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The aim of the study was to evaluate, after the first year of a national information campaign, the effect on the frequency and severity of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) in children and adolescents in France. The following data were collected during a 2-year period in people younger than 15 years of age at diagnosis of T1D, in 146 pediatric centers: age, sex, duration of symptoms, patient's previous care, clinical and biological signs, and family history of T1D. DKA was defined as pH7.30 or bicarbonate15mmol/L, severe DKA as pH7.10 or bicarbonate5mmol/L. During the 2nd year, an information campaign targeting health professionals and families was launched with the objective of reducing the time to diagnosis. Data were compared between the year before the campaign (year 0) and the first year of the campaign (year 1). The number of new cases of T1D was 1299 for year 0 and 1247 for year 1. Between year 0 and year 1, the rate of DKA decreased from 43.9% to 40.5% (P=0.08), exclusively due to the decrease of severe DKA from 14.8 to 11.4% (P=0.01). In the 0- to 5-year-old and 5- to 10-year-old age groups, the relative decrease in the rate of DKA was 13% and 15%, and 23% and 41% for severe DKA, respectively. In patients referred to the hospital by a pediatrician or who came at the family's initiative, the decrease was 34% and 7%, and 39% and 32% for severe DKA, respectively. No change was observed in the 10- to 15-year-old group or in those children who were referred by a general practitioner. In multivariate analyses, a higher DKA rate was associated with the young age of the child (5 years), being hospitalized at the parents' initiative rather than being referred by a doctor, and the absence of a family history of T1D. A higher rate of severe DKA was associated with these last two factors but not with the child's age. The frequency of DKA at diagnosis of type 1 diabetes remains high in children and adolescents, but the first year of an information campaign decreased it. The results have also helped better define the strategy and targets of the continuing prevention campaign, to more efficiently reduce the morbidity and mortality of T1D at diagnosis in children and adolescents in France.

In all age groups, the aim of insulin treatment will be as close to physiological insulin replacement as possible in order to obtain optimum metabolic control. Rapid and long acting insulin analogs represent some improvement in the care of diabetes in children by improving glycaemic control and decreasing the occurrence of hypoglycaemia. Insulin dosage will be determined to allow appropriate insulin levels throughout the twenty-four hours to cover basal requirements and higher levels of insulin in an attempt to match the glycaemic effect of meals. The distribution of insulin dose across the days shows great individual variations and daily insulin dosage varies greatly between individuals end changes over time. Regardless of mode of insulin therapy, doses should be adapted based on the daily pattern of blood glucose and therefore require regular review and assessment. The device used for insulin administration must be adapted for paediatric patients. Whatever insulin regimen is chosen it must be supported by comprehensive education adapted for the age, maturity and individual needs of the child and family.

This study aimed at evaluating the screening of thyroïditis and coeliac disease, in a population of children and adolescents with type 1 diabetes, and at comparing the appearance of antibodies specific for these 2 diseases as a function of age.The study included 370 children and adolescents, 179 girls and 191 boys, aged 13.8 +/- 4.4 yr and with diabetes for 7.1 +/- 3.8 yr. Auto-immune thyroïditis was screened using antimicrosomal and antithyroglobulin auto-antibodies, at a mean rhythm of 3 tests per patient (1 every 2 yr), associated with dosages of TSH and FT4. Coeliac disease was screened using antigliadin (+/- antiendomysium) auto-antibodies, at a mean rhythm of 2 tests per patient, and was confirmed by duodenojejunal biopsy. Antithyroïd auto-antibodies were correlated with age following the "censured data analysis" type approach.Antithyroïd autoantibodies were found in 42 patients (11.4%), of whom 9 were treated for hypothyroïdism and 1 for Basedow disease, and coeliac disease autoantibodies were found in 9 patients (3.2% of tested patients). The cumulated frequency of antithyroïd auto-antibodies increased regularly with age and was significantly higher in girls, reaching 28% in girls and 12% in boys around 18 yr of age. As a consequence of this evolution, antithyroïd auto-antibodies were frequently found at the time of diagnosis of diabetes when it declared after 10 yr of age, while they often became positive secondarily when diabetes occurred before 10 yr of age. Coeliac disease specific auto-antibodies appeared much earlier and were found at the time of diagnosis of diabetes or at the first screening test.Antithyroïd autoantibodies are increasingly frequent with age in children with type 1 diabetes, and become very elevated in girls. The rhythm for screening should be adapted to this evolution of autoantibodies with age, which is very different between thyroïditis and coeliac disease.

