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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.
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Effects of dietary composition on energy expenditure during weight-loss maintenance.
Ebbeling, CB, Swain, JF, Feldman, HA, Wong, WW, Hachey, DL, Garcia-Lago, E, Ludwig, DS
JAMA. 2012;307(24):2627-34
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Many diets can produce weight loss over the short term, but most people struggle to maintain this loss over the long term. One explanation is that weight loss results in biological effects, such as a decline in energy expenditure and an increase in hunger, that promote weight regain. The aim of the study was to examine the effects of three different diets on energy expenditure, hormones (including leptin, insulin, cortisol and thyroid hormones) and metabolic indicators following a 10-15% weight loss. The three diets differed widely in macronutrient composition and were: low-fat/high glycaemic load (60% energy from carbohydrates, 20%, 20% protein) LF; low glycaemic index (40%-40%-20%) LGI; and very low carbohydrate/low glycaemic load (10%-60%-30%) VLC. Participants were assigned to one of the three diets for four weeks. Participants on the VLC diet had a resting energy expenditure (REE) of 67kcal/day greater than the LF diet, as well as a total energy expenditure (TEE) of 300kcal/day greater. The physiological basis for these differences is unclear. Although the VLC diet produced the greatest improvements in most metabolic syndrome markers, it also resulted in increased cortisol and inflammation markers. These could be deleterious to health in the long term.
Abstract
CONTEXT Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied. OBJECTIVE To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss. DESIGN, SETTING, AND PARTICIPANTS A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings. INTERVENTION After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks. MAIN OUTCOME MEASURES Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components. RESULTS Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged. CONCLUSION Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00315354.
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A nutrient-wide association study on blood pressure.
Tzoulaki, I, Patel, CJ, Okamura, T, Chan, Q, Brown, IJ, Miura, K, Ueshima, H, Zhao, L, Van Horn, L, Daviglus, ML, et al
Circulation. 2012;126(21):2456-64
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Elevated blood pressure (BP) is a major risk factor for coronary heart disease and stroke. This study aims to examine the association between a wide range of nutrients and BP using a systematic nutrient-wide association study (NWAS) approach. Data obtained from the cross-sectional International Study of Macro/Micro-nutrients and Blood Pressure (INTERMAP) were analysed. All foods and drinks, including supplements, from 24-hours dietary recalls as well as analytes from urine collection were recorded. Statistical analyses were then performed for the associations of 82 nutrients from food only, 73 nutrients from foods plus supplements, as well as 3 urinary electrolytes/electrolyte ratios with systolic and diastolic BP. The study found: direct associations between alcohol and urinary sodium/potassium ratio with systolic BP; inverse associations between dietary phosphorus, magnesium, non-heme iron, thiamin, folacin, and riboflavin with systolic BP; inverse associations between dietary folacin and riboflavin with diastolic BP; and inclusion of nutrients from supplements intake decreased the associations of folacin, thiamin and riboflavin intake with BP. Authors emphasised the importance of NWAS approach to identify the complex array of nutritional correlates of systolic and diastolic BP. Findings have a potential to represent causative relations that need to be further examined in observational and interventional studies.
Abstract
BACKGROUND A nutrient-wide approach may be useful to comprehensively test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner. METHODS AND RESULTS Data from 4680 participants aged 40 to 59 years in the cross-sectional International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. US National Health and Nutrition Examination Survey (NHANES) four cross-sectional cohorts (1999-2000, 2001-2002, 2003-2004, 2005-2006) were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (false discovery rate <5% in training, P<0.05 for internal and external validation). Among the validated nutrients, alcohol and urinary sodium-to-potassium ratio were directly associated with systolic BP, and dietary phosphorus, magnesium, iron, thiamin, folacin, and riboflavin were inversely associated with systolic BP. In addition, dietary folacin and riboflavin were inversely associated with diastolic BP. The absolute effect sizes in the validation data (NHANES) ranged from 0.97 mm Hg lower systolic BP (phosphorus) to 0.39 mm Hg lower systolic BP (thiamin) per 1-SD difference in nutrient variable. Inclusion of nutrient intake from supplements in addition to foods gave similar results for some nutrients, though it attenuated the associations of folacin, thiamin, and riboflavin intake with BP. CONCLUSIONS We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.
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The fall in leptin concentration is a major determinant of the metabolic adaptation induced by caloric restriction independently of the changes in leptin circadian rhythms.
