PubMed Health⌕ Search

Biomedical subjects

O Ziegler

Publications and source records attributed to O Ziegler.

At least 19 recordsLinked to original sources
PubMed2005

Development and validation of a French obesity-specific quality of life questionnaire: Quality of Life, Obesity and Dietetics (QOLOD) rating scale.

OBJECTIVE: To develop and validate a new health related quality of life (HRQOL) questionnaire specific to obesity and its management. METHODS: This study was in two parts. The first (Study 1) consisted of the creation of a new tool derived from the American "Impact of Weight on Quality of Life Questionnaire" (IWQOL, 74 items) by adding to it a 17 items specific complementary module. This initial questionnaire (91 items) was reduced so as to obtain a questionnaire adapted to socio-cultural factors of obesity and dietary weight management in France. The objective of the second (Study 2) was to validate this final questionnaire by evaluating its psychometric properties: construction validity, internal reliability, concurrent validity in relation to a generic questionnaire, the SF-12, clinical validity by studying the effects of age, gender and body mass index (BMI), and reproducibility. RESULTS: The results of Study 1, obtained in 128 obese patients (mean age: 42.5 12.1, BMI: 34.5 2.8 kg/m2, women: 83.6%) enabled reduction of the 91 questionnaire items to 36, grouped into 5 dimensions: physical impact, psycho-social impact, sex life, comfort with food and diet experience. Two hundred and twelve patients (mean age: 43.3 12.2, BMI: 35.8 7.4 kg/m2, women: 77.7%) were included in Study 2, among whom 75 filled out the questionnaire twice at a one week interval. Analyses enabled verification of the construction validity and internal reliability (Cronbach alpha > 0.7) of the questionnaire as well as its concurrent validity in relation to summarized SF-12 scores and its clinical validity. The "physical impact" dimension was significantly influenced by BMI and age, the dimensions "sex life" and "diet experience" by the factors gender and BMI, while "psycho-social impact" was influenced by the 3 factors cited. Its reproducibility was also deemed satisfactory (intra-class correlation coefficient > 0.8). CONCLUSION: This new questionnaire, called the "Echelle Qualité de Vie, Obésité et Diététique (EQVOD)"/"Quality of Life, Obesity and Dietetics (QOLOD)" rating scale is sufficiently reliable and reproducible to be used in clinical practice. It is a simple tool adapted to socio-cultural factors of obesity in France, enabling taking into account of the effects of dietary management on the HRQOL of obese people.

Activities of Daily Living↗
PubMed2005

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.

Adult↗
PubMed2005

X-PERT: weight reduction with orlistat in obese subjects receiving a mildly or moderately reduced-energy diet: early response to treatment predicts weight maintenance.

AIM: To determine the effect of two different levels of energy deficit on weight loss in obese patients treated with orlistat. METHODS: Patients (n=430) were randomized in a 1-year, multicentre, open-label, parallel group study conducted at 23 hospital centres and university medical departments worldwide. Obese outpatients (body mass index 30--43 kg/m(2)) aged 18--70 years with a body weight of >or=90 kg and a waist circumference of >or=88 cm (women) or >or=102 cm (men) were treated with orlistat 120 mg three times daily plus a diet that provided an energy deficit of either 500 or 1,000 kcal/day for 1 year. Orlistat treatment was discontinued in patients who did not achieve >or=5% weight loss after assessment at 3 and 6 months. The primary outcome measure was change in body weight from baseline at week 52. RESULTS: Reported mean difference in energy intake between the two groups (500-1,000 kcal/day deficit) at weeks 24 and 52 was actually 111 and 95 kcal/day respectively. Of the 430 patients involved in the study, 295 achieved >or=5% weight loss at both 3 and 6 months. In this population, at week 52, weight loss from baseline was similar for patients randomized to either the 500 or the 1,000 kcal/day deficit diet (-11.4 kg vs. -11.8 kg, respectively; p=0.778). After 12 months of treatment with orlistat, 84% (n=118/141) and 85% (n=131/154) of patients in the 500 and 1,000 kcal/day deficit groups, respectively, achieved >or=5% weight loss, and 50% (n=70/141) and 53% (n=82/154) of patients, respectively, achieved >or=10% weight loss. Patients in both the diet treatment groups showed similar significant improvements in blood pressure, lipid levels and waist circumference at week 52. CONCLUSIONS: Treatment with orlistat was associated with a clinically beneficial weight loss, irrespective of the prescribed dietary energy restriction (-500 or -1000 kcal/day). Patients who achieved >or=5% weight loss at 3 months achieved long-term, clinically beneficial weight loss with orlistat plus either diet. Therefore, identifying patients who lose at least 5% weight after 3 months and who maintain this weight loss up to 6 months is a valuable treatment algorithm to select patients who will benefit most from orlistat treatment in combination with diet.

