Fear of hypoglycemia in children with type 1 diabetes and their parents: Validation of the Italian version of the Hypoglycemia Fear Survey for Children and for Parents.

BACKGROUND: Currently, Italian versions of the Hypoglycemia Fear Survey for Children (CHFS) and for Parents (PHFS) quantifying Fear of Hypoglycemia (FoH) in pediatric diabetes are not available. OBJECTIVE: To validate the Italian version of the CHFS and PHFS. SUBJECTS AND METHODS: One hundred and seventy-four children with type 1 diabetes aged 6-18 and 178 parents completed the CHFS and PHFS, the PedsQL 3.0 Diabetes module and the KIDSCREEN-10. Internal consistency was good (α = 0.85 for CHFS, α = 0.88 for PHFS); validity was supported by correlations of CHFS total score (CHFS-T r = -0.50; p < 0.001, CI = -0.62 to -0.35) and Worry subscale (CHFS-W r = -0.49; p < 0.001, CI = -0.62 to -0.32) with measures of health-related quality of life (QoL), which were not related to PHFS scores. Factor analyses justified the structure and the separate scoring of Behavior and Worry subscales. Children's age was negatively correlated with CHFS-T (r = -0.16; p = 0.03, CI = -0.36 to 0.00), CHFS-W (r = -0.29; p = 0.02, CI = -0.39 to -0.07), PHFS-T (r = -0.20; p = 0.006, CI = -0.35 to -0.04), PHFS-B (r = -0.30; p = 0.001, CI = -0.43 to -0.17). Mean (SD) item scores of CHFS-T (1.47 ± 0.56 vs. 1.27 ± 0.57; p < 0.05) and CHFS-W (1.20 ± 0.73 vs. 0.96 ± 0.68; p < 0.05) were higher in children with HbA1c ≥7.5%. Higher levels of distress for upsetting hypoglycemia were associated with lower child's QoL scores as perceived by children (Peds-QL: 72.6 ± 12.8 vs. 80.4 ± 11.9; p < 0.001) and parents (Peds-QL: 70.6 ± 13.8 vs. 75.8 ± 12.9; p < 0.05). CONCLUSION: The Italian version of CHFS and PHFS appears to be a valid measure to assess FoH in clinical practice and factor analysis supports separate scoring for the Worry and Behavior subscales.

Decreasing prevalence of retinopathy in childhood-onset type 1 diabetes over the last decade: A comparison of two cohorts diagnosed 10 years apart.

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 < .003), respectively, and that of severe retinopathy was 1.7% and 9.6% (P = .018). Lifetime HbA1c was lower in the new cohort (7.8% ± 0.8% vs. 8.1% ± 0.8%; P = .002) during all periods following the first 5 years after diagnosis. Patients without retinopathy in the two cohorts had similar levels of HbA1c. Compared with patients without retinopathy, those with retinopathy had higher lifetime HbA1c and long-term HbA1c variability. However, on multiple regression analysis, only lifetime HbA1c was independently associated with retinopathy (P = .0018). CONCLUSIONS: The risk of developing retinopathy was nearly halved in children who developed type 1 diabetes in the new millennium compared with previous cohorts. These results confirm that maintaining the lowest possible levels of HbA1c throughout lifetime protects from diabetic retinopathy.

Role of the KCNJ Gene Variants in the Clinical Outcome of Type 1 Diabetes.

Diabetes is considered as a disease with a wide and continuous clinical spectrum, ranging from Type 1 (T1D) and Type 2 Diabetes (T2D) with complex multifactorial causes. In the last years, particular attention has been focused on the predictive value and therapeutic potential of single nucleotide polymorphisms (SNPs). SNPs can alter the seed-sequence in miRNA's loci and miRNA target sites causing changes in the structure and influencing the binding function. Only few studies have investigated the clinical influence of SNPs, in particular potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ) gene variants in T1D population. The aim of the study is to investigate the occurrence and the possible metabolic significance of KCNJ polymorphism in a group of pediatric patients with T1D. The study was performed in a cohort of 90 Caucasian children and adolescents with T1D and 93 healthy subjects. Rs5210 polymorphism has been analyzed with a prevalence of the GG genotype in the patient group suggesting its association with T1D. Therefore, a relationship was found between GG genotype and body mass index (BMI) at diagnosis and insulin requirement (IR) after 6 months. The study suggested an action for rs5210 in determining the metabolic features of T1D pediatric patients, by showing some clues of insulin resistance in patients carrying that polymorphism.

