Transition from pediatric to adult care. eight years after the transition from pediatric to adult diabetes care: metabolic control, complications and associated diseases.

BACKGROUND: Transition from pediatric to adult care is a critical process in the life of patients with diabetes. AIM: Primary aim of the study was to compare the metabolic control between pediatric care and adult care at least 5 years in a group of patients with type 1 diabetes mellitus (T1DM). Secondary aim was to evaluate the presence of complications, associated diseases and psychological-psychiatric disorders. SUBJECTS AND METHODS: We obtained data from 73 % (69/94) patients (current mean age 34 years) transferred to local adult centers between 1985 and 2005 at a mean age of 23.8 years. Data were collected for HbA1c, diabetic complications and associated diseases. RESULTS: Mean HbA1c did not change during the pediatric, transition and adult period [8.4 ± 1.8 % (68 ± 18 mmol/mol), 8.3 ± 1.4 % (67 ± 15 mmol/mol) and 8.4 ± 1.3 % (68 ± 14 mmol/mol), respectively]. 13 patients dropped out, after 2-12 years since transition, and their HbA1c mean value at transition was 10.4 %. After a mean of 25.9 years of disease, 35/69 patients (50.7 %) showed retinopathy, and 12/69 patients (17.3 %) nephropathy. Thyroid diseases were the most frequent associated diseases (18.3 %), followed by depression (11.2 %) and benign neoplasms (9.8 %). Drug or alcohol addictions were present in four cases (5.6 %). CONCLUSIONS: After a mean follow-up of 8 years metabolic control after transition did not change significantly in patients constantly attending to adult care centre. Patients with diabetes onset between 20 and 40 years ago were free from complications in 50 % of cases when considering retinopathy and in more than 80 % considering nephropathy. Thyroid problems were the most common associated diseases. Poor metabolic control at transition is associated with higher risk of drop-out and psychosocial morbidity.

Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy characterized by hemolysis, platelet consumption, and renal injury. Eculizumab, a mAb that blocks complement activity, has been successfully used in aHUS. OBJECTIVES: To optimize eculizumab therapy in aHUS patients by monitoring complement functional tests and markers of disease activity. PATIENTS/METHODS: We studied 18 patients with aHUS (10 males; eight females; age range, 2-40 years) treated with eculizumab to induce and/or maintain disease remission. Patients were followed up for a cumulative observation period of 160 months, during which blood samples were obtained at various time intervals to measure complement activity (Wieslab for the classical, alternative and mannose-binding lectin complement pathways) and the parameters of disease activity (haptoglobin and lactate dehydrogenase serum levels, and platelet count). The intravenous eculizumab doses of 12-33 mg kg(-1) were initially administered every week, with the interval between doses being gradually extended to 2 weeks, 3 weeks and 4 weeks on the basis of strict laboratory and clinical control. RESULTS: Complement activity was normal before eculizumab treatment, regardless of the state of the disease (activity or remission). It was completely suppressed 1 week, 2 weeks and 3 weeks after the last eculizumab infusion (mean values ± standard deviation: 1% ± 1% to 3% ± 5% for both the classical and alternative pathways; P = 0.0001 vs. baseline), and partially suppressed after 4 weeks (22% ± 26% and 16% ± 27%; P = 0.0001 vs. baseline). The increase in the time interval between eculizumab infusions did not change disease activity markers. CONCLUSIONS: Monitoring complement tests can allow a safe reduction in the frequency of eculizumab administration in aHUS while keeping the disease in remission.

A controlled, class-based multicomponent intervention to promote healthy lifestyle and to reduce the burden of childhood obesity.

BACKGROUND: Overweight and obesity prevention in childhood and adolescence represent a priority for public health; school is a privileged place for health promotion interventions. OBJECTIVES: The study aimed to test the effectiveness of a multicomponent 5-month intervention on the habits of primary school children, making the families aware of the importance of healthy choices. METHODS: Two hundred nine children attending the fourth class of primary school, divided into interventional (n = 103) and control arm (n = 106) were included in the study. In the intervention group, parents and teachers received more intense lifestyle counseling, associated with weekly motivational telephone calls to families to motivate further their lifestyle changes. Standard deviation score (SDS) body mass index (BMI) was the primary outcome measure; on open-air games and TV watching were secondary outcomes. RESULTS: At baseline, no differences were observed between groups. At 8-month follow-up, mean SDS BMI had decreased by 0.06 units in the intervention arm and increased by 0.12 in controls (time × treatment anova, P < 0.002). Outdoor activities increased from 6.23 h week(-1) to 9.93 in the intervention group (P < 0.001), not in controls. This change was associated differences in TV watching from baseline (intervention, -0.96 h week(-1); P = 0.037; controls, +1.33 h week(-1); P = 0.031). CONCLUSION: A multicomponent school-based intervention addressing the needs of children, teachers and families produced a significant and favourable short-term effect on overweight/obese schoolchildren.

