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. AIMS: To characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D. METHODS: We 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. RESULTS: Mean 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. CONCLUSIONS: In 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.

Adipose Tissue Can Have a Protective Effect on Outcome After Simultaneous Pancreas-Kidney Transplantation in Non-Obese Recipients.

BACKGROUND Obesity is suggested to impair the outcome after simultaneous pancreas-kidney transplantation, which affects survival, but the quantity and distribution of adipose tissue is not yet considered in obesity assessment. We aimed to evaluate the impact of body composition on outcome after simultaneous pancreas-kidney transplantation. MATERIAL AND METHODS We retrospectively analyzed data from 40 patients who underwent simultaneous pancreas-kidney transplantation due to type 1 diabetes mellitus with consecutive end-stage renal disease. Uni- and multivariate analyses, including donor's characteristics, were performed. RESULTS Only 6 (15%) recipients were obese. The incidence of postoperative complications was correlated with lower body fat proportion (p=0.03). This correlation remained significant in the multivariate analysis (p=0.015). Nevertheless, obesity was significantly associated with worse overall survival (p<0.001). Visceral tissue proportion was correlated with a higher level of glycated hemoglobin in long-term follow-up (p=0.003). CONCLUSIONS Fat quantity and distribution should be included in the assessment of obesity. A protective effect of adipose tissue was detected on outcome after simultaneous pancreas-kidney transplantation in normosthenic recipients, but obesity still appears to have a negative effect on outcome after transplantation. Visceral fat distribution can promote de novo diabetes mellitus.

[Training under normoxia and normobaric hypoxia in patients with type 1 diabetes]. / Wysilek fizyczny w warunkach normoksji i hipoksji normobarycznej u pacjentów z cukrzyca typu 1.

Apart from insulin, physical exercise is a crucial component of therapy in patients with type 1 diabetes mellitus (T1DM). The benefits of physical activity in such patients include improved insulin sensitivity, lowered blood glucose, reduced body fat and improved cardiovascular function and physical performance. Hypoglycemia is a crucial issue in the peri-training period in insulin-treated patients. Proper preparation for exercise is the key to reducing the risk of hypoglycemia. The selection of the training type and the patient's knowledge of the effect of such training on glycemia are also significant. Physical exercise under normobaric hypoxia in the training rooms is also available commercially and is becoming increasingly popular. Under such conditions, the air consists of 15.4% oxygen and 84.5% nitrogen, which corresponds to the conditions at an altitude of approximately 2,500 meters above sea level. Hypoxia induces the production of the hypoxia-inducible factor (HIF-1), which regulates the expression of over 100 genes. It modulates key metabolic pathways to optimize glucose utilization by increasing cell sensitivity to insulin, more efficient glucose uptake from the blood and activating effect on glycolytic enzymes. Additionally, HIF-1 shows beneficial effects on the lipid profile, vascular endothelium and performance as measured by the maximal oxygen uptake (VO2max). The aim of this paper was to review and summarize the most recent studies on the effects of exercise on glycemic control and physical performance under normoxia and normobaric hypoxia in patients with T1DM.

Engineered IRES-mediated promoter-free insulin-producing cells reverse hyperglycemia.

