Insulin pump failures in Italian children with Type 1 diabetes: retrospective 1-year cohort study.

AIMS: Insulin pump failure and/or malfunction requiring replacement have not been thoroughly investigated. This study evaluated pump replacement in children and adolescents with Type 1 diabetes using insulin pump therapy. METHODS: Data were collected for all participants younger than 19 years, starting insulin pump therapy before 31 December 2013. For each child, age, disease duration, date of insulin pump therapy initiation, insulin pump model, failure/malfunction/replacement yes/no and reason were considered for the year 2013. RESULTS: Data were returned by 40 of 43 paediatric centres belonging to the Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology. In total, 1574 of 11 311 (13.9%) children and adolescents with Type 1 diabetes were using an insulin pump: 29.2% Animas VIBE™ , 9.4% Medtronic MiniMed 715/515™ , 34.3% Medtronic MiniMed VEO™ , 24.3% Accu-Check Spirit Combo™ and 2.8% other models. In 2013, 0.165 insulin pump replacements per patient-year (11.8% due to pump failure/malfunction and 4.7% due to accidental damage) were recorded. Animas VIBE™ (22.1%) and Medtronic MiniMed VEO™ (17.7%) were the most replaced. CONCLUSIONS: In a large cohort of Italian children and adolescents with Type 1 diabetes, insulin pump failure/malfunction and consequent replacement are aligned with rates previously reported and higher in more sophisticated pump models.

Adolescents and young adults with type 1 diabetes display a high prevalence of endothelial dysfunction.

AIM: Little is known about endothelial function in adolescents with type 1 diabetes, and we evaluated endothelial dysfunction, using reactive hyperaemia peripheral arterial tonometry (RH-PAT). METHODS: This prospective, observational, 1-year study focused on 73 adolescents with type 1 diabetes, using multiple daily injections or continuous subcutaneous insulin infusion. The subjects were assessed using RH-PAT, body mass index, blood pressure, fasting lipid profile, glycated haemoglobin, insulin requirements and hours of physical exercise per week. RESULTS: Endothelial dysfunction was observed in 56 patients (76.7%), with lower mean RH-PAT scores (1.26 ± 0.22 versus 2.24 ± 0.48, p < 0.0001) and higher glycated haemoglobin values at baseline (8.27 ± 1.24% versus 7.37 ± 0.54%, p = 0.006) and as a mean of the whole period since diagnosis (8.25 ± 1.22% versus 7.72 ± 0.82%, p = 0.034). A higher percentage of patients with endothelial dysfunction showed abnormal cardiac autonomic tests (p = 0.02) and were more sedentary, exercising <4 hours a week, than patients with normal endothelial function. After follow-up in 64/73 patients, we observed endothelial dysfunction in 81.8% of patients, despite a modest improvement in glycated haemoglobin. CONCLUSION: Adolescents with type 1 diabetes displayed evidence of endothelial dysfunction. Good metabolic control (glycated haemoglobin ≤7.5%, 58 mmol/mol) and regular physical activity of at least 4 h a week might be protective.

Health-related quality of life and treatment preferences in adolescents with type 1 diabetes. The VIPKIDS study.

A multi-centre, observational, cross-sectional study was carried out to determine whether the health-related quality of life (HRQOL) of adolescents with type 1 diabetes is affected by different insulin treatment systems, and which features of HRQOL are impacted by the respective insulin treatment. The study regarded 577 adolescents, aged 10-17 years, with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) (n = 306) or multiple daily injections (MDI) (n = 271). The Insulin Delivery System Rating Questionnaire was validated in Italian and was self-completed by the subjects during a routine visit to the centres. Subjects were compared following the domains of the questionnaire. Good HRQOL was seen in subjects treated with either MDI or CSII. Significant differences were not found in the domains for general diabetes, including diabetes worries, social burden and psychological well-being. Multiple quantile regression analysis showed that CSII confers significant advantages in terms of HRQOL with improvements in treatment satisfaction, perceived clinical efficacy and reduction in treatment interference with daily activities. This favourable impact was more evident in subjects reporting lower HRQOL scores, suggesting that CSII may be especially useful for individuals perceiving a poor HRQOL. Analysis of the domains indicated that CSII was associated with a higher HRQOL than MDI. Life-course HRQOL evaluation using a standardised questionnaire can ensure better chronic disease management. This is particularly important when providing individualised care for adolescents, as they become increasingly responsible for managing their diabetes.

