Modelling the associations between fat-free mass, resting metabolic rate and energy intake in the context of total energy balance.

BACKGROUND: The relationship between body composition, energy expenditure and ad libitum energy intake (EI) has rarely been examined under conditions that allow any interplay between these variables to be disclosed. OBJECTIVE: The present study examined the relationships between body composition, energy expenditure and EI under controlled laboratory conditions in which the energy density and macronutrient content of the diet varied freely as a function of food choice. METHODS: Fifty-nine subjects (30 men: mean body mass index=26.7±4.0 kg m(-2); 29 women: mean body mass index=25.4±3.5 kg m(-)(2)) completed a 14-day stay in a residential feeding behaviour suite. During days 1 and 2, subjects consumed a fixed diet designed to maintain energy balance. On days 3-14, food intake was covertly measured in subjects who had ad libitum access to a wide variety of foods typical of their normal diets. Resting metabolic rate (RMR; respiratory exchange), total daily energy expenditure (doubly labelled water) and body composition (total body water estimated from deuterium dilution) were measured on days 3-14. RESULTS: Hierarchical multiple regression indicated that after controlling for age and sex, both fat-free mass (FFM; P<0.001) and RMR (P<0.001) predicted daily EI. However, a mediation model using path analysis indicated that the effect of FFM (and fat mass) on EI was fully mediated by RMR (P<0.001). CONCLUSIONS: These data indicate that RMR is a strong determinant of EI under controlled laboratory conditions where food choice is allowed to freely vary and subjects are close to energy balance. Therefore, the conventional adipocentric model of appetite control should be revised to reflect the influence of RMR.

Hypoglycaemia after gastric bypass: mechanisms and treatment.

Hypoglycaemia after gastric bypass can be severe, but is uncommon, and is sometimes only revealed through monitoring glucose concentrations. The published literature is limited by the heterogeneity of the criteria used for diagnosis, arguing in favour of the Whipple triad with a glycaemia threshold of 55 mg/dl as the diagnostic reference. Women who lost most of their excess weight after gastric bypass, long after the surgery was performed, and who did not have diabetes before surgery are at the greatest risk. In this context, hypoglycaemia results from hyperinsulinism, which is either generated by pancreas anomalies (nesidioblastosis) and/or caused by an overstimulation of ß cells by incretins, mainly glucagon-like peptide-1 (GLP-1). Glucose absorption is both accelerated and increased because of the direct communication between the gastric pouch and the jejunum. This is a post-surgical exaggeration of a natural adaptation that is seen in patients who have not undergone surgery in whom glucose is infused directly into the jejunum. There is not always a correspondence between symptoms and biological traits; however, hyperinsulinism is constant if hypoglycaemia is severe and there are neuroglucopenic symptoms. The treatment relies firstly on changes in eating habits, splitting food intake into five to six daily meals, slowing gastric emptying, reducing the glycaemic load and glycaemic index of foods, using fructose and avoiding stress at meals. Pharmacological treatment with acarbose is efficient, but other drugs still need to be validated in a greater number of subjects (insulin, glucagon, calcium channel blockers, somatostatin analogues and GLP-1 analogues). Lastly, if the surgical option has to be used, the benefits (efficient symptom relief) and the risks (weight regain, diabetes) should be weighed carefully.

Glucose Abnormalities and Inappropriate Weight Gain Predict Negative Pregnancy Outcomes After Gastric Bypass Surgery.

PURPOSE: Pregnancy after gastric bypass (RYGB) surgery remains at high risk for gestational diabetes mellitus, prematurity, and small for gestational age infants (SGA). Our objective was to describe the interstitial glucose (IG) profiles and weight changes during such pregnancies, and the association of these factors with adverse pregnancy outcomes. MATERIAL AND METHODS: One hundred twenty two pregnancies were analyzed in a monocentric retrospective study. IG profiles were evaluated by continuous glucose monitoring for 4 days. Maternal (hypertension, hospitalizations, and caesarean section) and neonatal outcomes (prematurity, weight for gestational age, hospitalizations, and malformations) were recorded. A logistic stepwise regression model assessed the influence of weight gain and impaired IG on pregnancy outcomes. RESULTS: Pregnancies occurred 33 (SD 21 months) after surgery. 73% of the women had IG abnormalities (55% with an increased % of time >140 mg/dl and 69% with an increased % of time <60 mg/dl). Five (4%) children were large for gestational age (LGA), 24 (20%) were SGA and 16 (13%) were born prematurely. There were 3 malformations but no stillbirth. LGA was associated with a high % of time >140 mg/dl and an excessive maternal weight gain. Prematurity was associated with a high % of time <60 mg/dl and an insufficient maternal weight gain. In the multivariate analysis, inappropriate weight gain explained LGA and prematurity independently. SGA was associated with a shorter % of time <60 mg/dl. CONCLUSION: The relationship between IG abnormalities and/or maternal weight gain and neonatal outcomes in pregnancies after RYGB, suggests a careful monitoring of these parameters.

