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    Highlighting the positive impact of increasing feeding frequency on metabolism and weight management. Louis-Sylvestre Jeanine,Lluch Anne,Neant Françoise,Blundell John E Forum of nutrition Research on feeding frequency started more than 20 years ago and some studies have shown evidence of nutritional benefits, especially on metabolism and body weight management. Advice on feeding frequency could play an important role in public health policies by reducing levels of overweight and obesity, the prevalence of which has dangerously increased in most countries over the last few decades. The 17th International Congress of Nutrition brought to the forefront the benefits of increasing feeding frequency (i.e. keeping the same total daily energy intake but dividing it into more frequent meals than usual). Recent epidemiological studies, mostly carried out in France, have provided evidence on the beneficial effects of a fourth meal for those individuals who habitually choose this pattern. Supported by metabolic data, these findings have now been supported by experimental studies. The "goûter", commonly eaten in the afternoon in France by most children and many adults, has the biological characteristics of a meal because it is eaten in response to hunger. Suppressing the "goûter" in "habitual fourth meal eaters" soon leads to an increase in Body Mass Index (BMI). Further, people who are regular "goûter" eaters have a higher carbohydrate intake and better metabolic profile than other adults, even though their total energy intake is not greater. Increased feeding frequency leads to a reduction in the total secretion of insulin, an improvement in insulin resistance and a better blood glucose control, as well as an improvement in the blood lipid profile. The experts agreed that, as long as we do not consume more energy than we use up and we only eat when we are hungry, it may be useful to split our total energy intake into as many meals as our social pattern allows. However, the pattern of eating cannot be completely dissociated from the composition of foods consumed. Therefore within this energy intake, we must take care to consume not only a good balance of macronutrients with high carbohydrate and low fat levels, but also ensure that we get an adequate intake of essential micronutrients. "What you eat" and "When you eat it" are public health messages to communicate: frequent consumption of low energy dense high carbohydrate foods, rich in micronutrients, must be encouraged ensuring that energy intakes are not greater than energy expenditures and that eating episodes occur in a hunger state.
    Appetite and energy balancing. Rogers Peter J,Brunstrom Jeffrey M Physiology & behavior The idea that food intake is motivated by (or in anticipation of) 'hunger' arising from energy depletion is apparent in both public and scientific discourse on eating behaviour. In contrast, our thesis is that eating is largely unrelated to short-term energy depletion. Energy requirements meal-to-meal are trivial compared with total body energy stores, and energy supply to the body's tissues is maintained if a meal or even several meals are missed. Complex and exquisite metabolic machinery ensures that this happens, but metabolic regulation is only loosely coupled with the control of energy intake. Instead, food intake needs to be controlled because the limited capacity of the gut means that processing a meal presents a significant physiological challenge and potentially hinders other activities. We illustrate the relationship between energy (food) intake and energy expenditure with a simple analogy in which: (1) water in a bathtub represents body energy content, (2) water in a saucepan represents food in the gut, and (3) the bathtub is filled via the saucepan. Furthermore, (4) it takes hours to process and pass the full energy (macronutrient) content of the saucepan to the bathtub, and (5) both the saucepan and bathtub resist filling, representing negative feedbacks on appetite (desire to eat). This model is consistent with the observations that appetite is reduced acutely by energy intake (a meal added to the limited capacity of the saucepan/gut), but