Long-lasting immunogenicity and safety of a 2009 pandemic influenza A(H1N1) MF59-adjuvanted vaccine when co-administered with a 2009-2010 seasonal influenza vaccine in young patients with type 1 diabetes mellitus.

AIMS: To evaluate the long-lasting immunogenicity and safety of a pandemic vaccine co-administered with a seasonal influenza vaccine in young subjects with Type 1 diabetes. METHODS: Eighty patients (mean age: 16.7 ± 5.5 years, disease duration: 10.2 ± 4.7 years) were randomly assigned to receive a single or a double dose (1 month apart) of MF59-adjuvanted influenza A(H1N1) vaccine, simultaneously with a single dose of a virosome-adjuvanted trivalent influenza vaccine for the 2009-2010 season. RESULTS: One month after immunization, the rate of seroconversion to 2009 pandemic A(H1N1) was 92.5% with an overall 100% proportion of vaccinees with protective antibody titres (≥ 1:40). No significant differences were observed between vaccinees who received the one-dose or the two-dose schedule. Seasonal vaccine induced a significant increase of both seroprotection rates and antibody levels. Local adverse events at the injection site of pandemic and seasonal vaccines were reported by 66.3% and 50% of subjects, respectively. Solicited systemic adverse events, mainly mild in intensity, were reported by 26.7% of vaccinees. No subjects had an influenza-like illness during the 6-month follow-up. CONCLUSIONS: One injection of 2009 pandemic influenza A(H1N1) MF59-adjuvanted vaccine is immunogenic and safe in young patients with Type 1 diabetes who are at increased risk of influenza morbidities. Pandemic vaccine can be safely co-administered with seasonal influenza vaccine.

Validation of SAPS 3 Admission Score and comparison with SAPS II.

BACKGROUND: The objective of this study was to validate the Simplified Acute Physiology Score SAPS 3 Admission Score (SAPS 3) and to compare its fit with that of SAPS II in an independent sample of patients admitted to a single-centre intensive care unit (ICU). METHODS: The data for all adult patients consecutively admitted to an eight-bed ICU of a 700-bed university hospital between 1 January 2006 and 2 September 2007 were collected. SAPS II and SAPS 3 were computed, as well as the predicted hospital mortality. The calibration of SAPS II and SAPS 3, according to the general equation (GE), and equations for Southern Europe and Mediterranean countries (SE&MC), and Central and Western Europe (C&WE), were assessed by the goodness-of-fit Hosmer-Lemeshow H and C statistics. Standardized mortality ratios (SMR) with 95% confidence interval (95% CI) were computed for SAPS II and SAPS 3 equations. RESULTS: Six hundred and eighty-four patients were studied (males 63%). The median age was 73 (quartiles 65-80) years. The fit of SAPS 3 using the C&WE equation (H 13.49, P=0.095; C 12.73, P=0.121) as well as that of SAPS II was acceptable (H 6.02, P=0.644; C12.08, P=0.147), while SAPS 3 GE (H 23.36, P=0.002; C 22.37, P=0.004) and S&MC (H 25.73, P=0.001; C 26.19, P=0.001) did not fit well. SAPS 3 GE, SAPS 3 SE&M Countries and the SAPS II significantly over estimated the mortality. Only 95% CI of SMR for SAPS 3 C&WE included 1 (SMR 0.97; 95% CI 0.89-1.05). CONCLUSION: Each ICU should identify the SAPS 3 equation most suitable for its case mix. The SAPS II model tended to overestimate the mortality.

