Marco Marigliano

Randomized summer camp crossover trial in 5-to 9-year-old children: Outpatient wearable artificial pancreas is feasible and safe

OBJECTIVE The Pediatric Artificial Pancreas (PedArPan) project tested a children-specific version of the modular model predictive control (MMPC) algorithm in 5- to 9-year-old children during a camp. RESEARCH DESIGN AND METHODS A total of 30 children, 5- to 9-years old, with type 1 diabetes completed an outpatient, open-label, randomized, crossover trial. Three days with an artificial pancreas (AP) were compared with three days of parent-managed sensor-augmented pump (SAP). RESULTS Overnight time-in-hypoglycemia was reduced with the AP versus SAP, median (25th–75th percentiles): 0.0% (0.0–2.2) vs. 2.2% (0.0–12.3) (P = 0.002), without a significant change of time-in-target, mean: 56.0% (SD 22.5) vs. 59.7% (21.2) (P = 0.430), but with increased mean glucose 173 mg/dL (36) vs. 150 mg/dL (39) (P = 0.002). Overall, the AP granted a threefold reduction of time-in-hypoglycemia (P < 0.001) at the cost of decreased time-in-target, 56.8% (13.5) vs. 63.1% (11.0) (P = 0.022) and increased mean glucose 169 mg/dL (23) vs. 147 mg/dL (23) (P < 0.001). CONCLUSIONS This trial, the first outpatient single-hormone AP trial in a population of this age, shows feasibility and safety of MMPC in young children. Algorithm retuning will be performed to improve efficacy.

Screening for impaired glucose tolerance in obese children and adolescents: a validation and implementation study

What is already known about this subject Fasting triglycerides above 1.17 mmol/L have been shown to be useful to select obese children and adolescents who may present impaired glucose tolerance in a Canadian cohort. Fasting plasma glucose is associated with the risk to present impaired glucose tolerance in several cohorts of obese children and adolescents.

A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes

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.

Fluid intake and hydration status in obese vs normal weight children

Background/Objectives:Little is known on the relationship between obesity and hydration levels in children. This study assessed whether and by which mechanisms hydration status differs between obese and non-obese children.Subjects/Methods:Hydration levels of 86 obese and 89 normal weight children (age: 7–11 years) were compared. Hydration was measured as the average free water reserve (FWR=urine output/24 h minus the obligatory urine output [total 24 h excreted solutes/97th percentile of urine osmolality of children with adequate water intake, that is, 830 mOsm/kg]) over 2 days. Three days of weighed dietary and fluid intakes were recorded. Non-parametric tests were used to compare variables that were skewed and to assess which variables correlated with hydration. Variables mediating the different hydration levels of obese and normal weight children were assessed by co-variance analysis.Results:Obese children were less hydrated than normal weight peers [FWR=median (IQR): 0.80 (−0.80–2.80) hg/day vs 2.10 (0.10–4.45) hg/day, P<0.02; 32% of obese children vs 20% of non-obese peers had negative FWR, P<0.001]. Body mass index (BMI) z-score (z-BMI) and water intake from fluids correlated with FWR (ρ=−0.18 and 0.45, respectively, both P<0.05). Water intake from fluids completely explained the different hydration between obese and normal weight children [FWR adjusted for water from fluids and z-BMI=2.44 (0.44) hg vs 2.10 (0.50) hg, P=NS; B coefficient of co-variation between FWR (hg/day) and water intake from fluids (hg/day)=0.47, P<0.001].Conclusions:Obese children were less hydrated than normal weight ones because, taking into account their z-BMI, they drank less. Future prospective studies are needed to explore possible causal relationships between hydration and obesity.

