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Aims: To summarize the results of clinical studies of insulin icodec, an investigational insulin analog designed for once‐weekly administration, in adults with type 1 and type 2 diabetes. Methods: Thirteen published articles describing clinical studies of insulin icodec were identified in PubMed, and data pertinent to key study outcomes were selected for inclusion in this review. Results: In insulin‐naïve and insulin‐treated individuals, icodec demonstrated efficacy in glycaemic control superior or noninferior to that of insulins glargine U100, glargine U300 and degludec. Icodec exhibited a safety profile comparable to marketed insulins, with the exception of hypoglycaemic event rates. Conclusions: As a once‐weekly alternative to daily basal insulin, icodec is expected to improve patient adherence and satisfaction, reducing the required number of injections per year from 365 to 52 and providing a dosing option potentially attractive to a wide range of insulin users. However, clinical data suggest a notable risk of hypoglycaemia with weekly icodec administration, especially in individuals with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims: The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real‐world setting. Methods: This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre‐eclampsia, pre‐term delivery, large for gestational age at birth, stillbirth and fetal malformations. Results: There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score‐adjusted analyses. However, maternal HbA1c was lower in the IAsp group at the end of the third trimester (adjusted difference, −0.16% point [95% CI −0.28;−0.05]; −1.8 mmol/mol [95% CI −3.1;−0.6]; p = 0.0046). Conclusions: No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA1c with IAsp in late pregnancy should be confirmed in other studies. [ABSTRACT FROM AUTHOR]

Aims: Women with diabetes (WWD) (type 1 and type 2) are around four times more likely to experience baby loss: miscarriage, stillbirth, neonatal death or termination of pregnancy for medical reasons. Many WWD become pregnant again soon after loss. This study aimed to explore healthcare professional perspectives on improving inter‐pregnancy care for WWD after baby loss, as they play a crucial role in facilitating access to support for WWD to prepare for subsequent pregnancy. Methods: Eighteen healthcare professionals recruited through social media and professional networks between November 2020 and July 2021 participated in a semi‐structured remote interview. Data were analysed using thematic analysis. Results: Three main themes were identified: (1) supporting WWD who want to become pregnant again after baby loss; (2) recognising multiple hidden burdens in the inter‐pregnancy interval after loss; (3) discontinuities and constraints in inter‐pregnancy care. Most participants tended to assume WWD wanted time and space before thinking about pregnancy after loss, so they did not routinely broach the subject. Participants reported receiving little or no training on managing sensitive conversations. Care provision varied across providers, and unclear referral pathways were challenging to navigate. Participants reported concerns that not all healthcare professionals knew how to mitigate pregnancy risks. Conclusions: It is unclear who is responsible for supporting WWDs preconception health between baby loss and subsequent pregnancy. Healthcare professionals may be reticent to initiate conversations about pregnancy for fear of causing upset or distress. Future research is required to scope out ways to raise awareness among healthcare professionals and practical tips on sensitively raising the topic of subsequent pregnancy. [ABSTRACT FROM AUTHOR]

Background: Premature cardiovascular disease is the leading cause of death in people living with type 1 diabetes. Therapies are urgently needed to address cardiovascular risk in this group. Semaglutide, a long‐acting glucagon‐like peptide‐1 receptor agonist, has been shown to reduce cardiovascular events and improve weight and glycaemia in type 2 diabetes. Semaglutide may offer cardioprotective and metabolic benefits in type 1 diabetes. Methods: We will study 60 adults aged 25–70 years with type 1 diabetes of duration at least 2 years, body mass index ≥25 kg/m2, HbA1c ≥7% and at least one cardiovascular risk factor (microalbuminuria, hypertension or anti‐hypertensive treatment, hyperlipidemia or lipid lowering therapy, current smoking). Participants will receive semaglutide up to 1.0 mg weekly or matched placebo for 26 weeks. The primary outcome is carotid femoral pulse wave velocity, a measure of arterial stiffness, as a surrogate marker of cardiovascular risk. Potential mechanisms for metabolic changes will be explored including change in insulin sensitivity determined by hyperinsulinaemic‐euglycaemic clamp; and incretin and pancreatic hormone action measured during mixed meal tolerance test. Conclusion: The REducing cardiometabolic risk with SEmaglutide in Type 1 diabetes study will investigate whether semaglutide, a long acting glucagon‐like peptide receptor agonist, can improve markers of cardiometabolic health in T1D. Underlying mechanisms predicting response, including insulin resistance and incretin hormone status, will also be explored. [ABSTRACT FROM AUTHOR]

Aims: The DAFNEplus programme seeks to promote sustained improvements in glycaemic management by incorporating techniques from behavioural science. It includes five sessions of structured individual support delivered over 12 months following group education. As part of a broader evaluation, and to inform decision‐making about roll‐out in routine care, we explored participants' experiences of, and engagement with, that individual support. Methods: We interviewed DAFNEplus participants (n = 28) about their experiences of receiving individual support and the impact they perceived it as having on their self management practices. We analysed data thematically. Results: Participants described several important ways individual support had helped strengthen their self management, including: consolidating and expanding their understandings of flexible intensive insulin therapy; promoting ongoing review and refinement of behaviour; encouraging continued and effective use of data; and facilitating access to help from healthcare professionals to pre‐empt or resolve emergent difficulties. Participants characterised themselves as moving towards independence in self management over the time they received individual support, with their accounts suggesting three key stages in that journey: 'Working with healthcare professionals'; 'Growing sense of responsibility'; and, 'Taking control'. Whilst all portrayed themselves as changed, participants' progress through those stages varied; a few continued to depend heavily on DAFNEplus facilitators for advice and/or direction at 12 months. Conclusions: While all participants benefited from individual support, our findings suggest that some may need, or gain further benefit from, longer‐term, tailored support. This has important implications for decision‐making about roll‐out of DAFNEplus post‐trial and for the development of future programmes seeking to bring about sustainable changes in self management practices. [ABSTRACT FROM AUTHOR]

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article is part of a special article collection from the T1D Exchange Quality Improvement Collaborative. It describes an initiative to increase the use of connected insulin pens in two primary care clinics and one endocrinology clinic serving diverse populations within the Stanford Health Care system in the San Francisco Bay area of California. [ABSTRACT FROM AUTHOR]

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article is part of a special article collection from the T1D Exchange Quality Improvement Collaborative. It describes an initiative to reduce inequities in diabetes technology access and use and increase the use of connected insulin pens at an academic endocrinology practice in Chicago, IL. [ABSTRACT FROM AUTHOR]

