Increasing Trend of Type 1 Diabetes Incidence in the Pediatric Population of the Calabria Region in 2019-2021

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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. Children diabetic ketoacidosis epidemiology SARS-CoV-2 Figures Figure 1 Background According to the International Diabetes Federation, the prevalence of diabetes in the general population is increasing worldwide and has nearly tripled in the past 20 years ( 1 , 2 ). Type 1 diabetes (T1D) accounts for 5–10% of all causes of diabetes. It is a chronic disease, which is characterized primarily by deficiency of insulin secretion and mainly occurs in the first decades of life ( 3 ). Despite several innovations and improvements in disease management, T1D still represents a heavy burden for pediatric patients and their families ( 4 ). Diabetes-related chronic complications are not uncommon among adolescents and are related to severe impairment of patients’ quality of life ( 5 ). Furthermore, mortality from T1D has been reported also in the pediatric population, especially in Africa and many low- and middle-income countries ( 6 ). Although in recent years several clinical trials aimed at preventing T1D onset have been conducted ( 7 , 8 ), established and approved strategies are still lacking and T1D remains a widespread public health concern. Few studies on the epidemiology of T1D exist globally and the exact prevalence of the disease is unknown. In many countries, there are no national registries, while in other countries completeness of registries is uncertain as case ascertainments are often under-reported and under-estimated ( 6 ). The incidence of T1D is extremely heterogeneous among countries, and even among regions within countries. It has been estimated that overall age-adjusted incidences of T1D vary from very low rates (0.1 per 100,000 person-years) in China and Venezuela to remarkable rates (62.3 per 100,000 person-years) in Scandinavian countries ( 9 , 10 ). Some authors have hypothesized that these significant differences may be related to the heterogeneity of hereditary and genetic factors that account for the pathogenesis of T1D ( 11 ). However, it is well-known that the etiology of T1D is multifactorial, and environmental and/or lifestyle-related changes have been proposed as potential factors that may interfere with different incident trends worldwide ( 12 ). Methods The aim of this study was to assess T1D incidence in the Calabria region (southern Italy) in the resident population aged 0–14 years in the period 2019–2021. The secondary objective was to describe the main demographical, clinical and immunological features of incident cases. Case ascertainment was conducted 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. Rete Diabetologica Calabrese is a recognized clinical network of the Calabria region aimed at the diagnosis, treatment, and follow-up of youth-onset diabetes, as well as at performing clinical and epidemiological research. The network was founded in 2007 and includes ten Pediatric Departments (Castrovillari, Cetraro, Cosenza, Crotone, Catanzaro, Lamezia Terme, Locri, Reggio Calabria, Polistena, and Vibo Valentia) throughout the region. To reduce the risk of potential lack of diagnoses, data from two tertiary Diabetes Centers located in neighboring regions (Napoli, in Campania and Messina, in Sicily) were also collected. The diagnosis and etiological classification of diabetes was made according to the International Society for Pediatric and Adolescent Diabetes Clinical Practice Consensus Guidelines ( 13 ). The following clinical and anamnestic data were collected at the time of diagnosis: sex, age, anthropometric factors, presence of diabetic ketoacidosis, glycated hemoglobin (HbA1c), T1D-associated autoimmunity, diabetic ketoacidosis (DKA)-related complications if present, additional autoimmune comorbidities. DKA at diagnosis was identified as blood glucose > 11 mmol/L (200 mg/dL), venous pH < 7.3 or bicarbonate < 15 mmol/L, presence of ketonemia and ketonuria. T1D was defined as immune mediated or idiopathic on the basis of detection of one or more T1D-associated antibodies (glutamic acid decarboxylase, protein tyrosine phosphatase, islet cell, insulin, anti-cell-specific zinc transporter 8 autoantibodies). In patients suspicious for monogenic diabetes, a proper genetic testing was performed at the Molecular Genetic Laboratory, Grande Ospedale Metropolitano, Reggio Calabria. Raw data obtained from the genetic investigations were evaluated according to American College of Medical Genetics and Genomics guidelines. Confirmation studies were performed for variants that were considered to be pathogenic, or likely pathogenic, using Sanger sequencing. The average crude annual T1D incidence rate was calculated using the 0-14-year-old population for the entire region and separately for each province. Incidence rates were also stratified according to age group (0–4 years, 5–9 years, and 10–14 years) and gender. Crude incidence rate was age-adjusted to the 2020 Italian census population using a direct method of standardization. Data were derived from the National Institute for Statistics ( http://demo.istat.it/ accessed 16 February 2022). Standardized incidence ratios (SIRs) of the single provinces were calculated using the indirect method of standardization and adopting the average annual incidence rate estimated for the entire region as standard. Quantitative variables were described using median and interquartile ranges. Categorical variables were described as absolute frequencies and percentages. Ninety-five per cent confidence intervals (CIs) were calculated assuming a Poisson distribution. Data were analyzed using STATA 12.0 software packages (STATA Corporation, College Station, TX, USA). The formal p-value used to define a statistically significant variation in incidence rates through the study period was set to 0.05. Results During the study period, a total of 163 patients aged 0–14 years were newly diagnosed with diabetes. Of these, 154 (94.5%) had a diagnosis of T1D. Other diagnoses included type 2 diabetes (4 cases, 2.5%) and monogenic diabetes (5 cases, 3%). T1D was diagnosed at the median age of 8.9 [IQR 5.2; 12.1] years. T1D-associated autoimmunity was present in 141 (91.6%) subjects, while the remaining patients were diagnosed with idiopathic T1D. The median HbA1c value at diagnosis of T1D was 11.6% [IQR 10.1; 13.4]. Less than half of the patients (71 subjects, 46.1%) experienced DKA at onset of diabetes. A higher percentage of DKA episodes were reported during 2020 compared to other years (50.9% vs 44.1% in 2019 and 43.1% in 2021). During the study period, there were no reports of DKA-related neurological complications or deaths. Other autoimmune diseases were present in 18 (11.7%) children and adolescents at the time of diabetes diagnosis. Only 9 (5.8%) patients had at least one first-degree relative affected by T1D. Demographical, anamnestic and clinical characteristics of patients newly diagnosed with T1D in the study period are reported in Table 1. The overall crude T1D incidence rate was 20.6 (95%CI 17.6–24.1) cases per 100,000 person-years, with no significant differences between females (23.4/100,000; 95%CI 18.6–28.5) and males (17.9/100,000; 95%CI 14.1–22.6; p = 0.102). The