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Aims/hypothesis: The aim of this work was to explore molecular amino acids (AAs) and related structures of HLA-DQA1-DQB1 that underlie its contribution to the progression from stages 1 or 2 to stage 3 type 1 diabetes. Methods: Using high-resolution DQA1 and DQB1 genotypes from 1216 participants in the Diabetes Prevention Trial-Type 1 and the Diabetes Prevention Trial, we applied hierarchically organised haplotype association analysis (HOH) to decipher which AAs contributed to the associations of DQ with disease and their structural properties. HOH relied on the Cox regression to quantify the association of DQ with time-to-onset of type 1 diabetes. Results: By numerating all possible DQ heterodimers of α- and β-chains, we showed that the heterodimerisation increases genetic diversity at the cellular level from 43 empirically observed haplotypes to 186 possible heterodimers. Heterodimerisation turned several neutral haplotypes (DQ2.2, DQ2.3 and DQ4.4) to risk haplotypes (DQ2.2/2.3-DQ4.4 and DQ4.4-DQ2.2). HOH uncovered eight AAs on the α-chain (−16α, −13α, −6α, α22, α23, α44, α72, α157) and six AAs on the β-chain (−18β, β9, β13, β26, β57, β135) that contributed to the association of DQ with progression of type 1 diabetes. The specific AAs concerned the signal peptide (minus sign, possible linkage to expression levels), pockets 1, 4 and 9 in the antigen-binding groove of the α1β1 domain, and the putative homodimerisation of the αβ heterodimers. Conclusions/interpretation: These results unveil the contribution made by DQ to type 1 diabetes progression at individual residues and related protein structures, shedding light on its immunological mechanisms and providing new leads for developing treatment strategies. Data availability: Clinical trial data and biospecimen samples are available through the National Institute of Diabetes and Digestive and Kidney Diseases Central Repository portal (https://repository.niddk.nih.gov/studies). [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Dietary patterns characterised by high intakes of vegetables may lower the risk of pre-eclampsia and premature birth in the general population. The effect of dietary patterns in women with type 1 diabetes, who have an increased risk of complications in pregnancy, is not known. The aim of this study was to investigate the relationship between dietary patterns and physical activity during pregnancy and maternal complications and birth outcomes in women with type 1 diabetes. We also compared dietary patterns in women with and without type 1 diabetes. Methods: Diet was assessed in the third trimester using a validated food frequency questionnaire in participants followed prospectively in the multi-centre Environmental Determinants of Islet Autoimmunity (ENDIA) study. Dietary patterns were characterised by principal component analysis. The Pregnancy Physical Activity Questionnaire was completed in each trimester. Data for maternal and birth outcomes were collected prospectively. Results: Questionnaires were completed by 973 participants during 1124 pregnancies. Women with type 1 diabetes (n=615 pregnancies with dietary data) were more likely to have a 'fresh food' dietary pattern than women without type 1 diabetes (OR 1.19, 95% CI 1.07, 1.31; p=0.001). In women with type 1 diabetes, an increase equivalent to a change from quartile 1 to 3 in 'fresh food' dietary pattern score was associated with a lower risk of pre-eclampsia (OR 0.37, 95% CI 0.17, 0.78; p=0.01) and premature birth (OR 0.35, 95% CI 0.20, 0.62, p<0.001). These associations were mediated in part by BMI and HbA1c. The 'processed food' dietary pattern was associated with an increased birthweight (β coefficient 56.8 g, 95% CI 2.8, 110.8; p=0.04). Physical activity did not relate to outcomes. Conclusions/interpretation: A dietary pattern higher in fresh foods during pregnancy was associated with sizeable reductions in risk of pre-eclampsia and premature birth in women with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Type 1 diabetes is associated with excess coronary artery disease (CAD) risk even when known cardiovascular risk factors are accounted for. Genetic perturbation of haematopoiesis that alters leukocyte production is a novel independent modifier of CAD risk. We examined whether there are shared genetic determinants and causal relationships between type 1 diabetes, CAD and leukocyte counts. Methods: Genome-wide association study summary statistics were used to perform pairwise linkage disequilibrium score regression and heritability estimation from summary statistics (ρ-HESS) to respectively estimate the genome-wide and local genetic correlations, and two-sample Mendelian randomisation to estimate the causal relationships between leukocyte counts (335,855 healthy individuals), type 1 diabetes (18,942 cases, 501,638 control individuals) and CAD (122,733 cases, 424,528 control individuals). A latent causal variable (LCV) model was performed to estimate the genetic causality proportion of the genetic correlation between type 1 diabetes and CAD. Results: There was significant genome-wide genetic correlation (rg) between type 1 diabetes and CAD (rg=0.088, p=8.60 × 10−3) and both diseases shared significant genome-wide genetic determinants with eosinophil count (rg for type 1 diabetes [rg(T1D)]=0.093, p=7.20 × 10−3, rg for CAD [rg(CAD)]=0.092, p=3.68 × 10−6) and lymphocyte count (rg(T1D)=−0.052, p=2.76 × 10−2, rg(CAD)=0.176, p=1.82 × 10−15). Sixteen independent loci showed stringent Bonferroni significant local genetic correlations between leukocyte counts, type 1 diabetes and/or CAD. Cis-genetic regulation of the expression levels of genes within shared loci between type 1 diabetes and CAD was associated with both diseases as well as leukocyte counts, including SH2B3, CTSH, MORF4L1, CTRB1, CTRB2, CFDP1 and IFIH1. Genetically predicted lymphocyte, neutrophil and eosinophil counts were associated with type 1 diabetes and CAD (lymphocyte OR for type 1 diabetes [ORT1D]=0.67, p=2.02−19, ORCAD=1.09, p=2.67 × 10−6; neutrophil ORT1D=0.82, p=5.63 × 10−5, ORCAD=1.17, p=5.02 × 10−14; and eosinophil ORT1D=1.67, p=5.45 × 10−25, ORCAD=1.07, p=2.03 × 10−4. The genetic causality proportion between type 1 diabetes and CAD was 0.36 ± 0.16 (pLCV=1.30 × 10−2), suggesting a possible intermediary causal variable. Conclusions/interpretation: This study sheds light on shared genetic mechanisms underlying type 1 diabetes and CAD, which may contribute to their co-occurrence through regulation of gene expression and leukocyte counts and identifies cellular and molecular targets for further investigation for disease prediction and potential drug discovery. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Although statistical models for predicting type 1 diabetes risk have been developed, approaches that reveal the heterogeneity of the at-risk population by identifying clinically meaningful clusters are lacking. We aimed to identify and characterise clusters of islet autoantibody-positive individuals who share similar characteristics and type 1 diabetes risk. Methods: We tested a novel outcome-guided clustering method in initially non-diabetic autoantibody-positive relatives of individuals with type 1 diabetes, using the TrialNet Pathway to Prevention study data (n=1123). The outcome of the analysis was the time to development of type 1 diabetes, and variables in the model included demographic characteristics, genetics, metabolic factors and islet autoantibodies. An independent dataset (the Diabetes Prevention Trial of Type 1 Diabetes Study) (n=706) was used for validation. Results: The analysis revealed six clusters with varying type 1 diabetes risks, categorised into three groups based on the hierarchy of clusters. Group A comprised one cluster with high glucose levels (median for glucose mean AUC 9.48 mmol/l; IQR 9.16–10.02) and high risk (2-year diabetes-free survival probability 0.42; 95% CI 0.34, 0.51). Group B comprised one cluster with high IA-2A titres (median 287 DK units/ml; IQR 250–319) and elevated autoantibody titres (2-year diabetes-free survival probability 0.73; 95% CI 0.67, 0.80). Group C comprised four lower-risk clusters with lower autoantibody titres and glucose levels (with 2-year diabetes-free survival probability ranging from 0.84–0.99 in the four clusters). Within group C, the clusters exhibit variations in characteristics such as glucose levels, C-peptide levels and age. A decision rule for assigning individuals to clusters was developed. Use of the validation dataset confirmed that the clusters can identify individuals with similar characteristics. Conclusions/interpretation: Demographic, metabolic, immunological and genetic markers may be used to identify clusters of distinctive characteristics and different risks of progression to type 1 diabetes among autoantibody-positive individuals with a family history of type 1 diabetes. The results also revealed the heterogeneity in the population and complex interactions between variables. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Diabetic kidney disease (DKD) is a severe diabetic complication that affects one third of individuals with type 1 diabetes. Although several genes and common variants have been shown to be associated with DKD, much of the predicted inheritance remains unexplained. Here, we performed next-generation sequencing to assess whether low-frequency variants, extending to a minor allele frequency (MAF) ≤10% (single or aggregated) contribute to the missing heritability in DKD. Methods: We performed whole-exome sequencing (WES) of 498 individuals and whole-genome sequencing (WGS) of 599 individuals with type 1 diabetes. After quality control, next-generation sequencing data were available for a total of 1064 individuals, of whom 541 had developed either severe albuminuria or end-stage kidney disease, and 523 had retained normal albumin excretion despite a long duration of type 1 diabetes. Single-variant and gene-aggregate tests for protein-altering variants (PAV) and protein-truncating variants (PTV) were performed separately for WES and WGS data and combined in a meta-analysis. We also performed genome-wide aggregate analyses on genomic windows (sliding window), promoters and enhancers using the WGS dataset. Results: In the single-variant meta-analysis, no variant reached genome-wide significance, but a suggestively associated common THAP7 rs369250 variant (p=1.50 × 10−5, MAF=49%) was replicated in the FinnGen general population genome-wide association study (GWAS) data for chronic kidney disease and DKD phenotypes. The gene-aggregate meta-analysis provided suggestive evidence (p<4.0 × 10−4) at four genes for DKD, of which NAT16 (MAFPAV≤10%) and LTA (also known as TNFβ, MAFPAV≤5%) are replicated in the FinnGen general population GWAS data. The LTA rs2229092 C allele was associated with significantly lower TNFR1, TNFR2 and TNFR3 serum levels in a subset of FinnDiane participants. Of the intergenic regions suggestively associated with DKD, the enhancer on chromosome 18q12.3 (p=3.94 × 10−5, MAFvariants≤5%) showed interaction with the METTL4 gene; the lead variant was replicated, and predicted to alter binding of the MafB transcription factor. Conclusions/interpretation: Our sequencing-based meta-analysis revealed multiple genes, variants and regulatory regions that were suggestively associated with DKD. However, as no variant or gene reached genome-wide significance, further studies are needed to validate the findings. [ABSTRACT FROM AUTHOR]

