Permanent diabetes during the first year of life: multiple gene screening in 54 patients.

AIMS/HYPOTHESIS: The aim of this study was to investigate the genetic aetiology of permanent diabetes mellitus with onset in the first 12 months of age. METHODS: We studied 46 probands with permanent, insulin-requiring diabetes with onset within the first 6 months of life (permanent neonatal diabetes mellitus [PNDM]/monogenic diabetes of infancy [MDI]) (group 1) and eight participants with diabetes diagnosed between 7 and 12 months of age (group 2). KCNJ11, INS and ABCC8 genes were sequentially sequenced in all patients. For those who were negative in the initial screening, we examined ERN1, CHGA, CHGB and NKX6-1 genes and, in selected probands, CACNA1C, GCK, FOXP3, NEUROG3 and CDK4. The incidence rate for PNDM/MDI was calculated using a database of Italian patients collected from 1995 to 2009. RESULTS: In group 1 we found mutations in KCNJ11, INS and ABCC8 genes in 23 (50%), 9 (19.5%) and 4 (8.6%) patients respectively, and a single homozygous mutation in GCK (2.1%). In group 2, we identified one incidence of a KCNJ11 mutation. No genetic defects were detected in other loci. The incidence rate of PNDM/MDI in Italy is estimated to be 1:210,287. CONCLUSIONS/INTERPRETATION: Genetic mutations were identified in ~75% of non-consanguineous probands with PNDM/MDI, using sequential screening of KCNJ11, INS and ABCC8 genes in infants diagnosed within the first 6 months of age. This percentage decreased to 12% in those with diabetes diagnosed between 7 and 12 months. Patients belonging to the latter group may either carry mutations in genes different from those commonly found in PNDM/MDI or have developed an early-onset form of autoimmune diabetes.

The ALBA project: an evaluation of needs, management, fears of Italian young patients with type 1 diabetes in a school setting and an evaluation of parents' and teachers' perceptions.

OBJECTIVE: To determine how Italian parents and school personnel of 6-13-year-old children with type 1 diabetes (T1D) manage during school hours, including insulin administration, management of hypoglycemia, and glucagon use. A further aim was an investigation into the responsibilities and training of school personnel regarding diabetes. RESEARCH DESIGN AND METHODS: After an initial qualitative phase, semi-structured questionnaires were completed by a sample of parents and teachers. RESULTS: 220 parent and 52 teacher questionnaires were completed. 43.6% of parents said diabetes had negatively influenced school activities. Children either self-administer insulin, or have help from a parent, since there is very rarely a nurse present (3.6%) or a teacher who will take responsibility for the treatment (2.9%). Most parents (55.9%) stated either that the school had no refrigerator to store glucagon or that they did not know if the school was so equipped. A small percentage of teachers considered their schools to be equipped to manage an emergency (23%) and said they would use glucagon directly in an emergency (14.9%). Only 40.4% of teachers said that they had received any specific training. CONCLUSIONS: The study shows that people who are not directly involved have superficial knowledge of the different aspects of diabetes, even though no parents reported episodes of neglect/incorrect management. There is no legislation which clearly defines the role of the school in the care of children with T1D, and teachers are not trained to help them. Training sessions for school personnel and greater legislative clarity about the 'insulin and glucagon question' are key factors that may improve the full integration of the child with diabetes.

Target setting in intensive insulin management is associated with metabolic control: the Hvidoere childhood diabetes study group centre differences study 2005.

OBJECTIVE: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. METHODS: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. RESULTS: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). CONCLUSIONS: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.

Serum Th1 (CXCL10) and Th2 (CCL2) chemokine levels in children with newly diagnosed Type 1 diabetes: a longitudinal study.