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a quality improvement project focused on increasing the use of continuous glucose monitoring among emerging adults with type 1 diabetes enrolled in a health care transition program in the state of Washington. [ABSTRACT FROM AUTHOR]

This study used data from the T1D Exchange Quality Improvement Collaborative to compare depression rates in youth with type 1 diabetes before and during the coronavirus disease 2019 (COVID-19) pandemic and identify characteristics of individuals with moderate-to-severe depressive symptoms. Rates of moderate-to-severe depressive symptoms remained stable before and during the pandemic, at 9.6–10.7%. During the pandemic, youth who screened positive for depression were more likely to be female and on public insurance, to have a higher A1C, and to have a history of diabetic ketoacidosis or severe hypoglycemia. They were less likely to identify as non-Hispanic White and more likely to identify as Hispanic. [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]

As part of their treatment, patients with type 1 diabetes mellitus (DM) have to be very careful with what they eat and with their insulin doses. Therefore, the risk of eating disorders increases in this patient group. In this study, we aimed to determine the disordered eating behaviors of patients with type 1 DM and to evaluate the sociodemographic characteristics, diabetes care behaviors, and quality-of-life scale results that these behaviors may be related to. The sociodemographic characteristics and diabetes treatment data of 191 patients aged 9–18 years with type 1 DM were analyzed. The Pediatric Quality of Life Inventory (PedsQL), the PedsQL 3.0 Diabetes Module, and the Diabetes Eating Problem Survey-Revised (DEPS-R) were applied. The median DEPS-R score of the patients was 18 (19.00), and 44.5 % had a DEPS-R score above 20. A significant correlation was found between age, duration of diabetes, frequency of blood glucose measurement, hemoglobin A 1c (HbA 1c) level, body mass index standard deviation score (BMI-SDS), and DEPS-R score. There was no significant difference between girls and boys. Patients with a high DEPS-R score had low scores on the PedsQL and on the PedsQL 3.0 Diabetes Module. The DEPS-R scale is a diabetes-specific, easy-to-use, and effective method for screening patients with type 1 DM for disordered eating behaviors. It can help prevent the progression of disordered eating behaviors to clinical eating disorders in patients with type 1 DM. It would be beneficial to use this scale as a routine screening, especially in clinics where access to a psychologist is not possible. [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: Clinical fundus examination in addition to fundus photography of Type 1 diabetes mellitus (T1DM) children patients to detect complications like diabetic retinopathy (DR). This study aimed to evaluate direct ophthalmoscopy accuracy compared to fundus photography in diagnosing diabetic retinopathy in children with T1DM at Zagazig University Hospital. Methods: We carried out this cross-sectional study on 42 children diagnosed with T1DM for over five years who attended the Pediatrics Outpatient Clinic at Zagazig University Hospital. Routine laboratory investigations, such as complete blood count and blood glucose level, HbA1c, and albumin/creatinine ratio in urine, were done on all patients, in addition to direct ophthalmoscopy and fundus photography, for diagnosis of diabetic retinopathy. Results: Direct ophthalmoscopy had a sensitivity of 25% and a specificity of 100%. On the other hand, fundus photography demonstrated a sensitivity of 80.69% and a specificity of 92.23%.Regarding positive predictive value (PPV) and negative predictive value (NPV), direct ophthalmoscopy showed a PPV of 100% and an NPV of 75%. In comparison, fundus photography in another study demonstrated a PPV of 62% and an NPV of 90%. Direct ophthalmoscopy and fundus photography identified one case of DR concordantly, while three cases initially identified as absence of DR by direct ophthalmoscopy were later confirmed as DR by fundus photography. Conclusion: Direct ophthalmoscopy's sensitivity and specificity for detecting the presence and severity of DR were found to be lower than the recommended levels for a DR screening test. This suggests that fundus photography is more accurate than direct ophthalmoscopy for screening DR. [ABSTRACT FROM AUTHOR]

Background: Intense exercise leads to neutrophil extracellular traps (NETs) formation, which triggers cell disintegration. NET, as well as other processes of apoptosis, necrosis, and spontaneous secretion, result in increased levels of cell-free DNA (cf-DNA) in the circulation. An increment of cf-DNA is also observed in autoimmune diseases, such as type 1 diabetes mellitus (T1DM). Repeated exhaustive exercises are an impulse for physiological adaptation; therefore, in this case–control study, we compared the exercise-induced increase in cf-DNA in men with T1DM and healthy controls to determine the development of the tolerance to exercise. Methods: Volunteers performed a treadmill run to exhaustion at a speed matching 70% of their personal VO2 max at three consecutive visits, separated by a 72 h resting period. Blood was collected before and after exercise for the determination of plasma cell-free nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, blood cell count and metabolic markers. Results: Each bout of exhaustive exercise induced a great elevation of cf n-DNA levels. An increase in cf mt-DNA was observed after each run. However, the significance of the increase was noted only after the second bout in T1DM participants (p < 0.02). Changes in cf-DNA concentration were transient and returned to baseline values during 72 h of resting. The exercise-induced increment in circulating cf n-DNA and cf mt-DNA was not significantly different between the studied groups (p > 0.05). Conclusions: Cf-DNA appears to be a sensitive marker of inflammation, with a lower post-exercise increase in individuals with T1DM than in healthy men. [ABSTRACT FROM AUTHOR]

