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Aim To analyze sleep quality and its relationships with clinical and biochemical features in a large cohort of adults with autoimmune diabetes. Methods We administered to 553 patients with autoimmune diabetes the questionnaires: Pittsburgh Sleep Quality Index (PSQI), diabetes distress scale, diabetes-related quality of life and diabetes treatment satisfaction questionnaire. We excluded patients with missing HbA1c ± 4 months from PSQI administration or incorrect PSQI compilation (n = 110). Results Altered sleep quality was recorded in 142/443 subjects (32%), insufficient total sleep time in 177/443 (40%). The altered sleep quality group had higher HbA1c (median 56 mmol/mol [interquartile range-IQR 49–62] vs 59 [IQR 52–68]; P P 53 mmol/mol (74.6% vs 62.8%; P = 0.014). Diabetes duration (P = 0.63), type of insulin delivery (P = 0.48) and glucose monitoring (P = 0.35) were uninfluential. Patients with altered sleep quality showed higher prevalence of autoimmune (42 vs 28%; P = 0.005) and mental diseases (12 vs 4%; P = 0.002); there were greater emotional distress, and lower quality of life and treatment satisfaction (P Conclusion One-third of the patients with autoimmune diabetes showed altered sleep quality, which associates with worse glycemic control, and autoimmune and mental disorders, with sex-specific differences.

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Xarxes reguladores de gens; Marcadors predictius Redes reguladoras de genes; Marcadores predictivos Gene regulatory networks; Predictive markers Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855. This work was supported by Merck KGaA, Darmstadt, Germany.

Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

AIM To ascertain whether the prevalence of retinopathy has declined over the last 2 decades in individuals with childhood-onset type 1 diabetes and whether this might be explained by changes in lifetime HbA1c. MATERIALS AND METHODS A multicentre, retrospective, observational study, comparing 128 subjects with diabetes onset in 2000-2003 assessed for retinopathy in 2016-2019, with a previous cohort of 115 individuals diagnosed in 1990-1993 and assessed for retinopathy in 2007-2009, was conducted. The two cohorts had both a similar diabetes duration and age at diagnosis. Retinal photographs were centrally graded. Lifetime HbA1c and its variability, estimated as the ratio between intrapersonal mean and standard deviation of HbA1c, were evaluated. RESULTS The prevalence of any retinopathy in the new and old cohort was 24.2% and 43.5% (P

Cystic fibrosis related diabetes (CFRD) is a comorbidity of cystic fibrosis (CF) that negatively impacts on its clinical course. Prediabetes is an important predictor of either CFRD development and unfavorable prognosis of CF in both pediatric and adult patients. International guidelines recommend insulin only in case of CFRD diagnosis. Whether early detection and treatment of prediabetes may contribute to improve the clinical course of CF is still debated. A subgroup of pediatric diabetologists of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) performed a systematic review of the literature based on predefined outcomes: impact of pre-diabetes on clinical outcomes and on the risk of developing CFRD; diagnosis of diabetes and pre-diabetes under 10 years of age; effectiveness of therapy on glycemic control, impact of therapy on pulmonary function and nutritional status. Thirty-one papers were selected for the analysis data presented in these papers were reported in tables sorted by outcomes, including comprehensive evidence grading according to the GRADE approach. Following the grading of the quality of the evidence, the entire ISPED diabetes study group achieved consensus for the Italian recommendations based on both evidence and clinical experience. We concluded that in patients with CF, prediabetes should be carefully considered as it can evolve into CFRD. In patients with CF and prediabetic conditions, after complete evaluation of the OGTT trend, glucometrics, glycemic values measured during pulmonary exacerbations and/or steroid therapy, early initiation of insulin therapy could have beneficial effects on clinical outcomes of patients with CF and prediabetes.