AIMS: Cell-mediated immunity and pro-inflammatory cytokines are implicated in the pathogenesis of Type 1 diabetes. The aim of this study was to investigate whether circulating chemokines involved in T-helper 1 (CXCL10) and T-helper 2 (CCL2) autoimmunity are increased in children with Type 1 diabetes at onset and follow-up. METHODS: Serum CXCL10 and CCL2 were measured in 96 children with newly diagnosed Type 1 diabetes, 59 age-matched first-degree relatives of diabetic children and 40 age-matched non-diabetic children with no family history of diabetes. In the diabetic children, an additional serum sample was obtained a median of 16 months after diagnosis. RESULTS: Serum CXCL10 levels were significantly higher in Type 1 children than in relatives or control children (P < 0.001); 44.7% of patients had a serum CXCL10 level >or= 2 standard deviation above the mean value of the control group vs. 3.4% of relatives (P < 0.0001). In contrast, serum CCL2 levels were similar in patients, relatives and control subjects. In the Type 1 diabetic patients at follow-up, CXCL10 was significantly reduced vs. baseline (P = 0.01), while CCL2 did not change. CONCLUSIONS: In children with newly diagnosed Type 1 diabetes, raised serum CXCL10 and normal CCL2 concentrations signal a predominant T-helper 1-driven autoimmune process, which shifts toward T-helper 2 immunity over the first 1-2 years from diagnosis.

Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?

AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood. RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen. CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres.

Anti-CD38 autoimmunity in children with newly diagnosed type 1 diabetes mellitus.

AIMS: To test for anti-CD38 autoimmunity in children with newly-diagnosed type 1 diabetes mellitus (DM1). METHODS: Serum anti-CD38 autoantibodies were detected by Western blot in 270 children (130 girls, 140 boys, mean age 8 +/- 4 years) with newly-diagnosed DM1 and 179 gender- and age-matched non-diabetic children. In 126 diabetic children, another blood sample was obtained 15 +/- 4 months after the diagnosis. RESULTS: Anti-CD38 autoantibody titers at least 3 SD above the mean value for the control group were found in 4.4% of children with DM1 vs 0.6% of controls (chi2 = 5.8, p <0.016). No statistical differences were observed between anti-CD38 positive and negative patients in terms of phenotype. At follow-up, of six diabetic children who were positive for anti-CD38 antibodies, two were new cases. A positive correlation was found between the antibody titer of diabetic sera at diagnosis and follow up (r = 0.46, p <0.0001). CONCLUSION: An autoimmune reaction against CD38, a protein expressed in human islets, is associated with newly-diagnosed DM1. In children with DM1, CD38 autoimmunity increases with time and persists.

Effectiveness of a prevention program for diabetic ketoacidosis in children. An 8-year study in schools and private practices.

OBJECTIVE: To shorten the period of carbohydrate intolerance preceding the diagnosis of IDDM in children. RESEARCH DESIGN AND METHODS: The incidence of diabetic ketoacidosis (DKA) was studied in newly diagnosed diabetic children aged 6-14 years, in the area of Parma, Italy, 8 years after an information program on DKA was introduced to teachers, students, parents, and pediatricians. Information was provided by displaying a poster with a few practical messages in 177 primary and secondary public schools. The pediatricians working in the same area were given equipment for the measurement of both glycosuria and blood glucose levels, as well as cards listing guidelines for the early diagnosis of diabetes, to be given to patients. A toll-free number was also provided. Clinical and laboratory features of 24 young diabetic patients diagnosed in the Parma area (group 1) were compared with those of 30 patients coming from two nearby areas in which no campaign for the prevention of DKA had been carried out (group 2). RESULTS: From 1 January 1991 to 31 December 1997, DKA was diagnosed in 3 children from group 1 (12.5%) and in 25 children from group 2 (83.0%) (chi 2 = 26.8; P = 0.0001). The three cases of DKA in group 1 were observed in 1991 (n = 1) and in 1992 (n = 2). No patients from the Parma area who had DKA were admitted to our unit after 1992. The duration of symptoms before diagnosis was 5.0 +/- 6.0 and 28.0 +/- 10.0 days (P < 0.0001), in groups 1 and 2, respectively, Metabolic derangements were less severe in patients of group 1 than in those of group 2. Hospitalization for the treatment of overt diabetes and for the teaching of self-management of the disease lasted 5.4 +/- 1.2 days in group 1 and 13.3 +/- 2.4 days in group 2 (P = 0.002). The total cost of the 8-year campaign was $23,470. CONCLUSIONS: The prevention program for DKA in diabetic children aged 6-14 years, carried out in the Parma area during the last 8 years, was successful. Thanks to this program, cumulative frequency of DKA in new-onset IDDM decreased from 78% during 1987-1991 to 12.5% during 1991-1997. None of the newly diagnosed diabetic children aged 6-14 years and from the Parma area were ever admitted to the hospital for DKA after 1992.

