Explore the vast range of titles available.

\"Witness the electrifying exploits of the UNSC Spartans--including the origin of Sarah Palmer, the Master Chief back in action immediately following the events of Halo 4, and more--as they defend humanity across the galaxy! \"-- Provided by publisher.

Aims/hypothesisWeight reduction is fundamental for type 2 diabetes management and remission, but uncertainty exists over which diet type is best to achieve and maintain weight loss. We evaluated dietary approaches for weight loss, and remission, in people with type 2 diabetes to inform practice and clinical guidelines.MethodsFirst, we conducted a systematic review of published meta-analyses of RCTs of weight-loss diets. We searched MEDLINE (Ovid), PubMed, Web of Science and Cochrane Database of Systematic Reviews, up to 7 May 2021. We synthesised weight loss findings stratified by diet types and assessed meta-analyses quality with A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. We assessed certainty of pooled results of each meta-analysis using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) (PROSPERO CRD42020169258). Second, we conducted a systematic review of any intervention studies reporting type 2 diabetes remission with weight-loss diets, in MEDLINE (via PubMed), Embase and Cochrane Central Register of Controlled Trials, up to 10 May 2021. Findings were synthesised by diet type and study quality (Cochrane Risk of Bias tool 2.0 and Risk Of Bias In Non-randomised Studies – of Interventions [ROBINS-I]), with GRADE applied (PROSPERO CRD42020208878).ResultsWe identified 19 meta-analyses of weight-loss diets, involving 2–23 primary trials (n = 100–1587), published 2013–2021. Twelve were ‘critically low’ or ‘low’ AMSTAR 2 quality, with seven ‘high’ quality. Greatest weight loss was reported with very low energy diets, 1.7–2.1 MJ/day (400–500 kcal) for 8–12 weeks (high-quality meta-analysis, GRADE low), achieving 6.6 kg (95% CI −9.5, −3.7) greater weight loss than low-energy diets (4.2–6.3 MJ/day [1000–1500 kcal]). Formula meal replacements (high quality, GRADE moderate) achieved 2.4 kg (95% CI −3.3, −1.4) greater weight loss over 12–52 weeks. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets (high quality, GRADE high). High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3–2 kg) or no difference from control diets (low to critically low quality, GRADE very low/moderate). For type 2 diabetes remission, of 373 records, 16 met inclusion criteria. Remissions at 1 year were reported for a median 54% of participants in RCTs including initial low-energy total diet replacement (low-risk-of-bias study, GRADE high), and 11% and 15% for meal replacements and Mediterranean diets, respectively (some concerns for risk of bias in studies, GRADE moderate/low). For ketogenic/very low-carbohydrate and very low-energy food-based diets, the evidence for remission (20% and 22%, respectively) has serious and critical risk of bias, and GRADE certainty is very low.Conclusions/interpretationPublished meta-analyses of hypocaloric diets for weight management in people with type 2 diabetes do not support any particular macronutrient profile or style over others. Very low energy diets and formula meal replacement appear the most effective approaches, generally providing less energy than self-administered food-based diets. Programmes including a hypocaloric formula ‘total diet replacement’ induction phase were most effective for type 2 diabetes remission. Most of the evidence is restricted to 1 year or less. Well-conducted research is needed to assess longer-term impacts on weight, glycaemic control, clinical outcomes and diabetes complications.

The investigators sought evidence-based criteria for identifying late-onset hypogonadism in men between the ages of 40 and 79 years on the basis of the association between symptoms and a low testosterone level. The data suggest that late-onset hypogonadism can be defined by the presence of at least three sexual symptoms with a total testosterone level of less than 11 nmol per liter and a free testosterone level of less than 220 pmol per liter. The data suggest that late-onset hypogonadism can be defined by the presence of at least three sexual symptoms with a total testosterone level of less than 11 nmol per liter and a free testosterone level of less than 220 pmol per liter. The clinical importance of an age-related reduction in the testosterone level 1 – 3 remains controversial. 4 , 5 Because of the uncertainty regarding the nature of testosterone deficiency in aging men, 6 – 9 recent guidelines have suggested that so-called late-onset hypogonadism be regarded as a clinical and biochemical state with advancing age, characterized by particular symptoms and a low level of serum testosterone. 10 , 11 However, few data on hypogonadism in aging men are available 4 , 8 , 12 because of the lack of evidence regarding the exact criteria for identifying testosterone deficiency in older men who do not have pathological hypogonadism. 6 , 13 Although a familiar array . . .