Purpose: ANGPTL8, commonly referred to as betatrophin, has demonstrated promise as a dependable marker for the onset of complications associated with diabetes mellitus, such as dyslipidemia. The objective of this study is to evaluate the lipid profile and ANGPTL8 levels in people diagnosed with Type 1 Diabetes Mellitus (T1DM). Methods: A retrospective case-control study was performed on a group of 100 adolescent females, aged 13–17 years. This group consisted of individuals diagnosed with T1DM from the Diabetes and Endocrine Department at Medina's King Fahad Hospital in Saudi Arabia. Additionally, 100 healthy adolescent females of the same age range were included as controls. The hospital conducted laboratory studies to evaluate glucose, HbA1c, insulin, and lipid profiles. The ANGPTL8 levels were quantified using Enzyme-Linked Immunosorbent Assay (ELISA). Results: Patients with T1DM had ANGPTL8 levels that were twice as high as those observed in individuals without any health conditions. The two groups had contrasting levels of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), C-peptides, triacylglycerol (TG), and cholesterol, along with elevated Atherogenic Index of Plasma readings. Diabetes mellitus patients had considerably elevated values compared to the control group. There was a significant correlation between ANGPTL8 concentrations and lipid abnormalities, with P-values less than 0.05. 56% of the 100 patients exhibited dyslipidemia. The research found a correlation between dyslipidemia and elevated levels of ANGPTL8 in diabetic patients. The concentration of ANGPTL8 had a positive correlation with glucose, HbA1c, TG, and C-peptides while displaying a negative correlation with high-density lipoprotein cholesterol (HDL-C). Conclusion: ANGPTL8 levels were found to be elevated in Saudi young women who were diagnosed with TIDM. ANGPTL8 may potentially contribute to dyslipidemia in individuals with T1DM, hence increasing the susceptibility to cardiovascular disease (CVD). Therefore, ANGPTL8 has the potential to impact lipid metabolism, namely Triglycerides, as a biological route. The results highlight the need to analyze lipid profiles and do ANGPTL8 testing in young females diagnosed with T1DM at an early stage to prevent complications. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the time in tight range (TITR), and its relationship with other glucometric parameters in patients with type 1 diabetes (T1D) treated with advanced hybrid closed-loop (AHCL) systems. Methods: A prospective observational study was conducted on pediatric and adult patients with T1D undergoing treatment with AHCL systems for at least 3 months. Clinical variables and glucometric parameters before and after AHCL initiation were collected. Results: A total of 117 patients were evaluated. Comparison of metabolic control after AHCL initiation showed significant improvements in HbA1c (6.9 ± 0.9 vs. 6.6 ± 0.5%, p < 0.001), time in range (TIR) (68.2 ± 11.5 vs. 82.5 ± 6.9%, p < 0.001), TITR (43.7 ± 10.8 vs. 57.3 ± 9.7%, p < 0.001), glucose management indicator (GMI) (6.9 ± 0.4 vs. 6.6 ± 0.3%, p < 0.001), time below range (TBR) 70–54 mg/dl (4.3 ± 4.5 vs. 2.0 ± 1.4%, p < 0.001), and time above range (TAR) > 180 mg/dl (36.0 ± 7.6 vs. 15.1 ± 6.4%, p < 0.001). Coefficient of variation (CV) also improved (36.3 ± 5.7 vs. 30.6 ± 3.7, p < 0.001), while time between 140–180 mg/dl remained unchanged. In total, 76.3% achieved TITR > 50% (100% pediatric). Correlation analysis between TITR and TIR and GRI showed a strong positive correlation, modified by glycemic variability. Conclusions: AHCL systems achieve significant improvements in metabolic control (TIR > 70% in 93.9% patients). The increase in TIR was not related to an increase in TIR 140–180 mg/dl. Despite being closely related to TIR, TITR allows for a more adequate discrimination of the achieved control level, especially in a population with good initial metabolic control. The correlation between TIR and TITR is directly influenced by the degree of glycemic variability. [ABSTRACT FROM AUTHOR]

Age-related cataracts is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation, and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear. Our study identified 101 independent genome-wide significant loci, 57 of which are novel. We identified multiple genes and biological pathways associated with the cataracts, including four drug-gene interactions. Our results suggest a causal association between type 1 diabetes and cataracts. Also, we highlighted a surrogate measure of UV light exposure as a marker of cataract risk in adults. Here, the authors expand knowledge of the genetic architecture of age-related cataracts, exploring associated pathways and drug-gene interactions, and clarify the roles of type 1 diabetes and UV exposure in cataract etiology. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by hyperglycemia resulting from the destruction of insulin-producing β-cells that is traditionally deemed irreversible, but partial remission (PR) with temporary reversal of hyperglycemia is sometimes observed. Here we use single-cell RNA sequencing to delineate the immune cell landscape across patients in different T1D stages. Together with cohort validation and functional assays, we observe dynamic changes in TIGIT+CCR7− Tregs and CD226+CCR7−CD8+ cytotoxic T cells during the peri-remission phase. Machine learning algorithms further identify TIGIT+CCR7− Tregs and CD226+CD8+ T cells as biomarkers for β-cell function decline in a predictive model, while cell communication analysis and in vitro assays suggest that TIGIT+CCR7− Tregs may inhibit CD226+CCR7−CD8+ T cells via TGF-β signaling. Lastly, in both cyclophosphamide-induced and streptozotocin (STZ)-induced mouse diabetes models, CD226 inhibition postpones insulitis onset and reduces hyperglycemia severity. Our results thus identify two interrelated immune cell subsets that may serve as biomarkers for monitoring disease progression and targets for therapeutic intervention of T1D. Type 1 diabetes (T1D) manifests as hyperglycemia, with spontaneous remission occasionally observed, but the underneath mechanisms are unclear. Here the authors analyses patients at different stages to find two populations of immune cells correlating with disease progression or remission, while results from mouse diabetes models validate these observations. [ABSTRACT FROM AUTHOR]

Purpose: Ketogenic diets are proposed as a therapeutic approach for type 1 and type 2 diabetes due to their low glucose intake. However, their potential effects on the immune system need investigation. This study aims to explore how glucose concentration and beta-hydroxybutyrate (BHB) impact T cell phenotype, metabolism, and function, with a focus on systemic inflammatory response (T2D) and autoimmunity (T1D). Methods: T cells from healthy donors were cultured in vitro under varying glucose concentrations with or without BHB. Flow cytometry was employed to analyze changes in T cell phenotype, while proliferation was evaluated through a CFSE dilution assay. Additionally, we used a novel flow cytometry method allowing a direct assessment of T cell metabolism. Results: Culturing T cells in low glucose concentrations revealed their dependency on glucose metabolism, leading to reduced proliferation rates, overexpression of exhaustion markers and increased susceptibility to Treg suppression and the influence of immune-modulating drugs such as rapamycin, FK506, and MMF. Notably, T cells cultured in low glucose concentrations increased the expression of BDH1 to utilize BHB as an alternative fuel source. Finally, the addition of BHB to the culture effectively rescued T cell impairments caused by insufficient glucose levels. Conclusions: T cells display limited capacity to adapt to low glucose levels, resulting in profound functional impairment. However, T cell functions can be efficiently recovered by the presence of 2mM BHB. [ABSTRACT FROM AUTHOR]

