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Biomedical subjects

M A Charles

Publications and source records attributed to M A Charles.

At least 19 recordsLinked to original sources

Niacin treatment of the atherogenic lipid profile and Lp(a) in diabetes.

OBJECTIVE: We tested the hypotheses that niacin is effective for the separate treatments of abnormalities of LDL particle size, HDL2 percentage and Lp(a) without potential negative effects on glycated haemoglobin. RESEARCH DESIGN AND METHODS: The atherogenic lipid profile lipids, such as triglycerides, small, dense LDL cholesterol (LDLc) particle mass, LDL particle size, total HDLc and HDL2 percentage as well as Lp(a), were measured in 42 diabetic patients with abnormalities of LDL particle size, HDL2 percentage and/or Lp(a) levels before and after niacin treatment. LDL particle size and HDL2 were measured using polyacrylamide gradient gel electrophoreses and Lp(a) was measured by enzyme-linked immunoabsorbance assay (ELISA). RESULTS: After niacin treatment, LDL peak particle diameter increased from 252 +/- 7 A to 263 +/- 7 (p < 0.0001), small, dense LDLc particle mass decreased from 27 +/- 11 mg/dL to 15 +/- 4 (p < 0.0001), total HDLc increased from 39 +/- 7 mg/dL to 51 +/- 11 (p < 0.0001), HDL2 as the percentage of total HDLc mass increased from 29 +/- 8% to 45 +/- 10 (p < 0.0001) and Lp(a) decreased from 43 +/- 17 mg/dL to 25 +/- 10 (p < 0.0001). Mean haemoglobin A1c level was improved during treatment from 7.6 +/- 1.8% to 6.5 +/- 1.0 (p < 0.0001) using increased oral agent and insulin treatment doses in more than 90% of the patients. A total of 21% of the patients were unable to tolerate niacin owing to reversible side-effects, and 14% were unable to adhere to the niacin dosing regimen of three times daily. CONCLUSIONS: These data indicate that in diabetic patients, niacin (i) is effective for treating diabetic dyslipidaemias associated with both the atherogenic lipid profile and Lp(a); (ii) must be used with modern and aggressive oral hypoglycaemic agents or insulin treatment; and (iii) is an important drug to treat diabetes dyslipidaemias because of its broad spectrum of effectiveness.

Arteriosclerosis↗

Circulating nonesterified fatty acid level as a predictive risk factor for sudden death in the population.

BACKGROUND: In ischemic conditions, concentration of circulating nonesterified fatty acids (NEFA) is increased and has a proarrhythmic effect that is responsible for ventricular tachyarrhythmias. In nonischemic patients, high NEFA plasma concentration has been shown to be associated with frequent premature ventricular complexes and increased familial risk of cardiovascular disease, but its relation to sudden death has not been studied. We assessed the role of circulating NEFA in sudden death in asymptomatic men in a long-term cohort study. METHODS AND RESULTS: A total of 5250 men employed by the city of Paris, aged 42 to 53 in 1967 to 1972, free of known ischemic cardiac disease, and included in the Paris Prospective Study I, completed a second annual examination and had fasting plasma circulating NEFA measured. Each subject underwent a physical examination and ECG, provided blood for laboratory tests, and answered questionnaires administered by trained interviewers. Vital status was obtained for each subject from specific inquiries until he retired; after retirement, it was obtained from death certificates. Body mass index, systolic and diastolic blood pressures, tobacco consumption, parental history of sudden death, fasting cholesterol level, and circulating NEFA concentration were independent factors associated with sudden death during follow up (average, 22 years). When adjusted for confounding factors, circulating NEFA concentration remained an independent risk factor for sudden death (relative risk, 1.70; 95% confidence interval, 1.21 to 2.13) but not for fatal myocardial infarction. CONCLUSIONS: Circulating NEFA concentration is an independent risk factor for sudden death in middle-aged men. Some form of primary prevention could be envisaged in subjects at high risk of sudden death.

Adult↗

High plasma nonesterified fatty acids are predictive of cancer mortality but not of coronary heart disease mortality: results from the Paris Prospective Study.

