Polymorphism of the 5' untranslated region of NHE1 gene associated with type-I diabetes.

The ubiquitous form of the sodium-hydrogen exchanger, NHE1, is devoted to the regulation of intracellular pH and cell volume. In addition, NHE1 activity is stimulated by growth factors and increased NHE rates are found in both circulating and immortalized cells during diabetes or diabetic nephropathy. In this context, we searched for polymorphisms of the 5'-flanking regulatory region of NHE1 gene in subjects with type-I diabetes. We identified a C/T transition 696 bases upstream the translation initiation start site which disrupts a repeated palindromic GC sequence. The TT genotype was significantly more frequent in type-1 diabetics and may have functional importance. Genetic linkage between NHE1 and diabetes has been previously described in NOD mice strains with consequences on NHE rates. Hence, the polymorphism described hereby may act as a predisposition factor to type-I diabetes or to diabetic complications, and may be useful to investigate the genetic involvement of NHE1 in human pathophysiology.

Factors associated with glycemic control. A cross-sectional nationwide study in 2,579 French children with type 1 diabetes. The French Pediatric Diabetes Group.

OBJECTIVE: To determine on a large scale the multiple medical and nonmedical factors that influence glycemic control in the general population of children with diabetes, we performed a nationwide French cross-sectional study. RESEARCH DESIGN AND METHODS: We enrolled 2,579 patients aged 1-19 years with type 1 diabetes of > 1 year's duration. The study was center based: 270 centers were identified, 206 agreed to participate, and 147 included at least 90% of their patients. Questionnaires were completed by physicians interviewing patients and family, and HbA1c measurements were centralized. To identify explanatory variables for HbA1c level and frequency of severe hypoglycemia, we performed multiple regression analysis using all the quantitative variables collected and stepwise logistic regression for the qualitative variables. RESULTS: Mean HbA1c value for the whole population was 8.97 +/- 1.98% (normal 4.7 +/- 0.7% [SD]). Only 19 children (0.7%) had ketoacidosis during the 6 months before the study, whereas 593 severe hypoglycemia events occurred in 338 children (13.8%). Control was better in university-affiliated hospitals and centers following > 50 patients, reflecting the importance of access to experienced diabetologists. Children had a mean of 2.3 injections, allegedly performed 2.8 glucose measurements per day, and were seen an average of 4.6 times per year at the center. In the multiple regression analysis, 94% of the variance of HbA1c was explained by our pool of selected variables, with the highest regression coefficient between HbA1c and age (Rc = 0.43, P < 0.0001), then with daily insulin dosage per kilogram (Rc = 0.28, P < 0.0001), mother's age (Rc = 0.26, P < 0.0001), frequency of glucose measurements (Rc = 0.21, P < 0.0001), and diabetes duration (Rc = 0.14, P < 0.0001). Logistic regression identified quality of family support and dietary compliance, two related qualitative and possibly subjective variables, as additional explanatory determinants of HbA1c. The frequency of severe hypoglycemia was 45 per 100 patient-years and correlated with diabetes duration, but not with HbA1c levels or other variables. CONCLUSIONS: Although overall results remain unsatisfactory, 33% of studied French children with type 1 diabetes had HbA1c < 8%, the value obtained in Diabetes Control and Complications Trial adolescents treated intensively. Diabetes management in specialized centers should be encouraged.

Metabolic studies in twin brothers with 2-methylacetoacetyl-CoA thiolase deficiency.

We report clinical and biological investigations in two patients (twin brothers) with 2-methylacetoacetyl-CoA thiolase deficiency. Main clinical features included important staturo-ponderal delay, frequent infectious rhinopharyngitis episodes and an acute metabolic acidosis at the age of 4 years, this metabolic decompensation being adequately halted by bicarbonate supplementation. Since that age, patients developed rather favorably, however, with persistence of the staturo-ponderal delay. Organicaciduria typical of 2-methylacetoacetyl-CoA thiolase deficiency was recorded consisting of excessive excretion of tiglylglycine, 2-methyl-3-hydroxybutyrate, 3-hydroxyisovalerate, 2-methylglutaconate, adipate and 2-methylacetoacetate. Blood carnitine levels were altered in patients with increased total and esterified carnitine concentrations and enhanced acyl/free carnitine ratios. Determination of acylcarnitine profiles showed that patients excreted excessive amounts of several acylcarnitines in urine including propionyl, butyryl, isobutyryl, isovaleryl, 2-methylbutyryl and tiglyl-carnitine, the latter acylcarnitine being prominent with, in one of the patients, occurrence of a previously undescribed isomer of this carnitine ester, possibly 2-ethylacrylyl-carnitine. Excretion of these acylcarnitines in urine was increased in response to L-carnitine although, as a whole, this therapy resulted in a less important stimulation of esterified carnitine removal in urine from patients than in the case of supplemented controls. Biochemical investigations on cultured skin fibroblasts confirmed 2-methylacetoacetyl-CoA thiolase deficiency. Through the present report on this rare disease in two siblings, we would like to underline that acylcarnitines can be used in the diagnosis of 2-methylacetoacetyl-CoA thiolase deficiency, a view supported by acylcarnitine profiles further determined in another patient with proven oxothiolase deficiency, adding this pathology to the list of beta-oxidation disorders that may be screened successfully through determination of acylcarnitine profiles in body fluids.

