Diagnosis Of Type 1 Diabetes Research Articles

Increased cardiovascular risk in people with LADA in comparison to type 1 diabetes and type 2 diabetes: Findings from the DPV registry in Germany and Austria.

We aimed to characterise and compare individuals diagnosed with type 1 diabetes (T1D), latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D), in a real-world setting. Anthropometric and clinical data from 36 959 people with diabetes diagnosed at age 30-70 years enrolled in the prospective diabetes patients follow-up (DPV) registry from 1995 to 2022 were analysed cross-sectionally at diagnosis and follow-up (≥6 months after diagnosis). LADA was defined as clinical diagnosis of T2D, positivity of ≥1 islet autoantibody and an insulin-free interval of ≥6 months upon diabetes diagnosis. At diagnosis, age, body mass index, waist circumference, C-peptide and HbA1c in people with LADA (n = 747) fell in between individuals with T1D (n = 940) and T2D (n = 35 272) (all p-values < 0.01). At follow-up, after adjusting for age, sex and diabetes duration, the prevalence of dyslipidemia and hypertension was the highest in people with LADA (90.6%, 77.7%) compared to people with T2D (81.8%, 60.4%) and T1D (75.7%, 39.7%) (p < 0.01). The prevalence of diabetic kidney disease (DKD) was higher in LADA (44.2%), than in T1D (19.9%) (p < 0.01). The prevalence of peripheral neuropathy was higher in individuals with LADA (55.1%) than in T2D (43.9%) and T1D (42.1%) (p < 0.05). Coverage of treatment for hypertension and dyslipidemia were 22.4% and 15.0% in T1D, 63.0% and 36.6% in LADA and 29.4% and 18.2% in T2D. People with LADA had a higher prevalence of cardiovascular risk factors (dyslipidemia, hypertension) and cardiovascular complications (DKD and peripheral neuropathy), suggesting that people with LADA are at need for improved recognition and care.

Shifting the paradigm of type 1 diabetes: a narrative review of disease modifying therapies

A new diagnosis of type 1 diabetes (T1D) may be accompanied by numerous lifelong financial, emotional, and physical challenges, thus advancements in therapies that can delay the onset of clinical disease are crucial. T1D is an autoimmune condition involving destruction of pancreatic beta cells leading to insulin deficiency, hyperglycemia, and long-term insulin dependence. The pathogenesis of T1D is classified into stages, with the first signal being the detection of autoantibodies without any glycemic changes. In the second stage, dysglycemia develops without symptoms, and in stage 3, symptoms of hyperglycemia become apparent, and at this time a clinical diagnosis of T1D is made. As a greater understanding of these stages of T1D have evolved, research efforts have been devoted to delaying the onset of clinical disease. To date, only one medication, teplizumab, has been approved by the Food and Drug Administration (FDA) for the treatment of stage 2 T1D. This narrative review present published trials and ongoing research on disease modifying therapies (DMT) in T1D, the mechanisms of action for each therapy, and the stages of T1D that these interventions are being studied.

Real-World Comparison of Oral Versus Injectable Semaglutide for the Reduction of Hemoglobin A1C and Weight in Patients with Type 2 Diabetes.

