Metabolic changes with intermittent fasting.

BACKGROUND: The prevalence of obesity is rising globally and effective strategies to treat obesity are needed. Intermittent fasting, a dietary intervention for weight management, has received growing interest from the general public, as well as healthcare professionals, as a form of lifestyle intervention. METHODS: We executed a rapid review using PUBMED database to identify systematic reviews that examined the impact of intermittent fasting on metabolic indices, published between 2011 and 2022. RESULTS: Intermittent fasting leads to weight loss of a similar magnitude to continuous energy restriction. Most of the evidence shows that intermittent fasting leads to greater fat loss as measured by fat mass (kg) or body fat percentage compared to an ad libitum diet, but fat loss attained during intermittent fasting is not significantly different to continuous energy restriction, although recent evidence shows intermittent fasting to be superior. There is mixed evidence for the impact of intermittent fasting on insulin resistance, fasting glucose and lipid profile. Some studies focused on populations of Muslim people, which showed that Ramadan fasting may lead to weight loss and improvement of metabolic parameters during fasting, although the effects are reversed when fasting is finished. CONCLUSIONS: Intermittent fasting is more effective than an ad libitum dietary intake, and equally or more effective as continuous energy restriction, for weight management. However, there is inconclusive evidence on whether intermittent fasting has a clinically beneficial effect on glucose and lipid metabolism.

Health Outcomes Following Engagement With a Digital Health Tool Among People With Prediabetes and Type 2 Diabetes: Prospective Evaluation Study.

BACKGROUND: Diabetes is a worldwide chronic condition causing morbidity and mortality, with a growing economic burden on health care systems. Complications from poorly controlled diabetes are associated with increased socioeconomic costs and reduced quality of life. Smartphones have become an influential platform, providing feasible tools such as health apps to deliver tailored support to enhance the ability of patients with diabetes for self-management. Gro Health is a National Health Service division X-certified digital health tool used to deliver educational and monitoring support to facilitate the development of skills and practices for maintaining good health. OBJECTIVE: This study aims to assess self-reported outcomes of the Gro Health app among users with diabetes and prediabetes and identify the factors that determine engagement with the digital health tool. METHODS: This was a service evaluation of self-reported data collected prospectively by the developers of the Gro Health app. The EQ-5D questionnaire is a standardized tool used to measure health status for clinical and economic appraisal. Gro Health users completed the EQ-5D at baseline and 6 months after using the app. Users provided informed consent for the use of their anonymized data for research purposes. EQ-5D index scores and visual analogue scale (VAS) scores were calculated at baseline and 6 months for individuals with prediabetes and type 2 diabetes. Descriptive statistics and multiple-regression models were used to assess changes in the outcome measures and determine factors that affected engagement with the digital tool. RESULTS: A total of 84% (1767/2114) of Gro Health participants completed EQ-5D at baseline and 6 months. EQ-5D index scores are average values that reflect people's preferences about their health state (1=full health and 0=moribund). There was a significant and clinically meaningful increase in mean EQ-5D index scores among app users between baseline (0.746, SD 0.23) and follow-up (0.792, SD 0.22; P<.001). The greatest change was observed in the mean VAS score, with a percentage change of 18.3% improvement (61.7, SD 18.1 at baseline; 73.0, SD 18.8 at follow-up; P<.001). Baseline EQ-5D index scores, age, and completion of educational modules were associated with significant changes in the follow-up EQ-5D index scores, with baseline EQ-5D index scores, race and ethnicity, and completion of educational modules being significantly associated with app engagement (P<.001). CONCLUSIONS: This study provides evidence of a significant positive effect on self-reported quality of life among people living with type 2 diabetes engaging with a digital health intervention. The improvements, as demonstrated by the EQ-5D questionnaire, are facilitated through access to education and monitoring support tools within the app. This provides an opportunity for health care professionals to incorporate National Health Service-certified digital tools, such as Gro Health, as part of the holistic management of people living with diabetes.

Metabolic-Associated Fatty Liver Disease and the Gut Microbiota.