Background: Endogenous insulin supplementation is essential for individuals with type 1 diabetes (T1D). However, current treatments, including pancreas transplantation, insulin injections, and oral medications, have significant limitations. The development of engineered cells that can secrete endogenous insulin offers a promising new therapeutic strategy for type 1 diabetes (T1D). This approach could potentially circumvent autoimmune responses associated with the transplantation of differentiated ß-cells or systemic delivery of viral vectors. Methods: We utilized CRISPR/Cas9 gene editing coupled with homology-directed repair (HDR) to precisely integrate a promoter-free EMCVIRES-insulin cassette into the 3' untranslated region (UTR) of the GAPDH gene in human HEK-293T cells. Subsequently quantified insulin expression levels in these engineered cells, the viability and functionality of the engineered cells when seeded on different cell vectors (GelMA and Cytopore I) were also assessed. Finally, we investigated the therapeutic potential of EMCVIRES-based insulin secretion circuits in reversing Hyperglycaemia in T1D mice. Result: Our results demonstrate that HDR-mediated gene editing successfully integrated the IRES-insulin loop into the genome of HEK-293T cells, a non-endocrine cell line, enabling the expression of human-derived insulin. Furthermore, Cytopore I microcarriers facilitated cell attachment and proliferation during in vitro culture and enhanced cell survival post-transplantation. Transplantation of these cell-laden microcarriers into mice led to the development of a stable, fat-encapsulated structure. This structure exhibited the expression of the platelet-endothelial cell adhesion molecule CD31, and no significant immune rejection was observed throughout the experiment. Diabetic mice that received the cell carriers reversed hyperglycemia, and blood glucose fluctuations under simulated feeding stimuli were very similar to those of healthy mice. Conclusion: In summary, our study demonstrates that Cytopore I microcarriers are biocompatible and promote long-term cell survival in vivo. The promoter-free EMCVIRES-insulin loop enables non-endocrine cells to secrete mature insulin, leading to a rapid reduction in glucose levels. We have presented a novel promoter-free genetic engineering strategy for insulin secretion and proposed an efficient cell transplantation method. Our findings suggest the potential to expand the range of cell sources available for the treatment of diabetes, offering new avenues for therapeutic interventions.

Association and causality between diabetes and activin A: a two-sample Mendelian randomization study.

Activin A, a cytokine belonging to the transforming growth factor-beta (TGF-ß) superfamily, mediates a multifunctional signaling pathway that is essential for embryonic development, cell differentiation, metabolic regulation, and physiological equilibrium. Biomedical research using diabetes-based model organisms and cellular cultures reports evidence of different activin A levels between diabetic and control groups. Activin A is highly conserved across species and universally expressed among disparate tissues. A systematic review of published literatures on human populations reveals association of plasma activin A levels with diabetic patients in some (7) but not in others (5) of the studies. With summarized data from publicly available genome-wide association studies (GWASs), a two-sample Mendelian randomization (TSMR) analysis is conducted on the causality between the exposure and the outcome. Wald ratio estimates from single instruments are predominantly non-significant. In contrast to positive controls between diabetes and plasma cholesterol levels, inverse-variance-weighted (IVW), Egger, weighted median, and weighted mode MR methods all lead to no observed causal link between diabetes (type 1 and type 2) and plasma activin A levels. Unavailability of strong instruments prevents the reversal MR analysis of activin A on diabetes. In summary, further research is needed to confirm or deny the potential association between diabetes and plasma activin A, and to elucidate the temporal incidence of these traits in human populations. At this stage, no causality has been found between diabetes and plasma activin A based on TSMR analysis.

Acute effects of exercise on macro- and microvasculature in individuals with type 1 diabetes - a secondary outcome analysis.

Background: Type 1 diabetes is a chronic autoimmune disease associated with insulin-producing beta cell destruction, declining insulin secretion, and elevated blood glucose. Physical activity improves glycaemic control and cardiovascular health. This study explores acute effects of maximal exhaustion induced by a cardiopulmonary exercise on macro- and microvascular parameters in type 1 diabetes. Methodology: Twenty-five participants with type 1 diabetes (14 males, 11 females), aged 41.4 ± 11.87 years, BMI 23.7 ± 3.08, completed a repeated-measure study. Measurements pre-, post-, 30- and 60-minutes post-exhaustion involved a maximal incremental cardio-pulmonary exercise test. Macro- and microvascular parameters were assessed using VICORDER® and retinal blood vessel image analysis. Repeated measures ANOVA in SPSS (Version 27.0) analysed data. Results: Post-exercise, heart rate increased (p<.001), and diastolic blood pressure decreased (p=.023). Diabetes duration correlated with pulse wave velocity (r=0.418, p=.047), diastolic blood pressure (r=0.470, p=.023), and central retinal arteriolar equivalent (r=0.492, p=.023). Conclusion: In type 1 diabetes, cardiopulmonary exercise-induced exhaustion elevates heart rate and reduces diastolic blood pressure. Future research should explore extended, rigorous physical activity protocols for greater cardiovascular risk reduction.