Background: Adolescence is a particularly crucial period of physical, emotional, and social development and adaptation, rendering these formative years rather challenging for individuals with chronic conditions like type 1 diabetes (T1D). Despite rapid improvement in diabetes therapies, adolescents with T1D are characterized by poorer adherence to treatment regimens compared with other pediatric age groups. Insufficient adherence is strongly related to low diabetes control, increasing morbidity, and risk for premature mortality. This study aimed to provide a comprehensive overview of adolescents' most common barriers to T1D adherence, stressing the need for a deep and comprehensive understanding of these barriers. The complexity of these barriers is underscored by the diverse factors contributing to poor T1D adherence in adolescents. Methods: A narrative review was conducted, surveying four databases (PubMed, Scopus, EMBASE, and Web of Science) for full-text articles in the English language published up to June 2024. All studies related to barriers to T1D adherence in adolescents were considered. The literature was selected using selection and exclusion criteria and extracted and organized using Mendeley. Exclusion criteria included studies with insufficient data and non-peer-reviewed articles. This review revealed that adolescents face numerous obstacles to T1D adherence related to psychological factors, flux in family dynamics, perceived social pressures, therapy-related factors, transitioning responsibility, risk-taking behaviors, and pubertal changes. Conclusions: Navigating the adaptations to the different aspects of T1D, from treatment to complications and adolescents' personal growth, effectively requires a thorough understanding of the barriers of a treatment regimen that patients at this critical age face. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy (DN) is a common complication of long-lasting type 1 and type 2 diabetes, with no curative treatment available. Here, we tested the effect of the incretin mimetic liraglutide in DN in mice with early-stage type 1 diabetes bred in a standard laboratory or enriched environment. With a single i.p. injection of streptozotocin 150 mg/kg, we induced murine diabetes. Liraglutide (0.4 mg/kg once daily, i.p. for ten days since the eighth post-streptozotocin day) failed to decrease the glycemia in the diabetic mice; however, it alleviated their antinociceptive behavior, as tested with formalin. The second phase of the formalin test had significantly lower results in liraglutide-treated mice reared in the enriched environment vs. liraglutide-treated mice under standard conditions [2.00 (0.00–11.00) vs. 29.00 (2.25–41.50) s, p = 0.016]. Liraglutide treatment, however, decreased the threshold of reactivity in the von Fray test. A significantly higher neopterin level was demonstrated in the diabetic control group compared to treatment-naïve controls and the liraglutide-treated diabetic mice (p < 0.001). The glutamine/glutamate ratio in both liraglutide-treated groups, either reared under standard conditions (p = 0.003) or an enriched environment (p = 0.002), was significantly higher than in the diabetic controls. This study demonstrates an early liraglutide effect on pain sensation in two streptozotocin-induced diabetes mouse models by reducing some inflammatory and oxidative stress parameters. [ABSTRACT FROM AUTHOR]

Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease that results in the destruction of pancreatic β cells, leading to hyperglycaemia and the need for lifelong insulin therapy. Although genetic predisposition and environmental factors are considered key contributors to T1DM, the exact causes of the disease remain partially unclear. Recent evidence has focused on the relationship between the gut, the oral cavity, immune regulation, and systemic inflammation. In individuals with T1DM, changes in the gut and oral microbial composition are commonly observed, indicating that dysbiosis may contribute to immune dysregulation. Gut dysbiosis can influence the immune system through increased intestinal permeability, altered production of short chain fatty acids (SCFAs), and interactions with the mucosal immune system, potentially triggering the autoimmune response. Similarly, oral dysbiosis may contribute to the development of systemic inflammation and thus influence the progression of T1DM. A comprehensive understanding of these relationships is essential for the identification of biomarkers for early diagnosis and monitoring, as well as for the development of therapies aimed at restoring microbial balance. This review presents a synthesis of current research on the connection between T1DM and microbiome dysbiosis, with a focus on the gut and oral microbiomes in pediatric populations. It explores potential mechanisms by which microbial dysbiosis contributes to the pathogenesis of T1DM and examines the potential of microbiome-based therapies, including probiotics, prebiotics, synbiotics, and faecal microbiota transplantation (FMT). This complex relationship highlights the need for longitudinal studies to monitor microbiome changes over time, investigate causal relationships between specific microbial species and T1DM, and develop personalised medicine approaches. [ABSTRACT FROM AUTHOR]

Monogenic defects of beta cell function refer to a group of rare disorders that are characterized by early-onset diabetes mellitus due to a single gene mutation affecting insulin secretion. It accounts for up to 5% of all pediatric diabetes cases and includes transient or permanent neonatal diabetes, maturity-onset diabetes of the young (MODY), and various syndromes associated with diabetes. Causative mutations have been identified in genes regulating the development or function of the pancreatic beta cells responsible for normal insulin production and/or release. To date, more than 40 monogenic diabetes subtypes have been described, with those caused by mutations in HNF1A and GCK genes being the most prevalent. Despite being caused by a single gene mutation, each type of monogenic diabetes, especially MODY, can appear with various clinical phenotypes, even among members of the same family. This clinical heterogeneity, its rarity, and the fact that it shares some features with more common types of diabetes, can make the clinical diagnosis of monogenic diabetes rather challenging. Indeed, several cases of MODY or syndromic diabetes are accurately diagnosed in adulthood, after having been mislabeled as type 1 or type 2 diabetes. The recent widespread use of more reliable sequencing techniques has improved monogenic diabetes diagnosis, which is important to guide appropriate treatment and genetic counselling. The current review aims to summarize the latest knowledge on the clinical presentation, genetic confirmation, and therapeutic approach of the various forms of monogenic defects of beta cell function, using three imaginary clinical scenarios and highlighting clinical and laboratory features that can guide the clinician in reaching the correct diagnosis. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokines play a role in the failure of β cells in type 1 and type 2 diabetes. While existing data from 'omics' experiments allow for some understanding of the molecular mechanisms behind cytokine-induced dysfunction in β cells, no report thus far has provided information on the direct imaging of the β cell landscape with nanoscale resolution following cytokine exposure. In this study, we use Airyscan-based optical super-resolution microscopy of Insulinoma 1E (INS-1E) cells to investigate the structural properties of two subcellular membranous compartments involved in the production, maturation and secretion of insulin-containing granules, the endoplasmic reticulum (ER) and the Golgi apparatus (GA). Our findings reveal that exposure of INS-1E cells to IL-1β and IFN-γ for 24 h leads to significant structural alterations of both compartments. In more detail, both the ER and the GA fragment and give rise to vesicle-like structures with markedly reduced characteristic area and perimeter and increased circularity with respect to the original structures. These findings complement the molecular data collected thus far on these compartments and their role in β cell dysfunction and lay the groundwork for future optical microscopy-based ex vivo and in vivo investigations. [ABSTRACT FROM AUTHOR]