No head-to-head comparisons of semaglutide formulations currently exist in the literature. In practice, many may think that oral and injectable semaglutide formulations are interchangeable, although there is currently limited real-world data to determine whether this is accurate. The purpose of this study was to determine the effect of oral versus injectable semaglutide on hemoglobin A1C (HbA1C) and weight in patients with type 2 diabetes (T2D). This was a retrospective single-center review of adult patients who had a diagnosis of T2D and were treated with oral or injectable semaglutide between November 1, 2019, and July 31, 2022. Primary outcome was a comparison of changes in HbA1C (%) and weight (kg) from baseline to 6 months between patients receiving oral versus injectable semaglutide, stratified according to highest dose received. Secondary outcomes included frequency of dose reductions and discontinuations, achievement of clinical goals, and presence of an embedded clinical pharmacist at patients' primary care office. A total of 105 patients were included. Patients experienced mean decreases in HbA1C and weight from baseline to 6 months of -1.75% (P < 0.001) and -3.64 kg (P = 0.015), respectively, in the oral semaglutide group and -1.35% (P < 0.001) and -5.26 kg (P < 0.001), respectively, in the injectable semaglutide group. When directly comparing semaglutide formulations, oral semaglutide demonstrated a 0.4% greater numerical reduction in HbA1C (P = 0.523) and injectable semaglutide demonstrated a 1.62-kg greater numerical reduction in weight (P = 0.312). Adverse events (AEs) occurred more frequently with oral semaglutide than with injectable semaglutide (16.7% vs 4.9%). Discontinuation due to AEs was more common with oral semaglutide. In this study, patients with T2D who received oral semaglutide demonstrated greater reductions in HbA1C, whereas those treated with injectable semaglutide had greater reductions in weight, although there were no statistically significant reductions in HbA1C or weight between the 2 formulations. Rates of AEs and discontinuation were more common in the oral semaglutide group.

Hyponatremia and risk of new-onset heart failure in patients with type 2 diabetes - a real-world study of 70,000 patients

Abstract Background Hyponatremia is common in patients with heart failure and in patients with type 2 diabetes (T2D), and is a risk marker for increased morbidity and mortality. However, it is unclear whether hyponatremia in patients with T2D is associated with an increased risk of new-onset heart failure. Purpose To investigate whether hyponatremia is associated with an increased risk of new-onset heart failure in patients with T2D. Methods From Danish nationwide registers, all patients with T2D with no history of heart failure were identified from 2013-2021. Patients with at least two samples of plasma sodium measured (at least one month apart), during the first six months following their T2D diagnosis, were included with follow-up start six months after T2D diagnosis as well. Patients were categorized in two groups according to the mean plasma sodium concentration at baseline: 1) sodium &amp;gt;137 mmol/L; and 2) sodium &amp;lt;137mmol/L. Cumulative incidence curves and Cox proportional hazards models (crude and adjusted for age, sex, comorbidities, and potential hyponatremia-inducing medications including diuretics, anticonvulsants, and antidepressants) were used to investigate the association of sodium concentration with the incidence of heart failure during follow-up. Incidence rates of heart failure per 1000 person-years were calculated across the spectrum of the measured sodium levels. Results We included 69,750 patients where 57% were male and the median age was 63 (interquartile range: 54-71). At index, 57,723 (83%) patients had a mean sodium concentration of &amp;gt;137 mmol/L and 12,027 (17%) patients had a mean sodium concentration &amp;lt;137 mmol/L (hyponatremia). Patients with a sodium level &amp;lt;137 mmol/L were associated with a significantly higher hazard rate of heart failure compared to patients with sodium concentrations &amp;gt;137 mmol: adjusted hazard ratio (HR) 1.27 (95% confidence interval 1.15-1.41, p-value &amp;lt;0.001). In analyses where sodium concentration was considered a continuous variable, increasing concentration of 1 mmol/L was associated with a decreasing hazard rate of heart failure: adjusted HR 0.96 (0.94-0.97, p-value &amp;lt;0.001). Conclusions Hyponatremia was common and associated with a significantly higher risk of new-onset heart failure in patients newly diagnosed with T2D. Whether hyponatremia could be a new treatment target to prevent heart failure in T2D remains to be determined.Cumulative incidence of heart failureIncident heart failure

Exploring Type 2 Diabetes Self-Management Practices Among African Americans in Rural Counties: A Qualitative Study.

