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Biomedical subjects

M Laville

Publications and source records attributed to M Laville.

At least 19 recordsLinked to original sources
PubMed2006

Low protein diets for chronic kidney disease in non diabetic adults.

BACKGROUND: For more than fifty years, low protein diets have been proposed to patients with kidney failure. However, the effects of these diets in preventing severe renal failure and the need for maintenance dialysis have not been resolved. OBJECTIVES: To determine the efficacy of low protein diets in delaying the need to start maintenance dialysis. SEARCH STRATEGY: Cochrane Renal Group trials register, the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987). Direct contacts with investigators. Date of most recent search: December 2004. SELECTION CRITERIA: Randomised trials comparing two different levels of protein intake in adult patients suffering from moderate to severe renal failure, followed for at least one year. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). Collection of the number of "renal deaths" defined as the need for starting dialysis, the death of a patient or a kidney transplant during the trial. MAIN RESULTS: Eight trials were identified from over 40 studies. A total of 1524 patients were analysed, 763 had received reduced protein intake and 761 a higher protein intake. Two hundred and fifty one renal deaths were recorded, 103 in the low protein diet and 148 in the higher protein diet group (RR 0.69, 95% CI 0.56 to 0.86, P = 0.0007). To avoid one renal death, 2 to 56 patients need to be treated with a low protein diet during one year. AUTHORS' CONCLUSIONS: Reducing protein intake in patients with chronic kidney disease reduces the occurrence of renal death by 31% as compared with higher or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.

Adult↗
PubMed2006

Activation of liver X receptors promotes lipid accumulation but does not alter insulin action in human skeletal muscle cells.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of liver X receptor (LXR) activation on lipid metabolism and insulin action in human skeletal muscle cells prepared from control subjects and from patients with type 2 diabetes. SUBJECTS AND METHODS: Cultured myotubes were obtained from muscle biopsies of 11 lean, healthy control subjects and ten patients with type 2 diabetes. The mRNA levels of LXR isoforms and lipogenic genes were estimated by RT-quantitative PCR, and the effects of LXR agonists on insulin action were evaluated by assays of protein kinase B serine 473 phosphorylation and glycogen synthesis. RESULTS: Both LXRalpha and LXRbeta were expressed in human skeletal muscle and adipose tissue and there was no difference in their mRNA abundance in tissues from patients with type 2 diabetes compared with control subjects. In cultured muscle cells, LXR activation by T0901317 strongly increased expression of the genes encoding lipogenic enzymes, including sterol regulatory element binding protein 1c, fatty acid synthase and stearoyl-CoA desaturase 1, and also promoted triglyceride accumulation in the presence of a high glucose concentration. Importantly, these effects on lipid metabolism did not affect protein kinase B activation by insulin. Furthermore, LXR agonists did not modify insulin action in muscle cells from patients with type 2 diabetes. CONCLUSIONS/INTERPRETATION: These data suggest that LXR agonists may lead to increased utilisation of lipids and glucose in muscle cells without affecting the mechanism of action of insulin. However, the long-term consequences of triglyceride accumulation in muscle should be evaluated before the development of effective LXR-based therapeutic agents.

Adult↗
PubMed2006

Metabolic consequences of pancreatic systemic or portal venous drainage in simultaneous pancreas-kidney transplant recipients.

AIMS: The aim was to investigate pancreatic B-cell function and insulin sensitivity in simultaneous pancreas-kidney (SPK) recipients with systemic or portal venous drained pancreas allograft using simple and easy tests. METHODS: The study included 44 patients with Type 1 diabetes and end-stage renal disease who had undergone SPK transplantation: 20 recipients received a pancreas allograft with systemic venous drainage (S-SPK) and 24 with portal venous drainage (P-SPK). We studied only recipients with functioning grafts, with normal serum glucose, HbA(1c) and serum creatinine values, on a stable drug regimen. The subjects were studied at 6, 12, 24, 36, 48 and 60 months after transplantation. Insulin sensitivity and B-cell function indices were derived from blood samples and oral glucose tolerance tests. RESULTS: All patients from both groups had normal fasting glucose, body mass index and HbA(1c) values by selection. The homeostatic model (HOMA) beta-cell index was significantly lower in P-SPK recipients at several points of the follow-up. HOMA-IR was significantly higher in S-SPK recipients at 6 and 24 months after transplantation and was positively correlated with fasting insulin values, but never exceeded 3.2. There was no significant difference in QUICKI index values between the two groups. Although all patients from both groups always had normal glucose tolerance, the area under the insulin curve was higher in the S-SPK group. Cholesterol, low-density lipoprotein-cholesterol and triglycerides were higher in the P-SPK group. CONCLUSIONS: The results suggest sustained long-term endocrine function in both groups and show that portal venous drainage does not offer major metabolic advantages.

