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Biomedical subjects

C Levy-Marchal

Publications and source records attributed to C Levy-Marchal.

At least 19 recordsLinked to original sources
PubMed2001

Relatively low serum leptin levels in adults born with intra-uterine growth retardation.

BACKGROUND: In-utero under-nutrition dramatically alters the development of adipose tissue, during the fetal and the neonatal period. THE AIM OF THE STUDY: To investigate whether adults born with intra-uterine growth retardation (IUGR) show evidence of impaired adipose tissue development and leptin regulation. DESIGN: Serum leptin concentrations were measured in 26 healthy adults born with IUGR and 25 controls aged 24 y who have been studied previously, 3 y ago. RESULTS: The IUGR group demonstrated a significant increase of body mass index (BMI) in comparison to controls between 21 and 24 y of age (4.8+/-7.7%, P=0.004 vs 0.8+/-6.7%, P=0.70). Percentage of total body fat mass was significantly higher in IUGR-born subjects than in controls (27.2+/-7.6 vs 22.0+/-7.3%, P=0.02). Fasting insulin was significantly higher in the IUGR group (7.5+/-3.8 vs 5.3+/-2.3 miccroU/ml, P=0.03). Surprisingly, crude serum leptin concentrations did not significantly differ between the two groups. Moreover, adjusted means of serum leptin levels were significantly lower in IUGR-born subjects than in controls when corrected for body fat mass, gender and fasting insulin (11.3 vs 13.8 ng/ml, P=0.02). SUMMARY: Adults born with IUGR developed an excess of adipose tissue associated with relatively low serum leptin levels suggestive of an altered adipocyte function. Considering the close relationship between adipose tissue and insulin-sensitivity, these observations point to the potential implication of abnormal adipose tissue development in the long-term metabolic consequences associated with in-utero undernutrition.

Adipocytes↗
PubMed2001

Impaired regulation of glucose transporter 4 gene expression in insulin resistance associated with in utero undernutrition.

The aim of this study was to investigate whether insulin resistance-associated in utero undernutrition was related to changes in insulin action on gene expression of molecules involved in the insulin signaling pathway and peripheral glucose metabolism in muscle and adipose tissue. Thirteen insulin-resistant subjects born with intrauterine growth retardation (IUGR) were matched for age, gender, and body mass index to 13 controls. Gene expression of insulin receptor, insulin receptor substrate-1, p85alpha phosphatidylinositol 3-kinase, glucose transporter-4 (GLUT4), hexokinase II, and glycogen synthase was studied in skeletal muscle at baseline and after a 3-h euglycemic insulin stimulation. Target messenger ribonucleic acid (mRNA) levels were quantified using the RT-competitive PCR method. Insulin-stimulated glucose uptake was significantly lower in IUGR-born subjects than in controls (36.9 +/- 12, 7 vs. 53.9 +/- 12.7 micromol/kg.min; P = 0.007), affecting both the glucose oxidation rate and the nonoxidative glucose disposal rate. At baseline, the expression of the six genes in muscle did not significantly differ between the two groups. The insulin-induced changes over baseline were comparable in both groups for all mRNAs, except GLUT4. In contrast to what observed in the control group (mean increment, 49 +/- 23%; P = 0.0009), GLUT4 expression was not stimulated by insulin in the IUGR group (8 +/- 8%; P = 0.42). Moreover, the magnitude of the defect in GLUT4 mRNA regulation by insulin was correlated to the degree of insulin resistance (r = 0.73; P = 0.01). A similar lack of significant GLUT4 mRNA stimulation by insulin was observed in the adipose tissue of IUGR-born subjects. In conclusion, insulin resistance in IUGR-born subjects is associated with an impaired regulation of GLUT4 expression by insulin in muscle and adipose tissue. Our data provide additional information about the mechanism of insulin resistance associated with in utero undernutrition and strengthen the role of glucose transport in the control of insulin sensitivity.

Adipose Tissue↗
PubMed2001

beta Cell autoimmunity in a child with M.O.D.Y. (Maturity Onset Diabetes in the Young).