Mechanistic Pathways and Clinical Implications of GLP-1 Receptor Agonists in Type 1 Diabetes Management.

GLP-1 receptor agonists, which were initially intended to treat type 2 diabetes patients, have demonstrated promise as an adjuvant therapy for type 1 diabetes (T1D). These medications can manage T1D by improving ß-cell function, reducing glucose fluctuation, and providing cardioprotective effects. Recent research suggests that boosting cell proliferation and lowering apoptosis can help maintain the bulk of ß-cells. Furthermore, GLP-1 receptor agonists have potent anti-inflammatory characteristics, improving immunological control and lowering systemic inflammation, both of which are critical for reducing autoimmune damage in T1D. Beyond glucose control, these agonists have neuroprotective qualities and aid in weight management. Combining these medications with insulin could significantly change how T1D is managed. The clinical data and biological mechanisms discussed in this review support the potential use of GLP-1 receptor agonists in T1D.

The Impact of Thyroiditis on the Immune Profile in Young Patients with Uncomplicated Type 1 Diabetes.

Autoimmune thyroid disease (AIT) is the most frequently linked autoimmune condition to type 1 diabetes (T1D). The analysis of immune profiles could provide valuable insights into the study of these diseases. This knowledge could play a crucial role in understanding the relationship between immune profiles and microcirculation structures and functions. The present study aimed to test the hypothesis that cytokine levels in T1D patients without and those with comorbid Hashimoto's disease differ significantly. The total study group (total T1D) consisted of 62 diabetic young patients: 43 T1D and 19 T1D + AIT matched for age, age at onset, and duration of diabetes. The control group consisted of 32 healthy young subjects. The levels of cytokines (including TNF-α, IL-35, IL-4, IL-10, IL-18, IL-12, VEGF, and angiogenin) were quantified throughout this investigation. A comparative assessment of the cytokines profiles between the control group and total T1D revealed a statistically significant elevation in the levels of IL-4, TNF-α, IL-18, VEGF, and angiogenin, accompanied by a notable decline in IL-10. However, IL-35 and IL-12 exhibited comparable levels between the two groups. A comparison of cytokine levels between T1D + AIT and T1D groups revealed that only angiogenin levels were statistically significantly higher in T1D + AIT. The results of our study indicated that the alterations in cytokine levels associated with AIT did not correspond to the observed changes in T1D-related outcomes. The sole notable observation was the elevation of angiogenin expression, an angiogenic factor.

Mealtime prediction using wearable insulin pump data to support diabetes management.

Many patients with diabetes struggle with post-meal high blood glucose due to missed or untimely meal-related insulin doses. To address this challenge, our research aims to: (1) study mealtime patterns in patients with type 1 diabetes using wearable insulin pump data, and (2) develop personalized models for predicting future mealtimes to support timely insulin dose administration. Using two independent datasets with over 45,000 meal logs from 82 patients with diabetes, we find that the majority of people ( ∼ 60%) have irregular and inconsistent mealtime patterns that change notably through the course of each day and across months in their own historical data. We also show the feasibility of predicting future mealtimes with personalized LSTM-based models that achieve an average F1 score of > 95% with less than 0.25 false positives per day. Our research lays the groundwork for developing a meal prediction system that can nudge patients with diabetes to administer bolus insulin doses before meal consumption to reduce the occurrence of post-meal high blood glucose.

Transcutaneous vagus nerve stimulation has no anti-inflammatory effect in diabetes.