Diabetes Remission and Relapse After Bariatric Surgery: a Nationwide Population-Based Study.

PURPOSE: The long-term impact of bariatric surgery on the remission of type 2 diabetes (T2DM) remains to be clarified through large nationally representative cohorts. The objectives were to determine the incidence of T2DM remission and relapse after bariatric surgery, to determine the factors associated with remission and to establish a profile for patients at risk for relapse. MATERIALS AND METHODS: We conducted a population-based cohort study using data from the French national health insurance database (Systeme national des données de santé [SNDS]). We had access to exhaustive regional data between 2013 and 2017 and to a national representative sample of the French population (EGB) from 2008 to 2018. Patients were included if they were adults and diabetics with incidental bariatric surgery. RESULTS: This study shows that 50% of patients are in remission from diabetes after bariatric surgery within a median of 2 to 4 months. Diabetes relapse was observed in 13-20% within 10 years. The factors favouring remission already described were noted (non-insulin-dependent diabetes) and original factors were also identified, in particular the advantage of bypass surgery over sleeve gastrectomy, with more remissions and fewer relapses. CONCLUSION: This study highlights a 50% prevalence of remission and a low prevalence of relapse. There are non-modifiable risk factors for remission and relapse (characteristics of diabetes, age, lipid-lowering therapy) and modifiable factors (type of surgery). Identifying these factors is essential for optimal management of patients. Additional data are essential to confirm the results of our analysis of the factors associated with relapse.

Bariatric surgery and the perioperative management of type 2 diabetes: Practical guidelines.

BACKGROUND: Metabolic surgery is now considered as a therapeutic option in type 2 diabetes (T2D). However, few data are available regarding perioperative management of T2D. OBJECTIVES: To assess current practice among bariatric teams regarding perioperative management of T2D in order to propose guidelines. METHODS: A two-round Delphi method using online surveys was employed among bariatric teams experts (surgeons, diabetologists, anesthetists, nutritionists): first round, 63 questions covering 6 topics (characteristics of experts/teams, characteristics of patients, operative technique, pre/postoperative management, diabetes remission); second round, 44 items needing clarification. They were discussed within national congress of corresponding learned societies. Consensus was defined as ≥66% agreement. RESULTS: A total of 170 experts participated. Experts favored gastric bypass to achieve remission (76.7%). Screening for retinopathy, cardiac ultrasound, and reaching an HbA1c<8% are required in the pre-operative period for 67%, 75.3% and 56.7% of experts, respectively. After surgery, insulin pump should not be stopped, basal insulin should be halved, and bolus insulin should be stopped except if severe hyperglycemia. DPP-IV inhibitors and metformin are preferred after surgery. Patients should be seen by a diabetologist within one month if on oral antidiabetic agents (71.8% of experts), 2 weeks if on injectable treatments (77.1% of experts), and immediately after surgery if on insulin pump (93.5% of experts). Long-term monitoring of HbA1c is necessary even if diabetes remission (100%). CONCLUSION: Rapid postoperative modifications of blood glucose require a close monitoring and a prompt adjustment of diabetes medications.

A MOOC About Bariatric Surgery Improves Knowledge and Promotes Patients' Soft Skills.

The ASMBS recommends that patients should be provided with educational materials to improve informed consent about bariatric surgery. Massive online open courses (MOOCs) are learning sources which are free, online, and available to people in remote situations. A French language MOOC regarding preparation for obesity surgery targets patients, as well as HCP, and people curious about this treatment. The patients' knowledge and skills after completion of the 5-week learning sessions (evaluated with semi-direct interviews) improved. Soft skills such as feeling empowered to ask questions to their HCP and explaining their plan to their relatives improved. This study suggests that MOOC can be a resource to improve knowledge and soft skills in patients for a better consent to surgery and follow-up.

Is skeletal muscle mitochondrial dysfunction a cause or an indirect consequence of insulin resistance in humans?

