Anal incontinence incidence is high in patients with obesity prior to bariatric surgery: Prevalence, risks-factors.

INTRODUCTION: Anal incontinence (AI) prevalence in general population is estimate to range from 1.4 to 19.5% (Wexner ≥ 1). Obesity could be an AI risk factor. However, AI prevalence in patients with obesity is not clearly established. The main objective of this study was to assess the prevalence of AI in patients with extreme obesity prior to bariatric surgery and to identify specific AI risk factors in this subset of patients. MATERIAL: A cross-sectional study, in a tertiary referral center in obesity was performed during one year. Patients who presented criteria for bariatric surgery (BMI>40 or BMI > 35 with co-morbidities) were asked to fill in preoperative self-questionnaires. A Wexner score ≥ 3 was used to define AI to identified patients who had a clinic impact of AI, by frequency of symptoms or alteration of quality of life. RESULTS: Two hundred and fifty patients were included. Corresponded to, 196 women (78.4%) and 54 men (21.6%). Median BMI was 44.53kg/m2. AI was diagnosed in 41 patients (prevalence 16.4%, 95CI 0.59). Constipation, urinary incontinence and the history of pregnancy (P = 0.03, OR 2.79; P = 0.01, OR 3.53 and P=0.02, OR 4.71, respectively) were significantly associated with AI. CONCLUSION: AI is frequently observed in patients with extreme obesity scheduled for bariatric surgery and should be routinely evaluated. Modifiable risk factors as constipation should be manage before surgery as well as the specific management of AI, to prevent AI exacerbation after surgery. The choice of bariatric surgical procedure should be discussed and evaluated for the treatment of patients with obesity and AI. LEVEL OF EVIDENCE: Moderate.

Recommendations for nutritional care after bariatric surgery: Recommendations for best practice and SOFFCO-MM/AFERO/SFNCM/expert consensus.

Nutritional care after bariatric surgery is an issue of major importance, especially insofar as risk of deficiency has been extensively described in the literature. Subsequent to the deliberations carried out by a multidisciplinary working group, we are proposing a series of recommendations elaborated using the Delphi-HAS (official French health authority) method, which facilitates the drawing up of best practice and consensus recommendations based on the data of the literature and on expert opinion. The recommendations in this paper pertain to dietary management and physical activity, multivitamin and trace element supplementation and the prevention and treatment of specific deficiencies in vitamins B1, B9, B12, D and calcium, iron, zinc, vitamins A, E and K, dumping syndrome and reactive hypoglycemia.

Six-month outcomes of teduglutide treatment in adult patients with short bowel syndrome with chronic intestinal failure: A real-world French observational cohort study.

BACKGROUND & AIMS: Teduglutide, a GLP-2-analog, has proven effective in two placebo-controlled studies in reducing parenteral support (PS) in patients with short bowel syndrome-associated intestinal failure (SBS-IF) after 24 weeks. The aim of this study was to describe in a real-life situation the effects of teduglutide treatment and their predictive factors. METHODS: We included 54 consecutive SBS-IF patients treated with teduglutide in France for at least 6 months from 10 expert centers. Small bowel length was 62 ± 6 cm and 65% had colon in continuity. PS was 4.4 ±0 .2 infusions per week, started 9.8 ± 1.2 years before. Response (PS reduction ≥ 20%) and PS discontinuation rates were assessed at week 24. Adjusted p values of factors associated with response and weaning were calculated using a multivariate logistic regression model. RESULTS: At week 24, 85% of patients were responders and 24% had been weaned off PS, with a 51% reduction of PS needs and 1.5 ± 0.2 days off PS per week. Response to teduglutide was influenced by a higher baseline oral intake (p = 0.02). Weaning off PS was influenced by the presence of colon (p = 0.04), a lower PS volume (p = 0.03) and a higher oral intake (p = 0.01). There were no differences based on age, bowel length or SBS-IF causes. CONCLUSIONS: Our study confirms the effectiveness of teduglutide in reducing PS needs in SBS-IF patients. We associated reduced parenteral support volume with baseline parenteral volume support, bowel anatomy, and oral intake. These findings underline the role of nutritional optimization when starting the treatment.