To assess the association of fasting plasma nonesterified fatty acid (NEFA) concentration with the risk of death from coronary heart disease and cancer, the authors computed 15-year mortality rates for the 4,589 working men aged 43-53 years who were included in the Paris Prospective Study between 1967 and 1972. A total of 251 and 126 men died from cancer and coronary heart disease, respectively. For coronary heart disease death, the age- and tobacco-adjusted relative risk for men in the highest 20% of the fasting plasma NEFA concentrations compared with those in the lowest 80% was 1.54 (95% confidence interval (CI): 1.01, 2.34). It became nonsignificant after further adjustment for blood pressure, iliac/thigh ratio, and plasma insulin and cholesterol concentrations. In contrast, a high fasting plasma NEFA concentration exhibited a strong independent relation with cancer mortality (relative risk = 1.66, 95% CI: 1.25, 2.21, after adjustment for age, cigarette consumption, heart rate, and body mass index). Despite pathophysiologic mechanisms linking NEFA metabolism with visceral fat and plasma glucose, insulin, and triglyceride concentrations, the plasma NEFA concentration does not appear to be a good marker for coronary heart disease risk. In contrast, an unexpected association with cancer mortality was found that may point to the need for further investigation.

Adult↗

Gender differences in the relation between food cravings and mood in an adult community: Results from the fleurbaix laventie ville santé study.

OBJECTIVE: The aim of this survey was to study food cravings and its indulgence in community adults (538 women and 506 men) and to compare nutritional parameters, weight preoccupations, and weight history between cravers and noncravers. METHOD: Cravers experienced a strong urge to eat specific foods more than once a week during the past 6 months. Food intake was estimated by a 3-day food record. RESULTS: 28% of women and 13% of men were food cravers. Cravers, especially women, were more frequently concerned about their weight than noncravers. Energy intake during snacks was higher in cravers. Less than 40% of cravers reported being hungry when they experienced cravings. Women cravers indulged their cravings as often as men. They reported more frequently negative feelings, whereas men reported more frequently positive feelings. DISCUSSION: This study shows that food craving episodes are strongly associated with mood but in a different way in women and men.

Adult↗

Accumulation of triglyceride-rich lipoprotein in subjects with abdominal obesity: the biguanides and the prevention of the risk of obesity (BIGPRO) 1 study.

The present study represents a new insight into the Biguanides and the Prevention of the Risk of Obesity (BIGPRO) 1 study population at inclusion. This population, selected basically on the basis of a high waist-to-hip ratio (>/=0.95 for men and >/=0.80 for women), is supposed to represent a group of patients with insulin resistance. The present study was undergone to establish whether apolipoprotein C-III (apoC-III) and apolipoprotein E (apoE) associated with apo B (apoC-III LpB and apoE LpB, respectively), considered to be markers of remnant accumulation, play a role in the hypertriglyceridemia associated with insulin resistance and whether they are related to other biological abnormalities frequently observed in this syndrome. In this population, the concentration of the markers of remnant accumulation increases with triglyceride levels. Therefore, correlation studies were realized to assess the relative effect of insulin and the markers of remnant accumulation on triglyceride plasma level. As a first attempt, a simple correlation analysis revealed that insulin is positively related to the markers of remnant accumulation only in hypertriglyceridemic patients (triglycerides >/=1.7 mmol/L). To assess the independent contribution of these markers, insulin, and other parameters related to the plasma triglyceride concentration, a stepwise multiple regression analysis was run. Results revealed that insulin and the markers of remnant accumulation (specifically, apoE LpB) are independent contributors to the plasma triglyceride concentration. Markers of the endothelial damage, plasminogen activator inhibitor-1, tissue plasminogen activator, and von Willebrand factor, which are often increased in the case of insulin resistance, were tested for their correlation with the markers of remnant accumulation. Plasminogen activator inhibitor-1 is positively correlated with these markers only in hypertriglyceridemic male subjects. It is concluded that increased insulin levels found in insulin resistance syndrome are associated with an increased production of triglyceride-rich lipoproteins enriched in apoC-III and apoE. The accumulation of these remnants and/or their abnormal composition in apoC-III and apoE could be an explanation for the development of hypertriglyceridemia in this syndrome.