Younger age at diagnosis of type 1 diabetes mellitus in children of immigrated families born in Italy.

The aim of this study was to evaluate the age of immigrants' children at diagnosis of Type 1 diabetes (T1DM) according to their country of birth. Immigration from developing countries to a westernised area causes rapid changes in the environmental conditions, and we investigated whether the location of birth, either inside or outside Italy, is associated with age at diagnosis of diabetes. Out of a prevalent hospital-based cohort of 5718 T1DM children cared for in 2002 in 47 Italian Pediatric Diabetes Units, we recruited 195 children (M: 97) of immigrants from developing countries--119 were born in Italy and 76 outside the European Union. Children with only one immigrant parent (no. 42) were also included. Age at diagnosis of T1DM, and other variables were compared with those of Italian children. Children of immigrated families born in Italy developed T1DM at a median age of 4.0 yr (IQR 2.2-6.9), whereas those born in developing countries and that had immigrated to Italy after birth developed T1DM at a median age of 7.9 yr (IQR 5.1-10.7, p < 0.001). Among the children born in Italy, 77 had parents who were both immigrants and the children's median age at diagnosis was 3.8 yr (IQR 2.1-6.3); 42 had only one immigrant parent and, when it was the father (no. = 23), median age was even younger (2.9 yr, IQR 2.0-8.2). Ten children had immigrated in their first yr of life and their median age was 9.1 yr (IQR 5.0-10.6). The median age of the Italian children was 6.6 yr (IQR 3.6-9.5). Results show that the outbreak of T1DM is earlier in immigrants' children born in Italy than in original countries.

Lymphocyte dysmetabolism: an immunocytochemical comparative approach in IDDM and control subjects.

We have investigated by immuno-electron microscopy the presence of phosphotyrosine in cells as a whole and in different cell districts (nucleus, cytoplasm, plasma membrane, and mitochondria) in peripheral blood lymphocytes of IDDM (insulin-dependent diabetes mellitus) patients and age-matched controls. Immuno-gold particle density was highest in mitochondria and decreased in cytoplasm, nucleus and plasma membrane. The time dependence of phosphotyrosine labelling after cell isolation was very strong in all subcellular populations, with a fall in immunogold staining after 30 min. Staining levels at zero time were similar in controls and IDDM patients; the loss of phosphotyrosine labelling was much stronger in controls, except in the plasma membrane. Plasma membrane NADH oxidoreductase activity, studied using cytosolic NADH as substrate and assayed with DCIP as acceptor, was significantly increased in IDDM patients, suggesting a response to a deficient mitochondrial energetic activity. The fact that NADH oxidoreductase is a growth factor related to tyrosine phosphorylation pathways raises intriguing questions on the cellular derangement occurring in peripheral lymphocytes in IDDM, although the relationships among the immunocytochemical and biochemical changes is still obscure.

Diabetic retinopathy in childhood: long-term follow-up by fluorescein angiography beginning in the first months of disease.

BACKGROUND: Little is known about minimal retinal lesions occurring in the first months of disease in children with type 1 diabetes mellitus (DM). OBJECTIVE: To detect any early retinal change and to evaluate its progression in children diagnosed with type 1 DM. PATIENTS: From 1979 to 1997 we examined by fluorescein angiography at diagnosis or within 15 months from the onset of DM 130 young patients with type 1 DM (mean age at diagnosis 10.08 +/- 2.62 yr). In 112 patients follow-up by fluorescein angiography was performed every 1.26 years with a mean of 5.41 fluorescein angiographies/patient. METHODS: The stage of retinopathy was graded to detect minimal lesions. We also considered sex, pubertal stage, HLA, family history of DM, disease duration and HbA1c levels. RESULTS: At first examination, 14 out of 127 (11%) readable angiographies showed minimal retinal changes. There was no statistically significant difference between the patients with or without lesions for all parameters considered. The 112 patients examined during follow-up were divided as follows: Group A: no retinopathy at first examination; Group A1: no retinopathy during follow-up; Group A2: retinal changes during follow-up; Group B: retinal changes at the first examination. Mean HbA1c value evaluated during the whole follow-up was lower in group A1 than in group A2. HbA1c levels at onset of the disease were significantly different in the three groups: in group A1 it was lower than in group A2 and in group B. CONCLUSIONS: The presence of early lesions in the first year of disease in 11% of patients is probably due to the method of examination, which may detect even minimal retinal changes. This may be correlated to the acute metabolic failure present at the onset of disease. The prolonged follow-up seems to demonstrate that the early changes are not necessarily a negative prognostic factor in the evolution of diabetic retinopathy. We confirm that duration of DM and metabolic control are the main factors influencing the course of retinopathy in these young patients. Early fluorescein angiography is not particularly useful in the management of children with DM.