Evaluation of risk factors for complications after bariatric surgery.

The decision to perform a bariatric surgical procedure, the conclusion of a clinical pathway in which management is individually adapted to each patient, is taken after multidisciplinary consultation. Paradoxically, the patients who would most benefit from surgery are also those who have the highest operative risk. In practice, predictive factors of mortality and severe postoperative complications (Clavien-Dindo>III) must be used to evaluate the benefit/risk ratio most objectively. The main risk factors are age, male gender, body mass index, obstructive sleep apnea syndrome, insulin resistance and diabetes, tobacco abuse, cardiovascular disease, ability to lose weight before surgery, hypoalbuminemia and functional disability. Routine preoperative evaluation of high perioperative risk patients provides the attending physician with information to: (1) correct several of these risk factors before surgery and thereby limit the operative risk; (2) orient the patient to a less risky surgical procedure and/or to a facility with a more adapted technical capacity, as necessary; (3) contra-indicate the operation if the risks exceed the expected benefits. All in all, this preoperative evaluation combined with management of comorbidities contributes to decrease the risk of postoperative complications and to improve the overall management of obese patients.

Carotenoid deficiency in chronic pancreatitis: the effect of an increase in tomato consumption.

BACKGROUND/OBJECTIVES: Carotenoids are potentially malabsorbed in patients with chronic pancreatitis (CP). The aims of this study were: (1) to determine the prevalence of low levels of each of the major carotenoids in subjects with CP; (2) to compare carotenoids in CP subjects with or without vascular disease and (3) to test the effect of an increase in dietary lycopene intake in patients with low plasma lycopene concentration. SUBJECTS/METHODS: Simultaneous determination of carotenoids was done in 80 patients with CP and 20 healthy subjects, using high-performance liquid chromatography. Of the CP patients who had low lycopene concentration, 22 (<120 µg/l) had to consume daily 40 g tomato paste (approximately 24 mg lycopene). RESULTS: Of these patients, 84.7% had at least one carotenoid deficiency and 27.5% had more than four carotenoid deficiencies. Low plasma concentrations in ß-carotene and lycopene were correlated, in CP group, with a low body mass index (BMI), a low low-density lipoprotein (LDL) cholesterol concentration, alcohol consumption and current smoking status, whereas low plasma concentration in ß-cryptoxanthine was correlated with a low BMI, a low LDL cholesterol concentration and alcohol consumption. Lycopene concentration was decreased in patients with vascular disease (171±197 vs 99±72 µg/l; P=0.02). After an intervention period of 8±2 months, lycopene concentration increased from 67.5±30 to 121.8±102 µg/l (P=0.025). CONCLUSION: Carotenoid concentrations are dramatically decreased in CP, especially lycopene in CP patients with vascular disease. Despite malabsorption, it is possible to increase lycopene plasma concentration by increasing heated tomato consumption.

Medical follow up after bariatric surgery: nutritional and drug issues. General recommendations for the prevention and treatment of nutritional deficiencies.