In the approval process for new weight management therapies, regulators typically require estimates of effect size. Usually, as with other drug evaluations, the placebo-adjusted treatment effect (i.e., the difference between weight losses with pharmacotherapy and placebo, when given as an adjunct to lifestyle intervention) is provided from data in randomized clinical trials (RCTs). At first glance, this may seem appropriate and straightforward. However, weight loss is not a simple direct drug effect, but is also mediated by other factors such as changes in diet and physical activity. Interpreting observed differences between treatment arms in weight management RCTs can be challenging; intercurrent events that occur after treatment initiation may affect the interpretation of results at the end of treatment. Utilizing estimands helps to address these uncertainties and improve transparency in clinical trial reporting by better matching the treatment-effect estimates to the scientific and/or clinical questions of interest. Estimands aim to provide an indication of trial outcomes that might be expected in the same patients under different conditions. This article reviews how intercurrent events during weight management trials can influence placebo-adjusted treatment effects, depending on how they are accounted for and how missing data are handled. The most appropriate method for statistical analysis is also discussed, including assessment of the last observation carried forward approach, and more recent methods, such as multiple imputation and mixed models for repeated measures. The use of each of these approaches, and that of estimands, is discussed in the context of the SCALE phase 3a and 3b RCTs evaluating the effect of liraglutide 3.0 mg for the treatment of obesity.

Type 2 diabetes mellitus is common, disabling and expensive, despite improved glucose-lowering management and guidelines. Its dominant cause is weight gain, with ectopic fat accumulation in vital organs, reflected by a large waist circumference. Addressing the underlying cause, by low-calorie formula diets and integrated support for long-term weight-loss maintenance, produces remissions in almost half the treated population.

The frequency of obesity has risen dramatically in recent years but only few safe and effective drugs are currently available. We assessed the effect of liraglutide on bodyweight and tolerability in obese individuals without type 2 diabetes. We did a double-blind, placebo-controlled 20-week trial, with open-label orlistat comparator in 19 sites in Europe. 564 individuals (18–65 years of age, body-mass index 30–40 kg/m 2) were randomly assigned, with a telephone or web-based system, to one of four liraglutide doses (1·2 mg, 1·8 mg, 2·4 mg, or 3·0 mg, n=90–95) or to placebo (n=98) administered once a day subcutaneously, or orlistat (120 mg, n=95) three times a day orally. All individuals had a 500 kcal per day energy-deficit diet and increased their physical activity throughout the trial, including the 2-week run-in. Weight change analysed by intention to treat was the primary endpoint. An 84-week open-label extension followed. This study is registered with ClinicalTrials.gov, number NCT00422058. Participants on liraglutide lost significantly more weight than did those on placebo (p=0·003 for liraglutide 1·2 mg and p<0·0001 for liraglutide 1·8–3·0 mg) and orlistat (p=0·003 for liraglutide 2·4 mg and p<0·0001 for liraglutide 3·0 mg). Mean weight loss with liraglutide 1·2–3·0 mg was 4·8 kg, 5·5 kg, 6·3 kg, and 7·2 kg compared with 2·8 kg with placebo and 4·1 kg with orlistat, and was 2·1 kg (95% CI 0·6–3·6) to 4·4 kg (2·9–6·0) greater than that with placebo. More individuals (76%, n=70) lost more than 5% weight with liraglutide 3·0 mg that with placebo (30%, n=29) or orlistat (44%, n=42). Liraglutide reduced blood pressure at all doses, and reduced the prevalence of prediabetes (84–96% reduction) with 1·8–3·0 mg per day. Nausea and vomiting occurred more often in individuals on liraglutide than in those on placebo, but adverse events were mainly transient and rarely led to discontinuation of treatment. Liraglutide treatment over 20 weeks is well tolerated, induces weight loss, improves certain obesity-related risk factors, and reduces prediabetes. Novo Nordisk A/S, Bagsvaerd, Denmark.