Objective: Diabetes can lead to microvascular complications such as diabetic neuropathy, nephropathy, and retinopathy. Hyperglycemia may initiate microvascular function impairment early in the course of diabetes, even prior to its clinical establishment during the pre‐diabetes stage. Microvascular vasomotion, that is, the rhythmic arteriolar constriction and dilation, is an important function that regulates oxygen and nutrient delivery within the tissue and regulates peripheral resistance. Using laser Doppler flowmetry (LDF), vasomotion in skin microcirculation can be measured as flowmotion. Changes in flowmotion have been shown in individuals with obesity, and type 1 or type 2 diabetes mellitus. However, no data are available on associations between hyperglycemia and flowmotion in the general population. Our aim was to study whether measures of hyperglycemia were associated with different components of skin microvascular flowmotion (SMF) in a population‐based cohort (The Maastricht Study). Methods: Data from 7293 participants of The Maastricht Study were used. SMF was measured using LDF. Endothelial, neurogenic and myogenic component SMF power were used as dependent variables. We investigated the associations of glucose metabolism status (normal glucose metabolism, prediabetes, and type 2 diabetes mellitus), measures of hyperglycemia (fasting plasma glucose [FPG], 2‐h post‐load glucose [2 h‐PG], HbA1c, advanced glycation end‐products [AGEs] assessed as skin autofluorescence [SAF]), and indices of glucose variability (incremental glucose peak [IGP] and continuous glucose monitoring [CGM] ‐assessed as standard deviation [SD]) with each component of SMF power. We used linear regression analyses with adjustments for confounders, and trend analyses. Results: We observed consistent negative associations between HbA1c levels and all three (endothelial, neurogenic, and myogenic) skin microvascular flowmotion (SMF) powers in the additionally adjusted model. Similarly, in the conservative model, we found that multiple hyperglycemia metrics such as GMS trend, PreD, T2DM, FPG, 2 h‐PG, and HbA1c were consistently negatively associated with all three SMF powers. Conclusions: We showed that skin microvascular flowmotion is reduced in individuals with (pre)diabetes. In addition, different measures of hyperglycemia are negatively associated with skin microvascular flowmotion. [ABSTRACT FROM AUTHOR]

Common ways to test associations between two repeatedly measured constructs have two primary limitations. Studies often report the average effects and ignore the heterogeneity. Independently interpreted autoregression and cross-lagged coefficients (i.e. local effects) may not match the holistic dynamic patterns (i.e. considering all coefficients simultaneously). Our paper aims to address the limitations by introducing vector plots to visualize holistic person-specific dynamic patterns. We utilized a case example of 14-day daily diary data of diabetes self-efficacy and self-care from 200 emerging adults with type 1 diabetes. A dynamic structural equation model was used to generate person-specific coefficients. Vector plots and eigenvalues were generated to visualize person-specific holistic patterns. We found heterogeneity in both local and holistic dynamic patterns. Most participants (N = 178) had mismatching local and holistic patterns. Our study provided important evidence that failing to capture person-specific holistic dynamic patterns might result in incomplete interpretations of dynamic associations. [ABSTRACT FROM AUTHOR]

Background: The TrialNet Oral Insulin (OI) prevention trial showed no overall treatment effect, using the diagnosis of type 1 diabetes as an endpoint. A significant delay in onset was only found in a high‐risk stratum (termed secondary stratum 1) of participants with low first‐phase insulin release (FPIR). Methods: Since trials with an endpoint of type 1 diabetes take years to complete, in this post hoc analysis, we assessed whether a novel combination of glucose and C‐peptide markers could identify a therapeutic benefit after 1 year of follow‐up (trial participants followed for a median 2.7 years). Results: Participants were relatives with multiple islet autoantibodies and low FPIR (n = 40). Glucose rose, and C‐peptide declined in the placebo group, whereas glucose rose minimally, and C‐peptide increased in the OI group. When glucose and C‐peptide were plotted on two‐dimensional grids using 30–120‐min oral glucose tolerance test (OGTT) time points, changes in ratios of their central points (centroid ratio) differed between groups (p = 0.037 adjusted for age, BMI, and baseline C‐peptide and glucose). Conclusions: These findings support a favorable early effect of OI on combined glucose and C‐peptide endpoints in high‐risk individuals, indicating metabolic benefit. With further study, these measures may allow for shorter trials compared to the standard endpoint of type 1 diabetes diagnosis. [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 and Objectives: Intravenous immunoglobulins (IVIgs) contain various autoantibodies, including those against glutamic acid decarboxylase (GADAb), a valuable biomarker of type 1 diabetes mellitus. Passive transfer of GADAb from IVIgs to patients poses a risk of misdiagnosis, and information on the specific titres of GADAb and their impact on diagnostic accuracy remains limited. This study aimed to provide further insights into the origin of GADAb detected in patient serum following IVIg infusion. Materials and Methods: GADAb titres in IVIg products from Japan and the United States were measured using enzyme‐linked immunosorbent assay‐based assays. For reliable quantification, GADAb titres in pooled plasma were quantified and compared with those in the IVIg products. The determined titres were used to estimate the likelihood of passively detecting acquired GADAb in individuals receiving IVIgs. Results: GADAbs were prevalent in IVIg products; however, the titres varied significantly among different lots and products. Importantly, IVIg‐derived GADAb was estimated to remain detectable in patient serum for up to 100 days following a dosage of 2000 mg/kg. Conclusion: Clinicians should consider that IVIg preparations may contain GADAb, which can lead to false‐positive results in serological assays. Careful interpretation of the assay results is key to the definitive diagnosis of type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Youth starting Omnipod 5 (OP5) can onboard with a diabetes educator or self-start with support from online, industry-provided educational modules. We compared glycemic control and pump interaction by training type among youth initiating OP5. Methods: This retrospective review included 297 youth with type 1 diabetes (T1D) aged <22 years initiating OP5. We analyzed baseline continuous glucose monitor (CGM) data and pump and CGM data from the first 90 days of OP5 use. Multilevel mixed-effects regression assessed for changes in time in range (TIR) from baseline to 90 days by training type. Results: Of youth initiating OP5, 42.4% trained with a diabetes educator and 57.6% self-started. At baseline, self-starters had a longer T1D duration (5.0 (2.6,7.9) vs. 2.5 (1.3, 5.5) years, P = 0.001), more time <54 mg/dL (0.3% (0.1,1) vs. 0.15% (0,1), P = 0.01), and a higher coefficient of variation (40.2% (37, 44.4) vs. 38.7% (34.4, 42.4), P = 0.004). After 90 days of OP5 use, groups did not differ in time in automated mode or boluses per day. In a longitudinal model, after adjusting for baseline TIR and T1D duration, 90-day TIR was 10.5%-points higher (CI: 9.2–11.8, P < 0.0001), positively associated with baseline TIR (β = 0.82, CI: 0.78–0.85, P < 0.0001), and 1.1%-points greater among self-starters (CI: 0.06−2.2; P = 0.04). Conclusions: After 90 days of OP5 use, glycemic control and pump interactions were minimally different between youth who self-started and those who trained with a diabetes educator. For youth at a tertiary care center previously using an Omnipod system, online educational modules offered by industry provide sufficient training for use. [ABSTRACT FROM AUTHOR]