not increased by an acute increase in energy expenditure (energy removed from the large store of energy in the bathtub/body). The existence of relatively very weak but chronic negative feedback on appetite proportional to body fatness is supported by observations on the dynamics of energy intake and weight gain in rat dietary obesity. (We use the term 'appetite' here because 'hunger' implies energy depletion.) In our model, appetite is motivated by the accessibility of food and the anticipated and experienced pleasure of eating it. The latter, which is similar to food reward, is determined primarily by the state of emptiness of the gut and food liking related to the food's sensory qualities and macronutrient value and the individual's dietary history. Importantly, energy density adds value because energy dense foods are less satiating kJ for kJ and satiation limits further intake. That is, energy dense foods promote energy intake by virtue (1) of being more attractive and (2) having low satiating capacity kJ for kJ, and (1) is partly a consequence of (2). Energy storage is adapted to feast and famine and that includes unevenness over time of the costs of obtaining and ingesting food compared with engaging in other activities. However, in very low-cost food environments with energy dense foods readily available, risk of obesity is high. This risk can be and is mitigated by dietary restraint, which in its simplest form could mean missing the occasional meal. Another strategy we discuss is the energy dilution achieved by replacing some sugar in the diet with low-calorie sweeteners. Perhaps as or more significant, though, is that belief in short-term energy balancing (the energy depletion model) may undermine attempts to eat less. Therefore, correcting narratives of eating to be consistent with biological reality could also assist with weight control. 10.1016/j.physbeh.2016.03.038
    Effect of a Lifestyle Intervention Program With Energy-Restricted Mediterranean Diet and Exercise on Weight Loss and Cardiovascular Risk Factors: One-Year Results of the PREDIMED-Plus Trial. Salas-Salvadó Jordi,Díaz-López Andrés,Ruiz-Canela Miguel,Basora Josep,Fitó Montse,Corella Dolores,Serra-Majem Luís,Wärnberg Julia,Romaguera Dora,Estruch Ramon,Vidal Josep,Martínez J Alfredo,Arós Fernando,Vázquez Clotilde,Ros Emilio,Vioque Jesús,López-Miranda José,Bueno-Cavanillas Aurora,Tur Josep A,Tinahones Francisco J,Martín Vicente,Lapetra José,Pintó Xavier,Daimiel Lidia,Delgado-Rodríguez Miguel,Matía Pilar,Gómez-Gracia Enrique,Díez-Espino Javier,Babio Nancy,Castañer Olga,Sorlí José V,Fiol Miquel,Zulet María Ángeles,Bulló Mònica,Goday Albert,Martínez-González Miguel Á, Diabetes care OBJECTIVE:The long-term impact of intentional weight loss on cardiovascular events remains unknown. We describe 12-month changes in body weight and cardiovascular risk factors in PREvención con DIeta MEDiterránea (PREDIMED)-Plus, a trial designed to evaluate the long-term effectiveness of an intensive weight loss lifestyle intervention on primary cardiovascular prevention. RESEARCH DESIGN AND METHODS:Overweight/obese adults with metabolic syndrome aged 55-75 years ( = 626) were randomized to an intensive weight loss lifestyle intervention based on an energy-restricted Mediterranean diet, physical activity promotion, and behavioral support (IG) or a control group (CG). The primary and secondary outcomes were changes in weight and cardiovascular risk markers, respectively. RESULTS:Diet and physical activity changes were in the expected direction, with significant improvements in IG versus CG. After 12 months, IG participants lost an average of 3.2 kg vs. 0.7 kg in the CG ( < 0.001), a mean difference of -2.5 kg (95% CI -3.1 to -1.9). Weight loss ≥5% occurred in 33.7% of IG participants compared with 11.9% in the CG ( < 0.001). Compared with the CG, cardiovascular risk factors, including waist circumference, fasting glucose, triglycerides, and HDL cholesterol, significantly improved in IG participants ( < 0.002). Reductions in insulin resistance, HbA, and circulating levels of leptin, interleukin-18, and MCP-1 were greater in IG than CG participants ( < 0.05). IG participants with prediabetes/diabetes significantly improved glycemic control and insulin sensitivity, along with triglycerides and HDL cholesterol levels compared with their CG counterparts. CONCLUSIONS:PREDIMED-Plus intensive lifestyle intervention for 12 months was effective in decreasing adiposity and improving cardiovascular risk factors in overweight/obese older adults with metabolic syndrome, as well as in individuals with or at risk for diabetes. 10.2337/dc18-0836