age-adjusted incidence rate to the 2020 Italian population was 20.7/100,000 person-years. Incidence was higher among children aged 5–9 years (24.1/100,000; CI 18.6–30.8) with respect to other age classes (0–4 years 15.7/100,000, 95%CI 11.1–21.6; 10–14 years 21.6/100,000; CI 16.5–27.7). Interestingly, the annual incidence progressively increased from 17.0 to 23.6 per 100,000 person-years, although not significantly (p = 0.098). This finding seems to be specific of younger patients and females, while incidence trends were not linear in the other age groups and males (Table 2). The crude incidence of T1D was higher in the province of Reggio Calabria (26.5 per 100,000 person-years) (Fig. 1 ). The provinces of Crotone, Catanzaro, and Vibo Valentia showed significantly lower SIRs when standardized to the regional population (Table 3). Discussion In Italy, previous attempts to realize a national epidemiological registry have been hindered by the difficulty of obtaining reliable data from all regions ( 14 ). Data on the incidence of T1D in Italian children and adolescents can be extracted by isolated regional experiences. The island of Sardinia is known to have one of the highest incidence rates in the world (45 per 100,000 person-years) ( 15 , 16 ). In the rest of the country, T1D incidence appears to have high variability ( 17 ). The overall calculated incidence in Veneto, a north-eastern Italian region, has recently been estimated at 19.7 new diagnoses per 100,000 person-years in the 2015–2020 time-span ( 18 ), while in the Puglia region, in the south-eastern of Italy, an average annual incidence rate of 25.2/100,000 inhabitants was described in the period 2009–2013 ( 19 ). In these epidemiological studies, case assessment was carried out by linking multiple regional electronic health archives (i.e. hospital discharges, pharmacy records, exemptions from medical charges, emergency room visits). This methodology used to collect data may be related to a relevant weakness, i.e. the inability to distinguish T1D from other rare types of diabetes such as neonatal/monogenic diabetes, cystic fibrosis-related diabetes, diabetes due to endocrine disorders and oncological diseases. In our study, regional data were easily accessible through the sharing of electronic medical records by Diabetes Centers belonging to the Rete Diabetologica Calabrese , which includes all Pediatric Departments of the Calabria region. Therefore, the lack of T1D diagnosis and the risk of misdiagnosing among different types of diabetes have been minimized. As reported, the incidence rate of T1D in Calabrian children and adolescents was 20.6 cases per 100,000 person-years. The overall crude incidence is higher compared to recently published worldwide estimates (20.6 vs 15.0/100,000 person-years) ( 12 ), similar to Northern Europe estimates (20–30/100.000 person-years) ( 1 ). In our population, the highest incidence rates were found in the age group 5–9 years and 10–14 years (24.1 and 21.6 per 100,000 person-years, respectively). These findings are consistent with those reported by the SEARCH study ( 20 ). Although the rate was lowest in younger children, incidence tends to progressively increase in this age group. This data is consistent with the suggested steady rise of T1D frequency in the first years of life ( 21 , 22 ). A recent systematic review reported that the overall pooled incidence of T1D in children aged 0–4 years globally is 11.2 per 100,000 child-years, accounting for 100,000-150,000 cases among new diagnosis of T1D each year in the world. Highest rates were identified in European countries ( 6 ). In our experience, the crude incidence rate in younger children was higher compared to these data. One of the most interesting results was the extreme increase in annual incidence that was estimated at 43%. 2019–2021 were characterized by the COVID-19 pandemic. The relationship between T1D and COVID-19 has several facets. In adults, diabetes has been demonstrated to be a risk factor for long-term complications of SARS-CoV-2 infection ( 23 , 24 ). Pediatric and adult patients with T1D were forced to modify the approach to the management of their chronic disease, particularly during the lockdown phases ( 25 ). Potential psychological consequences in patients with diabetes related to the pandemic were also noteworthy ( 26 ). On the other hand, however, the impact of SARS-CoV-2 on the pathogenesis of T1D is controversial. In Germany, T1D incidence in the period March-May 2020 followed the increasing trend observed between 2011 and 2019 without up- or downward deviation, suggesting no short-term influence of the COVID-19 pandemic. However, in that period, the COVID-19 infection rate was relatively low ( 27 ). On the contrary, a Romanian study reported a marked increase in incidence of T1D in 2020, particularly in the second half of the year, which was much higher compared to the previous years ( 28 ). Indeed, strong direct diabetogenic effects of SARS-CoV-2 have been hypothesized. Unsworth et al. have already reported an apparent increase in new-onset T1D in children during the COVID-19 pandemic, with evidence of SARS-CoV-2 infection or exposure in a proportion of those tested ( 29 ). More recently, the Center for Disease Control and Prevention (CDC) revealed that people 30 days after infection than were those without COVID-19 and those with pre-pandemic acute respiratory infections ( 30 ). Several theories have been put forward to explain the link between COVID-19 and T1D. SARS-CoV-2 infection could lead to diabetes through a direct attack of pancreatic cells expressing angiotensin converting enzyme 2 receptors. Alterations in glucose metabolism could be the result of hyperglycemia caused by the cytokine storm. Finally, it seems that COVID-19 could facilitate precipitation of prediabetes to diabetes ( 31 ). Another relevant result of our study concerns the increase in number and severity of DKA episodes in newly diagnosed children during 2020. This finding is in line with several other studies that reported a significant increase in the number of children requiring admission to the pediatric intensive care unit for severe ketoacidosis ( 32 – 35 ). Delays in the diagnostic process of T1D and the resulting increase in DKA frequency are likely to be attributed to an indirect effect of the COVID pandemic. The main reasons that could explain this relationship are changes in the functionality of the healthcare system, closure of non–COVID-19 services, and parental fears over contracting SARS-CoV-2 infection. These aspects were more evident ( 33 , 36 ) during the first pandemic wave. Conclusions Analyzed data showed a relatively high incidence of T1D in the Calabria region. New onset of T1D is increasingly found among preschool children suggesting the importance of promoting diabetes awareness campaigns to allow early identification of the classic symptoms, also in very young children. The marked increasing incidence trend over the past two years could be related to the global impact of the SARS-CoV-2 pandemic, but further long-scale population-based studies are needed to confirm these findings. List Of Abbreviations CI: confidence interval DKA: diabetic ketoacidosis HbA1c: glycated hemoglobin SIRs: standardized incidence ratios T1D: type 1 diabetes Declarations Ethics approval and consent to participate The study was conducted in accordance with the Helsinki Declaration, good clinical practice and all applicable laws and regulations. The study was exempt from ethical committee approval since it was confined to anonymized and unidentifiable data routinely collected at each Diabetes Centre belonging to Rete Diabetologica Calabrese . At least one parent of each patient gave their written informed consent before the start of study procedures. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding The paper received no funding. Author’s contributions FL conceived the designed study and approved the final version of the manuscript. SP and GS drafted and wrote the paper, MA, BB, FC, FD, RDM, NL, MCL, RL, FM, FAS, RMRT, and CV collected the data; DI contributed to the discussion. The paper has been read and approved by all the authors and each author considers that the paper represents their honest work. Acknowledgements We would like to acknowledge Rosario Vasta for his contribution on statistical analysis. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. References Patterson CC, Karuranga S, Salpea P, Saeedi P, Dahlquist G, Soltesz G, et al. Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019; 157:107842. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. 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Demographical, anamnestic and clinical characteristics of patients with a new diagnosis of type 1 diabetes in the period 2019-2021. 2019 2020 2021 2019-2021 Number of T1D diagnosis 43 53 58 154 Age at diagnosis (years) 8.9 (5.8; 12.2) 8 (3.3; 10.7) 8.3 (4.5; 11) 8.9 (5.2; 12.1) Gender Male Female 18 (41.9%) 25 (58.1%) 27 (50.9%) 26 (49.1%) 24 (41.4%) 34 (58.6%) 69 (44.8%) 85 (55.2%) BMI (z-score) 0.63 (-0.91; 1.71) 0.25 (-1.04; 1.2) 0.1 (-1.24; 0.79) 0.2 (-1.07; 1.2) HbA1c at diagnosis (%) 11.4 (9.8; 13.1) 11.7 (10.4; 13.3) 11.9 (10.5;13.4) 11.6 (10.1; 13.4) DKA Yes No 19 (44.1%) 24 (55.9%) 27 (50.9%) 26 (49.1%) 25 (43.1%) 33 (56.9%) 71 (46.1%) 83 (53.9%) Severity DKA Mild Moderate Severe 7 (36.8%) 4 (21.1%) 8 (42.1%) 11 (40.7%) 4 (26.9%) 12 (44.4%) 11 (44%) 6 (24%) 8 (32%) 29 (41%) 14 (19.7%) 28 (39.3%) DKA-related complications Yes No 0 43 (100%) 0 53 (100%) 0 58 (100%) 0 154 (100%) T1D autoimmunity Yes No 38 (88.4%) 5 (11.6%) 47 (88.7%) 6 (11.3%) 56 (96.6%) 2 (3.4%) 141 (91.6%) 13 (8.4%) Other autoimmune disorders Yes No 5 (11.6%) 38 (88.4%) 8 (15.1%) 45 (84.9%) 5 (8.6%) 53 (91.4%) 18 (11.7%) 137 (88.3%) T1D in first-degree relatives Yes No 3 (7.0%) 40 (93.0%) 3 (5.7%) 50 (94.3%) 3 (5.2%) 55 (94.8%) 9 (5.8%) 145 (94.2%) BMI: body mass index; DKA: diabetic ketoacidosis; T1D: type 1 diabetes Table 2. Differences in type 1 diabetes incidence trend between male and female subjects and among different age groups. 2019 2020 2021 Age groups 0-4 years 5-9 years 10-14 years 6.4/100,000 22.5/100,000 21/100,000 19.7/100,000 30.3/100,000 16.8/100,000 21.3/100,000 22/100,000 27/100,000 Gender Female Male 20.3/100,000 13.8/100,000 21.6/100,000 21.2/100,000 28.4/100,000 19/100,000 Table 3 . Standardized incidence ratios (SIRs) of each province of the Calabria region. Standardized to the Region population Province Observed cases Expected cases SIR 95% C.I. Catanzaro 22 40.6 0.5 0.3 – 0.8 Cosenza 51 49.5 1.0 0.8 – 1.4 Crotone 14 47.3 0.3 0.2 – 0.5 Reggio Calabria 58 65.7 0.9 0.7 – 1.1 Vibo Valentia 9 22.3 0.4 0.2 – 0.8 C.I. confidence interval; SIR: standardized incidence ratio Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 17 Mar, 2022 Reviewers invited by journal 15 Mar, 2022 Editor assigned by journal 09 Mar, 2022 First submitted to journal 24 Feb, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1392128","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":90890651,"identity":"59785472-67fb-479a-85fa-97b0d6c5a403","order_by":0,"name":"Stefano Passanisi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYFADZgaGAx8YGHhA7AN4VbIhaTk4A6YFrx42JDYzD4yFT4v8/OZjD378qZM3Z2d/eNi27Y6MbnsD4+EPeLQYHGNLN+xtO2y4s5nH4HBu2zMeszMH8DvMgI3HTIK34QDjhsM8DEAth3nMbiTg1yLfxv9N8s+fOvsNh9kfHLYEabn/gID3j/GwSfOwMSduOMxgcJgRbAuBEDM4lmZuLNt2OBnoMIODPeeAWs4kNhw4g89hzYefPXzzp852w/njjz/8KDtsb3b88OEPFfgchhozYMDYgF8DFi2jYBSMglEwClABAJuoVsYEoqRcAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-4369-7798","institution":"Universita degli Studi di Messina","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Passanisi","suffix":""},{"id":90890652,"identity":"4d5be146-3e91-495a-9fdc-7ac57a4b0bf4","order_by":1,"name":"Giuseppina Salzano","email":"","orcid":"","institution":"University of Messina: Universita degli Studi di Messina","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Giuseppina","middleName":"","lastName":"Salzano","suffix":""},{"id":90890653,"identity":"c1aca141-b1eb-4d0f-a13a-32776532dcb6","order_by":2,"name":"Monica Aloe","email":"","orcid":"","institution":"Ospedale Civile di Lamezia Terme","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Monica","middleName":"","lastName":"Aloe","suffix":""},{"id":90890654,"identity":"17fb5f06-f90b-48e5-ba0b-af0f9504accb","order_by":3,"name":"Bruno Bombaci","email":"","orcid":"","institution":"University of Messina: Universita degli Studi di Messina","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bruno","middleName":"","lastName":"Bombaci","suffix":""},{"id":90890655,"identity":"365e6aef-c6ec-4dbb-b661-babf5733e786","order_by":4,"name":"Felice Citriniti","email":"","orcid":"","institution":"Azienda Ospedaliera di Catanzaro Pugliese Ciaccio: Azienda Ospedaliera Pugliese Ciaccio","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Felice","middleName":"","lastName":"Citriniti","suffix":""},{"id":90890656,"identity":"89fde9a4-b900-41ea-8ac9-569712540cff","order_by":5,"name":"Fiorella De Berardinis","email":"","orcid":"","institution":"Azienda Ospedaliera di Cetraro","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fiorella","middleName":"","lastName":"De Berardinis","suffix":""},{"id":90890657,"identity":"cbccb49e-536d-4e7d-aed6-b61945abf570","order_by":6,"name":"Rosaria De Marco","email":"","orcid":"","institution":"Azienda Ospedaliera di Cosenza","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rosaria","middleName":"","lastName":"De Marco","suffix":""},{"id":90890658,"identity":"dcc145e2-b75d-40b3-9945-aa136af29f5d","order_by":7,"name":"Nicola Lazzaro","email":"","orcid":"","institution":"Ospedale Giovanni Di Dio, Crotone","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nicola","middleName":"","lastName":"Lazzaro","suffix":""},{"id":90890659,"identity":"9ec65a4c-fc25-4c22-879f-43f4e2dab48c","order_by":8,"name":"Maria C. Lia","email":"","orcid":"","institution":"Azienda Ospedaliera BMM, Reggio Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maria","middleName":"C.","lastName":"Lia","suffix":""},{"id":90890660,"identity":"58ea1902-0f2f-48b7-857a-2293848ff4be","order_by":9,"name":"Rosanna Lia","email":"","orcid":"","institution":"Ospedale Civile di Locri","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rosanna","middleName":"","lastName":"Lia","suffix":""},{"id":90890661,"identity":"747257fe-6c44-4c60-8da8-67c172696ae5","order_by":10,"name":"Francesco Mammì","email":"","orcid":"","institution":"Ospedale Civile di Locri","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Francesco","middleName":"","lastName":"Mammì","suffix":""},{"id":90890662,"identity":"201a39af-88fd-457b-a734-2a32d598eb5e","order_by":11,"name":"Filomena