Is statural growth predictable in utero? Follow-up from the second trimester of gestation to the 8th year of life.

BACKGROUND: It is well known that birth weight is related to later childhood growth and adult height. It can therefore be hypothesized that this relationship exists also for fetal size before birth. OBJECTIVE: To verify whether a child's final height can be predicted by sonographic biometry in utero. SUBJECTS: We evaluated in 116 healthy children both ultrasound measurements in utero and postnatal measurements at a mean age of 6.0 +/- 1.4 years. METHODS: The following fetal ultrasound measurements were obtained: crown-rump length in the first trimester; biparietal diameter, head circumference and femur length in the second and third trimester. RESULTS: Midparental height of the children was correlated both with crown-rump length in the first trimester and with femur length (FL) in the second and third trimester. Predicted adult height was correlated both with FL in the second and third trimester, while present height of the child was correlated with FL only at the third trimester. CONCLUSIONS: FL showed a close relationship with postnatal measurements. For the extreme values of FL, it seems possible to make quite an accurate prediction of the limits of future height. We can reasonably speculate, therefore, that the basis for the future growth of the child can be found in utero.

Homocysteinemia, serum folate and vitamin B12 in very young patients with diabetes mellitus type 1.

BACKGROUND: Recently a link between hyperhomocysteinemia [HH(e)] and diabetic micro- and macrovascular complications has been reported. However, it is far from clear whether HH(e) is an epiphenomenon or a cause of angiopathic complications. OBJECTIVE: To try to clarify this question we studied adolescents and young diabetic patients without or with only initial complications. SUBJECTS: Plasma levels of basal homocysteinemia [H(e)], folate and vitamin B12 were measured in 76 young diabetic patients (age range 13.6-32.2 yr) and 70 normal volunteers matched for sex and age. In 68 diabetic patients and 53 controls we evaluated the levels of homocysteinemia 2 h after a methionine-loading test. METHODS: Total (free + protein bound) plasma H(e) level was measured by HPLC. RESULTS: Basal or post-load HH(e) occurred in 4.1% of diabetic patients and 12.4% of controls (frequencies not statistically different). In diabetic patients plasma homocysteine values were statistically lower than in controls, but this difference was present only in females. The females showed lower homocysteine values and higher folate levels than males only in the diabetic group. We did not find significant differences in H(e) levels between patients with early complications, late complications or without complications of any type. CONCLUSIONS: Considering very young diabetic patients, the risk of hyperhomocysteinemia does not appear to be greater than in normal controls. Furthermore, our data seem to demonstrate that HH(e) is not a preexisting condition in diabetic patients, even in those predisposed to early complications.

Evidence for an interaction between adducin and Na(+)-K(+)-ATPase: relation to genetic hypertension.