Congenital hyperinsulinism (HI) is the most important cause of hypoglycaemia in early infancy. The inappropriate oversecretion of insulin is responsible for profound hypoglycaemias requiring aggressive treatment to prevent severe and irreversible brain damage. Several classifications of HI can be attempted, based on: 1) the onset of hypoglycemia in the neonatal period or later in infancy; 2) the histological lesion: focal or diffuse; 3) the genetic transmission: sporadic, recessive, or less frequently dominant. The most common underlying mechanism of HI is dysfunction of the pancreatic ATP-sensitive potassium channel (K(+)(ATP)). The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region. Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion. Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous. The distinction between the focal and the diffuse HI is very important, because the treatments are different. To distinguish between focal and diffuse HI, transhepatic catheterisation with pancreatic venous sampling was the reference technique, but will likely be replaced by [(18)F] Fluoro-L-Dopa PET scan, which is easier to perform. In absence of response to the medical treatment (diazoxide) a limited pancreatectomy permits to cure focal HI, while a diffuse HI requires a subtotal pancreatectomy with high risk of subsequent diabetes mellitus.

In the last twenty years, blood glucose self-monitoring has attained a nearly optimal level, with reliability, easiness, quickness and safety, which makes it tolerable to a greater number of patients and allows young diabetics to make more easily something which is mandatory to the management of type 1 diabetes. The principles of treatment are identical in children, adolescents and adults. However, many patients experience difficulties in applying the ideal therapeutic model. This must be particularly taken into account in children, who are in a stage of full intellectual and psychological development. Inappropriate demands can drive them to failure and go against the main objective at this period of life, which is education. Reference documents help pediatricians to the daily practice of home blood glucose monitoring and, more generally, management of childhood diabetes: ISPAD Consensus Guidelines (ISPAD=International Society for Pediatric and Adolescent Diabetes), which has been translated in French, and Cahiers de l'AJD (AJD Note books), for educating new patients. Blood glucose monitoring is recommended: to evaluate the glycemic response to the effect of insulin; to confirm hypoglycemia; to prevent hyperglycemia in case of disease; in case of physical exercise. The frequency of home blood glucose monitoring should be individualized, depending on the acceptability for the young patients and the insulin therapeutic regimen.

Evaluate the correlation between psychopathological disorders in type 1 insulin-dependent diabetic (IDD) children and adolescents and the occurrence of micro-angiopathic complications.Two hundred and five IDD children (104 girls and 101 boys with a mean age of 13.4 +/- 3.5 years on inclusion) were longitudinally monitored between 1994 and 2000. Somatic complications were systematically searched for during a yearly control visit to the day hospital. Psychiatric disorders had been assessed initially by self-administered questionnaires filled-in by the children (Spielberger's STAIC-Trait for anxiety, CESD for depression and Child-EAT for eating habits), by the parents (CBCL, CPRS or GHQ-28) or the principle teachers (CTRS) and diagnostic screening of psychopathological disorders every year.More than 140% of the IDD children (n = 86) were diagnosed DSM-IV, with predominant anxiety (n = 41), during the longitudinal evaluation. Positive screening was significantly associated with higher psychopathological scores before inclusion in the study, with children considered more perturbed by the parents, teachers and the children themselves and mothers who considered themselves more perturbed (GHQ-28 mean 5.6 +/- 7.5 vs. 3.5 +/- 4.8; t = 2.211 p = 0.028). These children were less compliant. Disorders were associated with metabolic imbalance, measured by HbA1c, overweight and an excess of micro-angiopathic, particularly retinopathic, complications.Our results show the frequency of mental disorders in IDD children, the importance of the parents' psychopathology and its association with increased somatic risk. The nature of this relationship requires clarification and the incidence of prevention measures targeted on the psychological problems. The interest of associating a paedopsychiatric element in the therapeutic management of these patients and their families is emphasized.

