Search PubMed⌕ Search

Biomedical subjects

M A Charles

Publications and source records attributed to M A Charles.

At least 55 records · Page 3Linked to original sources
PubMed1999

Gender differences in the relation between fibrinogen, tissue-type plasminogen activator antigen and markers of insulin resistance: effects of smoking. D.E.S.I.R. Study Group. Data from an Epidemiological Study on Insulin Resistance Syndrome.

A stronger positive association between fibrinogen or tissue-type plasminogen activator antigen (tPA-ag) and fasting insulin is observed in women than in men. We investigated whether this effect could be explained by a difference in smoking habits. The relations between markers for insulin resistance [fasting insulin and insulin resistance as estimated by the homeostasis model assessment (HOMA-IR)] and fibrinogen and tPA-ag were examined cross-sectionally in 4976 (582 for tPA-ag) subjects from the D.E.S.I.R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) study. The modifying effect of smoking habits were evaluated. Seventeen percent of women and 27% of men were smokers. Fibrinogen concentrations were higher in smokers than in non-smokers, in men only. Female smokers had lower concentrations of tPA-ag than non-smokers. In both women and men, fibrinogen was positively associated with fasting insulin [women: beta = 0.33 mg/U (95% confidence interval: 0.29, 0.37); men: beta = 0.15 mg/U (0.11, 0.19)] and with HOMA-IR [women: beta = 0.17 microg/microU mol/l (0.15, 0.19): men: beta = 0.06 (0.04, 0.08)]. For tPA-ag these associations were for insulin beta = 0.76 mg/U (0.54, 0.98) and beta = 0.89 mg/U (0.67, 1.11), and for HOMA-IR beta = 0.47 microg/microU mol/l (0.33, 0.61) and beta = 0.45 microg/microU mol/l (0.33, 0.57), women and men respectively. The associations of fibrinogen and tPA-ag with insulin and HOMA-IR were sharply reduced in male smokers compared to male non-smokers, however the strength of the associations in male non-smokers did not reach that in women. Fibrinogen and tPA-ag are independently related with markers of insulin resistance, with the relation with fibrinogen being stronger in women than in men. The strong modifying effect of smoking habits does not completely explain this gender difference.

Adult↗
PubMed1999

[Epidemiology, management and costs of type 2 diabetes in France in 1998].

Almost 10 years after the Saint Vincent declaration, a large effort was undertaken in France to improve medical care of type 2 diabetes and to limit the dreadful complications of this pathology. As expert recommendations grow in number, it appears necessary to update knowledge on the epidemiological, medical care, and cost aspects of this illness in France. In this aim, a systematic review of the medical and economic literature on type 2 diabetes was performed. Prevalence of type 2 diabetes probably reaches 2.2% in the general population, which represents 1.3 million people in France. Among these people, almost 60% are overweighted, 50% suffer high blood pressure and 30% have a treated dyslipaemia. Coronary pathologies concern 20% to 30% of type 2 diabetes patients, neuropathies 10% to 30% and ocular problems 10% to 35%. Medical care consumption of type 2 diabetes patients probably represents almost 20,000 FF per patient and per year, i.e., twice the average medical care consumption in the French population. Yet, these estimates should be considered with caution since a lot of uncertainty remains on the epidemiological, medical care, and cost aspects of type 2 diabetes in France. As diabetes has become a national public health priority, it is important to initiate new studies to have precise indicators in these different fields.

Aged↗
PubMed1998

Glycaemic control and development of retinopathy in type 2 diabetes mellitus: a longitudinal study.

Relationships between glycaemic control, hypertension, and development of microangiopathy have been well documented in Type 1 (insulin-dependent) but not in Type 2 (non-insulin-dependent) diabetes mellitus. Therefore, we have investigated these relationships in a cohort of 64 Type 2 patients free of retinopathy (by angiofluorography), who were regularly followed until development of retinopathy or for at least 7 years as outpatients. Glycaemic control was assessed by 1 to 4 HbA1 determinations per year. Retinal status was monitored by annual angiofluorography. Nonproliferative retinopathy developed in 14 patients (cumulative incidence at 13 years: 29.8%) after a mean diabetes duration of 14.3+/-8.9 years (range 2-27). In multivariate analysis (Cox model), mean HbA1 during follow-up (p < 0.001), and hypertension at first examination (p = 0.09) were associated with the development of retinopathy, but age, sex, BMI, diabetes duration, smoking, and fasting blood glucose were not. The relative risk for developing retinopathy (RR) was 7.2 (IC 95%: 1.61-32.4) in patients with a mean HbA1 during follow-up above the median value of the cohort (8.3%) compared with patients with HbA1 during follow-up below this value. RR was 2.5 (IC 0.8-8) in patients with HbA1 at first examination above compared to below the median value (8.4%). RR was 3.0 (IC 0.9-10) in patients treated for hypertension at baseline compared to those without treatment. A sixfold increase in retinopathy prevalence was observed between patients with mean HbA1 in the highest or lowest quartile of mean HbA1 distribution during follow-up. This longitudinal study indicates a strong association between long-term glycaemic control and the development of diabetic retinopathy in Type 2 diabetes.