As an important sequela of the burgeoning global obesity problem, metabolic-associated fatty liver disease (MAFLD) has gained increasing prominence recently. The gut-liver axis (GLA) provides a direct conduit to the liver for the gut microbiota and their metabolic by-products (including secondary bile acids, ethanol, and trimethylamine). These GLA-related factors, including the host inflammatory response and integrity of the gut mucosal wall, likely contribute to the pathogenesis of MAFLD. Accordingly, these GLA-related factors are targets for possible preventive and treatment strategies for MAFLD, and include probiotics, prebiotics, bile acids, short-chain fatty acids, fecal microbiota transplantation, carbon nanoparticles, and bacteriophages.

Implementation of a Digital Health Tool for Patients Awaiting Input From a Specialist Weight Management Team: Observational Study.

BACKGROUND: Digital tools are increasingly used on a population level as a weight loss strategy for people living with overweight and obesity. Evidence supports the feasibility of digital tools for the management of obesity in a community setting, but there is only emerging evidence for the feasibility of such tools in specialist weight management services. No study has assessed the uptake of digital tools among patients awaiting their first appointment with a specialist weight management service. OBJECTIVE: The objective of this study was to understand interest, acceptance, and engagement with a digital behavioral change platform to support specialist weight management. METHODS: This was an observational study registered as a service innovation. All patients on the waiting list for a first appointment in the tier 3 weight management service at University Hospitals Coventry and Warwickshire National Health Service (NHS) Trust were eligible to access the NHS-approved digital tool. Data on interest and engagement with the digital tool were collected. Routine clinical data were used to describe patient demographics. Focus groups were held to explore patients' views on the use of digital tools as part of a specialist weight management service. RESULTS: A total of 199 patients on the waiting list were informed about the available digital tool. Just over a half (n=102, 51.3%) of patients were interested in using the app, with over one-third (n=68, 34%) of all patients engaging with the app. Overall, a third of patients on the waiting list (n=63, 32%) did not respond to the invite and 34 (17%) of patients expressed no interest in the app. Emotional eating and higher BMI was associated with interest in the Gro Health app. Male gender was associated with reduced engagement with the app. There were no differences in interest in the Gro Health app according to age, ethnicity, metabolic measures of glycemia, and lipid profile. CONCLUSIONS: It is feasible to offer digital tools such as Gro Health to patients awaiting their first appointment with specialist weight management services. Future research should explore barriers and facilitators of engagement with digital tools. Additionally, there is a need to further evaluate the effectiveness of such tools in specialist weight management services.

Designer GLP1 poly-agonist peptides in the management of diabesity.

INTRODUCTION: To date, the 21st Century has witnessed key developments in the management of diabesity (a conflation of obesity and Type 2 Diabetes Mellitus [T2D]), including Glucagon Like Peptide 1 (GLP1) receptor agonist therapies, and recently the 'designer' GLP1 Poly-agonist Peptides (GLP1PPs). AREAS COVERED: A PubMed search of published data on the GLP1PP class of therapies was conducted. The gut-brain axis forms complex multi-directional interlinks that include autonomic nervous signaling, components of the gut microbiota (including metabolic by-products and gram-negative cell wall components [e.g. endotoxinaemia]), and incretin hormones that are secreted from the gut in response to the ingestion of nutrients. The development of dual-incretin agonist therapies includes combinations of the GLP1 peptide with Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon (Gcg), Cholecystokinin (CCK), Peptide YY (PYY), and Glucagon-Like Peptide 2 (GLP2). Triple incretin agonist therapies are also under development. EXPERT OPINION: At the dawn of a new era in the therapeutic management of diabesity, the designer GLP1PP class holds great promise, with each novel combination building on a preexisting palimpsest of clinical data and insights. Future innovations of the GLP1PP class will likely enable medically induced weight loss and glycemic control in diabesity to rival or even out-perform those resulting from bariatric surgery.

Effect of an Online Mindfulness Course for Hospital Doctors During COVID-19 Pandemic on Resilience and Coping.