Increased Na+/Li+ countertransport activity may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria.

OBJECTIVE: To evaluate whether erythrocyte sodium-lithium countertransport (Na+/Li+ CT) activity may identify adolescents and young adults with childhood-onset of type 1 diabetes to be at greater risk to develop persistent microalbuminuria and incipient diabetic nephropathy. RESEARCH DESIGN AND METHODS: In January 1989, Na+/Li+ CT was measured in 170 normoalbuminuric diabetic adolescents and young adults (age 12-23 years; onset of diabetes before age 18 years; duration of diabetes longer than 7 years). Participants were clinically examined at baseline and biennially thereafter. Na+/Li+ CT activity was measured every 2 years during the 8-year follow-up period. Na+/Li+ CT activity was measured also in parents of diabetic offspring. RESULTS: Over 8 years, 18 (10 male, 8 female) out of 170 patients (10.5%) developed persistent microalbuminuria; no patient developed overt nephropathy. The risk of developing microalbuminuria was higher in children with increased Na+/Li+ CT (using 300 mumol.1 erythrocytes-1.h-1 as the arbitrary cutoff point) (group 1) compared with those with normal Na+/Li+ CT at the beginning of the study (group 2) (18.98 vs. 3.29%, P < 0.01; sensitivity 96.7%; specificity 57.9%). Sex did not influence predictive value, sensitivity, or specificity. Na+/Li+ CT was not significantly correlated with HbA1c or duration of type 1 diabetes. The percentage of offspring with both parents having Na+/Li+ CT activity above the median values was significantly higher in patients in group 1 than in group 2. The odds ratio for the occurrence of microalbuminuria after adjustment for confounding variables (albumin excretion rate [AER], sex, HbA1c, mean blood pressure, cholesterol, triglycerides) in type 1 diabetic adolescents with elevated baseline erythrocyte Na+/Li+ CT was 4.5 (95% CI of 2.1-11.4). CONCLUSIONS: These results confirm those of previous studies and suggest that Na+/Li+ CT may be one of the predictors and risk factors for incipient diabetic nephropathy in adolescents and young adults with onset of diabetes during childhood. Persistently increased Na+/Li+ CT activity may help to identify normotensive, normoalbuminuric patients with type 1 diabetes who are predisposed to develop microalbuminuria and incipient diabetic nephropathy.

Good metabolic control is associated with better quality of life in 2,101 adolescents with type 1 diabetes.

OBJECTIVE: It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families. RESEARCH DESIGN AND METHODS: The study involved 2,101 adolescents, aged 10-18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA(1c) was analyzed centrally (normal range 4.4-6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires. RESULTS: Mean HbA(1c) was 8.7% (range 4.8-17.4). Lower HbA(1c) was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores. CONCLUSIONS: In a multiple regression model, lower HbA(1c) was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.

Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidøre Study Group.

OBJECTIVE: Twenty-one international pediatric diabetes centers from 17 countries investigated the effect of simple feedback about the grand mean HbA(1c) level of all centers and the average value of each center on changes in metabolic control, rate of severe hypoglycemia, and insulin therapy over a 3-year period. RESEARCH DESIGN AND METHODS: Clinical data collection and determination of HbA(1c) levels were conducted at a central location in 1995 (n = 2,780, age 0-18 years) and 1998 (n = 2,101, age 11-18 years). RESULTS: Striking differences in average HbA(1c) concentrations were found among centers; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. They were apparent even in patients with short diabetes duration and remained stable 3 years later (mean adjusted HbA(1c) level: 8.62 +/- 0.03 vs. 8.67 +/- 0.04 [1995 vs. 1998, respectively]). Three centers had improved significantly, four centers had deteriorated significantly in their overall adjusted HbA(1c) levels, and 14 centers had not changed in glycemic control. During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, the adjusted number of injections by 0.23 injections per day, and the adjusted BMI by 0.95 kg/m(2). The 1995 versus 1998 difference in glycemic control for the seven centers could not be explained by prevailing insulin regimens or rates of hypoglycemia. CONCLUSIONS: This study reveals significant outcome differences among large international pediatric diabetes centers. Feedback and comparison of HbA(1c) levels led to an intensification of insulin therapy in most centers, but improved glycemic control in only a few.

