Reduced Autonomic Function in Patients with Long-COVID-19 Syndrome is Mediated by Cardiorespiratory Fitness.

BACKGROUND: Long-COVID-19 syndrome (LCS) exhibits neurological problems such as peripheral neuropathy and autonomic nervous system (ANS) dysfunction. Exercise intolerance and, consequently, low cardiorespiratory fitness (CRF) are some of the most common symptoms of LCS. We describe a series of individuals exhibiting LCS symptoms compared to a control group and posit that this condition may be related to the exercise capacity-mediated disruption of the ANS resulting particularly in exercise intolerance. METHODS: This study included 87 individuals with LCS and 71 control participants without COVID-19 diagnoses. Heart rate variability (HRV) in supine position is commonly measured to diagnose autonomic dysregulation and subsequently analyzed using the Kubios software (Kuopio, Finland). CRF (peak VO2), post-COVID-19 patient-reported symptoms, maximal muscle strength (grip strength, bilateral leg press, leg extension, pectoral press, and back press exercises), and body composition were also measured. Analysis of covariance (ANCOVA) and mediation analysis were employed to assess the associations among LCS, peak VO2, and HRV indicators. Two-sided p < 0.05 was considered as significant. RESULTS: The HRV parameters-RR interval, RMSSD, SDNN, PNS index, LF, HF, total power, SD1, and SD2-were significantly elevated (p < 0.05) in the control group when compared to the LCS patients. In contrast, the HR, stress index, and SNS index parameters were significantly higher (p < 0.05) in the LCS group. When adjusted for RR intervals, these parameters remained statistically significant (p < 0.05). A mediation effect was found between peak VO2 and RMSSD (mediation effect = 24.4%) as well as peak VO2 and SDNN (mediation effect = 25.1%) in the LCS patients. CONCLUSIONS: These findings contribute new insights on the interplay between CRF and HRV indicators as well as endorse that dysautonomia may be related to the low peak VO2 observed in long COVID-19 patients.

Nonpharmacological interventions on glycated haemoglobin in youth with type 1 diabetes: a Bayesian network meta-analysis.

The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI -  1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI -  1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.

Association of physical activity patterns with nocturnal hypoglycemia events in youth with type 1 diabetes.

AIMS: This study sought to elucidate the interactions among physical activity (PA) patterns, mean glucose concentrations, and the incidence of nocturnal hypoglycemia events in children and adolescents with type 1 diabetes, examining the moderating influence of daily dosage on these associations. MATERIAL AND METHODS: Eighty-two participants aged 6 to 18 years (43.9% girls) from the Diactive-1 Cohort Study, diagnosed with type 1 diabetes, were included. Data collection involved continuous glucose monitoring, accelerometry to assess real-world PA, as well as documentation of daily insulin doses and carbohydrate counting over the same seven days. RESULTS: A total of 19 participants experienced at least one nocturnal hypoglycemia event over a span of 574 measurement days (106 days with and 451 days without nocturnal hypoglycemia). Higher levels of vigorous PA (VPA) were associated with lower same-day mean glucose levels (p = 0.014). Additionally, higher levels of moderate PA (p = 0.023), VPA (p = 0.011), and moderate-to-vigorous PA (p = 0.010) were associated with a greater number of nocturnal hypoglycemia events. Specifically, a significant association was identified between VPA and nocturnal hypoglycemia events when the daily insulin dose were at or above 1.04 units per kilogram of body weight per day (p = 0.016). CONCLUSIONS: Daily VPA is associated with glucose reductions, potentially leading to more hypoglycemic episodes, particularly when there's an excess of daily insulin. This highlights the need for careful insulin management in children and adolescents with type 1 diabetes engaging in VPA.

Diagnostic cost-effectiveness of a two-stage cardiovascular evaluation program in young-adolescent athletes. Role of echocardiography.

