Separation of blood microsamples by exploiting sedimentation at the microscale.

Microsample analysis is highly beneficial in blood-based testing where cutting-edge bioanalytical technologies enable the analysis of volumes down to a few tens of microliters. Despite the availability of analytical methods, the difficulty in obtaining high-quality and standardized microsamples at the point of collection remains a major limitation of the process. Here, we detail and model a blood separation principle which exploits discrete viscosity differences caused by blood particle sedimentation in a laminar flow. Based on this phenomenon, we developed a portable capillary-driven microfluidic device that separates blood microsamples collected from finger-pricks and delivers 2 µL of metered serum for bench-top analysis. Flow cytometric analysis demonstrated the high purity of generated microsamples. Proteomic and metabolomic analyses of the microsamples of 283 proteins and 1351 metabolite features was consistent with samples generated via a conventional centrifugation method. These results were confirmed by a clinical study scrutinising 8 blood markers in obese patients.

[Rehabilitation: a case for obese patients?]. / Readaptation: les patients obèses aussi?

In the word obesity, a clinical concept of chronic systemic disease pairs up with pejorative individual or social representations. Being obese is also facing situations of disability, organ failure, uncertainty of the fate and stigmatization. A care concept inspired by rehabilitation and therapeutic patient education could offer a new way and other purposes to the treatment of obesity. Restoring functions, learning how to adapt and change their environment, obese people may live better today, out of their isolation and develop partners in their projects of life and health. Rehabilitation of an obese patient is much more than weight loss!

[The role of patient education in bariatric surgery]. / Place de l'éducation thérapeutique du patient dans lato chirurgie bariatrique.

Therapeutic patient education (TPE) has demonstrated its efficacy in treating numerous chronic conditions, including obesity. Currently, TPE has broadened its field of activity to the preparation of obese patients undergoing bariatric surgery. A preparative program allows informing patients about the surgery, the necessity of the follow-up and the risk of weight regain. It also aims to allow the patient to understand the behaviors which initially brought about its obesity and to help modify these behaviors in order to avoid weight regain after the surgery. A follow-up post surgery by trained health care providers is also recommended. Current literature suggests that patients are satisfied with such educational programs, and that they help them to lose weight before surgery. The efficacy on post surgery weight loss and compliance is yet to be proved.

[Understanding obesity in Africa: the effect of [economic] development and [mental] concepts]. / Comprendre l'obésite en Afrique: poids du développement et des representations.

Obesity is becoming more and more common in Africa. It is the direct consequence of the socio-economic development that the continent is going through and the changes in lifestyle that it entails: greater consumption of calorically dense foods accompanied by a more sedentary lifestyle. Furthermore, there are various representations and beliefs that promote voluntary weight gain. Studies have shown that obesity is not only a criterion of beauty but also often perceived as a sign of wealth and even good health. To remedy this problem, the authorities in collaboration with health care professionals must develop populational strategies that take into account the different representations and beliefs in order for them to be effective.

Diabetic foot infections: state-of-the-art.

Foot infections are frequent and potentially devastating complications of diabetes. Unchecked, infection can progress contiguously to involve the deeper soft tissues and ultimately the bone. Foot ulcers in people with diabetes are most often the consequence of one or more of the following: peripheral sensory neuropathy, motor neuropathy and gait disorders, peripheral arterial insufficiency or immunological impairments. Infection develops in over half of foot ulcers and is the factor that most often leads to lower extremity amputation. These amputations are associated with substantial morbidity, reduced quality of life and major financial costs. Most infections can be successfully treated with optimal wound care, antibiotic therapy and surgical procedures. Employing evidence-based guidelines, multidisciplinary teams and institution-specific clinical pathways provides the best approach to guide clinicians through this multifaceted problem. All clinicians regularly seeing people with diabetes should have an understanding of how to prevent, diagnose and treat foot infections, which requires familiarity with the pathophysiology of the problem and the literature supporting currently recommended care.

Fasting insulin at baseline influences the number of cardiometabolic risk factors and R-R interval at 3years in a healthy population: the RISC Study.

AIM: This was a cross-sectional and longitudinal study of factors contributing to the number of cardiometabolic risk factors, common carotid artery intima-media thickness (CCA-IMT) and R-R interval in clinically healthy subjects without diabetes. METHODS: Anthropometric and cardiometabolic parameters were measured in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Study cohort at baseline (n=1211) and 3years later (n=974). At baseline, insulin sensitivity was assessed by the euglycaemic clamp technique. The CCA-IMT was echographically measured and the R-R interval was electrocardiographically evaluated at baseline and at the 3-year follow-up. RESULTS: Higher baseline BMI, fasting insulin and tobacco use as well as greater changes in BMI and fasting insulin but lower adiponectin levels, were associated with a greater number of cardiometabolic risk factors at the 3-year follow-up independently of insulin sensitivity (all P<0.02). The CCA-IMT increased with the number of cardiometabolic risk factors (P=0.008), but was not related to fasting insulin, whereas higher fasting insulinaemia and its 3-year changes were significantly associated with a smaller R-R interval (P=0.005 and P=0.002, respectively). These relationships were independent of baseline age, gender, BMI, adiponectin, insulin sensitivity, tobacco use and physical activity. CONCLUSION: In clinically healthy subjects, fasting insulinaemia, adiponectin and lifestyle parameters are related to the presence of one or two cardiometabolic risk factors before criteria for the metabolic syndrome are met. These results underline the importance of fasting insulinaemia as an independent cardiometabolic risk factor at an early stage of disease development in a healthy general population.

Impact of lifestyle intervention on body weight and the metabolic syndrome in home-care providers.

AIM: The study evaluated the impact of lifestyle intervention on body weight, metabolic syndrome parameters, nutrition and physical activity in home-care providers (HCPs). METHODS: Of 551 screened employees of a nursing agency, 173 were eligible to participate and were assigned to either the intervention (n=129) or the control (n=44) group. Participants in the intervention group followed an educational programme that encouraged physical activity and healthy nutrition, and were equipped with bicycles free of charge. Anthropometric, biological and lifestyle parameters were assessed at baseline, and after 6 and 12 months. RESULTS: Body weight, waist circumference and systolic blood pressure significantly decreased at 12 months in both study groups. Incidence of the metabolic syndrome in the intervention group at 12 months was reduced by 50% (from 17 to 9.2%; P=0.04). There were also decreases in LDL cholesterol (-0.36 mmol/L; P<0.01), total cholesterol/HDL cholesterol ratio (-0.57; P<0.01) and fasting glucose (-0.4 mmol/L; P<0.05), and an increase in HDL cholesterol (+0.22 mmol/L; P<0.01) in the intervention group. At 12 months, a decrease in daily caloric intake (-391 kcal/day; P<0.001) and an increase in the percentage of participants engaging in physical activity (+3.4%; P<0.05) were also observed in the intervention group. CONCLUSION: Lifestyle changes among HCPs are possible with relatively modest behavioural education and within a short period of time. Educational strategies and workshops are effective, efficient and easy to perform, and should be encouraged in HCPs to promote the implementation of lifestyle modifications in their patients.

Biofeedback can reduce foot pressure to a safe level and without causing new at-risk zones in patients with diabetes and peripheral neuropathy.

BACKGROUND: Plantar pressure reduction is mandatory for diabetic foot ulcer healing. Our aim was to evaluate the impact of a new walking strategy learned by biofeedback on plantar pressure distribution under both feet in patients with diabetic peripheral neuropathy. METHODS: Terminally augmented biofeedback has been used for foot off-loading training in 21 patients with diabetic peripheral sensory neuropathy. The biofeedback technique was based on a subjective estimation of performance and objective visual feedback following walking sequences. The patient was considered to have learned a new walking strategy as soon as the peak plantar pressure (PPP) under the previously defined at-risk zone was within a range of 40-80% of baseline PPP in 70% of the totality of steps and during three consecutive walking sequences. The PPP was measured by a portable in-shoe foot pressure measurement system (PEDAR(®)) at baseline (T0), directly after learning (T1) and at 10-day retention test (T2). RESULTS: The PPP under at-risk zones decreased significantly at T1 (165 ± 9 kPa, p < 0.0001) and T2 (167 ± 11, p = 0.001), as compared with T0 (242 ± 12 kPa) without any increase of the PPP elsewhere. At the contralateral foot (not concerned by off-loading), the PPP was slightly higher under the lateral midfoot at T1 (68 ± 8 kPa, p = 0.01) and T2 (65 ± 8 kPa, p = 0.01), as compared with T0 (58 ± 6 kPa). CONCLUSIONS: The foot off-loading by biofeedback leads to a safe and regular plantar pressure distribution without inducing any new 'at-risk' area under both feet.

Efficacy of rimonabant in obese patients with binge eating disorder.

