Gastroparesis in Adolescent Patient with Type 1 Diabetes: Severe Presentation of a Rare Pediatric Complication

Gastroparesis is a long-term complication of diabetes related to autonomic neuropathy. It is characterized clinically by delayed gastric emptying and upper gastrointestinal symptoms, including early satiety, postprandial fullness, nausea, vomiting, and abdominal pain. Gastric emptying scintigraphy is the gold standard for diagnosis as it reveals delayed gastric emptying. Therapeutic strategies include dietary modifications, improvement of glycemic control, and prokinetic drugs. Case descriptions of diabetic gastroparesis in pediatric ages are very scarce. We report the case of a 16-year-old adolescent with severe presentation of diabetic gastroparesis. She presented with recurrent episodes of nausea, vomiting and abdominal pain which led progressively to reduced oral intake and weight loss. Her past glycemic control had been quite brittle, as demonstrated by several hospitalizations due to diabetic ketoacidosis and recurrent episodes of severe hypoglycemia. After the exclusion of infectious, mechanical, metabolic, and neurological causes of vomiting, a gastric emptying scintigraphy was performed, leading to the diagnosis of gastroparesis. Treatment with metoclopramide was started with progressive relief of symptoms. To improve glycemic control, insulin therapy with an advanced hybrid, closed loop system was successfully started. Pediatricians should consider diabetic gastroparesis in children and adolescents with long-standing, poorly controlled diabetes and appropriate symptomology

The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020

To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

The Impact of Insulin-Induced Lipodystrophy on Glycemic Variability in Pediatric Patients with Type 1 Diabetes

Lipodystrophy is the most common dermatological complication in patients with diabetes on insulin therapy. Despite the high frequency of lipodystrophy, there are still several difficulties in giving advice about avoidance into practice among children and adolescents with type 1 diabetes and their caregivers. This cross-sectional study aims to evaluate the prevalence of insulin-induced lipodystrophy in a cohort of pediatric patients with type 1 diabetes, to identify associated clinical factors and to assess its influence on glycemic control. Two hundred and twelve patients attending our Diabetes Center during a three-month period were enrolled. The presence of lipodystrophy was assessed by inspection and palpation procedures. Demographic and clinical data including type of treatment, frequency of rotation of insulin administration sites, and glucose metrics of the previous 30 days were assessed and statistically analyzed. Prevalence of lipohypertrophy was 44.3%. Two patients were affected by lipoatrophy (0.9%). Improper rotation of insulin administration sites and low awareness on lipodystrophy were associated to the occurrence of this skin condition (p = 0.050 and p = 0.005, respectively). When comparing patients with and without lipodystrophy, a significant difference in glycemic variability parameters was detected (p = 0.036 for coefficient of variation, p = 0.029 for standard deviation score of glucose levels). Lipodystrophy still represents a common complication in patients on insulin therapy. The present study reveals its negative impact on glycemic variability. This finding emphasizes the importance of prevention strategies to minimize the occurrence of this dermatological complication that may interfere with clinical history of the disease

Discordance between Glucose Management Indicator and Glycated Hemoglobin in a Pediatric Cohort with Type 1 Diabetes: A Real-World Study

The introduction of continuous glucose monitoring (CGM) systems in clinical practice has allowed a more detailed picture of the intra- and interdaily glycemic fluctuations of individuals with type 1 diabetes (T1D). However, CGM-measured glucose control indicators may be occasionally inaccurate. This study aims to assess the discrepancy between the glucose management indicator (GMI) and glycated hemoglobin (HbA1c) (ΔGMI-HbA1c) within a cohort of children and adolescents with T1D, exploring its correlation with other CGM metrics and blood count parameters. In this single-center, cross-sectional study, we gathered demographic and clinical data, including blood count parameters, HbA1c values, and CGM metrics, from 128 pediatric subjects with T1D (43% female; mean age, 13.4 ± 3.6 years). Our findings revealed higher levels of the coefficient of variation (CV) (p 250 mg/dL (p = 0.033) among subjects with ΔGMI-HbA1c > 0.3%. No association was observed between blood count parameters and ΔGMI-HbA1c. In conclusion, despite the advancements and the widespread adoption of CGM systems, HbA1c remains an essential parameter for the assessment of glycemic control, especially in individuals with suboptimal metabolic control and extreme glycemic variability