We present the case of a well characterised M.O.D.Y. type 2 diabetes family in which one of the children associated beta cell autoimmunity and a HLA DQB1 at risk for immune-mediated type 1 diabetes mellitus. The search for autoantibodies against beta cell should be considered in cases of genetically defined form of diabetes mellitus to exclude the possibility of a concomitant risk to develop type 1 diabetes mellitus.

Autoantibodies↗
PubMed2001

Emergence of type 2 diabetes in an hospital based cohort of children with diabetes mellitus.

OBJECTIVES: Increasing awareness of the heterogeneity of diabetes mellitus (DM) at presentation is changing our approach to this disease. We used the 1999 American Diabetes Association (ADA) criteria to determine the distribution of DM patterns in a large pediatric cohort with the aim of documenting the emergence of type 2 diabetes mellitus. MATERIAL AND METHODS: Charts of diabetic children aged 1 to 16 years and admitted to our center between 1993 and 1998 were reviewed for data needed to achieve classification of the type of diabetes mellitus. RESULTS: Of the 382 study patients, 327 (85.6%) had autoimmune type 1 DM (clinical insulin-treated type 1 DM with immunologic and/or genetic evidence of autoimmunity) and 6 (1.6%) had idiopathic type 1 DM (clinical insulin-treated type 1 DM without evidence of autoimmunity). Four (1.0%) patients met all the criteria for type 2 DM; all were obese and three had acanthosis nigricans; in one the diagnosis was changed from type 1 to type 2 DM during follow-up. Four patients could be classified as lean patients with type 2 DM. In keeping with recent reports of a rise in the incidence of type 2 DM, 6 of these type 2 cases were diagnosed in the last year of the study. CONCLUSION: The ADA classification helps to understand the pathophysiology of pediatric DM, thus providing useful therapeutic guidance. At presentation, most cases of pediatric DM are type 1, but we show here that type 2 DM becomes now a diagnosis to consider although in children. Our study, from a one large study center is not an epidemiological one but is consistent with population studies. Systematic or targeted screening for type 2 in children should be discussed.

Adolescent↗
PubMed2001

Effects of clinical audit on the quality of care in patients with type 2 diabetes: results of the DIABEST pilot study.

OBJECTIVE: To improve the quality of diabetes care in general practice by the use of audit. MATERIAL AND METHODS: A prospective multicenter pilot study. Thirty-five groups of ten general practitioners (GPs) have been set up throughout France on a voluntary basis. These groups were led by a steering committee that includes a diabetologist and a GP. Each group established a consensus on healthcare standards and carried out 2 data collections over a 12-month period, with adoption of corrective measures between these 2 collections. RESULTS: 309 (90.4%) of the 342 practitioners completed the first data collection, assessing the management of 3,125 patients over a year. Less than half the groups have reached the 80% reference threshold for quality of care with regard to foot examination, microalbuminuria, ECG, fundoscopy and assessment of diet. The audit also found no intervention within one year in case of poor glucose control for 47% of patients, unsatisfactory quality of HbA(1c) measurement and insufficient resources for diet and education. 226 (66.1%) practitioners completed the second data collection assessing the management of 2,248 patients. Comparison between the two phases of the audit showed significant improvements for all the indicators of the process of care (p<0.001). Quality of HbA(1c) measurement and diet assessment by GPs progressed (p<0.01). Outcomes of care also improved with respect to the proportion of patients with HbA(1c)<=8% (p=0.007), fasting glycaemia<1.40 g/l (p=0.05) and SBP<140 mmHg (p=0.02). CONCLUSIONS: This pilot study confirms the feasibility of using clinical audit at the national level. It seems to be an effective measure to improve the management of patients with type 2 diabetes in primary care. It is intended that the large-scale DIABEST study will address this issue.

Albuminuria↗
PubMed2000

No evidence for a major beta-cell dysfunction in young adults born with intra-uterine growth retardation.