In the last decade, technology developed by people with diabetes and their loved ones has added to the options for diabetes management. One such example is that of automated insulin delivery (AID) algorithms, which were created and shared as open source by people living with type 1 diabetes (T1D) years before commercial systems were first available. Now, numerous options for commercial systems exist in some countries, yet tens of thousands of people with diabetes are still choosing Open-Source AID (OS-AID), previously called "do-it-yourself" (DIY) systems, which are noncommercial versions of these open-source AID systems. In this article, we provide point and counterpoint perspectives regarding (1) safety and efficacy, (2) regulation and support, (3) user choice and flexibility, (4) access and affordability, and (5) patient and provider education, for open source and commercial AID systems. The perspectives reflected here include that of a person living with T1D who uses and has developed OS-AID systems, a physician-researcher based in the United States who conducts clinical trials to support development of commercial AID systems and supports people with diabetes using all types of AID, and an endocrinologist with T1D who uses both systems and treats people with diabetes using all types of AID [ABSTRACT FROM AUTHOR]

Objective: To predict hypoglycemia and hyperglycemia risk during and after activity for adolescents with type 1 diabetes (T1D) using real-world data from the Type 1 Diabetes Exercise Initiative Pediatric (T1DEXIP) study. Methods: Adolescents with T1D (n = 225; [mean ± SD] age = 14 ± 2 years; HbA1c = 7.1 ± 1.3%; T1D duration = 5 ± 4 years; 56% using hybrid closed loop), wearing continuous glucose monitors (CGMs), logged 3738 total activities over 10 days. Repeated Measures Random Forest (RMRF) and Repeated Measures Logistic Regression (RMLR) models were used to predict a composite risk of hypoglycemia (<70 mg/dL) and hyperglycemia (>250 mg/dL) within 2 h after starting exercise. Results: RMRF achieved high precision predicting composite risk and was more accurate than RMLR Area under the receiver operating characteristic curve (AUROC 0.737 vs. 0.661; P < 0.001). Activities with minimal composite risk had a starting glucose between 132 and 160 mg/dL and a glucose rate of change at activity start between −0.4 and −1.9 mg/dL/min. Time <70 mg/dL and time >250 mg/dL during the prior 24 h, HbA1c level, and insulin on board at activity start were also predictive. Separate models explored factors at the end of activity; activities with glucose between 128 and 133 mg/dL and glucose rate of change between 0.4 and −0.6 mg/dL/min had minimal composite risk. Conclusions: Physically active adolescents with T1D should aim to start exercise with an interstitial glucose between 130 and 160 mg/dL with a flat or slightly decreasing CGM trend to minimize risk for developing dysglycemia. Incorporating factors such as historical glucose and insulin can improve prediction modeling for the acute glucose responses to exercise. [ABSTRACT FROM AUTHOR]

Objective: A subgroup analysis of the Hypoglycemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycemia persisting despite optimized care (HARPdoc) trial was conducted to explore the impact of Blood Glucose Awareness Training (BGAT, a hypoglycemia awareness training program) and the HARPdoc (a psychoeducation addressing unhelpful hypoglycemia beliefs) in reducing severe hypoglycemia (SH) in individuals using advanced diabetes technologies (ADTs). Methods: Data from trial participants who utilized ADTs, including continuous glucose monitors or automated insulin delivery systems, were extracted. Generalized linear mixed-effects models with Poisson distribution or linear mixed-effects models were used to evaluate SH incidence, and Gold questionnaire, Attitudes to Awareness of Hypoglycemia (A2A), Problem Areas in Diabetes (PAID), Hospital Anxiety and Depress Scale (HADS)-anxiety, and HADS-depression scores as measures of hypoglycemia awareness, unhelpful hypoglycemia beliefs, diabetes distress, and anxiety and depression symptoms, respectively. Results: In the 45 participants using ADTs, the BGAT and HARPdoc interventions both reduced SH incidence by more than 50% (P < 0.0001) and yielded improvements in hypoglycemia awareness (P < 0.05). HARPdoc outperformed BGAT in reducing SH at month 24 (P = 0.01). HARPdoc also mitigated unhelpful hypoglycemia beliefs (P < 0.0001), diabetes distress (P < 0.05), and anxiety symptoms (P < 0.05); BGAT demonstrated no significant impacts in these respects. Neither HARPdoc nor BGAT had significant effects on depression symptoms. Conclusion: Psychoeducation (BGAT and HARPdoc) was effective in reducing SH in people using ADTs. HARPdoc may also provide greater long-term SH reduction and improves psychological well-being in this patient group. [ABSTRACT FROM AUTHOR]

Background: Computer simulators of human metabolism are powerful tools to design and validate new diabetes treatments. However, these platforms are often limited in the diversity of behaviors and glycemic conditions they can reproduce. Replay methodologies leverage field-collected data to create ad hoc simulation environments representative of real-life conditions. After formal validations of our method in prior publications, we demonstrate its capacity to reproduce a recent clinical trial. Methods: Using the replay methodology, an ensemble of replay simulators was generated using data from a randomized crossover clinical trial comparing the hybrid closed loop (HCL) and fully closed loop (FCL) control modalities in automated insulin delivery (AID), creating 64 subject/modality pairs. Each virtual subject was exposed to the alternate AID modality to compare the simulated versus observed glycemic outcomes. Equivalence tests were performed for time in, below, and above range (TIR, TBR, and TAR) and high and low blood glucose indices (HBGI and LBGI) considering equivalence margins corresponding to clinical significance. Results: TIR, TAR, LBGI, and HBGI showed statistical and clinical equivalence between the original and the simulated data; TBR failed the equivalence test. For example, in the HCL mode, simulated TIR was 84.89% versus an observed 84.31% (P = 0.0170, confidence interval [CI] [−3.96, 2.79]), and for FCL mode, TIR was 76.58% versus 77.41% (P = 0.0222, CI [−2.54, 4.20]). Conclusion: Clinical trial data confirm the prior in silico validation of the UVA replay method in predicting the glycemic impact of modified insulin treatments. This in vivo demonstration justifies the application of the replay method to the personalization and adaptation of treatment strategies in people with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Managing exercise in type 1 diabetes is challenging, in part, because different types of exercises can have diverging effects on glycemia. The aim of this work was to develop a classification model that can classify an exercise event (structured or unstructured) as aerobic, interval, or resistance for the purpose of incorporation into an automated insulin delivery (AID) system. Methods: A long short-term memory network model was developed with real-world data from 30-min structured sessions of at-home exercise (aerobic, resistance, or mixed) using triaxial accelerometer, heart rate, and activity duration information. The detection algorithm was used to classify 15 common free-living and unstructured activities and relate each to exercise-associated change in glucose. Results: A total of 1610 structured exercise sessions were used to train, validate, and test the model. The accuracy for the structured exercise sessions in the testing set was 72% for aerobic, 65% for interval, and 77% for resistance. In addition, we tested the classifier on 3328 unstructured sessions. We validated the session-associated change in glucose against the expected change during exercise for each type. Mean and standard deviation of the change in glucose of −20.8 (40.3) mg/dL were achieved for sessions classified as aerobic, −16.2 (39.0) mg/dL for sessions classified as interval, and −11.6 (38.8) mg/dL for sessions classified as resistance. Conclusions: The proposed algorithm reliably identified physical activity associated with expected change in glucose, which could be integrated into an AID system to manage the exercise disturbance in glycemia according to the predicted class. [ABSTRACT FROM AUTHOR]

