions did not have a profound effect on the various structural properties of lupin protein isolates, and properties were mainly determined by varietal differences.

Meat Consumption and Gut Microbiota: a Scoping Review of Literature and Systematic Review of Randomized Controlled Trials in Adults.

Emerging research indicates the importance of gut microbiota in mediating the relationship between meat intake and human health outcomes. We aimed to assess the state of available scientific literature on meat intake and gut microbiota in humans (PROSPERO, International Prospective Register of Systematic Reviews, CRD42020135649). We first conducted a scoping review to identify observational and interventional studies on this topic. Searches were performed for English language articles using PubMed, Cochrane Library, Scopus, and CINAHL (Cumulated Index to Nursing and Allied Health Literature) databases from inception to August 2021 and using keywords related to meat (inclusive of mammalian, avian, and aquatic subtypes) and gut microbiota. Of 14,680 records, 85 eligible articles were included in the scoping review, comprising 57 observational and 28 interventional studies. One prospective observational study and 13 randomized controlled trials (RCTs) were identified in adults without diagnosed disease. We included the 13 RCTs, comprising 18 comparisons, in the systematic review to assess the effects of higher and lower intakes of total meat and meat subtypes on the gut microbiota composition. The bacterial composition was differentially affected by consuming diets with and without meat or with varied meat subtypes. For example, higher meat intake tended to decrease population sizes of genera Anerostipes and Faecalibacterium, but it increased the population size of Roseburia across studies. However, the magnitude and directionality of most microbial responses varied, with inconsistent patterns of responses across studies. The data were insufficient for comparison within or between meat subtypes. The paucity of research, especially among meat subtypes, and heterogeneity of findings underscore the need for more well-designed prospective studies and full-feeding RCTs to address the relationships between and effects of consuming total meat and meat subtypes on gut microbiota, respectively.

Differential Glycemic Effects of Low- versus High-Glycemic Index Mediterranean-Style Eating Patterns in Adults at Risk for Type 2 Diabetes: The MEDGI-Carb Randomized Controlled Trial.

A Mediterranean-style healthy eating pattern (MED-HEP) supports metabolic health, but the utility of including low-glycemic index (GI) foods to minimize postprandial glucose excursions remain unclear. Therefore, we investigated the relative contribution of GI towards improvements in postprandial glycemia and glycemic variability after adopting a MED-HEP. We conducted a randomized, controlled dietary intervention, comparing high- versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of adults at risk for type 2 diabetes. For 12 weeks, participants consumed either a low-GI or high-GI MED-HEP. We assessed postprandial plasma glucose and insulin responses to high- or low-GI meals, and daily glycemic variability via continuous glucose monitoring at baseline and post-intervention. One hundred sixty adults (86 females, 74 males; aged 55 ± 11 y, BMI 31 ± 3 kg/m2, mean ± SD) with ≥two metabolic syndrome traits completed the intervention. Postprandial insulin concentrations were greater after the high-GI versus the low-GI test meals at baseline (p = 0.004), but not post-intervention (p = 0.17). Postprandial glucose after the high-GI test meal increased post-intervention, being significantly higher than that after the low-GI test meal (35%, p < 0.001). Average daily glucose concentrations decreased in both groups post-intervention. Indices of 24-h glycemic variability were reduced in the low-GI group as compared to baseline and the high-GI intervention group. These findings suggest that low-GI foods may be an important feature within a MED-HEP.

The MEDGICarb-Study: Design of a multi-center randomized controlled trial to determine the differential health-promoting effects of low- and high-glycemic index Mediterranean-style eating patterns.

Adults with central adiposity and other features of the metabolic syndrome have a markedly elevated risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD). A Mediterranean-style healthy eating pattern (MED-HEP) and consumption of foods with a lower glycemic index (GI) are potential dietary approaches to curb the T2D and CVD epidemic. However, experimental evidence of the effectiveness of MED-HEP and of the contribution of GI towards improving indices of glucose homeostasis, especially among non-diabetic people, are lacking. Therefore, we developed the MedGI-Carb trial, a multi-center (Italy, Sweden, and United States) intervention in adults with at least two components of the metabolic syndrome (elevated waist circumference + one other component) that aims to improve markers of glucose homeostasis through dietary modification. All participants were randomized to consume an isocaloric high- or low-GI MED-HEP for 12 weeks. We hypothesized that indexes of insulinemia (primary outcome: postprandial insulin and glucose after standardized breakfast and lunch; secondary outcomes: fasting plasma glucose and insulin, HbA1c, 24-h continuous glucose monitoring) would be improved more with the low-GI versus the high-GI MED-HEP. Additionally, we hypothesized that consumption of a MED-HEP would improve other markers of cardiometabolic health and well-being (fasting blood pressure, fasting lipid profile, sleep quality, satiety, global metabolic alterations in the plasma metabolome, changes in the gut microbiota, subjective health and well-being), with no difference between groups. Collectively, the design of MEDGI-Carb allows several different research questions to be explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03410719.

A high-protein meal does not improve blood pressure or vasoactive biomarker responses to acute exercise in humans.