Aim: To evaluate the impact of a virtual educational camp (vEC) on glucose control in children and adolescents with type 1 diabetes using a closed-loop control (CLC) system. Materials and Methods: This was a prospective multicentre study of children and adolescents with type 1 diabetes using the Tandem Basal-IQ system. Insulin pumps were upgraded to Control-IQ, and children and their parents participated in a 3-day multidisciplinary vEC. Clinical data, glucose metrics and HbA1c were evaluated over the 12 weeks prior to the Control-IQ update and over the 12 weeks after the vEC. Results: Forty-three children and adolescents (aged 7-16 years) with type 1 diabetes and their families participated in the vEC. The median percentage of time in target range (70-180 mg/dL; TIR) increased from 64% (interquartile range [IQR] 56%-73%) with Basal-IQ to 76% (IQR 71%-81%) with Control-IQ (P&nbsp

Aims: To evaluate the relationships between HbA1c and Continuous Glucose Monitoring (CGM) metrics in children/adolescents with Type 1 Diabetes (T1D). Methods: HbA1c and real-life CGM data of the 12 weeks preceding its measurement were retrospectively collected from 654 children/adolescents with T1D. The relationships between HbA1c and CGM metrics were assessed by Spearman correlation coefficient. Participants were categorized into groups based on HbA1c and CGM metrics values. ANOVA was run across HbA1c and CGM metrics groups in the entire study population and in subjects stratified by CGM type, insulin therapy, age and puberty. Results: HbA1c was positively correlated with mean glucose, SD, %TAR > 180 mg/dL, %TAR > 250 mg/dL, HBGI and negatively with %TIR, %TBR and %time < 54 mg/dL. HbA1c-based groups were significantly associated with these metrics, but for each group their value widely ranged with a substantial overlap between them. HbA1c and HbA1c-based groups were not associated with %CV and LBGI, as well as %CV and LBGI-based groups had not significantly different HbA1c. Comparable results were found analysing subjects according to age, type of CGM, insulin therapy and puberty. Conclusions: The relationships between HbA1c and CGM metrics described in this cohort of paediatric subjects with T1D support the importance of the evaluation of these metrics, in particular %CV and LBGI, independently of HbA1c value.

Background: Glucose sensors consist of real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM). Their clinical use has been widely increasing during the past 5 years. The aim of this study is to evaluate percentage of time in range (TIR) in a large group of children with type 1 diabetes (T1D) using glucose sensors with nonautomated insulin delivery systems, in a real-world setting. Methods: An 11-center cross-sectional study was conducted during January-May 2019. Children with T1D 1 year, treated with multiple daily injections (MDI) or nonautomated insulin pump (IP), were recruited consecutively. Clinical data, HbA1c measurement, and CGM downloaded data were collected by each center and included in a centralized database for the analysis. Glucose metrics of four treatment strategies were analyzed: isCGM-MDI, rtCGM-MDI, isCGM-IP, and rtCGM-IP. Results: Data from 666 children with T1D (51% male and 49% female), median age 12 years, diabetes duration 5 years, were analyzed. An rtCGM was used by 51% of the participants, and a nonautomated IP by 46%. For isCGM-MDI, rtCGM-MDI, isCGM-IP, and rtCGM-IP, the median TIR 70-180 mg/dL values were 49%, 56%, 56%, and 61% (P < 0.001), respectively; HbA1c 7.6%, 7.5%, 7.3%, and 7.3% (P < 0.001), respectively. Use of rtCGM was associated with significant lower time below target range 180 mg/dL and lower HbA1c. If there are no barriers, an upgrade of the treatment strategy with a higher performing technology should be offered to all children who do not achieve blood glucose metrics within the suggested range.

Background: No studies have assessed if 2-week of continuous glucose monitoring (CGM) data provide good estimation of long-term glycemic control and glucose variability (GV) in pediatric patients with type 1 diabetes (T1D) as in adults. Methods: Six hundred fifty-four T1D pediatric patients were enrolled and 12-weeks of CGM data, before HbA1c measurement, were collected. Metrics of glycemic control and GV in incremental sampling periods were calculated. The agreement between metrics calculated in the sampling periods and the full 12-week period was assessed with correlation analysis (R2), median relative absolute difference (RAD) or absolute difference in the entire study populations and subjects stratified by age, pubertal status, insulin therapy (MDI,CSII), type of CGM (intermittently scanned [isCGM], real-time [rtCGM]), and HbA1c level. Results: Correlations with metrics of the full 12-week period improved by extending the sampling periods. R2 values close to 0.90 using 4-week period were significantly higher than 2-week period, particularly for coefficient of variation, mean glucose SD, percentage of time below the range

