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Pancreatic islet transplantation is proposed as a cure for type 1 diabetes mellitus (T1D). Despite its success in optimal regulation of glucose levels, limitations in longevity of islet grafts still require innovative solutions. Inflammatory stress post-transplantation and loss of extracellular matrix attribute to the limited β-cell survival. Pancreatic stellate cells (PSCs), identified as pancreatic-specific stromal cells, have the potential to play a crucial role in preserving islet survival. Our study aimed to determine the effects of PSCs co-cultured with human CM β-cells and human islets under inflammatory stress induced by a cytokine cocktail of IFN-γ, TNF-α and IL-1β. Transwell culture inserts were utilized to assess the paracrine impact of PSCs on β-cells, alongside co-cultures enabling direct interaction between PSCs and human islets. We found that co-culturing PSCs with human CM β-cells and human cadaveric islets had rescuing effects on cytokine-induced stress. Effects were different under normoglycemic and hyperglycemic conditions. PSCs were associated with upregulation of β-cell mitochondrial activity and suppression of inflammatory gene expression. The rescuing effects exist both in indirect and direct co-culture methods. Furthermore, we tested whether PSCs have rescuing effects on human islets in conventional alginate-based microcapsules and in composite microcapsules composed of alginate-pectin collagen type IV, laminin sequence RGD, Nec-1, and amino acid. PSCs partially prevented cytokine-induced stress in both systems, but beneficial effects were stronger in composite capsules. Our findings show novel effects of PSCs on islet health. Islets and PSCs coculturing or co-transplantation might mitigate the inflammation stress and improve islet transplantation outcomes.

[This corrects the article DOI: 10.3389/fimmu.2023.1207108.].

• Type 1 diabetes reduces exploration without reducing novelty-seeking motivation. • Deletion of TNFR1 attenuates the reduction in gait speed induced by type 1 diabetes. • Type 1 diabetes induces anxiety-like behavior in the first week post-streptozotocin. • Deletion of TNFR1 induces working memory impairment in normoglycemic mice. Type 1 diabetes mellitus (T1D) is associated with cognitive impairments in humans. A well-established animal model of T1D is induced through the administration of streptozotocin (STZ), a glucose analog that induces pancreatic β-cell death, resulting in hyperglycemia and cognitive impairment linked to neuroinflammation and oxidative stress. Tumor necrosis factor (TNF)-α, a key inflammatory mediator, is elevated in the central nervous system (CNS) of diabetic animals. In this study, we utilized TNFR1 knockout mice to investigate the role of TNFR1 signaling in short-term T1D-related cognitive impairment. Our findings showed that diabetic animals did not develop cognitive damage within the first 2 weeks of T1D but exhibited reduced exploration in all behavioral tests. Our findings suggest that this reduction in exploration was attributable to motor impairment, as there was no reduction in motivated novelty-seeking behavior. Additionally, deletion of TNFR1 signaling attenuated gait speed impairment in diabetic mice, but did not affect other motor-related or exploratory behaviors. [ABSTRACT FROM AUTHOR]

Introduction and aim. Orthorexia nervosa is described as an obsession with consuming solely healthy foods accompanied by restrictive behaviors. Patients with chronic conditions frequently require dietary interventions alongside medication to manage symptoms and slow down disease progression. However, when dietary restrictions are taken to extremes, individuals may develop orthorexia nervosa, resulting in malnutrition and weight loss. This poses risks during treatment, where maintaining a balanced diet is vital. In this review we aim to display the prevalence of orthorexia nervosa in patients suffering from selected chronic diseases. Material and methods. A literature review was performed to investigate the prevalence of orthorexia nervosa among individuals with type 1 diabetes, inflammatory bowel disease, celiac disease, rheumatoid arthritis, and cancer. Description of the State of Knowledge. The occurrence of orthorexia reaches up to 7% in the general population, 72% in patients with type 1 diabetes mellitus, 77% in case of inflammatory bowel disease, 71% among individuals suffering from celiac disease, 75% in those with rheumatoid arthritis, and 50% in case of cancer. Orthorexia nervosa predominantly affects females who are younger, have higher levels of education, select organic foods, prepare their own meals, and have other concurrent chronic illnesses. The distress associated with diagnosis is considered the primary factor contributing to the development of this condition. Orthorexia ultimately leads to malnutrition, weight loss, impaired social functioning, and poses a risk of complications during the management of patients suffering from chronic diseases. Conclusion. The prevalence of orthorexia nervosa in patients suffering from the exhibited chronic illnesses is significantly higher compared to the general population. Therefore, early detection of this condition and intervention are necessary to improve patient management. Further research is needed to assess the frequency of orthorexia among individuals suffering from other chronic diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims/Introduction Materials and Methods Results Conclusions We evaluated the effect of the MiniMed™ 770G, an insulin pump using hybrid closed‐loop technology, on blood glucose management and quality of life in Japanese people with type 1 diabetes.This was a 52‐week, prospective, observational study. Fifty Japanese people with type 1 diabetes switched from the MiniMed™ 640G to 770G, and we analyzed the continuous glucose monitoring data of 24 subjects who used auto mode throughout the study. We also analyzed the scores of the Diabetes Therapy‐Related Quality of Life questionnaire completed by 26 auto‐mode users before and after the treatment change.The baseline time in range 70–180 mg/dL was 67.3 (54.8–78.4)%, with a significant improvement beginning 8 weeks after the switch and lasting until 52 weeks. The baseline time below range <70 mg/dL was 1.9 (0.6–3.6)%, with a significant increase at week 8; however, the mean value was less than 4% throughout the study period. On the other hand, the number of blood glucose measurements significantly increased. While there was no significant difference in the overall change in the total Diabetes Therapy‐Related Quality of Life score, there was a significant decrease in the treatment satisfaction score.Use of the MiniMed™ 770G improved continuous glucose monitoring metrics. However, treatment satisfaction decreased, probably due to the increased frequency of blood glucose monitoring necessary to maintain auto mode. [ABSTRACT FROM AUTHOR]

This opinion paper evaluates the potential of porcine islets as a promising alternative in beta cell replacement therapy for Type 1 Diabetes (T1D), juxtaposed with the current limitations of human donor islets. It analyzes the compatibility of pig islets with human glucose metabolism, their prospects as a limitless and high-quality source of beta cells, and the unique immunogenic challenges they present in xenotransplantation. Additionally, the paper discusses the regulatory and ethical considerations pertinent to the use of porcine islets. By synthesizing current research and expert perspectives, the paper highlights both the opportunities and significant barriers that need addressing to advance pig islets as a viable therapeutic option. The findings advocate for a balanced and forward-looking approach to the integration of pig islets in T1D treatment, underscoring the need for continued research and dialogue in this evolving field. [ABSTRACT FROM AUTHOR]

The primary purpose of the original NAPCHD project was to develop a national Strategic Document of Diabetes Care for Care Homes which has now been completed and well received as a worthwhile, sustainable, and effective guidance for delivering quality diabetes care in the UK. A Working Group of NAPCHD was established to produce a Position Statement on type 1 diabetes in care homes since this area was recommended as a topic to further develop. There are currently limited data on the prevalence and clinical outcomes associated with type 1 diabetes in care homes and management policies have been non‐existent in the UK. Communication among all key stakeholders involved in direct care of residents with type 1 diabetes is generally fragmented and lacks coordination. This is compounded by a slowly growing utilisation of diabetes technology and the absence of a standard/agreed community‐based model of interdisciplinary collaboration. The Rationale and Objectives were defined prior to commencing the work and a work plan with individual tasks was initially set out. After multiple correspondences and Team calls over a period of 9 months, the Group successfully generated a first draft in October 2023. This draft was then finalised the following month and circulated among stakeholders for feedback. Nine chapters have been provided including minimum standards of diabetes care, insulin regimens, avoiding hospitalisation and discharge planning. A scheme for a community‐based model of care for type 1 diabetes has been included. Eight key messages were developed. In addition, an Appendix has been created which includes key assessments such as nutritional assessment, detection of frailty, sick day rules and foot risk stratification (available online). [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusion Coeliac disease (CD) is common in patients with type 1 diabetes (T1D), but prevalence varies globally due to differing screening protocols. There have been substantial changes in screening guidelines over the past two decades.To evaluate CD prevalence in patients with T1D, focusing on screening studies using antitissue transglutaminase (anti‐tTG) antibody.We searched PubMed, Web of Science, Embase and Scopus for studies published up to 11 December 2023 using keywords related to CD and diabetes. We used random‐effects models for overall prevalence and all subgroups, with heterogeneity assessed using Cochran's Q test and the I2 statistic performed in STATA 18.We included 106 articles involving 65,102 T1D patients across 40 countries. The pooled CD seroprevalence and confirmed CD prevalence were 9% (95% confidence interval, CI, 8%–10%) and 6% (95% CI 5%–7%), respectively. The prevalence was higher in females and children. Denmark, Saudi Arabia and Libya exhibited the highest prevalence (11%), followed by India and Egypt (10%). Belgium, France, Germany, South Africa and the United States had the lowest prevalence (2%). High‐income countries showed significantly a lower CD prevalence than middle‐income countries (p = 0.03). Meta‐regression based on the Human Development Index (HDI) indicated that countries with higher HDI have lower seroprevalence and confirmed CD prevalence.Approximately 1 in 16 patients globally and 1 in 12 patients in Asia and the Middle East with T1D has CD. We suggest that all patients with T1D should be screened for CD. [ABSTRACT FROM AUTHOR]

