The obesity treatment dilemma: Why dieting is both the answer and the problem? A mechanistic overview.

Restricted-calorie diets are the most worldwide used treatments for obesity. Although such strategies are based on the first law of thermodynamics, the real life clinical practice demonstrates that the observed weight losses are divergent from those theoretically predicted. Loosely adherence to recommendations is one of the main causes for the limited efficacy of dieting, but many additional factors can be involved in the hurdles to weight loss. According to the second law of thermodynamics any restriction in dietary energy intake results in energy sparing with a diminution in the basal metabolic rate and a concomitant loss in the lean body mass. This "thrifty" energetic adaptation is associated with a progressive reduction in the difference between levels of energy intake and expenditure, thus resulting in a drastic fall in weight loss rates on the medium and long-term regardless of the dietary carbohydrate/fat ratio. This loss of efficacy is aggravated by the misadaptation of the production and action of anti-obesity hormones such as leptin. During the latest past decades the discovery of changes in the gut microbiota of obese people referred to as "obese dysbiosis" has raised the question as to whether these alterations can participate to diet-resistance. Combined with the behavioral and psychological barriers to low-calorie diets, there is a broad physiologic spectrum of evidence indicating that weight loss is a hard challenge. Consequently, the answer would be primarily to prevent the development of obesity and at worst to avoid its ominous progression from metabolically healthy to unhealthy stages.

Effect on blood lipids of two daily servings of Camembert cheese. An intervention trial in mildly hypercholesterolemic subjects.

As a concentrated source of saturated fat, cheese consumption is considered to be associated with increased cholesterolemia and generally forbidden in dietary guidelines for adults with hypercholesterolemia. The aim of this study was to evaluate the impact of saturated fatty acids on lipid parameters and blood pressure with regards to different types of dairy products: Camembert and full-fat yoghurt. One-hundred and fifty-nine moderate hypercholesterolemic subjects without treatment were instructed to consume two full-fat yoghurts (2 × 125 g) per day for 3 weeks (run-in period) and then for a further period of 5 weeks, either two full-fat yoghurts or two 30 g servings of Camembert cheese per day. We observed that over the 5-week daily consumption of two servings of Camembert cheese, blood pressure and serum lipids did not change in moderate hypercholesterolemic subjects. These results suggest that fermented cheese such as Camembert could be consumed daily without affecting serum lipids or blood pressure.

[Type 2 diabetes complications]. / Complications du diabète de type 2.

People with type 2 diabetes are at increased risk of many complications, which are mainly due to complex and interconnected mechanisms such as hyperglycemia, insulino-resistance, low-grade inflammation and accelerated atherogenesis. Cardi-cerebrovascular disease are frequently associated to type 2 diabetes and may become life threatening, particularly coronaropathy, stroke and heart failure. Their clinical picture are sometimes atypical and silencious for a long time. Type 2 diabetes must be considered as an independent cardiovascular risk factor. Nephropathy is frequent in type 2 diabetes but has a mixed origin. Now it is the highest cause of end-stage renal disease. Better metabolic and blood pressure control and an improved management of microalbuminuria are able to slowdown the course of the disease. Retinopathy which is paradoxically slightly progressive must however be screened and treated in these rather old patients which are globally at high ophthalmologic risk. Diabetic foot is a severe complication secondary to microangiopathy, microangiopathy and neuropathy. It may be considered as a super-complication of several complications. Its screening must be done on a routine basis. Some cancer may be considered as an emerging complication of type 2 diabetes as well as cognitive decline, sleep apnea syndrome, mood disorders and bone metabolism impairments. Most of the type 2 diabetes complications may be prevented by a strategy combining a systematic screening and multi-interventional therapies.

Impact of altered alveolar volume on the diffusing capacity of the lung for carbon monoxide in obesity.