Posterior capsule opacification and lens epithelial cell layer formation: Hydroview hydrogel versus AcrySof acrylic intraocular lenses.

PURPOSE: To quantitatively compare the incidence of visually significant posterior capsule opacification (PCO) and lens epithelial cell (LEC) layer formation on the anterior surface of Hydroview hydrogel and AcrySof acrylic foldable intraocular lenses (IOLs) after implantation. SETTING: Single-surgeon ophthalmology practice, Orange Base Hospital, and Dudley Private Hospital, Orange, New South Wales, Australia. METHODS: This retrospective study comprised 166 eyes of 150 patients (after exclusions) who had cataract extraction and insertion of a foldable IOL in the capsular bag by a single surgeon using a standardized phacoemulsification technique from December 1997 to September 1998. The mean follow-up was 13.1 months (range 6.0 to 23.6 months). The eyes were divided into 2 groups based on the type of IOL implanted: Storz Hydroview H60M (81 eyes) or Alcon AcrySof MA30BA (85 eyes). A neodymium:YAG posterior capsule laser capsulotomy (PC YAG) was performed for an objective decrease in Snellen best corrected visual acuity (BCVA) of more than 1 line, significant visual symptoms, or both. This was used as a measure of visually significant PCO. An Nd:YAG anterior surface clearance (ASC YAG) was done for LEC layer formation anterior to the IOL to better visualize or facilitate treatment of PCO. The rates of PC YAG and ASC YAG after Hydroview and AcrySof IOL implantation were statistically compared. RESULTS: Forty-five eyes (55.6%) in the Hydroview IOL group and 3 eyes (3.5%) in the AcrySof IOL group required a PC YAG; the risk difference was 52.0% (P <.001). An ASC YAG was required in 27 eyes (33.3%) in the Hydroview group and 1 eye (1.2%) in the AcrySof group; the risk difference was 32.2% (P <.001). Survival analysis demonstrated that the only independent predictor of the incidence of PC YAG and ASC YAG over time was IOL type, with the Hydroview IOL group having a statistically significantly higher incidence of both procedures. CONCLUSION: There was a greater incidence of visually significant PCO and LEC layer formation on the anterior surface of Hydroview IOLs than of AcrySof IOLs.

Cardiovascular autonomic testing in adolescents with type I (insulin-dependent) diabetes mellitus: an 18-month follow-up study.

1. Autonomic abnormalities are frequent in adult patients with diabetes mellitus and progress slowly; little is known about frequency and progression of autonomic abnormalities in childhood. 2. To assess whether autonomic abnormalities are already present in childhood, we evaluated the cardiovascular reflexes, the spectral analysis of spontaneous fluctuations in RR interval and blood pressure (low- and high-frequency), and the baroreflex sensitivity at rest, and after vagal (controlled breathing) and sympathetic activation (tilting) in 25 adolescents with Type I diabetes mellitus, aged 10-17 years, at baseline and after 18 months follow-up, and in 20 age- and sex-matched controls. 3. Cardiovascular reflexes were similar in both patients and controls. Similar significant changes in percentage low- and high-frequency (P < 0.005) from rest to tilting and to control breathing were observed in both patients and controls. The baroreflex sensitivity was also similar in patients and controls. Mild and non-systematic correlations were observed between autonomic tests and disease duration or metabolic control. After 18 months follow-up no changes were observed in any of the measured variables. Correlations with metabolic control remained unchanged. 4. These results indicate a substantial stability of cardiovascular autonomic function in childhood diabetes, and suggest that autonomic abnormalities are likely to develop at an older age.

Normal values of overnight albumin excretion rate in a sample of healthy Italian children and adolescents.