Adult↗
PubMed1998

Preclinical studies of glimepiride.

The treatment of NIDDM is advancing on a number of fronts, ranging from the understanding of the mechanisms of action of existing agents to the development of new drugs. Glimepiride, the most recently U.S. approved sulfonylurea, is evaluated for its pancreatic and extrapancreatic activities in addition to safety, when compared with glibenclamide in preclinical studies. Glimepiride uniquely binds to the 65 kDa protein K(ATP) channel in pancreatic islet beta-cell membranes and directly stimulates insulin secretion. Glimepiride has a lower binding affinity and causes less insulin release than glibenclamide in normal dogs and humans. However, in various animal models, glimepiride produces a more rapid and pronounced blood glucose-decreasing activity than glibenclamide. In vivo studies indicate that glimepiride also significantly reduces HbA1c, blood glucose and fasting insulin levels via extrapancreatic activities. These insulin mimetic effects are supported by demonstration of stimulated lipogenesis in 3T3 adipocytes and glycogenesis in rat diaphragm, by more efficient translocation of GLTU4 in fat and skeletal muscle tissues, and by activation of key metabolic enzymes. The insulin sensitivity effects of glimepiride have been demonstrated in vivo by increased glucose disposal rates in euglycemic clamp studies and in vitro by increased sensitivity and responsiveness of insulin-induced glucose uptake. Moreover, glimepiride might stimulate insulin-mediated glucose utilization in hepatocytes. With exercise-induced hypoglycemia, a suppression of endogenous insulin secretion was observed for glimepiride only. Data accumulated from in vitro and animal studies suggest that glimepiride has the least cardiotoxic potential. Its relative activities in multiple cardiovascular studies do not correlate with its potency to lower blood glucose levels. Similar cardiovascular effects have been seen in human studies. In contrast to the lack of an acute action, chronic application of glimepiride to cultured cardiomyocytes was found to produce an approximate doubling of the basal glucose uptake rates by an insulin-independent pathway most probably involving increased protein expression of both GLUT1 and GLUT4. Like glibenclamide, glimepiride possibly has antiatherogenic activity by inhibiting platelet aggregation via suppression of arachidonic acid metabolism. Our recent studies on rats and humans indicated that glimepiride has immunomodulatory activity and this action appears to be related to lowering autoimmune responses rather than metabolic action. These studies have been extended to include glimepiride involvement with prevention of diabetes in BB rats using an islet transplantation model. Finally, sulfonylureas, including glimepiride, may be useful for treating and preventing NIDDM.

Journal Article↗
PubMed1998

Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPRO1 Study. Biguanides and the Prevention of the Risk of Obesity.

OBJECTIVE: Insulin resistance is associated with hypofibrinolysis. Metformin has been shown to improve insulin sensitivity and fibrinolysis. Its action on fibrinolysis and the von Willebrand factor was evaluated in the Biguanides and the Prevention of the Risk of Obesity (BIGPRO)1 trial in nondiabetic men (n = 151) and women (n = 306) aged between 34 and 65 years with a central fat distribution and a mean BMI of 32.5 kg/m2. RESEARCH DESIGN AND METHODS: The subjects were randomly allocated to a 1-year treatment with metformin (850 mg b.i.d.) or placebo, in addition to diet and exercise recommendations. RESULTS: Plasminogen activator inhibitor 1 (PAI-1) activity and antigen decreased significantly but similarly by 30 and 40%, respectively, in both the placebo and the metformin groups. This decrease occurred mainly in subjects who lost weight. Metformin did not have any significant additional effect on PAI-1. In contrast to the results for PAI-1, there was a significantly greater decrease in tissue-type plasminogen activator (tPA) antigen in the metformin than in the placebo group (mean+/-SD: -1.1+/-3.1 vs. 0.2+/-3.2 ng/ml, P < 0.02). The von Willebrand factor (vWF) also decreased significantly more in the metformin group (-0.17+/-0.42 vs. -0.05+/-0.38 U/I, P < 0.02). CONCLUSIONS: Weight loss was the main factor associated with the decrease in PAI-1, in accordance with the recent demonstration of production of PAI-1 by adipocytes. Metformin had a significant effect on two factors, tPA antigen and vWF, mainly secreted by the endothelial cells, which suggests an effect of the drug on the production or the metabolism of these two hemostatic proteins.

