Clinical relevance of short-term glycemic variability in children and adolescents with type 1 diabetes: a narrative review.

Background and Objective: In recent years, there has been growing interest in glycemic variability within the scientific community, particularly regarding its potential as an independent risk factor for diabetes-related long-term complications. This narrative review aimed to provide a comprehensive overview of short-term glycemic variability in children and adolescents with type 1 diabetes (T1D). Methods: We performed a search of published literature on the PubMed MEDLINE database using the following combination of search terms: "glycemic variability", "pediatric", "type 1 diabetes", and "children". Key Content and Findings: The widespread use of continuous glucose monitoring (CGM) systems has facilitated the characterization and quantification of glycemic fluctuations. Over the years, several metrics for assessing glycemic variability have been developed. Children and adolescents with T1D often experience wide and frequent glycemic excursions due to behavioral and hormonal factors. Several studies suggest a potential link between glycemic variability and an increased risk of diabetes-related complications. Conclusions: Glycemic variability has become an integral aspect of the routine clinical management of youths with T1D, serving as a valuable therapeutic target. However, achieving recommended glycemic targets in this population remains challenging. Further long-term data are needed to definitively establish the role of glycemic variability in the development of complications.

Exploring the Continuous Glucose Monitoring in Pediatric Diabetes: Current Practices, Innovative Metrics, and Future Implications.

Continuous glucose monitoring (CGM) systems, including real-time CGM and intermittently scanned CGM, have revolutionized diabetes management, particularly in children and adolescents with type 1 diabetes (T1D). These systems provide detailed insights into glucose variability and detect asymptomatic and nocturnal hypoglycemia, addressing limitations of traditional self-monitoring blood glucose methods. CGM devices measure interstitial glucose concentrations constantly, enabling proactive therapeutic decisions and optimization of glycemic control through stored data analysis. CGM metrics such as time in range, time below range, and coefficient of variation are crucial for managing T1D, with emerging metrics like time in tight range and glycemia risk index showing potential for enhanced glycemic assessment. Recent advancements suggest the utility of CGM systems in monitoring the early stages of T1D and individuals with obesity complicated by pre-diabetes, highlighting its therapeutic versatility. This review discusses the current CGM systems for T1D during the pediatric age, established and emerging metrics, and future applications, emphasizing the critical role of CGM devices in improving glycemic control and clinical outcomes in children and adolescents with diabetes.

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 < 0.001) and time above range > 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.

Use of teplizumab in children and adolescents at risk of type 1 diabetes: perspectives of parents and caregivers from an Italian Pediatric Diabetes Center.

AIMS: In view of the imminent introduction of a novel category of disease-modifying treatments for type 1 diabetes (T1D) in European countries, it becomes imperative to understand the existing awareness and viewpoints of parents and caregivers of children and adolescents predisposed to T1D. This study aims to evaluate the perspectives of a cohort of parents and caregivers regarding using teplizumab to delay the onset of T1D in predisposed children and adolescents. METHODS: This single-center study used a survey-based approach. Parents or caregivers of children and adolescents with T1D having at least one additional child without T1D answered 15 questions assessing their awareness about teplizumab, their potential willingness to provide consent for its administration in case of eligibility, and their expectations regarding potential outcomes. RESULTS: Approximately half of the participants (52.6%) expressed readiness to consent to teplizumab administration for their child if the prescription criteria were met in the future. Only 6.3% of parents claimed detailed knowledge about this innovative medication. Notably, parents with prior experience of diabetic ketoacidosis (DKA) demonstrated a higher inclination to consent to teplizumab treatment (p = 0.018). CONCLUSIONS: Our findings underscore the necessity for comprehensive awareness campaigns spreading the current evidence concerning teplizumab in terms of both effectiveness and possible side effects. Additionally, our study reinforces the pivotal role of DKA prevention in successfully integrating disease-modifying treatments into clinical practice.

Aiming for the Best Glycemic Control Beyond Time in Range: Time in Tight Range as a New Continuous Glucose Monitoring 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. Materials 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 [MDI] + real-time CGM, MDI + 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% (area under curve [AUC] 0.98; 95% confidence interval 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 hemoglobin (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.

Safety, Metabolic and Psychological Outcomes of Medtronic MiniMed 780G™ in Children, Adolescents and Young Adults: A Systematic Review.