BACKGROUND: Sports medical examinations are a tool to detect potentially life-threatening situations during physical activity, but their usefulness and protocols in young athletes remain controversial. The aim was to describe the diagnostic performance of a 2-step ECG and echocardiogram screening model in a large sample of healthy young-adolescent athletes (aged 11-16 years), evaluating its cost-effectiveness for cardiovascular disease (CVD) detection. METHODS: Cross-sectional study of 2617 individuals (81% male, mean age 15 years), over 20 federated sports (La Rioja-Spain). A cardiological examination included family and personal history, physical examination, ECG, and transthoracic echocardiogram. The previous ECG, conducted at 11-13 years old, was reviewed in 1589 individuals (60%). ECGs were interpreted according to 2017 international criteria. The prevalence of structural cardiac disease (CD) was investigated, and the diagnostic performance of both tests and the cost of screening was evaluated. RESULTS: CVD was diagnosed in 63 athletes (2.4%) and 16 (0.6%) with pathology related to sudden cardiac death (SCD). In 3 cases (0.11%), cessation of sporting activity was indicated, and in 2 cases (0.07%), treatment for congenital CD was indicated. ECG alterations were infrequent (2.5%). Eighty percent of the structural CD diagnosed by echocardiogram had a normal ECG. The cost per CVD detected was €3,080, and for CVD associated with SCD, it was €12,323. CONCLUSIONS: Our study shows the diagnostic cost-effectiveness of a two-step cardiac screening protocol, including ECG, and highlights the role of echocardiography in young adolescent athletes, which could be implemented at a low and reasonable cost.

Dose-Response Relationship Between Exercise Duration and Enhanced Function and Cognition in Acutely Hospitalized Older Adults: A Secondary Analysis of a Randomized Clinical Trial.

Background and Objectives: Exercise may reverse functional decline in hospitalized older adults, but the optimal duration is unclear. This study examined the potential relationship between in-hospital multicomponent exercise program duration and changes in physical function, cognition, and muscle function to maximize exercise-related health benefits in acutely hospitalized older patients. Research Design and Methods: This secondary analysis of a multicenter randomized controlled trial examined the relationship between the duration of an in-hospital multicomponent exercise program and changes in physical function, cognition, and muscle strength in 570 acutely hospitalized older adults. Participants completed 3, 4, or 5-7 consecutive days of exercise based on the progression of their acute medical illness. The acute clinical condition of the older patients was similar across the study groups (i.e., 3/4/5-7 days) at admission. Outcomes included the Short Physical Performance Battery (SPPB) for functional capacity, Gait Velocity Test for gait speed, handgrip for muscle strength, and cognitive tests. Results: Of the 570 patients included in the analysis, 298 were women (52.3%), and the mean (SD) age was 87.3 (4.8) years. Exercise groups increased SPPB scores compared with controls, with gains of 1.09 points after three days, 1.97 points after four days, and 2.02 points after 5-7 days (p < .001). The 4-day program showed the most significant benefit for functional capacity. Gait velocity increased by 0.11 m/s after 4 and 5-7 days (p = .032). Similar dose-response relationships were seen for handgrip strength and cognition, with 5-7 days showing more significant gains than three days (p < .05). Discussion and Implications: Multicomponent exercise programs enhance physical and cognitive function in hospitalized older adults, regardless of exercise dosage. A 4-day program significantly boosts functional capacity, although 5-7 days improves handgrip strength and cognition, highlighting the importance of exercise dosage in countering functional decline. Implementing evidence-based inpatient exercise prescriptions can help reverse muscle weakness and improve cognitive and physical function.Clinical Trial Registration: NCT04600453.

Effects of Therapies Involving Plyometric-Jump Training on Physical Fitness of Youth with Cerebral Palsy: A Systematic Review with Meta-Analysis.

The aim of this systematic review was to assess the effects of plyometric-jump training (PJT) on the physical fitness of youth with cerebral palsy (CP) compared with controls (i.e., standard therapy). The PRISMA 2020 guidelines were followed. Eligibility was assessed using the PICOS approach. Literature searches were conducted using the PubMed, Web of Science, and SCOPUS databases. Methodological study quality was assessed using the PEDro scale. Data were meta-analyzed by applying a random-effects model to calculate Hedges' g effect sizes (ES), along with 95% confidence intervals (95% CI). The impact of heterogeneity was assessed (I2 statistic), and the certainty of evidence was determined using the GRADE approach. Eight randomized-controlled studies with low-to-moderate methodological quality were included, involving male (n = 225) and female (n = 138) youth aged 9.5 to 14.6 years. PJT interventions lasted between 8 and 12 weeks with 2-4 weekly sessions. Compared with controls, PJT improved the muscle strength (ES = 0.66 [moderate], 95% CI = 0.36-0.96, p < 0.001, I2 = 5.4%), static (ES = 0.69 [moderate], 95% CI= 0.33-1.04, p < 0.001, I2 = 0.0%) and dynamic balance (ES = 0.85 [moderate], 95% CI = 0.12-1.58, p = 0.023, I2 = 81.6%) of youth with CP. Therefore, PJT improves muscle strength and static and dynamic balance in youth with CP compared with controls. However, more high-quality randomized-controlled trials with larger sample sizes are needed to provide a more definitive recommendation regarding the use and safety of PJT to improve measures of physical fitness.