Adolescent↗
PubMed2005

[How to manage the metabolic syndrome?].

The metabolic syndrome represents the association in a single individual of a cluster of metabolic and hemodynamic factors, leading to an increased risk of type 2 diabetes and/or cardiovascular diseases. Several definitions exist (WHO, EGIR, NCEP-ATP III, AACE), but all of them include a cluster of criteria (hyper glycemia or type 2 diabetes, arterial hypertension, dyslipidemia, abdominal obesity) which increased these risks in parallel to their aggregation. The prevalence of the metabolic syndrome in industrialized countries represents 10 to 30% of the adult population, depending on the definition used and of the range of age, with a regular progression, particularly in women. Thus, it is needed to identify subjects with metabolic syndrome in the general population, and not only in overweight/obese subjects. This review, briefly presents the main definitions, as well as current data on pathophysiology, prevalence and consequences of the metabolic syndrome. Steps to diagnose it and guidance for the therapeutic management of metabolic syndrome in primary care practice are described.

Humans↗
PubMed2003

[French diabetologists' standpoint on the prevention of type 2 diabetes. A survey carried out during the ALFEDIAM Convention Bordeaux 2003].

An opinion poll was carried out during the ALFEDIAM Congress Bordeaux 2003. One hundred and thirty-seven participants (mean age 43.6 +/- 8.3 years/sex Ratio approximately 1) among whom 22.6% run private practices, 51.8% work in hospitals and 21.3% are both private and hospital practitioners, have been questioned about their conception of the prevention of type 2 diabetes. Prediabetes is an acknowledged entity for 61% of the people surveyed. Two thirds use as a diagnostical criterion, moderate fasting hyperglycemia and/or a impaired glucose tolerance. Oral glucose tolerance test (OGTT) is still commonly practised among 51.9% but that is done sparingly only to confirm the diagnosis of diabetes in presence either of several risk factors or of a moderate fasting hyperglycemia. According to 70% of the answers, the detection of diabetes must be repeated every year among at risk subjects aged over 45. The metabolic syndrome is defined according to diverse criteria. The right definition of ATP III is given only in 5% of the cases. As regards the treatment, the combined requirements of physical activity and dietary rules are approved by 97% of the answers. The majority of the persons questioned in the survey consider that a slight loss of weight (less than 5% of the initial weight) is sufficient in a high risk risk individual.On the other hand, opinions are divided as regards the use of drugs at the pre-diabetes stage. Metformin is the only one that is accepted by more than 50% with a rate of 58.4% of positive answers, acarbose and orlistat rating respectively 37.2% and 35%. However a great majority (83.6%) are in favour of the reimbursement of antidiabetic drugs in this indication, for high risk individuals, provided a study has clearly demonstrated the efficiency of the molecule concerned.

Diabetes Mellitus, Type 2↗
PubMed2003

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.

Adult↗
PubMed2003

[Should the prevention of obesity be demedicalised?].