Aims: In this study we evaluated the use of Continuous Glucose Monitoring system in adults with insulin-dependent diabetes in the course of Wolfram syndrome (WFS) in comparison to patients with type 1 diabetes (T1D). Methods: Individuals with WFS (N = 10) used continuous glucose monitoring for 14 days and were compared with 30 patients with T1D matched using propensity score for age and diabetes duration. Glycemic variability was calculated with Glyculator 3.0. Results: We revealed significant differences in glycemic indices between adults with Wolfram syndrome-related diabetes and matched comparison group. Patients with Wolfram syndrome presented lower mean glucose in 24-h and nighttime records [24h: 141.1 ± 30.4mg/dl (N = 10) vs 164.9 ± 31.3mg/dl (N = 30), p = 0.0427; nighttime: 136.7 ± 39.6mg/dl vs 166.2 ± 32.1mg/dl (N = 30), p = 0.0442]. Moreover, they showed lower standard deviation of sensor glucose over all periods [24h: 50.3 ± 9.2mg/dl (N = 10) vs 67.7 ± 18.7 mg/dl (N = 30), p = 0.0075; daytime: 50.8 ± 8.7mg/dl (N = 10) vs 67.4 ± 18.0mg/dl (N = 30), p = 0.0082; nighttime: 45.1 ± 14.9mg/dl (N = 10) vs 65.8 ± 23.2mg/dl (n = 30), p = 0.0119] and coefficient of variation at night [33.3 ± 5.8% (N = 10) vs 40.5 ± 8.8% (N = 30), p = 0.0210]. Additionally, WFS patients displayed lower time in high-range hyperglycemia (> 250mg/dl) across all parts of day [24h: 4.6 ± 3.8% (N = 10) vs 13.4 ± 10.5% (N = 30), p = 0.0004; daytime: 4.7 ± 3.9% (N = 10) vs 13.8 ± 11.2% (N = 30), p = 0.0005; nighttime: 4.2 ± 5.5% (N = 10) vs 12.1 ± 10.3% (N = 30), p = 0.0272]. Conclusions: Adult patients with Wolfram syndrome show lower mean blood glucose, less extreme hyperglycemia, and lower glycemic variability in comparison to patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

The article published in Acta Diabetologica discusses the role of M-LP/Mpv17L, an atypical phosphodiesterase, in alleviating diabetic conditions in mice. The study found that knockout of the M-LP/Mpv17L gene led to pancreatic β-cell hyperplasia and improved glucose tolerance in mice with streptozotocin-induced diabetes. The research suggests that suppression of M-LP/Mpv17L may be a potential target for treating diabetes by alleviating hyperglycemia and other associated conditions. The study was supported by Grants-in-Aid from the Japan Society for the Promotion of Science. [Extracted from the article]

Introduction: Type 1 and type 2 diabetes mellitus (DM) are often accompanied by mild forms of pancreatic exocrine insufficiency (PEI). The prevalence rates of PEI in diabetic patients are unclear and variable depending on the testing modality and the studies published. The clinical consequences of PEI in diabetics are also not well defined. Aim: We aimed to determine the prevalence of PEI in a diabetic cohort using the faecal elastase-1 (FE-1) assay as a screening test and to validate a patient-reported symptom-based scoring system, the (PEI-S) for diagnosing PEI within this patient population. Methods: Two hundred and three diabetic patients attending diabetic and gastroenterology outpatients of a university hospital without previously known PEI were recruited for the study. Demographic parameters, PEI score (PEI-S), and glycated hemoglobin (HBA1c) were documented in standardized data sheets, and a stool sample was obtained. A FE-1 value < 200 μg/g and or a PEIS of > 0.6 was used as the screening cut-off for PEI. Results: One hundred sixty-six patients returned faecal samples. The prevalence of PEI, as measured by low FE-1, was 12%. Smoking was associated with an increased risk of developing PEI in this diabetic population. No other independent risk factors were identified. The PEI-S system did not differentiate between people with diabetes having a normal and low FE1. Conclusion: 12% of this mixed, real-life cohort of type 1 and 2 DM patients had undiagnosed PEI, as defined by an FE-1 score of less than 200 μg/g. While this may appear low, given the rising prevalence of type 2 DM worldwide, there is likely an unrecognized burden of PEI, which has long-term health consequences for those affected. The PEI-S, a symptom-scoring system for patients with PEI, did not perform well in this patient group. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate longitudinal changes in optical coherence tomography angiography (OCTA) metrics in children and adolescents with type 1 diabetes (T1D). Methods: This prospective observational cohort study included thirty-two eyes from thirty T1D children with no history of diabetic retinopathy (DR) who were followed up for 4 years. Participants underwent OCTA examinations at baseline and during follow-up. Quantitative OCTA metrics were measured using a customized MATLAB algorithm. Generalized mixed-effect models were used to determine their relationship with DR development. Systemic parameters and OCTA metrics were screened using least absolute shrinkage and selection operator to identify predictors for visual function. Results: Over the 4-year period, seven of the included eyes developed DR, and most OCTA metrics decreased with diabetes duration. Higher peripapillary and parafoveal nasal quadrant vessel area density (VAD) in the superficial capillary plexus (SCP) and vessel skeleton density (VSD) in both the SCP and the deep capillary plexus (DCP) were associated with a lower risk of DR in T1D. Parafoveal DCP VSD and VAD in the temporal and inferior quadrants were anticorrelated with changes in best corrected visual acuity. Conclusions: OCTA metrics dynamically change over the duration of diabetes and can be used as biomarkers to improve the risk evaluation of DR development and visual function in T1D children and adolescents. [ABSTRACT FROM AUTHOR]

Aim: To analyze the prevalence of anxiety and depression in a large cohort of adults with autoimmune diabetes, identifying sex-driven associated factors. Materials and methods: In this cross-sectional study, we enrolled 553 consecutive adults with Type 1 diabetes mellitus or latent autoimmune diabetes in adults who came to the Division of Endocrinology of the S.Orsola-Malpighi Polyclinic, Bologna (Italy), to receive their second dose of SARS-CoV-2 vaccine. We administered the questionnaires: Hospital Anxiety and Depression Scale, Diabetes Distress Scale, Diabetes-related Quality of Life, Diabetes Treatment Satisfaction Questionnaire. We collected clinical and biochemical data and 14 days glucose metrics in patients with sensor use > 70% in a time span of ± 4 months from the questionnaires' administration. We excluded 119 patients from our analyses with missing data (final cohort n = 434: 79% of those enrolled). Results: Anxiety and depression prevalence was respectively 30.4% and 10.8%. According to the multivariate analysis, higher diabete-related emotional burden, lower treatment satisfaction, but not physician-related distress, were risk factors for anxiety and depression; female sex was associated with anxiety (OR 0.51, 95% 0.31–0.81; p = 0.005); in women, depression was associated with increasing age (males vs. females OR 0.96 per 1 year increase, 95% CI 0.92–1.00; p = 0.036), whilst in men with HbA1c (OR 1.08 per 1 mmol/mol increase, 95% CI 1.03–1.13; p = 0.002). Conclusion: Nearly 1/3 of patients with autoimmune diabetes suffers from anxiety and 1/10 from depression. These conditions are associated with independent modifiable and non-modifiable characteristics. For depression, these characteristics differ between males and females. [ABSTRACT FROM AUTHOR]

Background: Poorly controlled adolescents living with type 1 diabetes (T1D) and pump failure of insulin delivery leading to diabetic ketoacidosis (DKA) are still challenging in the western world. Aim: To investigate the effect of a combination modality of long-acting insulin for basal coverage and a pump for boluses, on the incidence of DKA and glycemic parameters in pediatric and young adults with poorly controlled T1D. Methods: This multicenter, observational retrospective study included 55 patients (age range 3–25 years, 52.7% males) who were treated with the combination modality for a median of 18 months [(IQR)12,47], as part of their clinical care. Data were retrieved at initiation of the combined modality, after 6 months, and at last visit. Results: Cohort's median age at combination modality initiation was 14.5 years [IQR12.4,17.3], and its median HbA1c level was 9.2% [IQR 8.2,10.2]. The main reasons for combination modality initiation were: (a) concern about sustained hyperglycemia on current management in 41.8%, (b) previous DKA episodes in 30.8%, and (c) refusal to wear a pump continuously in 14.6%. The percent of patients experiencing DKA who used the modality till end decreased from 25.4 to 8.8%. The frequency of DKA events per patient month decreased after 6 months from 0.073 (min 0, max 0.5) to 0.020 (min 0, max 0.5), p = 0.01, and at end to 0.016 (min 0, max 0.25), p = 0.007. Conclusions: The combination modality of once-daily long-acting insulin and pump for boluses is safe, feasible, and effective in preventing DKA among poorly controlled young people living with T1D, unable or un-willing to use advanced closed pumps. [ABSTRACT FROM AUTHOR]