Reference values and associated factors of controlled attenuation parameter and liver stiffness in adults: A cross-sectional study.

BACKGROUND & AIMS: The utilization of non-invasive techniques for liver fibrosis and steatosis assessment has gained acceptance as a viable substitute for liver biopsy in clinical practice. This study aimed to establish normative data for the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by age and gender, as well as to explore the relationship between anthropometric measures, clinical status, and biochemical profile according to the 90th percentile cut-off values for CAP/LSM in a U.S. adult population. METHODS AND RESULTS: In this cross-sectional analysis, 7.522 US adults aged 20-80 years from the National Health and Nutrition Examination Survey (NHANES 2017-2020) were included. CAP and LSM were quantified using the FibroScan® 502-v2 device. A comprehensive range of data was collected, including sociodemographic, anthropometric, biochemical, lifestyle, and clinical conditions. Participants were segmented by sex and age. The median ± standard deviation (SD) for CAP was significantly lower in women (258.27 ± 61.02 dB/m) than in men (273.43 ± 63.56 dB/m), as was the median ± SD for LSM (women: 5.50 ± 4.12 kPa, men: 6.36 ± 5.63 kPa). Although median CAP and LSM values displayed an upward trend with age, statistical significance was not achieved. Notably, higher liver CAP values (above the 90th percentile) correlated with more pronounced clinical and biochemical profile differences compared to lower CAP values (below the 90th percentile) (p < 0.001). CONCLUSIONS: Our study provides age- and sex-stratified standard values for CAP and LSM in a sizeable, nationally representative cohort of adults. The evidence of sex-specific variations in TE test results from our study sets the stage for future research to further corroborate these findings.

Effects of Exercise on DNA Methylation: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Regular exercise reduces chronic disease risk and extends a healthy lifespan, but the underlying molecular mechanisms remain unclear. DNA methylation is implicated in this process, potentially altering gene expression without changing DNA sequence. However, previous findings appear partly contradictory. OBJECTIVE: This review aimed to elucidate exercise effects on DNA methylation patterns. METHODS: PubMed, Scopus and Web of Science databases were searched following PRISMA 2020 guidelines. All articles published up to November 2023 were considered for inclusion and assessed for eligibility using the PICOS (Population, Intervention, Comparison, Outcomes and Study) framework. Randomized controlled trials that assessed the impact of exercise interventions on DNA methylation in previously inactive adults were included. We evaluated the methodological quality of trials using the PEDro scale. RESULTS: A total of 852 results were identified, of which 12 articles met the inclusion criteria. A total of 827 subjects were included in the studies. Intervention lengths varied from 6 weeks to 12 months. Most trials indicated that exercise interventions can significantly alter the DNA methylation of specific genes and global DNA methylation patterns. CONCLUSIONS: The heterogeneity of results may arise from differences in participant demographics, intervention factors, measurement techniques, and the genomic contexts examined. Future research should analyze the influences of activity type, intensity, and duration, as well as the physical fitness outcomes on DNA methylation. Characterizing such dose-response relationships and identifying genes responsive to exercise are crucial for understanding the molecular mechanisms of exercise, unlocking its full potential for disease prevention and treatment.

Assessing basic motor competences, physical fitness, and executive function in 4-5-year-old children: a longitudinal study in a primary care setting.