Abdomen↗

Characterization of Drosophila hibris, a gene related to human nephrin.

Hibris encodes a protein that is a newly identified member of the immunoglobulin superfamily and has homology to vertebrate Nephrins and Drosophila Sticks-and-Stones. The Hibris protein has eight Ig-like domains, a fibronectin domain and a 160 amino acid cytoplasmic tail. The hibris transcript is expressed in a broad range of tissues and across life stages. In the embryo, hibris transcript is present in the mesectoderm, then in a group of cells at the developing CNS midline and in a subset of glia. In the periphery, hibris is expressed by fusion competent myoblasts and the epidermal muscle attachment site cells. Deletion analyses show that loss of hibris does not visibly affect embryonic CNS or somatic muscle development. However overexpressing hibris in the somatic mesoderm disrupts myoblast fusion. Furthermore, when overexpressed in the epidermis, Hibris causes comprehensive derangement of muscle insertion locations. A similar myoblast fusion defect is observed when the Drosophila homologs of DM-GRASP/BEN/SC1 (irregular chiasm-roughest and dumbfounded) are deleted together. Our S2 cell aggregation assays have revealed a heterotypic interaction between Hibris and Dumbfounded, but not between Hibris and Irregular Chiasm-Roughest. We propose that Hibris is an extracellular partner for Dumbfounded and potentially mediates the response of myoblasts to this attractant.

Amino Acid Sequence↗

Reproducibility of the diagnosis of diabetes over a 30-month follow-up: the Paris Prospective Study.

OBJECTIVE: To describe the change in diabetic status over 30 months. RESEARCH DESIGN AND METHODS: Cohort study of 5,400 Caucasian men from the Paris Prospective Study, aged 44-55 years, who were not known as having diabetes at baseline. Oral glucose tolerance tests were performed at baseline and after 30 months. RESULTS: At baseline, diabetes was diagnosed in 2.9% of the men by fasting plasma glucose (FPG) > or =7.0 mmol/l and in 0.9% by isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and 2-h plasma glucose concentration > or =11.1 mmol/l), i.e., one in four of all men with newly diagnosed diabetes. Thirty months later, 42% of the men with diabetes diagnosed by FPG reverted to nondiabetic status, compared with 72% of those with diabetes diagnosed by IPH (P < 0.0001). For the men with diabetes diagnosed by FPG at baseline, diabetes had been diagnosed by a physician at 30 months in 11.5%, in contrast to only 3.9% of those with diabetes diagnosed by IPH (P < 0.05). For the 51 men with diabetes diagnosed by IPH at baseline, those who reverted to nondiabetic status had a lower frequency of family history of diabetes (P < 0.1), a higher mean corpuscular volume (P < 0.08), and a significantly higher total cholesterol concentration (P < 0.006) at baseline; in contrast, for the 156 men with diabetes diagnosed by FPG at baseline, the men who reverted to nondiabetic status and those who remained diabetic had similar characteristics. CONCLUSIONS: In this epidemiological study, diabetes diagnosed by one FPG concentration was more stable than diabetes diagnosed by one IPH; in clinical practice, the diagnosis of diabetes requires confirmation of the hyperglycemia.

Adult↗

From policemen to policies: what is the future for 2-h glucose? The Kelly West Lecture, 2000.