Aims to assess the prevalence of cardiovascular risk factors (CVRFs) and to identify the variables associated with CVRFs in a cohort of children and adolescents with Type 1 Diabetes. Methods 2,021 subjects, 2-18 year-old, were recruited in 17 Italian Pediatric Diabetes Centers. Anthropometric, blood pressure, biochemical (HbA1c, lipid profile, ACR), insulin therapy, physical activity level, smoking and family socio-economic status data were collected. CVRFs prevalence and their distribution were analyzed according to age and binary logistic regression was performed with positivity for at least one major CVRF (BMI-SDS>+2SD, blood pressure>90th percentile, LDL cholesterol>100 mg/dl) as dependent variable and age, duration of illness, gender, HbA1c and physical activity, as independent variables. Results The prevalence of CVFRs not at the recommended target was respectively: 32.5% one CVRF, 6.7% two CVRFs and 0.6% three CVRFs, with no significant differences across the 3 age groups (2-10, 10-15, 15-18 years). In the total sample, HbA1c and inadequate physical activity were associated with a higher probability of having at least one major CVRF. This probability was associated with physical activity in the 2-10-year-old group, with physical activity and HbA1c in the 10-15-year-old group and with HbA1c only in subjects older than 15 years. Conclusions More than 30% of subjects had at least a major CVRF. Early detection of CVRFs may be useful to enforce the therapeutic intervention in this subgroup, in order to reduce the risk to develop cardiovascular complications. This article is protected by copyright. All rights reserved.

Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response can only account for up to 60% of the variance. The aim of this work was to take a novel genomic approach to growth prediction. GHD (n=71) and TS patients (n=43) were recruited in a study on the long term response to r-hGH over five years of therapy. Pharmacogenomic analysis was performed using 1219 genetic markers and baseline blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria required for predictive value. However, we demonstrated that transcriptomic data can be used to predict growth with a high accuracy (AUC > 0.9) for short and long term therapeutic response in GHD and TS. Network models identified an identical core set of genes in both GHD and TS at each year of therapy whose expression can be used to classify therapeutic response to r-hGH. Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. We have characterised the utility of baseline transcriptome for the prediction of growth response including the identification of a set of common genes in GHD and TS. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management.One Sentence SummaryA blood transcriptome signature predicts response to recombinant human growth hormone in both growth hormone deficient and Turner syndrome childrenTrial registration numbers:NCT00256126&NCT00699855

Aim To assess the association between alcohol consumption and/or cigarette smoking with other unhealthy behaviors and clinical cardiovascular risk factors in youth with type 1 diabetes. Methods Two hundred and twenty-eight youth with type 1 diabetes (age 13–19 years) were consecutively enrolled in three Regional Pediatric Diabetes Centers in Italy. Demographic, anthropometric, lifestyle (adherence to the Mediterranean diet pattern and sports participation) and laboratory parameters were compared among youth reporting isolated or combined alcohol consumption and/or cigarette smoking. Results Ten percent of the youth reported alcohol consumption, 10% cigarette smoking and 6% both alcohol and cigarette use; 74% did not report alcohol or cigarette use. Compared to non-drinker non-smoker youth, smokers showed significantly higher percentages of each of the behavioral and clinical cardiovascular risk factors. Drinkers showed a significantly higher proportion of abdominal adiposity, dyslipidemia and poor adherence to the Mediterranean diet. Alcohol consumption was independently associated with both dyslipidemia and high glycosylated hemoglobin. Conclusions Our findings emphasize the need to increase the awareness of youth with T1D about the negative impact of alcohol drinking on cardiovascular risk, since the effects of alcohol might be underestimated with respect to the well-known detrimental effects of smoking. Clustering of unhealthy lifestyle should be discouraged in type 1 diabetes youth in order to promote cardiovascular protection.