Blood pressure (BP) responses to exercise yield prognostic information beyond resting BP. While habitual higher dietary protein intake is associated with reduced resting BP, few studies have assessed the impact of high-protein meals on acute BP and vasoactive biomarker responses to exercise. To test the hypothesis that consuming a higher-protein, lower fat meal (HP; 30 g protein, 17 g fat, 52 g carbohydrate) would attenuate the BP response to exercise and result in a more robust post-exercise hypotensive response compared to a lower-protein, higher-fat meal (LP; 13 g protein, 25 g fat, 54 g carbohydrate), we recruited 31 pre-hypertensive subjects to complete this randomized, double-blind, cross-over acute feeding study. One hundred sixty-five minutes after consuming the test HP or LP meal, subjects exercised on a cycle ergometer at 70% VO2 max for 30 minutes. Blood pressure was measured prior to the meal and periodically before, during, and after exercise for a 315-minute period. Blood samples were periodically collected to quantify plasma arginine, arginine metabolites (asymmetric dimethylarginine, symmetric dimethylarginine; ADMA, SDMA), endothelin-1, nitrates, and nitrites in a subset of subjects (n = 15) as shown in Supplemental Table S1. Consuming the HP meal did not influence the BP responses to exercise, including the post-exercise return to baseline BP or systolic BP area under the curve. While the HP meal resulted in greater postprandial plasma arginine concentrations, ADMA, SDMA, endothelin-1, nitrates, and nitrites were unaltered. These results suggest that consuming a higher-protein, lower-fat meal does not influence BP or vasoactive biomarker responses to exercise compared to a lower-protein, higher-fat meal.

Differential Relationship between Intermuscular Adipose Depots with Indices of Cardiometabolic Health.

BACKGROUND: Globally, accumulation of intermuscular adipose tissue (IMAT) is positively associated with insulin resistance. Whether this association is observed consistently in different skeletal muscles and encompasses other markers of cardiometabolic health is not well known. OBJECTIVES: The purpose of this secondary analysis study was to investigate associations among thigh or calf IMAT stores and indices of cardiometabolic health in adults who are overweight and obese participating in dietary interventions. A subset of calf data was analyzed to assess relations between IMAT in the gastrocnemius (type II fiber predominance) and soleus (type I fiber predominance) with markers of cardiometabolic health. MATERIALS AND METHODS: Thigh and calf compositions were assessed via magnetic resonance imaging in 113 subjects (mean ± SD, age: 50 ± 16 y (range: 21-77 y), BMI: 31 ± 3 kg/m2), 103 of which completed dietary interventions with or without energy restriction-induced weight loss. A subset of data (n = 37) was analyzed for relations between muscle compartments (gastrocnemius and soleus) and cardiometabolic health. IMAT was regressed separately against fasting serum glucose concentrations, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), and lipids and lipoproteins. RESULTS: In general, total thigh IMAT was predictive of markers of glucose control, while total calf IMAT was not. Specifically, baseline thigh IMAT was positively associated with fasting glucose, insulin, and HOMA-IR. IMAT content changes in any depot did not predict improvement in cardiometabolic health. CONCLUSIONS: The strength of the relationship between IMAT and glucose control-related indices of cardiometabolic health is dependent on IMAT location. Specifically, greater IMAT in the thigh is a better predictor of cardiometabolic risk than greater IMAT in the calf in adults who are overweight and obese.

Effects of protein supplements consumed with meals, versus between meals, on resistance training-induced body composition changes in adults: a systematic review.

Context: The impact of timing the consumption of protein supplements in relation to meals on resistance training-induced changes in body composition has not been evaluated systematically. Objective: The aim of this systematic review was to assess the effect of consuming protein supplements with meals, vs between meals, on resistance training-induced body composition changes in adults. Data Sources: Studies published up to 2017 were identified with the PubMed, Scopus, Cochrane, and CINAHL databases. Data Extraction: Two researchers independently screened 2077 abstracts for eligible randomized controlled trials of parallel design that prescribed a protein supplement and measured changes in body composition for a period of 6 weeks or more. Results: In total, 34 randomized controlled trials with 59 intervention groups were included and qualitatively assessed. Of the intervention groups designated as consuming protein supplements with meals (n = 16) vs between meals (n = 43), 56% vs 72% showed an increase in body mass, 94% vs 90% showed an increase in lean mass, 87% vs 59% showed a reduction in fat mass, and 100% vs 84% showed an increase in the ratio of lean mass to fat mass over time, respectively. Conclusions: Concurrently with resistance training, consuming protein supplements with meals, rather than between meals, may more effectively promote weight control and reduce fat mass without influencing improvements in lean mass.

Effect of whey protein supplementation on body composition changes in women: a systematic review and meta-analysis.

Context: A preponderance of evidence supports the beneficial effects of whey protein (WP) supplementation on body composition in men; however, there is currently insufficient evidence to make an equivalent claim in women. Objective: This systematic review and meta-analysis assessed the effects of WP supplementation with or without energy restriction (ER) and resistance training (RT) on changes in body mass, lean mass, and fat mass in women. Data Sources: Pubmed, Scopus, Cochrane, and CINAHL were searched using the keywords "whey protein," "body composition," and "lean mass." Data Extraction: Two researchers independently screened 1845 abstracts and extracted 276 articles. Thirteen randomized controlled trials with 28 groups met the inclusion criteria. Results: Globally, WP supplementation increased lean mass (WMD, 0.37 kg; 95% confidence interval [CI], 0.06 to 0.67) while not influencing changes in fat mass (-0.20 kg; 95%CI, -0.67 to 0.27) relative to non-WP control. The beneficial effect of WP on lean mass was lost when only studies with RT were included in the analysis (n = 7 comparisons; 0.23 kg; 95%CI, -0.17 to 0.63). The beneficial effect of WP on lean mass was more robust when only studies with an ER component were included (n = 6 comparisons; 0.90 kg; 95%CI, 0.31 to 1.49). There was no effect of WP on lean mass in studies without ER (n = 9 comparisons; 0.22 kg; 95%CI, -0.12 to 0.57). Conclusion: Whey protein supplementation improves body composition by modestly increasing lean mass without influencing changes in fat mass. Body composition improvements from WP are more robust when combined with ER .