OBJECTIVE: To describe the characteristics and vital prognosis of men with diabetes diagnosed by one fasting plasma glucose (FPG) concentration > or =7.0 mmol/l, with diabetes diagnosed by one isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and a 2-h plasma glucose concentration > or =11.1 mmol/l), or with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: This study involved a cohort of 6,881 Caucasian nondiabetic men from the Paris Prospective Study, aged 44-55 years, who were followed for cause of death for 20 years. RESULTS: Diabetes was diagnosed in 4.3% of the men (1.0% diabetes diagnosed by IPH), and IGT was diagnosed in 9% of the men. At baseline, the men with diabetes diagnosed by IPH had a lower cardiovascular risk profile than those with diabetes diagnosed by FPG, as did the men with IGT and a normal fasting glucose level (<6.1 mmol/l, IGT and normal fasting glucose), compared with men with impaired fasting glucose (6.1-6.9 mmol/l, IGT and impaired fasting glucose [IFG]). At 20 years of follow-up, all-cause and cancer death rates were higher in men with diabetes diagnosed by IPH than in men with diabetes diagnosed by FPG (55 vs. 44%, P < 0.1 and 31 vs. 17%, P < 0.01, respectively) but were not significantly different for coronary causes (6 vs. 11%). Men with IGT and normal fasting glucose also had significantly higher cancer death rates than men with IGT and IFG. CONCLUSIONS: The most likely explanation for the high cancer and low coronary death rates is that men with diabetes diagnosed by IPH consumed alcohol; the men in this study drank 49 g of pure alcohol on average per day, equivalent to 0.6 l of wine. If these results are confirmed by other prospective studies, screening subjects for isolated postchallenge hyperglycemia may not be worthwhile.

Adult↗

Plasma levels of free and total TFPI, relationship with cardiovascular risk factors and endothelial cell markers.

Free-TFPI (f-TFPI) presents high anticoagulant activity and its plasma level correlates with unfavorable outcomes in unstable angina. Total TFPI (t-TFPI) represents mainly the lipid-bound form which seems to have a poor anticoagulant activity. Until now, it is not known whether the variations of f-TFPI plasma levels are determined by environmental factors. The aim of our study was to evaluate the influence of cardiovascular risk factors on plasma levels of f-TFPI and relations with other endothelial derived molecules in a population of 626 patients (277 men and 349 women) attending a metabolic ward for primary prevention of coronary disease. Free and total TFPI plasma levels were poorly correlated. f-TFPI levels increased with age in both sexes, t-TFPI in women only. Age-adjusted correlations of TFPI levels with conventional cardiovascular risk factors and endothelial cell markers showed different patterns for f-TFPI and t-TFPI. f-TFPI correlated with parameters associated with insulin resistance, particularly in females. f-TFPI was also positively associated in both genders with fibrinogen and endothelial cell markers: t-PA, thrombomodulin (TM) and von Willebrand factor (vWF). t-TFPI correlated strongly with LDL-C in both sexes. It also correlated negatively with parameters of the insulin resistance syndrome. t-TFPI also correlated with TM but not with other endothelial cell markers. The results of the multivariate step by step analysis showed that cardiovascular risk factors poorly explained the f-TFPI variability (7% and 4% in men and women, respectively), whereas they explained 16 and 20% of t-TFPI variability in men and women respectively (mostly related to LDL-C). In conclusion, this study showed that free- and total-TFPI are regulated differently. f-TFPI strongly correlates with endothelial cell markers and t-TFPI is more related to conventional cardiovascular risk factors. The strong gender effect on f-TFPI levels remains to be explained.

Age Factors↗

[Insulin sensitivity and ethnic groups].

Epidemiological surveys show a large variation of type 2 diabetes (DT2) prevalence from one country to another, suggesting ethnic discrepancies in insulin sensitivity. Many data seem to confirm this hypothesis. We will show them while concentrating on data provided by surveys performed in French-speaking countries. The mechanisms of the ethnic differences in insulin sensitivity are unclear and further insights are needed. More than genetic factors, environmental factors appear to be involved in the occurence of insulin resistance and DT2. The epidemic nature of obesity and subsequent DT2 in the world urges health authorities in each country to raise campaigns to promote changes in life style and nutritional habits before the announced pandemy of DT2 becomes reality.

Africa↗

Puberty-associated differences in total cholesterol and triglyceride levels according to sex in French children aged 10-13 years.