Adult↗
PubMed2005

[How to manage my patients' psychological disturbances?].

Psychological disturbances are frequently encountered in obese patients. The physician specialised in nutrition should take them into account within the therapeutic project and all along the patient's management. This review describe, according to the main obese patients' profiles (typology), the conditions for an optimal adequation between hopes and expectations from both the patient and the physician, as well as the psychiatrist role within the therapeutic project and during the management period.

Humans↗
PubMed2004

The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes.

AIMS/HYPOTHESIS: We investigated the effects of rosiglitazone on NEFA and triglyceride metabolism in type 2 diabetes. METHODS: In a double-blind, placebo-controlled, cross-over study of rosiglitazone in diet-treated type 2 diabetic subjects, we measured arteriovenous differences and tissue blood flow in forearm muscle and subcutaneous abdominal adipose tissue, used stable isotope techniques, and analysed gene expression. Responses to a mixed meal containing [1,1,1-(13)C]tripalmitin were assessed. RESULTS: Rosiglitazone induced insulin sensitisation without altering fasting NEFA concentrations (-6.6%, p=0.16). Postprandial NEFA concentrations were lowered by rosiglitazone compared with placebo (-21%, p=0.04). Adipose tissue NEFA release was not decreased in the fasting state by rosiglitazone treatment (+24%, p=0.17) and was associated with an increased fasting hormone-sensitive lipase rate of action (+118%, p=0.01). Postprandial triglyceride concentrations were decreased by rosiglitazone treatment (-26%, p<0.01) despite unchanged fasting concentrations. Rosiglitazone did not change concentrations of triglyceride-rich lipoprotein remnants. Adipose tissue blood flow increased with rosiglitazone (+32%, p=0.03). Postprandial triglyceride [(13)C]palmitic acid concentrations were unchanged, whilst NEFA [(13)C]palmitic acid concentrations were decreased (p=0.04). In muscle, hexokinase II mRNA expression was increased by rosiglitazone (+166%, p=0.001) whilst the expression of genes involved in insulin signalling was unchanged. Adipose tissue expression of FABP4, LPL and FAT/CD36 was increased. CONCLUSIONS/INTERPRETATION: Rosiglitazone decreases postprandial NEFA and triglyceride concentrations. This may represent decreased spillover of NEFAs from adipose tissue depots. Decreased delivery of NEFAs to the liver may lead to lowered postprandial triglyceride concentrations. Upregulation of hexokinase II expression in muscle may contribute to insulin sensitisation by rosiglitazone.

Adipose Tissue↗
PubMed2004

WY-14643 and 9- cis-retinoic acid induce IRS-2/PI 3-kinase signalling pathway and increase glucose transport in human skeletal muscle cells: differential effect in myotubes from healthy subjects and Type 2 diabetic patients.

AIMS/HYPOTHESIS: To determine the effects of peroxisome proliferator-activated receptor alpha (PPARalpha) and retinoid X receptor (RXR) agonists on insulin action, we investigated the effects of Wy-14643 and 9- cis-retinoic acid (9- cis-RA) on insulin signalling and glucose uptake in human myotubes. METHODS: Primary cultures of differentiated human skeletal muscle cells, established from healthy subjects and Type 2 diabetic patients, were used to study the effects of Wy-14643 and 9- cis-RA on the expression and activity of proteins involved in the insulin signalling cascade. Glucose transport was assessed by measuring the rate of [(3)H]2-deoxyglucose uptake. RESULTS: Wy-14643 and 9- cis-RA increased IRS-2 and p85alpha phosphatidylinositol 3-kinase (PI 3-kinase) mRNA and protein expression in myotubes from non-diabetic and Type 2 diabetic subjects. This resulted in increased insulin stimulation of protein kinase B phosphorylation and increased glucose uptake in cells from control subjects. Myotubes from diabetic patients displayed marked alterations in the stimulation by insulin of the IRS-1/PI 3-kinase pathway. These alterations were associated with blunted stimulation of glucose transport. Treatment with Wy-14643 and 9- cis-RA did not restore these defects but increased the basal rate of glucose uptake. CONCLUSIONS/INTERPRETATION: These results demonstrate that PPARalpha and RXR agonists can directly affect insulin signalling in human muscle cells. They also indicate that an increase in the IRS-2/PI 3-kinase pathway does not overcome the impaired stimulation of the IRS-1-dependent pathway and does not restore insulin-stimulated glucose uptake in myotubes from Type 2 diabetic patients.