The purpose of the study was to understand diabetes self-management practices among African American individuals living with type 2 diabetes (T2D) in rural communities. This qualitative descriptive study, undergirded by the theory of integration, purposively sampled African Americans (N = 34) diagnosed with T2D living in rural communities. Thematic analysis employed both a priori and inductive coding to identify salient themes. Participants' mean age was 65.9 (SD 12.3) years, with an average T2D diagnosis duration of 14 (SE 11.2) years. Two major themes emerged: deciphering the cues and body sensing, which the participants used to monitor their glucose level using a personalized feedback loop. Those with longer diabetes duration demonstrated an ability to recognize hypoglycemic or hyperglycemic symptoms (deciphering the cues), informing their decision-making and self-management strategies (body sensing). The decision-making involved in glycemic level management emerges as a complex developmental process influenced by disease trajectory and cultural and environmental factors. These findings may inform a conceptual framework to guide future inquiries and provide insights for primary care clinicians and diabetes educators to better understand the complexities of T2D management among African American individuals in rural settings.

49 Effects of numeracy and literacy on glycemic control and self-perceived efficacy in youth with type 1 diabetes in Haiti

Abstract Background The management of type 1 diabetes (T1D) in low-resource settings remains a challenge in the context of unfavourable social determinants of health. The effects of literacy and numeracy on glycemic control and self-perceived efficacy in youth living with T1D in low-resource settings have been insufficiently investigated. Objectives We described literacy and numeracy in Haitian youth with T1D and their caregivers and we evaluated their association with hemoglobin A1c (HbA1c) and perceived diabetes management self-efficacy. Design/Methods We conducted a cross-sectional cohort study of youth with T1D treated at the Montrouis clinic in Haiti, between June to December 2017. Inclusion criteria were a diagnosis of T1D at age 0-25 years and at least one parent of Haitian ancestry. One principal caregiver of each youth was also included. Exclusion criteria were inability of informed consent and declined home visit. The study was approved by our Institution Research Ethics Board. Data collection included demographics, clinical data, numeracy questionnaire adapted to the population and the standardized self-efficacy 8-item Perceived Diabetes Self-Management Scale (PDSMS). We used univariate and multivariate linear regression models to evaluate predictors of HbA1c and PDSMS scores. Results We included 85 patients (60% female) and 73 caregivers. Median age at diagnosis and diabetes duration were 14.3 and 3.1 years, respectively. Over 90% of patients had suboptimal (HbA1c &amp;gt;7.0%), poor (HbA1c &amp;gt;9%) or very poor (HbA1c &amp;gt;12%) glycemic control. 76 patients (90.5%) self-reported being able to read, 78 (91.8%) to write and 84 (98.8%) to count. Mothers’ and fathers’ median education years were 7.0 and 11, respectively. 54 parents (74.0%) self-reported being able to read and write. Normalized to 100%, median patient numeracy score was 75.0% and the mean PDSMS score was 65.9%. In univariate models, lower HbA1c was predicted by younger age (p=0.013), but not by gender, diabetes duration, numeracy score, mother’s education or PDSMS score. Higher PDSMS score was predicted by higher numeracy scores (p=0.003), marginally by sex (p=0.057), but not by age, diabetes duration, or mother’s education; in a multivariate model adjusted for age, sex and diabetes duration, higher numeracy remained significant (p=0.006). Conclusion In youth with T1D in Haiti who have ubiquitously poor glycemic control and suboptimal family literacy and numeracy, numeracy is a predictor of self-perceived efficacy of T1D. Further public health interventions addressing numeracy in youth living with T1D in low-resource settings are advised.

Risk of type-2-diabetes after breast cancer treatment: a population-based cohort study in Denmark.