A. Stamati","email":"","orcid":"","institution":"Ospedale Civile di Castrovillari","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Filomena","middleName":"A.","lastName":"Stamati","suffix":""},{"id":90890663,"identity":"443a90c6-2217-4fd0-8a39-98cf4f6ced75","order_by":12,"name":"Rosanna MR Toscano","email":"","orcid":"","institution":"Ospedale Civile di Vibo Valentia","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rosanna","middleName":"MR","lastName":"Toscano","suffix":""},{"id":90890664,"identity":"0d5ecc45-8272-4d10-9f78-5bec806a49da","order_by":13,"name":"Claudia Ventrici","email":"","orcid":"","institution":"Ospedale Civile Santa Maria degli Ungheresi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Claudia","middleName":"","lastName":"Ventrici","suffix":""},{"id":90890665,"identity":"49075b37-eb96-45f9-acbb-6adf164754a3","order_by":14,"name":"Dario Iafusco","email":"","orcid":"","institution":"University of Campania Luigi Vanvitelli: Universita degli Studi della Campania Luigi Vanvitelli","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dario","middleName":"","lastName":"Iafusco","suffix":""},{"id":90890666,"identity":"7d3c06a2-fa1d-435d-a8eb-f597809e4185","order_by":15,"name":"Fortunato Lombardo","email":"","orcid":"","institution":"University of Messina: Universita degli Studi di Messina","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fortunato","middleName":"","lastName":"Lombardo","suffix":""}],"badges":[],"createdAt":"2022-02-24 10:52:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1392128/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1392128/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":19299191,"identity":"19d1e929-8b12-4db7-b43a-23cf5ea56d0a","added_by":"auto","created_at":"2022-03-16 16:29:35","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":55246,"visible":true,"origin":"","legend":"\u003cp\u003eDifferent crude incidence of type 1 diabetes among provinces of the Calabria region.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1392128/v1/e3fc737eba379cfbba1d87c8.jpg"},{"id":19299192,"identity":"1bd4de65-d6d9-4b6e-9474-45a5d5d41fb4","added_by":"auto","created_at":"2022-03-16 16:29:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":336960,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1392128/v1/f4f3d8cf-4dcd-4ad3-95df-25dd691f23eb.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eIncreasing Trend of Type 1 Diabetes Incidence in the Pediatric Population of the Calabria Region in 2019-2021\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eAccording to the International Diabetes Federation, the prevalence of diabetes in the general population is increasing worldwide and has nearly tripled in the past 20 years (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Type 1 diabetes (T1D) accounts for 5\u0026ndash;10% of all causes of diabetes. It is a chronic disease, which is characterized primarily by deficiency of insulin secretion and mainly occurs in the first decades of life (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Despite several innovations and improvements in disease management, T1D still represents a heavy burden for pediatric patients and their families (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Diabetes-related chronic complications are not uncommon among adolescents and are related to severe impairment of patients\u0026rsquo; quality of life (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Furthermore, mortality from T1D has been reported also in the pediatric population, especially in Africa and many low- and middle-income countries (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Although in recent years several clinical trials aimed at preventing T1D onset have been conducted (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), established and approved strategies are still lacking and T1D remains a widespread public health concern.\u003c/p\u003e \u003cp\u003eFew studies on the epidemiology of T1D exist globally and the exact prevalence of the disease is unknown. In many countries, there are no national registries, while in other countries completeness of registries is uncertain as case ascertainments are often under-reported and under-estimated (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The incidence of T1D is extremely heterogeneous among countries, and even among regions within countries. It has been estimated that overall age-adjusted incidences of T1D vary from very low rates (0.1 per 100,000 person-years) in China and Venezuela to remarkable rates (62.3 per 100,000 person-years) in Scandinavian countries (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Some authors have hypothesized that these significant differences may be related to the heterogeneity of hereditary and genetic factors that account for the pathogenesis of T1D (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, it is well-known that the etiology of T1D is multifactorial, and environmental and/or lifestyle-related changes have been proposed as potential factors that may interfere with different incident trends worldwide (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe aim of this study was to assess T1D incidence in the Calabria region (southern Italy) in the resident population aged 0\u0026ndash;14 years in the period 2019\u0026ndash;2021. The secondary objective was to describe the main demographical, clinical and immunological features of incident cases.\u003c/p\u003e \u003cp\u003eCase ascertainment was conducted by retrospectively reviewing the electronic medical records of children and adolescents diagnosed with diabetes at any Pediatric Diabetes Center belonging to the \u003cem\u003eRete Diabetologica Calabrese\u003c/em\u003e (Calabria Region Diabetes Network), from January 2019 to December 2021. \u003cem\u003eRete Diabetologica Calabrese\u003c/em\u003e is a recognized clinical network of the Calabria region aimed at the diagnosis, treatment, and follow-up of youth-onset diabetes, as well as at performing clinical and epidemiological research. The network was founded in 2007 and includes ten Pediatric Departments (Castrovillari, Cetraro, Cosenza, Crotone, Catanzaro, Lamezia Terme, Locri, Reggio Calabria, Polistena, and Vibo Valentia) throughout the region. To reduce the risk of potential lack of diagnoses, data from two tertiary Diabetes Centers located in neighboring regions (Napoli, in Campania and Messina, in Sicily) were also collected.\u003c/p\u003e \u003cp\u003eThe diagnosis and etiological classification of diabetes was made according to the International Society for Pediatric and Adolescent Diabetes Clinical Practice Consensus Guidelines (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The following clinical and anamnestic data were collected at the time of diagnosis: sex, age, anthropometric factors, presence of diabetic ketoacidosis, glycated hemoglobin (HbA1c), T1D-associated autoimmunity, diabetic ketoacidosis (DKA)-related complications if present, additional autoimmune comorbidities. DKA at diagnosis was identified as blood glucose\u0026thinsp;\u0026gt;\u0026thinsp;11 mmol/L (200 mg/dL), venous pH\u0026thinsp;\u0026lt;\u0026thinsp;7.3 or bicarbonate\u0026thinsp;\u0026lt;\u0026thinsp;15 mmol/L, presence of ketonemia and ketonuria. T1D was defined as immune mediated or idiopathic on the basis of detection of one or more T1D-associated antibodies (glutamic acid decarboxylase, protein tyrosine phosphatase, islet cell, insulin, anti-cell-specific zinc transporter 8 autoantibodies). In patients suspicious for monogenic diabetes, a proper genetic testing was performed at the Molecular Genetic Laboratory, Grande Ospedale Metropolitano, Reggio Calabria. Raw data obtained from the genetic investigations were evaluated according to American College of Medical Genetics and Genomics guidelines. Confirmation studies were performed for variants that were considered to be pathogenic, or likely pathogenic, using Sanger sequencing.