INTRODUCTION: Physicians' wellbeing is a priority to prevent increasing rates of poor mental health and burnout, exacerbated by caregiving during the COVID-19 pandemic. Structured mindfulness courses have been shown to be beneficial, but face-to-face delivery is not always feasible in the context of busy health services. Remotely delivered structured mindfulness courses could enable wider participation, particularly at time when social distancing to prevent infection transmission is necessary. Our objective was to test the feasibility of a remotely delivered structured mindfulness course for hospital doctors during the COVID-19 pandemic. METHODS: This was a feasibility study run at one English hospital between January and March 2021, when COVID-19 admissions were at a high. Interested doctors participated in a 6-session remotely delivered mindfulness course. Sessions lasted 90 min and could be attended on-line or the recording watched at later time. Main outcome measures were data on interest, course attendance and engagement, together with validated psychological outcome measures at baseline and follow-up after course completion. RESULTS: 20 doctors expressed interest to participate and 16 started the course. Of these, 12 completed at least 3 sessions (median = 4); difficulty attending resulted from conflicting clinical commitments and rosters. Twelve participants completed the follow-up survey. They rated the course highly and all perceived it to have been useful, with statistically significant (P < .01) improvements in wellbeing and mindfulness scores. They all stated that they would recommend this course to their colleagues and most (10/12) were interested in follow-up mindfulness sessions. CONCLUSION: Remotely delivered structured mindfulness training for hospital doctors was feasible, but there is a need to address the difficulties that affected attendance in order to optimize accessibility and completion of such programs.

The role of mindfulness training in sustaining weight reduction: retrospective cohort analysis.

BACKGROUND: Psychological stress has an established bi-directional relationship with obesity. Mindfulness techniques reduce stress and improve eating behaviours, but their long-term impact remains untested. CALMPOD (Compassionate Approach to Living Mindfully for Prevention of Disease) is a psychoeducational mindfulness-based course evidenced to improve eating patterns across a 6-month period, possibly by reducing stress. However, no long-term evaluation of impact exists. AIMS: This study retrospectively evaluates 2-year outcomes of CALMPOD on patient engagement, weight and metabolic markers. METHOD: All adults with a body mass index >35 kg/m2 attending an UK obesity service during 2016-2020 were offered CALMPOD. Those who refused CALMPOD were offered standard lifestyle advice. Routine clinic data over 2 years, including age, gender, 6-monthly appointment attendance, weight, haemoglobin A1C and total cholesterol, were pooled and analysed to evaluate CALMPOD. RESULTS: Of 289 patients, 163 participated in the CALMPOD course and 126 did not. No baseline demographic differences existed between the participating and non-participating groups. The CALMPOD group had improved attendance across all 6-monthly appointments compared with the non-CALMPOD group (P < 0.05). Mean body weight reduction at 2 years was 5.6 kg (s.d. 11.2, P < 0.001) for the CALMPOD group compared with 3.9 kg (s.d. 10.5, P < 0.001) for the non-CALMPOD group. No differences in haemoglobin A1C and fasting serum total cholesterol were identified between the groups. CONCLUSIONS: The retrospective evaluation of CALMPOD suggests potential for mindfulness and compassion-based group educational techniques to improve longer-term patient and clinical outcomes. Prospective large-scale studies are needed to evaluate the impact of stress on obesity and the true impact of CALMPOD.

The DAPA-DIET study: Metabolic response to Dapagliflozin combined with dietary carbohydrate restriction in patients with Type 2 Diabetes Mellitus and Obesity-A longitudinal cohort study.