Diabetic ketoacidosis: A consensus statement of the Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology and Pediatric Diabetoloy (SIEDP).

BACKGROUND AND AIM: Diabetic ketoacidosis (DKA) is a serious medical emergency once considered typical of type 1 diabetes (T1DM), but now reported to occur in type 2 and GDM patients as well. DKA can cause severe complications and even prove fatal. The aim of our study was to review recent international and national guidelines on diagnosis, clinical presentation and treatment of diabetic ketoacidosis, to provide practical clinical recommendations. METHODS AND RESULTS: Electronic databases (MEDLINE (via PUB Med), Scopus, Cochrane library were searched for relevant literature. Most international and national guidelines indicate the same accurate flow chart to diagnose, to evaluate from clinical and laboratory point of view, and treat diabetic ketoacidosis. CONCLUSION: Prompt diagnosis, rapid execution of laboratory analysis and correct treatment are imperative to reduce the mortality related to diabetic ketoacidosis. These recommendations are designed to help healthcare professionals reduce the frequency and burden of DKA.

Yq Microdeletion in a Patient with VACTERL Association and Shawl Scrotum with Bifid Scrotum: A Real Pathogenetic Association or a Coincidence?

VACTERL association is defined by the occurrence of congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, and limb defects. No genetic alterations have been discovered except for some sporadic chromosomal rearrangements and gene mutations. We report a boy with VACTERL association and shawl scrotum with bifid scrotum who presented with a de novo Yq11.223q11.23 microdeletion identified by array CGH. The deletion spans 3.1 Mb and encompasses several genes in the AZFc region, frequently deleted in infertile men with severe oligozoospermia or azoospermia. Herein, we discuss the possible explanation for this unusual genotype-phenotype correlation. We suggest that the deletion of the BPY2 (previously VCY2) gene, located in the AZFc region and involved in spermatogenesis, contributed to the genesis of the phenotype. In fact, BPY2 interacts with a ubiquitin-protein ligase, involved in the SHH pathway which is known to be implicated in the genesis of VACTERL association.

Optimal predictive low glucose management settings during physical exercise in adolescents with type 1 diabetes.

OBJECTIVES: To assess the optimal setting of the predictive low glucose management (PLGM) algorithm for preventing exercise-induced hypoglycemia in adolescents with type 1 diabetes. METHODS: Thirty-four adolescents, 15 to 20 years, wearing PLGM system, were followed during 3 days exercise during a diabetes camp. PLGM threshold was set at 70 mg/dL between 8 am and 10 pm and 90 mg/dL during 10 pm and 8 am Adolescents were divided into group A and B, with PLGM threshold at 90 and 70 mg/dL, respectively, during exercise. Time spent in hypoglycemia and AUC for time slots 8 am to 1 pm, 1 to 4 pm, 4 to 11 pm, 11 pm to 3 am, 3 to 8 am, in 3 days were compared between groups by Wilcoxon rank sum test. RESULTS: We analyzed 31 patients (median age 15.0 years, 58.1% males, median diabetes duration 7.0 years, hemoglobin A1c [HbA1c] 7.1%). No significant difference has been observed in time spent in hypoglycemia between groups using threshold 70 or 90. Time spent in target was similar in both groups, as well as time spent in hypo or hyperglycemia. The trends of blood glucose over the 3 days in the 2 groups over-lapped without significant differences. CONCLUSIONS: A PLGM threshold of 90 mg/dL during the night was associated with reduced time in hypoglycemia in adolescents doing frequent physical exercise, while maintaining 65.1% time in range during the day. However, a threshold of 70 mg/dL seems to be safe in the duration of the physical exercise. PLGM system in adolescents with type 1 diabetes was effective to prevent hypoglycemia during and after exercise, irrespective of the PLGM thresholds used.

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

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.

Unmet needs in children with diabetes: the role of basal insulin.