In obesity, a dysregulation of the endocannabinoid system has been shown. The endocannabinoid receptor blockage by rimonabant demonstrated interesting metabolic effects. However, the role of rimonabant in weight loss of patients with binge eating disorder has not been investigated. Thus, our aim was to evaluate the effects of rimonabant on body weight in obese patients with binge eating disorders. This multicenter, randomized, double-blind, placebo-controlled study included 289 obese subjects (age 18-70 years, body mass index 30-45 kg/m(2)) with binge eating disorders. Subjects were randomized (1:1) to receive rimonabant 20 mg/day or placebo for 6 months. In total, 289 participants (age: 43.2±10.5 yrs, 91% of women) were randomized. The completer rate was similar (71%) in both treatment and placebo groups. Participants treated with rimonabant lost 4.7±5.2% of their initial body weight, vs. 0.4±4.5% in the placebo group (difference between both groups: 4.4±0.6 kg, p<0.0001). The rimonabant group showed a greater reduction on the binge eating scale total score (mean±SD - 40.9±35.2%) vs. placebo ( - 29.9±34.6%, p=0.02). The incidence of treatment emergent adverse events was comparable in both the rimonabant (82.5%) and placebo (76.0%) group. Discontinuations due to treatment emergent adverse events occurred in 13.3% rimonabant-treated vs. 6.2% placebo-treated participants. In conclusion, this is the only randomised, placebo-controlled, double-blind trial having assessed the effect of rimonabant in patients with binge eating disorders. The rimonabant treatment reduced body weight significantly more than placebo in obese subjects with binge eating. Trial registration number (clinicaltrials.gov): NCT00481975.

[What is the evolution of metabolically normal obesity?]. / Que deviennent tes sujets obèses "métaboliquement" normaux?

A subgroup of obese subjects which could be protected from the cardiometabolic complications of obesity is described in the literature as "metabolically normal obese subjects". However, the lack of a joint definition of metabolic normality makes the available data difficult to interpret and to compare. A recent analysis of more than 1200 subjects in a prospective study showed that 21% of obese metabolically normal subjects at baseline developed the metabolic syndrome after three years. The obese subjects who remained metabolically normal showed, at three years, significantly higher values of cardiometabolic parameters as compared to subjects with normal body weight. In conclusion, the obese subjects even without any metabolic abnormality should benefit of a closer medical monitoring as well as a regular follow-up to avoid further weight gain.

[A new program of therapeutic education for obese patients]. / Un nouveau programme d'éducation thérapeutique pour les patients obèses.

Obesity is a chronic disease which is increasing over the past thirty years. This disease is complex and its treatment is difficult and generally frustrating for the patients and the medical team because of a high risk of relapse. Indeed, a dietetic approach alone is most of the time not good enough to obtain a long-lasting weight loss; the few drugs on the market should also be prescribed as a part of a more global approach. A multidisciplinary approach with a long-standing follow-up including a cognitive-behavioral therapy coupled to a diet and physical activity is mandatory to avoid any weight regain. We propose a new multidisciplinary program of two years with in hospital-stay and ambulatory follow-up which is showing some promising results (90% of success at one year).

Metabolic normality in overweight and obese subjects. Which parameters? Which risks?

OBJECTIVES: The objective of this study was to define metabolic normality and to investigate the cardiometabolic profile of metabolically normal obese. DESIGN: Cross-sectional study conducted at 21 research centers in Europe. SUBJECTS: Normal body weight (nbw, n=382) and overweight or obese (ow/ob, n=185) subjects free from metabolic syndrome and with normal glucose tolerance, were selected among the Relationship between Insulin Sensitivity and Cardiovascular Disease study participants. MAIN OUTCOME MEASURES: Insulin sensitivity was assessed by the clamp technique. On the basis of quartiles in nbw subjects, the limits of normal insulin sensitivity and of normal fasting insulinemia were established. Subjects with normal insulin sensitivity and fasting insulin were defined as metabolically normal. RESULTS: Among ow/ob subjects, 11% were metabolically normal vs 37% among nbw, P<0.0001. Ow/ob subjects showed increased fasting insulin (P=0.0009), low-density lipoprotein cholesterol (LDL-cholesterol) (P=0.004), systolic (P=0.0007) and diastolic (P=0.001) blood pressure, as compared with nbw. When evaluating the contribution of body mass index (BMI), hyperinsulinemia and insulin resistance, BMI showed an isolated effect on high-density lipoprotein (P=0.007), high-sensitivity C-reactive protein (P<0.0001), systolic (P=0.002) and diastolic (P=0.008) blood pressures. BMI shared its influence with insulinemia on total cholesterol (P=0.04 and 0.003, respectively), LDL-cholesterol (P=0.003 and 0.006, respectively) and triglycerides (P=0.02 and 0.001, respectively). CONCLUSION: In obese subjects, fasting insulin should be taken into account in the definition of metabolic normality. Even when metabolically normal, obese subjects could be at increased risk for cardiometabolic diseases. Increased BMI, alone or with fasting insulin, is the major responsible for the less favorable cardio-metabolic profile.