Data on type 2 diabetes (T2D) risk after breast cancer (BC) could guide preventive strategies. Yet, studies had limitations regarding sample size, follow-up, and contemporary treatments. We evaluated the risk of T2D after BC overall, by cancer treatment, and compared with a matched cohort of cancer-free women. We assembled a population-based cohort of early-stage BC patients aged ≥30 years diagnosed during 1996-2021 in Denmark. We created a comparison cohort of five cancer- and T2D-free women for each BC case, matched six months after BC diagnosis date on age and region. We followed both cohorts until T2D diagnosis, emigration, death, or December 31, 2022. We computed 5-year cumulative incidences and used Cox models to calculate time-varying adjusted hazard ratios (aHR) of T2D. Among 74,526 BC survivors and 372,630 matched cancer-free women, 5-year cumulative incidences of T2D were 3.8% (95%CI = 3.7-3.9) and 3.3% (95%CI = 3.3-3.4), respectively. The aHR of T2D was elevated but attenuated over follow-up (aHR5-years=1.20, 95%CI = 1.15-1.25, and aHR15-years=1.09, 95%CI = 1.05-1.12). Adjuvant endocrine therapy (aHR = 1.14; 95%CI = 1.10-1.19), aromatase inhibitors (aHR = 1.25; 95%CI = 1.18-1.32), and less so tamoxifen (aHR = 1.05; 95%CI = 0.99-1.11), were associated with elevated risk of T2D in women with BC vs cancer-free women. Among BC patients, chemotherapy (aHR = 1.10, 95%CI = 1.03-1.17) and radiation therapy (right-sided aHR = 1.18, 95%CI = 1.09-1.27 and left-sided aHR = 1.24, 95%CI = 1.15-1.33) were associated with increased T2D risk. BC was associated with excess risk of T2D, though of lower magnitude than previously reported. The excess risk was temporary and related to BC treatment but could also be influenced by obesity and heightened T2D diagnostic activity.

Feasibility and Acceptability of a Self-Guided Digital Family Skills Management Intervention for Children Newly Diagnosed With Type 1 Diabetes: Pilot Randomized Controlled Trial.

Family dynamics play an important role in determining the glycemic outcomes of type 1 diabetes (T1D) in children. The time interval immediately following T1D diagnosis is particularly stressful for families, and interventions to support families in adjusting their family practices to support adjustment to and management of T1D in the months following diagnosis may improve glycemic outcomes. Self-guided digital interventions offer a sustainable model for interventions to support caregivers in learning evidence-based family management skills for adjustment to and management of T1D. We hypothesized that a self-guided, web-based, family skills management program (addressing caregiver social support as well as family problem-solving, communication, and supportive behavior change strategies) initiated at the time of T1D diagnosis would improve glycemic outcomes in children with T1D. In this study, we report on the feasibility and acceptability of this program. We prospectively evaluated a sample of 37 children newly diagnosed with T1D recruited from a pediatric endocrinology clinic. Parent participants were asked to complete web-based modules addressing social support, family problem-solving, communication, and supportive behavior change strategies. Module completion was analyzed for percentage completion, patterns of completion, and differences in completion rates by coparenting status. Qualitative open-ended feedback was collected at the completion of each module. A total of 31 (84%) of the 37 participants initiated the web-based program. Of those 31 participants, 25 (81%) completed some content and 15 (48%) completed all 5 modules. Completion rates were higher when coparenting partners engaged in the intervention together (P=.04). Of the 18 participants given a choice about the spacing of content delivery, 15 (83%) chose to have all sessions delivered at once and 3 (17%) chose to space sessions out at 2-week intervals. Qualitative feedback supported the acceptability of the program for delivery soon after T1D diagnosis. Families reported on positive benefits, including requesting future access to the program and describing helpful changes in personal or family processes for managing T1D. In this study, we found that a self-guided digital family support intervention initiated at the time of a child's T1D diagnosis was largely feasible and acceptable. Overall, rates of participation and module completion were similar to or higher than other self-guided digital prevention interventions for mental and physical health outcomes. Self-guided digital programs addressing family management skills may help prevent challenges common with T1D management and can decrease cost, increase access, and add flexibility compared to traditional interventions. ClinicalTrials.gov NCT03720912; https://clinicaltrials.gov/study/NCT03720912.

Nutritional diagnoses in people with type 2 diabetes: association with metabolic, anthropometric, and dietary parameters.