Background: Individuals with type 1 diabetes mellitus (T1DM) face impaired cardiorespiratory fitness and glycemic control, increasing the risk of cardiovascular complications. High-intensity interval training (HIIT) has emerged as a promising exercise modality with potential benefits for both aspects in this population. Objectives: The primary aim was to investigate the effects of HIIT on cardiorespiratory fitness and glycemic parameters in patients with T1DM. The secondary aim was to examine the most effective HIIT protocol for cardiorespiratory fitness and glycemic parameters in patients with T1DM. Design: Systematic review and meta-analysis. Data Sources: Two major electronic databases (Web of Science and PubMed) were searched up to February 2024. Eligibility Criteria for Selecting Studies: Randomized and non-randomized trials involving adult patients with T1DM, free of complications and other diseases examining the effects of HIIT (HIIT pre vs. post; HIIT vs. control group or HIIT vs. moderate-intensity continuous training (MICT)) on cardiorespiratory fitness and glycemic parameters were included. Results: A total of ten studies met the inclusion criteria. The meta-analysis revealed a significant improvement in cardiorespiratory fitness following HIIT interventions (pre vs. post) in patients with T1DM (standardized mean difference (SMD) = 0.59, 95% confidence interval (CI) = 0.16 to 1, p = 0.01). Furthermore, HIIT (pre vs. post) was associated with significant improvements in 24-h mean glucose control (SMD = − 0.44, 95% CI = − 0.81 to − 0.06, p = 0.02), but the results (pre vs. post) failed to identify significant improvements in fasting glucose (SMD = − 0.26, 95% CI = − 0.78 to 0.24, p = 0.3) and glycated hemoglobin (HbA1C) values (SMD = − 0.28, 95% CI = − 0.61 to 0.05, p = 0.1). However, in comparison with a control group, HIIT showed significantly favorable effects on HbA1C (SMD = − 0.74, 95% CI = − 1.35 to − 0.14, p = 0.02). Finally, the meta-regression analysis did not find any moderating effect of any HIIT characteristics (i.e., intervention duration, session duration, work time, rest time, number of bouts, and intensity) on cardiorespiratory fitness and glycemic parameters. Conclusion: Our systematic review and meta-analysis show that T1DM patients who performed a HIIT intervention significantly improved cardiorespiratory fitness and reduced their 24-h mean glucose levels, but not their HbA1C and fasting glucose. These findings support the application of HIIT interventions in T1DM patients. However, the guidelines for the most effective protocol remain unclear; hence, future studies are needed. [ABSTRACT FROM AUTHOR]

Background: Adults with type 1 or type 2 diabetes often face financial challenges and other unmet social needs to effective diabetes self-management. Objective: Whether a digital intervention focused on addressing socioeconomic determinants of health improves diabetes clinical outcomes more than usual care. Design: Randomized trial from 2019 to 2023. Participants: A total of 600 adults with diabetes, HbA1c ≥ 7.5%, and self-reported unmet social needs or financial burden from a health system and randomized to the intervention or standard care. Intervention: CareAvenue is an automated, e-health intervention with eight videos that address unmet social needs contributing to poor outcomes. Measures: Primary outcome was HbA1c, measured at baseline, and 6 and 12 months after randomization. Secondary outcomes included systolic blood pressure and reported met social needs, cost-related non-adherence (CRN), and financial burden. We examined main effects and variation in effects across predefined subgroups. Results: Seventy-eight percent of CareAvenue participants completed one or more modules of the website. At 12-month follow-up, there were no significant differences in HbA1c changes between CareAvenue and control group (p = 0.24). There were also no significant between-group differences in systolic blood pressure (p = 0.29), met social needs (p = 0.25), CRN (p = 0.18), and perceived financial burden (p = 0.31). In subgroup analyses, participants with household incomes 100–400% FPL (1.93 (SE = 0.76), p < 0.01), 201–400% FPL (1.30 (SE = 0.62), p < 0.04), and > 400% FPL (1.27 (SE = 0.64), p < 0.05) had significantly less A1c decreases compared to the control group. Conclusions: On average, CareAvenue participants did not achieve better A1c lowering, met needs, CRN, or perceived financial burden compared to control participants. CareAvenue participants with higher incomes achieved significantly less A1c reductions than control. Further research is needed on social needs interventions that consider tailored approaches to population subgroups. Clinical Trials Registry: ClinicalTrials.gov ID NCT03950973, May 2019. [ABSTRACT FROM AUTHOR]

Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM). Prerenal acute kidney injury (AKI) is associated with profound hypovolemia and reduced renal perfusion. Results regarding hyperchloremia-associated AKI in patients with DKA are conflicting; we therefore investigated the potential relationship between hyperchloremia status and the risk of developing AKI. This single-center cohort study included 113 newly diagnosed T1DM patients with DKA admitted to the pediatric intensive care unit. Laboratory parameters, including Na, K, urea, creatinine, and chloride levels, were retrospectively reviewed at the time of presentation and at 12, 24 and 36 h. AKI was defined using the eGFR according to the pediatric RIFLE classification criteria. Twenty-two (19.5%) of the 113 patients were in the AKI group. Two-way repeated-measures ANOVA showed significant (P values ≤ 0.01) time interaction effects within the groups based on the eGFR and the serum chloride, hyperchloremia, and phosphate levels. Serum chloride levels did not differ between the groups during the first 12 h (p > 0.05) but were significantly greater in the AKI group than in the non-AKI group at 24 h and 36 h (p < 0.01). The final DKA resolution time was significantly greater in the AKI group than in the non-AKI group [22.2 (9.5) vs. 17.0 (12.0) h, respectively; p = 0.03]. However, the groups had similar lengths of hospital stay [13.0 (8.0) days vs. 12.0 (4.0) days, respectively; p = 0.17]. Conclusions: Hyperchloremia may be iatrogenic rather than causative during treatment. This may worsen renal failure and prolong the recovery and treatment time for DKA patients. What is Known? • Acute kidney injury resulting from severe volume depletion is a common occurrence in diabetic ketoacidosis and typically requires significant volume replacement therapy. • In recent years, hyperchloremia has been associated with increased risks of AKI, morbidity, and mortality in some conditions, such as diabetic ketoacidosis. What is New? • The incidence of hyperchloremia increases over time during the treatment of diabetic ketoacidosis. • Hyperchloremia may be an iatrogenic element rather than a cause of acute kidney injury during the treatment of diabetic ketoacidosis. [ABSTRACT FROM AUTHOR]

Increased cardiovascular risk has been associated with certain platelet morphological parameters, and several single nucleotide polymorphisms (SNPs) have been reported to be linked. Still, little is known about their role among children with type 1 diabetes mellitus (T1DM). So, we aimed to investigate platelet parameters and lipid profile changes in relation to rs7961894 SNP in children with T1DM. Eighty children with T1DM and eighty apparently healthy controls participated in this cross-sectional study. Platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), HbA1c, triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol were measured, and atherogenic indices were calculated. Using a real-time polymerase chain allelic discrimination technique, rs7961894 SNP was genotyped. Children with T1DM had significantly higher MPV, PDW, TC, and LDL-C compared to controls. 25% of patients had rs7961894 CT genotype with significantly higher MPV, PDW, PCT, LDL-C, triglycerides, Castelli's risk index II (CRI II), and atherogenic index of plasma (AIP) compared to CC genotyped patients. MPV correlated significantly with CRI II and AIP, PDW with CRI II, while PCT correlated substantially with HbA1c, LDL-C, CRI II, and AIP. rs7961894 CT genotype was a significant dependent predictor of the changes in MPV, PDW, and PCT in multivariate regression analysis. Conclusion: In children with T1DM, rs7961894 CT genotype is significantly linked to MPV, PDW, and PCT changes, which showed a substantial relationship to CRI II and AIP, highlighting the importance of monitoring these patients to identify potential cardiovascular risks early. What is Known: • Platelets and dyslipidemia are involved in atherosclerosis pathogenesis • Changes in platelet activity and morphological parameters in diabetes mellitus are contradictory • rs7961894 single nucleotide polymorphism is associated with significant changes in mean platelet volume (MPV) with no available data in children What is New: • Children with type 1 diabetes mellitus exhibited significantly higher values of MPV and platelet distribution width (PDW) • rs7961894 CT genotype was a dependent predictor of the changes in MPV, PDW, and plateletcrit (PCT) values • Diabetic children with the rs7961894 CT genotype showed substantial alterations in lipid parameters with a strong correlation between MPV, PDW, and PCT and Castelli's risk index II and the atherogenic index of plasma [ABSTRACT FROM AUTHOR]

Introduction: Screening for islet-specific autoantibodies can identify individuals at risk for type 1 diabetes (T1D). Despite calls for increased nationwide autoantibody screening efforts, it is unclear how many individuals have participated in screening among people who may benefit from it. Moreover, knowledge and perceptions of autoantibody screening in real-world samples are not well understood. Methods: We surveyed a sample of individuals (aged 18+ years old) from T1D Exchange Registry with a personal or family history of T1D to assess their self-reported T1D autoantibody knowledge, experiences, and attitudes. Participants belonged to one of three groups: adults with T1D who had a biological child without T1D or future plans for a child (PWD); parents without T1D who had a biological child with T1D and one or more biological children without T1D (Caregivers); and first-degree adult children or siblings to a person with T1D (Relatives). Descriptive analyses (means, standard deviations, frequencies) are presented by participant groups. Results: A total of 510 participants enrolled in the study. Across groups, participants reported feeling a little to somewhat knowledgeable about autoantibody screening and positive perceptions of autoantibody screening in general. However, few participants had screened their child without T1D (PWDs, 21.94%; Caregivers, 46.30%) or themselves (Relatives, 19.23%). Among those who had screened, participants reported generally positive experiences. Among those who had not screened, many participants were "undecided" about autoantibody screening (PWD, 38.46%; Caregivers, 40.52%; Relatives, 44.44%). Influences reported for participants' decisions to screen, not screen, or their current indecision differed by group: PWDs (21.70%) and Caregivers (26.87%) most often reported self-initiated research as an influence and Relatives reported they had not previously considered screening (48.28%). Conclusion: Results highlight the need for more accessible information about screening, including real experiences from those who have screened. [ABSTRACT FROM AUTHOR]