Adult↗
PubMed2004

Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients.

AIMS/HYPOTHESIS: Defective oxidation of long-chain fatty acids is a feature of insulin resistance and Type 2 diabetes. Our aim was to compare the expression levels of the genes encoding the major proteins and enzymes of this pathway in skeletal muscle of healthy subjects and Type 2 diabetic patients. METHODS: The basal and insulin-regulated mRNA concentration of 16 genes was quantified using real-time PCR in skeletal muscle biopsies taken before and at the end of a 3-hour hyperinsulinaemic-euglycaemic clamp in healthy lean subjects and in insulin-resistant obese patients with manifest Type 2 diabetes. RESULTS: Acetyl CoA carboxylase-2 mRNA expression was increased 2.5-fold in the muscle of the diabetic patients. The expression of carnitine palmitoyl transferase-1, of the two adiponectin receptors and of genes involved in fatty acid transport and activation was not altered in diabetic patients. Hyperinsulinaemia for 3 hours increased the expression of several genes of fatty acid oxidation, including adiponectin receptor-1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha. It also reduced pyruvate dehydrogenase 4 mRNA levels. The effects of insulin on gene expression were markedly altered in the muscle of Type 2 diabetic patients except for adiponectin receptor-1 and pyruvate dehydrogenase 4 mRNAs. CONCLUSIONS/INTERPRETATION: The expression of adiponectin receptors was not altered in the muscle of Type 2 diabetic patients. The observed overexpression of acetyl CoA carboxylase-2 is consistent with the hypothesis that increased skeletal muscle malonyl CoA concentrations in Type 2 diabetes may contribute to the inhibition of long-chain fatty acid oxidation.

Blood Glucose↗
PubMed2004

New strategies in anaemia management: ACORD (Anaemia CORrection in Diabetes) trial.

Anaemia is a key component of diabetic nephropathy, but its importance has only recently been recognised. Recombinant human erythropoietin (epoetin) is an established treatment for renal anaemia, and may help to reduce complications associated with diabetic nephropathy, such as cardiovascular disease. The limited experience with the use of epoetin in this patient group prompts the urgent need for clinical data on anaemia correction in early diabetic nephropathy, particularly with regard to benefits on cardiovascular risk reduction. The Anaemia CORrection in Diabetes (ACORD) study will investigate the effects of anaemia correction on cardiac structure and function in patients with early diabetic nephropathy. This 15-month multicentre study will recruit 160 adult patients with diabetes, mild or moderate chronic kidney disease (with creatinine clearance >or=30 ml/min at screening) and moderate anaemia (haemoglobin [Hb], 10.5-13.0 g/dl). Patients will be randomised to one of two groups: the early treatment group will receive subcutaneous epoetin beta (NeoRecormon) at study entry to maintain target Hb levels of 13-15 g/dl, while the control group will reflect current practice and will not receive epoetin therapy until Hb levels decline below 10.5 g/dl. The primary efficacy variable, change in left ventricular mass index, will be evaluated at 15 months following randomisation; secondary efficacy variables will include changes in cardiac structure and function over the study period. The ACORD study should provide valuable information on the benefits of anaemia correction in patients with early diabetic nephropathy. The study will also increase awareness of the importance of treating anaemia associated with diabetes.

Anemia↗
PubMed2003

[The place of mycophenolate mofetil in glomerular diseases].

VARIOUS EFFECTS: Mycophenolate mofetil (MMF) is a specific inosine monophosphate dehydrogenase inhibitor implied in the de novo synthesis of purine bases; it selectively decreases lymphocyte proliferation and is used for the prevention of acute organ rejection. It also decreases the expression of certain adhesion molecules and slows down the functional renal progression in many experimental models of glomerular nephritis. THE GLOMERULAR PATHOLOGY: To date there has been very few studies on the efficacy of MMF in human glomerular diseases and these have been sporadic clinical observations or series of cases with around ten patients. In general, these reports were of cases in which conventional treatment had failed. IN THE FUTURE: The experimental studies and clinical observations available suggest that MMF will eventually complete the therapeutic arsenal in the management of certain forms of glomerular nephritis.

Clinical Trials as Topic↗
PubMed2003

What kind of simple fasting index should be used to estimate insulin sensitivity in humans?

