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.