The association between low birth weight and the later development of type 2 diabetes is well established. It has been hypothesized that in utero undernutrition may affect pancreatic beta-cell development, leading to an impaired beta-cell function in adulthood. We have previously demonstrated that intrauterine growth retardation (IUGR) is associated with insulin-resistance early in adulthood. The aim of this study was to test whether IUGR would affect beta-cell function in young adults. Twelve 25-yr-old insulin-resistant subjects with IUGR were matched for age gender and body mass index (BMI) to 13 controls. All of them had normal glucose tolerance. Mean fasting plasma glucose did not significantly differ between the group with IUGR and the control group (97 +/- 7 vs. 98 +/- 4 mg/dL; p = 0.83). Blood glucose was maintained at 124.8 +/- 6.5 vs. 126.2 +/- 7.5 mg/dL above the basal glycemia in the IUGR and control groups (p = 0.64) throughout the hyperglycemic clamp. Serum insulin concentrations did not significantly differ between the group with IUGR and the control group either during the first (0-10 min) phase (311 +/- 252 vs. 248 +/- 184 pmol/L, p = 0.85) or during the second (80-100 min) phase (575 +/- 284 vs. 559 +/- 413 pmol/L, p = 0.72). C-peptide concentrations were similar in both groups during the two phases (2.35 +/- 1.44 vs. 2.59 +/- 1.10 nmol/L, p = 0.39 and 4.86 +/- 1.36 vs. 4.96 +/- 1.41 nmol/L, p = 0.91). In conclusion, our data do not argue in favor of an impairment of beta-cell function at 25 yr of age as a consequence of in utero undernutrition, but rather suggest that insulin resistance might be the primary defect responsible for the development of metabolic disorders associated with IUGR in adulthood.

Journal Article↗
PubMed2000

Insulin resistance early in adulthood in subjects born with intrauterine growth retardation.

In a case-control study that investigated the effect of intrauterine growth retardation (IUGR) on glucose homeostasis, 20-yr-old adults born with IUGR were shown to be hyperinsulinemic in an oral glucose tolerance test, suggestive of insulin resistance. The aim of this study was to ascertain the decreased insulin sensitivity in young IUGR-born adults compared to that in controls. We studied 26 IUGR-born subjects and 25 controls, aged 25 yr. Insulin sensitivity was assessed by peripheral glucose uptake and monitoring free fatty acid (FFA) concentrations under euglycemic hyperinsulinemic clamp. The percent body fat was significantly higher in the IUGR group (27.2 +/- 7.6% vs. 22.0 +/- 7.3%; P = 0.02), contrasting with comparable body mass index in both groups. Insulin-stimulated glucose uptake was significantly lower in IUGR-born subjects than in controls (6.7 +/- 2.9 vs. 8.0 +/- 1.9 mg/kg fat-free mass x min; P = 0.05), and the difference remained significant after adjustment for body mass index, total body fat, or waist to hip ratio. In IUGR-born subjects, insulin-stimulated FFA suppression correlated significantly with peripheral glucose uptake (r2 = 0.23; P = 0.02). First phase insulin release in the iv glucose tolerance test, adjusted for insulin sensitivity, did not significantly differ between IUGR and control groups (442 +/- 284 vs. 391 +/- 209 pmol/L; P = 0.86). In conclusion, IUGR subjects have decreased insulin-stimulated glucose uptake as early as 25 yr of age without major impairment of insulin secretion. Low glucose uptake is associated with a lesser degree of FFA suppression in adipose tissue, which suggests a role of adipose tissue at an early stage of insulin resistance in these subjects.

Adult↗
PubMed1999

Intrauterine growth retardation predisposes to insulin resistance but not to hyperandrogenism in young women.

