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A dietary intervention for vasomotor symptoms of menopause: a randomized, controlled trial.
Barnard, ND, Kahleova, H, Holtz, DN, Znayenko-Miller, T, Sutton, M, Holubkov, R, Zhao, X, Galandi, S, Setchell, KDR
Menopause (New York, N.Y.). 2023;30(1):80-87
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Postmenopausal vasomotor symptoms cause recurrent discomfort, disrupt sleep, and reduce quality of life. A role for nutritional factors in vasomotor symptoms was suggested by their low prevalence in areas where traditional dietary staples included grains, legumes, vegetables, and other plant-derived foods. The aim of this study was to investigate the effects of a dietary intervention on vasomotor symptoms and menopause-related quality of life. This study is a randomised controlled study. Eighty-four participants were randomly assigned, in two cohorts; the intervention or control group. Results show that the dietary intervention led to clinically important reductions in menopausal symptoms. In fact, there was an 88% reduction in moderate-to-severe vasomotor events among participants in the intervention-group, accompanied by weight loss and improvements in physical, psychosocial, and sexual domains. Authors conclude that a dietary intervention, combining a reduced-fat vegan diet and daily soybeans, was associated with a marked reduction in postmenopausal vasomotor events, significant weight loss, and reductions in physical and sexual symptoms.
Abstract
OBJECTIVE Postmenopausal vasomotor symptoms disrupt quality of life. This study tested the effects of a dietary intervention on vasomotor symptoms and menopause-related quality of life. METHODS Postmenopausal women (n = 84) reporting at least two moderate-to-severe hot flashes daily were randomly assigned, in two successive cohorts, to an intervention including a low-fat, vegan diet and cooked soybeans (½ cup [86 g] daily) or to a control group making no dietary changes. During a 12-week period, a mobile application was used to record hot flashes (frequency and severity), and vasomotor, psychosocial, physical, and sexual symptoms were assessed with the Menopause-Specific Quality of Life questionnaire. Between-group differences were assessed for continuous ( t tests) and binary ( χ2 /McNemar tests) outcomes. In a study subsample, urinary equol was measured after the consumption of ½ cup (86 g) of cooked whole soybeans twice daily for 3 days. RESULTS In the intervention group, moderate-to-severe hot flashes decreased by 88% ( P < 0.001) compared with 34% for the control group ( P < 0.001; between-group P < 0.001). At 12 weeks, 50% of completers in the intervention group reported no moderate-to-severe hot flashes at all. Among controls, there was no change in this variable from baseline ( χ2 test, P < 0.001). Neither seasonality nor equol production status was associated with the degree of improvement. The intervention group reported greater reductions in the Menopause-Specific Quality of Life questionnaire vasomotor ( P = 0.004), physical ( P = 0.01), and sexual ( P = 0.03) domains. CONCLUSIONS A dietary intervention consisting of a plant-based diet, minimizing oils, and daily soybeans significantly reduced the frequency and severity of postmenopausal hot flashes and associated symptoms.
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Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial.
Thomsen, MN, Skytte, MJ, Samkani, A, Carl, MH, Weber, P, Astrup, A, Chabanova, E, Fenger, M, Frystyk, J, Hartmann, B, et al
Diabetologia. 2022;65(3):506-517
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The carbohydrate restricted diet has been shown to be beneficial for Type 2 diabetes (T2D) management and reducing cardiovascular disease risk. This open-label, parallel randomised controlled trial involved Type 2 diabetic patients taking antidiabetic medications who restricted their energy intake by following either a carbohydrate-reduced high protein diet or a conventional diabetic diet. Participants in both groups had a 5.9% reduction in body weight, similar changes in fasting NEFA, apoB, apoA-1, total cholesterol, LDL-cholesterol, HDL-cholesterol, and non-HDL cholesterol, and a significant reduction in fasting glucose, insulin, C-peptide, and HOMA2-IR after 6 weeks of intervention. Carbohydrate-reduced high protein diet group showed a greater reduction in HbA1c and diurnal mean glucose, glycaemic variability, fasting triacylglycerol concentration and liver fat content. Carbohydrate-reduced high protein diet caused an adverse reaction in some patients, and those following a carbohydrate-reduced high protein diet excreted more urea than those eating a conventional diabetic diet. To confirm the results of this study, long-term robust studies are needed. This study can assist healthcare professionals in understanding the benefits of following a carbohydrate-reduced high protein diet in improving glycaemic control, triglyceride levels, and reducing body weight in Type 2 diabetes patients.