The precise cause of insulin resistance and type 2 diabetes is unknown. However, there is a strong association between insulin resistance and lipid accumulation - and, in particular, lipotoxic fatty acid metabolites - in insulin-target tissues. Such accumulation is known to cause insulin resistance, particularly in skeletal muscle, by reducing insulin-stimulated glucose uptake. Reduced fat-oxidation capacity appears to cause such lipid accumulation and, over the past few years, many studies have concluded that decreased mitochondrial oxidative phosphorylation could be the initiating cause of lipid deposition and the development of insulin resistance. The aim of this review is to summarize the latest findings regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance in humans. At present, there are too few studies to definitively conclude that, in this context, mitochondria are functionally impaired (dysfunction in the respiratory chain). Indeed, insulin resistance could also be related to a decrease in the number of mitochondria or to a combination of this and mitochondrial dysfunction. Finally, we also consider whether or not these aberrations could be the cause of the development of the disease or whether mitochondrial dysfunction may simply be the consequence of an insulin-resistant state.

A Case Report of Myotonic Disease and Gastric Bypass and a Literature Review.

We report the case of a woman with myotonic dystrophy type 1, followed for 8 years after a Roux-en-Y gastric bypass. Weigh loss was substantial (53% of initial body weight) with functional improvement in spite of the natural course of the pathology. Five other cases have been published and have reported a relatively positive benefit/risk ratio. Precautions are to be taken at the time of anesthesia and follow-up in order to detect possible degradation of muscle function.

An Application May Help Improve Protein Consumption after Bariatric Surgery.

This brief communication suggests that in patients who had bariatric surgery and in whom protein intake is lower than 60 g/d, the use of an application is likely to improve protein intake.

The prevalence of abnormal eating behaviour in a representative sample of the French diabetic population.

AIM: To assess the relationship between abnormal eating behaviour (AEB) and diabetes in a sample of French adult patients with type 1 (T1D) and type 2 (T2D) diabetes. METHODS: Ninety-four consecutively recruited patients self-completed a series of validated questionnaires. RESULTS: Over one-fourth of men with T1D (26%) or T2D (27%) and 11% of female T2D patients reported consistent and pathological overeating or binge-eating during the previous six months. Glycaemic control in these T1D patients was poorer than in T1D patients defined as normal eaters (NORM) (11.9% versus 9.6%), but did not reach statistical significance (P=0.08), and no significant difference was observed in the T2D group (P=0.61) either. T2D patients reported being markedly more restrained when eating than did the T1D patients (P=0.002), and their restraint increased along with their BMI (P<0.001). Patients who overate or binged also reported greater general hunger (P=0.02) and disinhibition (P=0.003) than did the NORM patients. CONCLUSION: AEB is present in French diabetic patients at levels that are probably higher than among the general population. These results highlight the need for: (1) greater awareness among diabetes clinicians of the problem; (2) regular screening of diabetic patients for AEB; and (3) adaptation of therapeutic and dietary recommendations for this patient subgroup.

Distribution of adipose tissue: quantification and relationship with hepatic steatosis and vascular profiles of type 2 diabetic patients with metabolic syndrome.

AIM: As the distribution of fat is increasingly related to cardiovascular events, we examined whether or not abdominal-fat quantification using magnetic resonance imaging (MRI) software is reliable, and whether or not it is related to clinical markers of fat distribution as well as to metabolic and vascular status. METHODS: We recorded the anthropometric measurements of 34 obese type 2 diabetic patients with metabolic syndrome. The patients were enrolled to evaluate their abdominal (visceral and subcutaneous) adipose tissue by single-slice L3-L4 MRI. Manual and automated analyses were compared. The relationships between anthropometric measurements, biological markers and intima-media thickness of the common carotid artery were also assessed. RESULTS: We validated the automated software to quantify abdominal-fat deposition with MRI compared with manual measurements (r2=0.95). The waist-to-hip-circumference ratio (WHR) was the only clinical parameter that correlated with the proportion and quantity of visceral and subcutaneous abdominal-adipose tissue evaluated by MRI (r=0.60). In addition, fat repartition as evaluated by WHR was related to hepatic steatosis parameters (ferritin and ALAT) and to intima-media thickness, whereas simple waist circumference was not a determinant in these obese patients. We also showed that the adiponectin-to-leptin ratio was related to adipose tissue distribution. CONCLUSION: Distribution of abdominal fat, as evaluated by MRI, can be reflected by clinical determination of the WHR. Differences in regional accumulations of abdominal fat may be specifically related to variations in the risks of steatosis and vascular rigidity among obese type 2 diabetic patients.