The goal of insulin therapy in people affected by type 1 diabetes mellitus consists in achieving an optimal metabolic control and so HbA1c levels below 7.5%, according to the conclusions of relevant scientific studies. In any case it seems that this target is far from being achieved, mostly in the pediatric population. However, many important pharmacological, technological and cultural milestones have been placed both in therapy and management of insulin-dependent diabetes even if the gap between growing knowledge in these fields and its application in daily clinical practice appears still too wide. A fundamental component of these advancements concerns the design of new insulin basal analogues; molecules used to realize a basal-bolus model of therapy with MDI scheme. Degludec insulin has been recently approved for the pediatric utilization (aged 1 to 17 years). A registration trial for pediatric population (aged 6 to 17 years) is in progress for glargine U-300 insulin. These two insulin types have different biochemical and pharmacological properties and they represent two different ways to achieve the ideal basal analogue. Insulin degludec and insulin glargine U-300 are the newest basal analogues and each of them has proper pharmacokinetic and pharmacodynamic characteristics. Their characteristics represent an effort to create the ideal solution. The aim of this review is to summarize the pharmacokinetic and pharmacodynamic properties of these new insulins, to list the most significant scientific findings regarding their pharmacology as well as clinical uses, with particular reference to the pediatric population in order to declare them to clinical experience and to report data on an initial experience with these analogues, especially with degludec insulin. Once again, evolution goes through the specialized training of the staff involved in the care of the diabetic patient and the constant education of the latter.

The effect of obesity and type 1 diabetes on renal function in children and adolescents.

BACKGROUND: Early signs of renal complications can be common in youths with type 1 diabetes (T1D). Recently, there has been an increasing interest in potential renal complications associated with obesity, paralleling the epidemics of this condition, although there are limited data in children. HYPOTHESIS: Obese children and adolescents present signs of early alterations in renal function similar to non-obese peers with T1D. SUBJECTS: Eighty-three obese (age: 11.6 ± 3.0 yr), 164 non-obese T1D (age: 12.4 ± 3.2 yr), and 71 non-obese control (age: 12.3 ± 3.2 yr) children and adolescents were enrolled in the study. METHODS: Anthropometric parameters and blood pressure were measured. Renal function was assessed by albumin excretion rate (AER), serum cystatin C, creatinine and estimated glomerular filtration rate (e-GFR), calculated using the Bouvet's formula. RESULTS: Obese and non-obese T1D youths had similar AER [8.9(5.9-10.8) vs. 8.7(5.9-13.1) µg/min] and e-GFR levels (114.8 ± 19.6 vs. 113.4 ± 19.1 mL/min), which were higher than in controls [AER: 8.1(5.9-8.7) µg/min, e-GFR: 104.7 ± 18.9 mL/min]. Prevalence of microalbuminuria and hyperfiltration was similar between obese and T1D youths and higher than their control peers (6.0 vs. 8.0 vs. 0%, p = 0.02; 15.9 vs. 15.9 vs. 4.3%, p = 0.03, respectively). Body mass index (BMI) z-score was independently related to e-GFR (r = 0.328; p < 0.001), and AER (r = 0.138; p = 0.017). Hemoglobin A1c (HbA1c) correlated with AER (r = 0.148; p = 0.007) but not with eGFR (r = 0.041; p = 0.310). CONCLUSIONS: Obese children and adolescents show early alterations in renal function, compared to normal weight peers, and they have similar renal profiles than age-matched peers with T1D.

Insulin degludec in combination with bolus insulin aspart is safe and effective in children and adolescents with type 1 diabetes.

