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C Levy-Marchal

Publications and source records attributed to C Levy-Marchal.

At least 37 records · Page 2Linked to original sources

[Risk markers of insulin-dependent diabetes in the normal population].

Risk factors for IDD have been studied in relatives of patients, in whom the risk is far higher than in the children from the background population. Several factors have been identified as the genetic background at the HLA level (DR and DQ regions) and autoantibodies like islet cells antibodies (ICA) and insulin autoantibodies (IAA). 8,363 sera from schoolchildren (age 6-17 yr) have been tested for the presence of ICA. 150 sera (1.8%) were found positive; the prevalence rate of high ICA titres (> or = 20 uJDF) was very low: 0.2%. ICA titres remained stable over a 8 mth follow-up period. IAA have been measured on the first 2,000 sera and the prevalence rate was 1.2%. Only 3 sera were found positive for the two antibodies, one coming from a diabetic girl. The distribution of the susceptibility alleles at the DQ-HLA region was similar among the ICA-positive and ICA-negative children.

Adolescent↗

Superiority of radiobinding assay over ELISA for detection of IAAs in newly diagnosed type I diabetic children.

OBJECTIVE: Liquid- or solid-phase assays have been used for insulin autoantibody (IAA) determination, and the method of IAA measurement has not been standardized. RESEARCH DESIGN AND METHODS: IAAs were determined by radiobinding assay (RBA) and enzyme-linked immunosorbent assay (ELISA) in two large age-matched groups of nondiabetic and newly diagnosed insulin-dependent (type I) diabetic children. RESULTS: Positivity for IAA by RBA (greater than or equal to nondiabetic mean + 3SD) was 2 of 178 (1.1%) and 55 of 173 (32%) in nondiabetic and diabetic children, respectively. Prevalence of IAA by RBA was significantly higher in the youngest age-group (63% between 0-4 yr). Positivity for IAA by ELISA was 1 of 178 (0.6%) and 8 of 169 (4.7%) in nondiabetic and diabetic children, respectively. Concordance rates between both assays were 0 of 3 (0%) in control subjects and 5 of 58 (8.6%) in diabetic children. CONCLUSIONS: We conclude that RBA is more appropriate than ELISA for IAA detection at the onset of the disease. In addition, because available data suggest that IAAs detected by RBA only are high-affinity antibodies, it is tempting to speculate that IAAs reflect a mature immune reaction against endogenous insulin.

Adolescent↗

Incidence of juvenile type 1 (insulin-dependent) diabetes mellitus in France.

The incidence rate of juvenile Type 1 (insulin-dependent) diabetes in France was reported as the lowest in Europe 13 years ago, but during the recent years increasing rates have been observed in different European countries. A prospective programme has been designed to study the incidence rate of Type 1 diabetes in patients up to 20 years of age in four regions located in the north and south of France (population less than 20 years = 2.31 million inhabitants; 15% of the French population). All cases were independently identified by four specially trained research assistants through hospital admission files, paediatricians, diabetologists and general practitioners. A specific questionnaire was filled out for each newly diagnosed case. Degree of ascertainment was 96% with the data from Sécurité Sociale, the French National Health Insurance. In 1988, 166 cases of juvenile Type 1 diabetes were identified. The incidence rate was 7.17 cases per 10(5) children (95% confidence interval = 6.1-8.2/10(5). The values were not statistically different among the four regions. Age specific incidence rates were as follows: 0-4 years = 3.8; 5-9 years = 8.0; 10-14 years = 9.7 and 15-19 years = 7.3/10(5). Sex ratio was 1.2 (male/female). These data indicate that incidence of juvenile Type 1 diabetes in France was higher in 1988 than previously reported but remains lower than in Northern Europe. This is consistent with the concept of a north to south gradient of the disease.

Adolescent↗

Glomerular function and microalbuminuria in children with insulin-dependent diabetes.

