Davide Tinti

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.

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.

Use of the predictive low glucose management (PLGM) algorithm in Italian adolescents with type 1 diabetes: CareLink™ data download in a real-world setting.

Actually, closed-loop systems have significantly enhanced, shifting from in-hospital to at-home studies [1], together with the use of integrated bi-hormonal artificial pancreas system [2]. However, Kovatchev et al. [3] summarize today’s artificial pancreas systems as a work in progress, as still there is much work to be done. Nonetheless, intermediate steps in introduction of automation of insulin delivery are already commercially available and in clinical use. As these early steps in automation need understanding and shift in mindset of both patients and care givers, a group of pediatrics endocrinologists formed a group (Sensor Experience Group) to study closely and intensively the onboarding of adolescent patients with type 1 diabetes on automated systems to gain first-hand experience and peer-to-peer insights in a unique free-living environment. The aim of our observational perspective anonymous data collection using CareLink was to evaluate safety and effectiveness of PLGM system under free-living conditions.

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.

Case Report: When an Induced Illness Looks Like a Rare Disease.

The recognition of fabricated illness (FI) in a child represents a diagnostic challenge. The suspicion of FI often arises from the discrepancy between laboratory tests and clinical history. For instance, (unnecessary) insulin injections by caregivers has been widely described as a common cause of factitious hypoglycemia that may be inferred from discrepancies between plasma insulin and c-peptide. However, contemporary administration of insulin with an insulin secretagogue (glyburide), and of additional drugs, can make the diagnostic pathway problematic. We report the case of a child 4 years and 11 months old, admitted for alternance of hypo- and hyperglycemia associated with hirsutism, hypokalemia, nephrocalcinosis, and neurodevelopmental delay. All these features were compatible with Rabson-Mendenhall syndrome, a rare disorder of severe insulin resistance linked to mutations of insulin receptor. At admission, plasma insulin levels were high during hypoglycemic episodes, but c-peptide was repeatedly in the normal range. The genetic analysis of insulin receptor was negative. The story of previous hospital admissions, inconsistency between insulin and c-peptide values, and association between hypoglycemic episodes in the child with the presence of the mother, raised the suspicion of FI. This hypothesis was confirmed by a video recording that revealed the administration by the mother of multiple drugs (insulin, glyburide, progesterone, and furosemide) that mimicked most of the features of Rabson-Mendenhall syndrome, including hirsutism and hypoglycemia with coincident, inappropriately normal c-peptide values due to the administration of the insulin secretagogue. Our case indicates that inconsistency among consecutive diagnostic tests should be regarded as a clue of FI.

Recommendations for the use of sensor‐augmented pumps with predictive low‐glucose suspend features in children: The importance of education

Abstract: Sensor‐augmented pumps, which consist of a pump and a continuous glucose monitoring system, offer considerable therapeutic opportunities, despite requiring close attention in the early phase of their use. The aim of this paper is to provide recommendations on the use of a predictive low glucose management (PLGM) system (Minimed 640G™, Medtronic, Northridge, CA, USA) in adolescents with type 1 diabetes either at the start of therapy or during follow‐up. Sound clinical recommendations on PLGM are of increasing importance since several recent papers have reported significant clinical improvements in patients with PLGM, especially in adults. These recommendations are based on the experience of a group of pediatric endocrinologists who collaborated to closely and intensively study the on‐boarding of adolescent patients with type 1 diabetes on automated systems to gain first‐hand experience and peer‐to‐peer insights in a unique free‐living environment. The suggestions provided here are indicative, so can be adapted to the individual realities and experiences of different diabetes centers. However, we believe that close adherence to the proposed scheme is likely to increase the chances of improving the clinical and metabolic outcomes of patients treated with this therapy.