Insulin degludec (IDeg) once-daily was compared with insulin detemir (IDet) once- or twice-daily, with prandial insulin aspart in a treat-to-target, randomized controlled trial in children 1-17 yr with type 1 diabetes, for 26 wk (n = 350), followed by a 26-wk extension (n = 280). Participants were randomized to receive either IDeg once daily at the same time each day or IDet given once or twice daily according to local labeling. Aspart was titrated according to a sliding scale or in accordance with an insulin:carbohydrate ratio and a plasma glucose correction factor. Randomization was age-stratified: 85 subjects 1-5 yr. (IDeg: 43), 138 6-11 yr (IDeg: 70) and 127 12-17 yr (IDeg: 61) were included. Baseline characteristics were generally similar between groups overall and within each stratification. Non-inferiority of IDeg vs. IDet was confirmed for HbA1c at 26 wk; estimated treatment difference (ETD) 0.15% [-0.03; 0.32]95% CI . At 52 wk, HbA1c was 7.9% (IDeg) vs. 7.8% (IDet), NS; change in mean FPG was -1.29 mmol/L (IDeg) vs. +1.10 mmol/L (IDet) (ETD -1.62 mmol/L [-2.84; -0.41]95% CI , p = 0.0090) and mean basal insulin dose was 0.38 U/kg (IDeg) vs. 0.55 U/kg (IDet). The majority of IDet treated patients (64%) required twice-daily administration to achieve glycemic targets. Hypoglycemia rates did not differ significantly between IDeg and IDet, but confirmed and severe hypoglycemia rates were numerically higher with IDeg (57.7 vs. 54.1 patient-years of exposure (PYE) [NS] and 0.51 vs. 0.33, PYE [NS], respectively) although nocturnal hypoglycemia rates were numerically lower (6.0 vs. 7.6 PYE, NS). Rates of hyperglycemia with ketosis were significantly lower for IDeg vs. IDet [0.7 vs. 1.1 PYE, treatment ratio 0.41 (0.22; 0.78)95% CI , p = 0.0066]. Both treatments were well tolerated with comparable rates of adverse events. IDeg achieved equivalent long-term glycemic control, as measured by HbA1c with a significant FPG reduction at a 30% lower basal insulin dose when compared with IDet. Rates of hypoglycemia did not differ significantly between the two treatment groups; however, hyperglycemia with ketosis was significantly reduced in those treated with IDeg.

Recommendations for recognizing, risk stratifying, treating, and managing children and adolescents with hypoglycemia.

There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using "smart pumps" or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L), although any form of carbohydrate (e.g., sucrose, which consists of glucose and fructose, or honey, sugary soft drinks, or fruit juice) containing glucose may be used. Using automatic insulin delivery systems, the oral glucose dose can be decreased to 0.1 g/kg. Practical flow charts are included to aid clinical decision-making. Although representing the official position of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED), these guidelines are applicable to the global audience and are especially pertinent in the era of CGM and other advanced technologies.

Measures of Patient-Reported Expectations, Acceptance, and Satisfaction Using Automated Insulin Delivery Systems: A Review.

In people with type 1 diabetes, Automated Insulin Delivery (AID) systems adjust insulin delivery in response to sensor glucose data and consist of three components: an insulin pump, a continuous glucose sensor, and an algorithm that determines insulin delivery. To date, all the available AID systems require users to announce carbohydrate intake and deliver meal boluses, as well as respond to system alarms. The use of AID devices both initially and over time may be influenced by a variety of psychological factors. Analysis of patient-related outcomes should be taken into account, while recruiting applicants for the systems who are motivated and have realistic expectations in order to prevent AID dropout. We report an up-to-date summary of the available measures and semi-structured interview content to assess AID expectations, acceptance, and satisfaction using the AID systems. In conclusion, we suggest, before and after starting using AID systems, performing a specific evaluation of the related psychological implications, using validated measures and semi-structured interviews, that allows diabetes care providers to tailor their education approach to the factors that concern the patient at that time; they can teach problem-solving skills and other behavioral strategies to support sustained use of the AID system.

A case of congenital hypothyroidism in PHACE syndrome.

Although hemangiomas, benign tumors of vascular origin, are very common among children and represent the most frequent benign tumor at that age, their association with other malformations constitutes a rare neurocutaneous disorder called PHACE syndrome. This condition is characterized by posterior fossa anomalies, hemangioma of the face, arterial alterations, cardiac defects, and eye anomalies (as represented by the acronym PHACE); sternum defects, endocrinopathies, and thyreopathies may be present as well. In this report, we describe a case of congenital hypothyroidism due to an empty thyroid site, as demonstrated by ultrasound, in an Italian child.

Incidence of Type 1 diabetes and factors associated with presence and severity of ketoacidosis at onset in children.