Renal function has been evaluated in 45 diabetic children (age 12.5 +/- 4 years) with a mean diabetes duration of 4.9 +/- 3.5 years. Glomerular filtration rate (GFR; inulin and creatinine clearances), renal plasma flow (RPF; PAH clearance), resting urinary albumin excretion (UAE) were measured and compared with indexes of metabolic control: Hb A1C and blood glucose values (mean, post-prandial and maximal excursion) on the same day. GFR (inulin clearance) and RPF were significantly increased in the diabetic group (171 +/- 31 and 778 +/- 172 ml/min per 1.73 m2) compared with controls (124 +/- 18 and 631 +/- 128 ml/min per 1.73 m2). Both parameters were strongly correlated (r = 0.73; P less than 0.001). Creatinine clearance was not correlated to inulin clearance. Hyperfiltration (inulin clearance above 160 ml/min per 1.73 m2) was noted in 61% of the patients and was independent of diabetes duration. Five diabetic children had a UAE level above 15 micrograms/min. No relationship could be established between UAE and any of the metabolic indexes; GFR was weakly correlated to HbA1C (r = 0.35; P less than 0.05), to mean (r = 0.37; P less than 0.05) and post-prandial blood glucose (r = 0.37; P less than 0.05). In contrast, there was a strong correlation between GFR and the maximal blood excursion (r = 0.62; P less than 0.001). The study shows that renal abnormalities can be detected with a high frequency in diabetic subjects characterized by both an early onset and a short duration of diabetes and suggests the need for a more systematic evaluation of renal parameters in this population.

Adolescent↗

Enalapril does not alter renal function in normotensive, normoalbuminuric, hyperfiltering type 1 (insulin-dependent) diabetic children.

Using a prospective randomised double-blind crossover design, the effect of the angiotensin converting enzyme inhibitor enalapril compared to a placebo was studied in 18 normotensive, normoalbuminuric Type 1 (insulin-dependent) diabetic children. Each patient had a high normal or clearly elevated glomerular filtration rate (145 ml.min-1.1.73 m2 or higher) in the 6 months prior to the study. Enalapril, 0.5 mg.kg-1.day-1, was given for 4 weeks followed by placebo for 4 weeks, or vice versa. At the end of each period, glomerular filtration rate, renal plasma flow, blood pressure, plasma renin activity, and converting enzyme activity were determined. Enalapril caused significant reduction (p = less than 0.001) in blood pressure and converting enzyme activity and a rise in plasma renin activity. A slight but not significant rise in glomerular filtration rate and renal plasma flow without change in filtration fraction was observed. These data suggest that the renin angiotensin system is not involved in the glomerular hyperfiltration of Type 1 diabetes, and can be interpreted as showing no evidence for the presence of intraglomerular hypertension in these patients.

Adolescent↗

Long term feasibility of multiple daily injections with insulin pens in children and adolescents with diabetes.

During a period of 17 months, 15 C-peptide negative insulin-dependent diabetic children (14 +/- 4 years old) have used an injector pen (Novopen, Novo, France) to deliver soluble insulin before meals, in association with an insulin syringe for long-acting insulin administration at bedtime. Despite frequent daily insulin injections (4-5) and blood glucose determinations (3-4), long-term patient acceptability as well as cutaneous tolerance were excellent. Novopen was experienced as a progress (100%) which made a multiple injection regimen acceptable and provided an improvement in the quality of life (77%), as recorded by questionnaires answered at the end of the study. Twelve out of 15 patients chose to continue this treatment. No significant change in glycaemic control was observed in the group as a whole. An improvement in glycosylated haemoglobin (HbA 1c) was noticed only in the previously "poorly-controlled" children (n = 8) with initial HbA1c greater than 7%. In this group HbA1c decreased from 8.4 +/- 1.8% (mean +/- SD), to 7.3 +/- 1.2% (P less than 0.05) within the first 6 months of Novopen therapy. No increment of hypoglycaemia frequency and mean daily insulin requirements was observed. No ketoacidotic episode was noticed during the study. In conclusion, in this group of diabetic children, no long term metabolic improvement was obtained, despite excellent acceptability of the multiple injection regimen with Novopen.