Obesity prevalence is rapidly growing, particularly in children and young adolescents. It is proved to be important to prevent it within a public health strategy. Primary prevention of obesity should not be focused on obesity itself, but should be part of a global public health national policy, targeted to improve the nutritional status of the community, to reduce the risk for chronic diseases, to improve the health status and the quality of life of the general population. This overall prevention programme should be conducted on a large scale, at all level of the country infrastructure and sectors of society, and should acquired a strong local and regional support from communities, consumers and government, but it has also to be particularly focused on young subjects (and their family and school workers), especially in groups with low socio-economic status. Secondary prevention should be particularly focused on children with a high-risk for obesity and/or those with potential associated risk factors. Medical involvement is of a particular importance in this secondary prevention, to identify and to manage these at-risk children and young adolescents. The various approaches from a paediatrician, a physician specialised in human nutrition, a sociologist and a consumer representative are presented in this review.

Adolescent↗
PubMed2002

Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans.

OBJECTIVE: Leptin plays a major role in the regulation of body weight. It circulates in both free and bound form. One of the leptin receptor isoforms exists in a circulating soluble form that can bind leptin. In the present study, we measured the soluble leptin receptor (SLR) levels in lean and obese humans. We investigated the relationship between plasma SLR levels, plasma leptin levels and the degree of obesity. We also examined whether SLR concentrations could be modulated by fat mass loss induced by a 3 month weight-reducing diet. SUBJECTS: A total of 112 obese (age 18-50 y; body mass index (BMI) 30-44 kg/m2; 23 men and 89 women), 38 overweight (age 19-48 y; BMI 25-29 kg/m2; 10 men and 28 women) and 63 lean (age 18-50 y; BMI 17-24 kg/m2; 16 men and 47 women) humans. MEASUREMENTS: A direct double monoclonal sandwich enzyme-linked immunosorbent assay (ELISA) was used for the quantitative measurement of the soluble human leptin receptor. Leptin was measured by radioimmunoassay (RIA). Body composition was assessed by biphotonic absorptiometry DEXA (dual energy X-ray absorptiometry). RESULTS: We observed that the SLR is present in human plasma (range 10-100 ng/ml). SLR levels were lower in obese and overweight than lean subjects (28.7+/-8.8, 40.2+/-14.9, 51.2+/-12.5 ng/ml, respectively) and were inversely correlated to leptin and percentage of body fat (r=-0.74 and r=-0.76; respectively; P<0.0001). The ratio of circulating leptin to SLR was strongly related to the percentage of body fat (r=0.91; P<0.0001). Interestingly a gender difference was observed in SLR levels, which were higher in obese and overweight men than in obese and overweight women. In obese subjects after a 3 month low-calorie diet, SLR levels increased in proportion to the decrease in fat mass. In the gel filtration profile, SLR coeluted exactly with the bound leptin fractions. CONCLUSION: Obesity, in humans is associated with decreasing levels of the circulating soluble leptin receptor (SLR). The relationship of SLR with the degree of adiposity suggests that high SLR levels may enhance leptin action in lean subjects more than in obese subjects.

Adipose Tissue↗
PubMed2002

[How do you really know if the obese patient has sleep apnea?].

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.

Accidents, Traffic↗
PubMed2001

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.

Adolescent↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Adult↗
PubMed2001

[Macronutrients, fat mass, fatty acid flux and insulin sensitivity].

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.

Adipose Tissue↗
PubMed2000

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.

Aged↗
PubMed2000

Adipocyte and erythrocyte plasma membrane phospholipid composition and hyperinsulinemia: a study in nondiabetic and diabetic obese women.