BACKGROUND AND AIM: To assess the incidence of Type 1 Diabetes Mellitus (T1DM) during the period 2012-2017, the frequency and severity of ketoacidosis (DKA) at diabetes onset, and the factors associated with DKA in children and adolescents younger than 18 years old in the Abruzzo region, Italy. METHODS: All incident cases of T1DM (0-17 years old) diagnosed between January 2012 and December 2017 were included. Data about the patients were obtained from two independent sources; insulin prescriptions and medical records. Clinical data at diabetes onset, as well as demographic and non-demographic data, including center of first hospitalization, distance to regional reference center and number of pediatricians (per 1000 residents younger than 18 years) were collected and evaluated. RESULTS: During 2012-2017 period, 177 patients were diagnosed with T1DM. In 2012, T1DM incidence was 15.6 per 100,000/year; in 2013, 16.4 per 100,000/year; in 2014, 11.6 per 100,000/year; in 2015, 14.2 per 100,000/year; in 2016, 16.2 per 100,000/year and in 2017, 12.2 per 100,000/year. DKA was present in 29.3% of patients, 6.9% with severe DKA. The DKA presence was correlated to age (p<0.02), ethnicity (p<0.04), being transferred to a specialist center instead of being directly admitted to one (p<0.002) and the number of pediatricians in the population (p<0.01). The DKA severity was associated with the delay of transfer (p<0.04). CONCLUSIONS: Being admitted directly to a specialist center is very important and it could be expression of high alertness of pediatricians. Availability of well-trained pediatricians is necessary for the prevention of DKA. (www.actabiomedica.it).

A Novel Heterozygous Mutation of the CYP17A1 Gene in a Child with a Micropenis and Isolated 17,20-Lyase Deficiency.

Disorders of sexual development (DSDs) are characterized by a heterogeneous group of congenital conditions associated with atypical development of the sex chromosomes, gonadal or anatomical sex. We report the case of a child with an isolated micropenis, a typical feature of the 46,XY DSD showing low basal testosterone levels and post-stimulation with the hCG test. Molecular analysis using a next-generation sequencing (NGS) panel of 50 genes involved in DSDs was performed, revealing a heterozygous mutation, c.1040G > ANM_000102.4, in the CYP17A1 gene. Sanger sequencing was used to confirm the gene variant detected by NGS; it was also performed to his parents, revealing the presence of the same mutation in the mother, who presented no features of the disease. Then, the serum steroid profile was determined by liquid chromatography coupled to tandem mass spectrometry analysis. Interestingly, this analysis highlighted low levels of testosterone, progesterone, and dehydroepiandrostenedione, as also confirmed by a stimulus test with ACTH. These results suggest that, in some cases, heterozygous mutations in recessive genes involved in adrenal steroidogenesis can also affect the patient's phenotype.

Variables associated with severe hypoglycemia in children and adolescents with type 1 diabetes: a population-based study.

OBJECTIVE: Hypoglycemia remains a central problem in the management of type 1 diabetes mellitus (T1DM) and limits the achievement of good or normal glycemic control. The Diabetes Control and Complication Trial showed that intensive treatment of T1DM increased the risk of severe hypoglycemia (SH) when compared to conventional therapy. The aim of our study was to determine the incidence of SH and associated variables in a population of children and adolescents with T1DM. RESEARCH DESIGN AND METHODS: We performed a 7.5-yr prospective study enrolling 195 patients aged 13.9 ± 6.6 yr. The study was carried out by referring to the T1DM population-based register in the Abruzzo region of Italy. The incidence of SH, defined as blood glucose levels <50 mg/dL (<2.77 mmol/L) associated with altered states of consciousness (including confusional state, seizures, and coma) was recorded. Glycated hemoglobin (HbA1c) percentage, insulin dose, insulin regimen, time since diagnosis, and age at onset were also recorded. RESULTS: One hundred and thirty-three severe hypoglycemic events occurred during the study period; the overall incidence was 9.4 episodes per 100 patient-years. Significant predictors of hypoglycemia were diabetes duration >10 yr (p = 0.01), basal/bolus insulin ratio (ratio of daily basal insulin units to daily bolus insulin units) >0.8 (p = 0.01). No relationship was found between hypoglycemic episodes and HbA1c levels, daily insulin requirements, or insulin regimen. CONCLUSIONS: In these patients, a relatively low incidence of SH was recorded, without pronounced association with lower HbA1c or multiple daily injection insulin therapy. SH seems to be mainly related to management of diabetes. We believe that the main path to SH prevention is through patient and family education in the management of T1DM.