Introduction: The transition from paediatric to adult diabetes care (TPA) of children/adolescents with type 1 diabetes (T1D) represents a unique challenge and remains a critical phase in the T1D care pathway. This study aims to describe and understand the experience of the transition process from a participant's perspective in young adults who are living in France with T1D and to measure their satisfaction. Methods: An online questionnaire was presented to people with T1D in France on a global online participant community platform. The questionnaire was developed by a scientific committee including paediatric and adult diabetologists and refined by a group of participants. Thematic qualitative analysis was performed on the responses. Results: A total of 104 respondents were included in the survey (mean age 24.4 years [95% CI 23.8–25.0]; 61.5% female). The mean age at the time of transition was 18.4 years (95% CI 17.8–18.9), and 56% of respondents had their first adult diabetology follow-up in the same institution. During TPA, of the 76 participants who experienced personal issues, 74% experienced at least one issue with their diabetes management in the months following the transition. In the following months, 61% experienced new or unexpected problems in monitoring their diabetes after transition and 44% reported unusual glycaemic imbalances, including hypoglycaemia (8%) and hyperglycaemia (9%) requiring hospitalisation. Presence of personal issues during TPA was significantly associated with occurrence of problems with diabetes management or glycaemic imbalance. Three factors identified for a successful transition were (i) early meeting with the 'adult' diabetes care team, (ii) letting the participants choose the right age to leave paediatric clinic and (iii) having good diabetes control at the beginning of the TPA process. Conclusion: Most young adults with T1D report experiencing issues around TPA with significant consequences on their disease management. Hence, it is necessary to identify these issues to better support them and improve diabetes management during this phase. [ABSTRACT FROM AUTHOR]

The Tandem t:slim X2 insulin pump is a second-generation automated insulin delivery system with Control-IQ technology. It consists of an X2 insulin pump, an integrated Dexcom sensor, and an embedded 'Control-IQ' algorithm, which predicts glucose levels 30 min in the future, adapting the programmed basal insulin rates to get glucose levels between 112.5 and 160 mg/dl (8.9 mmol/l). The system delivers automatic correction boluses of insulin when glucose levels are predicted to rise > 180 mg/dl (10 mmol/l). It has been commercially available since 2016. We reviewed the current evidence about the psychological, safety, and exercise-related outcomes of this device in children, adolescents, and young adults living with type 1 diabetes. We screened 552 papers, but only 21 manuscripts were included in this review. Fear of hypoglycemia is significantly reduced in young people with diabetes and their parents. Interestingly, diabetes-related distress is decreased; thus, the system is well accepted by the users. The sleeping quality of subjects living with diabetes and their caregivers is improved to a lesser extent as well. Despite the small number of data, this system is associated with a low rate of exercise-related hypoglycemia. Finally, evidence from the literature shows that this system is safe and effective in improving psychological personal outcomes. Even if further steps toward the fully closed loop are still mandatory, this second-generation automated insulin delivery system reduces the burden of diabetes. It properly addresses most psychological issues in children, adolescents, and young adults with type 1 diabetes mellitus; thus, it appears to be well accepted. [ABSTRACT FROM AUTHOR]

Purpose: Compared to the general stillbirth rate in Germany for term deliveries of 0.12% the risk in type 1 diabetes mellitus is reported to be up to ten times higher. The reasons for this excess risk of intrauterine demise are still not fully elucidated. Risk factors named in the literature include poor glycemic control before and during pregnancy and the occurrence of ketoacidosis. Additionally there might be a diabetes related type of placental dysfunction leading to organ failure in late pregnancy. Understanding the underlying causes is mandatory to develop strategies to reduce the incidences. The Purpose of this publication is to point out the difficulties in prediction of intrauterine death in pregnant type 1 diabetes patients and thus emphasizing the necessity of constant awareness to all caregivers. Methods: We present a case series of four cases of stillbirth that occurred in patients with type 1 diabetes mellitus at our tertiary care obstetric unit during a five-year period. Results: In all four presented cases the underlying cause of intrauterine demise was different and we could not find a common mechanism or risk profile. Furthermore, established monitoring tools did not become peculiar to raise awareness. We compared our cases to published data. Underlying causes of intrauterine death in type 1 diabetes are discussed in the light of the current literature. Conclusions: The main risk factors of stillbirth in diabetic pregnancies are high maternal blood glucose levels including pre-conceptional HbA1c and diabetic ketoacidosis. Late acute placental insufficiency are associated with intrauterine death in type 1 diabetes. Despite the elevated risk of near term intrauterine demise there are currently no guidelines on how to monitor pregnancies in type 1 diabetes for fetal distress during the third trimester. Established thresholds for fetal Doppler data indicating fetal distress in normal and growth restricted fetuses may not be applicable for overgrown fetuses. Future research on how to monitor the diabetic fetus needs to be initiated. [ABSTRACT FROM AUTHOR]

Environmental factors, in particular viral infections, are thought to have an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The COVID-19 pandemic reinforced this hypothesis as many observational studies and meta-analyses reported a notable increase in the incidence of T1DM following infection with SARS-CoV-2 as well as an association between SARS-CoV-2 infection and the risk of new-onset T1DM. Experimental evidence suggests that human β-cells express SARS-CoV-2 receptors and that SARS-CoV-2 can infect and replicate in β-cells, resulting in structural or functional alterations of these cells. These alterations include reduced numbers of insulin-secreting granules, impaired pro-insulin (or insulin) secretion, and β-cell transdifferentiation or dedifferentiation. The inflammatory environment induced by local or systemic SARS-CoV-2 infection might result in a set of signals (such as pro-inflammatory cytokines) that lead to β-cell alteration or apoptosis or to a bystander activation of T cells and disruption of peripheral tolerance that triggers autoimmunity. Other mechanisms, such as viral persistence, molecular mimicry and activation of endogenous human retroviruses, are also likely to be involved in the pathogenesis of T1DM following SARS-CoV-2 infection. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies. Many studies identified an increase in the incidence of type 1 diabetes mellitus (T1DM) during the COVID-19 pandemic, but other reports do not support this association. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies. Key points: Epidemiological studies and meta-analyses reported an increase in the incidence of type 1 diabetes mellitus during the COVID-19 pandemic as well as an association between SARS-CoV-2 infection and the risk of new-onset type 1 diabetes mellitus. Angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and alternative receptors of SARS-CoV-2 have been identified in several human cell types, including pancreatic islet β-cells. SARS-CoV-2 proteins are detected in both exocrine and endocrine cells (including β-cells) of post-mortem pancreas samples from patients with COVID-19 and in samples from non-human primates intranasally or intratracheally infected with SARS-CoV-2. SARS-CoV-2 can infect and replicate in pancreatic β-cells ex vivo, resulting in structural and functional alterations of these cells. Pro-inflammatory cytokines produced during SARS-CoV-2 infection can impair human pancreatic islet function. SARS-CoV-2 infection might promote islet autoimmunity through various mechanisms, including bystander activation of T cells, disruption of peripheral tolerance, viral persistence, molecular mimicry and activation of endogenous human retroviruses. [ABSTRACT FROM AUTHOR]

Whole-organ pancreas, pancreatic-kidney and islet transplantation are surgical therapeutic options for the treatment of type 1 diabetes. They can enable effective glycemic control, improve quality of life and delay/reduce the secondary complications of type 1 diabetes mellitus. Radiologists are integral members of the multidisciplinary transplantation team involved in these procedures, with multimodality imaging serving as the mainstay for early recognition and management of transplant related complications. This review highlights the transplantation procedures available for patients with type 1 Diabetes Mellitus with a focus on the imaging appearance of transplantation-related complications. [ABSTRACT FROM AUTHOR]