The purpose of this study was to evaluate the type and frequency of psychopathological disorders observed in obese children and adolescents. We also looked for a correlation between psychic disorders in the obese children, the degree of obesity and paternal psychopathology.The study group included 84 obese children and adolescents aged 5 to 16 years (mean age 10.9 +/- 2.8 years). There were 55 girls and 29 boys. The z-score expressing deviation from the ideal body mass index (IMC) varied from +2 to +10.6 (mean 4 + 1.9). Psychopathological disorders observed in these obese patients were compared in children and adolescents with insulin-dependent diabetes mellitus. The standard diagnostic interview (K-SADS PL) and self-administered questionnaires (Sielberger STAIC-Trait for anxiety and CDI for depression in children or CBCL or GHQ for their parents) were also used to evaluate psychic disorders.More than half of the obese children (47 out of 84) had a DSM-IV diagnosis, often involving anxiety (n = 28). The rate of internalized and externalized psychopathological disorders (measured by STAIC-Trait and CBCL) was higher in the obese children than in the diabetics. The children's psychopathological disorders were more marked if their parents were perturbed, particularly when their mother had an internalized disorder. No correlation was found between the degree obesity and psychopathological disorders in the obese children and adolescents.Our findings show the frequency of mental disorders in obese children and point out the importance of parental psychopathology. This underlines the usefulness of a pedopsychiatric approach implicating the entire family for therapeutic management of these patients.

As their life expectancy has improved, patients with cystic fibrosis have experienced an increasing incidence of diabetes. Diabetes mellitus is characterized by improved and delayed insulin secretion, normal insulin sensitivity, and it is most often accompanied by exocrine pancreatic insufficiency. The development of diabetes mellitus is insidious and symptomless, and the overall cystic fibrosis status deteriorate for years prior to the diagnosis of diabetes. Since insulin therapy seems to revert deterioration for years of clinical status, and since late diabetic complications may develop, diabetes mellitus in cystic fibrosis should be identified by screening with an OGTT from the age of 15 years, and treated with insulin from the time of diagnosis of diabetes.

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.

To assess the type of mental disorders met in the medical follow-up of insulin-dependent diabetic children (IDDM) and adolescents and their relationships with metabolic control (HbA1C) in young IDDM patients who consult in a department of child psychiatry.Twenty boys and 37 girls (mean age: 14.7 +/- 4.1 years and mean duration of IDDM: 5.6 +/- 4.3 years were followed during 1 year by the same child psychiatrist (mean duration of follow-up: 22 months). They were assessed with several clinical interviews (mean: three by subject); mental disorders were classified according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition revised (DSM III-R).The study showed the importance of emotional disorders, 30 patients presenting at least an anxiety disorder and 17 an affective disorder, 11 a major depressive disorder and eight a dysthymic disorder. The most frequent anxiety disorders were phobias and overanxious disorders. Two patients had an anorexia nervosa, one a bulimia nervosa and nine an eating disorder not otherwise specified. There were ten diagnoses of disruptive behaviour disorders, one toxic substance abuse and 11 adaptation disorders. Seven subjects had a reading and writing learning disorder, three a coordination disorder and three a borderline IQ. Familial factors seemed very important. Nine patients had a parent-child problem, four sibling rivalry disorder and two an attachment disorder. Family problems (conflicts, separations, economical difficulties...) were found in 63% of cases. The mother or the father had mental disorders in 24 cases (42%). The diabetic patients with mental disorders had poor metabolic control (HbA1C = 9.9 +/- 2.4%) and ten subjects (18%) had already somatic complications. Some mental disorders were significantly associated with high HbA1C. The poorer metabolic controls were observed for eating disorders. Somatic complications were associated only with IDDM duration.This study shows the presence of typical DSM III-R mental disorders in IDDM children and adolescents, principally emotional disorders, and their association with a higher somatic risk, maximum for eating disorders. It shows the interest of collaboration between diabetologist and child psychiatrist. The exact prevalence of these disorders should be assessed by epidemiological studies.

Insulin-dependent diabetes mellitus can be associated to an auto-immune disease. A similar association may be seen in the neonate.A one-day-old boy was admitted for ketoacidosis due to diabetes mellitus. Investigation showed that he also suffered from an auto-immune enteropathy with several types of autoantibodies, particularly anti-enterocytes antibodies. Immunotherapy was ineffective. Multi-organ lesions developed subsequently, particularly a pulmonary disease responsible for the death at the age of 2 years.Physiopathology of this association remains unclear and the report of further cases should help improve our knowledge.