BACKGROUND: To evaluate the progression of physical fitness (PF), basic motor competence (BMC), and executive function (EF) over one year in children aged 4-5 years at a health center. METHODS: In this longitudinal analysis, children's BMC was evaluated using the MOBAK KG test for object and self-movement. The PREFIT Battery gauged PF through handgrip strength, standing long jump, and other fitness measures, while the Early Years Toolbox appraised EF. RESULTS: Adjustments for confounding factors showed notable improvements in BMC, particularly in object movement (OM; mean difference 0.789, p = 0.044) and self-movement (SM; mean difference 0.842, p = 0.037), with overall MOBAK scores also increasing (mean difference 1.632, p = 0.018). Enhancements in the standing long jump (mean difference 9.036 cm, p = 0.014) and EF tasks "Mr. Ant" (mean difference 0.669, p < 0.001) and "Go/No-Go" (mean difference 0.120, p < 0.001) were evident, signifying substantial BMC gains and some progress in PF and EF. CONCLUSION: This research underscores the positive impact of regular training on BMC and PF in young children. Significant BMC development and associated improvements in PF and EF over the study period highlight the importance of structured activities in early childhood. These findings advocate for standardized training programs to enhance childhood health and encourage active lifestyles. TRIAL REGISTRATION: NCT05741879. Registered February 14, 2023, Version 1.

Effects of Exercise Intervention for the Management of Delirium in Hospitalized Older Adults: A Randomized Clinical Trial.

OBJECTIVE: Delirium is a serious neuropsychiatric syndrome frequently occurring in hospitalized older adults, for which pharmacological treatments have shown limited effectiveness. Multicomponent physical exercise programs have demonstrated functional benefits; however, the impact of exercise on the course of delirium remains unexplored. The aim of this study was to investigate the effect of an individualized, multicomponent exercise intervention on the evolution of delirium and patient outcomes. DESIGN: A single-center, single-blind randomized controlled trial. SETTING AND PARTICIPANTS: Medical inpatients with delirium in an acute geriatric unit of a tertiary public hospital. METHODS: Thirty-six patients (mean age 87 years) were recruited and randomized into 2 groups. The control group received usual care and the intervention group received individualized physical exercise (1 daily session) for 3 consecutive days. Primary endpoints were the duration and severity of delirium (4-AT, Memorial Delirium Assessment Scale) and change in functional status [Barthel Index, Short Physical Performance Battery, Hierarchical Assessment of Balance and Mobility (HABAM), and handgrip strength]. Secondary endpoints included length of stay, falls, and health outcomes at 1- and 3-month follow-up. RESULTS: The intervention group showed more functional improvement at discharge (HABAM, P = .015) and follow-up (Barthel, P = .041; Lawton P = .027). Less cognitive decline was observed at 1 and 3 months (Informant Questionnaire on Cognitive Decline in the Elderly, P = .017). Exercise seemed to reduce delirium duration by 1 day and contribute to delirium resolution at discharge, although findings did not reach statistical significance. No exercise-related adverse events occurred. CONCLUSION AND IMPLICATIONS: Findings suggest that individualized exercise in acutely hospitalized older patients with delirium is safe, may improve delirium course and help preserve post-hospitalization function and cognition.

Comprehensive management of children and adolescents with type 1 diabetes mellitus through personalized physical exercise and education using an mHealth system: The Diactive-1 study protocol.

Introduction: The use of new technologies presents an opportunity to promote physical activity, especially among young people with type 1 diabetes (T1DM), who tend to be less active compared to their healthy counterparts. The aim of this study is to investigate the impact of a personalized resistance exercise program, facilitated by the Diactive-1 App, on insulin requirements among children and adolescents diagnosed with T1DM. Methods and analysis: A minimum of 52 children and adolescents aged 8-18 years, who were diagnosed with T1DM at least 6 months ago, will be randomly assigned to either a group engaging in an individualized resistance exercise program at least 3 times per week over a 24-week period or a waiting-list control group. The primary outcome will be the daily insulin dose requirement. The secondary outcomes will include glycemic control, cardiometabolic profile, body composition, vascular function, physical fitness, 24-hour movement behaviors, diet, and psychological parameters. The usability of the app will also be assessed. Ethics and dissemination: Ethical approval to conduct this study has been granted by the University Hospital of Navarra Research Board (PI_2020/140). Parents or legal guardians of minors participating in the study will provide written consent, while children and adolescents will sign an assent form to indicate their voluntary agreement. The trial's main findings will be shared through conference presentations, peer-reviewed publications, and communication directly with participating families. This study aims to offer valuable insights into the holistic management of children and adolescents with T1DM by utilizing personalized exercise interventions through an mHealth system. Trial registration: NCT06048757.