BACKGROUND: Studies on the diffusing capacity of the lung for carbon monoxide (DL(CO)) in obese patients are conflicting, some studies showing increased DL(CO) and others unaltered or reduced values in these subjects. OBJECTIVES: To compare obese patients to controls, examine the contribution of alveolar volume (VA) and CO transfer coefficient (K(CO)) to DL(CO), and calculate DL(CO) values adjusted for VA. METHODS: We measured body mass index (BMI), waist circumference (WC), spirometry and DL(CO) in 98 adult obese patients without cardiopulmonary or smoking history and 48 healthy subjects. All tests were performed in the same laboratory. RESULTS: Using conventional reference values, mean DL(CO) and VA were lower (-6%, p < 0.05, and -13%, p < 0.001, respectively), and K(CO) was higher (+9%, p < 0.05) in obese patients than in controls. VA decreased whereas K(CO) increased with increasing BMI and WC in the obese group. Patients with lower DL(CO) had low K(CO) in addition to decreased VA. In contrast, some obese patients maintained normal VA, which, coupled with high K(CO), resulted in higher DL(CO). The main result is that diffusion capacity differences between obese patients and controls disappeared using reference equations adjusting DL(CO) for VA. CONCLUSIONS: Using conventional reference equations, our obese patients show slightly lower mean DL(CO,) lower mean VA and higher mean K(CO) than controls, but with a large range of DL(CO) values and patterns. Adjusting DL(CO) for VA suggests that low lung volumes are the main cause of low DL(CO) and high K(CO) values in obese patients.

[Radical complications of obesity]. / Conséquences pathologiques de l'obésité.

Obesity increases overall morbidity mainly by the increased mass of fat tissues and by the hyperproduction of pro-inflammatory molecules by the abdominal tissue. Coronary artery disease, metabolic syndrome or diabetes mellitus are the main complications linked to the inflammatory low-grade syndrome whereas arthritis is linked to the adipocytes mass. Many other complications are associated with obesity: steato-hepatitis, glomerulo-sclerosis, digestive diseases such as gallstones, hypofertility, psychosocial dysfunction and depression and certain cancers. Obesity is also a risk factor for pregnancy and surgery. Most of these complications are reversible after a substantial weight loss.

[Nutrition approaches to prevent chronic disease]. / Prévention nutritionnelle des maladies chroniques.

Chronic diseases such as obesity, diabetes, macrovascular disease including coronaropathy and stroke, osteoporosis and various cancer have, in one way or another, food and nutritional determinants and may be considered as nutritionally or environmental-related diseases. There is a growing literature indicating that specific dietary constituents or diet are able to influence the development and the outcome of chronic disease. Long term prospective clinical trials are yet locking to confirm on evidences-based medicine criteria the correlation described between food and disease. However animal as well as epidemiological data suggest that high energy density and low nutrient density which characterized diet in developed countries are the main targets that must be fight. On the basis of current researches, Mediterranean diet seemed to be the best and the more applicable diet in order to have optimal health. Such a diet low in calories and saturated fat and high in fruit and vegetables and in whole grain should become a key composant for reduce the oxidant, inflammatory, atherogenic, mutagenic and hyperinsulinic status and then prevent or delay chronic diseases.

Subclinical hyperthyroidism: considerations in defining the lower limit of the thyrotropin reference interval.

BACKGROUND: Although numerous reports have discussed the upper limit of the thyrotropin (TSH) reference interval, none have dealt with the lower limit. Recent recommendations regarding subclinical thyroid dysfunction give different advice about its management, depending on whether the TSH concentration is <0.1 mIU/L or 0.1-0.4 mIU/L. CONTENT: We review key studies that have investigated the links between low TSH concentrations, cardiovascular morbidity, and mortality, with a focus on the TSH measurement threshold and assay type. SUMMARY: Despite numerous consensus guidelines and publications of expert opinion, the management of subclinical hyperthyroidism remains largely intuitive and "nonevidence-based." The primary reason for this unsatisfactory situation is the absence of clinical-intervention trials. Important aspects that remain to be addressed are the influence of the method used to measure TSH, the definition of "normality," and the lack of evidence to base the grading of cardiovascular risk on the degree of TSH suppression. A risk-based approach should be adopted to determine the thresholds that would justify interventions. Such considerations assume, of course, that proof will emerge from ongoing clinical trials to support the medical utility of treating subclinical hyperthyroidism.