The MiniMed™ 780G is a second-generation automated insulin delivery system that implements a modified proportional-integral-derivative algorithm with some features of an MD-Logic artificial pancreas algorithm. The system may deliver automatic correction boluses up to every 5 min, and it allows the user to choose between three glucose target setpoints (100, 110 and 120 mg/dL). We aimed to review the current evidence on this device in children, adolescents, and young adults living with type 1 diabetes. We screened 783 papers, but only 31 manuscripts were included in this review. Data on metabolic outcomes show that this system is safe as regards severe hypoglycaemia and diabetic ketoacidosis. The glycated haemoglobin may drop to levels about 7%, with CGM reports showing a time in range of 75-80%. The time above range and the time below range are within the recommended target in most of the subjects. Few studies evaluated the psychological outcomes. This system seems to be more effective than the first-generation automated insulin delivery systems. The MiniMed™ 780G has been associated with an improvement in sleep quality in subjects living with diabetes and their caregivers, along with an improvement in treatment satisfaction. Psychological distress is as reduced as the glucose control is improved. We also discuss some case reports describing particular situations in clinical practice. Finally, we think that data show that this system is a further step towards the improvement of the treatment of diabetes as concerns both metabolic and psychological outcomes.

Psychological and Clinical Challenges in the Management of Type 1 Diabetes during Adolescence: A Narrative Review.

Adolescence, a critical period of physical and psychological development, presents unique challenges in type 1 diabetes (T1D) management due to endocrinological changes, reduced therapeutic adherence, and elevated susceptibility to psychological issues such as depression, anxiety, and eating disorders. This narrative review explores the impact of psychological and behavioral factors on glycemic control in adolescents with T1D. We examine the prevalence and influence of mental health disorders, lifestyle factors, harmful behaviors, and social dynamics on diabetes management and glycemic outcomes. Strategies for improving metabolic control are also reviewed, including cognitive behavioral therapy, technological devices, and educational interventions. The importance of tailored psychological support, family involvement, and targeted interventions to improve adherence to treatment and glycemic control in adolescents with T1D should be emphasized.

Device-Related Skin Reactions Increase Emotional Burden in Youths With Type 1 Diabetes and Their Parents.

BACKGROUND: Skin reactions due to technological devices pose a significant concern in the management of type 1 diabetes (T1D). This multicentric, comparative cross-sectional study aimed to assess the psychological impact of device-related skin issues on youths with T1D and their parents. METHODS: Participants with skin reactions were matched in a 1:1 ratio with a control group. Diabetes-related emotional distress was evaluated using the Problem Areas in Diabetes-Teen version (PAID-T) for participants aged 11 to 19 years and the Problem Areas in Diabetes-Parent Revised version (PAID-PR) completed by parents. In addition, glucose control was assessed through glycated hemoglobin (HbA1c) values and continuous glucose monitoring (CGM) metrics. RESULTS: A total of 102 children and adolescents were consecutively recruited. Adolescents with skin issues had higher PAID-T scores compared to those without (79.6 ± 21.1 vs 62 ± 16.8; P = .004). Parents of youths with skin reactions also reported higher PAID-PR scores than the control group (34.0 ± 11.0 vs 26.9 ± 12.3; P = .015). No differences were observed in HbA1c levels (6.9 ± 0.8% vs 6.8 ± 0.8%, P = .555) or CGM glucose metrics between the two groups. Remarkably, 25.5% were forced to discontinue insulin pumps and/or glucose sensors (21.5% and 5.9%, respectively). CONCLUSIONS: Our study highlighted the increased emotional burden experienced by youths with T1D and their parents due to device-related skin reactions, emphasizing the need for further research and interventions in this crucial aspect of diabetes management.

Sustained Effectiveness of an Advanced Hybrid Closed-Loop System in a Cohort of Children and Adolescents With Type 1 Diabetes: A 1-Year Real-World Study.

OBJECTIVE: To investigate glucose metrics and identify potential predictors of the achievement of glycemic outcomes in children and adolescents during their first 12 months of MiniMed 780G use. RESEARCH DESIGN AND METHODS: This multicenter, longitudinal, real-world study recruited 368 children and adolescents with type 1 diabetes (T1D) starting SmartGuard technology between June 2020 and June 2022. Ambulatory glucose profile data were collected during a 15-day run-in period (baseline), 2 weeks after automatic mode activation, and every 3 months. The influence of covariates on glycemic outcomes after 1 year of MiniMed 780G use was assessed. RESULTS: After 15 days of automatic mode use, all glucose metrics improved compared with baseline (P < 0.001), except for time below range (P = 0.113) and coefficient of variation (P = 0.330). After 1 year, time in range (TIR) remained significantly higher than at baseline (75.3% vs. 62.8%, P < 0.001). The mean glycated hemoglobin (HbA1c) over the study duration was lower than the previous year (6.9 ± 0.6% vs. 7.4 ± 0.9%, P < 0.001). Time spent in tight range (70-140 mg/dL) was 51.1%, and the glycemia risk index was 27.6. Higher TIR levels were associated with a reduced number of automatic correction boluses (P < 0.001), fewer SmartGuard exits (P = 0.021), and longer time in automatic mode (P = 0.030). Individuals with baseline HbA1c >8% showed more relevant improvement in TIR levels (from 54.3% to 72.3%). CONCLUSIONS: Our study highlights the sustained effectiveness of MiniMed 780G among youth with T1D. Findings suggest that even children and adolescents with low therapeutic engagement may benefit from SmartGuard technology.