Abstract
AIMS/HYPOTHESIS Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. METHODS This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), BMI >25 kg/m2, eGFR >30 ml min-1 [1.73 m]-2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). RESULTS Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol [-0.18 (-0.32, -0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] -0.8 [-1.2, -0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] -4.1 [-5.9, -2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] -18 [-29, -6]%, p < 0.01) and liver fat content (by mean [95% CI] -26 [-45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. CONCLUSIONS/INTERPRETATION Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. TRIAL REGISTRATION ClinicalTrials.gov NCT03814694. FUNDING The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg.
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The effect of periodic ketogenic diet on newly diagnosed overweight or obese patients with type 2 diabetes.
Li, S, Lin, G, Chen, J, Chen, Z, Xu, F, Zhu, F, Zhang, J, Yuan, S
BMC endocrine disorders. 2022;22(1):34
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Currently, the ketogenic diet is gaining popularity in managing Type 2 diabetes (T2D). Ketogenic diets replace carbohydrates with fat and include limited carbohydrates and adequate protein. This randomised controlled trial evaluated the effects of the 12-week ketogenic diet on sixty overweight or obese T2D patients. Both the ketogenic and control diabetes diet groups achieved significant reductions in weight, body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting blood glucose, fasting insulin, and HbA1c. However, the ketogenic group showed significantly greater reductions in body mass, blood lipids, and blood glucose than the control group. In the ketogenic diet group, serum uric acid levels were higher than those in the control diet group. It was found that the control diet group adhered to the diet for a longer period than the ketogenic diet group, whose willingness to adhere to the diet long-term was weaker. More robust long-term studies are needed to evaluate the long-term effects of a ketogenic diet. In this study, more patients who followed the ketogenic diet experienced hypoglycaemic events during the first four weeks. Healthcare providers should exercise caution when recommending a short term therapeutic ketogenic diet.
Abstract
BACKGROUND The ketogenic diet (KD) is characterized by fat as a substitute of carbohydrates for the primary energy source. There is a large number of overweight or obese people with type 2 diabetes mellitus (T2DM), while this study aims to observe periodic ketogenic diet for effect on overweight or obese patients newly diagnosed as T2DM. METHODS A total of 60 overweight or obese patients newly diagnosed as T2DM were randomized into two groups: KD group, which was given ketogenic diet, and control group, which was given routine diet for diabetes, 30 cases in each group. Both dietary patterns lasted 12 weeks, and during the period, the blood glucose, blood lipid, body weight, insulin, and uric acid before and after intervention, as well as the significance for relevant changes, were observed. RESULTS For both groups, the weight, BMI(body mass index), Waist, TG (triglyceride), TC(cholesterol), LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein cholesterol), FBG (fasting glucose), FINS (fasting insulin), HbA1c (glycosylated hemoglobin) were decreased after intervention (P < 0.05), while the decrease rates in the KD group was more significant than the control group. However, UA(serum uric acid) in the KD group showed an upward trend, while in the control group was not changed significantly (P > 0.05).The willingness to adhere to the ketogenic diet over the long term was weaker than to the routine diet for diabetes. CONCLUSION Among the overweight or obese patients newly diagnosed as type 2 diabetes mellitus, periodic ketogenic diet can not only control the body weight, but also control blood glucose and lipid, but long-term persistence is difficult.
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The potential prolonged effect at one-year follow-up after 18-month randomized controlled trial of a 90 g/day low-carbohydrate diet in patients with type 2 diabetes.