AimsMethodsResultsConclusionsWe compared sensor‐derived glycaemic metrics in pregnant women with type 1 diabetes (T1D) randomised to faster acting insulin aspart (faster aspart) or insulin aspart (IAsp).A pre‐planned secondary analysis of the CopenFast trial included women with T1D using intermittently scanned continuous glucose monitoring (isCGM) during pregnancy. Glycaemic metrics, including time in range (TIRp, 3.5–7.8 mmol/L) and time below range in pregnancy (TBRp, <3.5 mmol/L), were evaluated in the intervals: from randomisation (median 9.5 weeks, interquartile range 9.0–11.0) to 21 weeks, from 22 to 33 weeks and from 34 to 37 weeks.In total, 113 (91%) of 124 women using isCGM in the original trial were included. At randomisation, glycaemic metrics were comparable in both groups. Women randomised to faster aspart achieved higher TIRp from 22 to 33 weeks (estimated treatment difference 5.1% [95% confidence interval 0.3; 9.7], p = 0.04) and mean TIRp >70% from randomisation to 21 weeks onwards, while this was achieved after 34 weeks in women randomised to IAsp. TBRp remained stable around 4% throughout pregnancy in both groups. One (2%) versus 5 (9%) experienced ≥1 severe hypoglycaemic event (odds ratio 0.93 [−0.2; −0.01], p = 0.04). Infant birthweight standard deviation score was lower in the faster aspart group (estimated treatment difference −0.5 [−0.9; −0.03], p = 0.04); however, this attenuated when adjusting for parity (p = 0.10).Women using faster aspart achieved more TIRp and experienced less severe hypoglycaemia compared to women using IAsp. Infant birthweight was lower and thereby more appropriate in the faster aspart group; however, this attenuated when adjusting for parity. [ABSTRACT FROM AUTHOR]

There are still many insulin-containing β-cells in the pancreatic islets at diagnosis of clinical type 1 diabetes (T1D), with a morphological and functional reserve capacity for insulin production. The initiating event in the demise of the insulin-producing β-cells may be a low-grade persistent enterovirus infection. This sets in motion a cascade of both innate and adaptive immune responses (inflammation) and induces autoimmunity. Persistent infection may lead to endoplasmic reticulum stress, formation of neoantigens and autoantibodies, apoptosis, and loss of β-cells. Antiviral treatment preserves residual insulin production in newly diagnosed T1D. Type 1 diabetes (T1D), a severe disease requiring intensive insulin treatment, carries an increased risk for complications and reduced lifespan. Certain viruses have been implicated in T1D's etiology, with 'live', replicating enteroviruses (EVs) recently found in the pancreas at diagnosis. This discovery prompted a trial to slow down disease progression using antiviral drugs. A 6-month treatment combining pleconaril and ribavirin in new-onset T1D patients preserved residual insulin production after 1 year, unlike placebo. The results support the theory that viruses may cause T1D in genetically susceptible individuals. A low-grade, persistent viral infection may initiate a cascade of pathogenic mechanisms initially involving the innate immune system, inducing β-cell stress and neoantigen release, leading to autoimmunity, and eventually the destruction of insulin-producing β-cells. [ABSTRACT FROM AUTHOR]

Background Methods Key Results Conclusions & Inferences Diabetic gastroenteropathy can cause significant diagnostic challenges. Still, it remains unknown if measures of extraintestinal autonomic function reflect diabetic gastroenteropathy. We aimed to assess the associations between (1) gastrointestinal symptoms and motility measures and (2) gastrointestinal symptoms/motility measures and extraintestinal autonomic markers.We included 81 persons with type 1 or type 2 diabetes (65% female, mean age 54) with gastrointestinal symptoms and autonomic neuropathy. The Gastroparesis Cardinal Symptom Index (GCSI) and the Gastrointestinal Symptom Rating Scale (GSRS) assessed gastrointestinal symptoms. The wireless motility capsule (Smartpill™) assessed panenteric transit times and motility indices. Cardiovascular reflex tests (VAGUS™) and cardiac vagal tone (eMotion Faros) estimated cardiovascular autonomic neuropathy, while the SUDOSCAN™ evaluated sudomotor function.Proximal gastrointestinal symptoms were positively associated with the gastric motility index (GCSI: 1.18 (1.04–1.35), p = 0.01; GSRS: 1.15 (1.03–1.29), p = 0.02; median ratio (95% CI)), while only satiety correlated with gastric emptying time (1.24 (1.03–1.49), p = 0.02). Diarrhea was associated with decreased small bowel transit time (0.93 (0.89–0.98), p = 0.005), while constipation were associated with prolonged colonic transit time (1.16 (1.03–1.31), p = 0.02). Gastrointestinal symptoms increased with the degree of abnormal cardiovascular reflex tests (GCSI: 0.67 (0.16–1.19), p = 0.03; GSRS: 0.87 (0.30–1.45), p = 0.01; mean difference (95% CI)) but not with motility measures. Cardiac vagal tone and sudomotor function were not associated with gastrointestinal markers.Gastrointestinal and extraintestinal autonomic measures were not associated. However, proximal gastrointestinal symptoms were associated with the gastric motility index and cardiovascular reflex tests. Hence, the latter may contribute to evaluating whether proximal gastrointestinal symptoms are autonomically derived. [ABSTRACT FROM AUTHOR]

Introduction: In an uncontrolled study, we previously demonstrated the feasibility and preliminary efficacy of our virtual diabetes-specific version (Diabetes Body Project) of the eating disorder (ED) prevention program the Body Project. The aim of the current study was to evaluate further this program for women with type 1 diabetes (T1D) by assessing within-subject changes in outcomes from pretest over 6-month follow-up. Methods: Young women with T1D aged 16–35 years were invited to participate in Diabetes Body Project groups. A total of 35 participants were allocated to five Diabetes Body Project groups (six meetings over 6 weeks). Primary outcome measures included ED risk factors and symptoms, and secondary outcomes included three T1D-specific constructs previously found to be associated with ED pathology: glycemic control as measured by HbA1c level, diabetes distress, and illness perceptions. Results: Within-subject reductions, with medium-to-large effect sizes, were observed for the primary (ED pathology, body dissatisfaction, thin-ideal internalization, and appearance ideals and pressures) and secondary outcomes (within-condition Cohen's ds ranged from.34 to 1.70). Conclusion: The virtual Diabetes Body Project appears to be a promising intervention worthy of more rigorous evaluation. A randomized controlled trial with at least a 1-year follow-up is warranted to determine its efficacy compared to a control condition. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the association between maternal glycemic control and the risk of congenital malformations in offspring of women with type 1 diabetes and to examine whether there is a hemoglobin A1C (Hb A1C) threshold value at which the risk for malformations increases significantly. METHODS: Analyses were performed on data from a multinational, observational cohort of 1,908 liveborn offspring of women with type 1 diabetes recruited in early pregnancy from 17 countries between 2013 and 2018. Offspring with malformations were identified according to European Surveillance of Congenital Anomalies version 1.4 and categorized as having one or more major malformations or minor malformations exclusively. The association between first-trimester Hb A1C levels and the risk of congenital malformations was investigated with splines in crude and adjusted logistic regression models. RESULTS: In total, 11.9% of the offspring (n5227) of women with type 1 diabetes had congenital malformations, including 2.1% (n540) with at least one severe malformation. Women giving birth to offspring with malformations had a higher prevalence of psychiatric disorders (13.2% vs 7.2%, P,.01), thyroid disorders (33.0% vs 26.7%, P,.05), and folic acid supplementation (87.1% vs 77.7%, P,.01). The Hb A1C levels in the first trimester were similar (median 6.8% [interquartile range 6.3-7.6%] vs 6.7% [6.2-7.6%], P5.13) compared with women giving birth to offspring without malformations. The spline analysis illustrated a curvilinear association between Hb A1C levels and the risk of malformations with no clear threshold values. Higher first-trimester Hb A1C levels were associated with an increased risk of malformations (crude odds ratio [OR] 1.13, 95% CI, 1.01-1.27, adjusted odds ratio [aOR] 1.29, 95% CI, 1.10-1.51) and major malformations (crude OR 1.49, 95% CI, 1.23-1.81, aOR 1.57, 95% CI, 1.15-2.09). CONCLUSION: An increased risk for congenital malformations was curvilinearly associated with higher Hb A1C levels in early pregnancy among women with type 1 diabetes without any threshold values identified. [ABSTRACT FROM AUTHOR]