Examining the associations between COVID-19 infection and pediatric type 1 diabetes.

INTRODUCTION: The COVID-19 pandemic represents an unprecedented challenge for public health worldwide, not only for the very high number of cases and deaths but also due to a wide variety of indirect consequences. Among these, the possible relationship between SARS-CoV-2 infection and type 1 diabetes (T1D) in pediatric age has aroused notable interest in the scientific community. AREAS COVERED: This perspective article aims to focus on the epidemiological trend of T1D during the pandemic, the diabetogenic role of SARS-CoV-2, and the influence of preexisting T1D on COVID-19 outcomes. EXPERT OPINION: The incidence of T1D has considerably changed during the COVID-19 pandemic, but any direct role of SARS-CoV-2 is uncertain. It is more likely that SARS-CoV-2 infection acts as an accelerator of pancreatic ß-cell immunological destruction, which is activated by known viral triggers whose spread has been abnormal during these pandemic years. Another interesting aspect to consider is the role of immunization as a potential protective factor both for T1D development and the risk of severe outcomes in already diagnosed patients. Future studies are still required to address unmet needs, including the early use of antiviral drugs to reduce the risk of metabolic decompensation in children with T1D.

Real-World Performance of First- Versus Second-Generation Automated Insulin Delivery Systems on a Pediatric Population With Type 1 Diabetes: A One-Year Observational Study.

BACKGROUND: The aim of this single-center observational study was to assess the real-world performance of first- and second-generation automated insulin delivery (AID) systems in a cohort of children and adolescents with type 1 diabetes over a one-year follow-up. METHODS: Demographic, anamnestic, and clinical data of the study cohort were collected at the start of automatic mode. Data on continuous glucose monitoring metrics, system settings, insulin requirements, and anthropometric parameters at three different time points (start period, six months, 12 months) were retrospectively gathered and statistically analyzed. RESULTS: Fifty-four individuals (55.6% of females) aged 7 to 18 years switching to AID therapy were included in the analysis. Two weeks after starting automatic mode, subjects using advanced hybrid closed-loop (AHCL) showed a better response than hybrid closed-loop (HCL) users in terms of time in range (P = .016), time above range 180 to 250 mg/dl (P = .022), sensor mean glucose (P = .047), and glycemia risk index (P = .012). After 12 months, AHCL group maintained better mean sensor glucose (P = .021) and glucose management indicator (P = .027). Noteworthy, both HCL and AHCL users achieved the recommended clinical targets over the entire study period. The second-generation AID system registered longer time spent with automatic mode activated and fewer shifts to manual mode at every time point (P < .001). CONCLUSIONS: Both systems showed sustained and successful glycemic outcomes in the first year of use. However, AHCL users achieved tighter glycemic targets, without an increase of hypoglycemia risk. Improved usability of the device may also have contributed to optimal glycemic outcomes by ensuring better continuity of the automatic mode activation.

Prevalence and clinical features of severe diabetic ketoacidosis treated in pediatric intensive care unit: a 5-year monocentric experience.

BACKGROUND: Diabetic ketoacidosis (DKA) is one of the most alarming concerns in the management of type 1 diabetes (T1D) in pediatric age. Prevalence of DKA at the onset of diabetes ranges from 30 to 40%. In selected cases of severe DKA, admission to pediatric intensive care unit (PICU) should be considered. METHODS: This study aims to assess the prevalence of severe DKA treated in PICU in our 5-year monocentric experience. Secondary outcome of the study was to describe the main demographical and clinical features of individuals who required admission to PICU. All clinical data were collected by retrospectively reviewing the electronic medical records of children and adolescents with diabetes hospitalized in our University Hospital from January 2017 to December 2022. RESULTS: During the study period, 103 children and adolescents were newly diagnosed with T1D. Among these, 51.5% presented clinical criteria for DKA and almost 10% needed to be treated in PICU. A higher rate of new T1D diagnoses was observed in 2021, as well as episodes of severe DKA being more frequent than in previous years. Due to severe clinical manifestations of DKA, 10 subjects (9.7%) with T1D onset needed to be treated in PICU. Of these, four children were younger than 5. The great majority came from a low household income and some of them had also immigrant background. The most common complication of DKA was acute kidney injury presented by four children. Other complications were cerebral edema, papilledema and acute esophageal necrosis. A 15-year-old girl had deep vein thrombosis (DVT) that evolved into multiple organ failure leading to death. CONCLUSIONS: Our findings demonstrated that severe DKA is still quite common in children and adolescents at T1D onset, especially in some areas such as Southern Italy. Public awareness campaigns should be increasingly promoted to facilitate the recognition of early symptoms of diabetes and to reduce morbidity and mortality related to DKA.