OBJECTIVE: The cardio-renal benefits of sodium glucose-like transporter 2 inhibitor (SGLT2i) therapies have been demonstrated in patients with and without type 2 diabetes. However, no studies have explored the long-term metabolic effects of SGLT2i, combined with dietary carbohydrate restriction. Our primary objective was to describe long-term changes in weight, energy expenditure, appetite and body composition after 12 months of Dapagliflozin therapy, with carbohydrate restriction, in people with type 2 diabetes and obesity. Our secondary objective was to assess changes in adiponectin and leptin. METHOD: This was a 12-month cohort study in a secondary care setting. Participants (n = 18) with type 2 diabetes (T2D) and class 3 obesity underwent baseline indirect calorimetry for determination of 24-h energy expenditure, body composition, fasting serum leptin and adiponectin levels, and appetitive assessments. Following initiation of Dapagliflozin (and dietary carbohydrate restriction), measurements were repeated at monthly intervals up to 12 months. RESULTS: Mean starting weight of participants was 129.4 kg (SD 25.9), mean BMI 46.1 kg/m2 (SD 8.3) and mean HbA1c 53.9 mmol/mol (14.1). Seventeen participants completed the study; after 12 months of Dapagliflozin and dietary carbohydrate restriction, mean weight loss was 8.1 kg (SD 11.3 kg; p = .009). This was mediated by reduced fat mass (mean loss, 9.9 kg; SD 10.4 kg; p = .002) associated with reduced serum leptin at 12 months (mean reduction 11,254 pg/ml; SD 16,075; p = .011). There were no significant changes in self-reported appetite, 24-h energy expenditure or serum adiponectin during follow-up. CONCLUSION: In this study, combined Dapagliflozin therapy and carbohydrate restriction in patients with T2D and obesity resulted in a significant reduction of body weight and fat mass at 12 months without any discernible changes in energy expenditure or appetite. These results offer a scientific and clinical rationale to conduct an exploratory trial investigating the effects of a low carbohydrate diet combined with SGLT2 inhibitors in patients with T2D.

Novel perspectives of sodium handling in type 2 diabetes mellitus.

INTRODUCTION: As a key regulator of body water, sodium homeostasis forms an essential component of human physiology. Type 2 Diabetes Mellitus (T2D)-associated sodium overload stems from chronic renal retention of sodium, contributing toward the development of adverse cardiovascular sequelae. AREAS COVERED: Our traditional model of sodium regulation invokes two compartments: extracellular fluid (ECF [plasma and interstitial fluid]) and intracellular fluid (ICF). Data from the Mars program reveal inconsistencies with this two-space model, including mismatches between net body sodium and water. Recent data utilizing 23Na magnetic resonance imaging (MRI) show a preponderance of bound sodium within human dermis, consistent with a third space repository and providing compelling evidence to support a three-space model in which dermal sodium binding facilitates sodium homeostasis within the ECF and ICF. This buffer is impaired in T2D, with diminishment of dermal bound sodium that may promote deleterious sequelae of sodium overload within the ECF and ICF. EXPERT OPINION: Future studies should focus on novel therapeutic opportunities for sodium regulation in T2D and other conditions of sodium dysregulation. The ratio of free:bound dermal sodium (reflecting sodium storage capacity) could be utilized as a clinical biomarker for salt and water balance, to improve diagnostic accuracy and facilitate clinical decision-making.

A rapid review of the evidence for children's TV and online advertisement restrictions to fight obesity.

The World Health Organisation has urged all governments to address rising rates of obesity by implementing population-based interventions, such as restrictions on the marketing to children of unhealthy food and beverage items. However, the relationship between unhealthy food advertisements and childhood obesity is disputed by industry-sponsored reports, which recommend promoting physical activity and weight loss campaigns rather than policies to limit exposure to advertisements. We aimed to elucidate this debate by providing a narrative review of the evidence on the relationship between unhealthy TV and online food advertisements, short-term food consumption and childhood obesity. We also examined the impact of unhealthy food advertisements on vulnerable groups and identified which policy interventions are supported by current evidence. We conducted a rapid overview of reviews published since 2006. From a synthesis of 18 reviews meeting the inclusion criteria, we conclude that exposure to unhealthy TV and online food advertising is a contributing factor to childhood obesity. Evidence of a relationship between exposure to unhealthy food advertisements and childhood obesity was evident at all stages of the causal pathway, including a clear dose-response relationship. The evidence base was particularly strong for children aged 3-12 years of age and for children from socio-economically disadvantaged and minority ethnic backgrounds. The introduction of statutory regulation is a potentially cost-effective policy option, in terms of healthcare savings outweighing the costs of implementing the policy, although voluntary codes were shown to be ineffective, with exposure to unhealthy food advertisements similar in countries before and after their introduction. Food advertising, however, is just one factor in the wider obesogenic environment and further advertising restrictions must be implemented alongside population-based interventions that aim to address systemic causes of poor diet.

COVID-19 Outcomes in Minority Ethnic Groups: Do Obesity and Metabolic Risk Play a Role?