Evaluating the Experience of Children With Type 1 Diabetes and Their Parents Taking Part in an Artificial Pancreas Clinical Trial Over Multiple Days in a Diabetes Camp Setting

OBJECTIVE To explore the experiences of children with type 1 diabetes and their parents taking part in an artificial pancreas (AP) clinical trial during a 7-day summer camp. RESEARCH DESIGN AND METHODS A semistructured interview, composed of 14 questions based on the Technology Acceptance Model, was conducted at the end of the clinical trial. Participants also completed the Diabetes Treatment Satisfaction Questionnaire (DTSQ, parent version) and the AP Acceptance Questionnaire. RESULTS Thirty children, aged 5–9 years, and their parents completed the study. A content analysis of the interviews showed that parents were focused on understanding the mechanisms, risks, and benefits of the new device, whereas the children were focused on the novelty of the new system. The parents’ main concerns about adopting the new system seemed related to the quality of glucose control. The mean scores of DTSQ subscales indicated general parents’ satisfaction (44.24 ± 5.99, range 32–53) and trustful views of diabetes control provided by the new system (7.8 ± 2.2, range 3–12). The AP Acceptance Questionnaire revealed that most parents considered the AP easy to use (70.5%), intended to use it long term (94.0%), and felt that it was apt to improve glucose control (67.0%). CONCLUSIONS Participants manifested a positive attitude toward the AP. Further studies are required to explore participants’ perceptions early in the AP development to individualize the new treatment as much as possible, and to tailor it to respond to their needs and values.

Monogenic Diabetes Accounts for 6.3% of Cases Referred to 15 Italian Pediatric Diabetes Centers During 2007 to 2012

Context An etiologic diagnosis of diabetes can affect the therapeutic strategy and prognosis of chronic complications. Objective The aim of the present study was to establish the relative percentage of different diabetes subtypes in patients attending Italian pediatric diabetes centers and the influence of an etiologic diagnosis on therapy. Design, Setting, and Patients This was a retrospective study. The clinical records of 3781 consecutive patients (age, 0 to 18 years) referred to 15 pediatric diabetes clinics with a diagnosis of diabetes or impaired fasting glucose from January 1, 2007 to December 31, 2012 were examined. The clinical characteristics of the patients at their first referral to the centers, type 1 diabetes-related autoantibodies, molecular genetics records, and C-peptide measurements, if requested for the etiologic diagnosis, were acquired. Main Outcome Measures The primary outcome was to assess the percentage of each diabetes subtype in our sample. Results Type 1 diabetes represented the main cause (92.4%) of diabetes in this group of patients, followed by monogenic diabetes, which accounted for 6.3% of cases [maturity onset diabetes of the young (MODY), 5.5%; neonatal diabetes mellitus, 0.6%, genetic syndromes, 0.2%]. A genetic diagnosis prompted the transfer from insulin to sulphonylureas in 12 patients bearing mutations in the HNF1A or KCNJ11 genes. Type 2 diabetes was diagnosed in 1% of the patients. Conclusions Monogenic diabetes is highly prevalent in patients referred to Italian pediatric diabetes centers. A genetic diagnosis guided the therapeutic decisions, allowed the formulation of a prognosis regarding chronic diabetic complications for a relevant number of patients (i.e.,GCK/MODY), and helped to provide genetic counseling.

Accuracy of a CGM Sensor in Pediatric Subjects With Type 1 Diabetes. Comparison of Three Insertion Sites: Arm, Abdomen, and Gluteus:

Background: Patients with diabetes, especially pediatric ones, sometimes use continuous glucose monitoring (CGM) sensor in different positions from the approved ones. Here we compare the accuracy of Dexcom® G5 CGM sensor in three different sites: abdomen, gluteus (both approved) and arm (off-label). Method: Thirty youths, 5-9 years old, with type 1 diabetes (T1D) wore the sensor during a clinical trial where frequent self-monitoring of blood glucose (SMBG) measurements were obtained. Sensor was inserted in different sites according to the patient habit. Accuracy metrics include absolute relative difference (ARD) and absolute difference (AD) of CGM with respect to SMBG. The three sites were compared with ANOVA. If the test detected a difference, an additional pair-wise comparison was performed. Results: Overall, no accuracy difference was detected: the mean ARD was 13.3% (SD = 13.5%) for abdomen, 13.4% (12.9%) for arm and 12.9% (20.2%) for gluteus (P value = .83); the mean AD was 17.0 mg/dl (17.2 mg/dl) for abdomen, 17.2 mg/dl (17.1 mg/dl) for arm and 18.3 mg/dl (18.5 mg/dl) for gluteus (P value = .30). In hypo- and euglycemia ARD (P value = .87 and .15, respectively), and AD (P value = .68 and .37, respectively) were not statistically different. At variance, in hyperglycemia, a significant difference was detected between the two approved sites, abdomen and gluteus (ΔARD = −2.2% [CI = −4.2%, −0.1%], P value = .04), whereas the comparisons with the off-label location, arm-abdomen, and arm-gluteus were not significant. Conclusions: These results suggest that the accuracy of the sensor placed on the arm was not significantly different with respect to the two approved insertion sites (abdomen and gluteus). Larger, randomized trials are needed to draw final conclusions.