Leptin, cortisol, and GH secretion interactions in short normal prepubertal children.

The hormonal regulation of the ob gene and leptin secretion in humans is still unclear. To investigate the interactions among leptin, cortisol, and GH, we analyzed and time-cross-correlated their spontaneous 24-h secretion in 12 short normal prepubertal children of both sexes (6 females and 6 males). Time-cross-correlation analyses demonstrated that leptin and cortisol were correlated in both a negative and positive fashion. The negative correlation, with cortisol leading leptin by 4 and 3 h for boys and girls, respectively, might reflect the stimulatory effect of CRH on the sympathetic system, which inhibits leptin secretion; the positive correlation, with leptin leading cortisol by 6 and 5 h for boys and girls, respectively, might reflect a direct effect of leptin on CRH secretion in the hypophyseal portal system. Time-cross-correlation analyses also showed a strong positive correlation between GH and leptin concentrations, with GH leading leptin by 5 and 2 h for boys and girls, respectively, suggesting a possible direct leptin-releasing effect of GH on adipocytes. We conclude that cross-correlation analyses of 24-h hormone secretions under baseline physiological conditions suggest that the hypothalamic-pituitary-adrenal axis might have a prevailing inhibitory effect on leptin secretion, whereas leptin might exert a positive effect on the hypothalamic-pituitary-adrenal axis. The relation between GH and leptin could be a direct one and characterized prevalently by a positive effect of GH on leptin secretion. Further investigations using different experimental systems are needed to ascertain the validity of these mathematically educed conclusions.

Spontaneous thyrotropin and cortisol secretion interactions in patients with nonclassical 21-hydroxylase deficiency and control children.

Both exogenous and endogenous hypercortisolism result in reduced TSH secretion and mild hypothyroidism. However, little is known about the relation between endogenous TSH and cortisol secretion under physiological or slightly disturbed conditions. To examine this, we evaluated the pulsatility and circadian rhythmicity and time-cross-correlated the 24-h secretory patterns of cortisol and TSH in eight prepubertal children with nonclassical congenital adrenal hyperplasia (NCCAH) and eight age-matched short normal children. In both groups, TSH and cortisol were secreted in a pulsatile and circadian fashion, with a clear nocturnal TSH surge. Although no difference in mean 24-h TSH levels was observed between the two groups, daytime TSH levels were lower in the NCCAH group than in control children (P < 0.05). The cross-correlation analysis of the 24-h raw data showed that TSH and cortisol were negatively correlated, with a 2.5-h lag time for both groups, with cortisol leading TSH. This correlation might reflect a negative glucocorticoid effect exerted on the hypothalamic-pituitary-thyroid axis under physiological conditions. A significant positive correlation with TSH leading cortisol was observed at 8.5 and 5.5 h lag times for the control and NCCAH groups, respectively. The substantially shorter lag time of this positive correlation in NCCAH children than in controls suggests that in the latter, the nocturnal TSH peak occurs temporally closer to their compromised morning cortisol peak. These data indicate that the hypothalamic-pituitary-adrenal axis has a primarily negative influence on endogenous TSH secretion and that even mild disturbances in cortisol biosynthesis are associated with slight alterations in TSH secretion.

Ovarian 17 alpha-hydroxyprogesterone responses to GnRH analog testing in oligomenorrheic insulin-dependent diabetic adolescents.