Can an active lifestyle reduce the risk of obesity in adulthood among adolescents with Attention-Deficit/Hyperactivity Disorder symptoms? An ambispective cohort study.

Various studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with obesity, but the role of physical activity in this connection is uncertain. This study examined whether adopting an active lifestyle can mitigate the link between adolescent ADHD and the risk of adult obesity. Longitudinal data from the Add Health Study (Waves I, III, and V) were used. Participants self-reported ADHD symptoms (hyperactivity/impulsivity, inattention, combined) during Wave III and self-assessed their recent moderate-to-vigorous physical activity. An "active lifestyle" required meeting activity criteria in both adolescence (Wave I) and adulthood (Wave III-V). Of 2609 participants, 1.42 % exhibited combined ADHD symptoms. A non-linear relationship was observed between inattentive/hyperactive scores and body mass index (BMI) and waist circumference (WC). Individuals with ≥ 6 hyperactivity/impulsivity symptoms had higher BMI (1.29 kg/m²) and WC (1.27 cm) at adulthood. Logistic regressions indicate that, compared to individuals without ADHD maintaining an active lifestyle, both inactive participants with and without ADHD show an elevated risk of obesity (odds ratio [OR]=1.56 to 2.63) and abdominal obesity in adulthood (OR = 1.51 to 2.50). Mediation analysis models further confirm these findings, suggesting that physical activity may explain this association. Though exact mechanisms warrant further exploration, adopting an active lifestyle offers promise for reducing obesity risk among individuals with ADHD symptoms.

Maintaining an active lifestyle from adolescence to adulthood might alleviate the adverse association of preterm birth with cardiometabolic health.

AIMS: We aimed to determine whether physical activity attenuates preterm birth's adverse effects on adult cardiometabolic health. METHODS: This retrospective study utilized data from the Add Health Study, a prospective cohort conducted in the United States. During Wave V (mean age: 37 years; 60.7% women; mean body mass index: 29 kg/m2; mean waist circumference: 95 cm), we evaluated cardiometabolic risk factors and preterm birth status (i.e., born <37 weeks). Self-reported physical activity data was collected through questionnaires during Waves I (ages 12-19) and Wave V. An "active lifestyle" was defined by adherence to recommendations during both waves, spanning from adolescence to adulthood. RESULTS: The sample, comprising 3320 individuals, with 9.5% being preterm, included 7.6% who remained physically active throughout both adolescence and adulthood. Preterm-born individuals who were inactive had higher rates of obesity (incidence rate ratio [IRR] = 1.39, 95% confidence interval (CI) 1.05-1.84), abdominal obesity (IRR = 1.46, 95% CI 1.11-1.92), hyperlipidemia (IRR 3.50, 95% CI 1.94-4.29), type 2 diabetes (IRR = 2.37, 95% CI 1.12-5.01), and metabolic syndrome (IRR = 2.61, 95% CI 1.17-5.80) compared to active term-born individuals. Maintaining an active lifestyle appeared to decrease the risk of obesity and hyperlipidemia in adults born preterm (p > 0.05). CONCLUSIONS: While preterm birth is associated with an elevated risk of adult cardiometabolic risk, maintaining an active lifestyle appeared to slightly mitigate the risk of obesity and hyperlipidemia in adults born preterm.

Hypoxic peripheral chemoreflex stimulation-dependent cardiorespiratory coupling is decreased in swimmer athletes.