Comparing different measures of energy expenditure in human subjects resident in a metabolic facility.

OBJECTIVE: To compare energy expenditure (EE) measured by doubly labeled water (DLW) with other measures, both physical and based on subjective questionnaires. DESIGN: A comparison of methods in a stratified sample of adult volunteers. SETTING: The feeding behaviour suite (FBS) at the Rowett Research Institute, Aberdeen. SUBJECTS: A total of 59 subjects, stratified for age, sex and body mass index (BMI). INTERVENTIONS: EE was assessed by DLW (validated using measurements of energy balance), heart rate monitor (HRM), activity monitor (Caltrac), 24-h physical activity diary (PAD) and 7-day physical activity recall. Energy intake was assessed using covert (investigator-weighed) food intake (EI). Data were collected over a 12-day period of residence in the Rowett's FBS. RESULTS: No methods correlated highly with physical activity assessed by DLW. Physical methods correlated more closely than did subjective recording. All methods (except EI) significantly underestimated EE, estimated by DLW. There were no significant differences in association between methods and sex, age, BMI or fat-free mass. CONCLUSION: EE is difficult to measure precisely or accurately with current approaches but physical methods are slightly better than subjective accounts.

A practical approach to estimate resting energy expenditure in frail elderly people.

OBJECTIVES: Some prediction equations of resting energy expenditure (REE) are available and can be used in clinical wards to determine energy requirements of patients. The aim of the present study was to assess the accuracy of those equations in sick elderly patients, using the Bland and Altman methods with our database of 187 REE measurements. DESIGN: The 3 equations tested were Harris and Benedict equation of 1919, WHO/FAO/UNU equation of 1985 and Fredrix et al. equation of 1990. In addition, three models developed from the present data were tested. RESULTS: The present study shows that the Fredrix et al equation gave an accurate prediction of REE without significant bias along the whole range of REE. It also shows that under-weight sick elderly patients (BMI

Frailty, osteoporosis and hip fracture: causes, consequences and therapeutic perspectives.

OBJECTIVE: The aim of this review of the literature is to report the factors which both contribute to the frailty syndrome and increase hip fracture risk in the elderly. This work is the fruit of common reflection by geriatricians, endocrinologists, gynecologists and rheumatologists, and seeks to stress the importance of detection and management of the various components of frailty in elderly subjects who are followed and treated for osteoporosis. It also sets out to heighten awareness of the need for management of osteoporosis in the frail elderly. DESIGN: The current literature on frailty and its links with hip fracture was reviewed and discussed by the group. RESULTS: The factors and mechanisms which are common to both osteoporosis and frailty (falls, weight loss, sarcopenia, low physical activity, cognitive decline, depression, hormones such as testosterone, estrogens, insulin-like growth factor-I (IGF-I), growth hormone (GH), vitamin D and pro-inflammatory cytokines) were identified. The obstacles to access to diagnosis and treatment of osteoporosis in the frail elderly population and common therapeutic pathways for osteoporosis and frailty were discussed. CONCLUSION: Future research including frail subjects would improve our understanding of how management of frailty can can contribute to lower the incidence of fractures. In parallel, more systematic management of osteoporosis should reduce the risk of becoming frail in the elderly population.

Prevention of progression to dementia in the elderly: rationale and proposal for a health-promoting memory consultation (an IANA Task Force).

Alzheimer's disease (AD) is the most frequent form of dementia and according to the most recent estimation it affects nearly 27 million people in the world. The onset of the disease is generally insidious. It is becoming increasingly evident that the underlying pathophysiological mechanisms are active long before the appearance of the clinical symptoms of the disease. In the current context, it is important to develop strategies to delay the onset of cognitive decline. Delaying the onset by 5 years would reduce the prevalence by half at term, and a delay of 10 years would reduce it by three-quarters. The effectiveness of currently suggested preventive approaches remains to be confirmed, but certain strategies could be applied straight away to at-risk subjects. We propose that a health-promoting memory consultation should be set up for elderly persons who have attended a specialized memory consultation and in whom the diagnosis of dementia and of AD in particular, has not been established by standardized tools. Through this consultation, they would be offered full multidimensional investigation of all aspects of their health status, follow-up could be organized, general practitioners in private practice could be made more conscious of this population and the elderly could be made more aware of the risk factors to which they are exposed. The development of an information policy for the elderly would meet a present need. In our reflection, we must take into account the question of how to give this preventive consultation its due place in the healthcare pathway of the elderly person in order to ensure coordinated follow-up with all the other health professionals involved. The principle of the health-promoting memory consultation is undergoing validation in a large French multicentre preventive trial in 1200 frail elderly persons aged 70 years followed for three years, the Multidomain Alzheimer Preventive Trial (MAPT).