OBJECTIVE: To investigate the pituitary-ovarian function in adolescent girls with insulin-dependent diabetes mellitus (IDDM). DESIGN: Clinical case-control study. METHODS: The GnRH analog leuprolide acetate was administered subcutaneously to 16 adolescents with IDDM (seven eumenorrheic and nine oligomenorrheic) and 13 controls between 0800 and 0900 h. Blood samples were collected at baseline and 0.5, 3, 6 and 24 h after leuprolide to measure levels of gonadotropins, 17 alpha-hydroxyprogesterone (17-OHP), androgens and estradiol. RESULTS: Mean baseline serum LH levels were significantly higher in eumenorrheic compared with oligomenorrheic IDDM patients, while peak LH responses to GnRH analog testing were similar in all subjects. Oligomenorrheic IDDM girls showed, as a group, a distinct 17-OHP response to GnRH analog stimulation, which in five out of nine girls was in the range of functional ovarian hyperandrogenism (> or = 8.6 nmol/l). Androgen and estradiol levels were not significantly altered in any group. No correlation was found between steroid levels and HbA1c levels, although the latter were significantly higher in oligomenorrheic than in eumenorrheic patients. CONCLUSION: About 50% of the oligomenorrheic IDDM adolescents had an increased ovarian 17-OHP response to GnRH analog stimulation in the range of functional ovarian hyperandrogenism. Factors other than metabolic control, such as stress, may play an etiologic role in IDDM ovarian dysfunction.

Vitreous fluorophotometry in juvenile diabetics after oral fluorescein.

Vitreous fluorophotometry was performed in young patients (8 to 19 years old) affected by insulin-dependent diabetes mellitus, with no signs of diabetic retinopathy. Oral fluorescein was administered, and measures were used to prevent hypoglycemia during the examination. The results showed a breakdown of the blood-retinal barrier in nine (43%) of the 21 patients. The oral fluorescein method allows a satisfactory evaluation of ocular fluorescence profiles, with minimal risk of systemic side effects.

Adrenal steroid and adrenocorticotropin responses to human corticotropin-releasing hormone stimulation test in adolescents with type I diabetes mellitus.

To determine whether abnormalities of hypothalamic-pituitary-adrenal axis function occur in type I diabetes mellitus, corticotropin, cortisol, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), and DHEA sulfate (DS) levels were measured after an intravenous (IV) injection of 1 microgram/kg human corticotropin-releasing hormone (CRH) in diabetic adolescents and normal age-matched subjects. CRH produced a consistent increase in corticotropin blood levels that was comparable in the two groups. In contrast, both baseline and stimulated cortisol concentrations were greater in diabetic patients. Levels of 17-OHP increased after CRH administration, and the magnitude of increase was similar in all subjects. Stimulation with CRH determined an attenuated integrated DS response in diabetics compared with normal subjects with a different pattern of the hormone secretion, whereas no differences in D4-A concentrations were detected between the two groups. DHEA serum levels of subjects from both groups underwent similar changes following administration of CRH. In conclusion, patients with type I diabetes have a discrete response of adrenal steroids to CRH stimulation that appears to be independent of corticotropin secretion. This phenomenon might be related to a direct effect of insulin on enzyme systems involved in the biosynthetic pathway of adrenal steroids or, alternatively, to an intra-adrenal CRH/corticotropin mechanism acting on the adrenal cortex in a paracrine manner.

Blood pressure tracking in adolescents with insulin-dependent diabetes mellitus.

Hypertension, one of the most frequent and important complications of insulin-dependent diabetes mellitus (IDDM), usually begins in the second decade of the disease and is rare in childhood. We analysed the blood pressure (BP) levels of 106 patients (48 males, 58 females, aged 2-16 years) in relation to sex and age and we studied the modification of BP with years (tracking). BP levels, registered every three to six months, were compared with the local standard levels for age and expressed as standard deviation scores (SDS) of the means. For each subject a regression line describing the change of the SDS over time was calculated by the method of least squares. The slope of this line is called trend and represents the tendency of BP to increase or decrease with time, i.e. to develop (or not) hypertension. All patients, except one 16 year old girl, had normal BP and no microalbuminuria but ten of them presented with mean levels in the upper quartile and/or a constantly upward BP trend and were considered at risk. After a three year follow-up four of these ten patients became frankly hypertensive with increased microalbuminuria. These results agree with previous findings and with the hypothesis that an increase of intraglomerular and/or systemic BP may precede the appearance of (and even could be responsible for) microalbuminuria. The BP tracking study in IDDM children and adolescents could be useful for an early recognition of patients at risk of developing hypertension and diabetic nephropathy.

