Ivana Rabbone

A cross‐sectional international survey of continuous subcutaneous insulin infusion in 377 children and adolescents with type 1 diabetes mellitus from 10 countries

Objective:  To document current practices using continuous subcutaneous insulin infusion (CSII) by downloading electronically the 90‐d pump data held within the pump memory and relating that to clinical data from children and adolescents in different pediatric diabetes centers from Europe and Israel.

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.

Use of integrated real-time continuous glucose monitoring/insulin pump system in children and adolescents with type 1 diabetes: A 3-year follow-up study

BACKGROUND Insulin pumps and real-time continuous glucose monitoring devices have recently been combined into the sensor-augmented pump (SAP) system. The objective of this study was the evaluation of the clinical use of SAP in a large series of children with type 1 diabetes using insulin pump therapy. METHODS A questionnaire was administered in all pediatric diabetologic centers in Italy; data were analyzed only regarding patients 18 years old or younger and using SAP for 6 months or more. RESULTS Among all patients using an insulin pump, 129 (13.5 ± 3.8 years old, with a disease duration of 6.3 ± 3.4 years) have been using SAP for 1.4 ± 0.7 years. Four hundred ninety-three patients (12.9 ± 3.4 years old, with a disease duration of 6.2 ± 3.3 years) using conventional insulin pump therapy for 1.7 ± 0.5 years have been evaluated as the control group. After 0.5-3 years of using SAP or conventional insulin pump therapy, glycosylated hemoglobin significantly improved (8.0 ± 1.5% vs. 7.4 ± 0.8% [P = 0.002] and 8.0 ± 1.6% vs. 7.7 ± 1.1% [P = 0.006], respectively); the improvement was higher with SAP (P = 0.005). Insulin requirement showed a significant decrease only in SAP patients (0.88 ± 0.25 vs. 0.7 ± 0.23 U/kg/day, P = 0.003). Body mass index did not change during the observation period. No diabetic ketoacidosis episodes were observed during the follow-up, and severe hypoglycemia significantly decreased in SAP patients (P = 0.04). CONCLUSIONS The increased availability of continuous glucose sensors is likely to have a significant impact on pediatric diabetes therapy and education in the near future. In daily settings, patients using SAP can achieve a better control than patients using conventional insulin pump.

Blood ketone bodies in patients with recent‐onset type 1 diabetes (a multicenter study)

Background:  Insulin deficiency with glucagon excess leads to the release of ketone bodies (KBs) by the liver and excretion in the urine. So far, only KB monitoring in urine has been used during assessment of children with diabetes. Currently used nitroprusside strips for urine KB detection react only with acetoacetate (AcAc) and not with the most prevalent KB moiety – 3β‐hydroxybutyrate (3HB) – that is in equilibrium with AcAc (up to 10:1 ratio).

Sensor-Augmented Pump Therapy in Very Young Children with Type 1 Diabetes: An Efficacy and Feasibility Observational Study

BACKGROUND Efficacy and feasibility of sensor-augmented pump (SAP) therapy were evaluated in very young children with type 1 diabetes (T1D). SUBJECTS AND METHODS SAP (Dexcom [San Diego, CA] Seven Plus™ usage combined with insulin pump) therapy was retrospectively evaluated in 28 children (15 boys) younger than 7 years (mean age, 5.8 ± 1.2 years; range, 3-7 years), with T1D. Glycosylated hemoglobin (HbA1c) was evaluated at baseline and at the end of the study, as were efficacy and feasibility of the system, using a rating scale (with 3 being the most positive). RESULTS SAP has been used for at least 6 months by 85% of patients, with an overall good satisfaction (92%). The greatest perceived benefit was the reduced fear of hypoglycemia (score of 3, 81%). HbA1c significantly improved only in patients with baseline HbA1c >7.5% (P = 0.026). CONCLUSIONS SAP therapy is effective and feasible in preschool children with T1D. In patients with high HbA1c at baseline it provide a 0.9% decrease, sustained for at least 6 months.

Insulin secretion and hepatic insulin clearance as determinants of hyperinsulinaemia in normotolerant grossly obese adolescents.

Obesity is characterized by variable degrees of hyperinsulinaemia, which has been attributed to either β‐cell hypersecretion or reduced hepatic insulin extraction, or both. To investigate this controversial issue, a 4‐h frequently sampled i.v. glucose tolerance test (glucose dose 12.8 g m‐2) was performed in 13 normotolerant, grossly obese adolescents (10 F/3 M; 13 ± 1 y; body mass index 32 ± 0.9; pubertal stage 4–5; obesity duration 7.8 ± 3 y) and in a comparable group of 8 healthy, normal‐weight subjects. Glucose, insulin and C‐peptide time‐course were analysed by the minimal model technique, which estimates β‐cell secretion, insulin sensitivity (Si), glucose effectiveness (SG) and hepatic insulin extraction (HE). Despite similar fasting and after load glucose patterns (SG similar in the two groups), obese adolescents showed sustained peripheral hyperinsulinaemia (total insulin area under the concentration curve 67.2 ± 10.8 vs 19.1 ± 1.2 pmol l‐1 in 240 min; p < 0:002) and a 71% reduction in Si (2.02 ± 0.33 vs 6.95 ± 1.03±104 min‐1 (μU ml‐1);p < 0:001). Compared with control subjects, the total amounts of prehepatic insulin secretion and posthepatic insulin delivery were also increased significantly in obese adolescents by 30% and 46%, respectively; HE was reduced by 15% during the first 30 min of the test, but recovered within the normal range during the rest of the test. In conclusion, severely obese adolescents are insulin resistant and their hyperinsulinaemia is primarily caused by β‐cell hypersecretion, whereas the reduction in insulin hepatic extraction is a transient metabolic phenomenon.