Based on the signaling hypothesis of blood glucose (BG), a rise in BG levels signals a positive energy budget for healthy individuals but cellular starvation for individuals with type 1 diabetes. We examined this novel prediction and its intervention implications in the context of delay discounting, the degree to which delayed rewards are discounted, and the regulatory effects of insulin ingestion. We recruited 44 adults with type 1 diabetes (mean age 30.8 years, diabetes duration 15.4 years) and recorded their BG levels. The delay discounting rate was measured using the intertemporal choice task, where participants were required to choose between sets of smaller-and-sooner (SS) and larger-and-later (LL) rewards. In addition, 82 age-matched healthy participants were recruited to provide a baseline comparison on delay discounting. Random forest analysis showed that among many diagnostic factors, delay discounting was most dominating in differentiating the individuals with type 1 diabetes from the control participants. A hierarchical linear mixed model revealed that participants with type 1 diabetes had a stronger preference for SS rewards (p <.001) after controlling for covariates. Participants who had insulin delivered before the last meal exhibited a stronger preference for LL rewards compared to after-meal delivery. In contrast, subjective measures (e.g., self-reported hunger) failed to predict the participants' actual BG levels and delay discounting rates. In sum, individuals with type 1 diabetes tend to discount future rewards excessively compared to the control participants. Pre-meal insulin ingestion was associated with a higher LL preference for future rewards. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the blood pressure (BP) status, including arterial stiffness parameters, hemodynamic indicators, circadian profile, and its association with albuminuria in adolescents with type 1 diabetes mellitus (DM1). Methods: The analysis included 46 patients, with diabetes duration of 7.38 ± 3.48 years. Ambulatory blood pressure monitoring (ABPM) was conducted using an oscillometric device, the Mobil-O-Graph, which is a Pulse Wave Analysis Monitor. Results: Hypertension (HT) was diagnosed in 31 adolescents (67% of patients), primarily due to isolated nocturnal BP (21 cases, 68% of HT cases). The HT group exhibited significantly increased diastolic load (DL). Pulse wave velocity (PWV, a measure of arterial stiffness) values showed a strong correlation with both peripheral systolic BP (r = 0.954) and central systolic BP (r = 0.838). Additionally, non-dipping status was found in 61% of the HT group. Urinary albumin excretion (UAE) was positively correlated with diastolic BP (particularly nocturnal) peripheral and central BP, DL, heart rate, augmentation index (AIx@75), and nocturnal total vascular resistance (TVR). Diastolic non-dippers exhibited a significant increase in UAE. Conclusions: Hypertension is a common complication in adolescents with type 1 diabetes mellitus, primarily caused by elevated nocturnal diastolic BP. Albuminuria is mainly associated with diastolic BP, especially during the nocturnal period and in cases of diastolic non-dipping status. The association of UAE with AIx@75 and nocturnal TVR suggests the presence of early-stage vascular disease in diabetic adolescents. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is characterized by the progressive destruction of insulin-producing beta cells in the pancreas. Despite improvements in insulin monitoring techniques, there remains no cure for T1D. Individuals with T1D require lifelong insulin therapy and some develop life-threatening complications. T1D is a complex, multifactorial, autoimmune condition. Understanding why people get T1D and how it progresses has advanced our knowledge of the disease and led to the discovery of specific targets that can be therapeutically manipulated to halt or reverse the course of T1D. Scientists investigating the potential of immunotherapy treatment for the treatment have recently had some encouraging results. Teplizumab, an anti-CD3 monoclonal antibody that has been approved by the FDA, delays the onset of clinical T1D in patients ≥ 8 years of age with preclinical T1D and improves beta cell function. Therapies targeting beta cell health, vitality, and function are now thought to be an essential component of successful combination therapy for T1D. The idea that the beta cells themselves may influence their own destruction during the development of T1D is a notion that has recently been gaining acceptance in the field. Researchers have recently made remarkable strides in beta cell replacement therapy and beta cell regeneration techniques. This review offers a detailed exploration of the pathophysiological mechanisms of T1D. It discusses the intricate interplay of factors leading to T1D development and the innovative approaches being explored to discover new treatments and a cure for the millions of people living with T1D worldwide. [ABSTRACT FROM AUTHOR]

A questionnaire survey on severe hypoglycemia (SH) in pediatric patients with diabetes was distributed to pediatric diabetes specialists and members of the Committee of Pediatric Diabetes in the Japan Diabetes Society. Thirty-three hospitals answered the questionnaire survey, and 17 had treated the eligible patients under 15 years of age, including 506 with type 1 diabetes and 302 with type 2 diabetes. Of these patients, 25 experienced SH from January 2017 to December 2021. SH occurred in 3 patients at 0–5 years, 5 at 5–10 years, and 15 at 10–15 years, and it most frequently occurred between the times of 0:00 and 08:00 a.m. The majority of the patients had SH at home during the nighttime. Only 4 patients experienced SH during school time. Eleven patients took glucose orally, while 5 used glucagon nasal powder. Fifteen patients were transferred to hospital emergency units for the management of SH. From these results, the frequency of SH was estimated to be 0.01/patient/year, and the treatment for SH seemed insufficient. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate potential predictors of effectiveness of SGLT2 inhibitors (SGLT2i) in individuals with type 1 diabetes (T1D) on sensor-augmented pump (SAP) therapy. Methods: We included individuals with T1D receiving SAP therapy at our hospital who were newly initiated on SGLT2i between 2019 and 2020 and were followed for at least 1 year. Data on BMI, blood tests, and continuous glucose monitoring (CGM) were compared before and 12 months after initiation of SGLT2i. Predictors of incremental increases in time in range (ΔTIR) were explored using a multiple regression analysis. Cutoff values for the predictors were determined using an ROC curve analysis. Results: A total of 17 individuals (females, 70.6%; median age, 44.0 years) were included, excluding three individuals who discontinued SGLT2i due to side effects. During follow-up, their median BMI decreased significantly (P = 0.013), while no significant change was seen in their total daily dose of insulin, basal-to-total insulin ratio. Again, their HbA1c, TIR, and time above range (TAR) improved significantly (P = 0.004, P = 0.003, and P = 0.003, respectively), while their time below range (TBR) showed no significant change. The predictor of increased ΔTIR was high urinary albumin-to-creatinine ratio (UACR) at baseline (P = 0.026) only, with the cutoff value determined to be 28.0 mg/g Cr or higher (AUC = 0.82, P = 0.003). Conclusions: It may be suggested that individuals with T1D on SAP therapy and having near-microalbuminuria or higher could be expected to show significant improvement in TIR. [ABSTRACT FROM AUTHOR]

Background: Severe hypoglycemia (SH) poses a significant challenge in the management of type 1 diabetes (T1D); however, the factors that offer protection other than diabetes technologies are under-studied. The primary objective of this study was to examine the association between hypoglycemia problem-solving (HPS) abilities and severe hypoglycemic events in adults with T1D using Poisson regression analysis. Methods: In this cross-sectional study, 287 adults with T1D (mean age: 50.3 ± 14.5 years, male: 36.2%, diabetes duration: 17.5 ± 11.2 years, mean HbA1c: 7.7 ± 0.9%) were included and categorized into two groups: non-SH (n = 262) and SH (n = 25). Data on diabetic complications, the hypoglycemia problem-solving scale (HPSS), and treatment details were collected. Impaired awareness of hypoglycemia (IAH) was evaluated using Gold's method. Univariate and multivariable Poisson regression models were used for the analysis, and the findings were presented as incidence rate ratios (IRRs) at 95% confidence interval (CI). Results: The incidence of SH was 16.7 (95% CI 7.5–26.0) per 100 person-years. In the univariate Poisson regression analysis, findings revealed associations between IAH, diabetic peripheral neuropathy (DPN), and HPSS1. On the other hand, the multivariate Poisson regression analysis, utilizing stepwise variable selection, identified DPN (IRR: 4.65, 95% CI 1.96–11.04; P < 0.001) and HPSS1 score (IRR: 0.51, 95% CI 0.34, 0.76; P = 0.001) as factors significantly associated with SH. Conclusion: We identified HPS abilities, in addition to DPN, were associated with SH in adults with T1D. Trial registration: University Hospital Medical Information Network (UMIN) Center: UMIN000039475), approval date: February 13, 2020. [ABSTRACT FROM AUTHOR]

Objective: Medical nutrition therapy is an essential component of management of type 1 diabetes (T1D). This study evaluated adherence of children with T1D to International Society for Pediatric and Adolescent Diabeties (ISPAD) 2018 dietary recommendations. Methods: Dietary assessment was conducted for 75 children with T1D of duration > 1 year. Results: Adherence to the recommendations was observed in 40% of participants. Mean (SD) calorie intake (%) from carbohydrate, fat and protein was 51.93 (6.08), 32.42 (5.66) and 15.95 (2.45), respectively. 68% participants had an energy deficit of >10% of the estimated average requirement. Children in "Adherent" group had significantly lower energy intake (%) from carbohydrates [50.26 (2.11) vs 53.18 (7.39)], saturated fats (<10%) and higher from proteins [16.74 (1.68) vs 15.42 (2.75)] as compared to "Non-adherent"group (P < 0.05). The mean (SD) HbA1c (%) was significantly lower in the "Adherent" group [7.5 (0.50) vs 9.17 (1.12)]. Conclusions: Diet in a large proportion of Indian children with T1D does not meet the ISPAD recommendations. [ABSTRACT FROM AUTHOR]

Challenges and fears related to managing glucose levels around planned and spontaneous exercise affect outcomes and quality of life in people living with type 1 diabetes. Advances in technology, including continuous glucose monitoring, open-loop insulin pump therapy and hybrid closed-loop (HCL) systems for exercise management in type 1 diabetes, address some of these challenges. In this review, three research or clinical experts, each living with type 1 diabetes, leverage published literature and clinical and personal experiences to translate research findings into simplified, patient-centred strategies. With an understanding of limitations in insulin pharmacokinetics, variable intra-individual responses to aerobic and anaerobic exercise, and the features of the technologies, six steps are proposed to guide clinicians in efficiently communicating simplified actions more effectively to individuals with type 1 diabetes. Fundamentally, the six steps centre on two aspects. First, regardless of insulin therapy type, and especially needed for spontaneous exercise, we provide an estimate of glucose disposal into active muscle meant to be consumed as extra carbohydrates for exercise ('ExCarbs'; a common example is 0.5 g/kg body mass per hour for adults and 1.0 g/kg body mass per hour for youth). Second, for planned exercise using open-loop pump therapy or HCL systems, we additionally recommend pre-emptive basal insulin reduction or using HCL exercise modes initiated 90 min (1–2 h) before the start of exercise until the end of exercise. Modifications for aerobic- and anaerobic-type exercise are discussed. The burden of pre-emptive basal insulin reductions and consumption of ExCarbs are the limitations of HCL systems, which may be overcome by future innovations but are unquestionably required for currently available systems. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: This study aimed to describe the relationship between breastfeeding episodes and maternal glucose levels, and to assess whether this differs with closed-loop vs open-loop (sensor-augmented pump) insulin therapy. Methods: Infant-feeding diaries were collected at 6 weeks, 12 weeks and 24 weeks postpartum in a trial of postpartum closed-loop use in 18 women with type 1 diabetes. Continuous glucose monitoring (CGM) data were used to identify maternal glucose patterns within the 3 h of breastfeeding episodes. Generalised mixed models adjusted for breastfeeding episodes in the same woman, repeat breastfeeding episodes, carbohydrate intake, infant age at time of feeding and early pregnancy HbA1c. This was a secondary analysis of data collected during a randomised trial (ClinicalTrials.gov registration no. NCT04420728). Results: CGM glucose remained above 3.9 mmol/l in the 3 h post-breastfeeding for 93% (397/427) of breastfeeding episodes. There was an overall decrease in glucose at nighttime within 3 h of breastfeeding (1.1 mmol l−1 h−1 decrease on average; p=0.009). A decrease in nighttime glucose was observed with open-loop therapy (1.2 ± 0.5 mmol/l) but was blunted with closed-loop therapy (0.4 ± 0.3 mmol/l; p<0.01, open-loop vs closed-loop). Conclusions/interpretation: There is a small decrease in glucose after nighttime breastfeeding that usually does not result in maternal hypoglycaemia; this appears to be blunted with the use of closed-loop therapy. [ABSTRACT FROM AUTHOR]