Chronic inflammation is associated with diabetes and contributes to the development and progression of micro- and macrovascular complications. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to reduce levels of circulating inflammatory cytokines in non-diabetics by activating the cholinergic anti-inflammatory pathway. We investigated the anti-inflammatory potential of tVNS as a secondary endpoint of a randomized controlled trial in people with diabetes (NCT04143269). 131 people with diabetes (type 1: n = 63; type 2: n = 68), gastrointestinal symptoms and various degrees of autonomic neuropathy were included and randomly assigned to self-administer active (n = 63) or sham (n = 68) tVNS over two successive study periods: (1) Seven days with four daily administrations and, (2) 56 days with two daily administrations. Levels of systemic inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α, IFN-γ) were quantified from blood samples by multiplex technology. Information regarding age, sex, diabetes type, and the presence of cardiac autonomic neuropathy (CAN) was included in the analysis as possible confounders. No differences in either cytokine were seen after study period 1 and 2 between active and sham tVNS (all p-values > 0.08). Age, sex, diabetes type, presence of CAN, and baseline levels of inflammatory cytokines were not associated with changes after treatment (all p-values > 0.07). A tendency towards slight reductions in TNF-α levels after active treatment was observed in those with no CAN compared to those with early or manifest CAN (p = 0.052). In conclusion, tVNS did not influence the level of systemic inflammation in people with diabetes.

Nutritional status and extended metabolic screening in Egyptian children with uncomplicated type 1 diabetes.

Nutritional status assessment, including amino acids, carnitine, and acylcarnitine profile, is an important component of diabetes care management, influencing growth and metabolic regulation. A designed case-control research included 100 Egyptian participants (50 T1DM and 50 healthy controls) aged 6 to 18 years old. The participants' nutritional status was assessed using the Body Mass Index (BMI) Z-score. Extended metabolic screening (EMS) was performed using a high-performance liquid chromatography-electrospray ionization-mass spectroscopy system to evaluate the levels of 14 amino acids, free carnitine, and 27 carnitine esters. T1DM children had considerably lower anthropometric Z-scores than the control group, with 16% undernutrition and 32% short stature. Total aromatic amino acids, phenylalanine, phenylalanine/tyrosine ratio, proline, arginine, leucine, isoleucine, free carnitine, and carnitine esters levels were considerably lower in the diabetic group, suggesting an altered amino acid and carnitine metabolism in type 1 diabetes. BMI Z-score showed a significant positive correlation with Leucine, Isoleucine, Phenylalanine, Citrulline, Tyrosine, Arginine, Proline, free carnitine, and some carnitine esters (Acetylcarnitine, Hydroxy-Isovalerylcarnitine, Hexanoylcarnitine, Methylglutarylcarnitine, Dodecanoylcarnitine, Tetradecanoylcarnitine, and Hexadecanoylcarnitine). HbA1c% had a significant negative correlation with Total aromatic amino acids, Branched-chain amino acid/Total aromatic amino acids ratio, Glutamic Acid, Citrulline, Tyrosine, Arginine, Proline, and certain carnitine esters (Propionylcarnitine, Methylglutarylcarnitine, Decanoylcarnitine, Octadecanoylcarnitine and Octadecenoylcarnitine), suggest that dysregulated amino acid and carnitine metabolism may be negatively affect the glycaemic control in children with TIDM. In conclusion, regular nutritional assessments including EMS of T1DM patients are critical in terms of diet quality and protein content for improved growth and glycemic management.

Mechanisms underlying the development of type 1 diabetes in ART-treated people living with HIV: an enigmatic puzzle.

The immunopathogenesis of HIV infection remains poorly understood. Despite the widespread use of effective modern antiretroviral therapy (ART), people living with HIV (PLWH) are known to develop several comorbidities, including type 1 diabetes (T1DM). However, the etiology and critical mechanisms accounting for the onset of T1DM in the preceding context remain unknown. This article proposes to address this topic in order to provide further understanding and future research directions.

Long-Term Glycemic Control Improvement After the Home and Self-Care Program for Patients With Type 1 Diabetes: Real-World-Based Cohort Study.