Continuous glucose monitoring (CGM) has the potential to revolutionize diabetes management during pregnancy by providing detailed and real-time data to patients and clinicians, overcoming many of the limitations of selfmonitoring of blood glucose. Although there are limited data on the role of CGM to improve pregnancy outcomes in patients with type 2 diabetes or gestational diabetes, CGM has been shown to reduce pregnancy complications in patients with type 1 diabetes. Despite the limited data in some populations, given its ease of use and recent U.S. Food and Drug Administration approval with expanding insurance coverage, CGM has gained widespread popularity among pregnant patients with all types of diabetes. It is critical for obstetric clinicians to understand how CGM can be successfully integrated into clinical practice. We present a practical, step-wise approach to CGM data interpretation that can be incorporated into diabetes management during pregnancy and common CGM pitfalls and solutions. Although technology will continue to advance with newergeneration CGM devices and diabetes technology such as automated insulin delivery (not covered here), these key principles form a basic foundation for understanding CGM technology and its utility for pregnant people. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Despite the well-recognized association between pre-existing diabetes mellitus and stillbirth or perinatal mortality, there remain knowledge gaps about the strength of association across different populations. The primary objective of this systematic review and meta-analysis was to quantify the association between pre-existing diabetes and stillbirth or perinatal mortality, and secondarily, to identify risk factors predictive of stillbirth or perinatal mortality among those with preexisting diabetes. DATA SOURCES: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to April 2022. METHODS OF STUDY SELECTION: Cohort studies and randomized controlled trials in English or French that examined the association between pre-existing diabetes and stillbirth or perinatal mortality (as defined by the original authors) or identified risk factors for stillbirth and perinatal mortality in individuals with pre-existing diabetes were included. Data extraction was performed independently and in duplicate with the use of prespecified inclusion and exclusion criteria. Assessment for heterogeneity and risk of bias was performed. Metaanalyses were completed with a random-effects model. TABULATION, INTEGRATION, AND RESULTS: From 7,777 citations, 91 studies met the inclusion criteria. Preexisting diabetes was associated with higher odds of stillbirth (37 studies; pooled odds ratio [OR] 3.74, 95% CI, 3.17-4.41, I2582.5%) and perinatal mortality (14 studies; pooled OR 3.22, 95% CI, 2.54-4.07, I2582.7%). Individuals with type 1 diabetes had lower odds of stillbirth (pooled OR 0.81, 95% CI, 0.68-0.95, I250%) and perinatal mortality (pooled OR 0.73, 95% CI, 0.61-0.87, I250%) compared with those with type 2 diabetes. Prenatal care and prepregnancy diabetes care were significantly associated with lower odds of stillbirth (OR 0.26, 95% CI, 0.11-0.62, I2587.0%) and perinatal mortality (OR 0.41, 95% CI, 0.29-0.59, I250%). CONCLUSION: Pre-existing diabetes confers a more than threefold increased odds of both stillbirth and perinatal mortality. Maternal type 2 diabetes was associated with a higher risk of stillbirth and perinatal mortality compared with maternal type 1 diabetes. [ABSTRACT FROM AUTHOR]