This review is an update of the long-term follow-up of nutritional and metabolic issues following bariatric surgery, and also discusses the most recent guidelines for the three most common procedures: adjustable gastric bands (AGB); sleeve gastrectomy (SG); and roux-en-Y gastric bypass (GBP). The risk of nutritional deficiencies depends on the percentage of weight loss and the type of surgical procedure performed. Purely restrictive procedures (AGB, SG), for example, can induce digestive symptoms, food intolerance or maladaptative eating behaviours due to pre- or postsurgical eating disorders. GBP also has a minor malabsorptive component. Iron deficiency is common with the three types of bariatric surgery, especially in menstruating women, and GBP is also associated with an increased risk of calcium, vitamin D and vitamin B12 deficiencies. Rare deficiencies can lead to serious complications such as encephalopathy or protein-energy malnutrition. Long-term problems such as changes in bone metabolism or neurological complications need to be carefully monitored. In addition, routine nutritional screening, recommendations for appropriate supplements and monitoring compliance are imperative, whatever the bariatric procedure. Key points are: (1) virtually routine mineral and multivitamin supplementation; (2) prevention of gallstone formation with the use of ursodeoxycholic acid during the first 6 months; and (3) regular, life-long, follow-up of all patients. Pre- and postoperative therapeutic patient education (TPE) programmes, involving a new multidisciplinary approach based on patient-centred education, may be useful for increasing patients'long-term compliance, which is often poor. The role of the general practitioner has also to be emphasized: clinical visits and follow-ups should be monitored and coordinated with the bariatric team, including the surgeon, the obesity specialist, the dietitian and mental health professionals.

What is the quality of information about bariatric surgery on the internet?

BACKGROUND: The purpose of this study was to evaluate the role of Internet on patients scheduled for bariatric procedures and the quality of information available on different websites. METHODS: Between July 2003 to July 2005, patients undergoing bariatric surgical procedures completed a survey. Data were collected prospectively. One hundred valid surveys were returned. Independently, two bariatric surgeons evaluated available French and English websites using major search engines. RESULTS: Forty-two of 100 patients (42%) sought information about bariatric surgery on the Internet. Seventy-four percent of these patients (n = 31/42) used search engines with 81% visiting less than ten websites. According to the patient's evaluation, 58% of the websites visited did not provide technical details of any surgical bariatric procedures, and only 61% provided information regarding postoperative weight loss. Furthermore, 58% of websites did not provide information about the laparoscopic approach, and 54% did not give any information on potential postoperative complications. Bariatric surgeon's evaluation was similar except for two differences: laparoscopic approach and postoperative weight loss information were discussed in 90% (p < 0.001) and 43% (p < 0.1) of visited websites, respectively. CONCLUSION: When the Internet was used to search for information about bariatric surgery, search engines were preferentially used but search duration was short. Available Internet websites can be considered as moderately reliable; however, 25% of visited websites contain misleading information. Comparison between patients and surgeons views showed that patients were effective in detecting misleading information.

Myocardial collagen turnover in normotensive obese patients: relation to insulin resistance.

OBJECTIVES: The present study was undertaken to assess the differential impact of insulin resistance, leptin and body composition on myocardial mass and serum markers of cardiac fibrosis in obese subjects, within a small range of elevated BMI (30-40 kg/m(2)), without pulmonary disease, cardiovascular disease, hypertension, cardiac hypertrophy or other cardiovascular disease. BACKGROUND: Obesity is an independent predictor of left ventricular mass (LVM) and is associated with disturbances in cardiac structure. The extent of the interstitial fibrosis in obese patients is not known, especially in the absence of cardiac hypertrophy. METHODS AND RESULTS: We included 160 obese subjects. The LVM was obtained using the Devereux formula. Body composition was estimated from a total body scan. Insulin sensitivity was assessed by homeostasis model assessment (HOMA), and cardiac collagen turnover by measurement of procollagen type III aminopeptide (PIIINP). PIIINP was correlated to the E/A ratio (r=0.24; P=0.012), a marker of ventricular function. PIIINP was independently correlated with glucose concentration (r=0.27; P=0.004), indexes of insulin resistance (HOMA (r=0.27; P=0.003), insulin (r=0.24; P=0.008)), and parameters associated with the insulin-resistance syndrome (HDL-cholesterol r=-0.27; P=0.004) and fat trunk/fat leg ratio (r=0.24; P=0.053)). The variable most correlated with PIIINP was HDL-cholesterol, followed by HOMA (r (2)=0.13). When HOMA was substituted for blood glucose concentration and insulinemia (Model 2), HDL-cholesterol was strongly related to lower PIIINP levels, followed by higher glucose concentration (r (2)=0.21). Regression analyses showed that LVM had the strongest independent positive correlation with fat-free mass (FFM) (r=0.39; P=0.0002), followed by systolic blood pressure (r=0.19; P=0.034). Neither adipose mass nor height independently added information to multivariate models. The ratio leptin/fat mass was correlated with LVM (r=-0.27; P=0.004), but not independently of the FFM. Markers for fibrosis were not significantly correlated with LVM. As a result, FFM was the most predictive factor of LVM in obese subjects. CONCLUSION: We found that serum levels of markers of cardiac collagen synthesis were significantly associated with insulin resistance in normotensive, nondiabetic obese subjects, and not related to the LVM. As a result, PIIINP could be a very early marker of ventricular dysfunction in these patients. Furthermore, we suggest that, for better detection of left ventricle hypertrophy in obese subjects, LVM should be indexed to FFM rather than to body surface area, or height.

Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression.

AIMS/HYPOTHESIS: Autotaxin is a lysophospholipase D that is secreted by adipocytes and whose expression is substantially up-regulated in obese, diabetic db/db mice. The aim of the present study was to depict the physiopathological and cellular mechanisms involved in regulation of adipocyte autotaxin expression. METHODS: Autotaxin mRNAs were quantified in adipose tissue from db/db mice (obese and highly diabetic type 2), gold-thioglucose-treated (GTG) mice (highly obese and moderately diabetic type 2), high-fat diet-fed (HFD) mice (obese and moderately diabetic type 2), streptozotocin-treated mice (thin and diabetic type 1), and massively obese humans with glucose intolerance. RESULTS: When compared to non-obese controls, autotaxin expression in db/db mice was significantly increased, but not in GTG, HFD, or streptozotocin-treated mice. During db/db mice development, up-regulation of autotaxin occurred only 3 weeks after the emergence of hyperinsulinaemia, and simultaneously with the emergence of hyperglycaaemia. Adipocytes from db/db mice exhibited a stronger impairment of insulin-stimulated glucose uptake than non-obese and HFD-induced obese mice. Autotaxin expression was up-regulated by treatment with TNFalpha (insulin resistance-promoting cytokine), and down-regulated by rosiglitazone treatment (insulin-sensitising compound) in 3T3F442A adipocytes. Finally, adipose tissue autotaxin expression was significantly up-regulated in patients exhibiting both insulin resistance and impaired glucose tolerance. CONCLUSIONS/INTERPRETATION: The present work demonstrates the existence of a db/db-specific up-regulation of adipocyte autotaxin expression, which could be related to the severe type 2 diabetes phenotype and adipocyte insulin resistance, rather than excess adiposity in itself. It also showed that type 2 diabetes in humans is also associated with up-regulation of adipocyte autotaxin expression.

Fatty acid abnormalities in chronic pancreatitis: effect of concomitant diabetes mellitus.