PURPOSE OF REVIEW: Globally, minority ethnic groups have been at higher risk of COVID-19 mortality and morbidity than majority populations. This review outlines factors that may interact to create these inequalities and explores the hypothesis that differing levels of cardio-metabolic risk, according to ethnic group, play a role. RECENT FINDINGS: Two UK Biobank studies have reported that the body mass index is more strongly associated with an increased risk of COVID-19 infection and mortality in minority ethnic populations than in White populations. A study of UK patients found that the strongest association between obesity and adverse COVID-19 outcomes was in people of Black ethnicity. Differences in the prevalence of obesity and its metabolic sequelae have been shown to partly mediate ethnic inequalities in COVID-19 outcomes, although not always consistently. It is possible that ethnic differences in the consequences of obesity may explain some of the remaining disparity in COVID-19 risk.

Healthy diets, lifestyle changes and well-being during and after lockdown: longitudinal evidence from the West Midlands.

Background: 'Lockdowns' to control the spread of COVID-19 in the UK affected many aspects of life and may have adversely affected diets. We aimed to examine (1) the effect of lockdowns on fruit and vegetable consumption, as a proxy for healthy diets more generally, and on weight and well-being, (2) whether any subgroup was particularly affected and (3) the barriers and facilitators to a healthy diet in lockdown. Methods: We conducted a mixed-method longitudinal study, involving an online survey of 1003 adults in the West Midlands, UK, 494 of whom were surveyed at two different points in time. Our first time point was during stringent COVID-19 lockdown and the second during a period of more relaxed restrictions. We asked quantitative questions about fruit and vegetable consumption; physical activity, sociodemographic characteristics, body mass index and well-being and qualitative questions about the reasons behind reported changes. Results: We find no evidence for decreased fruit and vegetable consumption during lockdown compared with afterwards. If anything, consumption increased by half a portion daily among women, particularly among those who normally have a long commute. This finding, combined with a significant increase in physical activity, suggests that behaviours were healthier during lockdown, consistent with higher self-reported health. However, well-being deteriorated markedly, and participants reported being heavier during the lockdown as well. Our qualitative data suggest that an abundance of resources (more time) supported higher fruit and vegetable consumption during lockdown, despite increased access issues. Conclusions: Our results may assuage concerns that lockdowns adversely affected diets. They may point to the impact of commuting on diet, particularly for women. We add longitudinal evidence to a growing body of literature on the adverse effect of lockdown on mental health.

Low Carb Program Health App Within a Hospital-Based Obesity Setting: Observational Service Evaluation.

BACKGROUND: Obesity underlies much chronic disease. Digitalization of obesity management provides an opportunity to innovate our traditional model of health care delivery within this setting, and to transform its scalability potentially to the population level. OBJECTIVE: The objective was to assess the feasibility and effectiveness of the Low Carb Program app for weight loss, applied within our hospital-based (tier 3) obesity service. Due to the disrupting effects of the COVID-19 pandemic on our obesity service, we compared the clinical outcomes from the Low Carb Program app applied in the context of remote patient appointments over the telephone with the prepandemic traditional standard of care. METHODS: We invited patients who attended our hospital-based obesity service to engage with the Low Carb Program smartphone app. We combined this approach with remote delivery (over the telephone) of obesity management from medical and psychology members of our obesity team during the COVID-19 pandemic. Outcome variables included changes in body weight and changes in HbA1c as a marker of glycemic control. We compared data from the Low Carb Program group with a retrospective control group (n=126) that had received traditional face-to-face obesity management from our team without concomitant use of the Low Carb Program app in the pre-COVID-19 era. T test comparisons were employed, with P<.05 considered significant. RESULTS: The mean weight of participants (n=105) was 130.2 kg, with 59% (n=62) females and a mean age of 48.8 years. Most participants (90/105, 86%) completed the Low Carb Program app registration process and engaged with the Low Carb Program app program; at follow-up, most participants (88/105, 84%) had actively engaged with the Low Carb Program app within the prior 30 days. The majority of participants (58/105, 55%) self-reported outcomes within the app. Mean duration of clinical follow-up for recruited participants who received the app was 7.4 months. Paired data were available for 48 participants for body weight and 41 participants for HbA1c. Paired sample t test analysis revealed a statistically significant mean loss of body weight of 2.7 kg (P=.001) and improvement in HbA1c of 3.3 mmol/mol (P=.01). The mean weight of control group patients (n=126) was 137.1 kg, with 74% (93/126) females and a mean age of 44.4 years. The mean follow-up for this group was 6 months. Data comparisons between the app user group and the pre-COVID-19 retrospective control group revealed equivalence for loss of body weight and change in HbA1c between the two groups. CONCLUSIONS: We provide evidence to support the feasibility of implementing the Low Carb Program app combined with remote management; this is the first proof of concept for digitalized management within a hospital-based (tier 3) obesity service. We demonstrate the potential clinical efficacy of the approach in terms of improvements in body weight and glycemic control.