Nutritional diagnosis involves identifying a nutritional problem, its cause, and the signs that indicate it to guide appropriate treatment. Few studies report on the most prevalent nutritional diagnoses in people living with type 2 diabetes (T2D). To define nutritional diagnoses across different domains and their association with metabolic, anthropometric, and dietary parameters in individuals with T2D. A personalized nutritional intervention was conducted using the Nutrition Care Process (NCP) model, which encompasses assessment, diagnosis, intervention, and evaluation, utilizing standardized terminology from the Nutrition Care Process Terminology (NCPT). Two dietitians, trained and standardized in applying the NCP and NCPT, performed patient assessments and established the diagnoses. Patients over 18 years old with a diagnosis of T2D for less than 5 years were included. Data from 2,050 patients were analyzed, of whom 55.3% were women, and 44.7% were men, with a median age of 57 and 54 years, respectively. The most prevalent nutritional diagnosis was excessive energy and carbohydrate intake. Diagnoses were distributed across domains: Intake (55.9%), Behavioral/Environmental (32.7%), Clinical (10.2%), and 1.2% without nutritional diagnosis. Significant intergroup differences were observed in anthropometric variables such as BMI, waist circumference, and body fat percentage (p < 0.05). HbA1c and glucose levels were significantly higher in the Intake and Behavioral groups (p < 0.001). Albumin/creatinine ratio (ACR) was higher in the ingestion group (p = 0.007). Caloric and carbohydrate intake were higher in the ingestion group, while protein and fat intake were higher in the clinical and behavioral groups (p < 0.001). Nutritional diagnoses in the intake domain, followed by behavioral/ environmental and clinical domains, are highly prevalent in people with T2D and are associated with worse metabolic control, higher BMI, and increased energy and carbohydrate intake. Timely identification of issues in these domains can support targeted nutritional therapy to improve disease management and promote a healthy lifestyle. https://clinicaltrials.gov/study/NCT02836808?term=caipadi&rank=2, Identifier (NCT02836808).

SARS-CoV-2 Infection and New-Onset Type 2 Diabetes Among Pediatric Patients, 2020 to 2022

In adults, diagnoses of new-onset type 2 diabetes (T2D) have increased following diagnosis with COVID-19, but whether this occurs in children is unclear. To determine whether risk of incident T2D diagnosis is increased during the 6 months after SARS-CoV-2 infection among children. This retrospective cohort study used electronic health records from the TriNetX analytics platforms between January 1, 2020, and December 31, 2022. Pediatric patients aged 10 to 19 years without preexisting diabetes were eligible for inclusion. Data were analyzed from August 15 to September 15, 2023, with supplemental analyses January 20 and August 8 to 13, 2024. Diagnosis of COVID-19 or a non-COVID-19 respiratory infection. New diagnosis of T2D compared by risk ratios (RRs) and 95% CIs at 1, 3, and 6 months after index infection. The main study population included 613 602 patients, consisting of 306 801 with COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.8% female) and 306 801 with other respiratory infections (ORIs) but no documented COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.6% female) after propensity score matching. Risk of a new diagnosis of T2D was significantly increased from day of infection to 1, 3, and 6 months after COVID-19 diagnosis compared with the matched cohort with ORIs (RR at 1 month, 1.55 [95% CI, 1.28-1.89]; RR at 3 months: 1.48 [95% CI, 1.24-1.76]; RR at 6 months: 1.58 [95% CI, 1.35-1.85]). Similar results were found in the subpopulation classified as having overweight or obesity (RR at 1 month: 2.07 [95% CI, 1.12-3.83]; RR at 3 months: 2.00 [95% CI, 1.15-3.47]; RR at 6 months: 2.27 [95% CI, 1.38-3.75]) and the hospitalized subpopulation (RR at 1 month: 3.10 [95% CI, 2.04-4.71]; RR at 3 months: 2.74 [95% CI, 1.90-3.96]; RR at 6 months: 2.62 [95% CI, 1.87-3.66]). Similar elevation in risk was found at 3 and 6 months when excluding patients diagnosed during the interval from the index date to 1 month after infection. In this retrospective cohort study of children and adolescents aged 10 to 19 years, the risk of an incident diagnosis of T2D was greater following a COVID-19 diagnosis than in children diagnosed with ORIs. Further study is required to determine whether diabetes persists or reverses later in life.