[Hyperglycemia in the critically ill: meaning and treatment]. / Hyperglycémie dans les maladies aiguës : signification et prise en charge.

Hyperglycemia is commun in critically ill patients without previously known diabetes. Hyperglycemia occurring in these patients is mainly a consequence of stress associated to complex glucose metabolism abnormalities which have deleterious effects on tissues and vascular function. Several epidemiologic and intervention studies had established that hyperglycemia is related to morbidity and mortality. Maintenance of normoglycemia with intensive insulin therapy seems to decrease morbidity and mortalities in severe acute illnesses. However the benefit of most of these intervention trials remain controversial mainly in stroke, myocardial infarction and severe sepsis. Moreover strict normoglycemia required to obtain an optimal benefit increases the risk of hypoglycaemia which may be particularly harmful in patients in critical state.

Effect of an educational program (PEGASE) on cardiovascular risk in hypercholesterolaemic patients.

BACKGROUND: Many studies have demonstrated a gap between guidelines for the prevention of cardiovascular disease (CVD) and their implementation in clinical practice. AIM: The PEGASE education program has been devised with an aim to improve the management of patients at high risk of CVD. METHODS: In a multicentre study carried out from 2001-2004 in France, 96 participating physicians were randomized into a "trained" group, which included 398 "educated" patients, and a "non-trained" group, which included 242 "non-educated" patients. Educated patients received six hospital-based educational sessions, four collective and two individual. Framingham score, smoking, lipid levels, glycaemia, blood pressure, dietary intake and drug compliance, as well as quality of life, were evaluated at baseline (M0) and 6 months (M6). The primary endpoint of the study was the efficacy of the PEGASE program in reducing global CVD risk in high-risk patients. RESULTS: The Framingham score was calculated for 473 patients. The Framingham score improved significantly at M6 vs M0 in the educated group (13.0 +/- 8.21 vs 13.6 +/- 8.48, d = -0.658, p = 0.016), but not in the non-educated group (12.5 +/- 8.19 vs 12.4 +/- 7.81, d = +0.064, p = 0.836); the mean change between the two groups did not reach significance. Quality of life, LDL-c level and diet scores improved in the "educated" group only. CONCLUSIONS: The PEGASE education program improved risk factors for CVD, although global assessment by Framingham score was not significantly different between groups. This program, aimed at meeting needs and expectations of patients and physicians, was easily implemented in all hospital centres.

[Subclinical hypothyroidism and quality of life of women aged 50 or more with hypercholesterolemia: results of the HYOGA study]. / Hypothyroïdie fruste et qualité de vie chez des femmes hypercholestérolémiques de plus de 50 ans: résultats de l'étude HYOGA.