Children with type 1 diabetes and their caregivers face numerous challenges navigating the unpredictability of this complex disease. Although the burden of managing diabetes remains significant, new technology has eased some of the load and allowed children with type 1 diabetes to achieve tighter glycaemic management without fear of excess hypoglycaemia. Continuous glucose monitor use alone improves outcomes and is considered standard of care for paediatric type 1 diabetes management. Similarly, automated insulin delivery (AID) systems have proven to be safe and effective for children as young as 2 years of age. AID use improves not only blood glucose levels but also quality of life for children with type 1 diabetes and their caregivers and should be strongly considered for all youth with type 1 diabetes if available and affordable. Here, we review key data on the use of diabetes technology in the paediatric population and discuss management issues unique to children and adolescents. [ABSTRACT FROM AUTHOR]

This review outlines some of the extraordinary recent advances in diabetes technology, which are transforming the management of type 1 diabetes before, during and after pregnancy. It highlights recent improvements associated with use of continuous glucose monitoring (CGM) but acknowledges that neither CGM nor insulin pump therapy are adequate for achieving the pregnancy glucose targets. Furthermore, even hybrid closed-loop (HCL) systems that are clinically effective outside of pregnancy may not confer additional benefits throughout pregnancy. To date, there is only one HCL system, the CamAPS FX, with a strong evidence base for use during pregnancy, suggesting that the pregnancy benefits are HCL system specific. This is in stark contrast to HCL system use outside of pregnancy, where benefits are HCL category specific. The CamAPS FX HCL system has a rapidly adaptive algorithm and lower glucose targets with benefits across all maternal glucose categories, meaning that it is applicable for all women with type 1 diabetes, before and during pregnancy. For women of reproductive years living with type 2 diabetes, the relative merits of using non-insulin pharmacotherapies vs diabetes technology (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium−glucose cotransporter 2 inhibitors) are unknown. Despite the urgent unmet need and potential benefits, studies of pharmacotherapy and technology use are extremely limited in pregnant women with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this work was to investigate the association between macronutrient intakes and continuous glucose monitoring (CGM) metrics in individuals with type 1 diabetes. Methods: In 470 individuals with type 1 diabetes of the GUTDM1 cohort (65% female, median age 40 [IQR 28–53] years, median diabetes duration 15 [IQR 6–29] years), we used logistic regression to establish associations between macronutrient intakes and the CGM metrics time in range (TIR, time spent between 3.9–10.0 mmol/l blood glucose, optimally set at ≥70%) and time below range (TBR, <3.9 mmol/l blood glucose, optimally set at <4%). ORs were expressed per 1 SD intake of nutrient and were adjusted for other macronutrient intakes, age, sex, socioeconomic status, BMI, duration of type 1 diabetes, pump use, insulin dose and alcohol intake. Results: The median (IQR) TIR was 67 (51–80)% and TBR was 2 (1–4)%; the mean ± SD energy intake was 6879±2001 kJ, fat intake 75±31 g, carbohydrate intake 162±63 g, fibre intake 20±9 g and protein intake 70±24 g. A higher fibre intake and a lower carbohydrate intake were associated with higher odds of having a TIR≥70% (OR [95% CI] 1.64 [1.22, 2.24] and 0.67 [0.51, 0.87], respectively), whereas solely a higher carbohydrate intake was associated with TBR<4% (OR 1.34 [95% CI 1.02, 1.78]). Conclusions/interpretation: A higher fibre intake is independently associated with a higher TIR. A higher carbohydrate intake is associated with less time spent in hypoglycaemia, a lower TIR and a higher time above range. These findings warrant confirmatory (interventional) investigations and may impact current nutritional guidelines for type 1 diabetes. [ABSTRACT FROM AUTHOR]

The role of automated insulin delivery systems in diabetes is expanding. Hybrid closed-loop systems are being used in routine clinical practice for treating people with type 1 diabetes. Encouragingly, real-world data reflects the performance and usability observed in clinical trials. We review the commercially available hybrid closed-loop systems, their distinctive features and the associated real-world data. We also consider emerging indications for closed-loop systems, including the treatment of type 2 diabetes where variability of day-to-day insulin requirements is high, and other challenging applications for this technology. We discuss issues around access and implementation of closed-loop technology, and consider the limitations of present closed-loop systems, as well as innovative approaches that are being evaluated to improve their performance. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). Methods: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. Results: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). Conclusion: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency (VDD) and anemia are both public health nutrition concerns. An association between VDD and anemia has been suggested in various healthy and diseased populations. The current study aimed to elucidate the effect of VDD on iron status in children with type I diabetes mellitus (T1DM). The study recruited two groups of children with T1DM: control group comprised of 38 T1DM children with sufficient vitamin D (> 30 ng/ml) and a case group, consisted of 52 T1DM children with VDD (< 20 ng/ml). Both groups had comparable gender, age, BMI, and disease duration. The laboratory measurements included analysis of blood indices, markers of iron metabolism, hepcidin and inflammatory markers included interleukin 6 (IL-6) and C-reactive protein (CRP). Compared to control group, T1DM children with VDD differs specifically in terms of some markers of blood indices, such as decreased hemoglobin and increased red blood cell distribution width. Moreover, decreased serum iron, ferritin, total iron-binding capacity and transferrin along with elevated inflammatory markers were observed in case group. Results of the study indicated that VDD had increased the risk of iron deficiency anemia in children with T1DM as well as inflammatory related anemia. Furthermore, in T1DM children, VDD had raised the incidence of both absolute and functional iron deficiency, with greater incidence of the former. This study may indicate that VDD may be a risk factor that may worsen iron deficiency anemia in T1DM. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes (T1D) management exerts a considerable financial burden on patients, caregivers, and developing nations at large. In Ghana, a key governments effort to attenuate the financial burden of T1D on patients was to fashion safety-net mechanisms through financial risk pooling/sharing known as the National Health Insurance Scheme (NHIS). However, there is limited research on patients and caregivers' experiences with the cost of managing T1D within the NHIS in Ghana. Objective: This study explored the cost of T1D management, and the impact of the NHIS policy on mitigating costs of care. Methods: A semi-structured interview guide was developed to collect qualitative data from 28 young people living with T1D (PLWD), 12 caregivers, 6 healthcare providers, and other stakeholders in Western, Central and the Greater Accra regions. Multiple data collection techniques including mystery client and in-depth interviews were used to collect data. Thematic content analysis was performed with QSR NVivo 14. Results: Five key domains/themes which are: cost of T1D management supplies; cost of clinical care; cost of transportation; cost of diet; and NHIS were identified. The daily cost of blood glucose testing and insulin injection per day was between GHC 5–7 (US$ 0.6 to 1.0). The NHIS did not cover supplies such as strips, glucometers, HbA1c tests, and periodic medical tests. Even for those cost which were covered by the NHIS (mainly pre-mixed insulin), marked government delays in funds reimbursement to accredited NHIS facilities compelled providers to push the financial obligation onto patients and caregivers. Such cost obligations were fulfilled through out-of-pocket top-up or full payment of insulin of about GHC 15–25 (US$ 2–4), and GHC 25–50 (US$4–8) depending on the region and place of residence. Conclusion: The cost of managing T1D was a burden for patients and their caregivers. There was a commodification of life-saving insulin on the Ghanaian market, and the NHIS did not function well to ease the cost-burden of T1D management on patients and caregivers. The findings call for the need to scale up NHIS services to include simple supplies, particularly test strips, and always ensure the availability of life-saving insulin in healthcare facilities. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a significant concern for individuals with type 1 diabetes (T1D), impacting their quality of life and healthcare costs. Identifying T1D patients at greater risk of developing CKD is crucial for preventive measures. However, it is challenging due to the asymptomatic progression of CKD and limited nephrologist availability in many countries. This study explores machine learning algorithms to predict CKD risk in T1D patients using ten years of retrospective data from the Epidemiology of Diabetes Interventions and Complications clinical trial. Eleven machine learning algorithms were applied to twenty-two readily available features from T1D patients' routine check-ups and self-assessments to develop 10-year CKD risk prediction models. In addition, we also proposed a heterogeneous ensemble model (STK) using a stacking generalization approach. The models' performance was evaluated using different evaluation metrics and repeated stratified k-fold cross-validation. Several predictive models showed reliable performance in CKD risk prediction, with the proposed ensemble model being the best performing with an average accuracy of 0.97, specificity of 0.98, sensitivity/recall of 0.96, precision of 0.98, F1 score of 0.97, Kappa and MCC score of 0.94, AUROC of 0.99, and Precision-Recall curve of 0.99. The proposed machine learning approach could be applicable for CKD risk prediction in T1D patients to ensure the necessary precautions to overcome the risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Autoimmune diseases such as systemic lupus erythematosus (SLE) display a strong female bias. Although sex hormones have been associated with protecting males from autoimmunity, the molecular mechanisms are incompletely understood. Here we report that androgen receptor (AR) expressed in T cells regulates genes involved in T cell activation directly, or indirectly via controlling other transcription factors. T cell-specific deletion of AR in mice leads to T cell activation and enhanced autoimmunity in male mice. Mechanistically, Ptpn22, a phosphatase and negative regulator of T cell receptor signaling, is downregulated in AR-deficient T cells. Moreover, a conserved androgen-response element is found in the regulatory region of Ptpn22 gene, and the mutation of this transcription element in non-obese diabetic mice increases the incidence of spontaneous and inducible diabetes in male mice. Lastly, Ptpn22 deficiency increases the disease severity of male mice in a mouse model of SLE. Our results thus implicate AR-regulated genes such as PTPN22 as potential therapeutic targets for autoimmune diseases. Androgen is a sex hormone that may contribute to sex biases in autoimmunity. Here the authors show that in T cells androgen induces the expression of Ptpn22 phosphatase to negatively regulate T cell activation, thereby contributing to protecting males from major autoimmune diseases such as systemic lupus erythematosus and type 1 diabetes. [ABSTRACT FROM AUTHOR]