    Impact of Lifestyle and Metformin Interventions on the Risk of Progression to Diabetes and Regression to Normal Glucose Regulation in Overweight or Obese People With Impaired Glucose Regulation. Herman William H,Pan Qing,Edelstein Sharon L,Mather Kieren J,Perreault Leigh,Barrett-Connor Elizabeth,Dabelea Dana M,Horton Edward,Kahn Steven E,Knowler William C,Lorenzo Carlos,Pi-Sunyer Xavier,Venditti Elizabeth,Ye Wen, Diabetes care OBJECTIVE:Both lifestyle and metformin interventions can delay or prevent progression to type 2 diabetes mellitus (DM) in people with impaired glucose regulation, but there is considerable interindividual variation in the likelihood of receiving benefit. Understanding an individual's 3-year risk of progressing to DM and regressing to normal glucose regulation (NGR) might facilitate benefit-based tailored treatment. RESEARCH DESIGN AND METHODS:We used the values of 19 clinical variables measured at the Diabetes Prevention Program (DPP) baseline evaluation and Cox proportional hazards models to assess the 3-year risk of progression to DM and regression to NGR separately for DPP lifestyle, metformin, and placebo participants who were adherent to the interventions. Lifestyle participants who lost ≥5% of their initial body weight at 6 months and metformin and placebo participants who reported taking ≥80% of their prescribed medication at the 6-month follow-up were defined as adherent. RESULTS:Eleven of 19 clinical variables measured at baseline predicted progression to DM, and 6 of 19 predicted regression to NGR. Compared with adherent placebo participants at lowest risk of developing diabetes, participants at lowest risk of developing diabetes who adhered to a lifestyle intervention had an 8% absolute risk reduction (ARR) of developing diabetes and a 35% greater absolute likelihood of reverting to NGR. Participants at lowest risk of developing diabetes who adhered to a metformin intervention had no reduction in their risk of developing diabetes and a 17% greater absolute likelihood of reverting to NGR. Participants at highest risk of developing DM who adhered to a lifestyle intervention had a 39% ARR of developing diabetes and a 24% greater absolute likelihood of reverting to NGR, whereas those who adhered to the metformin intervention had a 25% ARR of developing diabetes and an 11% greater absolute likelihood of reverting to NGR. CONCLUSIONS:Unlike our previous analyses that sought to explain population risk, these analyses evaluate individual risk. The models can be used by overweight and obese adults with fasting hyperglycemia and impaired glucose tolerance to facilitate personalized decision-making by allowing them to explicitly weigh the benefits and feasibility of the lifestyle and metformin interventions. 10.2337/dc17-1116
    Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort. Grunnet Louise G,Hansen Susanne,Hjort Line,Madsen Camilla M,Kampmann Freja B,Thuesen Anne Cathrine B,Granstrømi Charlotta,Strøm Marin,Maslova Ekaterina,Frikke-Schmidt Ruth,Damm Peter,Chavarro Jorge E,Hu Frank B,Olsen Sjurdur F,Vaag Allan Diabetes care OBJECTIVE:Offspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. RESEARCH DESIGN AND METHODS:We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. RESULTS:After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs. CONCLUSIONS:In summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy. 10.2337/dc17-0514