It was recently suggested that precocious pubarche associated with subsequent functional ovarian hyperandrogenism and hyperinsulinemia could have a common origin in reduced fetal growth. We previously reported that young women born with intrauterine growth retardation (IUGR: birth weight less than the third percentile) were hyperinsulinemic and less insulin sensitive than women born with normal birth weight. The aim of the present study was to investigate whether these IUGR-born women demonstrated hyperandrogenism compared with controls. Our study population was composed of 130 IUGR-born women and 150 controls, of similar age (20.6 +/- 3.2 vs. 20.4 +/- 2.0 yr). Hormonal contraception in terms of frequency and medication, including antiandrogenic therapy, was identical in the 2 groups. After adjustment for hormonal contraception, being born with IUGR had no independent effect on serum androgen concentrations. In women who were not receiving hormonal contraception, no statistical differences were found between IUGR-born women (n = 67) and controls (n = 64) for delta4-androstenedione (2.26 +/- 0.68 vs. 2.24 +/- 0.55 ng/mL; P = 0.76), dehydroepiandrosterone sulfate (2294 +/- 1117 vs. 2489 +/- 1235 ng/mL; P = 0.24), testosterone (0.82 +/- 0.85 vs. 0.70 +/- 0.26 ng/mL; P = 0.80), or serum sex hormone-binding protein concentrations (45.5 +/- 28.2 vs. 53.1 +/- 30.3 nmol/L; P = 0.27). In both IUGR and control groups, sex hormone-binding protein correlated negatively with fasting insulin (r = -0.23; P = 0.03 and r = -0.26; P = 0.05), but serum androgen levels did not correlate with insulin. In summary, hyperinsulinemia observed in young women born with IUGR is not associated with hyperandrogenism. Consequently, our results do not support the hypothesis of a common in utero programming of hyperandrogenism and hyperinsulinemia.

Adolescent↗
PubMed1999

High serum leptin concentrations during catch-up growth of children born with intrauterine growth retardation.

The aim of the study was to investigate how leptin could be involved in catch-up growth of children born with intrauterine growth retardation (IUGR). The study population was made up of 70 newborns with IUGR longitudinally studied during the first 2 yr of life and 35 newborns and 32, 66, and 61 children with normal birth weight aged 3 days, 12 months, and 24 months, respectively. Postnatal patterns of body mass index (BMI) were similar in the 2 groups, but BMI remained significantly lower in IUGR over the study period. In contrast, children born with IUGR aged 1 yr had significantly higher serum leptin levels than normal children (P < 0.0001) independently of BMI. The correlation observed between BMI and serum leptin at birth in both groups and in the control group thereafter disappeared in children born with IUGR. Similarly, sexual dimorphism observed in normal children over the study period was not observed in the IUGR group during the first 2 yr of life. In summary, serum leptin is effective and regulated during the first years of life as it is in older children. Children born with IUGR demonstrate high serum leptin values during the first year of life, with a loss of the regulatory effect of BMI and gender. We suggest that these children develop an adaptative leptin resistance beneficial for their catch-up growth. An alternative hypothesis is that these observations could reflect an adipocyte dysfunction, a consequence of the special time course of adipose tissue development in children born with IUGR.

Aging↗
PubMed1998

Ontogeny of leptin in human fetuses and newborns: effect of intrauterine growth retardation on serum leptin concentrations.

The aim of this study was to investigate the ontogeny of serum leptin concentrations during the second half of gestation and at birth in small for gestational age and normal fetuses and newborns. Serum leptin concentrations were measured in arterial cord blood of fetuses (n = 79) and newborns (n = 132), with or without intrauterine growth retardation, at 18-42 weeks gestation. Serum leptin was detectable in fetal cord blood in all subjects as early as 18 weeks gestation. Leptin levels dramatically increased after 34 weeks gestation. In newborns, serum leptin concentrations were positively correlated with body weight (P < 0.001) and body mass index (P < 0.001). Newborns with intrauterine growth retardation had significantly lower serum leptin values (P < 0.001) than those with normal growth, and leptin levels were only positively correlated with body mass index (P < 0.001). These results suggest that the development of adipose tissue and the accumulation of fat mass are the major determinants of fetal and neonatal serum leptin levels. In addition, a gender difference, with higher leptin concentrations in female fetuses, was observed during the last weeks of gestation and was confirmed at birth regardless of growth status, suggesting that a sexual dimorphism already exists in utero.