Insulin resistance is defined as the decrease of the biological action of insulin, and it mainly presents as an hyperinsulinaemia. The clinical investigation of the states of insulin resistance requires expertise in sophisticated in vivo and in vitro methods. The hyperinsulinaemic euglycemic clamp is the reference method for quantifying insulin resistance. The clamp technique consists in infusing insulin at constant rate and, to prevent any decrease in the plasma glucose level, by infusing dextrose. The rate of dextrose infused to maintain euglycaemia is an estimate of the amount of glucose which is taken up by the tissues under the effect of a defined plasma insulin concentration. Using several rates of insulin infusion allows to establish the relationship between the whole body glucose disposal and plasma insulin levels, and to discriminate between the states of decreased insulin sensitivity and/or altered maximal capacity to dispose of glucose. The measurement of glucose fluxes, using the constant infusion of stable isotope labelled glucose, allows to differentiate the hepatic and the peripheral components of insulin resistance. Insulin sensitivity may be estimated using other methods, such as the minimal model which consists in a mathematical analysis of the intravenous glucose tolerance test. In vitro studies include the search for anti-insulin antibodies and anti-insulin-receptor antibodies, the study of insulin receptors (insulin binding, tyrosine-kinase activity and gene structure) and of the post-receptor glucose metabolism. Genetic syndromes of extreme insulin resistance, the pathophysiology of which is poorly known, are the main applications of these investigations. However, insulin resistance plays an important role in non-insulin-dependent diabetes mellitus, and also in insulin-dependent diabetes and various pathological or physiological endocrine disorders.

Association between insulin-dependent diabetes mellitus (IDDM) and eating disorders (anorexia nervosa, bulimia nervosa) was recently described. We have reviewed the systematic studies that were conducted on this topic, particularly for prevalence of anorexia nervosa and bulimia nervosa and their relations with metabolic control (HBA1C) and somatic complications of insulin-dependent diabetes mellitus. We have discussed methodological problems of these studies and etiopathogenic aspects of eating disorders in this somatic disease.

The existence of a relationship between Insulin-Dependent Diabetes and eating disorders has recently been observed, but its prevalence and impact on somatic functioning remain poorly understood. These dimensions were evaluated in a population of 52 insulin-dependent diabetic adolescent girls and compared with evaluations of matched subjects from the general population. Results showed that the occurrence of anorexia nervosa is rare, the occurrence of unspecified eating disorders is frequent (35%) and the occurrence of bulimia nervosa is nearly six percent. Poor metabolic control as reflected in blood levels of glycosylated hemoglobin (HBA1C) was found in bulimic subjects and a tendency to be overweight was found in subjects with an unspecified eating disorder. Since such disorders frequently involve dietary restrictions, the role of a restrictive pattern in the occurrence of eating disorders is raised.

Posttransplant diabetes mellitus is ascribed to the use of corticosteroids. Because use of cyclosporine has been associated with increased rates of posttransplant diabetes mellitus, risk factors for this condition have been studied in adults and found to include older age, excessive body weight, and a family history for non-insulin-dependent diabetes mellitus. Only about 1% of children develop diabetes mellitus after transplant surgery. A study of pediatric transplant recipients with diabetes mellitus and of pediatric renal transplant recipients suggested that posttransplant diabetes mellitus may be more common in children with risk factors and may reveal types of diabetes which are infrequent in childhood, e.g., non-insulin-dependent diabetes mellitus which would have gone undiagnosed until adulthood in the absence of corticosteroid therapy. In contrast, corticosteroids apparently had little influence on glucose tolerance in subjects free of risk factors. The effect of corticosteroids seemed to be somewhat less marked than that of renal function impairment.

Jet injectors, which force a fluid under considerable pressure through a very small opening, have recently become available for subcutaneous administration of insulin. Use of the new devices introduced on the market is neither simpler nor more complicated than use of a syringe. Although jet injectors are highly attractive to both patients and parents, they can be used in only a limited range of diabetics. Main limitations to more widespread use include: 1) the small capacity of the devices which cannot inject more than 20 units of 40 unit/ml insulin; 2) modifications in the pharmacokinetic effects of insulins, especially long-acting insulins; 3) the high price of the injectors. Young children, who often find it difficult to accept injections, may be the main potential target for jet injector therapy. A trial period at home should always be scheduled before considering the purchase of a jet injector.