Lecoultre, V, Ravussin, E, Redman, LM
The Journal of clinical endocrinology and metabolism. 2011;96(9):E1512-6
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Weight loss induced by caloric restriction (CR) is associated with a drop in energy expenditure (EE) beyond that expected for the changes in body composition, often blunting weight loss and predisposing individuals to weight regain. Recent evidence has identified leptin to be associated with this exaggerated decrease in EE. The aim of this trial was to explore the changes in leptin over a 24-hour period in response to caloric restriction, and explore its association with metabolic adaptation. Forty-eight participants were assigned to one of four groups for six months: control, CR, CR with exercise and a low calorie diet. This study indicates that the decline in 24-hour leptin in response to CR is a significant determinant of metabolic adaptation. Based on this study, the authors conclude that this decrease in leptin may underlie the additional reduction in EE observed in individuals following diet-induced weight loss.
Abstract
CONTEXT Leptin is involved in the hormonal regulation of the reproductive, somatotropic, thyroid, and autonomic axes and ultimately in the regulation of energy balance. In parallel to the metabolic adaptation observed in response to caloric restriction (CR), plasma leptin concentrations are substantially decreased, suggesting a role for this hormone in the drop in energy expenditure beyond that predicted by the changes in body composition (metabolic adaptation). AIM: The aim of the study was to explore the changes in 24-h leptin circadian rhythm in response to CR and to investigate the relationship between these changes and metabolic adaptation. DESIGN In a randomized, controlled trial (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy), 48 subjects were assigned to a control group or one of three CR groups for 6 months. Leptin concentration was assessed every 30 min for 24 h, and leptin circadian variations were fitted by Cosinor analysis. Sedentary energy expenditure and urinary catecholamine excretion were measured for 24 h in a metabolic chamber. RESULTS Six months of CR decreased body weight by -11.4 ± 0.6% (mean ± sem; P < 0.001). Mean 24-h circulating leptin concentration decreased by -44 ± 3% (P < 0.001), whereas leptin diurnal amplitude slightly increased over the 6 months of CR. CR caused a metabolic adaptation of -126 ± 25 kcal/d (P <0.001) and a significant decrease in urinary norepinephrine (-13 ± 3%) and T(3) concentrations (10 ± 2%). The metabolic adaptation was significantly and independently related to the changes in 24-h leptin (r(2) = 0 .22, P < 0.01) but not to the changes in leptin amplitude. CONCLUSION Our results confirm an important role for leptin as an independent determinant of the metabolic adaptation in response to CR.
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Oral sensory and cephalic hormonal responses to fat and non-fat liquids in bulimia nervosa.
Bello, NT, Coughlin, JW, Redgrave, GW, Moran, TH, Guarda, AS
Physiology & behavior. 2010;99(5):611-7
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Bulimia nervosa (BN) is characterised by episodes of compulsive binge eating and compensatory behaviours such as restriction/fasting, over exercising or self-induced purging. Research suggests that sufferers may have alterations in their food evaluations and the cephalic phase of eating. This study explores whether the oral sensory responses from high fat liquids compared to non-fat liquids were different in BN subjects compared to healthy controls. The hormonal responses to each liquid were qualified by measuring glucose, insulin, ghrelin and pancreatic polypeptides (which have been found to be associated with cephalic phase of eating solid foods). Subjective hunger levels were also measured. Participants were 10 women aged between 18 and 42 years, and the control group consisted of 11 women without an eating disorder. The study found not significant differences between the fat and non-fat liquids in terms of hunger levels or hormonal responses. However, there were differences between the BN group and the control. BN compared to controls had higher levels of hunger at baseline. BN's also rated the liquids 'fattier' tasting regardless of the fat content of the liquids and also reported a 'fear of swallowing' more than the control group. There were also differences between the BN and control group in baseline hormonal levels - BN's had significantly elevated ghrelin and pancreatic polypeptide levels. BN's also had elevated ghrelin levels throughout. The authors concluded that BN women have different orosensory responses that are not influenced by opioid receptor antagonism, evident in hormonal responses, or dependent on the fat content of a similarly textured liquid.