Genital sanguineous discharge in prepuberty: a case of mullerian papilloma of vagina in a nine-year-old girl.

Vaginal bleeding in prepuberty is an alarming symptom that must be carefully investigated. Among quite common causes of genital sanguineous discharge, there are rarer conditions responsible for bleeding at this age like Mullerian papilloma of the genital tract. In this report, we describe a case of Mullerian papilloma of the vagina in a 9-year-old girl. We believe in the importance of a correct clinical setting and histological definition to avoid wrong diagnosis and consequent inadequate treatments. Mullerian papilloma, a benign tumor, can in fact be treated only with local excision.

Insulin/carbohydrates ratio during the first 6-month therapy with insulin degludec in a paediatric population with type 1 diabetes previously treated with insulin glargine. An observational longitudinal study.

BACKGROUND: No data exist about the changes induced by the transition from first-generation long-acting insulins to second-generation long-acting analogues in the paediatric population. OBJECTIVE: To assess changes in insulin/carbohydrate ratio (I:CHO) after the first 6 months of degludec therapy in a paediatric population with type 1 diabetes previously treated with glargine U100. SUBJECTS: All patients treated with degludec under routine clinical practice conditions were retrospectively analysed. METHODS: Nonprofit observational retrospective study. Changes during the follow-up in mean CHO/I ratio were assessed using longitudinal linear models for repeated measures. Rate of hypoglycaemia, ketoacidosis and adverse events was evaluated. RESULTS: Overall, 51 children (mean age 13.8 ± 4.6 years; mean diabetes duration 5.8 ± 3.9 years) started therapy with degludec in the period between April 2017 and April 2018. I:CHO ratio before starting degludec therapy significantly differed among the three meals, being the lowest at breakfast and the highest at dinner. After introducing degludec, I:CHO ratio at lunch (-1.29 95% CI -2.02;-0.57) and at dinner (-3.08 95% CI -4.35;-1.8) significantly decreased, while it slightly increased at breakfast (+1.37 95% CI 0.47;2.28). No episodes of severe hypoglycaemia, ketoacidosis and adverse event were recorded during 6 months. CONCLUSIONS: Our data show that the use of degludec is associated with a significant change in the I:CHO ratio at the different meals compared to the previous glargine therapy. This could derive from the flat and prolonged pharmacokinetic profile of degludec. This has important clinical implications for daily insulin dose adjustments.

Effectiveness and safety of flexible therapeutic schemes including first- and secondgeneration basal insulins during a pediatric summer diabetes camp.

Outcomes of insulin analogues in pediatric diabetes camps are poorly investigated; no data is available about insulin degludec (IDeg).Our aim was to assess impact of insulin therapy adopted by the participants to a 4-day diabetes camp held in 2017, hypothesizing a possible excess risk of hypoglycemia in patients treated with IDeg. Overall, 40 children with type 1 diabetes (mean age 13.4±3.0 years; 62.5% males) attended the camp (20.0% on continuous subcutaneous insulin infusion and 80.0% on multiple daily injections - MDI). Among children in MDI regimen, 71.9% were treated with IDeg as basal insulin and 28.1% with glargine U100 (IGlar). All patients used Lispro or Aspart as short-acting insulin. Daily plan of the camp included educational sessions, physical exercise, 3 main meals and 2 snacks. At the arrival, IGlar and short-acting insulin doses were revised according to existing guidelines, while IDeg dose was revised based on an empirical individualized approach. At the arrival, insulin doses were reduced in 22 participants (-19.4±10.5%), while doses were increased in 17 children (+17.8±12.7%), based on individual needs. No statistically significant between-group difference emerged in mean blood glucose and glucose variability. No excess risk of hypoglycemia was found in the IDeg group. The study suggests similar effectiveness and safety of different insulin schemes when associated with appropriate diabetes education and management, and flexible dose adjustments. Despite its longer halflife and the lack of a validated algorithm, IDeg was not associated with an excess risk of hypoglycemia.