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Background: There are limited data from randomized control trials to support or refute the contention that whole-grains can enhance protein metabolism in humans., Objectives: To examine: 1 ) the clinical effects of a whole-grain diet on whole-body protein turnover; 2 ) the cellular effects of whole-grains on protein synthesis in skeletal muscle cells; and 3 ) the population effects of whole-grain intake on age-related muscle loss., Methods: Adults with overweight/obesity ( n = 14; age = 40 ± 7 y; BMI = 33 ± 5 kg/m 2 ) were recruited into a crossover, randomized controlled trial (NCT01411540) in which isocaloric, macronutrient-matched whole-grain and refined-grain diets were fully provisioned for two 8-wk periods. Diets differed only in the presence of whole-grains (50 g/1000 kcal). Whole-body protein kinetics were assessed at baseline and after each diet in the fasted-state ( 13 C-leucine) and integrated over 24 h ( 15 N-glycine). In vitro studies using C2C12 cells assessed global protein synthesis by surface sensing of translation and anabolic signaling by Western blot. Complementary epidemiological assessments using the NHANES database assessed the effect of whole-grain intake on muscle function assessed by gait speed in older adults ( n = 2783)., Results: Integrated 24-h net protein balance was 3-fold higher on a whole-grain diet compared with a refined-grain diet ( P = 0.04). A whole-grain wheat extract increased submaximal rates of global protein synthesis (27%, P < 0.05) in vitro . In a large sample of older adults, whole-grain intake was associated with greater muscle function (OR = 0.92; 95% CI: 0.86, 0.98)., Conclusions: Consuming 50 g/1000 kcal whole-grains per day promotes greater protein turnover and enhances net protein balance in adults. Whole-grains impact skeletal muscle at the cellular level, and are associated with greater muscle function in older adults. Collectively, these data point to a new mechanism whereby whole-grain consumption favorably enhances protein turnover and improves health outcomes.This clinical trial is registered on clinicaltrials.gov (identifier: NCT01411540)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: The effect of whole-grain (WG) versus refined-grain (RG) diets on glucose-stimulated insulin secretion (GSIS) and β-cell function is unclear., Methods: In a double-blind crossover randomized controlled trial, 13 prediabetic adults (37.2 ± 1.8 y, BMI: 33.6 ± 1.4 kg m -2 , 2 h glucose: 146.9 ± 11.6 mg dL -1 ) are provided isocaloric-matched WG and RG diets for 8-weeks each, with an 8-10 week washout between diets. Glucose, insulin, and C-peptide are studied over 240 min following a 75 g OGTT. Incretins (GLP-1 and GIP), PYY, and total ghrelin are assessed at 0, 30, and 60 min. Mixed-meal diets for carbohydrate (54%), fat (28%), and protein (18%) contain either WG (50 g/1000 kcal) or equivalent RG., Results: Both diets induce fat loss (≈2 kg). While neither diet impacts early phase GSIS, the WG diet increases total GSIS (iAUC of C-peptide 0-240 /Glc 0-240 , p = 0.02) and β-cell function (disposition index; GSIS × insulin sensitivity, p = 0.02). GIP and PYY are unaltered by either diet, but GLP-1 is higher at 30 min following RG versus WG (p = 0.04). Ghrelin levels are higher at 60 min of the OGTT following both interventions (p = 0.01)., Conclusion: A WG-rich diet increases β-cell function independent of gut hormones in adults with prediabetes., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

New Findings: What is the central question of this study? Does short-duration, high-intensity exercise training that combines functional aerobic and resistance exercises into training sessions lasting 8-20 min benefit individuals with type 2 diabetes? What is the main finding and its importance? Functional high-intensity training improves insulin sensitivity and reduces cardiometabolic risk in individuals with type 2 diabetes. This type of exercise training may be an effective exercise mode for managing type 2 diabetes. The increase in insulin sensitivity addresses a key defect in type 2 diabetes., Abstract: Functional high-intensity training (F-HIT) is a novel fitness paradigm that integrates simultaneous aerobic and resistance training in sets of constantly varied movements, based on real-world situational exercises, performed at high-intensity in workouts that range from ∼8 to 20 min per session. We hypothesized that F-HIT would be an effective exercise mode for reducing insulin resistance in type 2 diabetes (T2D). We recruited 13 overweight/obese adults (5 males, 8 females; 53 ± 7 years; BMI 34.5 ± 3.6 kg m -2 , means ± SD) with T2D to participate in a 6-week (3 days week -1 ) supervised F-HIT programme. An oral glucose tolerance test was used to derive measures of insulin sensitivity. F-HIT significantly reduced fat mass (43.8 ± 83.8 vs. 41.6 ± 7.9 kg; P < 0.01), diastolic blood pressure (80.2 ± 7.1 vs. 74.5 ± 5.8; P < 0.01), blood lipids (triglyceride and VLDL, both P < 0.05) and metabolic syndrome z-score (6.4 ± 4.5 vs. -0.2 ± 5.2 AU; P < 0.001), and increased basal fat oxidation (0.08 ± 0.03 vs. 0.10 ± 0.04 g min -1 ; P = 0.05), and high molecular mass adiponectin (214.4 ± 88.9 vs. 288.8 ± 127.4 ng mL -1 ; P < 0.01). Importantly, F-HIT also increased insulin sensitivity (0.037 ± 0.010 vs. 0.042 ± 0.010 AU; P < 0.05). Increases in high molecular mass adiponectin and basal fat oxidation correlated with the change in insulin sensitivity (ρ, 0.75, P < 0.05 and ρ, 0.81, P < 0.01, respectively). Compliance with the training programme was >95% and no injuries or adverse events were reported. These data suggest that F-HIT may be an effective exercise mode for managing T2D. The increase in insulin sensitivity addresses a key defect in T2D and is consistent with improvements observed after more traditional aerobic exercise programmes in overweight/obese adults with T2D., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