Chen, CY, Huang, WS, Ho, MH, Chang, CH, Lee, LT, Chen, HS, Kang, YD, Chie, WC, Jan, CF, Wang, WD, et al
Nutrition & diabetes. 2022;12(1):17
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A low carbohydrate diet (LCD) could be an effective dietary strategy for managing Type 2 Diabetes and body weight. This follow-up of a randomised controlled study evaluated the effect of moderate LCD after 18 months of 90 g/day LCD in 85 poorly controlled Type 2 Diabetic patients and compared it with Traditional Diabetic Diet (TDD). Those who followed the LCD diet ate significantly fewer carbohydrates and more protein and fat at the follow up between 18 and 30 months compared to those who followed the TDD group. The LCD group also showed significant improvements in serum HbA1C, two-hour serum glucose, serum alanine aminotransferase and Medication Effect Score in comparison with the TDD group. However, the level of triglycerides increased, and HDL levels decreased significantly in the LCD group from 18 to 30 months. There was however no significant difference between the groups in the improvement of HbA1C, fasting serum glucose, 2 h serum glucose, as well as serum cholesterol, triglycerides, low-density lipoprotein, ALT, creatinine, and urine microalbumin. To confirm the benefits of LCD on glycaemic control, further robust studies are needed. Results of this study can help healthcare professionals gain a better understanding of the prolonged effects of LCD on glycaemic control, liver function, and medication effect scores.
Abstract
OBJECTIVES To evaluate the effect at a one-year follow-up after an 18-month randomized controlled trial (RCT) of 90 gm/day low-carbohydrate diet (LCD) in type 2 diabetes. RESEARCH DESIGN AND METHODS Eighty-five poorly controlled type 2 diabetic patients with an initial HbA1c ≥ 7.5% who have completed an 18-month randomized controlled trial (RCT) on 90 g/day low-carbohydrate diet (LCD) were recruited and followed for one year. A three-day weighted food record, relevant laboratory tests, and medication effect score (MES) were obtained at the end of the previous trial and one year after for a total of 30 months period on specific diet. RESULTS 71 (83.5%) patients completed the study, 35 were in TDD group and 36 were in LCD group. Although the mean of percentage changes in daily carbohydrate intake was significantly lower for those in TDD group than those in LCD group (30.51 ± 11.06% vs. 55.16 ± 21.79%, p = 0.0455) in the period between 18 months and 30 months, patients in LCD group consumed significantly less amount of daily carbohydrate than patients in TDD group (131.8 ± 53.9 g vs. 195.1 ± 50.2 g, p < 0.001). The serum HbA1C, two-hour serum glucose, serum alanine aminotransferase (ALT), and MES were also significantly lower for the LCD group patients than those in the TDD group (p = 0.017, p < 0.001, p = 0.017, and p = 0.008 respectively). The mean of percentage changes of HbA1C, fasting serum glucose, 2 h serum glucose, as well as serum cholesterol, triglyceride, low-density lipoprotein, ALT, creatinine, and urine microalbumin, however, were not significantly different between the two groups (p > 0.05). CONCLUSIONS The one-year follow-up for patients on 90 g/d LCD showed potential prolonged and better outcome on glycaemic control, liver function and MES than those on TDD for poorly controlled diabetic patients.
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A Double-Blind, Placebo-Controlled Randomized Phase IIa Study: Evaluating the Effect of Curcumin for Treatment of Cancer Anorexia-Cachexia Syndrome in Solid Cancer Patients.
Chaiworramukkul, A, Seetalarom, K, Saichamchan, S, Prasongsook, N
Asian Pacific journal of cancer prevention : APJCP. 2022;23(7):2333-2340
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Cancer anorexia–cachexia syndrome (CACS) is usually found in advanced cancer patients. CACS is a multifactorial process which comprises skeletal muscle and adipose tissue loss which may be compounded by anorexia and a dysregulated metabolic state. The hypothesis of this study was that curcumin will increase body compositions and body weight in patients with solid malignancy and CACS when compared to placebo after adjusting by age, gender, primary site of cancer, stage of cancer, performance status, and supplementary nutrition support. This study was a double-blind, placebo-controlled randomised phase lla study. A total of 46 patients were enrolled, of whom 33 underwent 1:1 block of four randomisations. Seventeen patients were randomly assigned to receive curcumin at dose of 800 mg twice daily orally and sixteen patients were randomly assigned to received placebo. Results show that curcumin supplementation: (1) did not statistically significantly improve body compositions and body weight when compared to placebo; (2) may cause clinical benefit in term of hand grip muscle strength and slow progress of CACS by decreasing in basal metabolic rate and preventing the decline in serum albumin; and (3) administered orally for two months at a dose of up to 2 grams daily appeared safe and no serious adverse events were reported. Authors conclude that curcumin inhibited process of CACS via reduction of basal metabolic rate and slowed down the progression of hand-grip muscle strength loss. Furthermore, nuclear factor kappa B [regulator of gene expression] levels merit further exploration as potentially suitable predictive biomarker for CACS treatment with curcumin.