The hyperinsulinemic euglycemic glucose clamp method is the gold standard for measuring insulin resistance. However it is complex, and simple indexes have been developed. Some of them are based on formulae that calculate the product or the addition of fasting plasma insulin and glucose values whereas others are based on their ratios. We calculated several simple indexes of insulin resistance and compared them to hyperinsulinemic euglycemic clamp data in 111 subjects with a wide range of insulin resistance. We showed that indexes using insulin and glucose ratios in their formulae are poorly correlated with clamp measurements and give false evaluations, particularly in glucose-intolerant and type 2 diabetic subjects. Thus, whatever the glucose profile of study subjects, we suggest the use of a simple index based on the product or the addition of fasting plasma insulin and glucose values instead of their ratios to obtain insulin resistance evaluations close to the hyperinsulinemic euglycemic clamp technique.

Blood Glucose↗
PubMed2003

The effects of exercise and protein-energy supplements on body composition and muscle function in frail elderly individuals: a long-term controlled randomised study.

Fighting against inactivity and inadequate nutritional intake are of utmost importance in the elderly. To our knowledge, the few studies which have been performed were conducted for only a short period and the results do not permit formal conclusions to be drawn. We therefore tried to fill this gap in our knowledge by determining whether an intervention combining an acceptable progressive exercise programme and nutritional supplements would be feasible for a long-term period in the very frail elderly, and would bring about concomitant benefits in body composition and muscle power. Accordingly, this exercise and nutritional combination was assessed in the frail elderly in a 9-month randomised trial with a factorial design. Fifty-seven elderly volunteers over 72 years, from sixteen retirement homes in Lyon, France participated in the study. Dietary supplements were compared with placebo, and physical exercise was compared with memory training. Main outcome measures were fat-free mass (FFM) and muscle power. FFM was determined by labelled water, and muscle power was measured by a leg-extensor machine. At 9 months, the compliance was 63 % for exercise sessions, and 54 % for nutritional supplements. In patients with dietary supplements, muscle power increased by 57 % at 3 months (P=0.03), and showed only a tendency at 9 months; although FFM increased by 2.7 % at 9 months, the difference was not significant (P=0.10). Exercise did not improve muscle power at 9 months, but improved functional tests (five-time-chair rise, P=0.01). BMI increased with supplements (+3.65 %), but decreased with placebo (-0.5 %) at 9 months (P=0.007). A long-term combined intervention is feasible in frail elderly individuals with a good rate of compliance. Nutritional supplements and exercise may improve muscle function. Despite no significant results on FFM, due to the limited number of volunteers, combined intervention should be suggested to counteract muscle weakness in the frail elderly.

Aged↗
PubMed2003

Efficacy of mycophenolate mofetil on recurrent glomerulonephritis after renal transplantation.

Recurrent glomerulonephritis in transplanted kidneys is not rare despite classical immunosuppressive drugs and depends on the etiology of nephropathy. Treatment of recurrence of renal disease on graft remains controversial. We report 6 cases of patients with recurrent glomerulonephritis after renal transplantation treated with mycophenolate mofetil (MMF). The glomerular diseases were Wegener's granulomatosis (n = 1), membranoproliferative glomerulonephritis type I (n = 1), focal and segmental glomerular sclerosis (n = 1), membranous glomerulonephritis (idiopathic membranous nephropathy (n = 1) and systemic lupus erythematous) (n = 1)) and immunoglobulin A nephropathy (n = 1). MMF was introduced because of intolerance of classical immunosuppressive treatment in 2 cases and because of its inefficiency in the other cases. MMF was introduced between 3 months and 36 months (13.5 +/- 7 months) after recurrence of the primitive glomerulonephritis. During combined MMF/cyclosporine/prednisone therapy, only 3 patients responded to MMF. MMF was disrupted precociously in 1 out of 3 patients who stabilized renal function because of discovery of lung cancer and in 2 out of the 3 other patients because of gastrointestinal intolerance and severe anemia. We supposed that MMF could represent a new effective alternative therapy of recurrent glomerulonephritis on renal graft in some cases.

Adult↗
PubMed2003

[Is it possible to prevent type 2 diabetes?].

Four prospective randomised long-term studies have been recently completed and published (Diabetes Prevention Study, Diabetes Prevention Program, STOP-NIDDM trial, XENDOS Study). Both of them clearly demonstrate the possibility to delay and/or prevent the onset of type 2 diabetes in at high-risk subjects with impaired glucose tolerance, through changes in lifestyle (dietary intervention, weight reduction, increased physical activity) or drug treatment (metformin, acarbose, orlistat). These studies are reviewed and practical implications of their results are discussed.

Acarbose↗
PubMed2002

Adipose tissue gene expression in patients with a loss of function mutation in the leptin receptor.