AIM: Subclinical hypothyroidism (SCHT) is defined by the combination of an increased TSH level and a normal free thyroxin concentration. The aim of this survey is the description of the prevalence, the symptoms and the quality of life in SCHT diagnosed in a group of hypercholesterolemic women. METHODS: A total of 1610 female patients aged 50 or more with hypercholesterolemia (total cholesterol between 240 and 400mg/dl, receiving or not a lipid-lowering treatment) were enrolled by 347 general practitioners (GPs). A clinical form including symptoms, clinical history, and treatments was completed by GPs while a SF-36 QOL form was filled up by the patients. Further GPs' prescriptions for tests and treatments were also recorded. RESULTS: Full data leading to subclinical hypothyroidism are available in 721 patients (44.8%) who were selected into the study. Among these patients, the prevalence of SCHT (SCHT+) is 16.6% (120 patients) and 76.3% of the patients have at least one symptom. Most frequent symptoms are physical and intellectual asthenia, muscular weakness, and sensitivity to cold but those symptoms are present in patients without SCHT (SCHT-) too and there is no significant difference between the two groups. TSH level was 4 to 10 mUI/l in 90% of SCHT+ patients. 38.6% of hypercholesterolemic SCHT+ patients never had any TSH measurement. QOL is affected in SCHT+ compared to SCHT- patients with a significantly decreased mental summary score of 36.21+/-9.4 versus 39.4+/-12.18 (p<0.006). QOL (mental health score) is significantly lower when TSH value raised from a 2.4-4 range up to a 4-10 mUI/L range. CONCLUSIONS: SCHT is frequent in a population of hypercholesterolemic female patients aged 50 or more. In the presence of suggestive symptoms, screening is important especially as QOL is affected even when TSH is < 10 mUI/L. It remains to show with controlled prospective studies whether thyroxin supplementation can improve symptoms and QOL.

Isolated microcytic anemia disclosing a unicentric Castleman disease: The interleukin-6/hepcidin pathway?

Castleman disease (CD) is a rare lymphoproliferative disorder of uncertain origin. Anemia is commonly reported and is related to an inflammatory mechanism. Occasionally an autoimmune hemolytic anemia appears as the leading clinical feature. Three histological types have been differentiated, a hyaline-vascular type (HV), a plasma cell type (PC), and a mixed type. Clinically CD is separated into unicentric (localized) or multicentric (generalized) forms. The former is most frequently of HV type (80-90%), affecting a single lymph node. The PC type is encountered in 10-20% of the unicentric CD and in almost all of the multicentric cases. Numerous systemic manifestations have been described usually associated with PC type. An isolated and markedly microcytic anemia revealing a unicentric CD has never been reported in English literature. Recent data concerning iron metabolism, interleukin-6 and hepcidin provide interesting clues to understand the particular microcytic anemia of CD.

Low-density lipoprotein apheresis in children with familial hypercholesterolemia: follow-up to 21 years.

Twenty-seven patients (14 girls, 13 boys) affected by familial hypercholesterolemia who had begun low-density lipoprotein (LDL) apheresis treatment before the age of 15 were studied. The median age at diagnosis was 4 years and the blood LDL cholesterol level was 704 +/- 163 mg/dL. Screening was performed for homozygous or double heterozygous mutations of the LDL cholesterol receptor gene and mutations were found in 24 of the patients. The mean age at the beginning of treatment was 8.5 years and the mean length of follow up was 12.6 years. The two main procedures used were direct adsorption of lipoproteins and dextran sulfate cellulose adsorption. Nine patients experienced anaphylactic reactions due to bradykinin and six had to have their treatment changed. The LDL cholesterol level before the session was lowered by 45 +/- 11% of the value at diagnosis. The LDL cholesterol reduction in a session was 72 +/- 10%. Tendinous xanthomas disappeared or diminished dramatically in 62% of the children. In 22 patients no cardiovascular event occurred during LDL apheresis treatment. Three had angina pectoris; two others had surgical management of aortic stenosis, but no clinical manifestations. Seven children had normal cardiovascular pictures while on treatment. Eleven had abnormalities of the aortic root or coronary arteries, which in six cases had appeared before treatment; the other five children did not undergo prior cardiac evaluation. In five children the abnormalities appeared during treatment. Based on these data, LDL-apheresis can be recommended for the treatment of homozygous familial hypercholesterolemia, even in young children, with good efficiency on biological parameters, cutaneous lesions and cardiovascular events.

Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking.