Sleep Irregularity and the Incidence of Type 2 Diabetes: A Device-Based Prospective Study in Adults.

To prospectively examine the association between device-measured sleep regularity and incidence of type 2 diabetes (T2D) in a population-based sample of adults. We also examined if meeting sleep duration recommendations attenuated or eliminated the effects of irregular sleep on T2D. We conducted a prospective cohort study of adults aged 40-79 years participating in the UK Biobank accelerometer substudy. Participants wore wrist-attached accelerometers for a duration of 7 days, which was used to compute the Sleep Regularity Index (SRI). Participants were categorized as irregular (SRI <71.6), moderately irregular (SRI between 71.6 and 87.3), and regular (SRI >87.3) sleepers. T2D diagnosis was obtained through self-reports and health records. We analyzed data from 73,630 individuals observed for 8 years, without a history of T2D and without an event in the first year of follow-up. Compared with regular sleepers, irregular (hazard ratio [HR] 1.38; 95% CI 1.20-1.59) and moderately irregular sleepers (HR 1.35; 95% CI 1.19-1.53) were at higher risk of T2D incidence. Dose-response analyses treating SRI as a continuous measure showed higher T2D incidence with SRI scores <80. Meeting current sleep duration recommendations did not counteract the adverse effects of irregular (HR 1.35; 95% CI 1.09-1.66) or moderately irregular (HR 1.29; 95% CI 1.08-1.54) sleep on T2D incidence. Moderate and high sleep irregularity were deleteriously associated with T2D risk, even in participants who slept ≥7 h per night. Future sleep interventions will need to pay more attention to consistency in bedtimes and wake-up times, in addition to sleep duration and quality.

Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment.

Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP and IL-6 predict the development of T2D and its complications, suggesting that LGI already increases before T2D diagnosis and remains elevated even after treatment. Overnutrition, unhealthy diets, physical inactivity, obesity, and aging are all recognized triggers of LGI, promoting insulin resistance and sustaining the pathogenesis of T2D. Once developed, and even before frank appearance, people with T2D undergo a pathological metabolic remodeling, with an alteration of multiple CVD risk factors, i.e., glycemia, lipids, blood pressure, and renal function. In turn, such variables foster a range of inflammatory pathways and mechanisms, e.g., immune cell stimulation, the accrual of senescent cells, long-lasting epigenetic changes, and trained immunity, which are held to chronically fuel LGI at the systemic and tissue levels. Targeting of CVD risk factors partially ameliorates LGI. However, some long-lasting inflammatory pathways are unaffected by common therapies, and LGI burden is still increased in many T2D patients, a phenomenon possibly underlying the residual inflammatory risk (i.e., having hs-CRP > 2 mg/dL despite optimal LDL cholesterol control). On the other hand, selected disease-modifying drugs, e.g., GLP-1RA, seem to also act on the pathogenesis of T2D, curbing the inflammatory trajectory of the disease and possibly preventing it if introduced early. In addition, selected trials demonstrated the potential of canonical anti-inflammatory therapies in reducing the rate of CVDs in patients with this condition or at high risk for it, many of whom had T2D. Since colchicine, an inhibitor of immune cell activation, is now approved for the prevention of CVDs, it might be worth exploring a possible therapeutic paradigm to identify subjects with T2D and an increased LGI burden to treat them with this drug. Upcoming studies will reveal whether disease-modifying drugs reverse early T2D by suppressing sources of LGI and whether colchicine has a broad benefit in people with this condition.