Feasibility, acceptability and effect of the Mindful Practice curriculum in postgraduate training of general practitioners.

BACKGROUND: Early career general practitioners are known to be at high risk of burnout. There is a need for widely applicable, cost-effective evidence-based interventions to develop trainees' protective skills and strategies. RESULTS: Of 120 eligible trainees, 23 (19.2%) expressed interest in participating, 17 subsequently started the course, and 15 completed at least 5 out of its 6 sessions. All psychological measures were stable for the six-week period prior to commencing the course. Following the course, there were statistically significant (p < 0.05) improvements in wellbeing, resilience, mindfulness, emotional exhaustion, disengagement, and stress scores. Participants described numerous benefits, and most stated that they would recommend it to colleagues. CONCLUSION: Including mindful practice within general practice vocational training is feasible, and in this study it benefited the psychological wellbeing of participants. Further research is needed to explore ways of increasing uptake and course completion, the sustainability of its effects, and the wider applicability of this approach.

Sodium in the dermis colocates to glycosaminoglycan scaffold, with diminishment in type 2 diabetes mellitus.

BACKGROUND: Dietary sodium intake mismatches urinary sodium excretion over prolonged periods. Our aims were to localize and quantify electrostatically bound sodium within human skin using triple-quantum-filtered (TQF) protocols for MRI and magnetic resonance spectroscopy (MRS) and to explore dermal sodium in type 2 diabetes mellitus (T2D). METHODS: We recruited adult participants with T2D (n = 9) and euglycemic participants with no history of diabetes mellitus (n = 8). All had undergone lower limb amputations or abdominal skin reduction surgery for clinical purposes. We used 20 µm in-plane resolution 1H MRI to visualize anatomical skin regions ex vivo from skin biopsies taken intraoperatively, 23Na TQF MRI/MRS to explore distribution and quantification of freely dissolved and bound sodium, and inductively coupled plasma mass spectrometry to quantify sodium in selected skin samples. RESULTS: Human dermis has a preponderance (>90%) of bound sodium that colocalizes with the glycosaminoglycan (GAG) scaffold. Bound and free sodium have similar anatomical locations. T2D associates with a severely reduced dermal bound sodium capacity. CONCLUSION: We provide the first evidence to our knowledge for high levels of bound sodium within human dermis, colocating to the GAG scaffold, consistent with a dermal "third space repository" for sodium. T2D associates with diminished dermal electrostatic binding capacity for sodium.

The Low-Carbohydrate Diet: Short-Term Metabolic Efficacy Versus Longer-Term Limitations.