Italian cross-sectional growth charts for height, weight and BMI (6-20 y).

OBJECTIVE: To trace growth charts for height, weight and body mass index (BMI) that apply to the whole Italian population. Different charts were drawn for central-north and south Italy since children in central-north regions are known to be taller and leaner. DESIGN: Cross-sectional study. SETTING: A sample of schoolchildren covering 16 of the 20 Italian regions, with data collected between 1994 and 2000. SUBJECTS: A total of 27 421 girls and 27 374 boys, aged 6-20 y. METHODS: Height and weight were measured using portable Harpenden stadiometers and properly calibrated scales, respectively. SIEDP references are presented both as centiles and as LMS curves for the calculation of standard deviation scores. According to International Obesity Task Force, SIEDP charts for BMI include the limits for overweight and obesity, ie the centiles having, at 18 y of age, the value of 25 and 30 kg/m(2), respectively. RESULTS: The comparison between SIEDP and Tanner et al's charts for height, still in use among most Italian paediatricians, shows that before puberty Italian children are 2-4 cm taller than their English peers. Because of these differences, Tanner's charts fail to detect, when applied to Italian children, 50-90% of short children aged 6-11 y, ie with stature below the 3rd centile of their reference population. Rolland-Cachera et al's centiles for BMI are lower than those of SIEDP standards, mainly during adolescence (up to 6.6 kg/m(2) for the 97th centile), and apply poorly to Italian children. The prevalence of overweight is 27 (boys) and 19% (girls) in south Italy vs 17 (boys) and 10% (girls) in central-north Italy. CONCLUSIONS: These references intend to supply Italian paediatricians with a tool that avoids the use of outdated or inadequate charts, and thus should be suitable for monitoring their patients' growth. SPONSORSHIP: Italian Society for Pediatric Endocrinology and Diabetes (SIEDP).

Transient neonatal diabetes mellitus: a relapse after 10 years of complete remission.

The follow-up study of a patient with permanent diabetes (DM) unrelated to islet cell antibody and anti-insulin antibodies and occurring 10 years after a transient neonatal DM episode is reported. A latent defect in insulin release was proved. It produced transient glucosuria during intercurrent illnesses and permanent hyperglycaemia and a decrease in growth velocity [with high stimulated growth hormone and low insulin-like growth factor I (IGF-I)] at the onset of puberty. After insulin therapy was re-introduced, catch-up growth and normalization of the blood glucose and IGF-I levels were noted.

Refill patterns of atypical and conventional antipsychotic medications at a national retail pharmacy chain.

This study examined whether patients who received prescriptions for conventional and atypical antipsychotics in routine outpatient care continued medication therapy. Prescription refill records of more than 25,000 patients from a national retail pharmacy chain were surveyed during a full eight-month period. At the start of the ninth month, 48 percent of the patients taking conventional agents were continuing therapy. The overall rate for those taking atypical agents was 44 percent; however, the rate for those taking clozapine was 71 percent. Atypical agents, despite their improved side effect profile, were not associated with higher rates of continued treatment. A highly supervised medication administration process, frequent patient-provider contact, and favorable patient selection may help explain the higher rate among patients taking clozapine.

Normal values of first-phase insulin response to intravenous glucose in healthy Italian children and adolescents. The Prediabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP).

This study reports the first-phase insulin response (FPIR) calculated on a wide pediatric population. 138 non-obese, ICA- and GAD65 antibody-negative subjects, without family history of IDDM, were tested in 21 Italian Pediatric Diabetic Centers, according to a standardized protocol. After an overnight fast, 0.5 g/kg body weight of 25% dextrose (maximum 35 g) was infused over 2.5-3 minutes. Blood samples were taken at -10, 1, 3, 5 and 10 minutes after dextrose infusion for determination of insulin levels by radioimmunoassay. A significant positive relationship was observed between FPIR and pubertal stage groups (p = 0.0043), suggesting a progressive rise of FPIR throughout puberty. These results have to be taken into consideration in evaluating early abnormalities of carbohydrate metabolism in pubertal subjects. According to Tanner's stage the first percentile was 53 microU/ml for stage I, 53.6 microU/ml for stages II-III and 76.6 microU/ml for stages IV-V.