Comparison of different methods to assess body composition of weight loss in obese and diabetic patients.

Estimating body composition is important to understand the metabolic and cardiovascular effects of adiposity. Estimating changes in body compartments arising from weight loss strategies is equally important to evaluate their benefits and risks, particularly in frail populations (elderly or diabetic), and following bariatric surgery. Body compartments were evaluated in 50 obese subjects (25 diabetic, 25 non-diabetic) before and after a 7 kg weight loss obtained after 6 months of calorie restriction and orlistat. Fat and fat-free mass (FFM) were estimated by bioelectrical impedance analysis (BIA), dual X-ray absorptiometry (DXA), plethysmography (BodPod) and a combination of these in a 3- or 4-compartment model, the latter being considered the reference method. FFM hydration was the ratio of total body water (BIA) to FFM. FFM hydration was significantly higher than classical values (75.9+/-3.0%, P<0.0001), and decreased with weight loss (74.2+/-3.3%). Compared to the 4-compartment, the 3-compartment model gave the most accurate fat and FFM estimation. A significant bias was observed with DXA, BodPod or BIA. Compartment changes induced by weight loss were accurately evaluated by DXA, being particularly precise in the 3-compartment analysis. No effect of diabetes per se was observed. A 3- or 4-compartmental analysis is necessary to accurately estimate body composition and its changes during weight loss.

Energy requirements in frail elderly people: a review of the literature.

This review collates studies of healthy, sick, underweight (BMI < or = 21 kg/m2) and very elderly people (> or = 90 yr), in whom resting energy expenditure (REE) was measured using indirect calorimetry. We have observed the following: (1) REE, when adjusted for differences in both body weight and fat-free mass (FFM), is similar in healthy and in sick elderly people being 20 and 28 kcal/kg of FFM per day, respectively, (2) their nutritional status influences their energy requirements given that weight-adjusted REE increases in line with a decrease in BMI, (3) total energy expenditure is lower in sick elderly people given that their physical activity level, i.e. the ratio of total energy expenditure to REE, is reduced during disease averaging at 1.36, (4) energy intake (EI) being only 1.23 x REE is insufficient to cover energy requirements in sick elderly patients, whereas the EI of healthy elderly people appears sufficient to cover requirements, and finally, (5) gender ceases to be a determinant of REE in people aged 60 yr or over, with the Harris & Benedict equation capable of accurately predicting mean REE in this population, whether healthy or sick.

Pharmacokinetics and drug toxicity in elderly patients: a case for geriatric core data in clinical trials.

The population in western countries is aging and elderly people are more likely to suffer diseases and receive treatments. Adverse reactions to drugs are more severe and frequent in the elderly patients, who are also less likely to report them. The present paper analyses the age induced changes in drug pharmacokinetics. For the purpose of improving the quality of clinical trials in geriatric patients and to set a network of clinical research centres, this paper proposes a series of 9 milestones. They are named geriatric core data and should be collected in each trial.

Nutritional risk score is not sensitive enough to predict weight loss in diseased elderly subjects.

OBJECTIVES: malnutrition is highly prevalent in diseased elderly people, especially in hospital departments, and weight loss also occurs during hospital stays. Among the tools proposed to define malnutrition and to screen persons at risk of malnutrition, the nutritional risk score (NRS) has been suggested as a simple tool. DESIGN AND PARTICIPANTS: the aim of the present study was to test the validity of the NRS to predict weight changes 3 months after discharge. NRS and visual analogue scales for hunger, early satiety, thirst, fatigue and pain were performed in 106 patients aged 65 yrs and over, 67 treated for cancer, without overt malnutrition. RESULTS: forty six patients lost more than 1 kg. None of the parameters tested was correlated with weight changes, except NRS which was weakly correlated (r=-0.22, P=0.037). However a 0 score at NRS was associated with weight changes ranging -9 to +5 kg. Furthermore, the 11 patients with a high NRS score and weight loss were in a clinical situation that made it very likely that they would lose weight. In conclusion, NRS is not a valid score to predict weight change.