OBJECTIVE: Patients with chronic pancreatitis suffer from malabsorption and nutritional deficiencies. However there is little data available concerning the fatty acid profile in chronic pancreatitis. Diabetes mellitus, a common complication of this disease, could interfere with the metabolism of fatty acids. SUBJECTS: We therefore compared the fatty acid composition of LDL from four groups of male patients with (a) chronic pancreatitis without diabetes (ND-CP; n=12), (b) diabetes secondary to chronic pancreatitis and insulin-treated (CP-D; n=35); (c) type 1 diabetes (n=25); and (d) controls (n=20). RESULTS: The patients in both groups of chronic pancreatitis (ND-CP and CP-D) had lower mean values for linoleic acid than that seen in the type 1 DM and control groups, whereas monounsaturated fatty acids (MUFA; 18 : 1(n-9) and (16 : 1(n-7)) were significantly increased in these two groups (ND-CP and CP-D). Docosa-hexaenoic-acid (22 : 6(n-3)) was significantly decreased in the CP-D group (P>0.05), a response that could be explained by the effects of diabetes mellitus and by selenium deficiency. In this way, diabetes was associated with a decrease in the docosa-hexaenoic-acid (22 : 6(n-3); r=0.30, P=0.005), and selenium was correlated with DHA (r=0.28, P=0.029) and with the 22 : 6(n-3)/20 : 5(n-3) ratio (evaluating the delta 4 desaturation); r=0.31, P=0.022), independently of the diabetes effect. Selenium was negatively correlated with 20 : 4(n-6)/20 : 3(n-6) ratio (evaluating the delta 5 desaturase; r=-0.30; P=0.025). These results suggest that these two factors may have a role in the regulation of the desaturation process. If we consider that a ratio of 16 : 1(n-7)/18 : 2(n-6) greater than 0.086 in plasma indicates an EFAn-6 deficiency, 40% of our CP patients, 57.6% of CP-D patients and 13.6% of type 1 DM patients were involved. CONCLUSIONS: The consequences of these deficiencies are not evaluated in this disease. However, correction of the fundamental deficiencies in essential fatty acids and in selenium seems desirable in chronic pancreatitis.

[How do you really know if the obese patient has sleep apnea?]. / Connaissez-vous vraiment l'apnée du sommeil chez le sujet obèse?

Obesity is known to predispose to obstructive sleep apnea (OSA), a condition characterized by repeated episodes of apnea or hypopnea during sleep, due to the interruption of airflow through the nose and mouth. These episodes lead to the fragmentation of sleep and to decrease in oxyhaemoglobin saturation. Patients with massive obesity, with or without daytime hypersomnolence should be systematically screened for OSA, because many of them appear to be asymptomatic and unaware of their breathing abnormalities during sleep. Polysomnography (PSG) in an attended hospital laboratory setting is the gold standard for the diagnosis of OSA. However portable recording devices can be used for screening with good sensibility and specificity, and even for diagnosis when the apnea-hypopnea index is high. However the final diagnosis can only be carried out in a sleep laboratory using PSG by highly-qualified personnel, because of the limitations of the portable recording device. There is a strong association between OSA and the risk of traffic accidents. It has been established that OSA affects quality of life. There is also increasing evidence that OSA is an independent risk factor for cardio-vascular diseases. This has been successfully demonstrated for hypertension by prospective studies. But the evidence remains weak for myocardial infarction, stroke or mortality. Treating OSA with continuous positive airway pressure (CPAP) is the treatment of choice. CPAP improves quality of life, driving simulator performance, blood pressure and sleepiness, as demonstrated by randomised placebo controlled trials. The majority of obese OSA patients are currently not being offered diagnosis testing and treatment. It's a real challenge due to the epidemic increase of obesity prevalence. Portable recording devices could be available outside the sleep laboratory in nutrition department, where morbid obesity is treated. This emphasizes the need for a real collaboration between these departments and sleep experts.

Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis.

