Pediatric Type 1 Diabetes Research Articles

Population-based prevalence of self-reported pediatric diabetes and screening for undiagnosed type 2 diabetes in Chinese children in years 2017–2019, a cross-sectional study

The worldwide geographical and temporal variation in the prevalence of diabetes represents a challenge, but also an opportunity for gaining etiological insights. Encompassing the bulk of East Asians, a large and distinct proportion of the world population, China can be a source of valuable epidemiological insights for diabetes, especially in early life, when pathophysiology begins. We carried out a nationwide, epidemiological survey of Prevalence and Risk of Obesity and Diabetes in Youth (PRODY) in China, from 2017 to 2019, to estimate the population-based prevalence of diagnosed pediatric diabetes and screen for undiagnosed pediatric type 2 diabetes (T2D). PRODY was a nation-wide, school population-based, cross-sectional, multicenter survey by questionnaire, fasting urine glucose test and simple oral glucose tolerance test (s-OGTT), among a total number of 193,801 general-population children and adolescents (covered a pediatric population of more than 96.8 million), aged 3-18, from twelve provinces across China. The prevalence of the self-reported pediatric diabetes, the proportion of subtypes, the crude prevalence of undiagnosed T2D and prediabetes in general juvenile population and the main risk factors of type 1 (T1D) and type 2 (T2D) diabetes had been analyzed in the study. The prevalence of all self-reported pediatric diabetes was estimated at 0.62/1000 (95% CI: 0.51-0.74), with T1D at 0.44/1000 (95% CI: 0.35-0.54) and T2D at 0.18/1000 (95% CI: 0.13-0.25). For undiagnosed T2D, the crude prevalence was almost ten-fold higher, at 1.59/1000, with an estimated extra 28.45/1000 of undiagnosed impaired glucose tolerance (IGT) and 53.74/1000 of undiagnosed impaired fasting glucose (IFG) by s-OGTT screening. Maternal diabetes history is the major risk factors for all subtypes of pediatric diabetes in China. The PRODY study provides the first population-based estimate of the prevalence of pediatric diabetes China and reveals a magnitude of the problem of undiagnosed pediatric T2D. We propose a practical screening strategy by s-OGTT to address this serious gap. The National Key Research and Development Programme of China, Key R&D Program of Zhejiang, the National Natural Science Foundation of China and the Zhejiang Provincial Key Disciplines of Medicine, Key R&D Program Projects in Zhejiang Province.

7366 Experience and perspectives of healthcare professionals regarding exercise directed guidance in pediatric type 1 diabetes

Abstract Disclosure: H. Reznik: None. A. Brener: None. F. Levy-Khademi: None. J. Yeshayahu: None. D. Pivko-Levy: None. I. Koren: None. O. Pinhas-Hamiel: None. M. Sharkia: None. L. Carmon: None. M. Rachmiel: None. M. Muller: None. L. de Vries: None. M. Cohen: None. Objective: Regular exercise can promote various aspects of health in pediatric type-1-diabetes (T1D). However, the management of exercise can be extremely challenging for the child, their family and the healthcare team involved. Studies suggest that children with T1D perform less than the recommended daily activity and that exercise does not always improve glycemic control. Multiple factors should be accounted for, including among others, the nature of the activity and individual child, as well as the treatment regimen. Proper guidance in preparation for exercise is crucial. We conducted a national study aimed at identifying strengths and limitations of exercise directed guidance (EDG) provided by staff in pediatric T1D clinics in Israel. Methods: Healthcare professionals from 8 pediatric diabetes clinics, including physicians, nurses and dietitians, were recruited. Participants completed an anonimized electronic questionnaire assessing: i) Demographics ii) Timing and content of the guidance provided to pediatric patients with T1D iii) Perceived challenges. Results: Ninety-nine professionals took part in this study, 53 physicians, 24 nurses and 23 dietitians. All reported providing EDG to pediatric T1D patients, 90 (90.9%) include EDG both during the initial post-diagnosis visits and periodically thereafter. However, while 83 (83.8%) reported offering guidance to all patients, 16 (16.1%) indicated guiding only specific children: either those that exercise, those that do not exercise or only those that asked for information. Only 64 (64.6%) reported to have specialized educational materials available in clinic, this varied even within the same clinic. The 3 most prevalent topics reported by participants as “usually included” in EDG, were: immediate effects on glucose (94.9%), adjusting carbohydrates (88.8%) and the equipment required during exercise (86.8%). The 3 least frequently addressed subjects were: addressing principals in planning exercise (28.2%) and involving family and friends (29.2% and 17.1% respectively). Challenges by order of prevalence were insufficient teaching aids, the complexity of the topic, lack of knowledge and insufficient time (reported by 44.4%, 39.4%, 34.3% and 34.3% respectively). The knowledge gap most commonly reported centered on understanding the impact of different types of exercise on blood glucose. Conclusions: Healthcare professionals recognize the importance of exercise in T1D management and all of them incorporate EDG in their routine practice. Interestingly, there is considerable variability in both timing and content of the EDG provided, even within the same clinic. We have identified important areas for improvement, with particular attention needed in increasing the availability of educational tools and enhancing staff knowledge. Our findings can assist in creating educational aids for both staff and patients. Presentation: 6/2/2024

8074 Investigating Viral Infections, Systemic Inflammation, and their Complex Interplay in Type 1 Diabetes Pathogenesis

Abstract Disclosure: K. Girdhar: None. E. Elko: None. A. Pina: None. M. Atkinson: None. J. Ludvigsson: None. J. Ladner: None. E. Altindis: None. Type 1 diabetes (T1D) is an autoimmune disorder characterized by the immune-mediated destruction of insulin-producing beta cells. The etiological factors triggering the immunogenicity of endogenous β-cell antigens remain a focal point of investigation. Viral infections, particularly enteroviruses, coxsackieviruses, and rotaviruses, have been proposed as potential contributors to T1D onset and progression. However, the causal relationship between viral infections and T1D pathogenesis remains elusive. To address this, we conducted an in-depth analysis of viral infection histories of T1D patients and pediatric T1D progressors compared to the controls. To this end, we employed highly multiplexed serology using PepSeq sequencing, an in vitro platform designed for conducting proteomic assays against customizable targets via DNA-barcoded peptides. Utilizing samples from the All Babies in Sweden (ABIS) study (n=58) and the TrialNet study (n=116 new-onset T1D, n=25 established T1D, n=128 controls), we assessed seropositivity against 79 different human viruses. Contrary to previous reports, no significant differences were identified in viral infection histories between T1D individuals and controls. Subsequent analyses of enriched Peptide Count and Viral Homology Search (VHS) species provided further confirmation of the absence of distinctions in T1D progression. Next, we determined whether there are any differences in the markers of systematic inflammation in spite of their similar viral history profile. Therefore, we employed Luminex assays to investigate cytokine profiles in established T1D individuals (n=25). While we could not identify any differences when we compared T1D patients to controls, we identified notable sex-specific differences. Anti-inflammatory cytokines (IL-4, IL-13, IL-22) were lower in female T1D patients compared to female controls. Likewise, female T1D patients had higher pro-inflammatory cytokines (IL-17E, TNF-β). On the other hand, male T1D patients exhibited increased levels of epidermal growth factor and platelet-derived growth factor compared to male controls, with IL-22 uniquely elevated. Our findings challenge the direct association between viral infections and T1D, highlighting the importance of investigating alternative factors. Moreover, the observed sex-specific cytokine alterations underscore the complex interplay between immune responses and T1D, emphasizing the need for sex-specific therapeutic strategies. This research contributes valuable insights into the intricate dynamics of viral infections, systemic inflammation, and their potential roles in T1D pathogenesis. Presentation: 6/2/2024

Does HLA explain the high incidence of childhood-onset type 1 diabetes in the Canary Islands? The role of Asp57 DQB1 molecules

The Canary Islands inhabitants, a recently admixed population with significant North African genetic influence, has the highest incidence of childhood-onset type 1 diabetes (T1D) in Spain and one of the highest in Europe. HLA accounts for half of the genetic risk of T1D.AimsTo characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D.MethodsWe analyzed classic HLA-DRB1 and HLA-DQB1 alleles in childhood-onset T1D patients (n = 309) and control children without T1D (n = 222) from the island of Gran Canaria. We also analyzed the presence or absence of aspartic acid at position 57 in the HLA-DQB1 gene and arginine at position 52 in the HLA-DQA1 gene. Genotyping of classical HLA-DQB1 and HLA-DRB1 alleles was performed at two-digit resolution using Luminex technology. The chi-square test (or Fisher's exact test) and odds ratio (OR) were computed to assess differences in allele and genotype frequencies between patients and controls. Logistic regression analysis was also used.ResultsMean age at diagnosis of T1D was 7.4 ± 3.6 years (46% female). Mean age of the controls was 7.6 ± 1.1 years (55% female). DRB1*03 (OR = 4.2; p = 2.13–13), DRB1*04 (OR = 6.6; p ≤ 2.00–16), DRB1* 07 (OR = 0.37; p = 9.73–06), DRB1*11 (OR = 0.17; p = 6.72–09), DRB1*12, DRB1*13 (OR = 0.38; p = 1.21–05), DRB1*14 (OR = 0.0; p = 0.0024), DRB1*15 (OR = 0.13; p = 7.78–07) and DRB1*16 (OR = 0.21; p = 0.003) exhibited significant differences in frequency between groups. Among the DQB1* alleles, DQB1*02 (OR: 2.3; p = 5.13–06), DQB1*03 (OR = 1.7; p = 1.89–03), DQB1*05 (OR = 0.64; p = 0.027) and DQB1*06 (OR = 0.19; p = 6.25–14) exhibited significant differences. A total of 58% of the studied HLA-DQB1 genes in our control population lacked aspartic acid at position 57.ConclusionsIn this population, the overall distributions of the HLA-DRB1 and HLA-DQB1 alleles are similar to those in other European populations. However, the frequency of the non-Asp-57 HLA-DQB1 molecules is greater than that in other populations with a lower incidence of T1D. Based on genetic, historical and epidemiological data, we propose that a common genetic background might help explain the elevated pediatric T1D incidence in the Canary Islands, North-Africa and middle eastern countries.

A Machine Learning Model for Risk Stratification of Postdiagnosis Diabetic Ketoacidosis Hospitalization in Pediatric Type 1 Diabetes: Retrospective Study.

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in pediatric type 1 diabetes (T1D), occurring in approximately 20% of patients, with an economic cost of $5.1 billion/year in the United States. Despite multiple risk factors for postdiagnosis DKA, there is still a need for explainable, clinic-ready models that accurately predict DKA hospitalization in established patients with pediatric T1D. We aimed to develop an interpretable machine learning model to predict the risk of postdiagnosis DKA hospitalization in children with T1D using routinely collected time-series of electronic health record (EHR) data. We conducted a retrospective case-control study using EHR data from 1787 patients from among 3794 patients with T1D treated at a large tertiary care US pediatric health system from January 2010 to June 2018. We trained a state-of-the-art; explainable, gradient-boosted ensemble (XGBoost) of decision trees with 44 regularly collected EHR features to predict postdiagnosis DKA. We measured the model's predictive performance using the area under the receiver operating characteristic curve-weighted F1-score, weighted precision, and recall, in a 5-fold cross-validation setting. We analyzed Shapley values to interpret the learned model and gain insight into its predictions. Our model distinguished the cohort that develops DKA postdiagnosis from the one that does not (P<.001). It predicted postdiagnosis DKA risk with an area under the receiver operating characteristic curve of 0.80 (SD 0.04), a weighted F1-score of 0.78 (SD 0.04), and a weighted precision and recall of 0.83 (SD 0.03) and 0.76 (SD 0.05) respectively, using a relatively short history of data from routine clinic follow-ups post diagnosis. On analyzing Shapley values of the model output, we identified key risk factors predicting postdiagnosis DKA both at the cohort and individual levels. We observed sharp changes in postdiagnosis DKA risk with respect to 2 key features (diabetes age and glycated hemoglobin at 12 months), yielding time intervals and glycated hemoglobin cutoffs for potential intervention. By clustering model-generated Shapley values, we automatically stratified the cohort into 3 groups with 5%, 20%, and 48% risk of postdiagnosis DKA. We have built an explainable, predictive, machine learning model with potential for integration into clinical workflow. The model risk-stratifies patients with pediatric T1D and identifies patients with the highest postdiagnosis DKA risk using limited follow-up data starting from the time of diagnosis. The model identifies key time points and risk factors to direct clinical interventions at both the individual and cohort levels. Further research with data from multiple hospital systems can help us assess how well our model generalizes to other populations. The clinical importance of our work is that the model can predict patients most at risk for postdiagnosis DKA and identify preventive interventions based on mitigation of individualized risk factors.

Pediatric Type 1 Diabetes: A Bibliometric Analysis of the 100 Most-cited Publications

Abstract Background: The most impactful research on pediatric type 1 diabetes (T1D) remains unknown. Objective: We aimed to evaluate the characteristics and impact of the 100 most-cited articles on pediatric T1D. Materials and Methods: Using a predefined bibliometric strategy, the Scopus database was searched for high-cited papers (HCPs) published from 2001 to 2020. Articles were evaluated for data on the publication year, countries, authors, journals, topics, and types. Social network analysis was performed to visualize the interaction among countries, organizations, and authors using VOSviewer software. Results: The top 100 HCPs received 390 to 4634 citations, averaging 773.5 citations per paper (CPP). The funded HCPs (n = 50) had a higher impact (CPP 791.5). The majority of HCPs (n = 83) were collaborative. Classifying by research type, 65 studies were clinical (n = 65), risk factors (n = 27), epidemiology (n = 26), pathophysiology (n = 16), treatment outcome (n = 13), genetics (n = 12), complications (n = 3), quality of life (n = 2), and prognosis (n = 1). The number of authors involved was 1,101, affiliated with 545 organizations in 27 countries; the USA (n = 64) and the UK (n = 24) were the most productive countries, whereas Australia and the UK were the most impactful. D.M. Nathan and J.M. Lawrence were the most prolific authors, while P. Raskin and J.M. Lachin were the most impactful. Conclusions: High-income countries such as the USA, UK, and Australia contribute significantly to high-impact pediatric T1D research. Funding and collaboration improve the impact of citations in publications. Less researched areas such as treatment outcomes, genetics, complications, quality of life, and prognosis should be the focus of future research on pediatric T1D.

Changes in Pediatric Type 2 Diabetes During the COVID-19 Pandemic.

Type 2 diabetes (T2D) is a growing concern among the pediatric population. During the coronavirus disease 2019 (COVID-19) pandemic, the incidence of pediatric T2D increased. This was more notable among males and Black people. Increased rates of T2D may be due to rising obesity rates observed during the pandemic, behavioral and nutritional changes due to the lockdown, and decreased structure typically provided by in-person schooling. New-onset T2D presentations are more severe than in years prior to the pandemic, with higher initial hemoglobin A1C levels and increased rates of diabetic ketoacidosis. Increased severity in presentation may be due to hesitation in seeking care, increased virtual care, and limited access to health care resources. The pathophysiology of the relationship between T2D and COVID-19 in youth is not clear at this time. More studies are needed to understand the true long-term impact of the COVID-19 pandemic on T2D in youth. [Pediatr Ann. 2024;53(7):e249-e253.].

Type 1 diabetes human enteroid studies reveal major changes in the intestinal epithelial compartment

Lack of understanding of the pathophysiology of gastrointestinal (GI) complications in type 1 diabetes (T1D), including altered intestinal transcriptomes and protein expression represents a major gap in the management of these patients. Human enteroids have emerged as a physiologically relevant model of the intestinal epithelium but establishing enteroids from individuals with long-standing T1D has proven difficult. We successfully established duodenal enteroids using endoscopic biopsies from pediatric T1D patients and compared them with aged-matched enteroids from healthy subjects (HS) using bulk RNA sequencing (RNA-seq), and functional analyses of ion transport processes. RNA-seq analysis showed significant differences in genes and pathways associated with cell differentiation and proliferation, cell fate commitment, and brush border membrane. Further validation of these results showed higher expression of enteroendocrine cells, and the proliferating cell marker Ki-67, significantly lower expression of NHE3, lower epithelial barrier integrity, and higher fluid secretion in response to cAMP and elevated calcium in T1D enteroids. Enteroids established from pediatric T1D duodenum identify characteristics of an abnormal intestinal epithelium and are distinct from HS. Our data supports the use of pediatric enteroids as an ex-vivo model to advance studies of GI complications and drug discovery in T1D patients.

The psychosocial outcomes of advanced hybrid closed-loop system in children and adolescents with type 1 diabetes

The study was carried out to determine the psychosocial outcomes of advanced hybrid closed-loop (AHCL) systems in children and adolescents with type 1 diabetes (T1D). Single-center and cohort study with a duration 6 months consisted of 60 children and adolescents with T1D. Standard clinical procedures, including both glycemic indicators, e.g., sensor-measured time within the 70–180 mg/dL range and glycated hemoglobin (HbA1c) levels, and psychosocial metrics were used for data collection. The psychosocial metrics included the Pediatric Quality of Life Inventory (PedsQL) 3.0 Diabetes Module for both children (8–12 years) and parents; the Quality of Life for Youth scale for adolescents (13–18 years); the Strengths and Difficulties Questionnaire (SDQ); the Hypoglycemia Fear Survey for Children (HFS-C); the Revised Child Anxiety and Depression Scale (R-CADS); and AHCLS-specific DTSEQ satisfaction and expectation survey. These metrics were evaluated at the baseline and after 6 months of AHCL use. Of the 60 children and adolescents with T1D for whom the AHCL system was utilized, 41 of them, 23 female and 18 male, completed the surveys. The mean age of the 41 children and adolescents was 12.5 ± 3.2 (min. 6.7, max. 18) years. The time spent within the target glycemic range, i.e., time-in-range (TIR), improved from 76.9 ± 9% at the baseline to 80.4 ± 5% after 6 months of AHCL system use (p = 0.03). Additionally, HbA1c levels reduced from 7.1% ± 0.7% at the baseline to 6.8% ± 0.8% after 6 months of AHCL system use (p = 0.03). The most notable decline in HbA1c was observed in participants with higher baseline HbA1c levels. All patients’ HFS-C and AHCL system-specific DTSEQ satisfaction and expectation survey scores were within the normal range at the baseline and remained unchanged during the follow-up period. No significant difference was found in the R-CADS scores of children and adolescents between baseline and after 6 months of AHCL system use. However, there was a significant decrease in the R-CADS scores of the parents. Patients’ PedsQL scores were high both at the baseline and after 6 months. The SDQ scores were high at baseline, and there was no significant improvement at the end of 6 months. Conclusion: This is the first study to investigate in detail the psychosocial outcomes of AHCL system use in T1D patients and their parents. Although state-of-the-art technologies such as AHCL provide patients with more flexibility in their daily lives and information about glucose fluctuations, the AHCL resulted in a TIR above the recommended target range without a change in QOL, HFS-C, SDQ, and R-CADS scores. The scores obtained from the R-CADS conducted by the parents of the children indicated that the use of pumps caused a psychological improvement in the long term, with a significant decrease in the R-CADS scores of the children and adolescents with T1D.What is Known:• Previous studies focused on clinical outcomes of AHCL systems in pediatric T1D patients, showing glycemic control improvements.• Limited attention given to psychosocial outcomes of AHCL systems in children and adolescents with T1D.• Crucial psychosocial factors like quality of life, emotional well-being, and fear of hypoglycemia underexplored in AHCL system context.What is New:• First study to comprehensively examine psychosocial outcomes of AHCL systems in pediatric T1D patients.• Study's robust methodology sets new standard for diabetes technology research and its impact on qualiy of life.

Elevated Serum IgA at Onset of Type 1 Diabetes in Children

Background. Elevated serum IgA levels have been observed in various autoimmune conditions, including type 1 diabetes (T1D). However, whether children with T1D and elevated serum IgA have unique features has not been studied. We aimed to evaluate the prevalence and characteristics associated with elevated serum IgA at the onset of pediatric T1D. Materials and Methods. We analyzed demographic, clinical, and laboratory data retrospectively collected from 631 racially diverse children (6 months–18 years of age) with T1D who had serum IgA levels measured within 90 days of T1D diagnosis. Univariable and multivariable logistic regression models were used to identify characteristics that were significantly associated with elevated versus normal IgA. Results. Elevated serum IgA was present in 20.3% (128/631) of the children with newly diagnosed T1D. After adjusting for other variables, A1c level (p=0.029), positive insulin autoantibodies (IAA) (p=0.041), negative glutamic acid decarboxylase autoantibodies (GADA) (p=0.005) and Hispanic ethnicity (p &lt;0.001) were significantly associated with elevated serum IgA. After adjustment for confounders, the odds of elevated serum IgA were significantly increased with positive IAA (OR 1.653, 95% CI 1.019–2.679), higher HbA1c (OR 1.132, 95% CI 1.014–1.268) and Hispanic ethnicity (OR 3.279, 95% CI 2.003–5.359) but decreased with GADA positivity (OR 0.474, 95% CI 0.281–0.805). Conclusions. Elevated serum IgA is present in 20.3% of the children at T1D onset and is associated with specific demographic and clinical characteristics, suggesting a unique pathogenesis in a subset of individuals. Further studies are warranted to investigate the IgA response, its role in T1D pathogenesis, and whether these associations persist over time.

The Complex Network of Cytokines and Chemokines in Pediatric Patients with Long-Standing Type 1 Diabetes.

Type 1 diabetes (T1D) is a progressive disorder leading to the development of microangiopathies and macroangiopathies. Numerous cytokines and chemokines are involved in the pathogenesis of T1D complications. The study aimed to assess the presence of complications in patients with long-standing T1D and its relationship with serum biomarker concentrations. We examined 52 T1D subjects, with a disease duration ≥4 years and 39 healthy controls. The group of T1D patients was further divided into subgroups based on the duration of the disease (<7 years and ≥7 years) and the metabolic control assessed by the HbAlc level (<8% and ≥8%). We used Luminex Technology to assess a wide range of biomarker concentrations. A 24 h urine test was done to evaluate the rate of albuminuria. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (IMT). T1D patients showed remarkably higher concentrations of EGF, eotaxin/CCL11, MDC/CCL22, sCD40L, TGF-α, and TNF-α. Moreover, we reported statistically significant correlations between cytokines and IMT. Biomarker concentrations depend on numerous factors such as disease duration, metabolic control, and the presence of complications. Although the majority of pediatric T1D patients do not present signs of overt complications, it is indispensable to conduct the screening for angiopathies already in childhood, as its early recognition may attenuate the further progression of complications.

Adverse Social Determinants of Health in Children with Newly Diagnosed Type 1 Diabetes: A Potential Role for Community Health Workers

Objective. There are significant socioeconomic and racial disparities in glycemic control among children with type 1 diabetes (T1D). Community health workers (CHWs) have been shown to improve outcomes in marginalized, high-risk populations. The purpose of this qualitative study was to describe the prevalence and the impact of adverse social determinants of health (SDOH) on diabetes care soon after a diagnosis of pediatric T1D, and investigate the potential supportive role of a CHW. Research Design and Methods. Caregivers of youth &lt;17-year old, with new onset T1D, and government insurance at the time of diagnosis were enrolled. Baseline demographic and SDOH questionnaires were administered at the time of enrollment. Semistructured interviews were performed at 3 months after diagnosis to explore the effect of SDOH on diabetes care and the impact of a CHW. Results. Seventeen caregivers were enrolled, 10 were randomly assigned to a CHW. Two-thirds of caregivers identified at least one SDOH need at enrollment; 35% of caregivers identified two SDOH needs. Interviews revealed that the two major themes identified as barriers to diabetes care were caregivers’ employment and financial issues. Social support was identified as a facilitator. The transition from hospital to home after the diagnosis of T1D was improved for families working with a CHW, and the CHW was identified as a strong source of support. Conclusions. There is a high prevalence of adverse SDOH in families from lower socioeconomic status at the time of diagnosis of pediatric T1D. These SDOH have a significant impact on families’ abilities to care for their children. Preliminary data suggest that CHWs can be a facilitator to the diabetes care. This trial is registered with NCT04238949.

The Relationship Between Glycated Hemoglobin and Time in Range in a Pediatric Population.

In adults with type 1 diabetes (T1D), time in range (TIR) [70-180 mg/dL] has been proposed as an additional metric besides glycated hemoglobin (HbA1c). This retrospective monocentric cohort study determined the correlation between HbA1c and TIR during the 2, 4, and 12 weeks (TIR2w, TIR4w, and TIR12w) before consultation in a pediatric T1D population. A total of 168 children with T1D were included. Continuous glucose monitoring data, HbA1c, and demographic variables were collected. We found strong linear correlations between HbA1c and TIR2w (R = -0.571), HbA1c and TIR4w (R = -0.603), and between HbA1c and TIR12w (R = -0.624). A strong correlation exists between TIR2w and TIR12w, HbA1c and time above range (TAR), and between TIR and TAR at different time points. In conclusion, a strong correlation was found between HbA1c and TIR, making TIR a potentially complementary metric to HbA1c. TIR2w seems a viable alternative to TIR12w. TAR also seems promising in assessing glycemic control.

Influencing factors for treatment escalation from metformin monotherapy in youth-onset type 2 diabetes in Northern Taiwan

With the increasing prevalence of obesity, childhood type 2 diabetes (T2D) is a growing concern in Taiwan. Unlike its adult counterpart, T2D in children exhibits a more aggressive nature and earlier onset of complications. Metformin represents the first line of drug, but if blood sugar levels do not improve, other drugs are used. This retrospective cohort study endeavors to scrutinize and assess the pattern of treatment modification and associate factors among 79 young people with T2D in Taiwan.The study categorized participants into three distinct groups based on their treatment trajectory and outcomes: (1) those maintaining metformin (n = 34); (2) cases achieving remission (n = 7); and (3) individuals experiencing escalation through oral drugs or insulin (n = 38). The average follow-up period spanned 3.48 years. Findings from univariate analysis using a Cox proportional hazards model and propensity score weighting revealed that HbA1c and weight gain correlated with elevated risk of treatment escalation. Conversely, factors such as hypertension, high weight or body mass index (BMI) SDS, leptin levels, c-peptide concentrations, peak c-peptide values during glucagon stimulation test and LDL-cholesterol levels were associated with reduced risk of escalation. However, in multivariate analyses employing stepwise selection, the sole predictive factor for treatment escalation emerged as weight gain one year post-therapy (HR: 1.06, p < 0.001).This study underscores the interconnectedness between weight management and the trajectory toward either treatment escalation or disease remission. Furthermore, it highlights the cost-effective potential of intervening in younger populations. Ultimately, these insights accentuate the considerable opportunity for enhancing health care management strategies concerning pediatric T2D in Taiwan.

Fracture patterns and associated risk factors in pediatric and early adulthood type 1 diabetes: Findings from a nationwide retrospective cohort study

PurposePeople with pediatric and early adulthood type 1 diabetes (T1D) might have a higher fracture risk at several sites compared to the general population. Therefore, we assessed the hazard ratios (HR) of various fracture sites and determined the risk factors associated with fractures among people with newly diagnosed childhood and adolescence T1D. MethodsAll people from the UK Clinical Practice Research Datalink GOLD (1987–2017), below 20 years of age with a T1D diagnosis code (n = 3100) and a new insulin prescription, were included and matched 1:1 by sex, age, and practice to a control without diabetes. Cox regression was used to estimate HRs of any, major osteoporotic fractures (MOFs) and peripheral fractures (lower-arm and lower-legs) for people with T1D compared to controls. The analyses were adjusted for sex, age, diabetic complications, medication (glucocorticoids, anti-depressants, anxiolytics, bone medication, anti-convulsive), Charlson-comorbidity-index (CCI), hypoglycemia, falls and alcohol. T1D was further stratified by diabetes duration, presence of diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) and boys versus girls. ResultsThe crude HRs for any fracture (HR: 1.30, CI95%: 1.11–1.51), lower-arm (HR: 1.22, CI95%: 1.00–1.48), and lower-leg fractures (HR: 1.54, CI95%: 1.11–2.13) were statistically significant increase in T1D compared to controls, but the effect disappeared in the adjusted analyses. For MOFs, no significant differences were seen. Risk factors in the T1D cohort were few, but the most predominantly one was a previous fracture (any fracture: HR: 2.00, CI95%: 1.70–2.36; MOFs: HR: 1.89, CI95%: 1.44–2.48, lower- arm fractures: HR: 2.08, CI95%: 1.53–2.82 and lower-leg fractures: HR: 2.08, CI95%: 1.34–3.25). Others were a previous fall (any fracture: HR: 1.54, CI95%: 1.20–1.97), hypoglycemia (Any fracture: HR: 1.46, CI95%: 1.21–1.77 and lower-leg fractures: HR: 2.34, CI95%: 1.47–3.75), and anxiolytic medication (Any fracture: HR: 1.52, CI95%: 1.10–2.11). Whereas girls had a lower risk compared to boys (Any fracture: HR: 0.78, CI95%: 0.67–0.90 and lower-arm fractures; HR: 0.51, CI95%: 0.38–0.68). The risk of any fracture in T1D did not increase with longer diabetes duration compared to controls (0–4 years: HR: 1.20, CI95%: 1.00–1.44; 5–9 years: HR: 1.17, CI95%: 0.91–1.50; <10 years: HR: 0.83, CI95%: 0.54–1.27). Similar patterns were observed for other fracture sites. Furthermore, one complication compared to none in T1D correlated with a higher fracture risk (1 complication: HR: 1.42, CI95%: 1.04–1.95). ConclusionThe overall fracture risk was not increased in pediatric and early adulthood T1D; instead, it was associated with familiar risk factors and specific diabetes-related ones.

Technology use and clinical outcomes in a racial-ethnic minority cohort of children and adolescents with type 1 diabetes.

Technology use has been shown to improve diabetes control, but minority youths tend to have low rates of technology use and exhibit suboptimal glycemic control. We examined the impact of continuous glucose monitors (CGM) and continuous subcutaneous insulin infusion (CSII) on glycemic control in a racial-ethnic minority cohort of children and adolescents with type 1 diabetes (T1D). A cross-sectional study was conducted among 140 pediatric T1D patients seen at a multidisciplinary clinic. From January to November 2022, data on demographics and glycated hemoglobin (HbA1c) levels were collected. Patients were categorized as technology (CGM, CSII, or both) or non-technology users (finger stick meter (FS) and multiple daily injections (MDI)). The majority identified as Hispanic (79 %) and had public health insurance (71 %). Sixty-nine percent used technology. Compared with non-technology users, technology users had significantly lower mean HbA1c levels (9.60 vs. 8.40 %, respectively) (p=0.0024), though no group (CGM+CSII, CGM+MDI, FS+CSII, and FS+MDI) achieved a mean HbA1c level of <7.0 %. Regarding minority status, no significant differences in mean HbA1c levels existed between Hispanics and Blacks in the CGM+MDI and FS+CSII groups (p=0.2232 and p=0.9224, respectively). However, there was a significant difference in mean HbA1c levels between Hispanic and Black non-technology users (9.19 vs. 11.26 %, respectively) (p=0.0385). Technology users demonstrated better glycemic control than non-technology users. Further research is needed to investigate factors affecting glycemic control in minority youths with T1D.

Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile.

Type 1 diabetes (T1D) is a serious autoimmune disease with high morbidity and mortality. Early diagnosis and treatment remain unsatisfactory. While the potential for development of T1D biomarkers in circulating exosomes has attracted interest, progress has been limited. This study endeavors to explore the molecular dynamics of plasma exosome proteins in pediatric T1D patients and potential mechanisms correlated with T1D progression. Liquid chromatography-tandem mass spectrometry with tandem mass tag (TMT)6 labeling was used to quantify exosomal protein expression profiles in 12 healthy controls and 24 T1D patients stratified by age (≤ 6 years old and > 6 years old) and glycated hemoglobin (HbA1c) levels (> 7% or > 7%). Integrated bioinformatics analysis was employed to decipher the functions of differentially expressed proteins, and Western blotting was used for validation of selected proteins' expression levels. We identified 1035 differentially expressed proteins (fold change > 1.3) between the T1D patients and healthy controls: 558 in those ≤ 6-year-old and 588 in those > 6-year-old. In those who reached an HbA1c level < 7% following 3 or more months of insulin therapy, the expression levels of most altered proteins in both T1D age groups returned to levels comparable to those in the healthy control group. Bioinformatics analysis revealed that differentially expressed exosome proteins are primarily related to immune function, hemostasis, cellular stress responses, and matrix organization. Western blotting confirmed the alterations in RAB40A, SEMA6D, COL6A5, and TTR proteins. This study delivers valuable insights into the fundamental molecular mechanisms contributing to T1D pathology. Moreover, it proposes potential therapeutic targets for improved T1D management.

Satisfaction with continuous glucose monitoring is positively correlated with time in range in children with type 1 diabetes

AimsContinuous glucose monitoring (CGM) can improve glucometrics in children with type 1 diabetes (T1D), and its efficacy is positively related to glucose sensor use for at least 60% of the time. We therefore investigated the relationship between CGM satisfaction as assessed by a robust questionnaire and glucose control in pediatric T1D patients. MethodsThis was a cross-sectional study of children and adolescents with T1D using CGM. The CGM Satisfaction (CGM-SAT) questionnaire was administered to patients and demographic, clinical, and glucometrics data were recorded. ResultsTwo hundred and ten consecutively enrolled patients attending 14 Italian pediatric diabetes clinics completed the CGM-SAT questionnaire. CGM-SAT scores were not associated with age, gender, annual HbA1c, % of time with an active sensor, time above range (TAR), time below range (TBR), and coefficient of variation (CV). However, CGM satisfaction was positively correlated with time in range (TIR, p < 0.05) and negatively correlated with glycemia risk index (GRI, p < 0.05). ConclusionsCGM seems to have a positive effect on glucose control in patients with T1D. CGM satisfaction is therefore an important patient-reported outcome to assess and it is associated with increased TIR and reduced GRI.

Development and Implementation of a Multidisciplinary Clinic Focused on the Care of Adolescents with Youth-Onset Type 2 Diabetes.

Diabetes self-management education and lifestyle interventions are the cornerstones of type 2 diabetes (T2D) care; however, the higher risk of comorbidities among youth with T2D requires a comprehensive care model. Traditionally, sub-specialty care relies on a referral model placing the burden on patients/families. In response, we developed a pediatric T2D multidisciplinary clinic (MDC)-A single physical location where patients can access various sub-specialists. The goals of the MDC are to aid with lifestyle modifications and provide referral/access to sub-specialists within the MDC, as determined through screening labs and assessment tools. We conducted a retrospective chart review of youth seen in the T2D MDC clinic at Cincinnati Children's Hospital from 1/2020 to 12/2021. We evaluated the frequency that youth met with each specialist and completion rates of annual screening labs. The cohort consisted of 227 youth with T2D (mean age 17.6 years, mean BMI 40.9kg/m2, 64% female, 50% Black or African American, 65% public insurance). All patients met with a diabetes provider and 81.2% met with a registered dietitian/certified diabetes education specialist. Exercise physiology met with 51.5% of patients, gastroenterology met with 34.8% of patients, social work met with 44.1% of patients, clinical psychology met with 27.3% of patients, and bariatric surgery met with 9.7% of patients. Percent completion of annual labs were: 98.2% for HbA1c, 84.6% for urine microalbumin, 83.7% for lipids, 90% for liver function, 59.5% for retinopathy, and 45.4% for the Patient Health Questionnaire-9. The majority of patients received diabetes and nutrition education and annual screening labs. Exercise counseling and sub-specialty care remain below 60% in part due to services not being available at every MDC. Our goals are to increase access to subspecialty care within the MDC's and consider additional care delivery methods to provide comprehensive care to youth with T2D.

Ongoing Increase in Incidence of Diabetes in Austrian Children and Adolescents (1989–2021): Results from a Nationwide Registry

Introduction. Since there is no uniform global diabetes trend in childhood and adolescence, regional epidemiological surveys of diabetes incidences are important. In Austria, the incidences of type 1 diabetes (T1D), type 2 diabetes (T2D), and other forms of diabetes have been recorded for decades. Methods. To analyze recent developments of diabetes incidence within the decades long-standing Austrian nationwide prospective population-based incidence study for diabetes in children aged &lt;15 years. We estimated time trends of age-standardized rates from 1989 to 2021 for T1D and T2D by joinpoint analysis. Annual percent changes (APCs) were calculated. Case ascertainment was 97%. Results. We observed an unusual increase of T1D incidence in the year 2021, reaching a peak of 28.7/100,000/PY (person years). From 2011 to 2020, there had been a constant plateau phase in the total cohort (APC 0.78, 95% CI [−0.99, 2.58], p = 0.379 ), which had followed a steep increase of T1D incidence (APC 4.6, 95% CI [3.94, 5.19], p &lt; 0.001 ) from 1989 to 2011. Age-specific differences in T1D incidence development were observed. For the first time, we observed a statistically significant constant increase in T2D during the observation period (APC 3.47, 95% CI [0.76, 6.26], p = 0.014 ). Other forms of diabetes are two times more common than T2D in this age group. Conclusion. The incidence of T1D in Austrian children &lt;15 years is still increasing and showed a peak in 2021. For the first time, a significant increase in pediatric T2D was observed in Austria.