Abstract
Sensory evaluation of food involves endogenous opioid mechanisms. Bulimics typically limit their food choices to low-fat "safe foods" and intermittently lose control and binge on high-fat "risk foods". The aim of this study was to determine whether the oral sensory effects of a fat versus a non-fat milk product (i.e., traditional versus non-fat half-and-half) resulted in different subjective and hormonal responses in bulimic women (n=10) compared with healthy women (n=11). Naltrexone (50mg PO) or placebo was administered 1h before, and blood sampling began 30 min prior to and 29 min after, a 3 min portion controlled modified sham-feeding trial. Following an overnight fast, three morning trials (fat, naltrexone; fat, placebo; and non-fat, placebo) were administered in a random double-blind fashion separated by at least 3 days. Overall, there were no differences between Fat and Non-Fat trials. Hunger ratings (p<0.001) and pancreatic polypeptide levels (p<0.05) were higher for bulimics at baseline. Bulimics also had overall higher ratings for nausea (p<0.05), fatty taste (p<0.01), and fear of swallowing (p<0.005). Bulimics had approximately 40% higher total ghrelin levels at all time points (p<0.001). Hormones and glucose levels were not altered by the modified sham-feeding paradigm. Naltrexone, however, resulted in an overall increase in blood glucose and decrease in ghrelin levels in both groups (p<0.05, for both). These data suggest that bulimic women have different orosensory responses that are not influenced by opioid receptor antagonism, evident in hormonal responses, or dependent on the fat content of a similarly textured liquid.
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Sex and menopausal status influence human dietary requirements for the nutrient choline.
Fischer, LM, daCosta, KA, Kwock, L, Stewart, PW, Lu, TS, Stabler, SP, Allen, RH, Zeisel, SH
The American journal of clinical nutrition. 2007;85(5):1275-85
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Choline is used to form cell membranes, and it is a precursor for the neurotransmitter acetylcholine. Other than from the diet, choline can also be derived from the de novo biosynthesis of phosphatidylcholine. The current Adequate Intake for choline is considered sufficient to prevent deficiency, however an Estimated Average Requirement cannot be generated due to lack of availability of adequate human data. The aim of this study was to evaluate the dietary choline requirement in healthy men and women (pre- and postmenopausal), and to identify the clinical and metabolic sequelae of choline deficiency. Fifty-seven adult participants (26 healthy men, 16 premenopausal women and 15 postmenopausal women) were recruited for the study. A randomised double-blind protocol was followed to assign participants in one of the 2 arms; folate only (100 DFE) vs a dietary supplement of 400μg folic acid/d (768 DFE). Results show that independent of folate status, most men and postmenopausal women developed liver or muscle dysfunction when fed a low-choline diet, whereas premenopausal women were more resistant to developing such organ dysfunction. AP activity increased in all subjects in response to the low-choline diet regardless of whether they manifested organ dysfunction. Liver and muscle dysfunction occurred in response to a low-choline diet in both men and women. The current AI for choline was not be sufficient for some of the participants who became depleted despite this level of intake.
Abstract
BACKGROUND Although humans require dietary choline for methyl donation, membrane function, and neurotransmission, choline can also be derived from the de novo synthesis of phosphatidylcholine, which is up-regulated by estrogen. A recommended Adequate Intake (AI) exists for choline; however, an Estimated Average Requirement has not been set because of a lack of sufficient human data. OBJECTIVE The objective of the study was to evaluate the dietary requirements for choline in healthy men and women and to investigate the clinical sequelae of choline deficiency. DESIGN Fifty-seven adult subjects (26 men, 16 premenopausal women, 15 postmenopausal women) were fed a diet containing 550 mg choline x 70 kg(-1) x d(-1) for 10 d followed by <50 mg choline x 70 kg(-1) x d(-1) with or without a folic acid supplement (400 microg/d per randomization) for up to 42 d. Subjects who developed organ dysfunction during this diet had normal organ function restored after incremental amounts of choline were added back to the diet. Blood and urine were monitored for signs of toxicity and metabolite concentrations, and liver fat was assessed by using magnetic resonance imaging. RESULTS When deprived of dietary choline, 77% of men and 80% of postmenopausal women developed fatty liver or muscle damage, whereas only 44% of premenopausal women developed such signs of organ dysfunction. Moreover, 6 men developed these signs while consuming 550 mg choline x 70 kg(-1) x d(-1), the AI for choline. Folic acid supplementation did not alter the subjects' response. CONCLUSION Subject characteristics (eg, menopausal status) modulated the dietary requirement for choline, and a daily intake at the current AI was not sufficient to prevent organ dysfunction in 19 of the subjects.