The aim of this study was to define normal values of albumin excretion rate (AER) in young people. We measured overnight timed AER (tAER, microgram/min) by a double-antibody radioimmunoassay in 281 healthy Italian children and adolescents (160 M and 121 F), aged 7-19 years. The frequency distribution of tAER deviated from normality, therefore percentiles were used: median and 95th percentile were 2.3 and 6.9 micrograms/min respectively. Log transformed tAER was not related to age or pubertal stage. "Borderline" AER refers to AER higher than normal 95th percentile in non-diabetic subjects but lower than microalbuminuria threshold level. Incipient nephropathy, expressed as "borderline" AER, has been reported in adult IDDM patients, and can be reversed by improving metabolic control. Because incipient diabetic nephropathy may be present in young IDDM patients without microalbuminuria, screening for AER should be recommended for pediatric diabetic patients, also before puberty, in order to detect early renal damage and the "borderline" AER state.

Successful immune response to a recombinant hepatitis B vaccine in young patients with insulin-dependent diabetes mellitus.

The study aimed to evaluate the immune response to a recombinant hepatitis B vaccine in young patients with insulin-dependent diabetes mellitus (IDDM), in view of reports of reduced efficacy in adults with IDDM. Sixty-five young people with IDDM, age 4.5 to 27.5 and diabetes duration 0.3 to 19 years and 174 age- and sex-matched healthy subjects were injected with a recombinant hepatitis B vaccine at 0, 1 and 6 months intramuscularly in the deltoid region. Three (4.6%) IDDM patients and 2 (1.1%) controls were non-responders (HBsAb titre, < 2 IU l-1) and 1 control was a low responder (HBsAb titre = 10 IU l-1). Among the 3 non-responder IDDM subjects, 2 had other autoimmune disease. Median HBsAb titre was similar in responding patients (120 IU l-1 and controls (125 IU l-1). There were no significant correlations between antibody titre and age, diabetes duration, HbA1c or insulin requirement. No association was found between HBsAb titre and any HLA genotype or the presence of microangiopathy. IDDM does not adversely affect the immune response to a recombinant hepatitis B vaccine in children, adolescents, and young adults, who can thus expect to benefit from its use in situations of risk of contracting hepatitis.

Celiac disease and type I (insulin-dependent) diabetes mellitus in childhood: follow-up study.

To ascertain the specificity of IgA and IgG antigliadin (IgA-AGA, IgG-AGA), IgA-antireticulin (R1-ARA), and antiendomysial (AEA) antibodies for the diagnosis of celiac disease, we evaluated 133 type I diabetic children aged 1.4-28.4 years (mean 14.1 +/- 6.6), with diabetes from onset to 20.5 years. Fifty-three patients were considered at onset and 49 of these also during follow-up. IgA-AGA and IgG-AGA were determined by enzyme-linked immunosorbent assay (ELISA), R1-ARA and AEA by indirect immunofluorescence. IgA-AGA were positive in 20 of 133 (15%), IgG-AGA were positive in seven of 133 (5.26%), while R1-ARA and AEA were positive in three patients. At the onset of disease we found elevated IgA-AGA in 17 of 53 (32%) patients, IgG-AGA in four (7.55%) patients, three of them with IgA-AGA as well; R1-ARA and AEA were present in three (5.66%) patients, all with high IgA-AGA levels. During 1-10 year follow-up IgA-AGA decreased to within the normal range in 13 patients, with elevated IgA-AGA at onset but without R1-ARA and AEA; in four patients with high IgA-AGA at onset, IgA-AGA remained constantly elevated as did R1-ARA and AEA in three of them; and two patients, without IgA-AGA, R1-ARA, and AEA at onset, became positive for all three antibodies. Intestinal biopsy confirmed a diagnosis of celiac disease in five of these with IgA-AGA, R1-ARA, and AEA, but not in one patient with persistent IgA-AGA but no AEA and R1-ARA, suggesting that R1-ARA and AEA are more reliable markers for the screening of celiac disease in type I diabetic patients.

