Trends and cyclic variation in the incidence of childhood type 1 diabetes in two Italian regions over 33 years and during the COVID-19 pandemic.

AIM: There is conflicting evidence about the impact of the COVID-19 pandemic on the incidence of type 1 diabetes. Here, we analysed long-term trends in the incidence of type 1 diabetes in Italian children and adolescents from 1989 to 2019 and compared the incidence observed during the COVID-19 pandemic with that estimated from long-term data. MATERIALS AND METHODS: This was a population-based incidence study using longitudinal data from two diabetes registries in mainland Italy. Trends in the incidence of type 1 diabetes from 1 January 1989 to 31 December 2019 were estimated using Poisson and segmented regression models. RESULTS: There was a significant increasing trend in the incidence of type 1 diabetes of 3.6% per year [95% confidence interval (CI): 2.4-4.8] between 1989 and 2003, a breakpoint in 2003, and then a constant incidence until 2019 (0.5%, 95% CI: -1.3 to 2.4). There was a significant 4-year cycle in incidence over the entire study period. The rate observed in 2021 (26.7, 95% CI: 23.0-30.9) was significantly higher than expected (19.5, 95% CI: 17.6-21.4; p = .010). CONCLUSION: Long-term incidence analysis showed an unexpected increase in new cases of type 1 diabetes in 2021. The incidence of type 1 diabetes now needs continuous monitoring using population registries to understand better the impact of COVID-19 on new-onset type 1 diabetes in children.

Increase in newly diagnosed type 1 diabetes and serological evidence of recent SARS-CoV-2 infection: Is there a connection?

Several studies have investigated the correlation between the COVID-19 pandemic and the onset of type 1 diabetes (T1D) in children, reporting an increased incidence of T1D and severe diabetic ketoacidosis (DKA). This study aimed to investigate the infection by SARS-CoV-2 in children with newly-diagnosed T1D to explore a possible link between SARS-CoV-2 infection, T1D and DKA. Thirty-nine children with a T1D new onset between October 15, 2020, and April 15, 2021, were enrolled. SARS-CoV-2 infection was investigated through a polymerase chain reaction on the nasal swab, dosage of specific antibodies, and an anamnestic question form. Nine (23%) of them had antibodies directed toward SARS-CoV-2, and five (12%) had a history of recent SARS-CoV-2 infection in themselves or in their family. No molecular swabs were positive. Compared to the general pediatric population, the overall incidence of COVID-19 was 5.6 times higher in the T1D patients' group (p < 0.00001). Referring only to the cases in the metropolitan area, we find a net increase in the incidence of T1D compared to the 5 years preceding our study, by 50% compared to the same months in 2016/2017 and 2017/2018, by 69% compared to 2018/2019 and by 77% compared to 2019/2020. The same trend was observed regarding DKA cases. The attributable risk of the pandemic cohort compared to the previous year is 44%. The abnormal disproportion of SARS-CoV-2 infection between children with T1D and the pediatric reference population, with a ratio of 5.6, appears to support the causative role of SARS-CoV-2 in triggering the immune response underlying diabetes, as often described for other viral infections. The difficulty accessing care services during the pandemic, with a consequent diagnosis delay, does not justify the increase in observed T1D cases, which could to be directly linked to the pandemic. The acceleration of the immune process provoked by SARS-CoV-2 may play a suggestive role in the development of T1D with DKA. Multicenter studies are needed to deepen and fully understand the pathophysiological link between SARS-CoV-2 and the onset of T1D in children.

Case Report: Role of Ketone Monitoring in Diabetic Ketoacidosis With Acute Kidney Injury: Better Safe Than Sorry.

Background: Type 1 Diabetes (T1D) is a well-known endocrinological disease in children and adolescents that is characterized by immune-mediated destruction of pancreatic ß-cells, leading to partial or total insulin deficiency, with an onset that can be subtle (polydipsia, polyuria, weight loss) or abrupt (Diabetic Keto-Acidosis, hereafter DKA, or, although rarely, Hyperosmolar Hyperglycemic State, hereafter HHS). Severe DKA risk at the onset of T1D has recently significantly increased during the SARS-CoV-2 pandemic with life-threatening complications often due to its management. DKA is marked by low pH (<7.3) and bicarbonates (<15 mmol/L) in the presence of ketone bodies in plasma or urine, while HHS has normal pH (>7.3) and bicarbonates (>15 mmol/L) with no or very low ketone bodies. Despite this, ketone monitoring is not universally available, and DKA diagnosis is mainly based on pH and bicarbonates. A proper diagnosis of the right form with main elements (pH, bicarbonates, ketones) is essential to begin the right treatment and to identify organ damage (such as acute kidney injury). Case Presentations: In this series, we describe 3 case reports in which the onset of T1D was abrupt with severe acidosis (pH < 7.1) in the absence of both DKA and HHS. In a further evaluation, all 3 patients showed acute kidney injury, which caused low bicarbonates and severe acidosis without increasing ketone bodies. Conclusion: Even if it is not routinely recommended, a proper treatment that included bicarbonates was then started, with a good response in terms of clinical and laboratory values. With this case series, we would like to encourage emergency physicians to monitor ketones, which are diriment for a proper diagnosis and treatment of DKA.

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy in Two Siblings: Same Mutations but Very Different Phenotypes.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), caused by mutations in the AIRE gene, is mainly characterized by the triad of hypoparathyroidism, primary adrenocortical insufficiency and chronic mucocutaneous candidiasis, but can include many other manifestations, with no currently clear genotype-phenotype correlation. We present the clinical features of two siblings, a male and a female, with the same mutations in the AIRE gene associated with two very different phenotypes. Interestingly, the brother recently experienced COVID-19 infection with pneumonia, complicated by hypertension, hypokalemia and hypercalcemia. Although APECED is a monogenic disease, its expressiveness can be extremely different. In addition to the genetic basis, epigenetic and environmental factors might influence the phenotypic expression, although their exact role remains to be elucidated.