Adult↗
PubMed1998

The relationship of menstrual irregularity to type 2 diabetes in Pima Indian women.

OBJECTIVE: Menstrual irregularity is associated with hyperinsulinemia and hyperandrogenemia in nondiabetic Pima Indian women of child-bearing age. In this population-based study, we determined the relationship of menstrual irregularity to type 2 diabetes in Pima Indian women. RESEARCH DESIGN AND METHODS: Participants for this cross-sectional analysis were 695 nonpregnant Pima Indian women, aged 18-44 years, involved in an ongoing epidemiologic study of diabetes among residents of the Gila River Indian Community of Arizona. Clinical data were collected by questionnaire and an examination that included a 75-g oral glucose tolerance test; diabetes was diagnosed by World Health Organization criteria. Menstrual irregularity was defined as an interval of 3 months or more between menses, when not pregnant, since age 18 years. RESULTS: History of menstrual irregularity was significantly associated with a high prevalence of diabetes (37 vs. 13%; odds ratio = 4.2, 95% CI = 1.6-10.8) in the least obese women (BMI < 30 kg/m2), adjusted for the effects of age and overall obesity. This association was, in part, because of greater central obesity in women with irregular menses. In more obese women, there was little association with menstrual irregularity, and diabetes was frequent regardless of menstrual history. CONCLUSIONS: Prevalence of type 2 diabetes is higher among Pima indian women with a history of menstrual irregularity. The difference is most pronounced among the least obese group of women. This association may be because of insulin resistance and hyperinsulinemia, which predict type 2 diabetes, also causing hyperandrogenism and menstrual irregularity. The findings reinforce the need to evaluate women with menstrual irregularity for hyperglycemia.

Adult↗
PubMed1997

The role of non-esterified fatty acids in the deterioration of glucose tolerance in Caucasian subjects: results of the Paris Prospective Study.

Although an increased plasma non-esterified fatty acid (NEFA) concentration has been shown to increase insulin resistance (Randle cycle), decrease insulin secretion and increase hepatic gluconeogenesis, the effect of NEFA on the deterioration of glucose tolerance has not been studied prospectively in Caucasian subjects. Therefore, we investigated whether plasma NEFA may be regarded as predictors of deterioration of glucose tolerance in subjects with normal (NGT, n = 3671) or impaired (IGT, n = 418) glucose tolerance who were participants in the Paris Prospective study. The subjects were first examined between 1967 and 1972 and underwent two 75-g oral glucose tolerance tests 2 years apart with measurements of plasma glucose, insulin and NEFA concentrations. Glucose tolerance deteriorated from NGT to IGT or non-insulin-dependent diabetes (NIDDM) in 177 subjects and from IGT to NIDDM in 32 subjects. In multivariate analysis, high fasting plasma NEFA in NGT subjects and high 2-h plasma NEFA and low 2-h plasma insulin concentrations in IGT subjects were significant independent predictors of deterioration along with older age, high fasting and 2-h plasma glucose concentrations and high iliac to thigh ratio. When subjects were divided by tertiles of plasma NEFA concentration at baseline, there was an increase in 2-h glucose concentration with increasing NEFA in the subjects who did not deteriorate, but no effect of plasma NEFA in those who deteriorated. In subjects with IGT who deteriorated compared with those who did not 2-h plasma insulin concentration was lower but there was no evidence that this resulted from an effect of plasma NEFA. Our data suggest that a high plasma NEFA concentration is a risk marker for deterioration of glucose tolerance independent of the insulin resistance or the insulin secretion defect that characterize subjects at risk for NIDDM.

Basal Metabolism↗
PubMed1997

Cytologic determinants of well-differentiated thyroid cancer.

OBJECTIVE: Fine-needle aspiration biopsy (FNAB) is the preferred diagnostic study for evaluating thyroid nodules. Despite its accuracy, many patients undergo thyroidectomy for benign nodules. This study was undertaken to identify risk factors that might increase the specificity of FNAB. METHODS: Medical records of 422 patients who underwent thyroid surgery between 1986 and 1996 were reviewed. All patients had FNAB prior to surgery. RESULTS: Of the 422 patients, 36% had benign cytology, 46% had indeterminate cytology, and 13% had cancer. In the indeterminate group, 29% of patients had cancer at surgery. Of patients with papillary cytology, 84% had malignancies. Five percent of FNABs were nondiagnostic. Neither age, gender, nor tumor size was associated with increased specificity of FNAB. CONCLUSION: There is no subpopulation of patients with indeterminate FNAB cytology at increased risk of having well-differentiated thyroid cancer.