Managing diabetes in pregnancy can be overwhelming, with numerous dramatic physiologic changes taking place that require constant diligence and attention. Advances in diabetes technology have improved glycemic outcomes, well-being, and quality of life for people with type 1 diabetes of all ages. However, regulatory approval and access to diabetes technology in pregnancy has lagged behind these advancements, leaving many pregnant individuals without tools that could dramatically improve diabetes care before, during, and after gestation. Here, we review the benefits of continuous glucose monitors and automated insulin-delivery systems in pregnancy and highlight specific scientific and structural supports to help implement diabetes technology safely, effectively, and equitably in pregnancy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the presentation, management, and outcomes of pregnancies complicated by diabetic ketoacidosis (DKA) in a contemporary obstetric population. METHODS: This is a case series of all admissions for DKA during pregnancy at a single Midwestern academic medical center over a 10-year period. Diabetic ketoacidosis was defined per the following diagnostic criteria: anion gapmore than 12 mEq/L, pH less than 7.30 or bicarbonate less than 15 mEq/L, and elevated serum or urine ketones. Demographic information, clinical characteristics, and maternal and neonatal outcomes were assessed. Patient characteristics and clinical outcomes were compared between individuals with type 1 and those with type 2 diabetes mellitus. RESULTS: Between 2012 and 2021, there were 129 admissions for DKA in 103 pregnancies in 97 individuals. Most individuals (n575, 77.3%) admitted for DKA during pregnancy had type 1 diabetes. The majority of admissions occurred in the third trimester (median gestational age 29 3/7 weeks). The most common precipitating factors were vomiting or gastrointestinal illness (38.0%), infection (25.6%), and insulin nonadherence (20.9%). Median glucose on admission was 252 mg/dL (interquartile range 181-343 mg/dL), and 21 patients (17.6%) were admitted with euglycemic DKA. Fifteen admissions (11.6%) were to the intensive care unit. Pregnancy loss was diagnosed during admission in six individuals (6.3%, 95% CI, 2.3-13.7%). Among pregnant individuals with at least one admission for DKA, the median gestational age at delivery was 34 6/7 weeks (interquartile range 33 2/7-36 3/7 weeks). Most neonates (85.7%, 95% CI, 76.8-92.2%) were admitted to the neonatal intensive care unit and required treatment for hypoglycemia. The cesarean delivery rate was 71.9%. Despite similar hemoglobin A1C values before pregnancy and at admission, individuals with type 1 diabetes had higher serum glucose (median [interquartile range], 256 mg/dL [181-353 mg/dL] vs 216 mg/dL [136-258 mg/dL], P5.04) and higher serum ketones (3.78 mg/dL [2.13-5.50 mg/dL] vs 2.56 mg/dL [0.81-4.69 mg/dL] mg/dL, P5.03) on admission compared with those with type 2 diabetes. Individuals with type 2 diabetes required intravenous insulin therapy for a longer duration (55 hours [29.5-91.5 hours] vs 27 hours [19-38 hours], P5.004) and were hospitalized longer (5 days [4-9 days] vs 4 days [3-6 days], P5.004). CONCLUSION: Diabetic ketoacidosis occurred predominantly in pregnancies affected by type 1 diabetes. Individuals with type 1 diabetes presented with greater DKA severity but achieved clinical resolution more rapidly than those with type 2 diabetes. These resultsmay provide a starting point for the development of interventions to decrease maternal and neonatal morbidity related to DKA in the modern obstetric population. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the frequency of, risk factors for, and adverse outcomes associated with diabetic ketoacidosis (DKA) at delivery hospitalization among individuals with pregestational diabetes (type 1 and 2 diabetes mellitus) and secondarily to evaluate the frequency of and risk factors for antepartum and postpartum hospitalizations for DKA. METHODS: We conducted a serial, cross-sectional study using the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2010 to 2020 of pregnant individuals with pregestational diabetes hospitalized for delivery. The exposures were 1) sociodemographic and clinical risk factors for DKA and 2) DKA. The outcomes were DKA at delivery hospitalization, maternal morbidity (nontransfusion severe maternal morbidity (SMM), critical care procedures, cardiac complications, acute renal failure, and transfusion), and adverse pregnancy outcomes (preterm birth, hypertensive disorders of pregnancy, and cesarean delivery) and secondarily DKA at antepartum and postpartum hospitalizations. RESULTS: Of 392,796 deliveries in individuals with pregestational diabetes (27.2% type 1 diabetes, 72.8% type 2 diabetes), there were 4,778 cases of DKA at delivery hospitalization (89.1% type 1 diabetes, 10.9% type 2 diabetes). The frequency of DKA at delivery hospitalization was 1.2% (4.0% with type 1 diabetes, 0.2% with type 2 diabetes), and the mean annual percentage change was 10.8% (95% CI, 8.2-13.2%). Diabetic ketoacidosis at delivery hospitalization was significantly more likely among those who had type 1 diabetes compared with those with type 2 diabetes, who were younger in age, who delivered at larger and metropolitan hospitals, and who had Medicaid insurance, lower income, multiple gestations, and prior psychiatric illness. Diabetic ketoacidosis during the delivery hospitalization was associated with an increased risk of nontransfusion SMM (20.8% vs 2.4%, adjusted odds ratio [aOR] 8.18, 95% CI, 7.20-9.29), critical care procedures (7.3% vs 0.4%, aOR 15.83, 95% CI, 12.59-19.90), cardiac complications (7.8% vs 0.8%, aOR 8.87, 95% CI, 7.32-10.76), acute renal failure (12.3% vs 0.7%, aOR 9.78, 95% CI, 8.16-11.72), and transfusion (6.2% vs 2.2%, aOR 2.27, 95% CI, 1.87-2.75), as well as preterm birth (31.9% vs 13.5%, aOR 2.41, 95% CI, 2.17-2.69) and hypertensive disorders of pregnancy (37.4% vs 28.1%, aOR 1.11, 95% CI, 1.00-1.23). In secondary analyses, the overall frequency of antepartum DKA was 3.1%, and the mean annual percentage change was 4.1% (95% CI, 0.3-8.6%); the overall frequency of postpartum DKA was 0.4%, and the mean annual percentage change was 3.5% (95% CI, 21.6% to 9.6%). Of 3,092 antepartum hospitalizations among individuals with DKA, 15.7% (n5485) had a recurrent case of DKA at delivery hospitalization. Of 1,419 postpartum hospitalizations among individuals with DKA, 20.0% (n5285) previously had DKA at delivery hospitalization. The above risk factors for DKA at delivery hospitalization were similar for DKA at antepartum and postpartum hospitalizations. CONCLUSION: The frequency of DKA at delivery hospitalization and antepartum hospitalizations for DKA increased between 2010 and 2020 among deliveries in individuals with pregestational diabetes in the United States. Diabetic ketoacidosis is associated with an increased risk of maternal morbidity and adverse pregnancy outcomes. Risk factors for DKA at delivery were similar to those for DKA during the antepartum and postpartum periods. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Underserved young adults (YA) with type 1 diabetes (T1D) experience the worst outcomes across the life span. We developed and integrated the Supporting Emerging Adults with Diabetes (SEAD) program into routine endocrinology care to address unmet social and medical challenges. RESEARCH DESIGN AND METHODS: This study was designed as a longitudinal cohort study, with prospective data collection over 4 years on YA in SEAD compared with usual endocrine care. We used propensity-weighted analysis to account for differences in baseline characteristics, and multivariate regression and Cox proportional hazard models to evaluate change in outcomes over time. Primary outcomes included incidence of hospitalizations, diabetes technology uptake, and annual change in HbA1c levels. RESULTS: We included 497 YA with T1D in SEAD (n = 332) and usual endocrine care (n = 165); mean age 25 years, 27% non-Hispanic Black, 46% Hispanic, 49% public insurance, mean HbA1c 9.2%. Comparing YA in SEAD versus usual care, 1) incidence of hospitalizations was reduced by 64% for baseline HbA1c >9% (HR 0.36 [0.13, 0.98]) and 74% for publicly insured (HR 0.26 [0.07, 0.90]); 2) automated insulin delivery uptake was 1.5-times higher (HR 1.51 [0.83, 2.77]); and 3) HbA1c improvement was greater (SEAD, −0.37% per year [−0.59, −0.15]; usual care, −0.26% per year [−0.58, 0.05]). CONCLUSIONS: SEAD meaningfully improves clinical outcomes in underserved YA with T1D, especially for publicly insured and high baseline HbA1c levels. Early intervention for at-risk YA with T1D as they enter adult care could reduce inequity in short and long-term outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine efficacy and safety of intrapartum and early postpartum advanced hybrid closed-loop (AHCL) therapy compared with standard insulin therapy in pregnant women with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: CRISTAL was a double-arm, open-label, randomized controlled trial performed in Belgium and the Netherlands that assigned 95 pregnant participants with T1D 1:1 to a MiniMed 780G AHCL system (n = 46) or standard insulin therapy (n = 49). This prespecified, secondary observational analysis focused on differences in glycemic control and safety outcomes between participants from the original AHCL group who continued AHCL intrapartum (n = 27) and/or early postpartum (n = 37, until hospital discharge) and those from the original standard insulin therapy group using standard insulin therapy intrapartum (n = 45) and/or early postpartum (n = 34). RESULTS: Of the 43 and 46 participants in the AHCL and standard insulin therapy groups, respectively, completing the trial, 27 (62.8%) in the AHCL group continued AHCL and 45 in the standard insulin therapy group (97.8%) continued standard insulin therapy intrapartum. Compared with standard insulin therapy, intrapartum AHCL was associated with more time in range 3.5–7.8 mmol/L (71.5 ± 17.7% vs. 63.1 ± 17.0%, P = 0.030) and numerically lower time above range >7.8 mmol/L (27.3 ± 17.4% vs. 35.3 ± 17.5%, P = 0.054), without increases in time below range <3.5 mmol/L (1.1 ± 2.4% vs. 1.5 ± 2.3%, P = 0.146). Early postpartum, 37 (86.0%) participants randomized to AHCL continued AHCL, with a median increase in insulin-to-carbohydrate ratios of 67% (interquartile range −14 to 126). Similar tight glycemic control (3.9–10.0 mmol/L: 86.8 ± 6.7% vs. 83.8 ± 8.1%, P = 0.124) was observed with AHCL versus standard insulin therapy. No severe hypoglycemia or diabetic ketoacidosis was reported in either group. CONCLUSIONS: AHCL is effective in maintaining tight glycemic control intrapartum and early postpartum and can be safely continued during periods of rapidly changing insulin requirements. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the prevalence of parental diabetes between children with and without type 1 diabetes (T1D), and to compare clinical characteristics at diagnosis of T1D in children with, versus without, a family history of diabetes. RESEARCH DESIGN AND METHODS: Parental diabetes among children with T1D was compared with a general population cohort. Clinical characteristics were compared by family history of diabetes in parents and grandparents of 3,603 children with T1D using relative risk (RR) and ANOVA. RESULTS: Children with T1D more often had parents with type 2 diabetes (T2D) (RR 1.88; P < 0.001) than did children without diabetes. Children with T1D and a family history of T2D were more likely to be overweight or obese (P = 0.002). CONCLUSIONS: A family history of T2D and being overweight may contribute to increased risk of T1D. [ABSTRACT FROM AUTHOR]

Context Diabetes is a global health concern, and diet is a contributing factor to diabetes. Findings regarding the connection between nitrate, nitrite, and nitrosamine and diabetes risk are inconsistent. Objective The aim was to examine the effects of these dietary compounds on diabetes risk. Data Sources The data were sourced from PubMed, EMBASE, Scopus, and Web of Science until February 28, 2023. Studies that reported individual-level consumption of these compounds were included. Review articles or ecological studies were excluded. Data Extraction The number of events and total observations were recorded. Data Analysis The pooled odds ratio (OR) was calculated and displayed in a forest plot. Subgroup and sensitivity analyses were predefined. A dose–response meta-analysis was conducted to determine the exposure intervals that may increase the risk of disease. Six observational reports that met the inclusion criteria were included, involving 108 615 individuals. Participants in the highest quantile of nitrite intake had a greater risk of diabetes compared with those in the lowest quantile (OR, 1.61; 95% confidence interval [CI], 1.08–2.39; I2 = 74%, P = 0.02). Higher nitrosamine consumption tended to increase diabetes risk (OR, 1.52; 95% CI, 0.76–3.04; I2 = 76%; P = 0.24). The relationship was stronger for type 1 (OR, 1.79; 95% CI, 1.20–2.67; I2 = 58%; P < 0.01) than for type 2 diabetes (OR, 1.42; 95% CI, 0.86–2.37; I2 = 71%; P = 0.17). Additionally, nitrite consumption had a dose-dependent association with both phenotypes. No association was found between diabetes risk and high nitrate intake (OR, 1.01; 95% CI, 0.87–1.18; I2 = 28%; P = 0.87). Conclusion Attention should be paid to the consumption of nitrite-containing foods. Systematic Review Registration PROSPERO registration no. CRD42023394462 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=394462). [ABSTRACT FROM AUTHOR]