\u003c/p\u003e \u003cp\u003eThe average crude annual T1D incidence rate was calculated using the 0-14-year-old population for the entire region and separately for each province. Incidence rates were also stratified according to age group (0\u0026ndash;4 years, 5\u0026ndash;9 years, and 10\u0026ndash;14 years) and gender. Crude incidence rate was age-adjusted to the 2020 Italian census population using a direct method of standardization. Data were derived from the National Institute for Statistics (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://demo.istat.it/\u003c/span\u003e\u003cspan address=\"http://demo.istat.it/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e accessed 16 February 2022). Standardized incidence ratios (SIRs) of the single provinces were calculated using the indirect method of standardization and adopting the average annual incidence rate estimated for the entire region as standard. Quantitative variables were described using median and interquartile ranges. Categorical variables were described as absolute frequencies and percentages. Ninety-five per cent confidence intervals (CIs) were calculated assuming a Poisson distribution. Data were analyzed using STATA 12.0 software packages (STATA Corporation, College Station, TX, USA). The formal p-value used to define a statistically significant variation in incidence rates through the study period was set to 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, a total of 163 patients aged 0\u0026ndash;14 years were newly diagnosed with diabetes. Of these, 154 (94.5%) had a diagnosis of T1D. Other diagnoses included type 2 diabetes (4 cases, 2.5%) and monogenic diabetes (5 cases, 3%). T1D was diagnosed at the median age of 8.9 [IQR 5.2; 12.1] years. T1D-associated autoimmunity was present in 141 (91.6%) subjects, while the remaining patients were diagnosed with idiopathic T1D. The median HbA1c value at diagnosis of T1D was 11.6% [IQR 10.1; 13.4]. Less than half of the patients (71 subjects, 46.1%) experienced DKA at onset of diabetes. A higher percentage of DKA episodes were reported during 2020 compared to other years (50.9% \u003cem\u003evs\u003c/em\u003e 44.1% in 2019 and 43.1% in 2021). During the study period, there were no reports of DKA-related neurological complications or deaths. Other autoimmune diseases were present in 18 (11.7%) children and adolescents at the time of diabetes diagnosis. Only 9 (5.8%) patients had at least one first-degree relative affected by T1D. Demographical, anamnestic and clinical characteristics of patients newly diagnosed with T1D in the study period are reported in Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003eThe overall crude T1D incidence rate was 20.6 (95%CI 17.6\u0026ndash;24.1) cases per 100,000 person-years, with no significant differences between females (23.4/100,000; 95%CI 18.6\u0026ndash;28.5) and males (17.9/100,000; 95%CI 14.1\u0026ndash;22.6; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.102). The age-adjusted incidence rate to the 2020 Italian population was 20.7/100,000 person-years. Incidence was higher among children aged 5\u0026ndash;9 years (24.1/100,000; CI 18.6\u0026ndash;30.8) with respect to other age classes (0\u0026ndash;4 years 15.7/100,000, 95%CI 11.1\u0026ndash;21.6; 10\u0026ndash;14 years 21.6/100,000; CI 16.5\u0026ndash;27.7). Interestingly, the annual incidence progressively increased from 17.0 to 23.6 per 100,000 person-years, although not significantly (p\u0026thinsp;=\u0026thinsp;0.098). This finding seems to be specific of younger patients and females, while incidence trends were not linear in the other age groups and males (Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eThe crude incidence of T1D was higher in the province of Reggio Calabria (26.5 per 100,000 person-years) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The provinces of Crotone, Catanzaro, and Vibo Valentia showed significantly lower SIRs when standardized to the regional population (Table\u0026nbsp;3).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn Italy, previous attempts to realize a national epidemiological registry have been hindered by the difficulty of obtaining reliable data from all regions (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Data on the incidence of T1D in Italian children and adolescents can be extracted by isolated regional experiences. The island of Sardinia is known to have one of the highest incidence rates in the world (45 per 100,000 person-years) (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In the rest of the country, T1D incidence appears to have high variability (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The overall calculated incidence in Veneto, a north-eastern Italian region, has recently been estimated at 19.7 new diagnoses per 100,000 person-years in the 2015\u0026ndash;2020 time-span (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), while in the Puglia region, in the south-eastern of Italy, an average annual incidence rate of 25.2/100,000 inhabitants was described in the period 2009\u0026ndash;2013 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In these epidemiological studies, case assessment was carried out by linking multiple regional electronic health archives (i.e. hospital discharges, pharmacy records, exemptions from medical charges, emergency room visits). This methodology used to collect data may be related to a relevant weakness, i.e. the inability to distinguish T1D from other rare types of diabetes such as neonatal/monogenic diabetes, cystic fibrosis-related diabetes, diabetes due to endocrine disorders and oncological diseases. In our study, regional data were easily accessible through the sharing of electronic medical records by Diabetes Centers belonging to the \u003cem\u003eRete Diabetologica Calabrese\u003c/em\u003e, which includes all Pediatric Departments of the Calabria region. Therefore, the lack of T1D diagnosis and the risk of misdiagnosing among different types of diabetes have been minimized.