Biopsy, Needle↗
PubMed1997

Determinants and nature of dietary underreporting in a free-living population: the Fleurbaix Laventie Ville Santé (FLVS) Study.

OBJECTIVE: To study the determinants and nature of dietary underreporting in a free-living population. DESIGN: Cross-sectional study of nutritional and behavioural characteristics. SUBJECTS: 1030 weight-stable subjects, 501 women and 529 men older than 15 y, included in the Fleurbaix Laventie Ville Santé study. MEASUREMENTS: Dietary intake was assessed using a 3 dy dietary record. Self assessed body weight and height were also recorded. Behavioural and socio-economic data were obtained from a questionnaire. Underreporters were defined as people with a reported ratio of energy intake to estimated basal metabolic rate lower than 1.05. RESULTS: Underreporting concerned 16% of the population and was significantly more frequent in obese than in non obese subjects (P < 0.001). Underreporting was significantly associated with a high socio-professional class (P < 0.05), having dieted at least once (P < 0.01) and to be in dietary restraint (P < 0.05). Furthermore, the contribution of protein to energy intake was significantly higher in underreporters than in non underreporters, independently of weight status. CONCLUSIONS: These data underline that underreporting may bias the assessment of energy and macronutrient intake, particularly in studies on obesity and dietary restraint. Questions about weight concern, dieting and dietary restraint may be useful to identify subjects who underestimate their food intake.

Adolescent↗
PubMed1997

Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: The Telecom Study.

The associations between androgens and cardiovascular risk factors in men are controversial. A nested case-control study was used to compare the levels of cardiovascular risk factors in two groups (n = 25 each) of healthy men contrasted by their plasma total testosterone (PTT) concentration, matched by age and ethnic origin. Compared to the men with normal PTT (mean +/- SEM, 19.8 +/- 0.7 nmol/L), the men with low PTT (10.1 +/- 0.3 nmol/L) had a significantly higher body mass index (P < 0.01), waist/hip ratio (P < 0.001), systolic blood pressure (P < 0.05), fasting and 2-h plasma glucose (P < 0.04 and P < 0.02 respectively), serum triglycerides (P < 0.001), total cholesterol (P < 0.04), low density lipoprotein cholesterol (P < 0.01), apolipoprotein B (P < 0.01), fasting and 2-h plasma insulin (both P < 0.0001), and lower values of serum high density lipoprotein cholesterol (P < 0.01) and apolipoprotein AI (P < 0.05). After adjustment for both body mass index and waist/hip ratio, fasting and 2-h plasma insulin and triglyceride levels remained significantly different between the two groups (P < 0.04, P < 0.001, and P < 0.03 respectively). Plasma sex hormone-binding globulin was markedly decreased in the low PTT group (P < 0.0001), whereas bioavailable testosterone was not significantly different. This case-control study provides further and stronger evidence of a negative association between PTT and plasma insulin in men, as suggested by cross-sectional studies. Because these are observational data, neither causality nor the direction of the associations among PTT, sex hormone-binding globulin, and insulin sensitivity can be determined. Intervention studies are needed to better assess the metabolic and cardiovascular benefits of androgen treatment that have been suggested by preliminary clinical trials.

Biological Availability↗
PubMed1997

Hepatitis B vaccination in diabetic patients. Randomized trial comparing recombinant vaccines containing and not containing pre-S2 antigen.

OBJECTIVE: To investigate the immunogenicity of two recombinant hepatitis B vaccines containing S antigen alone (Engerix B) or both S and pre-S2 antigens (GenHevac B) in diabetic patients. RESEARCH DESIGN AND METHODS: Of the adult diabetic patients, 71 (26 IDDM, 45 NIDDM) were randomized to receive Engerix B or GenHevac B at 0, 1, 2, and 12 months in a single-blind clinical trial; if the antibody to hepatitis B surface antigen (anti-HBs) titers were < 10 i.u./l at month 4, a fourth injection of vaccine was given. A positive response was defined by anti-HBs titer > or = 10 IU/l at month 13. RESULTS: The anti-HBs response rate and the titers of anti-HBs did not differ significantly between the two types of vaccine. Overall, > 90% of the patients responded at month 13. In patients vaccinated with GenHevac B, anti-pre-S2 antibodies appeared earlier than anti-HBs. The anti-HBs response tended to decrease with age (P = 0.07) and tended to be higher in IDDM patients than in NIDDM patients (P = 0.06). Metabolic control, as assessed by HbA1c level, did not influence the response rate. The presence of the HLA DQ2 allele was associated with a low response. CONCLUSIONS: A large majority of diabetic patients can be efficiently vaccinated against the hepatitis B virus using a booster dose at month 4. The choice of the vaccine (with or without pre-S2 antigen) appears to have little influence, if any, on the response rate.