BACKGROUND: The prevalence of type 1 diabetes (T1D) is increasing worldwide, with a much higher proportion of adult patients. However, achieving stable glycemic control is difficult in these patients. OBJECTIVE: After periodic implementation of structured education for patients with T1D through the Home and Self-Care Program, a pilot home health care project promoted by the Korean government, we evaluated the program's effects on glycemic control. METHODS: This study was conducted from April 2020 to March 2023. We analyzed 119 participants with T1D aged >15 years. Nursing and nutrition education were provided separately up to 4 times per year, with physician consultation up to 6 times per year. A distinguishing feature of this study compared with previous ones was the provision of remote support using a general-purpose smartphone communication app offered up to 12 times annually on an as-needed basis to enhance the continuity of in-person education effects. Patients were followed up on at average intervals of 3 months for up to 24 months. The primary end point was the mean difference in glycated hemoglobin (HbA1c) at each follow-up visit from baseline. For continuous glucose monitoring (CGM) users, CGM metrics were also evaluated. RESULTS: The mean HbA1c level of study participants was 8.6% at baseline (mean duration of T1D 10.02, SD 16.10 y). The HbA1c level reduction in participants who received at least 1 structured educational session went from 1.63% (SD 2.03%; P<.001; adjustment model=1.69%, 95% CI 1.24%-2.13% at the first follow-up visit) to 1.23% (SD 1.31%; P=.01; adjustment model=1.28%, 95% CI 0.78%-1.79% at the eighth follow-up visit). In the adjustment model, the actual mean HbA1c values were maintained between a minimum of 7.33% (95% CI 7.20%-7.46% at the first follow-up visit) and a maximum of 7.62% (95% CI 7.41%-7.82% at the sixth follow-up visit). Among CGM users, after at least 1 session, the mean time in the target range was maintained between 61.59% (adjusted model, 95% CI 58.14%-65.03% at the second follow-up visit) and 54.7% (95% CI 50.92%-58.48% at the eighth follow-up visit), consistently staying above 54.7% (corresponding to an HbA1c level of <7.6%). The mean time below the target range (TBR) also gradually improved to the recommended range (≤4% for TBR of <70 mg/dL and ≤1% for TBR of <54 mg/dL). CONCLUSIONS: The Home and Self-Care Program protocol for glycemic control in patients with T1D is effective, producing significant improvement immediately and long-term maintenance effects, including on CGM indexes.

Ten years trajectories of estimated glomerular filtration rate (eGFR) in a multiethnic cohort of people with type 1 diabetes and preserved renal function.

OBJECTIVES: We aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m2. DESIGN: Observational cohort. SETTING: People with a clinical diagnosis of type 1 diabetes, attending two university hospital-based outpatient diabetes clinics, in South London between 2004 and 2018. PARTICIPANTS: We studied 1495 participants (52% females, 81% white, 12% African-Caribbean and 7% others). PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical measures including weight and height, systolic blood pressure, diastolic blood pressure and laboratory results (such as serum creatinine, urine albumin to creatinine ratio (ACR), HbA1c were collected from electronic health records (EHRs) and eGFR was estimated by the Chronic Kidney Disease-Epidemiology Collaboration. Ethnicity was self-reported. RESULTS: Five predominantly linear patterns/groups of eGFR trajectories were identified. Group I (8.5%) had a fast eGFR decline (>3 mL/min/1.73 m2 year). Group II (23%) stable eGFR, group III (29.8%), groups IV (26.3%) and V (12.4%) have preserved eGFR with no significant fall. Group I had the highest proportion (27.6%) of African-Caribbeans. Significant differences between group I and the other groups were observed in age, gender, HbA1C, systolic and diastolic blood pressure, body mass index, cholesterol and urine ACR, p<0.05 for all. At 10 years of follow-up, 33% of group I had eGFR <30 and 16.5%<15 (mL/min/1.73 m2). CONCLUSIONS: Distinct trajectories of eGFR were observed in people with type 1 diabetes. The group with the highest risk of eGFR decline had a greater proportion of African-Caribbeans compared with others and has higher prevalence of traditional modifiable risk factors for kidney disease.