Maternal glucose is the principal macronutrient that sustains fetal growth. Prolonged exposure of the fetus to hyperglycemia from the early stages of pregnancy accelerates the maturation of the stimulus–secretion coupling mechanism in β cell autoimmunity, which leads to early hyperinsulinemia in type 1 diabetes mellitus (T1DM). Nowadays, diabetes mellitus (DM) is the most common medical complication of pregnancy, and among young women, the prevalence of overt diabetes and undiagnosed hyperglycemia is rising. Even though conventional medication is effective in treating DM, it is expensive and has harmful side effects. Herbal medicine will thus incorporate alternative therapy and be more effective and less toxic. Due to their bioactive components, olive leaves (Olea europaea) are frequently used medicinally; however, little is known about how this plant affects the immune system when it comes to diabetes. The current study used a pregnant mother rat model of alloxan-induced T1DM to examine the antidiabetic properties and embryonic safety of olive leaves. Forty adult female Sprague Dawley rats were split up into four groups as follows: nondiabetic, diabetic, olive, and diabetic-olive groups. All the mother rats were sacrificed on the 20th day of pregnancy, and fetuses were collected for further investigations. In diabetic pregnant mothers, fetuses had systemic modulation-negative effects. These effects were significantly reversed when the diabetic groups were supplemented with extracts from olive leaves. The findings showed that the olive leaf extract inhibits the diabetogenic effect mediated by alloxan with effective and protective systemic immunomodulation during embryonic development. [ABSTRACT FROM AUTHOR]

Insulin is essential for the survival of people with type 1 diabetes and for better management of people with type 2 diabetes. People with diabetes using insulin also require self-monitoring blood glucose (SMBG) devices (e.g., meters, strips, continuous monitoring systems) for day-to-day management. It is essential to ensure that insulin and these devices are available and affordable. This study aimed to evaluate the availability, price, and affordability of insulin and SMBG devices in Indonesia using an adaptation of the World Health Organization/Health Action International (WHO/HAI) price survey. A total of 34 public health facilities (hospitals, primary healthcare centres/Puskesmas) and 37 private pharmacies were sampled. Information from three major online marketplaces was also collected. Prices were expressed as median patient prices (US$). Affordability was defined as the number of days' wages needed by the lowest paid unskilled government worker (LPGW) to purchase 30 days' supply of insulin, delivery devices and SMBGs. Availability of analogue insulin was slightly higher in public facilities (63.6%) than in the private sector (43.2%), with no human insulin available in both sectors. Conversely, better availability was observed in private facilities for SMBG devices as public sector facilities did not supply devices for self-testing. Median prices for 1000IU analogues varied between the public sector (US$ 5.26) and the private sector (US$11.24). The highest median price of analogues was seen in online marketplaces (US$ 28.65). The least costly median price of SMBG devices were observed in online platforms (meter: US$ 18.37, test strip: US$ 0.27, lancet: US$ 0.02). A low-income person had to work 2–3 days to buy 1000IU of analogues. It required 5–7 days' and 4–5 day's wages to purchase a meter and a month's supply of test strips, respectively. The availability and affordability of insulin and SMBG devices remain important issues in Indonesia requiring holistic approaches for further improvement. [ABSTRACT FROM AUTHOR]

Background: The triglyceride-glucose (TyG) index is identified as an alternative indicator of insulin resistance (IR) and is associated with macro- and micro-vascular diseases among patients with type 2 diabetes mellitus. The relationship between the TyG index and IR and its impact on diabetic kidney disease (DKD) remains unclear among adults with type 1 diabetes mellitus(T1DM). Methods: This study comprised a cross-sectional analysis using data from the Guangdong T1DM Translational Medicine Study (GTT) and a longitudinal analysis using data from the type 1 diabetes (T1D) Exchange registry study. Correlation analysis was used to investigate the association between the TyG index and IR. Logistic regression and Cox proportional hazards regression were performed to explore the impact of the TyG index on DKD risk. Results: The GTT Study included 836 adults (216 with DKD and 620 without DKD). A significant correlation existed between the TyG index and the estimated glucose disposal rate (r=-0.64, p < 0.01). The TyG index was a risk factor for DKD after confounder adjustment (OR = 1.34, 95% CI:1.03–1.74). The T1D Exchange registry study included 8,771 adults (2,050 with DKD and 6,721 without DKD). After adjusting confounding factors, the TyG index was identified as an independent risk factor for DKD at enrollment, with the highest risk of DKD incidence observed in the highest TyG tertile group (OR = 1.92, 95%CI:1.67–2.20). During a median follow-up of 44.58(21.84, 67.09) months, the risk of developing DKD was increased by 32% at every 1 SD increase of the TyG index over time among participants without DKD at enrollment. Conclusions: The TyG index could be used to assess IR and was identified as an independent risk factor of DKD among adults with T1DM. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot ulcers are challenging to heal, increase the risk of lower extremity amputation, and place a significant burden on patients, families, and healthcare systems. Prioritizing preventive interventions holds the promise of reducing patient suffering, lowering costs, and improving quality of life. This study describes a scoping review protocol that will be used to delineate the preventive interventions for diabetic foot ulcers employed in different healthcare settings. Methods: The scoping review methodology was formulated in accordance with the PRISMA extension guidelines for scoping reviews and informed by the procedural insights provided by the JBI methodology group. Studies with participants diagnosed with type 1 and type 2 diabetes, aged 18 years or older, without an active ulcer at baseline, and studies of preventive interventions for foot ulcers in various healthcare settings will be screened. The search strategy was developed in collaboration with a research librarian using the PRESS checklist and no time or language limitations were applied. Data will be analyzed and summarized descriptively, including characteristics of studies, participants, and interventions. Discussion: Understanding the strategies and gaps in diabetic foot ulcer prevention is critical. The literature can provide valuable insights for developing tailored interventions and strategies to effectively address these gaps, potentially accelerating progress toward improved outcomes in diabetic foot ulcer prevention. Review registration: Open Science Framework DOI 10.17605/OSF.IO/FRZ97 [June 19, 2023] [ABSTRACT FROM AUTHOR]