\u003c/p\u003e \u003cp\u003eAs reported, the incidence rate of T1D in Calabrian children and adolescents was 20.6 cases per 100,000 person-years. The overall crude incidence is higher compared to recently published worldwide estimates (20.6 vs 15.0/100,000 person-years) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), similar to Northern Europe estimates (20\u0026ndash;30/100.000 person-years) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In our population, the highest incidence rates were found in the age group 5\u0026ndash;9 years and 10\u0026ndash;14 years (24.1 and 21.6 per 100,000 person-years, respectively). These findings are consistent with those reported by the SEARCH study (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Although the rate was lowest in younger children, incidence tends to progressively increase in this age group. This data is consistent with the suggested steady rise of T1D frequency in the first years of life (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). A recent systematic review reported that the overall pooled incidence of T1D in children aged 0\u0026ndash;4 years globally is 11.2 per 100,000 child-years, accounting for 100,000-150,000 cases among new diagnosis of T1D each year in the world. Highest rates were identified in European countries (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In our experience, the crude incidence rate in younger children was higher compared to these data.\u003c/p\u003e \u003cp\u003eOne of the most interesting results was the extreme increase in annual incidence that was estimated at 43%. 2019\u0026ndash;2021 were characterized by the COVID-19 pandemic. The relationship between T1D and COVID-19 has several facets. In adults, diabetes has been demonstrated to be a risk factor for long-term complications of SARS-CoV-2 infection (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Pediatric and adult patients with T1D were forced to modify the approach to the management of their chronic disease, particularly during the lockdown phases (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Potential psychological consequences in patients with diabetes related to the pandemic were also noteworthy (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). On the other hand, however, the impact of SARS-CoV-2 on the pathogenesis of T1D is controversial. In Germany, T1D incidence in the period March-May 2020 followed the increasing trend observed between 2011 and 2019 without up- or downward deviation, suggesting no short-term influence of the COVID-19 pandemic. However, in that period, the COVID-19 infection rate was relatively low (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). On the contrary, a Romanian study reported a marked increase in incidence of T1D in 2020, particularly in the second half of the year, which was much higher compared to the previous years (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Indeed, strong direct diabetogenic effects of SARS-CoV-2 have been hypothesized. Unsworth et al. have already reported an apparent increase in new-onset T1D in children during the COVID-19 pandemic, with evidence of SARS-CoV-2 infection or exposure in a proportion of those tested (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). More recently, the Center for Disease Control and Prevention (CDC) revealed that people\u0026thinsp;\u0026lt;\u0026thinsp;18 years with COVID-19 were more likely to receive a new diabetes diagnosis\u0026thinsp;\u0026gt;\u0026thinsp;30 days after infection than were those without COVID-19 and those with pre-pandemic acute respiratory infections (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Several theories have been put forward to explain the link between COVID-19 and T1D. SARS-CoV-2 infection could lead to diabetes through a direct attack of pancreatic cells expressing angiotensin converting enzyme 2 receptors. Alterations in glucose metabolism could be the result of hyperglycemia caused by the cytokine storm. Finally, it seems that COVID-19 could facilitate precipitation of prediabetes to diabetes (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnother relevant result of our study concerns the increase in number and severity of DKA episodes in newly diagnosed children during 2020. This finding is in line with several other studies that reported a significant increase in the number of children requiring admission to the pediatric intensive care unit for severe ketoacidosis (\u003cspan additionalcitationids=\"CR33 CR34\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Delays in the diagnostic process of T1D and the resulting increase in DKA frequency are likely to be attributed to an indirect effect of the COVID pandemic. The main reasons that could explain this relationship are changes in the functionality of the healthcare system, closure of non\u0026ndash;COVID-19 services, and parental fears over contracting SARS-CoV-2 infection. These aspects were more evident (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e) during the first pandemic wave.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAnalyzed data showed a relatively high incidence of T1D in the Calabria region. New onset of T1D is increasingly found among preschool children suggesting the importance of promoting diabetes awareness campaigns to allow early identification of the classic symptoms, also in very young children. The marked increasing incidence trend over the past two years could be related to the global impact of the SARS-CoV-2 pandemic, but further long-scale population-based studies are needed to confirm these findings.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eCI: confidence interval\u003c/p\u003e\n\u003cp\u003eDKA: diabetic ketoacidosis\u003c/p\u003e\n\u003cp\u003eHbA1c: glycated hemoglobin\u003c/p\u003e\n\u003cp\u003eSIRs: standardized incidence ratios\u003c/p\u003e\n\u003cp\u003eT1D: type 1 diabetes\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Helsinki Declaration, good clinical practice and all applicable laws and regulations.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was exempt from ethical committee approval since it was confined to anonymized and unidentifiable data routinely collected at each Diabetes Centre belonging to \u003cem\u003eRete Diabetologica Calabrese\u003c/em\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt least one parent of each patient gave their written informed consent before the start of study procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe paper received no funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFL conceived the designed study and approved the final version of the manuscript. SP and GS drafted and wrote the paper, MA, BB, FC, FD, RDM, NL, MCL, RL, FM, FAS, RMRT, and CV collected the data; DI contributed to the discussion. The paper has been read and approved by all the authors and each author considers that the paper represents their honest work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge Rosario Vasta for his contribution on statistical analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePatterson CC, Karuranga S, Salpea P, Saeedi P, Dahlquist G, Soltesz G, et al. Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019; 157:107842.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmerican Diabetes Association Professional Practice Committee, American Diabetes Association Professional Practice Committee:. Draznin B, Aroda VR, Bakris G, Benson G, et al. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. 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The incidence rate and prevalence of pediatric type 1 diabetes mellitus (age 0\u0026ndash;18) in the Italian region Friuli Venezia Giulia: population-based estimates through the analysis of health administrative databases. Acta Diabetol. 