Periodontal disease is one of the well-documented complications of diabetes mellitus in adulthood. The effects of diabetes mellitus on periodontal tissues in children and teenagers have been studied only in more recent years. Although clinical studies have demonstrated a few cases of severe periodontal disease in patients with "historical" diabetes mellitus, in the overwhelming majority of cases periodontal lesions seem comparable in young subjects with and without diabetes mellitus. However, reports on this topic published both in France and in the United States fail to give a clear picture of the existence, prevalence and severity of peridontal disease in youngsters with diabetes mellitus. Consequently, an epidemiologic study was undertaken at the Herold Hospital (Paris) and at the Association of Young Diabetics. Eighty-five young patients with diabetes mellitus and 38 controls were included. The purpose of the study was to determine whether periodontal disease is only a former or still a current complication of diabetes mellitus.

The mechanism of pancreatic beta-cell destruction in type I (insulin-dependent) diabetes mellitus (IDDM) involves autoimmune events directed against these cells. Anti-beta-cell autoimmunity occurs in genetically predisposed individuals and may precede clinical manifestations of IDDM by several years. Markers for beta-cell autoimmunity, especially islet-cell antibodies, are being used with increasing reliability both for detection of IDDM and for evaluating the risk of development of the disease. HLA alleles associated with IDDM include DR3 and DR4, with the risk of IDDM being especially high in individuals with the heterozygous combination DR3/DR4. Recent advances in molecular biology have resulted in more accurate identification of genetic variants and even of amino acid sequences associated with IDDM. These markers can be used to identify patients with genetic susceptibility to the disease. The mechanism of action of genes associated with IDDM is as yet unknown but probably involves the receptor function of HLA molecules for antigens during immune responses.

In order to study the capacity of the first phase insulin response (FPIR) for predicting insulin-dependent diabetes (IDDM), we have performed one or more intravenous glucose tolerance tests (IVGTT) and determined islet-cell antibodies (ICA) and HLA-types in 220 first degree relatives of IDDM patients (194 siblings, 26 offsprings) aged 2 to 29 years. They were prospectively followed for periods ranging from 18 months to 8 years. The immunological and metabolic changes in 9 subjects who have developed IDDM or impaired glucose tolerance during the study and in 3 ICA-positive non-diabetic subjects were compared to those in ICA-negative subjects. Although the mean FPIR (1 + 3 min. plasma insulin) was significantly lower in ICA-positive compared with ICA-negative subjects, a unique low FPIR had no predictive value at the individual level. At repeated tests, the two groups followed distinctive evolutive patterns: ICA-negative subjects usually had higher FPIRs at a 2nd test, while FPIRs remained low or still decreased in ICA-positive subjects. Follow-up of subjects at high risk showed good concordance between the different predictive factors: among the 9 subjects who have developed IDDM, 7 had persisting ICA, 8 were HLA-DR3, DR4; the FPIR was consistently low in 3 and low at least once in 4. Progressive loss of the FPIR allowing to predict the time of onset of IDDM, was not observed.

Superoxide dismutase, glutathione peroxidase and glutathione reductase activities were measured in erythrocytes of 214 young patients with insulin-dependent diabetes and 37 healthy subjects with similar age and sex distribution. The diabetic patients were divided into groups and subgroups according to sex, age, duration of disease, existence of diabetes complications and family history of atherogenic risks. Data analysis was performed by comparing enzyme activities in subgroups according to the degree of diabetes control and the plasmatic level of various lipid fractions. Results showed that superoxide dismutase, glutathione peroxidase and glutathione reductase activities in young diabetic patients were similar to those in controls, except for patients with retinopathy, whose glutathione peroxidase activity was decreased. This last finding might suggest that there is a relationship between the development of diabetic microvascular complications and the accumulation of free radicals and peroxide lipids.

Resistance to insulin consists in a decrease in insulin's biologic action and is manifested mainly by hyperinsulinism. Clinical investigation of insulin resistance states relies on specialized tests, performed both in vitro and in vivo. The hyperinsulinemic-euglycemic clamp is the reference method for quantifying insulin resistance and can differentiate decreased insulin sensitivity and decreased maximal capacity for glucose uptake. Glucose flux measurements, using glucose labelled with stable isotopes, distinguish hepatic and peripheral factors involved in insulin resistance. In vitro studies include investigations for antibodies against insulin and insulin receptors, studies of insulin receptors and their tyrosine kinase activity, and studies of postreceptor cell metabolism. These investigations are especially useful in genetic syndromes of extreme insulin resistance, whose pathophysiology is largely unelucidated, including: insulin resistance syndromes with acanthosis nigricans, obesity-acanthosis nigricans-hyperandrogenism syndrome, lipoatrophic diabetes, leprechaunism, and other syndromes. But insulin resistance also plays a major role in non-insulin-dependent diabetes mellitus, insulin-dependent diabetes mellitus, and various pathological or even physiological endocrine alterations.