Bone fragility is a serious yet under-recognised complication of diabetes mellitus (DM) that is associated with significant morbidity and mortality. Multiple complex pathophysiological mechanisms mediating bone fragility amongst DM patients have been proposed and identified. Fracture risk in both type 1 diabetes (T1D) and type 2 diabetes (T2D) continues to be understated and underestimated by conventional risk assessment tools, posing an additional challenge to the identification of at-risk patients who may benefit from earlier intervention or preventive strategies. Over the years, an increasing body of evidence has demonstrated the efficacy of osteo-pharmacological agents in managing skeletal fragility in DM. This review seeks to elaborate on the risk of bone fragility in DM, the underlying pathogenesis and skeletal alterations, the approach to fracture risk assessment in DM, management strategies and therapeutic options. [ABSTRACT FROM AUTHOR]

Purpose: Preexisting type 1 diabetes is a stressful situation for women in pregnancy. We aimed to evaluate health-related quality of life (HRQoL) during pregnancy in women with type 1 diabetes and examine the association between HRQoL and pregnancy outcomes. Methods: This multicenter prospective cohort study involved 115 pregnant women with type 1 diabetes from 11 participating centers in China. HRQoL was investigated in three trimesters using European Quality-of-life 5-Dimension 5-Level questionnaire (EQ-5D-5 L). Chinese time trade-off value method was used to calculate the EQ-5D-5 L score. Multivariable logistic regression model was used to evaluate the effect of HRQoL on maternal and neonatal outcomes. Receiver operating characteristic curves and distribution-based methods were employed to estimate minimally important differences of clinically important decline in HRQoL. Results: 50.43% of the studied women with type 1 diabetes reported impaired HRQoL in pregnancy. Estimated maternal HRQoL significantly decreased from early to mid-pregnancy (mean EQ-5D-5 L score 0.97 in the first trimester and 0.91 in the second trimester) and improved slightly in late pregnancy (mean EQ-5D-5 L score 0.95). Multivariable regression model showed that women who experienced impaired HRQoL in pregnancy had higher risk of hypertensive disorder, preterm birth, and composite pregnancy outcome. The estimated minimally important difference for composite pregnancy outcome was -0.045 to -0.043. Conclusions: Experiencing impaired HRQoL during pregnancy was associated with a higher risk of hypertensive disorder and preterm birth in women with type 1 diabetes. The estimated minimally important difference of EQ-5D-5 L might serve as a clinically important tool in prenatal care. Trial registration: No.ChiCTR1900025955 [ABSTRACT FROM AUTHOR]

Introduction: The use of most commercially available automated insulin delivery (AID) systems is off-label in pregnancy. However, an increasing number of women with type 1 diabetes (T1D) use such devices throughout pregnancy and delivery. We analysed the data of six women with T1D from a single centre (Diabetology Outpatient Clinic of District-63/Asl Salerno, Italy) who were able to start and maintain AID therapy with the MiniMed™ 780G (Medtronic, Minneapolis, MN, USA) throughout the pregestational care period, pregnancy, delivery, and postpartum. Methods: We retrospectively collected data from six patients with T1D who received training and initiation on use of the MiniMed™ 780G and attended follow-up visits throughout pregnancy (these visits were virtual because of the COVID-19 pandemic). All patients maintained their devices in the closed-loop setting throughout pregnancy and during labour and delivery. We analysed data from the pregestational phase to the first 30 days postpartum. Results: All patients achieved the recommended metabolic goals before conception [median time in range (TIR) of 88% for 70–180 mg/dL; median pregnancy-specific TIR 63–140 mg/dL (ps-TIR) of 66% and maintained the ps-TIR until delivery (median ps-TIR 83%). All patients had slightly better metrics during the night than during the day, with a very low time below range of < 63 mg/dL. Optimal glycaemic values were also maintained on the day of labour and delivery (median ps-TIR 92.5%) and in the first 30 days postpartum, with no severe hypoglycaemia. The only neonatal complications were jaundice in one child and an interatrial defect in another child. Conclusion: In our well-selected and trained patients, use of the MiniMed™ 780G helped to achieve and maintain ps-metrics from the pregestational period to delivery despite the fact that the algorithm is not set to achieve the ambitious glycaemic values recommended for pregnancy. [ABSTRACT FROM AUTHOR]

Aims: Glargine 300 U/mL (Gla-300) has been recently approved for use in children and adolescents with type 1 diabetes (T1D). However, real-world effectiveness data are scarce, and aim of this analysis was to assess clinical outcomes in young patients with T1D switching from 1st generation basal insulin (1BI) to Gla-300. Methods: ISPED CARD is a retrospective, multicenter study, based on data anonymously extracted from Electronic Medical Records. The study involved a network of 20 pediatric diabetes centers. Data on all patients aged < 18 years with T1D switching from 1BI to Gla-300 were analyzed to assess clinical characteristics at the switch and changes after 6 and 12 months in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and standardized body mass index (BMI/SDS). Titration of basal and short-acting insulin doses was also evaluated. Results: Overall, 200 patients were identified. The mean age at the switch to Gla-300 was 13 years, and mean duration of diabetes was 3.9 years. Average HbA1c levels at switch were 8.8%. After 6 months, HbA1c levels decreased by − 0.88% (95% CI − 1.28; − 0.48; p < 0.0001). The benefit was maintained after 12 months from the switch (mean reduction of HbA1c levels − 0.80%, 95% CI − 1.25; − 0.35, p = 0.0006). Trends of reduction in FBG levels were also evidenced both at 6 months and 12 months. No significant changes in short-acting and basal insulin doses were documented. Conclusions: The study provides the first real-world evidence of the effectiveness of Gla-300 in children and adolescents with T1D previously treated with 1BI. The benefits in terms of HbA1c levels reduction were substantial, and sustained after 12 months. Additional benefits can be expected by improving the titration of insulin doses. [ABSTRACT FROM AUTHOR]

Aims: To assess the effectiveness of the intermittent-scanned continuous glucose monitoring (isCGM) system in preventing severe hypoglycemic episodes and in improving glucose parameters and quality of life. Methods: Four hundred T1D individuals were enrolled in a prospective real-word study with an intermittently scanned continuous glucose monitoring device during the 12-months follow-up. The primary endpoint was the incidence of severe hypoglycemic events. Results: 82% of subjects were naïve to the use of the device (group A) and 18% were already wearing the system (group B). The cumulative incidence of severe hypoglycemia (SH) at 12 months was 12.06 per 100 person-year (95% CI: 8.35–16.85) in group A and 10.14 (95% CI: 4.08–20.90) in group B without inter-group differences. In group A there was a significant decrease in SH at 12 months compared to 3 months period (p = 0.005). Time in glucose range significantly increased in both groups accompanied with a significant decrease in glucose variability. HbA1c showed a progressive significant time-dependent decrease in group A. The use of the device significantly improved the perceived quality of life. Conclusion: This study confirmed the effectiveness of the isCGM in reducing hypoglycemic risk without glucose deterioration, with potential benefits on adverse outcomes in T1D individuals. Trial registration: ClinicalTrials.gov registration no. NCT04060732. [ABSTRACT FROM AUTHOR]