2016;53:629\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaffeis C, Mancioppi V, Piona C, Avossa F, Fedeli U, Marigliano M. Type 1 diabetes prevalence and incidence rates in the pediatric population of Veneto Region (Italy) in 2015\u0026ndash;2020. Diabetes Res Clin Pract. 2021;179:109020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFortunato F, Cappelli MG, Vece MM, Caputi G, Delvecchio M, Prato R, et al. Incidence of Type 1 Diabetes among Children and Adolescents in Italy between 2009 and 2013: The Role of a Regional Childhood Diabetes Registry. J Diabetes Res. 2016;2016:7239692.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, et al. Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002\u0026ndash;2012. N Engl J Med. 2017;376:1419\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarvonen M, Pitk\u0026auml;niemi J, Tuomilehto J. The onset age of type 1 diabetes in Finnish children has become younger. The Finnish Childhood Diabetes Registry Group. Diabetes Care. 1999;22:1066\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, Tuomilehto J. Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. Diabetes Care. 2000;23:1516\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequelae of COVID-19. Nature. 2021;594:259\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAyoubkhani D, Khunti K, Nafilyan V, Maddox T, Humberstone B, Diamond I, et al. Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study. BMJ. 2021;372:n693.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePassanisi S, Pecoraro M, Pira F, Alibrandi A, Donia V, Lonia P, et al. Quarantine Due to the COVID-19 Pandemic from the Perspective of Pediatric Patients with Type 1 Diabetes: A Web-Based Survey. Front Pediatr. 2020;8:491.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalzano G, Passanisi S, Pira F, Sorrenti L, La Monica G, Pajno GB, et al. Quarantine due to the COVID-19 pandemic from the perspective of adolescents: the crucial role of technology. Ital J Pediatr. 2021;47:40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTittel SR, Rosenbauer J, Kamrath C, Ziegler J, Reschke F, Hammersen J, et al. Did the COVID-19 Lockdown Affect the Incidence of Pediatric Type 1 Diabetes in Germany? Diabetes Care. 2020;43:e172\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVlad A, Serban V, Timar R, Sima A, Botea V, Albai O, et al. Increased Incidence of Type 1 Diabetes during the COVID-19 Pandemic in Romanian Children. Med Kaunas Lith. 2021;57:973.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUnsworth R, Wallace S, Oliver NS, Yeung S, Kshirsagar A, Naidu H, et al. New-Onset Type 1 Diabetes in Children During COVID-19: Multicenter Regional Findings in the U.K. Diabetes Care. 2020;43:e170\u0026ndash;1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarrett CE, Koyama AK, Alvarez P, Chow W, Lundeen EA, Perrine CG, et al. Risk for Newly Diagnosed Diabetes \u0026gt; 30 Days After SARS-CoV-2 Infection Among Persons Aged \u0026lt; 18 Years - United States, March 1, 2020-June 28, 2021. MMWR Morb Mortal Wkly Rep. 2022;71:59\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBronson SC. Practical scenarios and day-to-day challenges in the management of diabetes in COVID-19 - Dealing with the \u0026laquo;double trouble\u0026raquo;. Prim Care Diabetes. 2021;15:737\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLawrence C, Seckold R, Smart C, King BR, Howley P, Feltrin R, et al. Increased paediatric presentations of severe diabetic ketoacidosis in an Australian tertiary centre during the COVID-19 pandemic. Diabet Med J. 2021;38:e14417.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalmi H, Heinonen S, H\u0026auml;stbacka J, L\u0026auml;\u0026auml;peri M, Rautiainen P, Miettinen PJ, et al. New-onset type 1 diabetes in Finnish children during the COVID-19 pandemic. Arch Dis Child. 2022;107:180\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRabbone I, Schiaffini R, Cherubini V, Maffeis C, Scaramuzza A. Diabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetes. Has COVID-19 Delayed the Diagnosis and Worsened the Presentation of Type 1 Diabetes in Children? Diabetes Care. 2020;43:2870\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamrath C, M\u0026ouml;nkem\u0026ouml;ller K, Biester T, Rohrer TR, Warncke K, Hammersen J, et al. Ketoacidosis in Children and Adolescents with Newly Diagnosed Type 1 Diabetes During the COVID-19 Pandemic in Germany. JAMA. 2020;324:801\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLazzerini M, Barbi E, Apicella A, Marchetti F, Cardinale F, Trobia G. Delayed access or provision of care in Italy resulting from fear of COVID-19. Lancet Child Adolesc Health. 2020;4:e10\u0026ndash;1.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Demographical, anamnestic and clinical characteristics of patients with a new diagnosis of type 1 diabetes in the period 2019-2021.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e2019-2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003eNumber of T1D diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e154\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003eAge at diagnosis (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e8.9 (5.8; 12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e8 (3.3; 10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e8.3 (4.5; 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e8.9 (5.2; 12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18 (41.9%)\u003c/p\u003e\n \u003cp\u003e25 (58.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (50.9%)\u003c/p\u003e\n \u003cp\u003e26 (49.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24 (41.4%)\u003c/p\u003e\n \u003cp\u003e34 (58.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e69 (44.8%)\u003c/p\u003e\n \u003cp\u003e85 (55.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003eBMI (z-score)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e0.63 (-0.91; 1.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e0.25 (-1.04; 1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e0.1 (-1.24; 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e0.2 (-1.07; 1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003eHbA1c at diagnosis (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e11.4 (9.8; 13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e11.7 (10.4; 13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e11.9 (10.5;13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e11.6 (10.1; 13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003eDKA\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (44.1%)\u003c/p\u003e\n \u003cp\u003e24 (55.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (50.9%)\u003c/p\u003e\n \u003cp\u003e26 (49.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (43.1%)\u003c/p\u003e\n \u003cp\u003e33 (56.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e71 (46.1%)\u003c/p\u003e\n \u003cp\u003e83 (53.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003e\u003cem\u003eSeverity DKA\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (36.8%)\u003c/p\u003e\n \u003cp\u003e4 (21.1%)\u003c/p\u003e\n \u003cp\u003e8 (42.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (40.7%)\u003c/p\u003e\n \u003cp\u003e4 (26.9%)\u003c/p\u003e\n \u003cp\u003e12 (44.