Neonatal diabetes in a patient with IPEX syndrome: an attempt at balancing insulin therapy

few days of careful adjustments, insulin boluses were withdrawn and insulin pump was set to minimum deliverable basal dose (0.025 U/h). Despite that, we were forced to use diluted rapid analog insulin, with a 1:10 ratio, due to his low requirement (total daily dose: 0.2–0.3 U/kg/day). Aspart insulin was chosen (NovoRapid, Novo Nordisk, Denmark) because of very limited availability of other insulin diluents. Since four weeks of life, he developed persistent diarrhea associated with failure to thrive. Blood tests showed high eosinophil count and presence of specific IgE against milk. Despite fed by a protein hydrolyzed formula, he showed only poor weight gain (800 g/1.763 lbs. in 8 weeks) with a good glycemic control (Fig. 1). Endoscopic investigation was then performed and histological analysis demonstrated extensive villous atrophy with intense T-lymphocyte infiltration of duodenal mucosa and lamina propria, consistent with autoimmune enteropathy. Given the early-onset diabetes and autoimmune enteropathy associated with signs of immunedysregulation, in the suspicion of immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome, we tested anti-harmonin and anti-villin antibodies, which were both positive (> 100 UA, normal < 3, and 21 UA, normal < 11, respectively). For these reasons, at the age of 2 months, a immunosuppressive therapy with Sirolimus and steroids was introduced. Subsequently, high glucose peaks developed and insulin schedule was adapted according to circadian glycemic variation, providing a higher dose during the evening and first part of the night. At the same time, to reduce diarrhea, the child was placed under continuous total parenteral nutrition (TPN) through central line. Hence, insulin was given intravenously using an infusion pump through the same IV line; human regular insulin (Humulin R) with the same 1:10 dilution and protocol was chosen; and schedule was adapted according to CGM data. Repeated Case presentation

Fine tuning of nutritional therapy by using continuous glucose monitoring in an infant with a gastrointestinal malformation

A 4-month-old infant came to our attention for hyperglycemia during hospitalization for rectal bleeding and diarrhea. The baby was born at 35 weeks of gestation, with low weight (2290 g) and polyhydramnios. A diagnosis for longgap type 1 esophageal atresia, a very rare malformation, was made. Nutrition was performed through gastrostomy from the second day after birth, obtaining good growth and weight gain. The infant underwent traction of esophageal pouches (Foker technique) and gastrostomy at 3 months of age. One month after surgery, the baby was admitted to the emergency department for rectal bleeding and diarrhea. During rehydration with a solution containing glucose (5 %) and other electrolytes, hyperglycemia (395 mg/L or 20.8 mmol/L) and hyponatremia (128 mEq/L) were found. Glycemic measurements before and 2 h after meals showed a slight increase in glycemic values; viral studies in stool and blood resulted negative. The baby was discharged with a diagnosis of critical illness hyperglycemia during rectal bleeding after gastroenteritis. Clinical and nutritional follow-up was proposed. During a routine visit at 8 months of age, the infant showed low weight (6.140 kg, 2 SDS) and growth (68 cm, 0.94 SDS). According to the hypothesis of a low introduction of calories (60 mL/kg of artificial formula, four times a day through gastrostomy), we suggested an increase in the intake volume of meals. The baby had good milk transit tolerance. Thereafter, the baby developed again diarrhea associated with intense sweating and fine tremors after meals. Hematologic, electrolytes, hormonal profiles and milk protein allergy test resulted normal; we only observed episodes of hypoglycemia (40 mg/dL, 2.2 mmol/L) more than 2 h after meals. HbA1c was 46 mmol/mol (6.3 %), and glucose was present in the urinalyses (????). In order to investigate hypoglycemic episodes, we evaluated insulinemia that resulted elevated (421 mU/L) as well as C-peptide (39.9 ng/mL). To better investigate glycemic profiles, continuous glucose monitoring (CGM, G4 Platinum, Dexcom ), usually prescribed for type 1 diabetes management, was started as a diagnostic tool for a 7-day period. We observed hyperglycemic peaks immediately following meals and then hypoglycemic values after 2 h, with 19 % of time spent in hyperglycemia (above 180 mg/dL or 10 mmol/L) and 43 % in hypoglycemia (below 70 mg/dL or 3.9 mmol/L) (Fig. 1a). During hyperglycemic peaks, we took blood Managed by Antonio Secchi.