BACKGROUND: Diets have been a central component of lifestyle modification for decades. The Low-Carbohydrate Diet (LCD), originally conceived as a treatment strategy for intractable epilepsy (due to its association with ketogenesis), became popular in the 1970s and since then has risen to prominence as a weight loss strategy. OBJECTIVE: To explore the efficacy, limitations and potential safety concerns of the LCD. DATA SOURCES: We performed a narrative review, based on relevant articles written in English from a Pubmed search, using the terms 'low carbohydrate diet and metabolic health'. RESULTS: Evidence supports the efficacy of the LCD in the short-term (up to 6-months) for reduction in fat mass and remission of Type 2 Diabetes Mellitus (T2D). However, the longer-term efficacy of the LCD is disappointing, with diminishment of weight loss potential and metabolic benefits of the LCD beyond 6-months of its adoption. Furthermore, practical limitations of the LCD include the associated restriction of food choices that restrict the acceptability of the LCD for the individual, particularly over the longer term. There are also safety concerns of the LCD that stem from nutritional imbalances (with a relative excess of dietary fat and protein intake with associated dyslipidaemia and increased risk of insulin resistance and T2D development) and ketotic effects. Finally, the LCD often results in a reduction in dietary fibre intake, with potentially serious adverse consequences for overall health and the gut microbiota. CONCLUSIONS: Although widely adopted, the LCD usually has short-lived metabolic benefits, with limited efficacy and practicality over the longer term. Dietary modification needs tailoring to the individual, with careful a priori assessments of food preferences to ensure acceptability and adherence over the longer term, with avoidance of dietary imbalances and optimization of dietary fibre intake (primarily from plant-based fruit and vegetables), and with a posteriori assessments of the highly individual responses to the LCD. Finally, we need to change our view of diets from simply an excipient for weight loss to an essential component of a healthy lifestyle.

Dietary Influences on the Microbiota-Gut-Brain Axis.

Over unimaginable expanses of evolutionary time, our gut microbiota have co-evolved with us, creating a symbiotic relationship in which each is utterly dependent upon the other. Far from confined to the recesses of the alimentary tract, our gut microbiota engage in complex and bi-directional communication with their host, which have far-reaching implications for overall health, wellbeing and normal physiological functioning. Amongst such communication streams, the microbiota-gut-brain axis predominates. Numerous complex mechanisms involve direct effects of the microbiota, or indirect effects through the release and absorption of the metabolic by-products of the gut microbiota. Proposed mechanisms implicate mitochondrial function, the hypothalamus-pituitary-adrenal axis, and autonomic, neuro-humeral, entero-endocrine and immunomodulatory pathways. Furthermore, dietary composition influences the relative abundance of gut microbiota species. Recent human-based data reveal that dietary effects on the gut microbiota can occur rapidly, and that our gut microbiota reflect our diet at any given time, although much inter-individual variation pertains. Although most studies on the effects of dietary macronutrients on the gut microbiota report on associations with relative changes in the abundance of particular species of bacteria, in broad terms, our modern-day animal-based Westernized diets are relatively high in fats and proteins and impoverished in fibres. This creates a perfect storm within the gut in which dysbiosis promotes localized inflammation, enhanced gut wall permeability, increased production of lipopolysaccharides, chronic endotoxemia and a resultant low-grade systemic inflammatory milieu, a harbinger of metabolic dysfunction and many modern-day chronic illnesses. Research should further focus on the colony effects of the gut microbiota on health and wellbeing, and dysbiotic effects on pathogenic pathways. Finally, we should revise our view of the gut microbiota from that of a seething mass of microbes to one of organ-status, on which our health and wellbeing utterly depends. Future guidelines on lifestyle strategies for wellbeing should integrate advice on the optimal establishment and maintenance of a healthy gut microbiota through dietary and other means. Although we are what we eat, perhaps more importantly, we are what our gut microbiota thrive on and they thrive on what we eat.

Early Metabolic Benefits of Switching Hydrocortisone to Modified Release Hydrocortisone in Adult Adrenal Insufficiency.