IDDM and autoimmune thyroid disease in the pediatric age group.

Diabetic patients have increased chances of developing autoimmune thyroid disease. Thyroid autoantibodies (Th-AAb) are more frequent in IDDM children than in the general population, ranging between 7 and 40%. As markers of thyroid autoimmunity, we assessed Th-AAb (MsA and TgA) cross-sectionally in 212 children and adolescents (93 girls and 119 boys) aged 1.2-21 years with IDDM from 0-18 years, and longitudinally in 90/212 (43 girls and 47 boys) at diagnosis and during a 3-10 year follow-up. In the cross-sectional study Th-AAb were found in 22/93 girls (23.7%) and 13/119 boys (10.9%). In the longitudinal study Th-AAb were observed at diagnosis in 6 patients, and during the follow-up in 9 girls. In 11/15 Th-AAb positive patients anti-nuclear antibodies were also present. Hormonal assessment revealed hypothyroidism in 3 girls (afterwards on replacement therapy), thyroid ultrasonography showed abnormal patterns in 5 girls, fine needle aspiration biopsy confirmed Hashimoto's thyroiditis in 9 (8 girls and 1 boy), with a higher frequency than that reported among healthy subjects (1-2%). Thyrotoxicosis also occurs with increased frequency in diabetic children than in the general population. We observed Graves' disease in only 1/212 IDDM patients, a 13 year-old boy in whom thyrotoxicosis developed 4 years after diabetes was diagnosed. The high prevalence of thyroid autoimmunity in our patients, particularly in females, suggests that diabetic children and adolescents should be screened for thyroid autoimmunity even if asymptomatic for hypo- or hyperthyroidism. Patients with IDDM and autoimmune thyroid disease should be evaluated for autoantibodies against other organs, such as adrenal glands and gastric mucosa. It is known that patients affected by type 1 (insulin-dependent) diabetes mellitus (IDDM) may have autoantibodies against different organs, such as thyroid, adrenal glands, gastric mucosa, parathyroid, with or without evident dysfunction of the target organ /1-8/. Among organ-specific disorders, autoimmune thyroid disease (ATD) is frequently associated with IDDM and the presence of thyroid autoantibodies (Th-AAb) has been considered a risk factor for the development of hypo- or hyperthyroidism /9/.

Clinical aspects of coeliac disease in children with insulin-dependent diabetes mellitus.

Coeliac disease (CD) is heterogeneous in its clinical presentation and pathological expression. Silent, latent and potential forms represent the submerged part of the so-called "coeliac iceberg". The association of insulin-dependent diabetes mellitus (IDDM) and CD has been widely reported. For the screening of CD in diabetic patients, anti-reticulin R1 (ARA-R1) and anti-endomysium (AEA) antibodies are more reliable markers than anti-gliadin (AGA) antibodies. Recent studies have reported an increased prevalence of CD in children with IDDM. In our experience intestinal biopsy confirmed a diagnosis of CD in 6 out of 172 diabetic patients, with a prevalence of 3.5%. Only occasionally does CD precede the onset of IDDM; more often CD is diagnosed shortly or sometimes years after the onset of diabetes. Typical gastrointestinal complaints of CD (such as diarrhoea, abdominal distension) are rare in IDDM patients, while atypical isolated signs or symptoms of CD are more common, in particular sideropenic anemia, short stature, delayed puberty, epilepsy, hypertransaminasemia, dyspeptic symptoms, herpetiform dermatitis, and recurrent aphthous stomatitis. It is recommended that all diabetic children, even those asymptomatic, should be screened yearly for CD, using a combination of AGA plus ARA-R1 and AEA.

Cardiovascular reflex changes preceding episodes of vasovagal syncope in paediatric subjects.

