[Association of type 1 diabetes mellitus and epilepsy in children. A cohort of 10 cases]. / Association diabète de type 1et épilepsie chez l'enfant. À propos d'une série de 10 cas.

UNLABELLED: The association of type 1 diabetes mellitus (DM) and epilepsy has been previously reported. However, the physiopathology of this association remains misunderstood. OBJECTIVE: To describe epilepsy combined with type 1 DM in children. METHODS: Retrospective monocentric study of all the epileptic and type 1 diabetic children consulting at the Timone University Hospital, Marseille, France. For each patient, the type of epilepsy and its electroclinical and radiographic characteristics were studied as well as the type of diabetes (biological characteristics, glycemic control), and the onset of these 2 diseases. RESULTS: Ten patients are reported. Five suffered from generalized epilepsy (4 idiopathic, 1 nonidiopathic) and 5 from focal epilepsy (4 non-idiopathic, 1 idiopathic). For most of these cases, presence of GAD (glutamic acid decarboxylase) autoantibodies were confirmed and epilepsy followed diabetes. CONCLUSIONS: The 2 most common types of epilepsy in this association are idiopathic generalized epilepsy and non-idiopathic temporal epilepsy. Several mechanisms could be involved (immune, glycemia, and genetic disorders).

[Genetic aspects of growth hormone deficiency]. / Quelles causes génétiques rechercher en présence d'un déficit en hormone de croissance ?

Congenital growth hormone deficiency (GHD) is a rare cause of growth delay. It should be suspected when other causes of hypopituitarism (sellar tumor, postsurgical or radioinduced hypopituitarism, etc.) have been ruled out. GHD can be isolated (IGHD) or associated with at least one other pituitary hormone deficiency (CPHD) including thyrotroph, lactotroph, corticotroph, or gonadotroph deficiencies. CPHD is caused by mutations of genes coding for pituitary transcription factors involved in pituitary ontogenesis or in the hypothalamic-pituitary axis. Clinical presentation varies, depending on the type and severity of GHD, the age at diagnosis, the association with other pituitary hormone deficiencies, or extrapituitary malformations. Clinical, biological, and radiological work-up is very important to determine for which transcription factor the patient should be screened. There is a wide variety of phenotypes depending on the transcription factor involved: PROP1 (somatolactotroph, thyrotroph, gonadotroph, and sometimes corticotroph deficiencies ; pituitary hyper- or hypoplasia), POU1F1 (somatolactotroph and thyrotroph deficiencies, pituitary hypoplasia), HESX1 (variable pituitary deficiencies, septo-optic dysplasia), and less frequently LHX3 (somatolactotroph, thyrotroph, and gonadotroph deficiencies, deafness, and limited head and neck rotation), LHX4 (variable pituitary deficiencies, ectopic neurohypophysis, cerebral abnormalities), and OTX2 (variable pituitary deficiencies, ectopic neurohypophysis, ocular abnormalities). Mutations of PROP1 remain the first identified cause of CPHD, and as a consequence the first to be sought. POU1F1 mutations should be looked for in the postpubertal population presenting with GH/TSH deficiencies and no extrapituitary malformations. Once genetic diagnosis has been concluded, a strict follow-up is necessary because patients can develop new deficiencies (for example, late-onset corticotroph deficiency in patients with PROP1 mutations). Identification of gene defects allows early treatment of pituitary deficiency and prevention of their potentially lethal consequences. If untreated, the main symptoms include short stature, cognitive alterations, or delayed puberty. An appropriate replacement of hormone deficiencies is therefore required. Depending on the type of transmission (recessive transmission for PROP1 and LHX3, dominant for LHX4, autosomal dominant or recessive for POU1F1 and HESX1), genetic counseling might be proposed. Genotyping appears highly beneficial at an individual and familial level.

[Value of continuous glucose monitoring in screening for diabetes in cystic fibrosis]. / Holter glycémique et dépistage du diabète chez l'enfant atteint de mucoviscidose.

AIMS: In the past few years, survival has increased for people with cystic fibrosis (CF). Diabetes is an important complication of CF caused by pancreatic insufficiency, which reduces insulin secretion. Because of increased longevity of patients with CF, the prevalence of CF-related diabetes (CFRD) has increased. CFRD is associated with increased mortality and morbidity. Several studies have reported a decline in nutritional and pulmonary status 2-4 years before the diagnosis of CFRD. The introduction of insulin treatment can produce clinical improvement in weight and lung function. The oral glucose tolerance test is currently the reference method in screening for CFRD, but the current definition of diabetes based on the 2-h post-load plasma glucose level may not be the most accurate method for early detection of glucose tolerance abnormalities in CF. The continuous glucose monitoring system (CGMS) has been described as a useful tool for early detection of hyperglycemia in the CF patient. We tested the CGMS in CF patients with unexplained alteration of their general status. The aim of this study was to assess the value of the CGMS in this population. METHODS: An annual OGTT (following World Health Organization recommendations) was conducted as a screening test to identify CFRD in patients aged over 10 years or patients aged under 10 years with a poorer clinical status. The CGMS was performed in patients with unexplained worsened clinical status and without diabetes in OGTT. RESULTS: Forty-two patients aged from 8.5 to 19 years were screened using OGTT for CFRD. According to ADA criteria, 23 patients (54.8%) displayed normal glucose tolerance, 14 (33.3%) impaired glucose tolerance, and 5 diabetes (11.9%). Out of 37 nondiabetic, the CGMS was used in 20 patients with unexplained altered general status. The CGMS revealed peaks of glucose values greater than 2 g/L in 16 patients, 9 patients with normal glucose tolerance, and 7 patients with impaired glucose tolerance. The mean CGMS glucose and time of glycemic monitoring above 1.4 g/L increased in patients with peaks greater than 2 g/L compared to patients without peaks (p=0.0016 and p=0.0069 respectively). After analysis of the CGMS, the prevalence of diabetes increased from 11.9 to 50%. Three patients aged less than 10 years with a normal OGTT profile presented glycemic peaks greater than 2 g/L during CGMS. CONCLUSION: CGMS revealed more glucose metabolism abnormalities than OGTT in patients with unexplained altered general status.

C-Peptide effects on renal physiology and diabetes.

The C-peptide of proinsulin is important for the biosynthesis of insulin and has for a long time been considered to be biologically inert. Animal studies have shown that some of the renal effects of the C-peptide may in part be explained by its ability to stimulate the Na,K-ATPase activity. Precisely, the C-peptide reduces diabetes-induced glomerular hyperfiltration both in animals and humans, therefore, resulting in regression of fibrosis. The tubular function is also concerned as diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with the reduction of the diabetes-induced glomerular hyperfiltration. The tubular effectors of C-peptide were considered to be tubule transporters, but recent studies have shown that biochemical pathways involving cellular kinases and inflammatory pathways may also be important. The matter theory concerning the C-peptide effects is a metabolic one involving the effects of the C-peptide on lipidic metabolic status. This review concentrates on the most convincing data which indicate that the C-peptide is a biologically active hormone for renal physiology.