Purpose: To compare metabolic effects of modified release hydrocortisone (MR-HC) with standard hydrocortisone (HC) therapies in adults with Adrenal Insufficiency (AI). Methods: Adult patients (n = 12) with AI, established on HC therapy, were recruited from Endocrinology clinics at University Hospitals Coventry and Warwickshire (UHCW), UK. Baseline (HC) metabolic assessments included fasting serum HbA1C, lipid and thyroid profiles, accurate measures of body composition (BodPod), and 24-h continuous measures of energy expenditure including Sleeping Metabolic Rate (SMR) using indirect calorimetry within the Human Metabolism Research Unit, UHCW. All participants then switched HC to MR-HC with repeat (MR-HC) metabolic assessments at 3 months. Paired-sample t-tests were used for data comparisons between HC and MR-HC assessments: P-value <0.05 was considered significant. Results: Following exclusion of 2 participants, analyses were based on 10 participants. Compared with baseline HC data, following 3 months of MR-HC therapy mean fat mass reduced significantly by -3.2 kg (95% CI: -6.0 to -0.4). Mean (SD) baseline HC fat mass vs repeat MR-HC fat mass: 31.9 kg (15.2) vs 28.7 kg (12.8) respectively, P = 0.03. Mean SMR increased significantly by +77 kcal/24 h (95% CI: 10-146). Mean (SD) baseline HC SMR vs repeat MR-HC SMR: 1,517 kcal/24 h (301) vs 1,594 kcal/24 h (344) respectively, P = 0.03. Mean body fat percentage reduced significantly by -3.4% (95% CI: -6.5 to -0.2). Other measures of body composition, energy expenditure, and biochemical analytes were equivalent between HC and MR-HC assessments. Conclusions: In adults with AI, switching from standard HC to MR-HC associates with early metabolic benefits of reduced fat mass and increased SMR.

Older age does not influence the success of weight loss through the implementation of lifestyle modification.

OBJECTIVE: Age is sometimes a barrier for acceptance of patients into a hospital-based obesity service. Our aim was to explore the effect of age on the ability to lose weight through lifestyle interventions, implemented within a hospital-based obesity service. DESIGN: Retrospective study. PATIENTS: We included a cohort of randomly selected patients with morbid obesity (n = 242), who attended our hospital-based obesity service during 2005-2016 and received only lifestyle weight loss interventions. MEASUREMENTS: Primary outcome measures were percentage weight loss (%WL) and percentage reduction in body mass index (%rBMI) following implemented lifestyle interventions. Data were stratified according to patient age at referral: group 1 (age < 60 years, n = 167) and group 2 (age ≥ 60 years, n = 75). Weight loss was compared between groups, and correlations with age at referral were explored. RESULTS: The duration of hospital-based weight loss interventions ranged between 1 and 143 months (mean: 38.9 months; SD: 32.3). Baseline BMI at referral differed significantly between groups 1 and 2 (49.7 kgm-2 [SD: 8.7] vs 46.9 kgm-2 [SD: 6.1], respectively; P < .05). Following implemented lifestyle interventions, between groups 1 and 2 there were no differences in %WL (6.9% [SD: 16.7] vs 7.3% [SD: 11.60], respectively; P = NS) or %rBMI (8.1% [SD: 14.9] vs 7.8% [SD: 11.7], respectively; p = NS). Overall, there was no significant correlation between patient age at referral and %WL (r = -.13, p = NS). CONCLUSIONS: Older age does not influence the success of weight loss through the implementation of lifestyle modification within a hospital-based obesity service. Therefore, age per se should not influence clinical decisions regarding acceptance of patients to hospital-based obesity services.

Modification of fecal microbiota as a mediator of effective weight loss and metabolic benefits following bariatric surgery.

INTRODUCTION: Bariatric surgery (primarily Laparoscopic Sleeve Gastrectomy [LSG] and Roux-en-Y Gastric Bypass [RYGB]) is an efficacious and durable therapeutic option for weight loss in obesity. The mechanisms that mediate weight loss following bariatric surgery remain incompletely understood. AREAS COVERED: Pubmed search of published data on fecal microbiota, metabolic health, LSG, and RYGB. The fecal microbiome plays a key role in the establishment and maintenance of metabolic wellbeing, and may also contribute (through fecal dysbiosis) to metabolic dysfunction. LSG and RYGB both result in characteristic, procedure-specific changes to the fecal microbiota that may mediate at least some of the resultant weight-loss and metabolically beneficial effects, when applied to the management of obesity. EXPERT OPINION: The human fecal microbiome, containing around 100 trillion microbes, evolved over millions of years and interacts symbiotically with its human host. Rodent-based studies have provided insights into the complexities of the gut-microbiome-brain axis. This includes the important role of the gut microbiome in the mediation of normal immunological development, inflammatory pathways, metabolic functioning, hypothalamic appetite regulation, and the absorption of essential nutrients as by-products of bacterial metabolism. Fecal transformation is likely to provide an important therapeutic target for future prevention and management of obesity and metabolic dysfunction.