Adducin point mutations are associated with genetic hypertension in Milan hypertensive strain (MHS) rats and in humans. In transfected cells, adducin affects actin cytoskeleton organization and increases the Na(+)-K(+)-pump rate. The present study has investigated whether rat and human adducin polymorphisms differently modulate rat renal Na(+)-K(+)-ATPase in vitro. We report the following. 1) Both rat and human adducins stimulate Na(+)-K(+)-ATPase activity, with apparent affinity in tens of nanomolar concentrations. 2) MHS and Milan normotensive strain (MNS) adducins raise the apparent ATP affinity for Na(+)-K(+)-ATPase. 3) The mechanism of action of adducin appears to involve a selective acceleration of the rate of the conformational change E(2) (K) --> E(1) (Na) or E(2)(K). ATP --> E(1)Na. ATP. 4) Apparent affinities for mutant rat and human adducins are significantly higher than those for wild types. 5) Recombinant human alpha- and beta-adducins stimulate Na(+)-K(+)-ATPase activity, as do the COOH-terminal tails, and the mutant proteins display higher affinities than the wild types. 6) The cytoskeletal protein ankyrin, which is known to bind to Na(+)-K(+)-ATPase, also stimulates enzyme activity, whereas BSA is without effect; the effects of adducin and ankyrin when acting together are not additive. 7) Pig kidney medulla microsomes appear to contain endogenous adducin; in contrast with purified pig kidney Na(+)-K(+)-ATPase, which does not contain adducin, added adducin stimulates the Na(+)-K(+)-ATPase activity of microsomes only about one-half as much as that of purified Na(+)-K(+)-ATPase. Our findings strongly imply the existence of a direct and specific interaction between adducin and Na(+)-K(+)-ATPase in vitro and also suggest the possibility of such an interaction in intact renal membranes.

Helicobacter pylori infection and cytotoxic antigen associated gene "A" status in short children.

BACKGROUND: Helicobacter pylori is now an accepted gastroduodenal pathogen and is being investigated for possible implications in nongastroenterological conditions such as growth impairment. Subjects infected by cytotoxic Cag-A positive strains seem more likely to develop serious gastroduodenal diseases but the possible role of Cag-A positive strains in non gastroenterological diseases has not been fully investigated. OBJECTIVE: 1) To evaluate the prevalence of Helicobacter pylori infection and Cag-A positivity in short children compared to auxologically normal children. All the subjects were without gastro-intestinal symptoms and were not obese or significantly underweight. 2) To verify the reliability of the ELISA assay for H. pylori. SUBJECTS: H. pylori infection was assessed in 338 children, 182 auxologically normal and 156 short children, with and without deficiency in growth hormone, by the determination of specific IgG antibody. In 79 subjects (all seropositive and a random sample of seronegative children), 13C-urea breath test and cytotoxic Cag-A positive strains were examined. RESULTS: The overall seroprevalence of H. pylori infection by IgG antibody was 18/156 (11.5%) and 13/182 (7.1%) in short and auxologically normal children respectively. The 13C-urea breath test was positive in 29 children: 17 (10.9%) short and 12 (6.6%) auxologically normal. Western blotting documented infection by cytotoxic Cag-A positive strains in 12/17 (70.6%) and 8/12 (66.6%) of short and auxologically normal children respectively. None of the differences between the two groups were significant. CONCLUSIONS: 1) We found a similar prevalence of H. pylori infection and Cag-A positivity in two large pediatric populations of short or auxologically normal children. Therefore: 1) Our data did not confirm a role of H. pylori infection in short stature in children. 2) We found a high reliability of ELISA assay for the detection of IgG antibodies compared to breath test.

Helicobacter pylori and type 1 diabetes mellitus in children.

BACKGROUND: Helicobacter pylori is a recognized gastroduodenal pathogen and H. pylori infection is one of the most common bacterial infections, usually acquired during childhood. However, diabetes mellitus is characterized by an increased susceptibility to infections. METHODS: We compared the prevalence of H. pylori infection as well as cytotoxin-associated gene A-CagA-and vacuolating cytotoxin gene A-VacA-positivity in 103 children and adolescents with type 1 diabetes mellitus and in 236 nondiabetic children. We used a novel Recombinant ImmunoBlot Assay-Strip (RIBA SIA) with individual band for whole H. pylori lysate and recombinant CagA and VacA. RESULTS: H. pylori-positive subjects, both diabetics and controls, were significantly older than negative subjects. In the whole group of diabetic patients the prevalence of each of the three reactivities was higher than in control subjects, reaching significance only for lysate. Only diabetic patients over 12 years of age, with a longer disease duration, had a higher prevalence of positive cases, although not significantly so. CONCLUSIONS: In the first few years of disease, diabetic children do not differ from the nondiabetic population. Subsequently they show an H. pylori seroprevalence tendentially higher than that of controls of the same age. Therefore, H. pylori infection acquired in childhood and lasting several years, could be one of the causes of chronic atrophic gastritis, which is more frequent in longstanding diabetes mellitus.

Birth weight affects final height in patients treated for growth hormone deficiency.