Aiming for the Best Glycemic Control Beyond Time in Range: Time in Tight Range as a new CGM Metric in Children and Adolescents with Type 1 Diabetes using Different Treatment Modalities

Introduction: To evaluate time in tight range (TITR) 70-140 mg/dL (3.9- 7.8 mmol/L), its correlation with standard continuous glucose monitoring (CGM) metrics and the clinical variables that possibly have a substantial impact on its value, in a large cohort of pediatric subjects using different treatment strategies. Material and methods: A total of 854 children and adolescents with type 1 diabetes were consecutively recruited in this real-world, dual-center, cross-sectional study. Participants were categorized into four treatment groups (multiple daily injections + real-time CGM, multiple daily injections + intermittently scanned CGM, sensor augmented pump, and hybrid closed loop (HCL)). Demographical and clinical data, including CGM data, were collected and analyzed. Results: The overall study population exhibited an average TITR of 36.4±12.8%. HCL users showed higher TITR levels compared to the other treatment groups (p<0.001). A time in range (TIR) cut-off value of 71.9% identified subjects achieving a TITR≥50% (AUC 0.98; 95%CI 0.97-0.99, p<0.001), and a strong positive correlation between these two metrics was observed (r=0.95, p<0.001). An increase in TIR of 1% was associated with 1.84 (R2 Nagelkerke=0.35, p<0.001) increased likelihood of achieving TITR≥50%. Use of HCL systems (B=7.78; p<0.001), disease duration (B=-0.26, p=0.006), coefficient of variation (B=-0.30, p=0.004), and glycated haemoglobin (B=-8.82; p<0.001) emerged as significant predictors of TITR levels. Conclusions: Our study highlights that most children and adolescents with type 1 diabetes present TITR levels below 50%, except those using HCL. Tailored interventions and strategies should be implemented to increase TITR

MiniMed™ 780G six-month use on children and adolescents with type 1 diabetes: clinical targets and predictors of optimal glucose control

Background: The aim of this multicenter observational real-world study was to investigate glycemic outcomes in children and adolescents with type 1 diabetes over the first six-month use of MiniMed™ 780G. Secondary objective was to evaluate demographic and clinical factors that may be significantly associated with the achievement of therapeutic goals. Methods: Demographic, anamnestic, and clinical data of study participants were collected at time of enrolment. Data on ambulatory glucose profile were acquired at 3 and 6 months after activating Auto Mode. Aggregated glucose metrics and device settings of the entire study period were analyzed to identify predictors of optimal glycemic control, assessed by the concomitant achievement of time in range (TIR) > 70%, coefficient of variation (CV) < 36%, glucose management index (GMI) < 7%, and time below range (TBR) < 4%. Results: Our study cohort consisted of 111 children and adolescents (54.1% female) aged 7-18 years. All the most relevant clinical targets were achieved according to recommendations from the International Consensus both at 3 and 6 months. When considering aggregated data, primary goals in terms of TIR, CV, GMI, and TBR were achieved respectively by 72.1%, 74.8%, 68.5%, and 74.8% of participants. Additionally, 44 individuals (39.6%) concomitantly addressed all the above clinical targets. Regression analysis revealed that older age, briefer duration of disease, and shorter active insulin time were significant predictors of optimal glucose control. Comparing two groups of individuals stratified according to the HbA1c mean value in the year preceding MiniMed™ 780G use, achieving glycemic targets was observed in the subgroup with lower HbA1c. Conclusions: Our study highlights the effectiveness and safety of MiniMed™ 780G in the pediatric population. More extensive and personalized training on advanced hybrid closed loop use should be considered for younger people and those with long disease duration