Adolescent↗
PubMed1998

Appraisal and implications of predictive testing for insulin-dependent diabetes mellitus.

The risk of developing insulin-dependent diabetes mellitus (IDDM) is 50 times greater in first-degree relatives than in the general population. Although parents of a diabetic child are generally aware of the risk of disease recurrence in the family, the practice of screening for IDDM is often questioned by physicians themselves because of the likelihood that parents will experience anxiety. This paper reports the results of a questionnaire distributed to parents attending a pediatric clinic for their diabetic child who were asked to evaluate their attitudes about screening tests. One hundred and thirty-one families recruited over a 2-month period replied to the questionnaire without the assistance of medical staff. The mean age of diabetic children was 10 +/- 4.05 years, and the duration of IDDM 3 +/- 3.6 years. The results show that parents were stressed by the possible development of a second case of IDDM among their children. Eighty percent of them practised home strip--analysis on a regular basis for all their children. The parents wanted biological tests to be performed on their children before the occurrence of any clinical symptoms. They expected the screening tests "to reveal the truth about the health status of their children" (92%) and to "help prepare for an uncertain future" (60%). They indicated that recognition of an increased risk would not change their attitude toward their child. Recurrence of the disease was regarded as a problem with which the parents could cope realistically. Our data indicate that parents should continue to be informed about familial risk and the possibility of screening, despite the lack of preventive treatment.

Child↗
PubMed1997

Reduced final height and indications for insulin resistance in 20 year olds born small for gestational age: regional cohort study.

OBJECTIVE: To investigate whether the association between low birth weight and increased risk of developing impaired glucose tolerance, insulin resistance, hypertriglyceridaemia, and hypertension in middle age is apparent by the age of 20 in people born small for gestational age. DESIGN: Regional cohort study. SETTING: Maternity registry, Haguenau, France. SUBJECTS: 236 full term singleton babies born small for gestational age (birth weight or length, or both, below third centile) during 1971-8 and 281 with normal birth weight (between 25th and 75th centile). All subjects were contacted and evaluated at a mean (SD) age of 20.6 (2.1) years. MAIN OUTCOME MEASURES: Adult height; concentrations of glucose, insulin, and proinsulin during an oral glucose tolerance test; lipid and fibrinogen concentrations; and blood pressure. RESULTS: After sex and target height were adjusted for, subjects who had been born small for gestational age were significantly shorter at age 20 than those with a normal birth weight (men 4.5 cm shorter (95% confidence interval 6.0 to 3.0 cm); women 3.94 cm shorter (5.2 to 2.7 cm)). After sex and body mass index were adjusted for, mean plasma glucose concentration 30 minutes after a glucose load, fasting insulin concentration (in women), and insulin and proinsulin concentrations 30 and 120 minutes after a glucose load were significantly higher in subjects who had been born small for gestational age than in those with a normal birth weight. Mean lipid and fibrinogen concentrations and blood pressure were not different between the two groups. CONCLUSIONS: Intrauterine growth retardation has long term consequences such as reduced final height Raised insulin and proinsulin concentrations are present in young adults born small for gestational age and could be markers of early changes in insulin sensitivity.

Adolescent↗
PubMed1997

[Clinical diagnosis of childhood insulin dependent diabetes mellitus. Hungarian Epidemiological Group for Childhood Diabetes].

The aim of this study was to describe the clinical presentation and severity of the disease at onset in childhood during 1994. Based on the prospective national incidence registry, data were collected (using a modified version of the EURODIAB ACE questionnaire) from all diabetic children diagnosed during a full calendar year (1994). The ascertainment was 91%. Polyuria, polydipsia and weight loss were the most frequent clinical symptoms, but fatigue, abdominal pain and personality changes were also often reported. Almost one quarter of the children presented with diabetic ketoacidosis. There was no correlation between age, duration of symptoms, blood glucose levels and the severity of disease. The unacceptably high incidence of presentation ketoacidosis called for an urgent improvement of the diagnostic acumen of the physicians dealing with children.