Background: Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear., Purpose: We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet., Methods: A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ± 2 y; BMI, 34.0 ± 1.1 kg/m 2 ). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6- 2 H 2 ]-glucose and [U- 13 C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (R a ) iAUC 60-240  × insulin iAUC 60-240 , respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets., Results: Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic R a insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05)., Conclusion: Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility., (Copyright © 2018. Published by Elsevier Inc.)

Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R 2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R 2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D., (Copyright © 2017 the American Physiological Society.)

Background: Increased dietary whole-grain intake may protect against cardiovascular disease (CVD)., Objective: The objective was to evaluate the efficacy of whole grains compared with refined grains on body composition, hypertension, and related mediators of CVD in overweight and obese adults., Methods: We conducted a double-blind, randomized, controlled crossover trial in 40 overweight or obese men and women aged <50 y with no known history of CVD. Complete whole-grain and refined-grain diets were provided for two 8-wk periods, with a 10-wk washout between diets. Macronutrient composition was matched, except for the inclusion of either whole grains or refined grains (50 g/1000 kcal in each diet). Measurements included blood pressure, body composition, blood lipids and adiponectin, and markers of inflammation and glycemia., Results: Thirty-three participants (6 men and 27 women) completed the trial [mean ± SD age: 39 ± 7 y; mean ± SD body mass index (in kg/m 2 ): 33.1 ± 4.3]. Decreases in diastolic blood pressure were -5.8 mm Hg (95% CI: -7.7, -4.0 mm Hg) after the whole-grain diet and -1.6 mm Hg (95% CI: -4.4, 1.3 mm Hg) after the control diet (between effect, P = 0.01). Decreases in plasma adiponectin were -0.1 (95% CI: -0.9, 0.7) after the whole-grain diet and -1.4 (95% CI: -2.6, -0.3) after the control diet (between effect, P = 0.05). Decreases in diastolic blood pressure correlated with the circulating adiponectin concentration (r = 0.35, P = 0.04). Substantial reductions in body weight, fat loss, systolic blood pressure, total cholesterol, and LDL cholesterol were observed during both diet periods, with no relevant difference between them., Conclusions: The improvement in diastolic blood pressure was >3-fold greater in overweight and obese adults when they consumed a whole-grain compared with a refined-grain diet. Because diastolic blood pressure predicts mortality in adults aged <50 y, increased whole-grain intake may provide a functional approach to control hypertension. This may benefit patients at risk of vascular-related morbidity and mortality. This trial was registered at clinicaltrials.gov as NCT01411540., Competing Interests: 2Author disclosures: J-P Godin, S Kochhar, and AB Ross are employed by the Nestlé Research Center. JP Kirwan, SK Malin, AR Scelsi, EL Kullman, SD Navaneethan, MR Pagadala, JM Haus, and J Filion, no conflicts of interest. Nestlé marketing provided no input on the final data analysis, interpretation, or writing of this article., (© 2016 American Society for Nutrition.)