The metabolism of apolipoprotein (apo) A-IV in diabetes mellitus (DM) is poorly understood. Several factors, such as dietary fat intake, fat malabsorption, acute inflammation, and hormonal dysregulation can disturb the plasma apo A-IV concentration. We have compared the plasma apo A-IV concentrations in patients with type 1 DM and DM secondary to chronic pancreatitis to determine the effects of combinations of these factors. We examined 4 groups of male patients with chronic pancreatitis without diabetes (ND-CP) (n = 12), diabetes secondary to chronic pancreatitis and insulin-treated (CP-DM) (n = 32), type 1 diabetes (n = 25), and controls (n = 20). Plasma apo A-IV was significantly lower in the chronic pancreatitis patients (ND-CP and CP-DM) than in the other patients. Inflammatory proteins (fibrinogen, ceruloplasmin, and haptoglobin) were significantly elevated in the 2 chronic pancreatitis groups. The apo A-IV concentration was positively correlated with hemoglobin A(1c) (HbA(1c)) percentage in each group of diabetic patients (CP-DM, r =.35; P =.046; type 1 DM, r =.53; P =.010), in both groups of diabetic patients (r =.472; P <.0001) and negatively correlated with ceruloplasmin concentration in each group of diabetic patients (CP-DM, r = -.48; P =.0052; type 1 DM, r = -.66; P =.003), in both groups of diabetic patients (r = -.561; P <.0001), and in the whole population (r = -.463; P <.0001). Apo A-IV was also negatively correlated with haptoglobin in type 1 DM patients (r = -.434; P =.0435), in the both groups of diabetic patients (r = -.349; P =.0154), and in the whole population (r = -.351; P =.0019). Multiple linear regression analysis revealed that only HbA(1c) and ceruloplasmin were independent explanatory variables. Plasma apo A-IV is positively correlated with HbA(1c) suggesting that hyperglycemia per se selectively affects apo A-IV metabolism. The correlation between the concentrations of inflammatory protein and apo A-IV suggest a link between chronic inflammation and apo A-IV synthesis or catabolism. As apo A-IV is involved in reverse cholesterol transport, its low level in CP-DM may contribute to the accelerated development of atherosclerosis in these patients.

Impaired autonomic control of heart rate and blood pressure in obesity: role of age and of insulin-resistance.

The objectives of this study were to investigate cardiac and peripheral autonomic nervous system changes in normotensive overweight or obese subjects and the possible relation between these changes and insulin resistance independent of age. The authors used spectral analysis to measure simultaneously the short-term variability of heart rate (HR) and blood pressure (BP) using a Finapres device, in 67 normotensive overweight or obese patients (age 37 +/- 12 y, body mass index [BMI] = 37 +/- 9 kg/m2) and 45 never-obese subjects (controls; age 41 +/- 13 y, BMI 22 +/- 2 kg/m2). The spectral density was determined in three situations: subjects in the supine position, spontaneously breathing; subjects in the supine with controlled breathing; and subjects standing. The insulin sensitivity of overweight and obese subjects was determined from homeostatic model assessment (HOMA). The variability of normalized low-frequency (LF) spectral analysis of both HR and BP was lower in overweight or obese subjects than in controls, in the supine and standing positions (p <0.01). Normalized LF spectral analysis was negatively correlated to BMI independent of age, whatever the position. Homeostatic model assessment values were negatively correlated to the normalized LF spectral of HR, systolic BP and diastolic BP, in the standing position independent of BMI and age (p <0.05). Normalized high frequency (HF) of HR during controlled breathing decreased with age but not with BMI. In normotensive overweight or obese subjects, changes in sympathetic nervous system modulation are strongly correlated to insulin resistance. Decreased HR and BP variability could partly account for the higher cardiovascular risk and incidence of sudden death in obese persons.

Phytosterols have an unfavourable effect on bacterial activity and no evident protective effect on colon carcinogenesis.

The effects of physiological dietary phytosterol supplements on intestinal microflora activity and faecal sterols and their capacity to protect rats fed a normal or high saturated fatty-acid diet against tumour development were studied. A group of 80 female Wistar rats were fed an 8% lipid diet for 4 weeks (adaptation period) and then randomly assigned in a factorial experimental design study to diets containing 8% or 24% hydrogenated coconut oil, with or without a 24-mg/day/rat phytosterol supplement. They were instilled intrarectally with saline or methyl-nitroso-urea (MNU). Faecal sterol output was analysed for one week each month. Pathological analysis was done at the end of the 30-week experiment. Animals treated with MNU and given phytosterol supplements had tumour frequencies (8/20) similar to those not fed phytosterols (11/20). The fat-supplemented diet had no significant influence. Colonic glands were found in area of lymphoid follicles in all the groups, but were more frequent in rats on high-fat diets (P < 0.01). The coprostanol and the cholesterol excretion of the phytosterol-supplemented rats was significantly enhanced. Therefore phytosterols have an unfavourable effect on bacterial activity. These data confirm the capacity of phytosterols to decrease cholesterol absorption, but indicate that a large excess of phytosterol must be avoided until further research on its effects on carcinogenesis has been done.