[Milk feeding of infants and cow's milk protein hypersensitivity]. / Alimentation lactée du nourrisson et allergie aux protéines du lait de vache.

BACKGROUND: Cow milk protein intolerance (CMPI) is characterized by a wide range of symptoms and signs affecting the gastro-intestinal tract, the respiratory system and the skin. A better definition, a stricter application of diagnostic criteria and critical evaluation of certain immunologic correlates can contribute to a better understanding and preventive treatment of this entity. POPULATION AND METHODS: Two hundred-seventeen infants with CMPI seen between January 1980 and December 1993 were included in the study. They were classified into two groups: 1) acute reaginic CMPI (type I): 125 infants and 2) CMP enteropathy or colitis (type III or IV): 92 infants, according to classical diagnostic criteria. Careful investigation concerning the type of milk feeding (breast or artificial) proposed prior to clinical manifestations was performed. RESULTS: Among the 125 infants (aged 3 to 20 weeks) with acute reaginic CMPI, 121 (97%) had been breast-fed with a sudden weaning; 30 of these infants had also received one to three formula bottles during the first 3 days of life and 14 certainly had not received such formula bottles. Among the 92 infants with CMPI, type III or IV, 33 (38%) had been exclusively breast-fed, a figure quite similar to the breast feeding incidence in our region. CONCLUSIONS: These results clearly show the importance of breast-feeding in the personal history of CMPI. Acute reaginic type of CMPI is favored by early ingestion of formula bottles in breast-fed infants and by early sudden weaning. Hypoallergenic formula in five cases was unable to protect infants against further allergic manifestation.

[Hydrocephalus during central parenteral feeding. Role of vitamin A poisoning]. / Hydrocéphalies au cours de la nutrition parentérale centrale. Place de l'intoxication par la vitamine A.

Five children receiving central parenteral nutrition presented between the 6th and 16th day of renutrition with hydrocephalus unrelated to intercurrent neurologic disorder. Repeated determinations of plasma retinol and of the transport complex components made the proof of vitamin A intoxication in 2 cases. Vitamin A had been provided in the form of a water-soluble vitamin-solution incorporated in the nutrition mixture (doses: 1,500 micrograms and 3,000 micrograms retinol equivalent respectively). These 2 case reports have to be compared with 3 other cases of hydrocephalus occurring during total parenteral nutrition. One child presented with bilateral jugular thrombosis secondary to percutaneous venous approach trials, while the 2 other were probably within the framework of an accelerated weight recovery following nutritional marasmus.

[Food consumption of children eating lunch in school restaurants]. / Consommation alimentaire des enfants au cours du repas de midi pris en restaurants scolaires.

In order to study the dietary intakes of children having lunch at school, 150 children were observed: 60 aged 5-6 years, 60 aged 9-10 years and 30, aged 5-13 years, attending 5 different schools (4 in town, 1 in the country). The estimation of spontaneous ingesta was made according to the weighing method. Energizing rations, the percentages of caloric intakes, the amounts of total, animal and vegetal lipids, of total carbohydrates and pure carbohydrates, of total, animal and vegetal proteins were estimated for each meal and each child. The analysis of these ingesta suggests that the dietary habits of children at school is a major factor of nutritional lack of balance, much more important than that related with the quality of the proposed food.

[Oral treatment of acute infantile diarrhoea with sucrose/electrolyte solution (author's transl)]. / Traitement par voie orale par une solution hydroélectrolytique sucrée des diarrhées aiguës de l'enfant.

The value of oral re-hydratation in acute diarrhoea has been demonstrated in a study of 161 infants (mean age 6.8 months, range 1 to 26 months). One litre of solution contained sodium 50 mEq, potassium 25 mEq, bicarbonate 2 g, glucose 20 g, sucrose 20 g with an osmolarity of 300 milliosmoles/kg. Using this solution, rapid replacement of water osses was possible. Dehydratation, the major complication of acute diarrhoea, was thereby prevented and treated without the use of parenteral therapy. However parenteral treatment is still necessary in severe cases (shock, acidosis or severe diarrhoea).