1. The cardiovascular reflex changes preceding episodes of vasovagal syncope (VVS) in paediatric age were investigated in 12 subjects and in 20 controls, supine and upright, by spectral analysis of RR interval, respiration, systolic and diastolic blood pressure. 2. The sympatho-vagal control on the heart and blood pressure was assessed by the power of the low- (LF: index of sympathetic activity) and high-frequency oscillations (index of vagal activity to the heart). 3. In VVS group the supine blood pressure was lower than in controls and fell after tilt, while remained unchanged in controls. The blood pressure LF increased in control group during early and prolonged orthostasis, whereas in the VVS group the LF tended to decrease after early orthostasis and were not significantly greater than supine before VVS. 4. In the VVS group the sympathetic control of blood pressure appears reduced or ineffective, and progressively worsens before the VVS episode.

Increased urinary N-acetyl-beta-glucosaminidase (NAG) excretion in young insulin-dependent diabetic patients.

We evaluated urinary N-acetyl-beta-glucosaminidase (NAG) excretion in overnight and in second morning urine in 50 young diabetic patients, aged 7.4-25 years with a disease duration from 2-19.6 years. In all patients we evaluated urinary NAG and creatinine excretion, in both overnight and second morning urine, glycosuria, fasting blood glucose and HbA1c levels, insulin requirement, blood pressure, and the presence of microangiopathic complications. Urinary NAG excretion was also evaluated in 69 age- and sex-matched controls. NAG was determined using 3-cresolsulfonphtaleinyl-beta-N-acetylglucosaminide as substrate (Boehringer Mannheim, Germany). In the diabetic patients NAG/Cre ratios were significantly higher than in controls both in overnight and second morning urine (P < 0.0005, respectively). We observed significantly higher NAG/Cre ratio levels in the second morning than in overnight urine, both in controls and in diabetics (P < 0.0005, respectively). Elevated (above 2 S.D. of the mean) NAG/Cre ratios were found in 17/50 patients (34%) in overnight urine and in 29/50 (58%) in second morning urine. No correlation was observed between NAG/Cre ratio levels and age, duration of disease, pubertal stage, body mass index, fasting blood glucose, glycosuria, insulin requirement and blood pressure. The patients with one or more complications did show NAG/Cre ratio levels significantly higher than those without complications (P < 0.005) in second morning urine, but not in overnight urine. Our study has demonstrated an increased rate of urinary NAG excretion in young IDDM patients, in particular in those with microangiopathic complications.

Hyperinsulinemia in children and adolescents after bone marrow transplantation.

We report 34 patients (aged 5-18 years) with acute (n = 26) or chronic (n = 1) leukemia, non-Hodgkin's lymphoma (n = 3) or severe aplastic anemia (n = 4) evaluated for pancreatic beta-cell function 9 months to 10.2 years after autologous (n = 19) or allogeneic (n = 15) BMT. Before BMT, all patients received cytotoxic drugs, combined with total body irradiation (TBI) in 24 cases or thoracoabdominal irradiation (TAI) in 4 children. Patients were investigated for fasting blood glucose (FBG), HbA1C, anti-insulin (IAA) and islet cell antibodies (ICA), first-phase insulin response (FPIR) and insulinemia/glycemia (I/G) ratio on i.v. glucose tolerance test (GTT) and C-peptide response after glucagon 1 mg i.v. Results were compared with those obtained in 21 age- and sex-matched controls. None of the patients or controls had IAA and/or ICA. FBG and HbA1C were normal in all children. In the patients, glycemia on i.v. GTT was similar to controls whereas insulin levels I/G ratio and FPIR were significantly higher in patients than in controls, as well as C-peptide levels. We divided the patients on the basis of the radiotherapy into group I with TBI (n = 18), group II with TAI (n = 4) and group III who were not irradiated (n = 4). The I/G ratio, FPIR on i.v. GTT and C-peptide response were significantly higher in group I compared with the other two groups and controls. The increased insulin and C-peptide levels in our patients with normal glycemia might be interpreted as a state of insulin resistance, more evident in patients who received TBL.