OBJECTIVE: Birth weight influences both postnatal growth and the initial response to GH therapy in GH-deficient subjects, but its relationship to final height is uncertain. Therefore, we examined final height results in a group of subjects treated for GH deficiency who were born small, appropriate or large for gestational age (GA). DESIGN: Retrospective study. PATIENTS: 108 GH-treated patients (age at diagnosis 11.1 +/- 2.0 years) affected by idiopathic and isolated GH deficiency (peak < 8 microg/l after pharmacological and/or nocturnal mean GH concentration

Outcome of premature thelarche: relation to puberty and final height.

BACKGROUND: There is a debate about the possible progression of idiopathic premature thelarche towards precocious or early puberty. OBJECTIVE: To evaluate height and age at onset of puberty in a group of girls with a history of idiopathic premature thelarche. STUDY DESIGN: The height and age at onset of puberty of 42 girls now over 10 years of age who were diagnosed with isolated premature thelarche before the age of 3 years were evaluated. RESULTS: Menarche was reached before or at 11 years of age in 13.5% of this group of girls. This percentage of early menarche was higher than would be expected from historical controls in the general population, but was consistent with maternal age of menarche. The mean (SD) height of the girls (n = 15) who achieved adult height was 162.9 (6.3) cm, which was slightly higher than the mean (SD) relative mid-parental height (160.7 (6.7) cm). CONCLUSIONS: Isolated premature thelarche with onset before 3 years of age progresses towards precocious puberty, although this was consistent with the maternal age of menarche. Furthermore, adult height was normal when compared with population norms in all patients.

Unusual magnetic resonance imaging findings of the sellar region in subjects with hypopituitarism: report of 4 cases.

Out of 323 consecutive growth hormone deficient patients who underwent magnetic resonance imaging (MRI), we describe the clinical and neuroradiological characteristics of four patients in whom MRI revealed unusual pictures of the sellar area. They were selected as unique in their morphological picture and representative of rare conditions. At presentation all subjects had short stature, growth hormone (GH) deficiency and complex phenotypical abnormalities. Patient 1. Female affected by vaginal atresia and sinus urogenitalis, polydactyly and syndactyly with Y-shaped metacarpals. MRI at age 11.2 years revealed normal pituitary, but hypothalamic mass occupying the suprasellar and interpeduncular cistern. The diagnosis of Hall-Pallister syndrome was made. Patients 2 and 3. Two sisters with a history of epilepsy both showing mild intellectual deficiency, midface hypoplasia and ectodermal dysplasia. MRI at age 8 and 12 years respectively displayed in both cases a round hypointensity protruding from the dorsum sellae into a normal pituitary. The diagnosis was sellar spine. Patient 4. Male with a history of postnatal hypoglycemia showing microphallus and clinical features of severe hypopituitarism. Hormonal evaluation at age 8 months confirmed multiple pituitary hormone deficiencies and MRI at age 6 years showed absent anterior lobe, rudimentary stalk and posterior lobe ectopia. The diagnosis was pituitary aplasia. The patients described show that MRI in pituitary dwarfs can reveal unusual intrasellar findings and allow the correct diagnosis of rare syndromes. Our patients also demonstrate the wide variability in the association of hypopituitarism with midline congenital abnormalities and the possible combination with complex syndromes.

Helicobacter pylori and diminished growth in children: is it simply a marker of deprivation?

Helicobacter pylori is an accepted gastroduodenal pathogen and has recently been investigated for possible implications in non gastroenterological diseases such as growth impairment coronary heart disease and diabetes. Infection by cytotoxic, i.e., CagA or VacA positive strains seems more likely to lead to more serious gastroduodenal diseases compared to infection by non cytotoxic strains, but the possible role of CagA or VacA positive strains in non gastroenterological diseases has not been investigated. Aim of the present study was to evaluate the prevalence of Helicobacter pylori infection as well as CagA and VacA positivity in three paediatric populations auxologically normal, hyposomic and diabetic children. Sera from a total of 522 children (auxologically normal: 246, hyposomic: 164, diabetic: 112) were analyzed by a novel Recombinant ImmunoBlot Assay-Strip Immunoblot Assay--RIBA SIA--which contain individual band for whole Helicobacter pylori lysate and recombinant CagA and VacA. The overall seroprevalence of reactivities against Helicobacter pylori lysate, CagA and VacA were: 7.3%, 9.3%, 6.9% vs 11.6%, 7.9%, 8.5% vs 14.3%, 13.4%, 8% (p = NS) in auxologically normal, hyposomic and diabetic children, respectively. Summarizing, we found a similar prevalence of reactivity against both whole Helicobacter pylori lysate as well as recombinant CagA and VacA between auxologically normal, hyposomic and diabetic children. Our data do not support a possible role of Helicobacter pylori in diminished growth in children.

