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Foregut Exclusion Enhances Incretin and Insulin Secretion After Roux-en-Y Gastric Bypass in Adults With Type 2 Diabetes.
Kirwan, JP, Axelrod, CL, Kullman, EL, Malin, SK, Dantas, WS, Pergola, K, Del Rincon, JP, Brethauer, SA, Kashyap, SR, Schauer, PR
The Journal of clinical endocrinology and metabolism. 2021;(10):e4192-e4201
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Abstract
INTRODUCTION Patients with type 2 diabetes experience resolution of hyperglycemia within days after Roux-en-Y gastric bypass (RYGB) surgery. This is attributed, in part, to enhanced secretion of hindgut factors following exclusion of the gastric remnant and proximal intestine during surgery. However, evidence of the mechanisms of remission remain limited due to the challenges of metabolic evaluation during the early postoperative period. The purpose of this investigation was to determine the role of foregut exclusion in the resolution of type 2 diabetes after RYGB. METHODS Patients with type 2 diabetes (n = 15) undergoing RYGB had a gastrostomy tube (G-tube) placed in their gastric remnant at time of surgery. Patients were randomized to receive a mixed meal tolerance test via oral or G-tube feeding immediately prior to and 2 weeks after surgery in a repeated measures crossover design. Plasma glucose, insulin, C-peptide, incretin responses, and indices of meal-stimulated insulin secretion and sensitivity were determined. RESULTS Body weight, fat mass, fasting glucose and insulin, and circulating lipids were significantly decreased 2 weeks after surgery. The glycemic response to feeding was reduced as a function of total area under the curve but not after adjustment for the reduction in fasting glucose. Oral feeding significantly enhanced insulin and incretin secretion after RYGB, which was entirely ablated by G-tube feeding. CONCLUSION Foregut exclusion accounts for the rise in incretin and insulin secretion but may not fully explain the early improvements in glucose metabolism after RYGB surgery.
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A Whole-Grain Diet Increases Whole-Body Protein Balance Compared with a Macronutrient-Matched Refined-Grain Diet.
Mey, JT, Godin, JP, Scelsi, AR, Kullman, EL, Malin, SK, Yang, S, Floyd, ZE, Poulev, A, Fielding, RA, Ross, AB, et al
Current developments in nutrition. 2021;(11):nzab121
Abstract
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/m2) 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 (13C-leucine) and integrated over 24 h (15N-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).
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A Whole-Grain Diet Increases Glucose-Stimulated Insulin Secretion Independent of Gut Hormones in Adults at Risk for Type 2 Diabetes.
Malin, SK, Kullman, EL, Scelsi, AR, Godin, JP, Ross, AB, Kirwan, JP
Molecular nutrition & food research. 2019;(7):e1800967
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Abstract
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-peptide0-240 /Glc0-240 , 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.
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A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
Malin, SK, Kullman, EL, Scelsi, AR, Haus, JM, Filion, J, Pagadala, MR, Godin, JP, Kochhar, S, Ross, AB, Kirwan, JP
Metabolism: clinical and experimental. 2018;82:111-117
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Plain language summary
Literature shows that dietary whole-grain intake is associated with a lower incidence of type 2 diabetes. The aim of the study was to investigate the association between a whole-grain diet and insulin resistance and glucose use in individuals at risk for type 2 diabetes. The study was a randomized, double-blind, controlled crossover trial involving fourteen middle-aged, obese adults at risk for diabetes. Randomisation was carried out prior to metabolic testing. Results indicate that whole-grain intake as part of a mixed-meal diet significantly improved post-prandial (after a meal) glucose metabolism in middle-aged obese adults. Furthermore, both whole-grain and refined-grain interventions induced about 3–6% weight and fat loss. Authors conclude that whole-grain intake effectively promotes glycaemic control by improving insulin action.
Abstract
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/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, 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 Ra 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.
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A Whole-Grain Diet Reduces Cardiovascular Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial.
Kirwan, JP, Malin, SK, Scelsi, AR, Kullman, EL, Navaneethan, SD, Pagadala, MR, Haus, JM, Filion, J, Godin, JP, Kochhar, S, et al
The Journal of nutrition. 2016;(11):2244-2251
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Abstract
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/m2): 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.
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A Community-Based Exercise and Support Group Program in African-American Breast Cancer Survivors (ABCs).
Nock, NL, Owusu, C, Kullman, EL, Austin, K, Roth, B, Cerne, S, Harmon, C, Moore, H, Vargo, M, Hergenroeder, P, et al
Journal of physical therapy and health promotion. 2013;(1):15-24
Abstract
African-American (AA) women have higher rates of breast cancer (BCa) mortality than Caucasian women, and a recent study using data from the Surveillance, Epidemiology and End Results (SEER) registry suggests that this disparity may be due, in part, to the poorer health status of AAs at diagnosis and not treatment related issues. Randomized controlled trials involving supervised aerobic and resistance exercise have shown improved body composition and improvement in cancer-related biomarkers in BCa patients and may lead to improved recurrence and survival rates; however, most trials have focused on Caucasians and many have been conducted in academic- and clinic-based settings. We evaluated the feasibility of conducting a 20-week, supervised, resistance training, group exercise intervention coupled with a support group and home walking program utilizing facilities and personnel at a community cancer support center (The Gathering Place, Beachwood, Ohio) in AA Stage I-III BCa survivors who were within 12 months of completing treatment (surgery, chemotherapy, and/or breast irradiation); and, evaluated the potential effects of this intervention on physical measures and cancer-related biomarkers. 27 patients provided informed consent and 19 participated in the program. On average, attendance rates were 70.0% ± 19.1% for the exercise sessions and 63.1% ± 13.8% for the support group. We observed a significant decrease in circulating C-peptide levels (B: 893.9 ± 399.1 pg/mL; EOI: 723.9 ± 319.0 pg/mL; p=0.01). Although we did not observe a significant decrease in weight in the entire sample, there was a significant decrease in waist circumference and percent total body fat among those who attended 70% or more of the exercise sessions. In summary, we demonstrated that conducting lifestyle interventions in AA BCa survivors in a community setting is feasible. Future interventions should invoke strategies to enhance adherence and include a structured dietary intervention to enable greater weight loss.