Aims Management of type 1 diabetes mellitus (T1DM) influences several aspects of life, such as adherence to healthy lifestyle habits and health-related quality of life (HRQoL). Our aim was to evaluate the association between unhealthy lifestyle habits and HRQoL in adolescents and young adults with T1DM. Methods Two hundred and forty-two Caucasian patients (13–19 years) consecutively enrolled over a 12-month period in three Regional Pediatric Diabetes Centers in Italy. Demographics, clinical, and laboratory parameters, adherence to lifestyle habits (Mediterranean Diet assessed by KIDMED, Physical Activity levels and sedentary behavior by questionnaire) considered either separately or in cluster, and HRQoL by Pediatric Quality of Life Inventory Diabetes Module (PedsQL 3.0 DM) were collected. Metabolic control was determined by HbA1cmean of previous year. Results Only 15 (6.2%) patients fulfilled the cluster of three healthy lifestyle habits without gender differences (p = 0.353); 62 (25.6%) had 1 unhealthy lifestyle habit, and 165 (68.2%) had ≥2. Adolescents meeting physical activity recommendations had better PedsQL scores than those who did not meet. PedsQL total score and specific sub-scales decreased in patients with unhealthy lifestyle habits. High PedsQL was significantly associated with being male, living in South Italy, having lower HbA1c mean levels, and reporting lower adherence to unhealthy lifestyle habits. Conclusions The clustering of unhealthy lifestyle habits is associated with reduced HRQoL in adolescents and young adults with T1DM. Promoting multiple behavior changes may be a useful approach to improve the health status and the HRQoL in youths with T1DM.

We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0–18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records(n=2453)of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (n=1536, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05–0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers.

The association between low HDL cholesterol (HDL-C) concentrations and increased cardiovascular risk is well established. Low HDL-C levels were found in subjects with type 1 diabetes (T1D) who presented complications (1) and in untreated subjects with celiac disease (CD). The association between TID and CD might therefore enhance this lipid abnormality and accelerate the atherosclerotic process. We collected data from 13 centers belonging to the Italian Society of Pediatric Endocrinology and Diabetology (ISPED) of a large number of children with both T1D and concurrent biopsy-proven CD, at the exact time point a gluten-free diet (GFD) was initiated and after 1 year of a GFD, verified by means of CD-related antibodies. A total of 201 children with T1D diagnosed at age of 5.8 ± 3.8 years and CD diagnosed at age of 7.5 ± 4.5 years were enrolled. …

OBJECTIVE To evaluate the frequency of normalization, the persistence of remission, and the impact on normalization of glycemic control and lipid profile, we analyzed data from a retrospective observational cohort study of type 1 diabetic children and adolescents with abnormal urinary albumin excretion (UAE). RESEARCH DESIGN AND METHODS All diabetic children and adolescents (n = 41) who had persistent abnormal UAE in the period of 1984 to 2008 and followed up until 2009 (follow-up duration = 13.1 ± 6.2 years) were included in the study. Nine patients progressed to macroalbuminuria; 24 patients were administered ACE inhibitor treatment. RESULTS The cumulative prevalence of abnormal UAE was 9%. During follow-up, 14 of 17 untreated and 19 of 24 treated patients reverted to normoalbuminuria. In the remission group compared with the nonremission group, A1C levels during follow-up decreased (7.5 ± 1.0 vs. 9.4 ± 1.2%, P < 0.0001) and serum HDL cholesterol increased (52.7 ± 11.3 vs. 42.7 ± 8.6 mg/dL, P < 0.05). The micro-macroalbuminuric patients had lower HDL cholesterol (51.0 ± 11.4 vs. 62.4 ± 13.6 mg/dL, P < 0.0001) than 134 normoalbuminuric diabetic patients. CONCLUSIONS Microalbuminuria and macroalbuminuria were not permanent in most of our diabetic children and adolescents. If abnormal UAE values are high and persist for >1 year, only long-lasting treatment with ACE inhibitors seems able to induce persistent remission, especially when associated with good metabolic control and high HDL cholesterol levels.

BACKGROUND: Type 1 diabetes (T1DM) is an autoimmune disease often associated with thyroid abnormalities. PURPOSE: We investigated the correlation between thyroid function and metabolic derangement at onset and the influence of autoimmunity on thyroid function at onset and subsequently. METHODS: We evaluated 152 patients diagnosed with T1DM between 2000 and 2012 at onset and during a mean follow-up of 5.45 ± 2.8 years. Thyroid function at onset was correlated with metabolic derangement (degree of acidosis, metabolic control and adrenal function) and compared with that of 78 healthy children. Follow-up consisted of regular evaluation of thyroid function and autoimmunity. RESULTS: Thyroid hormonal pattern was not influenced at onset by thyroid autoimmunity, but only by metabolic derangement: pH and base excess in fact were significantly lower in patients with impaired thyroid function (p < 0.0001). Patients presenting normal thyroid function at onset showed a reduced conversion from FT4 to FT3 compared to nondiabetic children (FT3/FT4 0.3 ± 0.4 in the control group, 0.24 ± 0.4 in diabetic patients, p < 0.0001). Multiple regression analysis showed the highest correlation (negative) between FT3 levels at onset and base excess (p < 0.005). Thyroid abnormalities related to metabolic derangement disappeared during follow-up. Patients with thyroid antibodies at T1DM onset were at higher risk to require levothyroxine treatment during follow-up (p < 0.05). CONCLUSIONS: Thyroid function at T1DM onset is mainly influenced by metabolic derangement, irrespective of thyroid autoimmunity. Antithyroid antibodies evaluation at T1DM onset may be helpful to define which patients are at higher risk of developing hypothyroidism.