[Results of screening of congenital hypothyroidism and iodine excess in neonatal age]. / Risultati dello screening dell'ipotiroidismo congenito ed eccesso di iodio in epoca neonatale.

We evaluated the distribution of TSH levels on dried blood spots (Delfia system-threshold value for recall 20 microU/ml) in 27,282 consecutive samples examined during 1993, in the Emilia-Romagna region. We also evaluated, by questionnaire, the frequency of iodine disinfection in the perinatal period in all centers that do blood spots. We also evaluated the distribution of TSH spot values according to the localization of the center in endemic or not endemic area of the region. Among the parameters we considered, only the sampling day (p < 0.02) and the maternity center (p < 0.0001) showed a significant influence on TSH spot values. With regard to the questionnaire, the centers which habitually used iodine disinfection in obstetrics (20/28) showed significantly higher percentages of TSH values over 10 microU/ml than the centers which did not use (3/28) or rarely used (4/28) this type of disinfection (p < 0.0001). The only center which used regular iodine disinfection of umbilical cord in all newborns, showed a percentage of TSH values over 10 microU/ml (25.8%) and a recall rate (2.5%) significantly higher than all other centers (p < 0.0001).

Final height of patients treated for isolated GH deficiency: examination of 83 patients.

The aim of the present study was to evaluate retrospectively the influence of various auxological and laboratory parameters on final height in a group of GH-deficient children after replacement therapy and to compare their final height with that of a group of short children with normal GH secretion and hence not treated. The final height was evaluated of 83 patients (51 males and 32 females) affected by idiopathic isolated GH deficiency and treated with recombinant human GH (hGH) for 2-7 years. Inclusion criteria at the start of treatment were short stature (mean height for chronological age in standard deviation score (SDS) -2.21) due to idiopathic isolated GH deficiency (GH peak < 8 micrograms/l after two pharmacological tests and/or mean GH concentration < 3.3 micrograms/l during the night) and treatment with recombinant hGH for at least 2 years at a dose of 15-20 U/m2 per week by s.c. injection for 6 or 7 days/ week. Mean chronological age at diagnosis was 12.2 +/- 1.7 years; 35 were prepubertal and 48 pubertal. The final height of 51 untreated short stature (mean height for chronological age in SDS -2.13 at diagnosis) subjects (42 males and 9 females: 29 prepubertal and 22 pubertal at diagnosis with mean chronological age 11.6 +/- 2.4 years) with normal GH secretion was also evaluated. In the treated subjects final height SDS was higher than that of the untreated group (-1.3 vs -1.7 SDS; P = 0.01). Both treated and untreated subjects showed a final height lower than target height, but 39% of the treated subjects vs only 20% of the untreated group (P = 0.035) had a final height greater than target height. In the treated subjects this percentage was higher in the patients improving their height for bone age in the first years of therapy. While treated females showed a positive correlation only between target and final height (P = 0.0001), in treated males final height correlated with the Bayley-Pinneau prediction at diagnosis, height for chronological age and bone age at diagnosis and target height. Patients who started therapy before puberty also showed these correlations with data calculated at the onset of puberty, together with a correlation with chronological age at the onset of puberty. When considering the influence of GH response at tests on final height, the percentage of subjects exceeding target height increased progressively according to the severity of the GH deficiency. There was no difference in height gain between the patients starting therapy before or during puberty. The height gain, however modest, obtained by our treated patients, the number of patients with final height greater than target height and the favourable comparison with the untreated short-stature subjects represent a promising result, which could be improved by personalizing treatment.

Abnormal insulin response to glucose following treatment for Wilms' tumor in childhood.