Adult↗
PubMed1997

Catheter survival during long-term insulin therapy with an implanted programmable pump. The Implantable Insulin Pump Trial Study Group.

OBJECTIVE: To survey catheter complications and to analyze catheter survival during long-term intraperitoneal and intravenous insulin therapy with an implanted programmable pump with a sideport. RESEARCH DESIGN AND METHODS: Catheter occlusions were documented by measuring dynamic catheter resistance. Catheter migrations or breaks were demonstrated by X ray. When flushing the catheter with buffer solution through the sideport failed to clear the occlusion, catheters were replaced or laparoscopy was performed for the excision of fibrous tissue growth. Broken or migrated catheters were replaced. RESULTS: Occlusions were the most common catheter complications, and the majority of them (79% intraperitoneal and 84% intravenous) were cleared by flushing the catheter. Survival at 3 years was significantly higher for intraperitoneal catheters compared with intravenous catheters (60% intraperitoneal and 22% intravenous). CONCLUSIONS: Nonsurgical management of catheter occlusions contributed to extend catheter lifetime. Intraperitoneal catheters have a lower morbidity and a higher survival than intravenous catheters.

Catheters, Indwelling↗
PubMed1997

[Non-insulin-dependent diabetes in populations at risk: the Pima Indians].

Pima Indians have the highest prevalence of non-insulin-dependent diabetes mellitus reported in the world, reaching 70% in the 55-64 year age-group. Although obesity is also quite prevalent in this population, it cannot in itself be held responsible for the high frequency of the disease. Profound changes in the way of life of the Pima Indians during the past century have been associated with the emergence of diabetes. A genetic susceptibility in this population probably explains why diabetes became an "epidemic". Compared to Caucasians with similar degrees of obesity and glucose tolerance, Pima Indians are insulin-resistant. This characteristic, which is a strong predictor of diabetes, seems to be genetically determined in this population, and an active search for the gene(s) involved has started. Surprisingly, for an insulin-resistant population, cardiovascular mortality is low in Pima Indians. An understanding of the similarities and differences between diabetic Caucasians and Pima Indians is one means of advancing our knowledge of non-insulin-dependent diabetes mellitus and insulin resistance.

Diabetes Mellitus↗
PubMed1996

Relationship between prorenin, IGF-I, IGF-binding proteins and retinopathy in diabetic patients.

Plasma prorenin and renin, serum insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP-2 and IGFBP-3) concentrations were measured in 22 randomly selected male and female patients with insulin-dependent diabetes mellitus (IDDM) or non-IDDM (NIDDM). Plasma prorenin concentration was significantly elevated in patients with proliferative retinopathy (1869.5 +/- 785.0 mUL-1, mean +/- SEM) compared to patients with nonproliferative retinopathy (325.5 +/- 73.2 mUL-1, P < 0.003) and those without retinopathy (318.6 +/- 47.3 mUL-1, P < 0.007). Similarly, serum insulin-like growth factor-I (IGF-I) concentration in patients with proliferative retinopathy (126.3 +/- 21.5 micrograms L-1) was significantly higher than in patients with nonproliferative retinopathy (126.3 +/- 14.85 micrograms L-1, P < 0.004) and without retinopathy (135.2 +/- 37.26, P < 0.05). There was moderately strong positive correlation between plasma prorenin and serum IGF-I concentrations (r = 0.56, P < 0.01). Plasma prorenin concentration was uninfluenced by change in renal function (creatinine clearance, serum creatinine or BUN), but IGF-I levels were inversely related to creatinine clearance (r = 0.67, P < 0.002). There was no demonstrable relationship between IGF-binding proteins and prorenin or renin concentrations. In view of some overlap between plasma prorenin and serum IGF-I concentrations in diabetic patients with proliferative and nonproliferative retinopathy, measurement of both markers may be more useful in predicting the development of proliferative retinopathy in patients with diabetes mellitus than either measurement alone.

Adult↗