Epidemiology of type 1 diabetes mellitus in the pediatric population in Veneto Region, Italy

We assessed the prevalence and incidence of type 1 diabetes mellitus (T1DM) in Veneto Region in Italy. The average prevalence and incidence rates were 1.26/1000 subjects and 16.5/100,000 person-years, respectively. This study shows that the Veneto Region is an area with intermediate-high risk of T1DM.

A rare case of granuloma annulare in a 5-year-old child with type 1 diabetes and autoimmune thyroiditis.

Granuloma annulare (GA) has rarely been reported in childhood, and its etiology still remains unclear. Its association with type 1 diabetes (T1D) and other chronic systemic diseases such as autoimmune thyroiditis (AT) or rheumatoid arthritis has been reported. There is no description in the literature of pediatric cases and the simultaneous association of GA and multiple autoimmune diseases in the same subject. We report the case of a 5-year-old girl who presented onset signs and symptoms of T1D. The diagnosis of T1D was confirmed by the presence of autoimmune T1D antibodies. Moreover, AT was also diagnosed by autoantibodies and positive ultrasound. One month later, coin-size erythematous lesions appeared initially on the trunk but soon spread over the body. Once dermatophytosis had been excluded, a skin biopsy confirmed a diagnosis of GA. Although a clear mechanism remains still unknown, clinicians must take into consideration an association of GA in patients with T1D or AT to avoid unnecessary medical investigations and/or inadequate pharmacological treatment.

Anxiety, Depression and Quality of Life in Italian Youths with Type 1 Diabetes Mellitus

Background: Psychological problems and low quality of life (QoL) in children with type 1 Diabetes Mellitus T1DM) were reported as correlated with T1DM. This study wants to test if the prevalence of anxiety and depression is higher in young patients with T1DM than in controls, if the level of QoL is lower and if anxiety and QoL correlate with glyco-metabolic control. Methods: A total of 100 children with T1DM, aged 8-13 years, were recruited and 114 healthy children were recruited as controls. All children with T1DM were receiving a routine psychological support. Patients and controls underwent three questionnaires [the Self Administrated Psychiatric Scale Scales for Children and Adolescents (SAFA), the Children’s Depression Inventory (CDI) and the Pediatric Quality of Life Inventory (PedsQL)]. Diabetes–related, physical and socio-demographic parameters were also collected. Results: SAFA, CDI and PedsQL mean score were not statistically different in T1DM and in control group. Just the “separation anxiety” scale showed significantly higher mean score in the T1DM than in the control group (43.77 ± 10.34 vs. 23.11 ± 18.25, p<0.01). A significant correlation between QoL and metabolic control (HbA1c) (r=0.21, p<0.05) was found. HbA1c increased with the mother’s education (r=0.42, p<0.05) and occupation level (r=0.35, p<0.05), and with the number of siblings (r = 0.20, p<0.05). Conclusions: T1DM is not a condition promoting per se more psychological discomfort even if a higher level of separation anxiety was shown. Interestingly, a higher level of self-perceived QoL was associated with worse glycometabolic control. Significant findings of the study: 1. The anxiety, depression and QoL levels were not significantly different in children with T1DM vs healthy peers even if children with T1DM showed higher separation anxiety 2. There was not association between psychological parameters and the glycometabolic control (HbA1c) What this study adds: The self-perceived QoL, in subjects with T1DM, was higher in subjects with worse glycometabolic control and lower in patients with better glycometabolic control Psycho-educational and therapeutic programs should sustain parents and children with T1DM