UNLABELLED: To determine whether beta-cell function could be impaired by the treatment for Wilms' tumour (WT) in childhood. We investigated the insulin secretion of 44 survivors of WT (22 males) with a median off-treatment follow up of 8.3 years (range 1-19.8). All patients had an intravenous glucose tolerance test (IVGTT) (0.5 gm/kg, max 25 g) to determine the first-phase insulin response (FPIR) (sum of the 1- and 3-min insulin concentrations). Median age at the time of the study was 12.7 years (range 4.2-22.7). Eight subjects (7 males) had a FPIR value below the 3rd percentile, and 7 (3 males) above the 97th centile. Among the 22 patients who received radiotherapy. 7 (6 males) showed a FPIR < 3rd percentile versus only 1 (a male) of the 22 patients who received no radiation (31.8% vs 4.5%; P < 0.05). Analysis of variance showed that the time elapsed since therapy had a significant role on the development of low FPIR only in males. The 7 patients with an insulin release > 97th percentile did not show any significant difference compared to subjects with lower insulin values for weight, age at diagnosis, sex, time elapsed since treatment, radiotherapy and chemotherapy protocol. CONCLUSION: An impaired insulin response is evident in some patients treated for WT in childhood, mainly in male patients who received abdominal radiotherapy and were examined a longer time after therapy. We hypothesize that this decreased insulin release is related to damage due to radiotherapy and therefore a careful follow up is recommended in adulthood in these patients.

Developmental pattern of fetal growth hormone, insulin-like growth factor I, growth hormone binding protein and insulin-like growth factor binding protein-3.

AIMS: To evaluate the developmental pattern of fetal growth hormone (GH), insulin-like growth factor I (IGF-I), GH binding protein (GHBP) and IGF binding protein-3 (IGF-3); to determine the implications for fetal growth. METHODS: Serum GH, IGF-I, GHBP and IGFBP-3 were measured in 53 fetuses, 41 aged 20-26 weeks (group A) and 12 aged 31-38 weeks (group B). Fetal blood samples were obtained by direct puncture of the umbilical vein in utero. Fetal blood samples were taken to rule out beta thalassaemia, chromosome alterations, mother to fetus transmissible infections, and for maternal rhesus factor. GHBP was determined by gel filtration chromatography of serum incubated overnight with 125I-GH. GH, IGF-I and IGFBP-3 were determined by radioimmunoassay. RESULTS: Fetal serum GH concentrations in group A (median 29 micrograms/l, range 11-92) were significantly higher (P < 0.01) than those of group B (median 16.7 micrograms/l, range 4.5-29). IGF-I in group A (median 20 micrograms/l, range 4.1-53.3) was significantly lower (P < 0.01) than in group B (median 75.2 micrograms/l, range 27.8-122.3). Similarly, IGFBP-3 concentrations in group A (median 950 micrograms/l, range 580-1260) were significantly lower than those of group B (median 1920 micrograms/l, range 1070-1770). There was no significant difference between GHBP values in group A (median 8.6%, range 6.6-12.6) and group B (median 8.3%, range 6-14.3). Gestational age correlated positively with IGF-I concentrations (P < 0.0001) and IGFBP-3 (P < 0.0001) and negatively with GH (P < 0.0001). GHBP values did not correlate with gestational age. Multiple regression analysis showed a negative correlation between GH:IGF-I ratio and fetal growth indices CONCLUSIONS: The simultaneous evaluation of fetal GH, IGF-I, IGFBP-3 and GHBP suggests that the GH-IGF-I axis might already be functional in utero. The progressive improvement in the efficiency of this axis in the last part of gestation does not seem to be due to an increase in GH receptors.

Modifications of metabolic control in type 1 diabetic children and adolescents: experience over the last 20 years.

The aim of this retrospective study was to verify whether the daily number of insulin injections could have affected metabolic control in 181 unselected diabetic patients (age 0.66-14.75 yr at onset of diabetes) followed in our clinic from the 1970s to the 1990s. They were evaluated regularly since onset of disease for a mean follow-up period of 6.8 years. The factor with the greatest effect on HbA1c levels was the year of disease onset, which was negatively correlated with HbA1c independently of the daily number of injections and disease duration. Disease duration showed an effect on metabolic control only in the first 5 years of disease. Daily insulin injections affected metabolic control above all as regards 1 vs 2 or more injections. Regarding the change in insulin regimen from 2 to 3-4 injections, there was an improvement in metabolic control in patients with HbA1c > 9% and a worsening in those with HbA1c < 7%/ After the first 5 years of the disease HbA1c levels were higher in adolescent patients than in both younger and older patients. In conclusion, increasing the daily number of injections does not seem in itself capable of eliciting marked improvement in metabolic control, as in our young diabetic patients in the last decade. Multiple insulin injection therapy seems to be mostly indicated for patients with poor control and for adolescents.