BACKGROUND: The cell functions involved in the action of insulin--receptor binding, enzyme and transporter activities--are controlled by membrane properties. We have previously shown that the fasting plasma insulin (FPI) concentration and the homeostasis model assessment (HOMA) estimate of insulin resistance are associated with the sphingomyelin concentration in the erythrocyte membranes of obese women. OBJECTIVES: (1) To study the distribution of phospholipid classes in the plasma membrane and their association with insulin resistance markers in the adipocyte, an insulin-sensitive cell in obese women. (2) To investigate the influence of diabetes in a small group of obese women treated by diet alone. (3) To compare the distribution of phospholipids in erythrocyte membranes in a subgroup of obese nondiabetic and diabetic women. SUBJECTS: Subcutaneous fat biopsies were taken from the abdominal region of 19 obese non-diabetic and seven obese type 2 diabetic women. Erythrocyte membrane assessment was performed in a subgroup of 10 of the 19 obese nondiabetic and in the seven diabetic patients. METHODS: The phospholipid composition of adipocyte and erythrocyte plasma membranes was analyzed by high performance liquid chromatography. RESULTS: FPI was positively correlated with the adipocyte membrane contents of sphingomyelin (P < 0.001), phosphatidylethanolamine (P < 0.05), and phosphatidylcholine (P < 0.01) in the obese nondiabetic women. Similar correlations were obtained with HOMA. A stepwise multiple regression analysis indicated that sphingomyelin accounted for 45.6 and 43.8% of the variance in FPI and HOMA values as an independent predictor. There was a similar positive independent association between FPI and SM in the erythrocyte membranes of the studied subgroup. Diabetes per se did not influence the independent association between SM membrane contents and FPI in both cell types. CONCLUSION: These results suggest a link between membrane phospholipid composition, especially SM, and hyperinsulinemia in obese women.

Adipocytes↗
PubMed2000

A new missense mutation in the calcium-sensing receptor in familial benign hypercalcaemia associated with partial lipoatrophy and insulin resistant diabetes.

We studied two patients (a 54-year-old woman and her 16-year-old son) with familial benign hypocalciuric hypercalcaemia (FBHH) associated with severe insulin resistant diabetes in the context of a partial lipodystrophic syndrome. Sequencing of the entire coding sequence of the calcium-sensing receptor (CaR) gene revealed a novel heterozygous mutation at codon 395, leading to the substitution of a cysteine by an arginine residue (Cys395Arg) in the extracellular ligand-binding domain. This mutation was absent in two normocalcaemic relatives and in 54 control subjects. It was recently shown, in transfection studies, that the substitution of this amino acid results in incomplete receptor processing, a severe decrease in cell surface expression and altered signal transduction (Fan et al., 1998). This mutation is therefore likely to be responsible of the FBHH phenotype. A pathophysiological link between this mutation and insulin resistance remains unclear.

Adolescent↗
PubMed2000

Adipocyte membrane phospholipids and PPAR-gamma expression in obese women: relationship to hyperinsulinemia.

We have shown that membrane sphingomyelin (SM) is an independent predictor of the variance of fasting plasma insulin (FPI) concentrations and the homeostasis model assessment (HOMA) estimate of insulin resistance in obese women. The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a key component in adipocyte differentiation that may also contribute to the sensitivity of cells to insulin. PPAR-gamma is activated by fatty acids, and the membrane composition may have an impact on the activity of PPAR-gamma and thus on the sensitivity of adipocytes to insulin. We investigated these possible links by determining the phospholipid contents of adipocyte membranes, the mRNA expression of PPAR-gamma, and the FPI and HOMA estimate of insulin resistance in obese women. The mRNA levels of tumor necrosis factor-alpha (TNF-alpha), which is suspected to play a role in insulin resistance and which downregulates PPAR-gamma expression, were also quantified. FPI and HOMA were strongly positively correlated with membrane SM (P < 0.005) and cholesterol (P < 0.005). PPAR-gamma mRNA levels were negatively correlated with FPI (P < 0.05) and HOMA (P < 0.05) and positively correlated with high-density lipoprotein (HDL) cholesterol (P < 0.05), membrane SM (P < 0.05), and cholesterol contents (P < 0.05). TNF-alpha mRNA levels were not correlated with membrane parameters. In stepwise multiple regression analysis, the variations in PPAR-gamma mRNA levels were mainly explained by HDL cholesterol (31.9%) and membrane SM (17.7%). Our study shows that the expression of PPAR-gamma, a major factor controlling adipocyte functions, the lipid composition of the membrane, and insulin sensitivity are probably closely associated in the adipose tissue of obese women.

Adipocytes↗