MiniMed 780G Six-Month Use in 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 6-month use of MiniMed™ 780G. The 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 the time of enrollment. Data on ambulatory glucose profile were acquired at 3 and 6 months after activating automatic 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 indicator (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. In addition, 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 glycated hemoglobin (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.

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.

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 clinically characterized 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 the 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 age are very scarce. We hereby 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 advanced hybrid closed loop system was successfully practiced. Pediatricians should seriously consider diabetic gastroparesis in children and adolescents with long-standing, poorly controlled diabetes.

One-Year Real-World Study on Comparison among Different Continuous Subcutaneous Insulin Infusion Devices for the Management of Pediatric Patients with Type 1 Diabetes: The Supremacy of Hybrid Closed-Loop Systems.

Since their advent in daily clinical practice, continuous subcutaneous insulin infusion (CSII) systems have been increasingly improved, leading to a high percentage of both adult and pediatric patients with diabetes now using insulin pumps. Different types of CSII systems are currently available, which are characterized by different settings and technical features. This longitudinal observational study aims to evaluate real-word glycemic outcomes in children and adolescents with type 1 diabetes using three different CSII devices: hybrid closed-loop (HCL) systems, predictive low glucose (PLGS) systems, and non-automated insulin pumps. The secondary objective was to identify clinical variables that may significantly influence the achievement of therapeutic goals in our study cohort. One-hundred-and-one patients on CSII therapy attending our pediatric diabetes center were enrolled. When compared with the non-automated group, patients using HCL systems showed higher levels of time in target glucose range (p = 0.003) and lower glucose variability (p = 0.008). Similarly, we found significantly better glucose metrics in HCL users in comparison to PLGS patients (time in range p = 0.008; coefficient of variation p = 0.009; time above 250 mg/dL p = 0.007). Multiple linear regression models showed that HCL systems (time in range p < 0.001) and high daily percentage of glycemic sensor use (time in range p = 0.031) are predictors for good glycemic control. The introduction and increasing availability of novel technologies for diabetes represent a promising strategy to improve glycemic control and quality of life in pediatric patients with type 1 diabetes. Our real-world data confirm the superiority of HCL systems in terms of improvement of time spent in the target glucose range, prevention of hypoglycemia, and reduction of glycemic variability.

Increasing trend of type 1 diabetes incidence in the pediatric population of the Calabria region in 2019-2021.

BACKGROUND: Although type 1 diabetes (T1D) represents one of the most common chronic diseases in pediatric age, few studies on the epidemiology of T1D exist globally and the exact prevalence and incidence rates of the disease are unknown. In many countries, including Italy, national registries are missing. METHODS: This study aims to assess T1D incidence in the pediatric population of the Calabria region (southern Italy) in the period 2019-2021. The secondary objective was to describe the main demographical, clinical and immunological features of incident cases. Case ascertainment and all clinical data were assessed by retrospectively reviewing the electronic medical records of children and adolescents diagnosed with diabetes at any Pediatric Diabetes Center belonging to the Rete Diabetologica Calabrese (Calabria Region Diabetes Network), from January 2019 to December 2021. The incidence of T1D was estimated for the entire region and was stratified according to age group (0-4 years, 5-9 years, and 10-14 years) and gender. Standardized incidence ratios for each province in the region were also calculated. RESULTS: The crude incidence of T1D was 20.6/100,000 person/years. Incidence rates were higher among females and children aged 5-9 years. The crude incidence of T1D was higher in the province of Reggio Calabria (26.5/100,000 person-years). The provinces of Crotone, Catanzaro, and Vibo Valentia showed significantly lower standardized incidence ratios. The annual incidence in the region progressively increased by 43% during the study period. CONCLUSIONS: Our study revealed a relatively high incidence in the Calabria region. The marked increasing incidence trend over the past two years could be related to the global impact of the COVID-19 pandemic, but further long-scale population-based studies are needed to confirm these findings.

Corrigendum: 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.

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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.

Aim/Hypothesis: 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. Methods: Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019. Results: Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively). Conclusions/Interpretation: There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks.