Pediatric Diabetes[JOURNAL]
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200 papers
Comparative Effectiveness of Switching From First-Generation Basal Insulins to Either Glargine 300 U/mL or Degludec 100 U/mL in Children and Adolescents With Type 1 Diabetes: Results From the ISPED CARD Clinical Registry.
Rabbone I, Bonfanti R, Graziano G … +6 more , Lombardo F, Nicolucci A, Marigliano M, Rossi MC, Vespasiani G, Cherubini V
Pediatr Diabetes · 2025 · PMID 41323155 · Full text
BACKGROUND: To assess the real-world effectiveness of switching from first-generation basal insulins (1BIs) to either glargine U300 (Gla-300) or degludec U100 (Deg-100) in children and adolescents with type 1 diabetes (T...
BACKGROUND: To assess the real-world effectiveness of switching from first-generation basal insulins (1BIs) to either glargine U300 (Gla-300) or degludec U100 (Deg-100) in children and adolescents with type 1 diabetes (T1D), using data from the Italian ISPED CARD clinical registry. MATERIALS AND METHODS: This multicenter retrospective observational study included 1063 pediatric patients with T1D from 22 diabetes centers across Italy who switched from 1BI to either Gla-300 (64.6%) or Deg-100 (35.4%) between 2021 and 2023. Propensity score matching (PSM) was applied to create comparable groups ( = 353 per group). Primary endpoint was the change in HbA1c at 6 months. Secondary endpoints included fasting blood glucose (FBG), standardized body mass index (BMI/SDS), and insulin doses at 6 and 12 months. Longitudinal models for repeated measures were used to assess treatment effectiveness. RESULTS: Both groups showed significant and clinically relevant reductions in HbA1c at 6 months from ~ 8.7% to ~ 7.4% (-1.3 percentage points), maintained at 12 months, with no significant differences between groups. FBG also decreased significantly in both groups, slightly favoring Deg-100, but without statistical significance between groups. BMI/SDS remained stable. Gla-300 was associated with a slight increase in basal insulin dose over 12 months, while Deg-100 showed a temporary reduction at 6 months. A significant reduction in short-acting insulin dose (-0.03 U/kg) was observed in both groups. CONCLUSION: Switching from 1BI to either Gla-300 or Deg-100 significantly improves glycemic control in pediatric T1D patients without weight gain. Although both insulins showed comparable effectiveness, differences in titration patterns highlight the need for individualized treatment strategies and improved clinician education in insulin optimization. Safety outcomes, particularly hypoglycemia, could not be assessed.
Acidosis at Diagnosis of Type 1 Diabetes Mellitus: Relation With Kidney Function.
Guarino S, Iafusco D, Di Sessa A … +8 more , Tirelli P, Rivetti G, Ippolito G, Bartiromo M, Cirillo G, Zanfardino A, Miraglia Del Giudice E, Marzuillo P
Pediatr Diabetes · 2025 · PMID 41293549 · Full text
AIMS: Acidosis at type 1 diabetes mellitus (T1DM) onset results from unregulated massive overproduction of ketoacids. However, renal tubular damage (RTD), a complication of T1DM onset, may impair bicarbonate reabsorption...
AIMS: Acidosis at type 1 diabetes mellitus (T1DM) onset results from unregulated massive overproduction of ketoacids. However, renal tubular damage (RTD), a complication of T1DM onset, may impair bicarbonate reabsorption, exacerbating acidosis. We aimed to assess RTD role in acidosis at T1DM onset. METHODS: RTD was defined by urinary β2-microglobulin > 0.33 mg/L and/or neutrophil gelatinase-associated lipocalin (NGAL) > 95 percentile for age. Acute kidney injury (AKI) was classified using Kidney Disease/Improving Global Outcomes (KDIGO) criteria. Participants were grouped by serum ketone levels (cut-off: 3 mmol/L, above which indicates diabetic ketoacidosis [DKA]) and bicarbonate levels (cut-off: 22 mmol/L, below which indicates acidosis):- Group 1: Ketones ≥ 3 mmol/L, bicarbonate < 22 mmol/L.- Group 2: Ketones < 3 mmol/L, bicarbonate < 22 mmol/L.- Group 3: Ketones ≥ 3 mmol/L, bicarbonate ≥ 22 mmol/L.- Group 4: Ketones < 3 mmol/L, bicarbonate ≥ 22 mmol/L. RESULTS: Of 185 individuals, 111 (60%) were in Group 1, 18 (9.7%) in Group 2, 8 (4.3%) in Group 3, and 48 (26%) in Group 4. Group 1 had the most severe clinical and biochemical derangements, followed by Groups 2, 3, and 4. Logistic regression, adjusted for AKI, relative difference of weight loss and glycated hemoglobin (HbA1c), identified RTD (odds ratio [OR] = 22.3; 95% confidence interval [CI]: 6.9-71.5; < 0.001), and relative difference of weight loss, (OR = 1.2; 95% CI: 1.1-1.4; < 0.006), as significant factors associated with Group 1 and only RTD (OR = 29.9; 95% CI: 3.0-292.9; =0.004) as significant factor associated with Group 2. Serum bicarbonate and blood pH showed an inverse correlation with urinary NGAL ( = 0.61 and 0.56, respectively, both < 0.001) and β2-microglobulin ( = 0.67 and 0.59, respectively, both < 0.001), regardless of ketone levels. The ketone-to-bicarbonate ratio predicted RTD (area under the receiver-operating characteristic (ROC) curve (AUROC) = 0.94; 95% CI: 0.91-0.97; < 0.001), while serum bicarbonate levels predicted normal renal tubular function (AUROC = 0.95; 95% CI: 0.92-0.98; < 0.001). CONCLUSIONS: A link exists between biological markers of RTD and metabolic acidosis at T1DM onset.
Diabetes Treatment Satisfaction Is Associated With Health-Related Quality of Life Among Parents and Children With Type 1 Diabetes.
Agenäs H, Ödling M, Brorsson AL … +2 more , Kull I, Lindholm-Olinder A
Pediatr Diabetes · 2025 · PMID 41283064 · Full text
BACKGROUND: Type 1 diabetes (T1D) requires numerous daily self-management decisions and, for children, parents have a crucial role in this. The aim of this study was to evaluate treatment satisfaction among parents of ch...
BACKGROUND: Type 1 diabetes (T1D) requires numerous daily self-management decisions and, for children, parents have a crucial role in this. The aim of this study was to evaluate treatment satisfaction among parents of children with T1D and the associations with the child's health-related quality of life (HRQoL) and perceived diabetes control. A secondary aim was to evaluate treatment satisfaction among school children with T1D and the associations with HRQoL and perceived diabetes control. METHODS: In this cross-sectional study, 111 parents of children with T1D (0-12 years) and 75 children with T1D (8-12 years) were included. Treatment satisfaction was measured using the diabetes treatment satisfaction questionnaire (DTSQ), parent version, scored 0-60, or teens version, scored 0-48. HRQoL was measured with DISABKIDS. Differences between groups were analyzed using independent -tests and one-way analysis of variance. Linear regression was used to investigate associations between treatment satisfaction and HRQoL and perceived diabetes control. RESULTS: The mean value for treatment satisfaction among parents was 41.0 (95% confidence interval (CI): 39.5-42.5) and among children 36.3 (95% CI: 34.5-38.0). Parents' treatment satisfaction was associated with their child's HRQoL (by proxy), perceived diabetes control, and diabetes duration (correlations coefficient [ ] = 0.54, < 0.001). Children's treatment satisfaction was associated with HRQoL ( = 0.29, =0.005). CONCLUSION: The child's HRQoL and perceived diabetes control are important for treatment satisfaction among parents of children with T1D.
Sex-Based Differences in BMI and LDL-C Trajectories Following Type 1 Diabetes Diagnosis in Youth.
Tas E, Movva S, Muzumdar U … +1 more , Libman I
Pediatr Diabetes · 2025 · PMID 41262843 · Full text
INTRODUCTION: Cardiovascular disease (CVD) disproportionately affects females with type 1 diabetes (T1D), yet the emergence of sex-specific metabolic risk during early disease remains unclear. We evaluated whether sex di...
INTRODUCTION: Cardiovascular disease (CVD) disproportionately affects females with type 1 diabetes (T1D), yet the emergence of sex-specific metabolic risk during early disease remains unclear. We evaluated whether sex differences in BMI percentile (BMIp) and LDL-cholesterol (LDL-C) trajectories appear within the first 2 years following T1D diagnosis. METHODS: We conducted a retrospective cohort study of 542 youth with new-onset T1D (mean age 10.4 ± 3.9 years; 54.1% male) and assessed sex differences in BMIp and LDL-C trajectories using linear mixed-effects models, adjusting for age, HBA1c and diabetic ketoacidosis (DKA) status at diagnosis, and baseline weight category (LDL-C model only). RESULTS: At diagnosis, median BMIp did not differ by sex (females: 50.9 [IQR: 19.2-84.1] vs. males: 63.0 [17.8-93.0]; =0.15). Over 2 years, females experienced significantly greater BMIp increases (median change: 27.4 [5.1, 49.7] vs. 13.1 [-4.3, 30.5] percentage points; =0.002). Adjusted models confirmed steeper increases in BMIp for females compared to males (sex × time interaction: 7.54 [3.13, 11.94]; < 0.001). LDL-C was higher in females at diagnosis (2.51 ± 0.80 vs. 2.30 ± 0.70 mmol/L [97 ± 31 vs. 89 ± 27 mg/dL]; =0.003) and follow-up (2.25 ± 0.59 vs. 2.12 ± 0.65 mmol/L [87 ± 23 vs., 82 ± 25 mg/dL]; =0.02), with adjusted models confirming a persistent difference (0.17 [0.06, 0.27] mmol/L [6.39 [2.39, 10.40] mg/dL]; =0.002). DISCUSSION: Females with T1D exhibit steeper early increases in adiposity and persistently higher LDL-C levels compared to males, independent of age, glycemic control, and DKA status at diagnosis. These findings underscore the importance of sex-specific metabolic monitoring and early intervention beginning at diagnosis to mitigate long-term cardiovascular risk.
Comorbidity of Type 1 Diabetes and ADHD: A Longitudinal Cohort Study in Males and Females From the Norwegian Childhood Diabetes Registry.
Bakke KA, Brunborg C, Midtlyng E … +2 more , Helverschou SB, Skrivarhaug T
Pediatr Diabetes · 2025 · PMID 41255955 · Full text
AIMS: This study of interactions between attention-deficit hyperactivity disorder (ADHD) and type 1 diabetes has two aims. First, compare the prevalence of prescribed ADHD medications in individuals with type 1 diabetes...
AIMS: This study of interactions between attention-deficit hyperactivity disorder (ADHD) and type 1 diabetes has two aims. First, compare the prevalence of prescribed ADHD medications in individuals with type 1 diabetes to the general paediatric population in Norway. Second, study trajectories in mean glycated haemoglobin (HbA1c) in individuals with comorbid ADHD in comparison to individuals with type 1 diabetes only. METHODS: Part 1 uses data from the Norwegian Prescription Database and register linkage between the Norwegian Childhood Diabetes Registry (NCDR) and the Norwegian Prescribed Drug Registry to obtain yearly prevalence in the general population and NCDR between 2005 and 2019. Part 2 uses data from annual controls in NCDR between 2005 and 2022. Linear mixed-effects models adjusted for age and diabetes duration were used to compare mean HbA1c in 365 individuals (66% males) with comorbid ADHD to 5,888 individuals (54% males) with type 1 diabetes only. RESULTS: Part 1: Yearly prevalence (2009-2019) ranged from 0.02 to 0.52 percentage points higher in NCDR than in the general population. The difference was significant only for 2017. Part 2: Mean national HbA1c decreased from 2012 to 2022 but was higher in individuals with comorbid ADHD. This difference was significant from 2016 (67.6 mmol/mol [8.3%] vs. 64.5 mmol/mol [8.1%]) to 2022 (57.5 mmol/mol [7.4%] vs. 54.7 mmol/mol [7.2%]). When grouped by sex, these differences continued to be significant in males (except in 2018), but not in females. Individuals with ADHD were more likely to have experienced at least one episode of diabetic ketoacidosis (odds ratio [OR] = 1.39, 95% confidence interval [CI] [1.04, 1.86]; males: OR = 1.65, 95% CI [1.15, 2.36]; females: OR = 1.10, 95% CI [0.658, 1.83]). CONCLUSION: Mean national HbA1c decreased in Norway during the last decade, but continued to be higher in individuals with comorbid ADHD than in individuals with type 1 diabetes only.
Lived Experiences of Coping With Type 1 Diabetes Among Palestinian Youth: A Qualitative Study.
Nazzal B, Harazni L, Aqtam I … +2 more , Anabtawi R, Ayed A
Pediatr Diabetes · 2025 · PMID 41216603 · Full text
BACKGROUND: Type 1 diabetes mellitus (T1DM) in adolescents requires continuous self-care and emotional adjustment. Palestinian youth with T1DM face unique challenges within the context of the West Bank healthcare system,...
BACKGROUND: Type 1 diabetes mellitus (T1DM) in adolescents requires continuous self-care and emotional adjustment. Palestinian youth with T1DM face unique challenges within the context of the West Bank healthcare system, where political instability, resource limitations, and cultural factors create additional barriers to optimal diabetes management. These youth experience heightened social stigma, cultural dietary pressures, and restricted access to specialized healthcare services. AIM: To explore the lived experiences, challenges, and coping strategies of Palestinian youth with T1DM in the West Bank. METHODS: This qualitative content analysis study was conducted from May-June 2025. Eighteen Palestinian adolescents (12-18 years) with T1DM were recruited through purposive sampling from West Bank diabetes clinics. Participants were approached directly at clinics by trained researchers who explained the study's voluntary nature and ensured understanding that participation would not affect clinical care. For minors under 16, guardians were present during consent, and all participants provided appropriate consent/assent. Data were collected via semi-structured interviews (45-90 min) and analyzed using conventional content analysis methods. Credibility was established through prolonged engagement, peer debriefing, and member checking with five participants. RESULTS: Four main themes emerged from the analysis: challenges from social and cultural pressures, including stigma and dietary expectations; reliance on support systems involving family, peers, and healthcare access; emotional and spiritual coping through resilience, anxiety management, and faith-based strategies; daily self-management focused on insulin routines and food planning. Participants described significant barriers, including limited healthcare resources, medication shortages, cultural food pressures during religious fasting periods, and social misunderstandings about diabetes. Despite these challenges, many demonstrated remarkable resilience through family support, religious coping, and adaptive self-care routines. CONCLUSION: Palestinian adolescents with T1DM navigate complex challenges that extend beyond medical management to include cultural, social, and political barriers. Their coping strategies are deeply embedded in family support systems and religious faith. The findings highlight the critical need for culturally responsive, family-centered diabetes care that addresses both medical and psychosocial needs while considering the unique context of life in the West Bank.
HLA-C 0304 Associates With Beneficial Gut Microbiota and Later Onset of Type 1 Diabetes in Pediatric Cohorts.
Xu Z, Li X, Yuan X … +14 more , Sun C, Zhang M, Chen R, Wei H, Chen L, Du H, Li G, Yang Y, Chen X, Cui L, Fang X, Wu J, Li Q, Luo F
Pediatr Diabetes · 2025 · PMID 41195309 · Full text
OBJECTIVE: To investigate whether human leukocyte antigens (HLAs) influence gut microbiota composition and contributes to delayed type 1 diabetes mellitus (T1DM) onset in children. METHODS: This multicenter cross-section...
OBJECTIVE: To investigate whether human leukocyte antigens (HLAs) influence gut microbiota composition and contributes to delayed type 1 diabetes mellitus (T1DM) onset in children. METHODS: This multicenter cross-sectional study included 106 newly diagnosed pediatric T1DM patients (age <18 years) and 69 healthy controls from nine Chinese cities. Gut microbiota was profiled via whole-metagenome shotgun sequencing, and HLA alleles were genotyped by PCR sequence-based typing. Participants were stratified by HLA-risk scores. Statistical analyses included α/β-diversity metrics, linear discriminant analysis effect size analysis (LEfSe), and Spearman correlation adjusted for confounders. RESULTS: Principal coordinates analysis (PCoA) exposed discernible disparities in gut microbiota structures within the high-HLA-risk T1DM cohort relative to both high- and low-HLA-risk control groups ( = 0.0562, =0.003 and = 0.0343, =0.003). HLA-C 0304 carriers exhibited delayed T1DM onset compared to noncarriers (adjusted = 0.225, =0.017). High-HLA-risk T1DM patients showed distinct microbiota divergence from controls ( = 0.0562, =0.003), driven by reduced Lachnospiraceae and (butyrate producers) in noncarriers. Conversely, HLA-C 0304-positive T1DM patients had enriched (=0.005) and Lachnospiraceae (=0.039), alongside lower opportunistic pathogens (; < 0.05). High-HLA-risk patients also displayed lower fasting C-peptide levels than low-risk counterparts (0.19 ± 0.14 vs. 0.26 ± 0.19 µg/mL, =0.029). CONCLUSIONS: Our study demonstrates that specific HLA class I subtypes (e.g., C 0304) may modulate T1DM onset through selective enrichment of beneficial gut microbiota. Elucidating the mechanisms by which HLA variants regulate mucosal immunity and coordinate HLA-microbiota-immune interactions holds significant potential for developing targeted interventions against T1DM pathogenesis.
Caring Under Constraints: A Qualitative Study of Parental Needs in Pediatric Diabetes in Zabol.
Hedayati S, Sotoudeh A, Mohabati F
Pediatr Diabetes · 2025 · PMID 41185648 · Full text
AIM: This study aimed to explore the lived experiences and support needs of parents caring for children with type 1 diabetes mellitus (T1DM) in Zabol, Iran, a rural and resource-scarce region. METHODS: A qualitative phen...
AIM: This study aimed to explore the lived experiences and support needs of parents caring for children with type 1 diabetes mellitus (T1DM) in Zabol, Iran, a rural and resource-scarce region. METHODS: A qualitative phenomenological design was employed with 36 parents (25 mothers and 11 fathers) of children aged 4-17 years who had lived with T1DM for at least 6 months. Semistructured interviews were conducted in Persian, transcribed, translated, and thematically analyzed using Braun and Clarke's six-step framework, in accordance with Consolidated Criteria for Reporting Qualitative Research (COREQ) reporting guidelines. RESULTS: Three overarching themes emerged. Parents reported emotional and practical support gaps, including caregiver exhaustion, lack of respite opportunities, and limited guidance. They described social isolation and stigma driven by cultural misconceptions such as viewing diabetes as a curse, which led to exclusion of both parents and children. Families also faced healthcare system challenges, including limited specialist access, insufficient diabetes education, financial strain (2-15 million IRR monthly), and inadequate resources, all exacerbated by rural isolation. CONCLUSIONS: Parents of children with T1DM in Zabol experience substantial unmet emotional, social, and systemic needs. Addressing these challenges requires structured peer support, culturally sensitive community education to reduce stigma, and expanded access to affordable healthcare. These findings provide a foundation for developing targeted interventions to strengthen resilience and improve outcomes among families in underserved rural regions.
Depressive Symptoms and Glycemic Control Among Children and Adolescents With Diabetes: The Mediation Effect of Self-Care Behaviors.
Song H, Huang Y, Li J … +4 more , Ding Y, Luo Z, Chen M, Cao X
Pediatr Diabetes · 2025 · PMID 41181380 · Full text
OBJECTIVE: This study aimed to assess the association between depressive symptoms and glycemic control among children and adolescents with diabetes and to determine if their self-care behaviors mediate this association....
OBJECTIVE: This study aimed to assess the association between depressive symptoms and glycemic control among children and adolescents with diabetes and to determine if their self-care behaviors mediate this association. METHODS: A total of 207 patients of children and adolescents with diabetes were included in a cross-sectional survey study. The Chinese version of the Children's Depression Inventory (CDI) was used to evaluate the depressive symptoms of the patients. The Chinese version of the Summary of Diabetes of Self-Care Activities (SDSCA) was used to evaluate the level of diabetes self-care behaviors. The values of HbA1c of children and adolescents with diabetes were obtained from patients' medical history cases or self-reporting. Structural equation modeling (SEM) was used to examine the mediation effect of self-care behaviors between depressive symptoms and glycemic control. RESULTS: In 207 children and adolescents with diabetes, the total score of depressive symptoms was 12.71 ± 6.73 and the total score of self-care behaviors was 42.31 ± 14.09. The HbA1c of the patients was 9.14 ± 2.55%. High depressive symptoms and low self-care behaviors are related to high levels of HbA1c (all < 0.001). The results revealed that the effect of depressive symptoms on glycemic control was partly mediated by self-care behaviors and the mediation effect accounts for 30.65% of the total effect. CONCLUSIONS: Depressive symptoms show a significant association with glycemic control among children and adolescents with diabetes, with self-care behaviors serving as a partial mediator in this relationship. Depressive severity may influence glycemic control partly by affecting self-care behaviors.
Change in Age of Diagnosis and Demographics of Type 1 Diabetes Mellitus During the COVID-19 Era.
Sracic K, Uli N, Heksch R
Pediatr Diabetes · 2025 · PMID 41141333 · Full text
Since COVID-19 onset, pediatric endocrinologists have been making an assumption that there was a shift in diagnosis age of type 1 diabetes mellitus (T1DM) to younger children. Younger children are more likely to present...
Since COVID-19 onset, pediatric endocrinologists have been making an assumption that there was a shift in diagnosis age of type 1 diabetes mellitus (T1DM) to younger children. Younger children are more likely to present in DKA, are more difficult to diagnose and treat, and age at diagnosis can affect prognosis. We performed a retrospective chart review of patients diagnosed with T1DM for 3 years before COVID-19 and the 3 years during COVID-19. Demographics were evaluated using the Chi-squared test for categorical data and Student's -test or ANOVA for continuous data. During this time, 698 patients were diagnosed with T1DM, with more patients during COVID-19. The average age of diagnosis significantly increased by 0.7 years (=0.025). There was a significant difference in the distribution of age groups between the two time periods (=0.0065). There was a significant decrease in new cases among patients between the ages of 2-5 years from 2017 to 2020, a transient finding as they reverted back to previous rates by 2022. New diagnoses between 13 and 18 years were increasing prior to 2020 (7%-23%), subsequently leveling out. Patients were 1.6 times more likely to present in DKA during COVID-19; however, there was no significant change in hemoglobin A1c (HbA1c). There was no significant change in thyroperoxidase (TPO) antibody positivity. There was a significant decrease (=0.018) in patients with elevated tissue transglutaminase (TTG)-IgA from pre-COVID to post-COVID. Average age at diagnosis in our cohort increased since the start of COVID-19, contradicting previous studies and our hypothesis. The number of new cases increased, and the age distribution changed. There was a significant decrease in number of younger patients in 2020, followed by a normalization of new cases in those 2-5 years old, which may have led to the belief that more toddlers were being diagnosed. The rate of other antibodies did not increase. These results illustrate that changes in demographics may have been short-lived post-COVID-19.
Integration of Proteomic and Lipidomic Analysis Reveals Potential Markers of Insulin Resistance in Young Children With Obesity.
Liu L, Zhou J, Guo S … +6 more , Lian B, Zhang H, Dong Y, Liu Y, Zhang S, Yin C
Pediatr Diabetes · 2025 · PMID 41112506 · Full text
OBJECTIVE: This study aimed to identify novel proteomic and lipidomic biomarkers of insulin resistance (IR) in young children with obesity and to assess the ability of hub lipids and proteins in the diagnosis of IR. METH...
OBJECTIVE: This study aimed to identify novel proteomic and lipidomic biomarkers of insulin resistance (IR) in young children with obesity and to assess the ability of hub lipids and proteins in the diagnosis of IR. METHODS: The discovery cohort consisted of 50 prepubertal children, including 30 children with obesity and 20 lean. The validation cohort included 25 children with obesity and IR (obese-IR) and 25 children with obesity without IR (obese-NIR). Fasting plasma was collected from all participants for Olink proteomics and untargeted lipidomics. Pearson correlation analysis was used to identify proteins and lipids associated with IR, and area under the receiver operating characteristic (AUROC) was applied to compare the ability of the identified proteins and lipids with traditional indices in the diagnosis of IR. RESULTS: In the discovery cohort, a total of 15 lipids and 10 proteins had significant correlation with IR. In the validation cohort, protein fatty acid binding protein 4 (FABP4) and gene serpin family E member 1 (PAI) were overexpressed in obese-IR children compared to obese-NIR children, while insulin like growth factor binding protein 1 (IGFBP-1) and paraoxonase 3 (PON3) were lower in the IR group than in the obese-NIR group; five lipids including sphingosine (d16:0), coenzyme (Q8), ceramides phosphate (d42:2), phosphatidylethanolamine (37:2e), and phosphatidylcholine (18:1e_16:0), showed significant ( < 0.05) change in obese-IR children compared to obese-NIR children. In addition, the AUC-ROC was 0.89 for IGFBP-1, 0.81 for PON3, and 0.65 for PAI. The ability of IGFBP-1, PON3, and PAI to diagnose IR was better than that of adiponectin and leptin. The AUROC of phosphatidylcholine (18:1e_16:0) and coenzyme (Q8) were 0.80 and 0.73, respectively, which was significantly higher than the AUROC of triglycerides(TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). CONCLUSION: Proteomic and lipidomic analysis can allow for the identification of potential new candidate biomarkers for IR. The ability of novel biomarkers to diagnose IR was better than traditional indicators. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2300072179.
Diabetes Insipidus as an Early Clinical Indicator of Wolfram Syndrome Type 1: Evidence From a Symptom-Based Screening Approach.
Gundogdu Ogutlu OB, Cayır A, Donmez AS … +3 more , Koca SB, Yarali O, Demirbilek H
Pediatr Diabetes · 2025 · PMID 41080637 · Full text
Wolfram Syndrome Type 1 (WS1) is a rare neurodegenerative disorder characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and deafness (D) due to biallelic mutations in the gene. As the ca...
Wolfram Syndrome Type 1 (WS1) is a rare neurodegenerative disorder characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and deafness (D) due to biallelic mutations in the gene. As the cardinal symptoms of DI, polyuria and polydipsia, overlap with those of DM, DI might be underdiagnosed or delayed in the early stages of WS1. In the present study, we assessed whether DI could be an early sign of WS1 and analyzed genotype-phenotype correlations in a group of Turkish patients with Type 1 DM. We applied a polyuria/polydipsia questionnaire to 1278 children with Type 1 DM. Patients with suggestive symptoms of DI were further evaluated for other clinical features of WS1 and molecular genetic analysis of the gene. Clinical, laboratory, and genetic characteristics of cases identified using questionnaires were compared with a historical case series of seven children with WS1 and previously published literature data. Eighteen patients were considered to have a diagnosis of DI, thereby being eligible for genetic analysis of variants. Of those, six had biallelic variations (four missense variants, one in-frame duplication, and three frameshift variants) in the gene, and a diagnosis of WS1 was confirmed. The age of admission for DM was younger in the historical cases (5.1 ± 2.0 vs. 8.7 ± 3.4; =0.04). There was no statistically significant difference between the ages for the diagnosis of WS1 (12.9 ± 5.0 vs. 9.6 ± 2.7; =0.191), though the diagnostic delay from DM onset to WS1 diagnosis was significantly shorter in the screened group (median 1.8 vs. 6.9 years; ≈ 0.015). Our findings suggest that DI may present before OA in WS1. Enriching the diagnosis of DI using a simple polyuria/polydipsia questionnaire may provide an earlier diagnosis of WS1 in patients followed with Type 1 DM. Screening and early genetic testing of these patients enhances the diagnosis, follow-up, and management strategies of patients with WS1.
Alterations of Sublingual Microcirculation in Children With Compensated Type 1 Diabetes Mellitus-An Observational Study.
Krausova V, Neumann D, Stichova L … +3 more , Skvor J, Dostalova V, Dostal P
Pediatr Diabetes · 2025 · PMID 41064468 · Full text
INTRODUCTION: Type 1 diabetes is commonly associated with microvascular complications. Sublingual microcirculation examination using sidestream dark-field (SDF) imaging can reflect the situation in visceral microcirculat...
INTRODUCTION: Type 1 diabetes is commonly associated with microvascular complications. Sublingual microcirculation examination using sidestream dark-field (SDF) imaging can reflect the situation in visceral microcirculation. The main goals of this observational study were to assess the feasibility of SDF imaging in children with compensated type 1 diabetes, determine selected sublingual microcirculation parameters, and compare them with parameters obtained in healthy children. METHODS: In total 30 children with stable type 1 diabetes without clinical or laboratory signs of microvascular complications were included in the study, 15 males and 15 females in three age categories. Three video clips were recorded using an SDF probe from different parts of the sublingual area and analyzed by software-aided offline analysis. RESULTS: Videoclips were successfully recorded in all children. Compared with healthy children, the De Backer score (DeBS) in females and total vessel density (TVD), small vessel density (SVD), perfused vessel density (PVD), and perfused SVD (PSVD) in both genders were significantly lower in children with T1D. There were no differences in TVD, SVD, PVD, PSVD, and DeBS between age or gender categories. DeBS correlated with ketonemia; otherwise, no significant relationship was observed between microcirculatory and other recorded parameters. CONSLUSIONS: Sublingual microcirculation examination using SDF imaging is feasible in children with type 1 diabetes. Alteration of sublingual microcirculatory parameters is detectable in children with type 1 diabetes before they show clinical or laboratory signs of any microvascular complication. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05958264.
Identification of Peripheral Blood Endotypes Associated With Age in Pediatric Type 1 Diabetes.
Gomez-Muñoz L, Perna-Barrull D, Ventura PS … +4 more , Valls A, Castiello F, Vives-Pi M, Murillo-Vallés M
Pediatr Diabetes · 2025 · PMID 41049864 · Full text
This study aimed to identify age-related peripheral immune endotypes in pediatric patients with type 1 diabetes (T1D) at disease onset and assess their metabolic control 1 year post-diagnosis. Immune cell subpopulations...
This study aimed to identify age-related peripheral immune endotypes in pediatric patients with type 1 diabetes (T1D) at disease onset and assess their metabolic control 1 year post-diagnosis. Immune cell subpopulations (T and B lymphocytes, myeloid cells, and natural killer [NK] cells) were analyzed via multicolor flow cytometry in pediatric T1D patients and age- and sex-matched controls, grouped as <7 years, 7-12 years, and >12 years. Sociodemographic, clinical, and metabolic data were collected, including autoantibodies, bicarbonate (HCO), C-peptide, HbA1c, and time in range (TIR), with follow-up for 1 year to evaluate partial remission (PR) likelihood and metabolic control. Patients <7 years showed reduced regulatory immune cells (memory/activated regulatory T lymphocytes (Tregs), regulatory B cells, and Th17) and more severe disease onset (shorter symptoms, greater acidosis, and lower C-peptide). Ages 7-12 exhibited increased memory B cells, particularly the unswitched ones. Myeloid cells showed no significant variation in T1D, despite age trends in controls. Anti-insulinoma-antigen 2 (IA2) titers were lower in patients >12 years, while anti-glutamic acid decarboxylase 65 (GAD65) positivity remained constant. Younger patients had lower PR rates and poorer glycemic control at 1 year. Younger patients face greater immune dysregulation and β-cell loss, while older patients show better immune maturity and metabolic outcomes. These differences underline the need for age-specific T1D therapies.
Effect of an Intensive, Integrated Telehealth Intervention on Glycemic Control in Children and Adolescents With Type 1 Diabetes Using Continuous Glucose Monitoring: A Randomized, Crossover Trial.
Deeb A, Eldeeb L, Suliman S … +5 more , Chaturvedi D, Tomy M, Alkahlout G, Beck RH, Qahtani NA
Pediatr Diabetes · 2025 · PMID 41049863 · Full text
To examine the impact of adding an intensive, integrated telehealth intervention on glycemic control in children and adolescents with type 1 diabetes using continuous glucose monitoring (CGM) and multiple daily injection...
To examine the impact of adding an intensive, integrated telehealth intervention on glycemic control in children and adolescents with type 1 diabetes using continuous glucose monitoring (CGM) and multiple daily injections (MDIs) of insulin. In this randomized, two-period crossover trial conducted between May 2023 and June 2024, 105 children and adolescents with type 1 diabetes using FreeStyle Libre 2 CGM were randomized to receive intensive telehealth weekly over 12 weeks first followed by routine care ( = 50) or routine care over 12 weeks first followed by intensive telehealth weekly ( = 55), with a 2-week washout. Intensive telehealth was intensified follow-up with weekly teleconsultation (20 min, by telephone) and digital support from a trained diabetes educator delivering structured support, including review of the latest ambulatory glucose profile. The primary outcome measures were HbA1c and GCM metrics. The average (SD) age of the study cohort ( = 105) was 11.8 (4.2) years, 48.6% were female, with an average diabetes duration of 3.5 (3.0) years and suboptimally controlled diabetes in terms of HbA1c levels (9.4 (1.6) %, target < 6.5%), and other 14-day CGM metrics. Compared with routine care, intensified follow-up with weekly intensive telehealth was associated with a decrease in HbA1c (-0.29 (0.60) %, 95%CIs -0.41 to -0.17, < 0.001), significantly increased time in range (TIR), and decreased time above range (TAR), average glucose level, glucose variability, glucose management indicator (GMI), and frequency of low glucose events. Teleconsultation did not affect time below range (TBR), which was already within target. This randomized, controlled, and crossover study shows that intensified follow-up with a weekly telehealth intervention results in small but significant improvements in glycemic control metrics in children and adolescents. The clinical impact of these changes requires prospective study.
Predictors of Transitions From GADA as the Initial Autoantibody to Multiple Autoantibodies of Type 1 Diabetes in Children at Risk by a Dynamic Prediction Model.
You L, Salami F, Tamura R … +10 more , Törn C, Vehik K, Hagopian WA, Rewers MJ, McIndoe RA, Toppari J, Ziegler AG, Akolkar B, Krischer JP, Lernmark Å
Pediatr Diabetes · 2025 · PMID 40994736 · Full text
To design a dynamic prediction model for estimating the time of progression from a single glutamic acid decarboxylase autoantibody (GADA) to multiple islet autoantibodies and type 1 diabetes in children, exploring differ...
To design a dynamic prediction model for estimating the time of progression from a single glutamic acid decarboxylase autoantibody (GADA) to multiple islet autoantibodies and type 1 diabetes in children, exploring different longitudinally measured risk variables. GADA-positive children ( = 379) participating in The Environmental Determinants of Diabetes in the Young (TEDDY) study were followed for the appearance of additional autoantibodies against either insulin autoantibody (IAA), insulinoma-like 2 autoantibody (IA-2A), or zinc transporter 8 antibody (ZnT8A) and type 1 diabetes. A dynamic prediction model was designed, including trajectories of longitudinal risk variables, autoantibody titers, and metabolic variables (C-peptide, glucose, and HbA1c) together with time-invariant variables (gender, age at GADA positivity, and high-risk HLA genotypes). Transition risk from GADA to multiple autoantibodies was increased by lower age ( < 0.001) and by increased GADA titers during follow-up ( < 0.001), and was less likely in children with HLA DQ2/X but not DQ2/8 (=0.004). The transition risk from multiple autoantibodies without IA-2A to IA-2A positivity was associated with increased levels of 2 h glucose following oral glucose tolerance test (OGTT) ( < 0.001) and increased ZnT8A titers ( < 0.001). Increasing HbA1c ( < 0.001) and GADA titers ( < 0.001) were associated with an increased risk of transition from GADA only to type 1 diabetes; while increasing HbA1c ( < 0.001) was associated with the transition from multiple autoantibodies to type 1 diabetes. Risk of transition from multiple autoantibodies, including IA-2A to type 1 diabetes was also associated with 2 h glucose level ( < 0.001). The dynamic prediction model presented an individual time-specific risk of transition from a single GADA to multiple autoantibodies and type 1 diabetes.
Increasing Prevalence of Pediatric Type 2 Diabetes in the Republic of Ireland: A National Cross-Sectional Study.
Lynam K, O'Grady MJ
Pediatr Diabetes · 2025 · PMID 40980822 · Full text
To establish the current prevalence of type 2 diabetes in children and adolescents aged under 16 years in the Republic of Ireland, to identify modes of presentation, patient characteristics, comorbidities, management, an...
To establish the current prevalence of type 2 diabetes in children and adolescents aged under 16 years in the Republic of Ireland, to identify modes of presentation, patient characteristics, comorbidities, management, and outcomes. We conducted a cross-sectional study of children and adolescents aged under 16 years with a diagnosis of type 2 diabetes in September 2023 using a standardized proforma. This was circulated to all clinicians providing care to children with diabetes in all 19 centers in the Republic of Ireland. Thirty-two cases of type 2 diabetes were identified, giving an estimated prevalence in children and adolescents under 16 years of 3/100,000 population, a significant increase from 1.2/100,000 population in 2015 ( < 0.004). This was due to increased prevalence rates in, both White and Asian populations, as well as an increase in the size of the Asian population under 16. Nineteen (59%) were girls. Median duration of diabetes was 1.2 (0.1-4.9) years. Median body mass index (BMI) -score at diagnosis was identical to the 2015 study (+2.3). Sixteen (50%) achieved the target HbA1c specified by the International Society for Pediatric and Adolescent Diabetes (ISPAD) of 48 mmol/mol (6.5%) or less. Completion of screening for comorbidities and complications of type 2 diabetes were not in accordance with guidelines. There has been a significant increase in the prevalence of type 2 diabetes in under 16's in a short timeframe. Establishment of a National Diabetes Register will facilitate ongoing monitoring of disease epidemiology in this and other age cohorts.
Seasonal Variation in Type 1 Diabetes Incidence in Poland: Exploring the Impact of Viral Infections, Including COVID-19.
Matuszelański D, Winiarczuk A, Tuszyński M … +4 more , Wysocka-Mincewicz M, Piechnik Z, Groele L, Szypowska A
Pediatr Diabetes · 2025 · PMID 40951907 · Full text
Seasonal variation in type 1 diabetes (T1D) incidence has long been a focus of epidemiological research, with viral infections among the proposed contributing factors. Our aim was to examine the seasonal pattern of T1D o...
Seasonal variation in type 1 diabetes (T1D) incidence has long been a focus of epidemiological research, with viral infections among the proposed contributing factors. Our aim was to examine the seasonal pattern of T1D onset in Poland and to assess how viral infections-including COVID-19-may influence this seasonality. We analyzed data from 2381 children with newly diagnosed T1D admitted to two pediatric diabetes centers in the Masovian Voivodeship between 2015 and 2023 and compared them with epidemiological data on COVID-19 and influenza cases during the same period. Our analysis revealed a 30% increase in T1D cases over the study period, with a pronounced seasonal pattern: the highest number of diagnoses occurred in February and the lowest was noted in June. Children under 4 years of age exhibited a distinct pattern with a peak in October, suggesting age-specific differences in T1D pathogenesis. Overall, T1D onset was more frequent in autumn-winter than in spring-summer, with 1294 (54%) vs. 1087 (46%) cases, respectively ( < 0.0001). The influence of COVID-19 on T1D incidence was limited to the first wave of the pandemic. During this period, a strong association was observed ( = 0.96, < 0.001), whereas no correlation was found during the second wave ( = 0.086, = 0.87). The seasonality of T1D diagnoses closely correlated with that of influenza infections ( = 0.79, = 0.002). However, the overall trends differed, suggesting that other viruses with similar transmission patterns may contribute to the seasonality of T1D onset. These findings underline the complex interplay between viral infections and T1D seasonality and suggest that public health strategies aimed at mitigating severe viral infections, including vaccination, warrant further investigation for their potential role in modulating T1D onset in susceptible individuals.
Mauriac Syndrome in Sudanese Children: An Old Syndrome Still Existing in Resource-Limited Countries.
Ismail MM, Al-Hassan OA, Mohamadsalih G … +1 more , Abdullah MA
Pediatr Diabetes · 2025 · PMID 40904852 · Full text
Mauriac syndrome (MS) is a rare condition linked to inadequate glycemic control in type 1 diabetes mellitus (T1DM) and has also rarely been reported in patients with neonatal diabetes. MS manifests as growth failure, del...
Mauriac syndrome (MS) is a rare condition linked to inadequate glycemic control in type 1 diabetes mellitus (T1DM) and has also rarely been reported in patients with neonatal diabetes. MS manifests as growth failure, delayed puberty, cushingoid features, and hepatomegaly. The condition can be associated with complications like dyslipidemia, retinopathy, and nephropathy. The main objective of this study was to describe the magnitude of the condition, clinical features, management, and outcome of Sudanese children and adolescents with MS due to inadequate control of diabetes in our center. This is a cross-sectional hospital-based study. All medical records of patients with MS were reviewed. Data, including demographics, clinical features, investigations, management, and outcome, were obtained. Patients were re-educated and management intensified then followed up. Thirty-seven MS patients were enrolled in this study, with a male predominance of 59.5%. Neonatal diabetes was diagnosed in 5.4% of the patients, while others had T1DM. The median age at diagnosis of MS was 12 years. The diagnosis was based solely on clinical findings, including a history of prolonged unsatisfactory glycemic control, short stature, and hepatomegaly. Regarding the outcome, eight children (21.6%) were lost to follow-up, one patient died (2.7%), seven (18.9%) had a static condition, and those who showed improvement were 21 (56.8%). Signs of improvement were a decrease in liver size with or without an increase in growth velocity. Nephropathy was the most common associated complication; it was seen in 33.3% of our cohort. Some got it at a very young age. Despite many efforts that have been made to achieve better glycemic control in children with T1DM, MS still exists in our setting. Though liver biopsy is the gold standard for diagnosis, being invasive, the diagnosis could be made conservatively, based on clinical features and response to treatment. The condition can be reversed with good metabolic control.
Corrigendum to "ISPAD Clinical Practice Consensus Guidelines 2022: Type 2 Diabetes in Children and Adolescents".
Pediatr Diabetes · 2025 · PMID 40895168 · Full text
[This corrects the article DOI: 10.1111/pedi.13409.].
[This corrects the article DOI: 10.1111/pedi.13409.].
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