PURPOSE: To assess the relationships between lipid levels and sexual maturity, independently of age-related differences, and to investigate possible differences related to sexual maturity across the percentiles of the lipid distributions. METHODS: Fasting serum total cholesterol and triglyceride concentrations were measured in 6577 boys and 6605 girls, aged from 10 to 13 years, with different Tanner stages. The total cholesterol and triglyceride mean and percentile levels were estimated according to age and Tanner stage by ordinary least squares and percentile regression models, separately in both sexes. RESULTS: In boys and girls, total cholesterol levels were significantly associated with pubertal stage after controlling for age. At age 12, the estimated mean levels in boys varied from 4.82 mmol/L for Tanner 1 to 4.41 for Tanner 5. The corresponding values were 5.05 and 4.62 mmol/L in girls, for whom the association with maturity was stronger in the upper than in the lower percentiles (p < 0.0001); between the extreme Tanner stages, the 95th percentiles of total cholesterol differed by 0.80 mmol/L, in comparison to 0.19 mmol/L for the 5th percentiles. Therefore, 1. 8% of girls and 0.7% of boys were classified differently whether Tanner stage was used or not to assess hypercholesterolemia (concentrations in the upper 5% of the distributions). Triglycerides were positively related to sexual maturity independently of age, but the discrepancies between classifications were lower; 1.1% in girls and 0.4% in boys. CONCLUSIONS: Our findings emphasize the importance of sexual maturity, even for a given age, for interpreting lipid levels in children.

Adolescent↗

Infant-feeding patterns are related to blood cholesterol concentration in prepubertal children aged 5-11 y: the Fleurbaix-Laventie Ville Santé study.

OBJECTIVE: Several studies, mainly in animals, but also in humans, have shown that diet in infancy is associated with differences in blood cholesterol concentrations later in life. The objective was to examine this relationship in children aged 5-11 y after taking into account their current diet and parental hypercholesterolemia. SETTING AND SUBJECTS: 251 prepubertal boys and 223 prepubertal girls enrolled in the schools in two little towns in northern France. DESIGN AND METHODS: Cross-sectional evaluation including measurements of cholesterol concentrations on capillary blood and a single weekday food intake record. Infant feeding patterns were obtained by questionnaire given to the mothers. RESULTS: 50% of the children had been breast-fed for a median duration of less than 2 months. Cow's milk was introduced in the diet as whole milk for 33% of the children. After adjustment for age, height, and sibship, capillary cholesterol concentration was lower in boys who had been breast fed (geometric mean: 4.4, 95% confidence interval of the mean: 4.2-4.6 mmol/L) than in those fed with formula (4.7, 4.5-4.8 mmol/L, P<0.03). In girls, breastfeeding had no significant effect on blood cholesterol concentration, which was associated with the type of cow's milk given in infancy: whole milk: 4.9 mmol/L (4.7-5. 2); totally or partially skimmed milk: 4.5 mmol/L (4.2-4.6), P<0.008. The current saturated fat and cholesterol intakes and parental hypercyholesterolemia were associated with current blood cholesterol concentration in children, but did not modify its relationship with infant feeding patterns. CONCLUSION: Results of the present study suggest that diet in infancy may have longstanding effect on lipid metabolism. SPONSORSHIP: The study was supported by funds from Eridania Béghin-Say, Groupe Fournier, Lesieur and Nestlé France, Roche Diagnostic and of the MGEN (Mutuelle Générale de l'Education Nationale, contract INSERM-MGEN #9158) and a grant from the Association de Langue Française pour l'Etude du Diabète et du Métabolisme (ALFEDIAM). European Journal of Clinical Nutrition (2000) 54, 114-119

Animals↗

Obesity morbidity and health care costs in France: an analysis of the 1991-1992 Medical Care Household Survey.