Age Factors↗
PubMed1997

Sensitivity at diagnosis of combined beta-cell autoantibodies in insulin-dependent diabetic children. French Registry of IDDM in Children Study Group.

The purpose of this study was to test for the presence (alone or in combination) of 4 autoantibodies directed against beta cells in the sera of children at diagnosis of the overt clinical phase of insulin-dependent diabetes mellitus. Children recorded in 1989 in the population-based French Registry of Incidence of Insulin-Dependent Diabetes Mellitus were included in the present study. One hundred and thirty-eight sera were tested for islet cell antibodies (ICA), insulin autoantibodies (IAA) and antibodies against glutamic acid decarboxylase (GAD-Ab) and tyrosine phosphatase (IA2-Ab). IAA showed significantly lower sensitivity (36%) than the other antibodies (ICA: 84%; GAD-Ab: 74%; IA2-Ab: 81%). In the age-range of the registry, the prevalence rates for the 4 antibodies were not significantly affected by age. IAA and GAD-Ab were significantly associated with ICA, whereas GAD-Ab and/or IA2-Ab was(were) associated with 93% sensitivity at diagnosis. Sensitivity was 100% with the 4 antibodies combined. No significant association was found between the antibodies and HLA DR phenotypes. This study shows that a combination of the 4 major autoantibodies allows all children with insulin-dependent diabetes to be identified.

Adolescent↗
PubMed1995

Anti-37kDa antibodies are associated with the development of IDDM in individuals with islet cell antibodies.

Antibodies directed against a beta-cell specific antigen with a molecular weight of 37 kDa have recently been described. These anti-37kDa antibodies were measured by the immunoprecipitation technique in individuals at risk for insulin-dependent diabetes mellitus (IDDM), with islet cell antibodies (ICA) greater than 20 Juvenile Diabetes Foundation units (JDFU). These subjects were recruited from large population-based cohorts at various degrees of risk for developing the disease before adulthood. Anti-37kDa antibodies were measured in 25 ICA-positive first degree relatives with ICA greater than 20 JDFU, identified from a baseline cohort of 1,185 relatives (age: 0-75 years). Four relatives were positive for anti-37kDa antibodies since the first determination onwards. These relatives developed IDDM in a 2-year follow-up period. We included 300 children with an IDDM parent, and aged less than 7 years, in a prospective survey for the prediction of IDDM. Five (1.6%) showed ICA greater than 20 JDFU. None of them were found to be positive for anti-37kDa antibodies, and none have progressed to diabetes during a 2-year follow-up. Among a baseline cohort of 13,380 schoolchildren (age: 6-17 years), 28 (0.2%) were found to have ICA greater than 20 JDFU. One boy was positive for anti-37kDa antibodies on two consecutive occasions and developed IDDM after a 10-month follow-up. No other schoolchildren with ICA greater than 20 JDFU were found to be positive for anti-37kDa antibodies. Altogether 40 other ICA-positive sera (with titres < 20 JDFU) were found to be negative for anti-37kDa antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Multiple DNA variant association analysis: application to the insulin gene region in type I diabetes.

Association and linkage studies have shown that at least one of the genetic factors involved in susceptibility to insulin-dependent diabetes mellitus (IDDM) is contained within a 4.1-kb region of the insulin gene. Sequence analysis has led to the identification of 10 DNA variants in this region that are associated with increased risk for IDDM. These variants are in strong linkage disequilibrium with each other, and previous studies have failed to distinguish between the variant(s) that cause increased susceptibility to IDDM and others that are associated with the disease because of linkage disequilibrium. To address this problem, we have undertaken a large population study of French diabetics and controls and have analyzed genotype patterns for several of the variant sites simultaneously. This has led to the identification of a subset consisting of four variants (-2733AC, -23HphI, -365VNTR, and +1140AC), at least one of which appears to be directly implicated in disease susceptibility. The multiple-DNA-variant association-analysis approach that is applied here to the problem of identifying potential susceptibility variants in IDDM is likely to be important in studies of many other multifactorial diseases.

Diabetes Mellitus, Type 1↗