The approval of teplizumab to delay the onset of type 1 diabetes is an important inflection point in the decades-long pursuit to treat the cause of the disease rather than its symptoms. The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop of the Diabetes Mellitus Interagency Coordinating Committee titled "Evolving Concepts in Pathophysiology, Screening, and Prevention of Type 1 Diabetes" to review this accomplishment and identify future goals. Speakers representing Type 1 Diabetes TrialNet (TrialNet) and the Immune Tolerance Network emphasized that the ability to robustly identify individuals destined to develop type 1 diabetes was essential for clinical trials. The presenter from the U.S. Food and Drug Administration described how regulatory approval relied on data from the single clinical trial of TrialNet with testing of teplizumab for delay of clinical diagnosis, along with confirmatory evidence from studies in patients after diagnosis. The workshop reviewed the etiology of type 1 diabetes as a disease involving multiple immune pathways, highlighting the current understanding of prognostic markers and proposing potential strategies to improve the therapeutic response of disease-modifying therapies based on the mechanism of action. While celebrating these achievements funded by the congressionally appropriated Special Diabetes Program, panelists from professional organizations, nonprofit advocacy/funding groups, and industry also identified significant hurdles in translating this research into clinical care. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) results from β-cell destruction due to autoimmunity. It has been proposed that β-cell loss is relatively quiescent in the early years after seroconversion to islet antibody positivity (stage 1), with accelerated β-cell loss only developing around 6–18 months prior to clinical diagnosis. This construct implies that immunointervention in this early stage will be of little benefit, since there is little disease activity to modulate. Here, we argue that the apparent lack of progression in early-stage disease may be an artifact of the modality of assessment used. When substantial β-cell function remains, the standard assessment, the oral glucose tolerance test, represents a submaximal stimulus and underestimates the residual function. In contrast, around the time of diagnosis, glucotoxicity exerts a deleterious effect on insulin secretion, giving the impression of disease acceleration. Once glucotoxicity is relieved by insulin therapy, β-cell function partially recovers (the honeymoon effect). However, evidence from recent trials suggests that glucose control has little effect on the underlying disease process. We therefore hypothesize that the autoimmune destruction of β-cells actually progresses at a more or less constant rate through all phases of T1D and that early-stage immunointervention will be both beneficial and desirable. Article Highlights: The process of autoimmune destruction of insulin-producing beta-cells in type 1 diabetes (T1D) begins long before the onset of clinical symptoms. Most studies in preclinical T1D have used an oral glucose tolerance test (OGTT) and concluded that β-cell loss occurs late; however, the OGTT underestimates β-cell function in the earliest preclinical stage (stage 1). Loss of β-cell function is said to accelerate around the time of clinical diagnosis, but this is likely attributable to glucotoxicity rather than an acceleration of the autoimmune process. We conclude that autoimmune-mediated β-cell loss is likely progressive throughout the preclinical period, and immunointervention efforts should focus on time points earlier in the process. [ABSTRACT FROM AUTHOR]

Excessive formation of macrophage extracellular trap (MET) has been implicated in several autoimmune disease pathogeneses; however, its impact on type 1 diabetes (T1D) and related mechanisms remains enigmatic. We demonstrated the pivotal role of peptidyl arginine deiminase 4 (PAD4) in driving profuse MET formation and macrophage M1 polarization in intestinal inflammation in NOD mice. Genetic knockout of PAD4 or adoptive transfer of METs altered the proportion of proinflammatory T cells in the intestine, subsequently influencing their migration to the pancreas. Combining RNA sequencing and CUT&Tag analysis, we found activated PAD4 transcriptionally regulated CXCL10 expression. This study comprehensively investigated how excessive PAD4-mediated MET formation in the colon increases the aggravation of intestinal inflammation and proinflammatory T-cell migration and finally is involved in T1D progression, suggesting that inhibition of MET formation may be a potential therapeutic target in T1D. Article Highlights: The role of macrophage extracellular trap (MET) formation in the pathology of type 1 diabetes (T1D) remains unclear. We aimed to investigate the impact of MET formation on intestinal inflammation and its subsequent effect on the pathogenesis of T1D in NOD mice. Activated peptidyl arginine deiminase 4 (PAD4) facilitates MET formation and transcriptionally regulates CXCL10 expression, leading to accelerated T1D through the activation and migration of proinflammatory T cells via the gut/pancreas axis. Findings suggest that targeting PAD4-mediated MET formation could emerge as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

This scoping review synthesizes evidence on metformin's use during pregnancy, encompassing diverse conditions like gestational diabetes, type 1 and type 2 diabetes, polycystic ovary syndrome (PCOS), and obesity. Metformin demonstrates comparable efficacy to insulin in gestational diabetes, positive outcomes in type 2 diabetes pregnancies, and potential benefits in reducing complications. The review highlights nuances in its effects across conditions, indicating advantages such as reduced risk of macrosomia and cesarean section in gestational diabetes. However, its prophylactic role in preventing gestational diabetes and associated complications remains inconclusive. In obese pregnant women, mixed results are observed, with potential benefits in reducing pre‐eclampsia risk. Metformin shows promise in preventing preterm birth and late miscarriage in PCOS pregnancies. Categorizing patient subgroups is crucial for identifying advantages, especially in gestational diabetes and type 2 diabetes. Challenges arise from study heterogeneity, necessitating standardized indications for dosage, timing, and postpartum follow ups. Efforts to identify patient characteristics influencing metformin efficacy are crucial for tailored therapy. Although metformin emerges as a viable option in complicated pregnancies, comprehensive research, standardized protocols, and subgroup identification efforts will enhance clinical utility, ensuring evidence‐based therapies and optimal maternal and fetal outcomes. Bridging existing knowledge gaps remains imperative for advancing metformin's role in pregnancy management. [ABSTRACT FROM AUTHOR]

Objective: To compare ultrasound‐assessed fetal head circumference (HC), abdominal circumference (AC), HC/AC ratio, and estimated fetal weight (EFW) in prediction of large‐for‐gestational‐age (LGA) at birth in pregnancies affected by type 1 (T1DM) and type 2 (T2DM) diabetes. Methods: This retrospective cohort study included all women with T1DM and T2DM giving birth to singletons between 2010 and 2019 at Aalborg University Hospital, Denmark. Ultrasound scans were performed at 16, 20, 28 and 34 weeks of pregnancy. LGA was defined as birth weight deviation of 15% or greater from the expected for gestational age (≥90th centile). Prediction of LGA was assessed by logistic regression adjusted for maternal characteristics and glycated hemoglobin (HbA1c) and area under the receiver operating characteristics curve (AUC). Results: Among 180 T1DM pregnancies, 118 (66%) had an LGA neonate at birth. At 28 weeks of pregnancy, they were predicted with AUCHC/AC = 0.67, AUCAC = 0.85, and AUCEFW = 0.86. The multivariate analysis did not improve the predictive performance of the HC/AC ratio or AC. Among 87 T2DM pregnancies, 36 (41%) had an LGA neonate at birth. At 28 weeks, they were predicted with AUCHC/AC = 0.73, AUCAC = 0.83, and AUCEFW = 0.87. In T2DM, the multivariate analysis significantly improved the predictive performance for both HC/AC ratio and AC from 20 weeks of pregnancy. Conclusion: In T1DM and T2DM pregnancies, LGA is characterized by a general fetal overgrowth including both AC and HC. Therefore, AC and EFW perform better than the HC/AC ratio in the prediction of LGA. In T2DM, as opposed to T1DM, the predictive performance was improved by the inclusion of maternal characteristics and HbA1c in the analysis. Synopsis: In pregnancies involving type 1 and type 2 diabetes, estimated fetal weight and abdominal circumference are superior to head circumference/abdominal circumference ratio, in predicting large‐for‐gestational‐age. [ABSTRACT FROM AUTHOR]

Aims: The present analysis estimated the cost‐effectiveness of treatment with the Tandem t: slim X2 insulin pump with Control IQ technology (CIQ) in children with type 1 diabetes in Sweden. Methods: A four‐state Markov model and probabilistic sensitivity analyses (PSA) were used to assess the cost‐effectiveness of CIQ use compared with treatment with multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII) in conjunction with CGM. Data sources included clinical input data from a recent retrospective, observational study, cost data from local diabetes supply companies and government agencies, and published literature. Outcomes measures were quality adjusted life years (QALYs) at 10, 20 and 30‐year time horizons based on cost per QALY and incremental cost‐effectiveness ratio (ICER). Results: A total of 84 type 1 diabetes children were included (CIQ, n = 37; MDI, n = 19; CSII, n = 28). For all time horizons, the use of CIQ was a dominant strategy (e.g. more effective and less costly) compared with MDI or CSII use: 10‐year ICER, SEK ‐88,010.37 and SEK ‐91,723.92; 20‐year ICER, SEK −72,095.33 and SEK −87,707.79; and 30‐year ICER, SEK −65,573.01 and SEK ‐85,495.68, respectively. PSA confirmed that CIQ use was less costly compared with MDI and CSII. Conclusions: Initiation of CIQ use in children with type 1 diabetes is cost‐saving, besides previously shown improved glycaemic control, and increased quality of life. Further investigations are needed to more fully elucidate the cost‐effectiveness of these technologies in different countries with existing differences in payment models. [ABSTRACT FROM AUTHOR]