Association of COVID-19 infection and the risk of new incident diabetes: a systematic review and meta-analysis.

Background: As the world population recovers from the COVID-19 infection, a series of acute sequelae emerge including new incident diabetes. However, the association between COVID-19 infection and new incident diabetes is not fully understood. We purpose to determine the risk of new incident diabetes after COVID-19 infection. Methods: PubMed, Embase, and Cochrane Library were used as databases to search for cohort studies published from database inception to February 4, 2024. Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the hazard ratio (HR) with corresponding 95% confidence intervals (CI). Subgroup analysis was conducted to explore the potential influencing factors. Results: A total of 20 cohort studies with over 60 million individuals were included. The pooling analysis illustrates the association between COVID-19 infection and an increased risk of new incident diabetes (HR = 1.46; 95% CI: 1.38-1.55). In subgroup analysis, the risk of type 1 diabetes was HR=1.44 (95% CI: 1.13-1.82), and type 2 diabetes was HR=1.47 (95% CI: 1.36-1.59). A slightly higher risk of diabetes was found in males (HR=1.37; 95% CI: 1.30-1.45) than in females (HR=1.29; 95% CI: 1.22-1.365). The risk of incident diabetes is associated with hospitalization: non-hospitalized patients have an HR of 1.16 (95% CI: 1.07-1.26), normal hospitalized patients have an HR of 2.15 (95% CI: 1.33-3.49), and patients receiving intensive care have the highest HR of 2.88 (95% CI: 1.73-4.79). Conclusions: COVID-19 infection is associated with an elevated risk of new incident diabetes. Patients ever infected with COVID-19 should be recognized as a high-risk population with diabetes. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024522050.

Exploring senescence as a modifier of ß cell extracellular vesicles in type 1 diabetes.

Type 1 Diabetes (T1D) is a chronic metabolic disease resulting from insulin deficiency due to autoimmune loss of pancreatic ß cells. In addition to ß cell destruction, it is now accepted that ß cell stress and dysfunction, such as senescence, plays a crucial role in the development of the disease. Accumulation of senescent ß cells occurs during development of T1D in humans and contributes to the progression of T1D in the nonobese diabetic (NOD) mouse model. Senescent ß cells are thought to exacerbate the inflammatory response within the islets by production and secretion of senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) from ß cells have been shown to carry protein and microRNAs (miRNAs), influencing cellular signaling and may contribute to the development of T1D but it remains to be addressed how senescence impacts ß cell EV cargo. In this minireview, we discuss emerging evidence that EV cargo proteins and miRNAs associated with senescence could contribute to the development of T1D and could suggest potential biomarkers and therapeutic targets for the regulation of SASP and elimination of senescent ß cells in T1D. Future investigation exploring the intricate relationship between ß cell senescence, EVs and miRNAs could pave the way for the development of novel diagnostic techniques and therapeutic interventions.

The application of predictive value of diabetes autoantibody profile combined with clinical data and routine laboratory indexes in the classification of diabetes mellitus.

Objective: Currently, distinct use of clinical data, routine laboratory indicators or the detection of diabetic autoantibodies in the diagnosis and management of diabetes mellitus is limited. Hence, this study was aimed to screen the indicators, and to establish and validate a multifactorial logistic regression model nomogram for the non-invasive differential prediction of type 1 diabetes mellitus. Methods: Clinical data, routine laboratory indicators, and diabetes autoantibody profiles of diabetic patients admitted between September 2018 and December 2022 were retrospectively analyzed. Logistic regression was used to select the independent influencing factors, and a prediction nomogram based on the multiple logistic regression model was constructed using these independent factors. Moreover, the predictive accuracy and clinical application value of the nomogram were evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). Results: A total of 522 diabetic patients were included in this study. These patients were randomized into training and validation sets in a 7:3 ratio. The predictors screened included age, prealbumin (PA), high-density lipoprotein cholesterol (HDL-C), islet cells autoantibodies (ICA), islets antigen 2 autoantibodies (IA-2A), glutamic acid decarboxylase antibody (GADA), and C-peptide levels. Based on these factors, a multivariate model nomogram was constructed, which had an Area Under Curve (AUC) of 0.966 and 0.961 for the training set and validation set, respectively. Subsequently, the calibration curves demonstrated a strong accuracy of the graph; the DCA and CIC results indicated that the graph could be used as a non-invasive valid predictive tool for the differential diagnosis of type 1 diabetes mellitus, clinically. Conclusion: The established prediction model combining patient's age, PA, HDL-C, ICA, IA-2A, GADA, and C-peptide can assist in differential diagnosis of type 1 diabetes mellitus and type 2 diabetes mellitus and provides a basis for the clinical as well as therapeutic management of the disease.