OBJECTIVE: To estimate the direct medical costs associated with obesity in France. DESIGN: Analysis of the French 1991-1992 National Household Survey database comprising a representative sample of 14, 670 individuals aged 18 y and over. A subgroup of subjects with a body mass index (BMI)>/=30 kg/m2 was compared with a control group of normal-weight individuals (BMI 18.5-25 kg/m2) matched on age, gender and education level. MEASUREMENTS: Self-reported weight and height used to calculate individual body mass index and health expenditures in a 3 month period, and morbidity as declared by respondents to the national household survey and verified on medical records. RESULTS: The direct cost attributable to obesity (BMI>/=30 kg/m2) was estimated to be in the range 4.2-8.7 billion French Francs (FF) in 1992 value, that is between 0.7 and 1.5% of total health expenditures. CONCLUSION: These results were of the same order of magnitude as similar estimates obtained by a top-down approach for the same year and setting. International Journal of Obesity (2000) 24, 151-155

Adolescent↗

Does energy intake underreporting involve all kinds of food or only specific food items? Results from the Fleurbaix Laventie Ville Santé (FLVS) study.

OBJECTIVE: To determine if energy intake underreporting concerns all major food groups or if it occurs for specific food groups only. DESIGN: Cross-sectional study on dietary habits and food consumption. SUBJECTS: Five-hundred and four women and 529 men, aged between 25 and 55y participating in the Fleurbaix Laventie Ville Sante study. MEASUREMENTS: A nutritional survey was conducted between March and June 1993 using a 3-day food record. Reported weight and height were used to estimate body mass index and basal metabolic rate. Underreporters were defined as subjects whose ratio of mean energy intake to basal metabolic rate was lower than 1.05. Food consumption was compared between underreporters and non-underreporters. RESULTS: Energy percentage of fat and carbohydrate were lower in underreporters than in non-underreporters in contrast to the energy percentage of protein. This was due to the fact that food items rich in fat and/or carbohydrates (such as butter, French fries, sugars and confectionery, cakes and pastries) were reported to be less frequently eaten and/or in smaller quantities in underreporters compared to non-underreporters. CONCLUSION: Although this study presents some limitations, like the use of reported weight and a standard value for physical activity, it shows that reported foods differed, quantitatively and qualitatively, between severe underreporters and non-underreporters. Underreporting of food intake does not result from a systematical underestimation of portion sizes for all food items, but seems to concern specific food items which are generally considered 'bad for health'.

Adult↗

Macronutrient energy intake and adiposity in non obese prepubertal children aged 5-11 y (the Fleurbaix Laventie Ville Santé Study).

OBJECTIVE: To investigate associations between adiposity indices and food intake in nonobese prepubertal free-living children. SUBJECTS: Five-hundred and one children, 280 boys and 221 girls aged 5-11 y in two little towns in northern France. DESIGN: Cross-sectional survey. MAIN OUTCOME MEASURES: Height and weight, four skinfolds (biceps, triceps, subscapular, suprailiac), waist and hip girths, were measured. Sum of skinfolds (SSF), body mass index (BMI), and relative weight (RW) were calculated. Energy intake (EI), percentage of energy intake ascribed to carbohydrates (%EIC), complex carbohydrates (%EICC), fats (%EIF), saturated fats (%EISF) and proteins (%EIP) were assessed by a single 24 h record. Basal metabolic rate (BMRI was estimated according to Schofield's equations. Obese (RW > or = 120%), and underreporting children according to Goldberg's and Black's equations were excluded. RESULTS: In multiple linear regressions analyses performed with hierarchical mixed models, adiposity indices were significantly and inversely associated in girls with %EIC (all P-values < 0.02), and positively with %EIF (all P-values < 0.05, waist girth and BMI excepted). Similar but non-significant trends were observed in boys. The relationships were not linear, and thresholds close to current dietary recommendations were highlighted. When %EIF was low, a lower percentage of energy intake ascribed to %EISF was associated with thinness. These associations remained after the exclusion of children who had an EI/BMR > or = 1.50. CONCLUSIONS: In nonobese prepubertal children aged 5-11 y, a high %EIC, close to dietary recommendations (> or = 55%), was associated with thinness. A high %EIF, over the upper dietary recommendation (< or = 35%), was associated with a greater adiposity thickness. There was no further increase in adiposity beyond this threshold. Reasons for the absence of a linear relationship pattern between adiposity and macronutrient intake remain to be determined.

Adipose Tissue↗