Detection of moderate hyperhomocysteinemia: comparison of the Abbott fluorescence polarization immunoassay with the Bio-Rad and SBD-F high-performance liquid chromatographic assays.

The importance of accurate methods for homocysteine measurement has been emphasized. We compared the results obtained with the most commonly used high-performance liquid chromatography (HPLC) assay, and two recently commercially available methods: another HPLC and a fluorescence polarization immunoassay, in plasmas from normo- or hyperhomocysteinemic patients. A significant agreement between the different methods in classifying the results as hyper or normal-homocysteinemia was observed. However, a significant difference between the results was found. Standardization is urgently necessary to improve the concordance of homocysteine determination.

[Macronutrients, fat mass, fatty acid flux and insulin sensitivity]. / Macronutriments, masse grasse, flux d'acides gras et insulinosensibilité

Obesity and visceral or upper body fat distribution, have a major impact on insulin sensitivity. There is strong evidence to suggest that free fatty acids (FFA) contribute to the pathogenesis of insulin resistance and the metabolic syndrome. Increased FFA release from adipose tissue or failure of FFA using tissues to remove them normally, lead to increased triglycerides (TG) and FFA fluxes. Increased delivery of FFA to muscle reduces muscle glucose uptake and utilisation by substrate competition or direct inhibition of glucose transport. Insulin resistance has been correlated with the size of intramuscular TG store. Intracellular TG have been involved in beta cell failure the so called lipotoxicity phenomena. The rate of FFA to the liver is a major determinant of hepatic TG secretion. So the regulation of FFA distribution between FFA using tissues and the partition of FFA between storage and oxidation could be involved in the developpment of insulin resistance. The dietary macronutrients could play a role in nutrient partitioning but their role in the etiology of insulin resistance is poorly understood due to a paucity of credible intervention studies in humans. However deleterious effects of saturated fatty acids on insulin action and the beneficial effects of polyunsaturated fatty acids (PUFAs) could be suspected from animal studies, and from epidemiological or clinical studies in humans. A very high intake of sucrose or fructose could be deleterious but low glycemic index foods, and fibers could have protective effects. Weight loss can induce marked improvement in insulin resistance, but weight maintenance is also required to keep long term good metabolic results.

Evidence that diabetes mellitus favors impaired metabolism of zinc, copper, and selenium in chronic pancreatitis.

Diabetes mellitus, a common complication of chronic pancreatitis, can disturb the metabolism of zinc, copper, and selenium. We analyzed the effects of hyperglycemia, malabsorption, and dietary intake on these factors in 35 men with alcohol-induced chronic pancreatitis complicated by insulin-treated diabetes mellitus (CP-D), 12 men with chronic pancreatitis but no diabetes (nondiabetic CP), 25 men with type 1 diabetes mellitus (type 1 DM), and 20 control subjects. Diabetes due to chronic pancreatitis was associated with decreased plasma zinc and selenium concentrations and with increased urinary copper excretion. Of the chronic pancreatitis patients, 17% had low plasma zinc, and 41% of them had low plasma selenium. None of the type 1 diabetic patients had low plasma concentrations of zinc, but 12% of them had a low selenium concentration. Hyperglycemia, as assessed by fasting plasma glucose and by plasma HbAlc, was responsible for the increased zinc excretion and the decreased superoxide dismutase activity. The perturbations of the copper, selenium, and zinc metabolism were particularly pronounced in subjects with chronic pancreatitis plus diabetes mellitus. We have yet to determine whether the differences in trace-element status contribute to the clinical expression of the disease.

No acute response of leptin to an oral fat load in obese patients and during circadian rhythm in healthy controls.