Oral health status and oral health-related quality of life among children with type 1 diabetes mellitus in the age group of 11-14 years in Delhi-NCR Region.

PURPOSE: The purpose of this study was to assess the impact of oral health status (OHS) and sociodemographic indicators on oral health-related quality of life (OHRQoL) among children with type 1 diabetes mellitus (T1DM) aged 11-14 years and compare it with age-matched nondiabetic children. MATERIALS AND METHODS: This cross-sectional study included 80 children aged between 11 and 14 years with T1DM and 80 age-matched nondiabetic children. The OHRQoL was measured using a validated structured Hindi version of the child perception questionnaire (CPQ11-14) questionnaire. The clinical OHS was assessed using the decayed, missing, or filled teeth index, plaque index (PI), and gingival index (GI). Associations between OHRQoL and independent predictors were analyzed with the log-linear Poisson model regression method. RESULTS: CPQ11-14 scores were significantly lower in nondiabetic children than diabetic children, indicating better OHRQoL among nondiabetic children than diabetic children (P ≤ 0.05). The GI score exhibited a significantly lower value in nondiabetic children than in diabetic children (P = 0.014). In contrast, the mean decayed, missing, and filled teeth score showed a significantly higher value in nondiabetic children than in diabetic children (P ≤ 0.001). There was no difference in the mean PI of diabetic and nondiabetic children (P = 0.096). CONCLUSION: The result of the present study highlighted the detrimental effect of T1DM on OHRQoL in children.

Psychometric properties of the German versions of the Problem Areas in Diabetes Scale for Children (PAID-C) with Type 1 Diabetes and Their Parents (P-PAID-C).

Children with Type 1 diabetes (T1D) and their parent-caregivers often experience diabetes distress due to the daily demands of diabetes management. Regular screening for diabetes distress is needed to prevent the deterioration of metabolic control and the development of mental health disorders. The aim of this analysis was to examine the psychometric properties of the German versions of the Problem Areas in Diabetes Scale for Children (PAID-C) and for caregiver burden in Parents (P-PAID-C). Data were collected from 136 children aged 7-12 years (46.7% females) and 304 parents (Mage = 42.9 (SD 6.1) years; 78% mothers) by using linguistically translated questionnaires in a multicenter study. Confirmatory factor analysis and correlational analyses were conducted. Results confirmed the two-factor model for the PAID-C and the four-factor model for the P-PAID-C with a slight modification. Cronbach's αs for children and parents were 0.88 and 0.92, respectively. The PAID-C and P-PAID-C scores had small positive associations with HbA1c (rs = .220 and .139, respectively, all p < .05) and strong inverse association with the KIDSCREEN-10 index (r = -.643 and -.520, respectively, all p < .001). P-PAID-C scores increased with increasing depressive symptoms measured in nine-item Patient Health Questionnaire among parents (rs = .534, p < .001). The scores produced by the German PAID-C and P-PAID-C were reliable and valid in measuring diabetes burdens. These German versions of PAID can be utilized to assess diabetes-specific distress and to design interventions for children and their parents experiencing high levels of diabetes distress. (PsycInfo Database Record (c) 2024 APA, all rights reserved).