Aims: Advancements in type 1 diabetes (T1D) management, such as continuous glucose monitoring (CGM), have helped people achieve narrower glucose ranges, but associations between CGM and diabetes distress are unclear. Although higher HbA1c is associated with higher distress, associations with other glucose metrics are unknown. To better understand this relationship, we characterized diabetes distress in a sample of CGM users and compared differences in glucose metrics (measured via CGM) between those with higher versus lower distress. Methods: CGM users with T1D from the T1D Exchange Registry completed an online survey including diabetes distress (DDS‐2) and shared CGM data (N = 199). CGM metrics were computed from all available data within 3 months prior to survey completion. Participants were grouped by distress level: lower (DDS‐2 < 3, n = 120) or higher (DDS‐2 ≥ 3, n = 79). Welch's t‐tests were used to compare mean differences in CGM metrics between groups and MANCOVA was used to further probe mean differences. Results: Approximately 39.7% participants reported higher diabetes distress. Welch's t‐tests revealed participants with higher distress spent significantly more time in higher glucose ranges (above 180 mg/dL and above 250 mg/dL), less time in target glucose ranges (between 70 and 180 mg/dL and between 70 and 140 mg/dL) and had higher glucose management index values compared to those with lower distress (p < 0.01). MANCOVA models showed similar results. Conclusions: CGM users continue to experience diabetes distress. Moreover, higher distress appears to be associated with hyperglycaemia. These findings provide support for broader screening efforts for diabetes distress. [ABSTRACT FROM AUTHOR]

Aim: One third of Australian children diagnosed with type 1 diabetes present with life‐threatening diabetic ketoacidosis (DKA) at diagnosis. Screening for early‐stage, presymptomatic type 1 diabetes, with ongoing follow‐up, can substantially reduce this risk (<5% risk). Several screening models are being trialled internationally, without consensus on the optimal approach. This pilot study aims to assess three models for a routine, population‐wide screening programme in Australia. Methods: An implementation science‐guided pilot study to evaluate the feasibility, acceptability and costs of three screening models in children will be conducted between July 2022 and June 2024. These models are as follows: (1) Genetic risk‐stratified screening using newborn heel prick dried bloodspots, followed by autoantibody testing from 11 months of age; (2) genetic risk‐stratified screening of infant (6–12 months) saliva followed by autoantibody testing from 10 months of age; and (3) autoantibody screening using capillary dried bloodspots collected from children aged 2, 6 or 10 years. Cohorts for each model will be recruited from targeted geographic areas across Australia involving ≥2 states per cohort, with a recruitment target of up to 3000 children per cohort (total up to 9000 children). The primary outcome is screening uptake for each cohort. Secondary outcomes include programme feasibility, costs, parental anxiety, risk perception, satisfaction, well‐being and quality of life, and health professional attitudes and satisfaction. Conclusions: This pilot is the first direct comparison of three screening implementation models for general population screening. Findings will provide evidence to inform a potential national screening programme for Australian children. Trial Registration: ACTRN12622000381785. [ABSTRACT FROM AUTHOR]

Objective: People with Type 1 diabetes (T1D) face an increased risk of eating disorders/disordered eating (ED/DE), with adolescents being particularly vulnerable. Empirical knowledge on the mechanisms underlying development of ED/DE in T1D is crucial for evolving prevention strategies. Research Design and Methods: Fourteen semi‐structured interviews with adolescent females with T1D and ED/DE between 14 and 18 years were conducted and analyzed using reflexive thematic analysis. Results: Analyses identified four main themes; 'Interconnected afflictions', 'Judgment', 'Feeling Different', and 'Chaos & Control', These themes explore the interconnectedness of T1D and ED/DE, with shame and guilt emerging as common underlying mechanism. The development of a biopsychosocial model was based on the integration of these data with existing models. Conclusions: The study extends previous developmental pathways of ED/DE in adolescents with T1D. We propose a biopsychosocial model that incorporates various factors: predisposing factors such as parental management of T1D and weight gain during adolescence; precipitating factors including comments on weight, frequency of weighing, perceptions of surveillance; the perpetuating bilateral influence of ED/DE and T1D and finally highlighting the protective mechanisms of disease acceptance encompassing parental handling of diagnosis and the contribution of healthcare professionals (HCP's) role in psychoeducation. The present study highlight the vulnerability of adolescence in the presence of T1D, particularly concerning issues related to eating, weight, and body. It offers clinically relevant insights, with the aim to improve communication and management strategies for this very specific group. [ABSTRACT FROM AUTHOR]

Aims: There are marked inequities in clinical outcomes and rates of diabetes technology use among youth with type 1 diabetes (T1D). The quantitative data from our mixed methods cohort study identified significant improvements in glycaemia and quality of life in participants. We aimed to use qualitative methods to provide further insight into our quantitative findings in the setting of underlying health disparities. Methods: Fifteen publicly insured, insulin pump‐naïve non‐Hispanic Black youth aged 6–21 years with T1D and baseline haemoglobin A1c (HbA1c) ≥86 mmol/mol (10%) and their parents participated in a mixed methods cohort study. Semi‐structured interviews were conducted separately with parents and youth after completion of 6 months of HCL use. Three topic areas were explored: (1) Experience using HCL, (2) barriers to HCL and (3) facilitators to accessing HCL. Semantic content analysis and consensus coding involving two team members were used to generate themes. Thematic saturation was achieved. Results: Youth (Medianage 14.9 years, 67% female) and parents (92% female) were interviewed. Youth and their parents reported that access to HCL provides a new outlook on living with T1D, although managing T1D is still hard. They felt that diabetes technology is most helpful for those struggling with management. Participants experienced barriers to access including misconceptions of HCL systems, clinician bias and systemic racism. They suggested these barriers can be overcome by offering diabetes technology education for all people with T1D, increasing awareness of HCL in the community and providing resources to overcome barriers created by social determinants of health. Conclusions: The voices of historically minoritised youth with suboptimal T1D control and their parents provide important, previously unreported experiences and perspectives on barriers and facilitators to using HCL that will shape interventions to improve equity in access to diabetes technology. [ABSTRACT FROM AUTHOR]

Islet-antigen-specific tolerization is a key goal of experimental immunotherapies for type 1 diabetes. mRNA-based vaccines have demonstrated the feasibility of RNA delivery in inducing antigen tolerance in autoimmune diseases. In this study, mRNA vaccine, encoded tandem glutamic acid decarboxylase 65 (GAD65) epitopes and cholera toxin B subunit (CTB-GADIII), prepared by an in vitro transcription (IVT) system and encapsulated with lipid nanoparticles (LNP), was intramuscularly administered to non-obese diabetic (NOD) and cyclophosphamide (Cy)-NOD mice respectively. The results showed that the mRNA vaccines significantly reduced the incidence rate of type 1 diabetes, delayed the disease progression, improved glucose tolerance, and protected pancreatic morphology and function compared with the controls. Meanwhile, the vaccines also reduced the levels of autoantibodies to glutamic acid decarboxylase (GADA) and insulin (IAA) in the serum. Furthermore, the proportion of CD4+ T helper cell subsets was modulated in the spleen of mice treated with mRNA vaccines, in correspondence with the increased levels of IL-10 and TGF-β in serum, suggesting the possible mechanism of immune tolerance. This study provides experimental evidence for the application of mRNA vaccines encoding self-antigens in the prevention or treatment of type 1 diabetes. [Display omitted] • LNP-mRNA vaccines based on GAD65 effectively reduce the incidence of T1D in NOD and Cy-NOD mice. • These vaccines can induce immune tolerance by modulating the proportions of CD4+ T helper cell subsets. • This study provides experimental evidence for the application of mRNA vaccines in the prevention or treatment of T1D. [ABSTRACT FROM AUTHOR]

Diabetic Retinopathy Clinical Research Network Protocol T suggests that the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME and baseline BCVA of 20/50 or worse enrolled in faricimab phase III trials. YOSEMITE and RHINE were identically designed, multicenter, randomized, double-masked, active comparator–controlled, noninferiority trials. Adults ≥18 years of age with center-involving macular edema secondary to type 1 or 2 diabetes. Patients were randomized to faricimab every 8 weeks (Q8W), faricimab personalized treat-and-extend (T&E) regimen, or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intention-to-treat population with baseline BCVA of 20/50 or worse. Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. In YOSEMITE and RHINE, respectively, 220 and 217 patients in the faricimab Q8W arm, 220 and 219 patients in the faricimab T&E arm, and 219 and 214 patients in the aflibercept Q8W arm showed baseline BCVA of 20/50 or worse. In both trials, mean change in ETDRS BCVA was comparable between treatments across trials at years 1 and 2. In YOSEMITE, adjusted mean change from baseline in CST (μm) at year 1 was greater with faricimab Q8W (–232.8; P < 0.0001) and faricimab T&E (–217.4; P = 0.0004)) versus aflibercept Q8W (–190.4). In RHINE, this was faricimab Q8W (–214.2; P = 0.0006) and faricimab T&E (–206.6; P = 0.0116) versus aflibercept Q8W (–186.6). In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. The median time to first CST of <325 μm and first absence of intraretinal fluid was shorter in the faricimab arms versus the aflibercept arm, with fewer injections on average. In patients with DME and baseline ETDRS BCVA of 20/50 or worse, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Summary: Background: The possibility of preventing inflammatory bowel disease (IBD) is becoming more plausible due to advances in understanding preclinical disease and successful prevention trials in other immune‐mediated diseases, such as type 1 diabetes and rheumatoid arthritis. However, before that possibility becomes reality, several efforts need to occur in parallel and in a coordinated way. Aim: To propose some critical steps necessary for advancing the field of IBD prediction and prevention. Methods: We reviewed the current literature to identify the necessary steps toward a preventive strategy for IBD. Results: The first step should determine the most robust predictive biomarkers and validate them across independent cohorts, creating a multidimensional predictive tool. The second step is to gain a better understanding of the preferences of first‐degree relatives and people at risk for IBD, informing the implementation of screening and preventive strategies. Third, these efforts should contribute to the development of high‐risk clinics and establish the necessary networks for disease prevention trials. Conclusions: Advancing the field of IBD prediction and prevention will require a multifaceted approach, integrating biomarker discovery, understanding patient preferences, and establishing infrastructure for a collaborative network to support the practical implementation of IBD prevention strategies. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 5-month-old infant who developed new-onset Type 1 diabetes mellitus (T1DM) following a COVID-19 infection. Topics discussed include the relationship between viral infections and autoimmune diabetes, the challenges in diagnosing T1DM in very young patients, and the increased incidence of diabetic ketoacidosis (DKA) during the COVID-19 pandemic.