To explore the factors (including knowledge and attitude) influencing the decision to follow a low-carbohydrate diet (LCD) or not in a sample of the UK population. An online questionnaire was distributed electronically to adults who had either followed LCD or not (February–December 2019). Demographics and self-reported “LCD-status” (current, past and non-follower) were collected. Multivariable linear regression was used with carbohydrate knowledge, dietary guideline agreement and theory of planned behaviour (TPB) constructs (all as predictors) to explain the intention to follow a LCD (outcome). Respondents (n = 723, 71% women, median age 34; 85% white-ethnicity) were either following (n = 170, 24%) or had tried a LCD in the preceding 3 months (n = 184, 25%). Current followers had lower carbohydrate knowledge scores (1–2 point difference, scale − 11 to 11) than past and non-followers. A majority of current LCD followers disagreed with the EatWell guide recommendations “Base meals on potatoes, bread, rice and pasta, or other starchy carbohydrates. Choose whole grains where possible” (84%) and “Choose unsaturated oils and spreads and eat in small amounts such as vegetable, rapeseed, olive and sunflower oils” (68%) compared to past (37%, 10%, respectively) and non-followers (16%, 8%, respectively). Weight-loss ranked first as a motivation, and the internet was the most influencial source of information about LCDs. Among LCD-followers, 71% reported ≥ 5% weight loss, and over 80% did not inform their doctor, nurse, or dietitian about following a diet. Approximately half of LCD followers incorporated supplements to their diets (10% used multivitamin/mineral supplements), despite the restrictive nature of the diet. TPB constructs, carbohydrate knowledge, and guideline agreement explained 60% of the variance for the intention to follow a LCD. Attitude (std-β = 0.60), perceived behavioural control (std-β = 0.24) and subjective norm (std-β = 0.14) were positively associated with the intention to follow a LCD, while higher knowledge of carbohydrate, and agreeing with national dietary guidelines were both inversely associated (std-β = − 0.09 and − 0.13). The strongest primary reason behind UK adults’ following a LCD is to lose weight, facilitated by attitude, perceived behavioural control and subjective norm. Higher knowledge about carbohydrate and agreement with dietary guidelines are found among people who do not follow LCDs.

Background/objectivesWeight-loss maintenance is challenging, and few succeed in the long term. This study aimed to explain how appetite-related hormones, adaptive thermogenesis, perceived hunger and stress influence weight-loss maintenance.Subjects/methodsFifteen adult women (age, 46.3 ± 9.5 years; BMI, 39.4 ± 4.3 kg/m2) participated in a 24-month intervention, which included 3–5 months total diet replacement (825–853 kcal/d). Body weight and composition (Magnetic Resonance Imaging), resting metabolic rate (indirect calorimetry), and fasting plasma concentration of leptin, ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and growth differentiation factor 15 (GDF-15) were measured at baseline and after weight loss, around 6 months. Perceptions relating to weight-loss maintenance were explored using qualitative interviews.ResultsMean (SD) changes in body weight (−13.8 ± 6.3 kg) and total adipose tissue (−11.5 ± 4.9 kg) were significant (P < 0.001). Weight loss was associated with a significant reduction in resting metabolic rate (−291 ± 226 kcal/day, P < 0.001) and adaptive thermogenesis (−150 ± 162 kcal/day, P = 0.003), reduction in leptin (P < 0.001) and GLP-1 (P = 0.015), an increase in ghrelin (P < 0.001), and no changes in PYY and GDF-15. Weight regain between 6 and 24 months (6.1 ± 6.3 kg, P < 0.05) was correlated positively with change in GLP-1 (r = 0.5, P = 0.037) and negatively with GLP-1 at baseline (r = −0.7, P = 0.003) and after weight loss (r = −0.7, P = 0.005). Participants did not report increased hunger after weight loss, and stress-related/emotional eating was perceived as the main reason for regain.ConclusionsWeight regain is more likely with lower fasting GLP-1 and greater reduction in GLP-1 after weight loss, but psychological aspects of eating behaviour appear as important in attenuating weight-loss maintenance.

Key Words: obesity, type 2 diabetes, remission

Diabetes management relies on effective evidence-based advice that informs and empowers individuals to manage their health. Alongside other cornerstones of diabetes management, dietary advice has the potential to improve glycaemic levels, reduce risk of diabetes complications and improve health-related quality of life. We have updated the 2004 recommendations for the nutritional management of diabetes to provide health professionals with evidence-based guidelines to inform discussions with patients on diabetes management, including type 2 diabetes prevention and remission. To provide this update we commissioned new systematic reviews and meta-analyses on key topics, and drew on the broader evidence available. We have strengthened and expanded on the previous recommendations to include advice relating to dietary patterns, environmental sustainability, food processing, patient support and remission of type 2 diabetes. We have used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to determine the certainty of evidence for each recommendation based on findings from the commissioned and identified systematic reviews. Our findings indicate that a range of foods and dietary patterns are suitable for diabetes management, with key recommendations for people with diabetes being largely similar for those for the general population. Important messages are to consume minimally processed plant foods, such as whole grains, vegetables, whole fruit, legumes, nuts, seeds and non-hydrogenated non-tropical vegetable oils, while minimising the consumption of red and processed meats, sodium, sugar-sweetened beverages and refined grains. The updated recommendations reflect the current evidence base and, if adhered to, will improve patient outcomes. Graphical abstract