    Effects of acute and chronic protein intake on metabolism, appetite, and ghrelin during weight loss. Leidy Heather J,Mattes Richard D,Campbell Wayne W Obesity (Silver Spring, Md.) OBJECTIVE:This study evaluated the effects of acute and chronic consumption of higher dietary protein on energy expenditure, macronutrient use, appetite, and appetite-regulating hormones during weight loss in women. RESEARCH METHODS AND PROCEDURES:Thirty-eight women chronically consuming a 750 kcal/d energy-deficit diet with a protein content of 30% (higher protein-chronic diet, HP-CD, n = 21) or 18% (normal protein-chronic diet, NP-CD, n = 17) for 9 weeks were tested. On separate days, metabolic, appetite, and hormonal responses were measured over 4 hours when the women consumed a higher protein-acute meal (HP-AM) (30% of energy as protein) or a normal protein-acute meal (NP-AM) (18% of energy as protein). RESULTS:With chronic diet groups combined, HP-AM led to lower respiratory exchange ratio (0.829 +/- 0.005 vs. 0.843 +/- 0.008; p < 0.05), lower carbohydrate oxidation (p < 0.05), and higher fat oxidation (p < 0.05) compared with NP-AM. HP-AM also led to reduced self-reported postprandial hunger (p < 0.001) and desire to eat (p < 0.001) and lower postprandial ghrelin (252 +/- 16 vs. 274 +/- 18 ng/mL x 240 minutes, p < 0.05) compared with NP-AM. No differences in postprandial energy expenditure (PPEE) occurred between meals. When combining acute meals, respiratory exchange ratio was lower (p < 0.05) and protein oxidation (p < 0.001) was higher in the HP-CD vs. NP-CD. An acute meal-by-chronic diet interaction was observed with PPEE such that HP-AM led to greater PPEE in the HP-CD vs. NP-CD (28.7 +/- 2.7 vs. 19.9 +/- 2.7 kcal/min for 195 minutes; p < 0.05). CONCLUSIONS:During weight loss, thermogenesis and protein use appear to be influenced by chronic protein intake, while appetite and ghrelin are more responsive to acute protein intake. 10.1038/oby.2007.143
    Dietary Interventions for the Prevention of Type 2 Diabetes in High-Risk Groups: Current State of Evidence and Future Research Needs. Guess Nicola D Nutrients A series of large-scale randomised controlled trials have demonstrated the effectiveness of lifestyle change in preventing type 2 diabetes in people with impaired glucose tolerance. Participants in these trials consumed a low-fat diet, lost a moderate amount of weight and/or increased their physical activity. Weight loss appears to be the primary driver of type 2 diabetes risk reduction, with individual dietary components playing a minor role. The effect of weight loss via other dietary approaches, such as low-carbohydrate diets, a Mediterranean dietary pattern, intermittent fasting or very-low-energy diets, on the incidence of type 2 diabetes has not been tested. These diets-as described here-could be equally, if not more effective in preventing type 2 diabetes than the tested low-fat diet, and if so, would increase choice for patients. There is also a need to understand the effect of foods and diets on beta-cell function, as the available evidence suggests moderate weight loss, as achieved in the diabetes prevention trials, improves insulin sensitivity but not beta-cell function. Finally, prediabetes is an umbrella term for different prediabetic states, each with distinct underlying pathophysiology. The limited data available question whether moderate weight loss is effective at preventing type 2 diabetes in each of the prediabetes subtypes. 10.3390/nu10091245
    Very Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiological Changes in Responders and Nonresponders. Steven Sarah,Hollingsworth Kieren G,Al-Mrabeh Ahmad,Avery Leah,Aribisala Benjamin,Caslake Muriel,Taylor Roy Diabetes care OBJECTIVE:Type 2 diabetes mellitus (T2DM) is generally regarded as an irreversible chronic condition. Because a very low-calorie diet (VLCD) can bring about acute return to normal glucose control in some people with T2DM, this study tested the potential durability of this normalization. The underlying mechanisms were defined. RESEARCH DESIGN AND METHODS:People with a T2DM duration of 0.5-23 years (n = 30) followed a VLCD for 8 weeks. All oral agents or insulins were stopped at baseline. Following a stepped return to isocaloric diet, a structured, individualized program of weight maintenance was provided. Glucose control, insulin sensitivity, insulin secretion, and hepatic and pancreas fat content were quantified at baseline, after return to isocaloric diet, and after 6 months to permit the primary comparison of change between post-weight loss and 6 months in responders. Responders were