Purpose: To evaluate the five‐year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR‐screening programme. Methods: Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013–2018. According to the worse eye at first screening, DR was classified (levels 0–4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication. Results: At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five‐year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63–1.89, and HR 2.04, 95% CI 1.73–2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10–1.47, and HR 2.80, 95% CI 2.23–3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05–1.36, and HR 1.98, 95% CI 1.53–2.57). Conclusion: In a study of all patients with type 1 diabetes from the Danish DR‐screening programme, we identified duration of diabetes, systemic disease and use of anti‐hypertensive treatment as consistent risk markers for incident and progressive DR. [ABSTRACT FROM AUTHOR]

Aim: To analyse patterns of glucose‐lowering therapies among people with type 2 diabetes (T2D) in Denmark from 2016 to 2023. Materials and Methods: We examined time trends in the clinical profiles of people with T2D who initiated different glucose‐lowering therapy classes for the first time. We furthermore investigated individual‐level treatment trajectories following first‐ever glucose‐lowering therapy in people with or without cardiorenal disease. The study utilized data from the nationwide Danish health registries and included all individuals who filled a first‐ever prescription for metformin, dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) or insulin, excluding those without HbA1c‐confirmed T2D or probable type 1 diabetes. Results: We included 260 393 individuals initiating a new glucose‐lowering therapy class from 2016 to 2023, during which there were 6‐ and 3‐fold increases in initiators of GLP‐1RAs and SGLT‐2is, respectively. The median HbA1c level at treatment initiation with GLP‐1RAs or SGLT‐2is decreased, from 67‐68 mmol/mol in 2016‐2017 to 57‐58 mmol/mol in 2022‐2023. Among individuals who initiated metformin as first‐line therapy, the proportion who started additional glucose‐lowering therapy within 2 years increased from 25% in 2016 to 40% in 2021. Among the 38% of individuals who had established cardiorenal disease when they initiated first‐ever glucose‐lowering therapy in 2020, 22% used SGLT‐2is and 18% GLP‐1RAs after 2.5 years, compared with 17% and 21% among initiators without cardiorenal disease, respectively. Conclusions: Our study documents a trend towards earlier T2D treatment intensification and an increase in the use of GLP‐1RAs and SGLT‐2is in Denmark. However, optimal T2D treatment is still not received by most individuals with early T2D and established cardiorenal disease. [ABSTRACT FROM AUTHOR]

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have revolutionized the treatment of type 2 diabetes, chronic kidney disease (CKD), and chronic heart failure. Clinical trials have shown significant benefits in reducing blood glucose levels and improving cardiovascular outcomes. However, despite the growing evidence supporting their effectiveness, there is still a lack of widespread use of these drugs in clinical practice. The article emphasizes the need for better communication between healthcare providers and patients, addressing patient non-adherence and clinical inertia, and further research and education to bridge the gap between scientific knowledge and real-world practice. [Extracted from the article]

Aim: The aim was to investigate whether COVID‐19 increases new incidence of hypertension (HTN), chronic kidney disease (CKD) and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) up to 40 months post‐infection. Materials and Methods: Three groups of patients from the Montefiore Health System in the Bronx (1 March 2020 to 1 July 2023) were studied: T1D patients hospitalized for COVID‐19 (H‐COVID‐19, n = 511), T1D patients with COVID‐19 but not hospitalized for COVID‐19 (NH‐COVID‐19, n = 306) and T1D patients without a positive COVID‐19 test on record (non‐COVID‐19, n = 1547). COVID‐19 patients were those with a positive polymerase‐chain‐reaction test on record, and non‐COVID‐19 patients were either tested negative or not tested on record. Cumulative incidences and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed with adjustment for competing risks. Results: Compared to non‐COVID‐19 patients, both H‐COVID‐19 (unadjusted 19.72% vs. 3.14%, p < 0.001; aHR = 7.55 [3.33, 17.06], p < 0.001) and NH‐COVID‐19 (10.26% vs. 3.14%, p = 0.004; aHR = 5.08 [2.19, 11.78], p < 0.001) patients were more likely to develop new HTN. Compared to non‐COVID‐19 patients, both H‐COVID‐19 (11.41% vs. 1.14%, p < 0.001; aHR = 9.76 [4.248, 22.25], p < 0.001) and NH‐COVID‐19 (7.69% vs. 1.14%, p < 0.001; aHR = 6.54 [2.91, 14.67], p < 0.001) patients were more likely to develop new CKD. Compared to non‐COVID‐19 patients, both H‐COVID‐19 (4.09% vs. 1.06%, p < 0.001; aHR = 12.24 [4.09, 36.59], p < 0.001) and NH‐COVID‐19 (3.06% vs. 1.06%, p = 0.035; aHR = 12.94 [4.09, 40.89], p < 0.001) patients were more likely to develop new DKA at follow‐up. Conclusion: T1D patients with COVID‐19 are at higher risk of developing new HTN, CKD and DKA compared to T1D patients without COVID‐19. [ABSTRACT FROM AUTHOR]

Aim: To map the glycaemic variabilities and insulin requirements across different phases of the menstrual cycle and assess the efficacy and performance of the MiniMed 780G system on mitigating glycaemic variabilities during phases of the menstrual cycle. Materials and Methods: A pilot study recruiting 15 adolescent and young adult females with type 1 diabetes was conducted. Only females with regular spontaneous menstruation were enrolled in the current study. Phases of each menstrual cycle were determined as either follicular phase or luteal phase. The study analysed continuous glucose monitoring metrics during two study periods: the open loop period (OLP) and the advanced hybrid closed‐loop (AHCL) period; each period lasted 3 consecutive months. Results: During the OLP, the mean time in range (TIR) significantly decreased during the luteal phase compared with the follicular phase (65.13% ± 3.07% vs. 70.73% ± 2.05%) (P <.01). The mean time above range significantly increased from 21.07% ± 2.58% during the follicular phase to 24.87% ± 2.97% during the luteal phase (P <.01). After initiating the AHCL period, TIR was comparable during both phases of the menstrual cycle (P =.72), without increasing the time spent below 70 mg/dL (P >.05). Regarding insulin delivery during the AHCL period, the percentage of Auto basal and Auto correction delivered by the algorithm increased by 13.55% and 30.6%, respectively (P <.01), during the luteal phase. Conclusions: The fully automated adaptive algorithm of the MiniMed 780G system mitigated menstrual cycle‐dependent glycaemic variability, successfully attaining the recommended glycaemic outcomes with a TIR greater than 70% throughout the entire menstrual cycle. [ABSTRACT FROM AUTHOR]

Aim: To test the effect of the glucagon‐like peptide‐1 receptor agonist, liraglutide, on residual beta‐cell function in adults with newly diagnosed type 1 diabetes. Materials and Methods: In a multicentre, double‐blind, parallel‐group trial, adults with newly diagnosed type 1 diabetes and stimulated C‐peptide of more than 0.2 nmol/L were randomized (1:1) to 1.8‐mg liraglutide (Victoza) or placebo once daily for 52 weeks with 6 weeks of follow‐up with only insulin treatment. The primary endpoint was the between‐group difference in C‐peptide area under the curve (AUC) following a liquid mixed‐meal test after 52 weeks of treatment. Results: Sixty‐eight individuals were randomized. After 52 weeks, the 4‐hour AUC C‐peptide response was maintained with liraglutide, but decreased with placebo (P =.002). Six weeks after end‐of‐treatment, C‐peptide AUCs were similar for liraglutide and placebo. The average required total daily insulin dose decreased from 0.30 to 0.23 units/kg/day with liraglutide, but increased from 0.29 to 0.43 units/kg/day in the placebo group at week 52 (P <.001). Time without the need for insulin treatment was observed in 13 versus two patients and lasted for 22 weeks (from 3 to 52 weeks) versus 6 weeks (from 4 to 8 weeks) on average for liraglutide and placebo, respectively. Patients treated with liraglutide had fewer episodes of hypoglycaemia compared with placebo‐treated patients. The adverse events with liraglutide were predominantly gastrointestinal and transient. Conclusions: Treatment with liraglutide improves residual beta‐cell function and reduces the dose of insulin during the first year after diagnosis. Beta‐cell function was similar at 6 weeks postliraglutide treatment. [ABSTRACT FROM AUTHOR]