Open questions about metabolically normal obesity.

Subsets of obese subjects without any cardiometabolic risk factors have been repeatedly described. This raises questions whether obesity 'per se' enhances the risk for cardiovascular or metabolic diseases and whether healthy obese subjects would benefit from a medical treatment. In order to answer these questions, as a first step, an expert consensus should be reached for the definition of metabolic normality. In fact, up to now, different parameters related to the metabolic syndrome and/or to insulin sensitivity have been utilized across studies. Once an agreement is reached, population-based studies should be undertaken to establish the incidence of metabolic normality among obese subjects. Furthermore, many other parameters such as age, sex, race, fat distribution and physical activity should be monitored to obtain results representative of a general population. Longitudinal studies aimed at investigating the evolution of the cardiometabolic profile of healthy obese subjects are also needed. In conclusion, data from the literature strongly suggest that a regular surveillance of the cardiometabolic parameters and a prevention of any further weight gain should be applied to healthy obese individuals, whereas possible benefits of a weight loss treatment are still a matter of debate.

A 2-year multifactor approach of weight loss maintenance.

The overarching problem in the treatment of obesity is the consistency with which weight in treatment is regained. The aim of this study is to follow-up the patient using a multifactor approach (cognitive-behavioral therapies, diet and physical activity counselling, an "on-off" prescription of orlistat) during 4 years in order to assess the efficacy of this specific long-term weight loss maintenance programme. Weight maintenance is defined as a weight change of <2.5% of the study entry body weight. Fifty obese patients having previously lost at least 10% of their weight by any weight loss programme before entering the maintenance multifactor approach were enrolled. Ninety percent of the patients maintained more than 10% weight loss after 2 years. All the physical characteristics remained similar between study entry and 2 years after the weight loss maintenance programme. Waist and hip as well as fat mass did not show any significant differences and the mean fat mass remained stable 2 years later. In addition, all the psychological parameters analysed remained stable and in a normal range. In conclusion, this multifactor approach shows promising interim results at year-2. The multifactor approach with an "on-off" prescription of orlistat seems to be appropriate for the long term weight loss maintenance. But considering the clinical and psychological diversity of the patients, this approach has to be individually adapted for patients presenting eating behavior disorders which need a particular follow-up.

An exercise intervention to improve diabetic patients' gait in a real-life environment.

AIMS: Gait characteristics and balance are altered in diabetic individuals. Little is known about possible treatment strategies. This study evaluated the effect of a specific training program on diabetic patients' gait. METHODS: A randomized controlled trial (N=71) with an intervention (IG) (N=35), and control group (CG) (N=36). The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-oriented strengthening. Controls received no treatment. RESULTS: After intervention the IG increased their habitual walking speed by 0.149ms(-1) (0.54kmh(-1)) on tarred terrain and by 0.169ms(-1) (0.61kmh(-1)) on the cobblestones. This significant treatment effect (p<0.001) decreased slightly at the six-month follow-up, but remained significant (p<0.001). In a similar manner, significant improvement was observed for cadence, gait cycle time and stance time on both terrains. All outcomes except stance time on the tarred terrain remained significant at the six-month follow-up. No significant effect was observed for stride length and the coefficient of variation of gait cycle time (on either surface) at the corrected significance level of p<0.004. CG patients' parameters all remained unchanged or progressively deteriorated compared to baseline values. DISCUSSION: Cadence contributed 80%, whereas stride length only contributed 20% to the change of gait velocity. This may be due to the treatment or to diabetic patients' potential to regulate their cadence and stride length. CONCLUSION: A specific training program can improve diabetic patients' gait in a real life environment. A challenging environment highlights treatment effects on patients' gait better than an evenly tarred surface.

[Can an obese patient be metabolically normal?]. / Un patient obèse peut-il être métaboliquement normal?