defined as achieving fasting blood glucose <7 mmol/L after return to isocaloric diet. RESULTS:Weight fell (98.0 ± 2.6 to 83.8 ± 2.4 kg) and remained stable over 6 months (84.7 ± 2.5 kg). Twelve of 30 participants achieved fasting plasma glucose <7 mmol/L after return to isocaloric diet (responders), and 13 of 30 after 6 months. Responders had a shorter duration of diabetes and a higher initial fasting plasma insulin level. HbA1c fell from 7.1 ± 0.3 to 5.8 ± 0.2% (55 ± 4 to 40 ± 2 mmol/mol) in responders (P < 0.001) and from 8.4 ± 0.3 to 8.0 ± 0.5% (68 ± 3 to 64 ± 5 mmol/mol) in nonresponders, remaining constant at 6 months (5.9 ± 0.2 and 7.8 ± 0.3% [41 ± 2 and 62 ± 3 mmol/mol], respectively). The responders were characterized by return of first-phase insulin response. CONCLUSIONS:A robust and sustainable weight loss program achieved continuing remission of diabetes for at least 6 months in the 40% who responded to a VLCD by achieving fasting plasma glucose of <7 mmol/L. T2DM is a potentially reversible condition. 10.2337/dc15-1942
    Nutritional Lifestyle Intervention in Obese Pregnant Women, Including Lower Carbohydrate Intake, Is Associated With Increased Maternal Free Fatty Acids, 3-β-Hydroxybutyrate, and Fasting Glucose Concentrations: A Secondary Factorial Analysis of the European Multicenter, Randomized Controlled DALI Lifestyle Intervention Trial. Harreiter Jürgen,Simmons David,Desoye Gernot,Corcoy Rosa,Adelantado Juan M,Devlieger Roland,Galjaard Sander,Damm Peter,Mathiesen Elisabeth R,Jensen Dorte M,Andersen Lise Lotte T,Dunne Fidelma,Lapolla Annunziata,Dalfra Maria G,Bertolotto Alessandra,Wender-Ozegowska Ewa,Zawiejska Agnieszka,Mantaj Urszula,Hill David,Jelsma Judith G M,Snoek Frank J,Leutner Michael,Lackinger Christian,Worda Christof,Bancher-Todesca Dagmar,Scharnagl Hubert,van Poppel Mireille N M,Kautzky-Willer Alexandra Diabetes care OBJECTIVE:In our randomized controlled trial, we investigated the impact of healthy eating (HE) aiming for restricted gestational weight gain (GWG) and physical activity (PA) interventions on maternal and neonatal lipid metabolism. RESEARCH DESIGN AND METHODS:Obese pregnant women ( = 436) were included before 20 weeks' gestation and underwent glucose testing (oral glucose tolerance test) and lipid profiling at baseline and 24-28 and 35-37 gestational weeks after an at least 10-h overnight fast. This secondary analysis had a factorial design with comparison of HE ( = 221) versus no HE ( = 215) and PA ( = 218) versus no PA ( = 218). Maternal changes in triglycerides (TG), LDL cholesterol, HDL cholesterol, free fatty acids (FFAs), and leptin from baseline to end of pregnancy and neonatal outcomes were analyzed using general linear models with adjustment for relevant parameters. RESULTS:At 24-28 weeks' gestation, FFAs (mean ± SD, 0.60 ± 0.19 vs. 0.55 ± 0.17 mmol/L, < 0.01) were increased after adjustment for FFA at baseline, maternal age, BMI at time of examination, gestational week, insulin resistance, self-reported food intake, self-reported physical activity, and maternal smoking, and GWG was lower (3.3 ± 2.6 vs. 4.3 ± 2.8 kg, < 0.001, adjusted mean differences -1.0 [95% CI -1.5; -0.5]) in HE versus no HE. Fasting glucose levels (4.7 ± 0.4 vs. 4.6 ± 0.4 mmol/L, < 0.05) and 3-β-hydroxybutyrate (3BHB) (0.082 ± 0.065 vs. 0.068 ± 0.067 mmol/L, < 0.05) were higher in HE. Significant negative associations between carbohydrate intake and FFA, 3BHB, and fasting glucose at 24-28 weeks' gestation were observed. No differences between groups were found in oral glucose tolerance test or leptin or TG levels at any time. Furthermore, in PA versus no PA, no similar changes were found. In cord blood, elevated FFA levels were found in HE after full adjustment (0.34 ± 0.22 vs. 0.29 ± 0.16 mmol/L, = 0.01). CONCLUSIONS:HE intervention was associated with reduced GWG, higher FFAs, higher 3BHB, and higher fasting glucose at 24-28 weeks of gestation, suggesting induction of lipolysis. Increased FFA was negatively associated with carbohydrate intake and was also observed in cord blood. These findings support the hypothesis that maternal antenatal dietary restriction including carbohydrates is associated with increased FFA mobilization. 10.2337/dc19-0418