The mechanism of pancreatic B-cell destruction in type I (insulin-dependent) diabetes (IDDM) involves autoimmune phenomena based on genetic predisposition. The mechanism of action of the susceptibility genes is probably related to the function of the HLA molecules in the immune response. The genetic susceptibility is distinguished by increased frequency of the HLA antigens DR3 and DR4 and particularly their heterozygous combination DR3/DR4. Recent advances in molecular biology have resulted in a more precise definition of the genetic variants and corresponding amino acid sequences associated with IDDM. These markers may identify subjects at risk of developing the disease. However, the signs of islet-specific autoimmunity, e.g. islet-cell antibodies, which may be detected several years before the clinical onset of IDDM, are of greater predictive value. These and other arguments in favour of an autoimmune pathogenesis of type I diabetes have made preventive immunotherapy a goal for the future.

The information and counselling of diabetic patients and their families requires for the practitioner to know about some fundamental aspects of diabetes and in particular, to distinguish between the different types of diabetes with different causes, pathogenetic mechanism and modes of inheritance. Recent developments in the fields of immunogenetics have improved the understanding of type I diabetes, an auto-immune disease associated with HLA and made possible the identification of genetically susceptible individuals. The etiology of type II diabetes, by far the most frequent form, remains unknown. In the absence of genetical markers, the screening of predisposed subjects is, however, useful in order to propose preventive measures.

The current artificial pancreases, which are not wearable, are mainly used for physiological research. However, they may also become useful tools for clinical or therapeutic investigations in diabetes mellitus. This is clearly demonstrated by our own experience of the Biostator in 300 young diabetics. The steady state regulation of plasma glucose offers a wide range of possible investigations: clinical, such as measuring insulin activity in states of insulin resistance, urinary excretion of glucose and renal threshold; therapeutic, like evaluating the hypoglycemic activity of commercial insulins, or alternative routes of insulin administration, such as the peritoneum; physiopathological, for better evaluation of metabolic alterations in diabetes by measuring the turnover of various substrates. Experience of the artificial pancreas also appears to be crucial for a better handling of the many problems involved in the design of future wearable or implantable devices.

Although glycosuria is important in the control of diabetes in children, few studies clearly show its significance as compared to glycemia. The aim of the present study was therefore to determine the two parameters that control glucose presence in urine, i.e. glucose glomerular filtration rate (GFR) and tubular reabsorption (JrG). GFR was measured by using a 110 min polyfructosan perfusion in 96 diabetic children and adolescents. The results are as follows: 1) In this population there is a significant correlation (p less than 0.01) between the quantity of glucose in urine and mean glycemia during the test; 2) polyfructosan clearance that reflects GFR in diabetic children without renal complication is 2.11 +/- 0.04 ml/s 1.73 m2, or 126 +/- 2.4 ml/min 1.73 m2 (mean +/- SEM); it is higher than in the reference values already published; 3) JrG is correlated with glucose filtered load (p less than 0.01), GFR (p less than 0.01) and sodium reabsorption (p less than 0.01). The ratio JrG/GFR could be substituted for the classical concept of "renal threshold", as it can be easily measured and may help in interpreting glycosuria in some diabetic children. To conclude, in IDD children, the parameters controlling glycosuria may be studied by a simple method. The clinical value of such renal exploration has still to be determined.

Blood xylose level 60 min. after an oral dose of 10 g/m2 xylose was compared with the histology of the jejunal mucosa in 56 children. Ninety-two percent of children with blood xylose below 20 mg/100 ml had an abnormal jejunal mucosa; 98% of children with a normal mucosa had a blood xylose above 20 mg/100 ml. In children with coeliac disease the following observations were made: 1) blood xylose was above 20 mg/100 ml in 50% of children with flat mucosa; all were given a diet excluding gluten; 2) blood xylose levels which were initially below 20 mg/100 ml were found above this level 3 to 12 days after the onset of the diet; 3) all the histological relapses following re-introduction of gluten in the diet were not associated with a decrease of blood xylose level below 20 mg/100 ml.