Objectives Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs). Methods Out of all of the 5 339 804 Finnish citizens, individuals born 1964–1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes. Results Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1–1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis. Conclusion Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes. [ABSTRACT FROM AUTHOR]

Objectives Cardiovascular disease through accelerated atherosclerosis is a leading cause of mortality for patients with systemic lupus erythematosus (SLE), likely due to increased chronic inflammation and cardiometabolic defects over age. We investigated age-associated changes in metabolomic profiles of SLE patients and healthy controls (HCs). Methods Serum NMR metabolomic profiles from female SLE patients (n  = 164, age = 14–76) and HCs (n  = 123, age = 13–72) were assessed across age by linear regression and by age group between patients/HCs (Group 1, age ≤ 25, n  = 62/46; Group 2, age = 26–49, n  = 50/46; Group 3, age ≥ 50, n  = 52/31) using multiple t tests. The impact of inflammation, disease activity and treatments were assessed, and UK Biobank disease-wide association analysis of metabolites was performed. Results Age-specific metabolomic profiles were identified in SLE patients vs HCs, including reduced amino acids (Group 1), increased very-low-density lipoproteins (Group 2), and increased low-density lipoproteins (Group 3). Twenty-five metabolites were significantly altered in all SLE age groups, dominated by decreased atheroprotective high-density lipoprotein (HDL) subsets, HDL-bound apolipoprotein (Apo)A1 and increased glycoprotein acetyls (GlycA). Furthermore, ApoA1 and GlycA were differentially associated with disease activity and serological measures, as well as atherosclerosis incidence and myocardial infarction mortality risk through disease-wide association. Separately, glycolysis pathway metabolites (acetone/citrate/creatinine/glycerol/lactate/pyruvate) uniquely increased with age in SLE, significantly influenced by prednisolone (increased pyruvate/lactate) and hydroxychloroquine (decreased citrate/creatinine) treatment and associated with type 1 and type 2 diabetes by disease-wide association. Conclusions Increasing HDL (ApoA1) levels through therapeutic/nutritional intervention, whilst maintaining low disease activity, in SLE patients from a young age could improve cardiometabolic disease outcomes. Biomarkers from the glycolytic pathway could indicate adverse metabolic effects of current therapies. [ABSTRACT FROM AUTHOR]

The transition of young type 1 diabetic (T1D) patients from pediatric to adult healthcare is a high‐risk period of loss to follow‐up. Since 2015, we have implemented a transition program, involving both pediatric and adult clinicians. The main objective was to evaluate the number of patients who had succeeded this transition program at 1 year. We found that 86% of patients underwent the complete transition program. However, adverse outcomes occurred in 19.1% of patients at 1 year but decreased to 2.9% after 3 years. In 63% of patients their HbA1c level had deteriorated 1 year after the transition day and this level stabilized at around 8% in the following 2 and 3 years. In patients who had improved HbA1c levels the body mass index was lower (P = 0.03) and they lived alone (P = 0.04). Although our program seemed to allow a better follow‐up than previously described, this study highlights the importance of further supporting this transition period. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The FreeStyle Libre (FSL) intermittently scanned continuous glucose monitoring (isCGM) system continually measures interstitial glucose levels and provides the data to users in numerical and graphical formats that guide users in their daily diabetes self‐management. Although numerous studies have demonstrated the glycemic benefits of FSL in pediatric and adult populations, few studies have characterized FSL use specifically by Japanese adults with type 1 or 2 diabetes. We utilized established CGM metrics to assess glycemic control in a large cohort of Japanese adults with type 1 and 2 diabetes. Materials and Methods: A total of 3,463 anonymized FSL users provided categorization into one of four therapy groups of interest: type 1 diabetes (n = 1,768), type 2 diabetes‐multiple daily injections (MDI) (n = 612), type 2 diabetes‐basal (BOI) (n = 343), and type 2 diabetes‐non‐insulin (NIT) (n = 740). Established CGM metrics were used to assess glycemic control. Results: All study groups showed relatively good glycemic control. Type 1 diabetes users showed the highest glucose variability (SD, 61 mg/dL; and %CV, 40%), above the established target level (%CV ≤ 36%). type 2 diabetes‐MDI and type 2 diabetes‐BOI users had similar levels of glucose variability (both within target). Type 2 diabetes‐NIT users had the highest mean % time in range (TIR) (84.3%) and largest percentage of users that met the target of %TIR > 70% (87.4%). In contrast, type 1 diabetes users had the lowest mean %TIR (62.6%) and the lowest percentage meeting the established %TIR target (30.5%). Conclusions: By utilizing CGM devices in daily diabetes care, both healthcare professionals and patients can monitor glycemic excursions and gain insights into their historical glucose control patterns. [ABSTRACT FROM AUTHOR]

Introduction: Dual-expressing lymphocytes (DEs) are unique immune cells that express both B cell receptors (BCRs, surface antibody) and T cell receptors (TCRs). In type 1 diabetes, DE antibodies are predominated by one antibody (x-mAb), an IgM monoclonal antibody with a germline-encoded CDR3 that recognizes self-reactive TCRs. We explored if x-mAb and its interacting TCRs have distinct structural features. Methods: Using bioinformatics, we compared x-mAb and its most common interacting TCRαβ to billions of antigen receptor sequences to determine if they were unique or randomly generated. Results: X-mAb represents a unique class of human antibodies with a conserved CDR3 sequence (CARx1-4DTAMVYYFYDW), consisting of a fixed DJH motif (DTAMVYYFDYW) paired with various VH genes. A public TCRβ clonotype (CASSPGTEAFF) associated with x-mAb on DEs features two invariant segments, VβD (CASSPGT) and DJβ (PGTEAFF), key to two large families of public TCRβ clonotypes—CASSPGT-Jβx and CASSPGT-Jβx—formed by recombining the VβD motif with Jβ genes and the DJβ motif with Vβ genes. B cells also use CASSPGT as a VHD motif for public IGH clonotypes (CASSPGT—Jβx). Discussion: DEs, unlike conventional T and B cells, use invariant motifs to create public antibodies and TCRs, a trait previously seen only in cartilaginous fish. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To understand the challenges of managing diabetes mellitus alongside dementia • To learn about the importance of sharing patient information among healthcare professionals in various settings • To consider how the use of IT might promote more effective communication between specialties. Background: Managing diabetes mellitus alongside the onset and development of dementia poses many challenges for those living with these conditions as well as their families, carers and service providers. Aim: To describe nurses’ positive experiences when managing adults with diabetes and dementia, as well as the issues and challenges. Method: Qualitative, semi-structured focus group interviews were conducted with community and diabetes specialist nurses drawn from five health and social care trusts. Findings: Four themes were identified: whose responsibility is it?; community and diabetes specialist nurses – the pivot point; education to manage comorbidities; and interprofessional communication. Conclusion: Community and diabetes specialist nurses experience many challenges when supporting individuals living with diabetes and dementia. Sharing patient information among practitioners in different settings is critically important. IT could overcome the limitations of note-keeping ‘silos’, but further education is recommended to establish more effective communication and partnership working. [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]