Aim: To characterize and stratify health‐related quality of life in individuals with type 1 diabetes (T1D) using body mass index (BMI) and clustering analysis. Material and Methods: Baseline data on individuals with T1D were pooled from two studies. A post hoc analysis of health‐related quality of life, measured using the 36‐item Short‐Form questionnaire, was performed, referenced to the 2010 US general population. Descriptive statistics were presented for the pooled cohort and per BMI category. K‐means clustering was performed. One‐way analysis of variance was conducted to examine differences in clinical characteristics between clusters. Results: The pooled cohort consisted of 2256 individuals with T1D (age: 45.4 ± 15.0 years, BMI: 26.2 ± 4.6 kg/m2, diabetes duration: 22.7 ± 13.5 years). All quality‐of‐life domains were slightly lower than 50(the general population's mean), except for vitality. Individuals with a BMI ≥30 kg/m2 reported lower scores for bodily pain, physical functioning, general health, and vitality. A first cluster with a high and a second cluster with a low quality of life were identified, with significant differences in the mental (Cluster 1: 53.8 ± 6.8 vs. Cluster 2: 39.5 ± 10.7; p < 0.001) and physical component summary scores (Cluster 1: 49.6 ± 6.3 vs. Cluster 2: 35.2 ± 12.0; p < 0.001), which exceeded differences found between BMI categories. Conclusions: In our population of people living with T1D, higher BMI may have adversely impacted physical domains of quality of life, but larger differences between the high‐ and low‐quality‐of‐life cluster indicate that more factors play a role. [ABSTRACT FROM AUTHOR]

A pilot study was conducted to investigate the use of real-time continuous glucose monitoring (RT-CGM) in non-critical care insulin-treated inpatients under non-diabetes specialty teams in hospitals. The study found no significant differences in glycemic control between the group using RT-CGM and the group using capillary blood glucose (CBG) monitoring. While RT-CGM has been effective in outpatient settings, its effectiveness in hospitals without direct guidance from diabetes specialists is still uncertain. Further research is needed to determine the best use of RT-CGM in hospital settings. [Extracted from the article]

Aim: To establish trust in real‐world evidence (RWE) derived from CareLink Personal (CP), Medtronic's data management system for MiniMed system users, we show that this database and its analyses strictly adhere to the principles of RWE. Methods: The methodology is applicable to all MiniMed iterations. We described every step from raw data to predefined outcomes. In addition, we showed CP's fitness‐for‐research by the below metrics (using last year's MiniMed 780G system data as a case study): representative population, relevant endpoints, appropriate granularity, high data completeness, high data representativity and consistency in results. Results: The process from raw data to outcomes has been validated, and metrics/logics adhere to established definitions. Over 95% of users have a CP account; with 96% providing consent, this allows the use of >91% of the census population. There is no rationale for an over‐representation of a specific phenotype among users not included. CP includes >50 endpoints, including 'International Consensus on Time in Range' based metrics. Data are recorded at 5‐min intervals (maximum 288 per day), and on average there were 263 data points per person per day. Ninety‐nine per cent of uploads were automated. For the last year, only 1 in 6 users had a data gap >1 day, and 1 in 50 had a gap >1 week. The time in range from in‐silico studies was similar to that of real‐world studies from different geographies and with ever growing populations. Conclusion: RWE from CP adheres to the principles of RWE and can serve as robust evidence on the performance and safety of MiniMed systems. [ABSTRACT FROM AUTHOR]

Since certain types of diabetes are reversible and curable in the early stages, early detection is crucial for effective treatment. Exhaled breath analysis, a noninvasive technique, is increasingly recognized for its potential in health monitoring, providing insights into an organism's metabolic state more directly than blood glucose tests. This work developed an in situ method utilizing corona ion source mass spectrometry for real-time direct monitoring of volatile organic compounds (VOCs) in mouse exhaled breath. The method was used to track breath changes in two mouse models with streptozotocin-induced diabetes throughout disease progression. Notably, variations in certain VOCs in exhaled breath correlated with blood glucose levels (BGLs) during diabetes development. For instance, in the type 1 diabetes model, acetone levels remained stable within 8 days after hyperglycemia (not significant, n.s.) compared to those in controls but showed a significant increase after 10 days (p < 0.001). In the type 2 diabetes model, isopropanol levels decreased (p < 0.001) during the prediabetes phase, when BGL changes were not significant (n.s.) compared to those in the healthy state. These results indicate that specific substances in exhaled breath change prior to noticeable BGL alterations. This study thus established the viability of direct online mass spectrometry for breath analysis in early diabetes detection and showed that this technique has potential for identifying clear clinical markers for early diabetes screening. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the admission indicators and characteristics of individuals diagnosed with type 1 diabetes (T1D) to ascertain potential impact on the choice of glucose control therapy after discharge. Methods: A total of 398 eligible T1D patients were selected. We conducted multivariable logistic regression analysis to determine the independent influence of predictors on the selection of glucose control therapy after discharge. To explore the influencing factors of different subgroups, we additionally performed subgroup analyses based on gender and age. Results: Our study revealed that body mass index (BMI) was noteworthy influence factor for prescription of insulin and non-insulin antidiabetic drug (NIAD prescription) in T1D patients of general population [OR = 1.109 (1.033-1.195), p = 0.006], male [OR = 1.166 (1.040−1.318), p = 0.011] and individuals below the age of 30 years [OR = 1.146 (1.020−1.301), p = 0.028]. Diastolic blood pressure (DBP) was a protective factor for NIAD prescription in the general population [OR = 0.971 (0.949-0.992), p = 0.008] and women [OR = 0.955 (0.923−0.988), p = 0.008]. The other risk factor of NIAD prescription in men was dyslipidemia [OR = 4.824 (1.442−22.246), p = 0.020]. Pulse pressure [OR = 1.036 (1.007–1.068), p = 0.016] constituted an additional risk factor of NIAD prescription among individuals below the age of 30 years. The risk factors of NIAD prescription for people aged 30 to 50 years were length of stay [OR = 1.097 (1.014–1.196), p = 0.026] and initial blood glucose [OR = 1.078 (1.007–1.168), p = 0.047]. In the case of individuals aged above 50 years, physicians exhibited a higher tendency to prescribe supplementary non-insulin medications to men [OR = 9.385 (1.501–87.789), p = 0.029]. Conclusions: We identified notable factors that influence discharge prescriptions in patients with T1D. In order to enhance the treatment outcome for the patient, clinicians ought to have a special focus on these indicators or factors. [ABSTRACT FROM AUTHOR]

The intricate etiology of type 1 diabetes mellitus (T1D), characterized by harmful interactions between the immune system and insulin-producing beta cells, has hindered the development of effective therapies including human islet transplantation, which requires strong immunosuppressants that impair beta cell survival and function. As such alternative immunomodulating therapies are required for successful transplantation. The discovery that pharmacological activation of the nuclear receptor LRH-1/NR5A2 can reverse hyperglycemia inmousemodels of T1D by altering, and not suppressing the autoimmune attack, prompted us to investigate whether LRH-1/NR5A2 activation could improve human islet function/survival after xenotransplantation in immunocompetent mice. Human islets were transplanted under the kidney capsule of streptozotocin (STZ)-induced diabetic mice, and treatment with BL001 (LRH-1/NR5A2 agonist) or vehicle was administered one week post-transplant. Our study, encompassing 3 independent experiments with 3 different islet donors, revealed that mice treated for 8 weeks with BL001 exhibited lower blood glucose levels correlating with improved mouse survival rates as compared to vehicle-treated controls. Human C-peptide was detectable in BL001-treated mice at both 4 and 8 weeks indicating functional islet beta cells. Accordingly, in mice treated with BL001 for 8 weeks, the beta cell mass was preserved, while a significant decrease in alpha cells was observed compared to mice treatedwith BL001 for only 4 weeks. In contrast, vehicle-treated mice exhibited a reduction in insulin-expressing cells at 8 weeks compared to those at 4 weeks. These results suggest that BL001 significantly enhances the survival, engraftment, and functionality of human islets in a STZ-induced diabetic mouse model. [ABSTRACT FROM AUTHOR]