Swimmer athletes showed a decreased ventilatory response and reduced sympathetic activation during peripheral hypoxic chemoreflex stimulation. Based on these observations, we hypothesized that swimmers develop a diminished cardiorespiratory coupling due to their decreased hypoxic peripheral response. To resolve this hypothesis, we conducted a study using coherence time-varying analysis to assess the cardiorespiratory coupling in swimmer athletes. We recruited 12 trained swimmers and 12 control subjects for our research. We employed wavelet time-varying spectral coherence analysis to examine the relationship between the respiratory frequency (Rf ) and the heart rate (HR) time series during normoxia and acute chemoreflex activation induced by five consecutive inhalations of 100% N2 . Comparing swimmers to control subjects, we observed a significant reduction in the hypoxic ventilatory responses to N2 in swimmers (0.012 ± 0.001 vs. 0.015 ± 0.001 ΔVE /ΔVO2 , and 0.365 ± 0.266 vs. 1.430 ± 0.961 ΔVE /ΔVCO2 /ΔSpO2 , both p < 0.001, swimmers vs. control, respectively). Furthermore, the coherence at the LF cutoff during hypoxia was significantly lower in swimmers compared to control subjects (20.118 ± 3.502 vs. 24.935 ± 3.832 area under curve [AUC], p < 0.012, respectively). Our findings strongly indicate that due to their diminished chemoreflex control, swimmers exhibited a substantial decrease in cardiorespiratory coupling during hypoxic stimulation.

Association of postoperative delirium with serum and cerebrospinal fluid proteomic profiles: a prospective cohort study in older hip fracture patients.

Postoperative delirium (POD) is a common neuropsychiatric complication in geriatric inpatients after hip fracture surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the relationship between preoperative biomarkers in serum and cerebrospinal fluid (CSF) and the development of POD in older hip fracture patients, exploring the possibility of integrating objective methods into future predictive models of delirium. Sixty hip fracture patients were recruited. Blood and CSF samples were collected at the time of spinal anesthesia when none of the subjects had delirium. Patients were assessed daily using the 4AT scale, and based on these results, they were divided into POD and non-POD groups. The Olink® platform was used to analyze 45 cytokines. Twenty-one patients (35%) developed POD. In the subsample of 30 patients on whom proteomic analyses were performed, a proteomic profile was associated with the incidence of POD. Chemokine (C-X-C motif) ligand 9 (CXCL9) had the strongest correlation between serum and CSF samples in patients with POD (rho = 0.663; p < 0.05). Although several cytokines in serum and CSF were associated with POD after hip fracture surgery in older adults, there was a significant association with lower preoperative levels of CXCL9 in CSF and serum. Despite the small sample size, this study provides preliminary evidence of the potential role of molecular biomarkers in POD, which may provide a basis for the development of new delirium predictive models.

Incidence of type 1 diabetes mellitus in children and adolescents under 20 years of age across 55 countries from 2000 to 2022: A systematic review with meta-analysis.

AIMS: The aim of this study was to determine the global incidence of type 1 diabetes mellitus (T1DM) in children and adolescents under 20 years of age from 2000 to 2022. MATERIALS AND METHODS: Two reviewers searched three electronic databases (PubMed, Web of Science, and CINAHL) for studies published between January 2000 and November 2022. Pooled estimates of T1DM incidence with a 95% confidence interval (CI) per 100,000 person-years were calculated by country/region, sex, age, and COVID-19 pandemic period (pre-COVID-19 and pandemic). RESULTS: The study included 126 studies from 55 countries and 18 regions. The incidence rate (IR) of T1DM from 2000 to 2022 was 14.07 (95%CI, 12.15-16.29) per 100,000 person-years. Finland and high-income North America had the highest IR, with 56.81 (95%CI, 55.91-57.73) and 28.77 (95%CI, 26.59-31.13) per 100,000 person-years, respectively. The IR was 13.37 (95%CI, 10.60-16.88) per 100,000 person-years in boys and 13.87 (95%CI, 11.51-16.70) per 100,000 person-years in girls. There were statistically significant differences among different age ranges: 0-4 versus 5-9 and 10-14 years old (p < 0.001); 5-9 versus 15-19 (p < 0.001) and 10-14 versus 15-19 years old (p = 0.003). Finally, during the pandemic period (2020-2022), the IR was 24.84 (95%CI, 17.16-35.96) per 100,000 person-years, which was higher but not significant compared with the prepandemic period (2017-2019) of 13.56 (95%CI, 7.49-24.56) per 100,000 person-years (p = 0.090). CONCLUSIONS: The IR of T1DM in children and adolescents under 20 years of age is substantial, especially during the pandemic period, although it varies across regions. More reliable data from additional countries are needed to determine the worldwide incidence of T1DM.