BACKGROUND: In order to maintain body weight regulation, leptin directly or indirectly signals nutritional changes to key organs, but little is known about its target genes in human adipose tissue. Leptin receptor loss of function is a unique way to explore the role of leptin in the regulation of adipose tissue. OBJECTIVE: We studied the consequences of the absence of leptin signaling on adipocyte gene expression in two girls with a mutation in the leptin receptor. The expression levels of the ob gene and adipocyte transcription factors (SREBP1c, C/EPBalpha, beta, PPARgamma1, gamma2) were quantified by RT-PCR in subcutaneous adipose tissue of these patients and of 10 morbidly obese women. RESULTS: Ob mRNA levels in subjects lacking the leptin receptor were not overexpressed but were in the range that could be expected from their BMI (58 and 26 amol/ micro g total mRNA, range in obese women: 26-69). Expression of the five transcription factors was also in the same range in the affected patients and in morbidly obese women (7.7 and 6.8 amol/ micro g total mRNA, range: 2.2-9.4 for SREBP1c, 159 and 51 range: 51-406 for C/EPBalpha, 6.1 and 3.3 range: 2.4-24.8 for C/EPBbeta, 16.7 and 27.4 range: 9.4-29.7 for PPARgamma1 and 1.7 and 5.4 amol/ micro g total mRNA range: 1.7-8.8 for PPARgamma2). Significant correlation was found between the mRNA levels of leptin and PPARgamma2 and leptin and C/EBPalpha whereas no correlation was observed between leptin and SREBP1c, PPARgamma1, or C/EBPbeta mRNA levels. CONCLUSION: In patients lacking leptin signaling, the fact that ob gene expression is adequately adapted to their body fat mass argues against a direct negative feedback loop in the regulation of leptin expression in humans. The normal expression of several transcription factors, known to be dependent of the nutritional status, suggests that leptin is not a major contributor of their in vivo transcriptional regulation in human adipose tissue.

Adipocytes↗
PubMed2002

Albumin loss in on-line hemodiafiltration.

BACKGROUND: Based on the increased hydraulic permeability of the new high permeability polyethersulfone membrane, DIAPES HF-800, we investigated the kinetics and handling of albumin in high volume on-line hemodiafiltration (HDF). METHODS: Seven patients on predilutional HDF were studied in two consecutive sessions. Blood flow rate and transmembrane pressure were continuously monitored. Spent dialysate was spilled at 20 ml/h every hour. Albumin was measured in blood and dialysate by immunonephelometry. Albumin and proteins adsorbed onto the dialyzer membrane were eluted after treatment with Triton X. Ultrafiltrates collected at 1 and 2 hours of treatment were pooled from different patients and incubated for 24 hours at 37 degrees C with bovine serum albumin (BSA). Total sulphydryl groups were evaluated using Ellmann's reagent [5, 5'-dithio-bis(2-nitrobenzoic acid)]. RESULTS: In all 7 patients, the total loss of albumin was 3.99 +/- 1.81 g, ranging between 1.09 and 6.82 g/session. Most albumin loss occurred in the first 60 min of pre-dilutional hemodiafiltration (1.92+0.83 g). There was no correlation between transmembrane pressure, urea clearance and the loss of albumin. Plasma water urea clearance values were stable over the treatment (234 +/- 14.3 ml/min). Plasma albumin concentration did not decrease during HDF sessions. Albumin adsorbed onto the dialyzers was 0.7 +/- 1.6 mg but the total amount of adsorbed proteins was much higher (130 + 90 mg). In addition, the ultrafiltrate collected during HDF sessions was able to induce oxidation of bovine serum albumin as measured by total protein sulfhydryl groups: bovine serum albumin incubated in the presence of ultrafiltrate collected at 1 hour had a sulfhydryl loss of 56.3 +/- 5.7% (p < 0.0001 vs control), and bovine serum albumin incubated with ultrafiltrate collected at 2 hours had a loss of 67.5 +/- 3.8% (p < 0.003 vs control). CONCLUSION: The present study shows the high inter- and intra-patient variability of transmembrane passage of albumin in chronically uremic patients undergoing pre-dilutional HDF. Factors involved do not seem to be correlated to transmembrane pressure but rather to an interaction with the polymer surface. Albumin adsorption was minimal and was significantly lower than that of other plasma proteins. Albumin loss during HDF seemed to have no acute impact on plasma albumin. In addition, we demonstrated the presence of prooxidative compounds able to oxidize albumin, of which extracorporeal removal by HDF procedure could be beneficial for HD patients.

Adsorption↗