Treatment of adolescents with growth hormone deficiency (GHD) during the transition period is a controversial issue. This paper is a contribution from the Italian community of paediatric and adult endocrinologists surveyed in a Delphi panel. The Delphi method is a structured communication technique, originally developed as a systematic, interactive forecasting method that relies on a panel of experts. The experts answer questionnaires in two or more rounds. There was substantial agreement on the definition of the problems associated with the diagnosis and treatment of adolescents with GHD in the transition period, as well as on the identification of the controversial issues which need further studies. There is general consensus on the need of re-testing all isolated idiopathic GHD after at least 30-day withdrawn from treatment, while in patients with multiple pituitary deficiency and low IGF-I levels there is generally no need to re-test. In patients with permanent or confirmed GHD, a starting low rhGH dose (0.01-0.03 mg per day) to be adjusted according to IGF-I concentrations is also widely accepted. For those continuing treatment, the optimal therapeutic schedule to obtain full somatic maturation, normalization of body composition and bone density, cardiovascular function and Quality of Life, need to be evaluated.

BACKGROUND: Sensor-augmented continuous subcutaneous insulin infusion (CSII) therapy is superior to CSII therapy alone, but little is known on the effectiveness of sensor-augmented multiple daily injections (MDI) therapy. METHODS: We compared during everyday life mean glucose control and several variability indexes recorded for 3 days by a real-time glucose sensor (Medtronic, Northridge, CA) in two groups of children treated with either CSII or MDI. Fifty-five consecutive subjects were examined: 17 receiving CSII and 38 receiving MDI basal-bolus therapy (age range, 7-22 years). All subjects wore the sensor for 4 days, and 3 days were used for statistical analysis. Mean glucose and SD, coefficient of variation (CV), mean amplitude of glucose excursion (MAGE), mean of daily differences (MODD), continuous overall net glycemic action (CONGA) at 2 and 4 h, blood glucose (BG) rate, area under the curve (AUC) above 180 mg/dL and below 70 mg/dL, Low BG Index (LBGI), and High BG Index (HBGI) were calculated. RESULTS: Patients receiving CSII administered more daily boluses than patients receiving MDI (5.2±1.5 vs. 3.2±0.3, respectively; P=0.001). Mean glucose was lower in the CSII group. AUC above 180 mg/dL and HBGI were higher in the MDI group. CV, CONGA at 2 h, CONGA at 2 h during the day, and HBGI were worse in the MDI group, whereas MODD, LBGI, BG rate, and MAGE were similar. A positive correlation (r=0.95; P

Background/Aim: Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). Methods: A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. Results: Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1DM onset in 9 patients and after the onset of T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH was added subsequently, mean insulin dose increased during the first 6 months of therapy from 0.7 ± 0.2 to 1.0 ± 0.2 U/kg (p = 0.004). HbA1c was unchanged during the first 6 months of combined therapy. Conclusions: Most Italian physicians do not consider prescribing the combined GH-insulin therapy in diabetic children with growth problems. However, the results of the 17 patients identified would confirm that the combined therapy was feasible and only caused mild insulin resistance. GH therapy was effective in promoting growth in most patients and did not affect diabetes metabolic control.