Carbohydrate counting with an automated bolus calculator helps to improve glycaemic control in children with type 1 diabetes using multiple daily injection therapy: An 18-month observational study

AIMS This study aimed to investigate the effect of carbohydrate counting (carbC), with or without an automated bolus calculator (ABC), in children with type 1 diabetes treated with multiple daily insulin injections. METHODS We evaluated 85 children, aged 9-16 years, with type 1 diabetes, divided into four groups: controls (n=23), experienced carbC (n=19), experienced carbC+ABC (n=18) and non-experienced carbC+ABC (n=25). Glycated haemoglobin (HbA1c), insulin use, and glycaemic variability - evaluated as high blood glucose index (HBGI) and low blood glucose index (LBGI) - were assessed at baseline and after 6 and 18 months. RESULTS At baseline, age, disease duration, BMI, HbA1c, insulin use, and HBGI (but not LBGI; p=0.020) were similar for all groups. After 6 months, HbA1c improved from baseline, although not significantly - patients using ABC (according to manufacturers recommendations) HbA1c 7.14 ± 0.41% at 6 months vs. 7.35 ± 0.53% at baseline, (p=0.136) or without carbC experience HbA1c 7.61±0.62% vs. 7.95 ± 0.99% (p=0.063). Patients using ABC had a better HBGI (p=0.001) and a slightly worse LBGI (p=0.010) than those not using ABC. ABC settings were then personalised. At 18 months, further improvements in HbA1c were seen in children using the ABC, especially in the non-experienced carbC group (-0.42% from baseline; p=0.018). CONCLUSIONS CarbC helped to improve glycaemic control in children with type 1 diabetes using multiple daily injections. ABC use led to greater improvements in HbA1c, HBGI and LBGI compared with patients using only carbC, regardless of experience with carbC.

Insulin Pump Therapy Management in Very Young Children with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion

BACKGROUND Compared to older children and adolescents very young patients with type 1 diabetes represent a unique population. We analyzed the age-dependent characteristics and parameters of continuous subcutaneous insulin infusion (CSII) in children under 6 years of age with type 1 diabetes. METHODS We evaluated metabolic control and pump-dependent characteristics in 46 children with type 1 diabetes after 0.89 +/- 0.62 years of CSII. RESULTS Metabolic control significantly improved after CSII initiation (glycosylated hemoglobin, 8.12 +/- 1.24% vs. 7.30 +/- 0.67%; P < 0.05), without increased risk for diabetic ketoacidosis or hypoglycemia. Interestingly, very young patients required bigger boluses than expected, especially in the morning and at the afternoon snack. CONCLUSIONS These data support the need to personalize pump-dependent characteristics, especially in very young children with type 1 diabetes, in order to optimize CSII therapy in this unique age group of patients.

Derangements of pyruvate dehydrogenase in circulating lymphocytes of NIDDM patients and their healthy offspring

Pyruvate dehydrogenase (PDH) is poorly active in circulating lymphocytes of NID-DM patients; in vitro, it is unresponsive to insulin at 5 μU/ml and activated at 50 μU/ml, instead of activated and inhibited as in healthy controls. This study examines whether healthy offspring of NIDDM patients with a family history for this disease have these alterations. Twenty seven healthy offspring (23±10 yr, median 18 yr) and their parents (13 diabetic with a family history for NIDDM and 11 healthy without this history) were enrolled. Twenty healthy individuals without the history and matched for age and gender with the offspring served as controls. Minimum levels for enzyme activity before and after cell stimulation with insulin at 5 μU/ml were computed for a 95% CI with no more than 5% of the controls excluded. Increased or unvaried enzyme activity in response to insulin at 50 μU/ml was defined as abnormal. All NIDDM parents and 11/27 offspring had below normal enzyme activity and defective and reversed enzyme response to insulin at 5 and 50 μU/ml; three offspring had altered enzyme response to insulin at both concentrations, four to insulin at 5 μU/ml, three to insulin at 50 μU/ml and six, together with the healthy parents, had no alterations. We conclude that in healthy individuals a family history for NIDDM is frequently signaled, irrespective of age, by molecular derangements, with an apparent genetic background, in their circulating lymphocytes.

Prevalence, Presentation and Clinical Evolution of Graves’ Disease in Children and Adolescents with Type 1 Diabetes Mellitus

Aims: To ascertain the prevalence of Graves’ disease (GD) in 1,323 Caucasian children with type 1 diabetes mellitus (T1DM), and to compare the course of GD in T1DM patients with the one observed in 109 Caucasian peer patients with GD but without T1DM (group B). Results: Only 7 patients (0.53%) of the T1DM series also presented with GD (group A)which was diagnosed many years after diabetes presentation. At GD diagnosis, the prevalence of preclinical hyperthyroidism was higher in group A (p = 0.0001), whereas serum TSH receptor antibodies (TRABs) were higher in group B (p = 0.04). The subsequent course with methimazole therapy and after its withdrawal was very similar in both groups. Conclusions: GD prevalence in T1DM patients was 0.53%, i.e. almost identical to the one reported in the general population. GD was diagnosed many years after T1DM presentation. At GD diagnosis, the clinical picture was milder and TRAB serum levels were lower in diabetic patients. Preclinical diagnosis and early treatment of GD were not associated with better responsiveness to therapy. Screening programs based on periodical TRAB assessments are not useful in T1DM.