Objective: Individuals with type 1 diabetes (T1D) have increased risk for cognitive dysfunction and high rates of sleep disturbance. Despite associations between glycemia and cognitive performance using cross-sectional and experimental methods few studies have evaluated this relationship in a naturalistic setting, or the impact of nocturnal versus daytime hypoglycemia. Ecological Momentary Assessment (EMA) may provide insight into the dynamic associations between cognition, affective, and physiological states. The current study couples EMA data with continuous glucose monitoring (CGM) to examine the within-person impact of nocturnal glycemia on next day cognitive performance in adults with T1D. Due to high rates of sleep disturbance and emotional distress in people with T1D, the potential impacts of sleep characteristics and negative affect were also evaluated. Methods: This pilot study utilized EMA in 18 adults with T1D to examine the impact of glycemic excursions, measured using CGM, on cognitive performance, measured via mobile cognitive assessment using the TestMyBrain platform. Multilevel modeling was used to test the within-person effects of nocturnal hypoglycemia and hyperglycemia on next day cognition. Results: Results indicated that increases in nocturnal hypoglycemia were associated with slower next day processing speed. This association was not significantly attenuated by negative affect, sleepiness, or sleep quality. Conclusions: These results, while preliminary due to small sample size, showcase the power of intensive longitudinal designs using ambulatory cognitive assessment to uncover novel determinants of cognitive fluctuation in real world settings, an approach that may be utilized in other populations. Findings suggest reducing nocturnal hypoglycemia may improve cognition in adults with T1D. [ABSTRACT FROM AUTHOR]

Diabetic ketoacidosis (DKA) in pregnancy could be a disastrous event with increased maternal and perinatal morbidity and mortality. DKA can occur with a normal blood glucose level, known as euglycemic DKA. It particularly affects pregnant women with type I diabetes. Here, we report the case of a 28 year‐old primigravid patient, with a diagnosis of type 1 diabetes for 8 years. This patient consulted our department at 29 weeks of gestation with a previous history of headaches, vomiting and diarrhea for 9 h. Blood glucose level was 8.8 mmol/L with a ketone test positive (>15 mg/dL). Blood test showed high anion gap (17.9 mmol/L) with low serum bicarbonate rate (21 mmol/L). Systemic examination and fetal heart rate (FHR) was reassuring. The patient was subsequently discharged. She returned to the clinic 19 h later with further symptoms of nausea, polyuria‐polydipsia, asthenia and a weight loss of 4 kg since the day before. Blood sugar was 14.3 mmol/L and a ketone test was strongly positive. Cardiotocography showed fetal tachycardia and repeated late decelerations. A diagnosis of DKA was made and emergency cesarean was performed for fetal distress. At delivery, pH was acidosis (pH: 7.02, lactates: 6.2). The patient was successfully treated with intravenous hydration and insulin. Neonatal evolution was favorable. Pregnant women with type I diabetes can develop euglycemic DKA. Early recognition and prompt treatment could help prevent severe maternal and fetal adverse outcomes. DKA in pregnant women can induce fetal acidosis with abnormal FHR. In this situation, a cesarean can be performed to improve neonatal outcome even inducing a premature delivery. Prolonged pregnancy can lead to irreversible neonatal brain abnormalities. Synopsis: Diabetic ketoacidosis in pregnant women can induce fetal acidosis with abnormal fetal heart rate, which can lead to irreversible neonatal brain abnormalities. [ABSTRACT FROM AUTHOR]

• Brain alterations have been described in type 1 diabetes and diabetic neuropathy. • Metabolic profiles of neuropathic phenotypes using relevant brain regions were explored. • Specific metabolic brain profiles were linked to phenotypes of diabetes, neuropathy, and neuropathic pain. • Metabolic brain profiles could be relevant for detailed understanding of central neuropathy. The study aimed to investigate brain metabolites in type 1 diabetes and the associations with disease characteristics. We explored the metabolic profiles predicting different neuropathic phenotypes using multiple linear regression analyses. We compared brain metabolites in 55 adults with type 1 diabetes (including painful diabetic peripheral neuropathy (DPN), painless DPN, without DPN) with 20 healthy controls. Proton magnetic resonance spectroscopy measurements (N-acetylaspartate (NAA), glutamate (glu), myo-inositol (mI), and glycerophosphocholine (GPC) were obtained in ratios to creatine (cre)) from the parietal region, anterior cingulate cortex and thalamus. The overall diabetes group revealed decreased parietal NAA/cre compared to healthy controls (1.41 ± 0.12 vs. 1.55 ± 0.13,p < 0.001) and increased mI/cre (parietal: 0.62 ± 0.08 vs. 0.57 ± 0.07,p = 0.025, cingulate: 0.65 ± 0.08 vs. 0.60 ± 0.08,p = 0.033). Reduced NAA/cre was associated with more severe DPN (all p ≤ 0.04) whereas increased mI/cre was associated with higher hemoglobin A 1c (HbA 1c) (p = 0.02). Diabetes was predicted from decreased parietal NAA/cre, increased parietal ml/cre, and decreased thalamic glu/cre. DPN was predicted from decreased parietal NAA/cre and increased GPC/cre. Painful DPN was predicted from increased parietal GPC/cre and thalamic glu/cre. Specific metabolic brain profiles were linked to the different phenotypes of diabetes, DPN and painful DPN. Assessment of metabolic profiles could be relevant for detailed understanding of central neuropathy in diabetes. [ABSTRACT FROM AUTHOR]