OBJECTIVE: The objective of this study was to re-evaluate the adult C(T) reference values determined by five different immunoassays and by introducing criteria for selecting control subjects. DESIGN: A prospective multicenter study. PATIENTS: Three hundred and seventy-five clinically euthyroid subjects. METHODS: We used five different C(T) immunoassays. Sera were assayed for the concentration of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase antibodies. RESULTS: Screening for the various potential causes of hypercalcitoninemia led to the exclusion of 23% of the sera. Our reference value analysis dealt with 287 subjects (142 men and 145 women). The proportion of samples in which no C(T) was detected varied from 56% (for assay D) to 88% (for assay C). We observed significant correlations (whose magnitude depended on the assay used) between C(T) levels and age or body mass index (BMI) (primarily in men). The distribution of C(T) levels showed that 4.7, 9.8, 2.5, 6.5, and 8.0% of the values were over 10 pg/ml respectively. These values corresponded essentially to samples from 11 male subjects (median age: 55 years), most of whom were smokers. The highest C(T) values were around twice as high in men than women, and were higher in smokers than non-smokers. Conclusion In clinical practice (and after having excluded the usual causes of raised C(T) levels), the interpretation of C(T) assay results must take into account i) the method used; ii) the patient's gender, age, and weight; and iii) the potential influence of cigarette smoking.

Effect of low-fat, fermented milk enriched with plant sterols on serum lipid profile and oxidative stress in moderate hypercholesterolemia.

BACKGROUND: Plant sterol (PS)-enriched foods have been shown to reduce plasma LDL-cholesterol concentrations. In most studies, however, PSs were incorporated into food products of high fat content. OBJECTIVE: We examined the effect of daily consumption of PS-supplemented low-fat fermented milk (FM) on the plasma lipid profile and on systemic oxidative stress in hypercholesterolemic subjects. DESIGN: Hypercholesterolemic subjects (LDL-cholesterol concentrations >or=130 and

[Do we still have glucocorticoid-induced adrenal insufficiency?]. / Que reste-t-il de l'insuffisance surrénale post-corticothérapie?

Adrenal insufficiency (AI) induced by glucocorticoids was first described more than 50 years ago in patients undergoing surgical stress. Although considered the most frequent cause of AI, the true incidence of this complication of glucocorticoid treatment remains unknown. No factors are known to predict AI after glucocorticoid treatment. In particular, neither the dose nor the duration of treatment seems predictive. The minimum dose of cortisol necessary for the body to cope with medical or surgical stress is unknown. The adrenocorticotropin test is often used during corticosteroid withdrawal because it is well correlated with adrenal response to surgical stress, but not with clinical events. Studies over the past 15 years have shown that the perioperative risk of AI has been overestimated and that hydrocortisone doses should be decreased. A prospective study of patients after steroid withdrawal is the only means of assessing the true incidence of this complication to propose a rational strategy to prevent it.

Diet and physical activity profiles in French preadolescents.

Dietary patterns have been identified in adults, but less is known about children and adolescents. For the first time, we have investigated lifestyle patterns combining diet and physical activity in 12-year-old French preadolescents and examined their association with sociodemographic factors. Physical activity, sedentary activities and dietary habits were assessed by questionnaires given to 2724 students in 2001. Family income tax and parents' educational level, as indicators of socio-economic status, and the size of the residence commune were obtained from parents. After adjusting for socio-economic status, physical activity was positively associated with a consumption of fruit/vegetables/fruit juice on more than four occasions in the previous 24 h (P<0.001). Sedentary activities were positively associated with the consumption of French fries or potato chips (P<0.001), with sweetened drink as the most usual drink (P<0.001) and with nibbling while watching television (P<0.001), and inversely associated with a high consumption of fruit/vegetables/fruit juice (P=0.04). Multiple correspondence analysis identified two independent axes and specific combinations of behaviour: one axis characterised by sedentary activity, sweetened drink as the most usual drink, the consumption of French fries or potato chips and nibbling while watching television; a second one associating physical activity and the consumption of fruit/vegetables/fruit juice. Both socio-economic proxies were associated with the former axis (P<0.001). The size of the residence commune was associated with the latter (P<0.1). Combinations of diet and physical activity habits were identified in adolescents, indicating that prevention programmes targeting both behaviours may have an enhanced outcome.