Abstract
OBJECTIVE We aim to investigate the effect of curcumin on preventing cancer anorexia-cachexia syndrome (CACS) via through mechanism of inhibition on NF-kB signal pathway. Outcome measurement for primary end point was improvement of body tissue composition, and the secondary end points were body weight and body mass index, hand grip muscle strengthening, and safety. METHODS This is randomized, double-blind, placebo-controlled phase ll a study, 33 patients with CACS in solid malignancy were enrolled and randomized in 1:1 to receive oral curcumin (at a dose of 800 mg twice daily) or placebo for 8 weeks. RESULTS All parameters of body compositions were not statistically significant different between two groups, which were consist body fat mass [-1.25(SEM 0.87) vs. +0.63(SEM 0.55); p=0.119], skeletal muscle mass [-0.35(SEM 0.60) vs.+0.33(SEM 0.42); p=0.408] and percent body fat [-0.47(SEM 0.95) vs. -0.29(SEM 0.82); p=0.893] including with basal metabolic rate [-13.47(SEM 21.94) vs. +15.30(13.76); p=0.336]. The average of weight loss was also not statistically significant different between two groups. [-1.4 kg(SEM 0.89) in curcumin vs-1.12 kg(SEM 0.73), p=0.810]. Notably, patient with curcumin had less reduction of hand-grip muscle strength on both hands [Rt. handed: -2.47 in curcumin vs. -5.36 in placebo; p=0.318] [Lt. handed: -1.98 vs. -5.43; p=0.317], and basal metabolic rate than placebo group. Most adverse events were grade 1 on both groups similarly. CONCLUSION Curcumin was not shown to be superior to placebo with regard to increasing the body composition in cancer patients with CACS. However, curcumin might show some clinical benefits, including slow progression of hand-grip muscle strength loss, and basal metabolic rate. Further investigations should be explored.
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Effects of Dietary Protein and Fat Content on Intrahepatocellular and Intramyocellular Lipids during a 6-Day Hypercaloric, High Sucrose Diet: A Randomized Controlled Trial in Normal Weight Healthy Subjects.
Surowska, A, Jegatheesan, P, Campos, V, Marques, AS, Egli, L, Cros, J, Rosset, R, Lecoultre, V, Kreis, R, Boesch, C, et al
Nutrients. 2019;11(1)
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High sugar diets can lead to increased fat accumulation in the liver and skeletal muscles, as intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) respectively. Elevation in these lipid concentrations is associated with an increased risk of various chronic diseases. The aim of this randomised crossover trial was to assess whether the consequences of a high sugar diet differed according to the protein and fat composition in 12 healthy adults. At the beginning of each trial period, participants consumed a 3-day weight maintenance diet followed by a 6-day high calorie, high sugar diet consisting of either low protein-high fat or high protein-low fat with a 4-8 week washout period. IHCL and IMCL concentrations, energy expenditure and blood metabolites were monitored after each weight maintenance diet and after each 6-day intervention diet period. This study found that both diets led to increased lipid concentrations, most notably the in liver cells. Lipid increases induced by the high protein-low fat diet were significantly lower than those induced by the low protein-high fat diet. Based on these results, the authors conclude that when overfed on a high sugar diet, high protein-low fat markedly reduces the amount of fat accumulation in liver and muscle cells and suggest that either dietary protein may have a protective effect of sugar and fat may have an additive adverse effect.