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (44%)\u003c/p\u003e\n \u003cp\u003e6 (24%)\u003c/p\u003e\n \u003cp\u003e8 (32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (41%)\u003c/p\u003e\n \u003cp\u003e14 (19.7%)\u003c/p\u003e\n \u003cp\u003e28 (39.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003e\u003cem\u003eDKA-related complications\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e43 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e53 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e58 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e154 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003e\u003cem\u003eT1D autoimmunity\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38 (88.4%)\u003c/p\u003e\n \u003cp\u003e5 (11.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47 (88.7%)\u003c/p\u003e\n \u003cp\u003e6 (11.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56 (96.6%)\u003c/p\u003e\n \u003cp\u003e2 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e141 (91.6%)\u003c/p\u003e\n \u003cp\u003e13 (8.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003e\u003cem\u003eOther autoimmune disorders\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (11.6%)\u003c/p\u003e\n \u003cp\u003e38 (88.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (15.1%)\u003c/p\u003e\n \u003cp\u003e45 (84.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (8.6%)\u003c/p\u003e\n \u003cp\u003e53 (91.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18 (11.7%)\u003c/p\u003e\n \u003cp\u003e137 (88.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.838323353293415%\"\u003e\n \u003cp\u003e\u003cem\u003eT1D in first-degree relatives\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41317365269461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (7.0%)\u003c/p\u003e\n \u003cp\u003e40 (93.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (5.7%)\u003c/p\u003e\n \u003cp\u003e50 (94.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (5.2%)\u003c/p\u003e\n \u003cp\u003e55 (94.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.91616766467066%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (5.8%)\u003c/p\u003e\n \u003cp\u003e145 (94.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eBMI: body mass index; DKA: diabetic ketoacidosis; T1D: type 1 diabetes\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eDifferences in type 1 diabetes incidence trend between male and female subjects and among different age groups.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cem\u003eAge groups\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e0-4 years\u003c/p\u003e\n \u003cp\u003e5-9 years\u003c/p\u003e\n \u003cp\u003e10-14 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6.4/100,000\u003c/p\u003e\n \u003cp\u003e22.5/100,000\u003c/p\u003e\n \u003cp\u003e21/100,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19.7/100,000\u003c/p\u003e\n \u003cp\u003e30.3/100,000\u003c/p\u003e\n \u003cp\u003e16.8/100,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21.3/100,000\u003c/p\u003e\n \u003cp\u003e22/100,000\u003c/p\u003e\n \u003cp\u003e27/100,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cem\u003eGender\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFemale\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20.3/100,000\u003c/p\u003e\n \u003cp\u003e13.8/100,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21.6/100,000\u003c/p\u003e\n \u003cp\u003e21.2/100,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28.4/100,000\u003c/p\u003e\n \u003cp\u003e19/100,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. Standardized incidence ratios (SIRs) of each province of the Calabria region.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eStandardized to the Region population\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eProvince\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003eObserved cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003eExpected cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003eSIR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e95% C.I.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eCatanzaro\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e40.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.3 \u0026ndash; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eCosenza\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e49.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.8 \u0026ndash; 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eCrotone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e47.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.2 \u0026ndash; 0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eReggio Calabria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e65.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.7 \u0026ndash; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eVibo Valentia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e22.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.2 \u0026ndash; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eC.I. confidence interval; SIR: standardized incidence ratio\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Children, diabetic ketoacidosis, epidemiology, SARS-CoV-2","lastPublishedDoi":"10.21203/rs.3.rs-1392128/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1392128/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground.\u003c/h2\u003e \u003cp\u003eAlthough 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.\u003c/p\u003e\u003ch2\u003eMethods.\u003c/h2\u003e \u003cp\u003eThis study aims to assess T1D incidence in the pediatric population of the Calabria region (southern Italy) in the period 2019\u0026ndash;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 \u003cem\u003eRete Diabetologica Calabrese\u003c/em\u003e (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\u0026ndash;4 years, 5\u0026ndash;9 years, and 10\u0026ndash;14 years) and gender. Standardized incidence ratios for each province in the region were also calculated.\u003c/p\u003e\u003ch2\u003eResults.\u003c/h2\u003e \u003cp\u003eThe crude incidence of T1D was 20.6/100,000 person/years. Incidence rates were higher among females and children aged 5\u0026ndash;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.\u003c/p\u003e\u003ch2\u003eConclusions.\u003c/h2\u003e \u003cp\u003eOur 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.\u003c/p\u003e","manuscriptTitle":"Increasing Trend of Type 1 Diabetes Incidence in the Pediatric Population of the Calabria Region in 2019-2021","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-16 16:29:34","doi":"10.21203/rs.3.rs-1392128/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2022-03-17T21:36:41+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-03-15T08:48:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-03-09T05:44:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Italian Journal of Pediatrics","date":"2022-02-24T05:51:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d42904ed-cfee-4426-8eef-e3384f0c2bc7","owner":[],"postedDate":"March 16th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-04-27T09:07:17+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-16 16:29:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1392128","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1392128","identity":"rs-1392128","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}