Objective: To describe the rationale, design and first data from PATRO Children, a postmarketing surveillance of the long-term efficacy and safety of somatropin (Omnitrope®) for the treatment of children requiring growth hormone treatment. Methods: PATRO Children is a multicentre, open, longitudinal, noninterventional study being conducted in children’s hospitals and specialised endocrinology clinics. The primary objective is to assess the long-term safety of Omnitrope® in routine clinical practice. Eligible patients are infants, children and adolescents (male or female) who are receiving treatment with Omnitrope® and who have provided informed consent. Patients who have been treated with another recombinant human growth hormone (rhGH) product before starting Omnitrope® are eligible for inclusion. All adverse events (AEs) are monitored and recorded, with particular emphasis on: long-term safety; the recording of malignancies; the occurrence and clinical impact of anti-hGH antibodies; the development of diabetes during Omnitrope® treatment in children short for gestational age (SGA); safety issues in patients with Prader–Willi syndrome (PWS). Efficacy assessments include auxological parameters, plus insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Results: As of September 2012, 1837 patients were enrolled in the study from 184 sites in 10 European countries. To date, efficacy data are reassuring and consistent with previous studies. In addition, there have been no confirmed cases of diabetes occurring under Omnitrope® treatment, no reports of malignancy and no safety issues in PWS patients. Conclusions: The efficacy and safety profile of Omnitrope® in the PATRO Children study so far are as expected. The ongoing study will extend the safety database for Omnitrope®, and rhGH products more generally, in paediatric indications. Of particular interest, PATRO Children will add important information on the diabetogenic potential of rhGH in children born SGA, the risk of malignancies in children receiving rhGH, and AEs with a possible causal relationship to rhGH treatment in children with PWS.

OBJECTIVE We describe a maturity-onset diabetes of the young (MODY) case with mutations involving both HNF4A and HNF1A genes. RESEARCH DESIGN AND METHODS A male patient was diagnosed with diabetes at age 17; the metabolic control rapidly worsened to insulin requirement. At that time no relatives were known to be affected by diabetes, which was diagnosed years later in both the parents (father at age 50 years, mother at age 54 years) and the sister (at age 32 years, during pregnancy). RESULTS The genetic screening showed a double heterozygosity for the mutation p.E508K in the HNF1A/MODY3 gene and the novel variant p.R80Q in the HNF4A/MODY1 gene. The genetic testing of the family showed that the father carried the MODY3 mutation while the mother, the sister, and her two children carried the MODY1 mutation. CONCLUSIONS MODY1 and MODY3 mutations may interact by chance to give a more severe form of diabetes (younger age at presentation and early need of insulin therapy to control hyperglycemia).

Objectives To provide epidemiological data about psychological and sexual functioning during menopausal transition in a large Italian non-clinical sample, and to investigate their correlation with life events. Methods The study design was a cross-sectional postal survey of a menopausal sample of women recruited from the General Registry Office in Ferrara's province. The sample was composed of four thousand and seventy-three women; they were sent a questionnaire designed on the basis of the Women's Health Questionnaire (WHQ). Together with the WHQ, the subjects filled out a personal file to define social status, cultural level, family's characteristics, recent menstrual cycles, gynaecological history and operations, drug assumption, life events in the last year, and lifetime depression. Results One thousand three hundred and forty-five women provided usable questionnaires. Factor analysis resulted in eight clusters: somatic symptoms, depressive symptoms, depressed mood with anxiety symptoms, cognitive difficulties, anxiety, sexual functioning, vasomotor symptoms and sleep problems. Mood and sexual function were impaired through the menopausal transition, with depressive and sexual symptoms being higher in the post-menopausal group compared to the pre-menopausal one. Therefore, the correlation between the two was greater in the pre- and peri-menopausal period. Conclusion Depressive and sexual symptoms presented greater severity in the post-menopausal group. Both clusters of symptoms were strongly associated with life events. The parallel course of the two clusters could be related with a common pathoplastic action of life events, both on sexual symptoms and on depressive symptoms, occurring right at the time that a woman has to face the transition into menopause.

Oxidative stress is defined as an imbalance between prooxidants and antioxidants in favor of the former (1), and diabetic patients are considered a risk group for increased oxidative stress (2,3). Studies regarding oxidant/antioxidant balance in type 1 diabetic children and adolescents have given conflicting results (4–7). The aim of this study was to determine whether serum hydroperoxides (reactive oxygen metabolites [ROMs]) as oxidative markers and plasma α-tocopherol (vitamin E) and coenzyme Q10 as indexes of antioxidant capacity could be related to metabolic control in 75 unselected children, adolescents, and young adults with type 1 diabetes. ROMs are the first markers of oxidation and one of the most reliable indicators of oxidative stress. Vitamin E is an important chain-breaking …