Obesity is well recognized as a cardiovascular risk factor and being associated with cardio-metabolic diseases. However, certain authors describe the existence of metabolically benign obesity or not-complicated obesity. By examining various studies, one of the encountered difficulties is the criteria of normality among obese patients and the evaluated metabolic parameters. Even if traditional cardio-metabolic parameters such as the lipid profile, glycemia or blood pressure can be in normal ranges, the subjects in overweight or obesity are different from the subjects of normal body weight in terms of these parameters which are at the limit of normality. The purpose of this article is to summarize the current concepts of metabolic normality in obese subjects. We conclude that the body weight is the most important factor in the development of the cardio-metabolic consequences of obesity.

[Obesity in the elderly: which attitude?]. / Obésité chez la personne âgée: quelle attitude?

The body composition is changing with the age. The lean body mass reduces and the fat mass tends to accumulate at the visceral level. Because the weight loss induces a reduction of both fat mass and lean body mass, it is important to remain cautious about the weight loss among the elderly. However, the weight loss is important in obese patients in order to limit the cardio-metabolic complications and to improve the quality of life in term of mobility (e.g. in the context of osteoarthritis). We currently propose a balanced and slightly hypocaloric diet as well as a moderate and practicable physical activity for elderly patients. Cognitive behavioural approach or careful drug therapy can be proposed for obesity management concerning such patients.

[Long term weight loss maintenance]. / Maintien de la perte de poids à long terme.

A successful weight loss program leads to a new metabolic and endocrine balance that needs new long term management. Recent researches have shown some predictors as well as some barriers of the long term weight management. Predictors and barriers are linked to the lost weight, to the subject's habits and to the patient's psychosocial sphere. During the four-year follow-up, 78% of patients maintained 10% or more of their initial weight loss. The patients who maintained their weight presented less binge eating disorder, good motivation in diet and physical activity.

Biofeedback for foot offloading in diabetic patients with peripheral neuropathy.

AIMS: The reduction of high plantar pressure in diabetic patients with peripheral neuropathy is mandatory for prevention of foot ulcers and amputations. We used a new biofeedback-based method to reduce the plantar pressure at an at-risk area of foot in diabetic patients with peripheral neuropathy. METHODS: Thirteen diabetic patients (age 60.8 +/- 12.3 years, body mass index 29.0 +/- 5.0 kg/m(2)) with peripheral neuropathy of the lower limbs were studied. Patients with memory impairment were excluded. The portable in-shoe foot pressure measurement system (PEDAR) was used for foot offloading training by biofeedback. The learning procedure consisted in sequences of walking (10 steps), each followed by a subjective estimation of performance and objective feedback. The goal was to achieve three consecutive walking cycles of 10 steps, with a minimum of seven steps inside the range of 40-80% of the baseline peak plantar pressure. The peak plantar pressure was assessed during the learning period and at retention tests. RESULTS: A significant difference in peak plantar pressure was recorded between the beginning and the end of the learning period (when the target for plantar pressure was achieved) (262 +/- 70 vs. 191 +/- 53 kPa; P = 0.002). The statistically significant difference between the beginning of learning and all retention tests persisted, even at the 10-day follow-up. CONCLUSIONS: Terminal augmented feedback training may positively affect motor learning in diabetic patients with peripheral neuropathy and could possibly lead to suitable foot offloading. Additional research is needed to confirm the maintenance of offloading in the long term.

Obesity: a complex growing challenge.

The prevalence of overweight and obesity is increasing worldwide. The physiological mechanisms involved in body weight regulation are complex and incompletely understood. Increasing evidence suggests that obesity is a multifactorial disease where many, if not all, organs of the body are involved. The adipose tissue was considered as a simple fat accumulation for a long period of time. However, nowadays it is fascinating to progressively discover its involvement in hormonal, inflammatory or immune system dysregulation. Adipokines and cytokines are involved in control and regulation of appetite and energy balance, glucose and lipid metabolism, neuroendocrine function, reproduction, immunity, and cardiovascular function. The inflammatory background associated with obesity is closely related to insulin resistance. Moreover, the inhibitory effect of endocannabinoids on the expression of adiponectin could be involved in insulin resistance. Gut microbiota related factor may be responsible for the development of diet-induced obesity and diabetes through metabolic endotoxemia which triggers the inflammatory tone. Based on recent research, several physiopathological mechanisms involved in the development of obesity are reviewed.