Obesity-related nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease. Exercise and diet are uniformly prescribed treatments for NAFLD; however, there are limited empirical data on the effects of exercise training on metabolic function in these patients. The purpose of this study was to investigate the fasting and glucose-stimulated adaptation of gut peptides to short-term aerobic exercise training in patients with NAFLD. Twenty-two obese subjects, 16 with NAFLD [body mass index (BMI), 33.2 ± 1.1 (SE) kg/m(2)] and 6 obese controls (BMI, 31.3 ± 1.2 kg/m(2)), were enrolled in a supervised aerobic exercise program (60 min/day, 85% of their heart rate maximum, for 7 days). Fasting and glucose-stimulated glucagon-like peptide-1 (GLP-17-36) and peptide tyrosine tyrosine (PYYTotal) concentrations in plasma were assessed before and after the exercise program. Initially, the NAFLD group had higher fasting PYY (NAFLD = 117 ± 18.6, control = 47.2 ± 6.4 pg/ml, P < 0.05) and GLP-1 (NAFLD = 12.4 ± 2.2, control = 6.2 ± 0.2 pg/ml, P < 0.05) and did not significantly increase GLP-1 or PYY in response to glucose ingestion. After the exercise program, fasting GLP-1 was reduced in the NAFLD group (10.7 ± 2.0 pg/ml, P < 0.05). Furthermore, exercise training led to significant increase in the acute (0-30 min) PYY and GLP-1 responses to glucose in the NAFLD group, while the total area under the glucose-stimulated GLP-1 response curve was reduced in both NAFLD and controls (P < 0.05). In summary, 7 days of vigorous aerobic exercise normalized the dynamic PYY and GLP-1 responses to nutrient stimulation and reduced the GLP-1 response in NAFLD, suggesting that exercise positively modulates gut hormone regulation in obese adults with NAFLD., (Copyright © 2016 the American Physiological Society.)

Fetuin-A is synthesized in the liver and may be associated with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Lifestyle-induced weight loss reduces fetuin-A, but the effect of exercise alone is unknown. We determined the effect of short-term exercise training on plasma fetuin-A in 13 (50.5 ± 3.4 yr) obese adults (body mass index, 33.3 ± 0.9 kg/m(2)) with clinically diagnosed NAFLD. Subjects participated in 7 days of supervised exercise training (60 min/day at ∼85% maximum heart rate) and were instructed to maintain their normal caloric and macronutrient intake. Insulin resistance was assessed by an oral glucose tolerance test. Hepatic triglyceride content (HTGC) was determined by proton MRI. We used C2C12 skeletal muscle cells to examine the direct effect of fetuin-A on 2-deoxyglucose uptake, insulin signaling [phosphorylation of Akt and AS160 (pAkt and pAS160, respectively)], and glucose transporter-4 (GLUT-4) translocation. Insulin resistance was reduced by 29% (P < 0.05), and glucose area under the curve (AUC) was decreased by 13% (P < 0.01) after the 7 days of exercise. Furthermore, circulating fetuin-A was decreased by 11% (4.2 ± 03 vs. 3.6 ± 0.2 nM; P < 0.02), and this change correlated with reduced insulin resistance (r = 0.62; P < 0.04) and glucose AUC (r = 0.58; P < 0.04). Importantly, the exercise program did not change body weight (P = 0.12), HTGC (P = 0.73), or aerobic capacity (P = 0.14). In vitro experiments revealed that fetuin-A decreased skeletal muscle glucose uptake by downregulating pAkt and pAS160 and subsequent GLUT-4 translocation to the plasma membrane. Together, our findings highlight a role for fetuin-A in skeletal muscle insulin resistance and suggest that part of the exercise-induced improvement in glucose tolerance in patients with NAFLD may be due to lowering fetuin-A.

Context: Hepatic steatosis, insulin resistance, inflammation, low levels of polyunsaturated lipids, and adiponectin are implicated in the development and progression of nonalcoholic fatty liver disease (NAFLD)., Objective: We examined the effects of short-term aerobic exercise on these metabolic risk factors., Design and Participants: Obese individuals (N = 17, 34.3 ± 1.0 kg/m²) with clinically confirmed NAFLD were enrolled in a short-term aerobic exercise program that consisted of 7 consecutive days of treadmill walking at ~85% of maximal heart rate for 60 minutes per day. Preintervention and postintervention measures included hepatic triglyceride content, and a lipid saturation index and polyunsaturated lipid index (PUI) of the liver, obtained by (1)H magnetic resonance spectroscopy (N = 14). Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT), and mononuclear cells were isolated to assess reactive oxygen species production during the OGTT. Circulating glucose, insulin, and high molecular weight (HMW) adiponectin were determined from plasma., Main Outcome: Short-term aerobic exercise training improved hepatic lipid composition in patients with NAFLD., Results: Exercise training resulted in an increase in liver PUI (P < .05), increased insulin sensitivity (Matsuda Index: P < .05), HMW adiponectin (P < .05), and maximal oxygen consumption (P < .05). Reactive oxygen species production during the OGTT was reduced following exercise training (P < .05). HMW adiponectin was increased after the exercise program and the increase was positively correlated with the increase in liver PUI (r = 0.52, P = .05). Body weight remained stable during the program (P > .05)., Conclusion: Short-term exercise can target hepatic lipid composition, which may reduce the risk of NAFLD progression. The improvement in hepatic lipid composition may be driven by adiponectin.