This study was done to elucidate the relationship between postprandial leptin and obesity, and the possible influence of the circadian rhythm on the dynamic leptin response to an oral fat load (OFLT). In experiment 1, we measured the leptin and insulin responses to an oral fat load in 16 non-diabetic obese subjects and in 16 healthy controls, matched for age and gender. In experiment 2, we measured the leptin and insulin responses to an OFLT according to the time of fat load ingestion: 0700 h (diurnal (D) test) or 2200 h (nocturnal (N) test) in nine normal-weight healthy males. Baseline leptin concentration was correlated with the body mass index, body fat mass and percentage of body fat mass in both experiments. The leptin concentrations were higher in women than in men (P<0.001). In experiment 1, the leptin concentrations were higher in obese subjects than in controls, but did not change over time in either group. The plasma insulin concentrations at baseline and during the postprandial state, as well as the area under the curve (AUC) of insulin, were higher in obese subjects than in controls (P<0.05-0. 0001). There was no correlation between postprandial insulin responses and postprandial leptin responses in either obese or control groups. In experiment 2, leptin (D vs N, 2.9+/-1.4 vs 2. 9+/-1.0 ng/ml) and insulin (D vs N, 41+/-18 vs 25+/-9 pmol/l) concentrations were similar at the beginning of the D and N tests after a 10 h fast. The leptin concentrations did not change after D or N tests and were not statistically different for D and N tests. Our results indicate that the leptin concentration in healthy controls and in obese patients is not acutely influenced by a high fat load.

[Drug treatment of obesity and type 2 diabetes]. / Traitement médicamenteux de l'obésité et diabète de type 2.

Drug therapy of obesity (DTO) has not been extensively used in diabetic patients so far, although excessive adipose mass largely contributes to insulin resistance which characterizes this disease together with insulin secretion failure. Orlistat is the sole currently available treatment, but several other new treatments are under investigation, such as sibutramine already marketed in other countries. Both drugs were found to be efficient in long term studies (1 year). However it is puzzling to note that weight loss induced by the drug as well as during placebo treatment is less pronounced in diabetic patients as compared with non diabetic subjects. Short term studies had already documented a lower response to DTO in diabetic patients by 2-fold. The reasons for this weight loss resistance in diabetics under DTO remain unclear and could be linked with metabolism. A weight loss > or = 5% initial body weight is required to obtain a significant lowering of HbA1c. Weight variations (weight delta > or = 5-10% initial weight) and results on glucose control (HbA1c delta > or = 0.5% after 3 to 6 months, or fasting blood glucose delta > or = 1 mmol/l within a few weeks) allow to define good DTO responders which should preferentially be eligible for this treatment. A decisional diagram is suggested.

Sodium dodecyl sulphate gel electrophoretic preparation of protein standard human apolipoprotein B-48.

Quantitation of plasma apo B-48 is currently performed by densitometric analysis of SDS-PAGE zones stained with Coomassie Brilliant Blue, using standard solutions of purified apo B-48. Here, preparative gel electrophoresis with a continuous elution system was used for purifying apo B-48. A chylomicron fraction was isolated by 107,000 g ultracentrifugation of a chylous ascite. The proteins were delipidated and precipitated in ethanol-diethyl ether (3:1, v/v), subjected to preparative electrophoresis in a 5% polyacrylamide gel and eluted in 0.1% SDS. The peak containing apo B-48 was eluted at a retention time of 445-480 min. The purity of apo B-48 in this fraction was assessed by the detection of a single band (M(r) 260,000) after silver staining and Coomassie staining of 4-15% gradient SDS-PAGE. It was confirmed by the absence of apo B-100 contaminant in Western blot of the purified protein preparation. A linear relationship was observed between the densitometric analysis of SDS-PAGE bands and the apo B-48 in a protein range of 0-3 microg. In conclusion, preparative gel electrophoresis was used in a single step purification of apo B-48 that was adapted to the preparation of a standard solution.