Abstract
Sucrose overfeeding increases intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid concentrations in healthy subjects. We hypothesized that these effects would be modulated by diet protein/fat content. Twelve healthy men and women were studied on two occasions in a randomized, cross-over trial. On each occasion, they received a 3-day 12% protein weight maintenance diet (WM) followed by a 6-day hypercaloric high sucrose diet (150% energy requirements). On one occasion the hypercaloric diet contained 5% protein and 25% fat (low protein-high fat, LP-HF), on the other occasion it contained 20% protein and 10% fat (high protein-low fat, HP-LF). IHCL and IMCL concentrations (magnetic resonance spectroscopy) and energy expenditure (indirect calorimetry) were measured after WM, and again after HP-LF/LP-HF. IHCL increased from 25.0 ± 3.6 after WM to 147.1 ± 26.9 mmol/kg wet weight (ww) after LP-HF and from 30.3 ± 7.7 to 57.8 ± 14.8 after HP-LF (two-way ANOVA with interaction: p < 0.001 overfeeding x protein/fat content). IMCL increased from 7.1 ± 0.6 to 8.8 ± 0.7 mmol/kg ww after LP-HF and from 6.2 ± 0.6 to 6.9 ± 0.6 after HP-LF, (p < 0.002). These results indicate that liver and muscle fat deposition is enhanced when sucrose overfeeding is associated with a low protein, high fat diet compared to a high protein, low fat diet.
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Role of Calcium and Low-Fat Dairy Foods in Weight-Loss Outcomes Revisited: Results from the Randomized Trial of Effects on Bone and Body Composition in Overweight/Obese Postmenopausal Women.
Ilich, JZ, Kelly, OJ, Liu, PY, Shin, H, Kim, Y, Chi, Y, Wickrama, KKAS, Colic-Baric, I
Nutrients. 2019;11(5)
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A woman’s menopausal years are believed to bring about weight gain due to various biological mechanisms, such as depletion of oestrogen. Many women undertake weight loss diets, in an attempt to control the weight gain, and although weight loss can reduce the risk factors for metabolic and cardiovascular disease etc, it can also lead to accelerated loss bone density and muscle mass. The objective of this study was to investigate whether by complementing a low-calorie diet with 4 to 5 servings of low-fat dairy foods per day and/or supplementing with calcium and vitamin D supplements would aid weight loss and preserve either/both bone and muscle mass. The study was conducted on 189 early postmenopausal, obese women. It was a randomized, placebo-controlled clinical trial conducted over 6 months. Researchers found that results were better for the participants on the low-fat dairy foods and those supplementing with calcium and vitamin D when compared to the placebo group (who only had placebo pills). They suggest that when embarking on a weight loss program it is beneficial to include 4 to 5 servings of low-fat dairy foods each day and take calcium and vitamin D supplements will have a positive impact on weight loss, bone density and muscle mass in post-menopausal women.
Abstract
Several studies have investigated the possibility of dairy foods and calcium (Ca) mediating weight and body composition, but a consensus has not been reached. We aimed to investigate weight-loss-related outcomes during intervention with low-fat dairy foods or Ca + vitamin D supplements, both as complements to hypocaloric diets. Overweight/obese Caucasian, early-postmenopausal women (n = 135) were recruited for a 6 month energy-restricted weight loss study complemented with either low-fat dairy foods (D; 4-5 servings/day), or Ca + vitamin D supplements (S); both to amount a total of ~1500 mg/day and 600 IU/day of Ca and vitamin D, respectively, or placebo pills (C). Bone mineral density (BMD) and lean and fat tissue were measured by Lunar iDXA. Serum and urinary markers of bone turnover were analyzed. Diet and physical activity were assessed with 3-day records. Participants on average lost ~4%, ~3%, and ~2% of body weight, fat, and lean tissue, respectively. The significantly better outcomes were noticed in participants in the D group regarding body composition (fat loss/lean tissue preservation) and in participants in the S group regarding the BMD outcomes, compared to those in the C group. Therefore, increasing low-fat dairy foods to 4-5 servings/day and/or increasing Ca & vitamin D intake by supplements (in those who are at the borderline dietary intake) may be beneficial for weight loss/maintenance and may lead to more favorable bone and body composition outcomes in postmenopausal women during moderate weight loss.
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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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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.