Adolescent↗

Persisting glomerular hyperfiltration in short-term diabetic children without microalbuminuria.

The renal function in a group of diabetic children (n=29;age;4-17 yr; IDDM duration: 1,5-13 yr) was studied with a 3 year interval. At the first evaluation glomerular filtration rate (GFR) as assessed by inulin clearance was significantly increased compared to control values (167 +/- 32 vs. 124 +/- 18 ml/min/1.73 m2; pl less than 0.01). Eighteen out of 29 children exhibited a glomerular hyperfiltration (GFR greater than 160). Three years later mean GFR was identical (169 +/- 25 ml/min/1.73 m2) and 16 children were hyperfiltrating. Among them, 11 have had a persisting glomerular hyperfiltration over the 3-year period. Renal plasma flow (RPF) was positively correlated to GFR (r=0.7; p less than 0.01) and remained elevated at both evaluations (794 +/- 163 and 812 +/- 157 ml/min/1.73 m2, p greater than 0.01 vs, control values). When the children were separated into 3 groups according to IDDM duration no significant differences were observed in the results for GFR and RPF, Mean urinary albumin excretion was comparable at the 3-year interval, and not significantly different from the control values (5.2 +/- 3.7 and 8.2 +/- 6.6 respectively vs. 8.65 +/- 4 microgram/min). None of the children demonstrated a persistent microalbuminuria. This study reveals a high proportion of diabetic children with a persisting glomerular hyperfiltration, without any other symptom of incipiens nephropathy, If elevated GFR plays an important role in the development of diabetic nephropathy, this study emphasizes the value of regular evaluation of renal function in diabetic children.

Adolescent↗

[Analysis of diabetic microangiopathy using retinal angiography in 82 children].

Between 1979 and 1983, 116 retinal fluorescein angiographies were performed in 82 insulin-dependent diabetic children aged from 8 to 19 years. Abnormalities were observed in 7% of children with diabetes of less than 5 years duration. Retinal lesions were present in 30% of children with disease of 5-60 years duration. Most of the lesions encountered were capillary dilatations, fluorescein leakages and microaneurysms. The incidence and severity of these lesions increased with the duration of diabetes. Most of them, even of early onset, proved irreversible. It is therefore important to monitor their development by frequent angiographies (every 2 years) and to initiate an intensive treatment of diabetic children from the onset of the disease.

Adolescent↗

Biochemical evidence for presynaptic and postsynaptic alpha-adrenoceptors in rat heart membranes: positive homotropic cooperativity of presynaptic binding.

In crude rat cardiac membrane preparations, [3H]dihydroergocryptine (3H-DHE) appears to bind to two classes of sites with limited capacity, differing in their specificities and their affinities. The first class of binding sites interacts preferentially with the postsynaptic alpha-adrenoceptor blocker ARC239, as can be expected for postsynaptic alpha-adrenoceptors. The binding of 3H-DHE to these receptors follows the law of mass action, with a high affinity for 3H-DHE (Kd 25 degrees C = 1.67 +/- 0.37 nM). Postsynaptic saturating levels of 3H-DHE are necessary to occupy the second class of binding sites. These sites exhibit a preferential affinity for presynaptic ligands such as clonidine and yohimbine, as would be expected for presynaptic alpha-adrenergic receptors. This presynaptic binding shows a markedly positive homotropic cooperativity (Hill n = 2.88) with initial and final apparent Kds of 23 and 0.83 nM, respectively. Free energy of interaction between sites is of the order of 2 kcal (8.36 kJ)/mol of sites. These characteristics provide a rational molecular basis for the functional role of presynaptic alpha-adrenoceptors that mediate the inhibition of norepinephrine release from nerve endings.

Allosteric Regulation↗

Overnight metabolic control with pulsed intermittent versus continuous subcutaneous insulin infusion.

Subcutaneous insulin pumps deliver insulin both as a premeal bolus and as a continuous basal rate. It has been shown that the effect of the basal component is primarily to maintain normoglycemia overnight, but it is not known whether an intermittent pulsed infusion would achieve similar metabolic control. Six type I diabetic subjects (19-31 yr) were studied for 2 wk. Glycemic control was maintained by premeal injections of regular insulin with subcutaneous infusion overnight. A constant basal flow rate of insulin was delivered either continuously or intermittently as pulses spaced at 30-, 60-, and 120-min intervals. With each type of infusion, given in a randomized order, plasma glucose levels at 0600 h were: 81 +/- 12, 89 +/- 11, 102 +/- 14, and 94 +/- 13 mg/dl (mean +/- SEM), respectively. These values are not significantly different and remained stable until 1000 h. In addition, the hormonal responses (immunoreactive glucagon and "free" insulin levels) and metabolite levels (lactate, pyruvate, 3-hydroxybutyrate, alanine, and glycerol) were the same with continuous and pulsed insulin. These findings are in keeping with the expected kinetics for subcutaneously injected insulin. They may be of considerable interest for the design of smaller and more efficient subcutaneous insulin infusion pumps and demonstrate the wide physiologic limits for subcutaneous basal insulin replacement.

3-Hydroxybutyric Acid↗

Preprogrammed intravenous insulin infusion in diabetic humans: metabolic consequences of altering meal size.

New implantable, variable-rate, intravenous insulin infusion systems offer the possibility of increased dietary flexibility in the treatment of diabetes mellitus. However, the development of insulin infusion algorithms required to maintain near-normal glycemia in the presence of a nonconstant diet first requires information concerning the metabolic response to meals of varying size when the insulin dose is fixed. With this goal in mind, we studied five type I diabetics aged 16-40 yr who were treated for 3 wk with a portable intravenous insulin infusion system. Initially, the patient's usual prescribed diabetic diet was provided, and an individual waveform of insulin infusion resulting in diurnal normoglycemia was defined for each meal. Subsequently, small (12% of total daily calories) and large (36% of total daily calories) versions of the regular breakfast (24% of total daily calories) were provided without change in the insulin infusion waveforms, and the resulting metabolic profiles were studied. The overall mean fasting plasma glucose levels before the meals of varying size were not significantly different, but the incremental rises in plasma glucose with the small (31 +/- 5 mg/dl), regular (48 +/- 7 mg/dl), and large (64 +/- 5 mg/dl) breakfasts varied directly with the meal size. The subsequent mean plasma glucose levels before the regular lunch were significantly different (P less than .05) after the small (50 +/- 4 mg/dl) and large breakfasts (131 +/- 9 mg/dl), compared with the regular breakfast (81 +/- 7 mg/dl). Despite these differences, the plasma glucose levels before dinner were virtually identical. We conclude that large variations in meal size produce glycemic changes in keeping with the caloric content of the meal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Insulin autoantibodies and insulin-induced antibodies in children with insulin-dependent diabetes].

AIM OF THE STUDY: The aim was to study the time course of development of insulin antibodies during the first months of treatment in diabetic children, under human insulin therapy, and to see whether the presence of insulin autoantibodies influenced the subsequent binding to insulin. METHODS: Anti-insulin antibodies were measured using a radio-binding assay in 16 diabetic children, aged 4-13 years, before the first insulin injection and at regular intervals until the 9th month of treatment. RESULTS: Insulin autoantibodies were detected in 11 out of the 16 children at the time of diagnosis. Binding to insulin increased significantly after one month of treatment in these children, and after 2 months in the children with no insulin autoantibodies at diagnosis. After 2 months insulin therapy, all the children demonstrated antibodies against insulin. Insulin binding at 9 months was not correlated to the baseline values. Anti-insulin antibodies develop rapidly and frequently under human insulin, and are not influenced by the presence of insulin autoantibodies.

Adolescent↗