Clinical significances of circulating serum fetuin-A, netrin-1, and ɑ-hydroxybutyrate levels in type 2 diabetes mellitus patients with and without hypertension

Background &amp; Objective: Type 2 diabetes (T2D) is a rising global health issue, with biomarkers such as fetuin-A (Fet-A), netrin-1 (NTN-1), and alpha-hydroxybutyrate (α-HB) showing potential for early diagnosis and management. These biomarkers can help predict T2D risk and understand insulin resistance (IR), emphasizing the need for further research. The current investigation evaluated the effectiveness of Fet-A, NTN-1, and, α-HB as novel biomarkers to diagnose T2D with hypertension. Methodology: A cross-sectional study was conducted from August to December 2023, involved 60 diabetic participants, which were divided into two groups: T2D without hypertension and T2D with hypertension. A third group consisted of 30 healthy controls (HC) for comparison. Serum samples were analyzed for fasting blood glucose (FBG) using the Roche/Cobas c111 system, as well as insulin, Fet-A, NTN-1, and α-HB levels using kits for the enzyme-linked immune-sorbent assay (ELISA). Descriptive statistics were used in the statistical package for social sciences (SPSS) for data analysis. Results: The study found significantly elevated Fet-A, NTN-1, and α-HB levels in T2D patients compared to HC, with no significant differences between T2D subgroups. Fetuin-A and α-HB showed non-significant correlations with FBG and homeostatic model assessment of IR (HOMA-IR) across all groups. NTN-1 positively correlated with FBG and HOMA-IR in T2D patients with hypertension. Conclusions: Elevated levels of fetuin-A and netrin-1, regardless of the presence of hypertension, are suggested by the study as possible biomarkers for the diagnosis of T2D. Netrin-1's significant correlation with HOMA-IR in hypertensive T2D patients underscores its utility in assessing insulin resistance severity. Although alpha-hydroxybutyrate levels were higher in T2D patients, their non-significant correlation with FBG and HOMA-IR requires further research. These biomarkers could aid in early diagnosis and disease monitoring for T2D management. Abbreviations: α-KB - α-ketobutyrate; ELISA - enzyme linked immune-sorbent assay; FA - fatty acids; FBG - fasting blood glucose; Fet-A - fetuin-A; HOMA-IR - homeostatic model assessment of IR; IR - insulin resistance; NAD - nicotinamide adenine dinucleotide; NADH - nicotinamide adenine dinucleotide hydrogen; ng - nanograms; NTN-1 - netrin-1; PB - peripheral blood; pg - picogram; SPSS - Statistical Package for Social Sciences; T2D - Type-2 diabetes mellitus; α-HB - alpha-hydroxybutyrate Keywords: Diabetes, Fetuin-A, Netrin-1, α-HB, HOMA-IR. Citation: Sfayyih HS, Jewad AM, Khudhair HAA. Clinical significance of circulating serum fetuin-A, netrin-1, and ɑ-hydroxybutyrate levels in type-2 diabetes mellitus patients with and without hypertension. Anaesth. pain intensive care 2024;28(5):883−893; DOI: 10.35975/apic.v28i5.2569 Received: Jul 22, 2024; Reviewed: August 10, 2024; Accepted: August 15, 2024

6519 BCG Clinical Trial Programs in Advanced Type 1 Diabetes - 2024 Update

Abstract Disclosure: W.M. Kühtreiber: None. B. Thach: None. H. Hayashi: None. L. Adams: None. N. Hullavarad: None. D.A. Mounier: None. K. Le: None. E. Bulczynski: None. J.L. Dorsey: None. N. Kartsounis: None. J. Braley: None. H. Zheng: None. D.L. Faustman: None. The bacillus Calmette-Guerin (BCG) vaccine, originally developed a century ago to prevent tuberculosis infection, has today advanced in multiple clinical trials for the treatment of the type 1 diabetes (T1D), other forms of autoimmunity and infectious disease. At our institution, over 500 individuals with type 1 diabetes have been enrolled in ongoing BCG clinical protocols to test BCG’s ability to lower HbA1c, reduce insulin requirements and stabilize day-to-day fluctuations in blood sugars; 300 have been treated with BCG. In a completed randomized, placebo-controlled Phase I trial in adults with established T1D, long-term follow up continues to show that HbA1c values are durably lowered for 8+ years after multi-dose BCG treatment. In two open-label clinical trials in adults with juvenile-onset diabetes, a 10-15% reduction of HbA1c was observed after multi-dose BCG treatment. A randomized, double-blinded Phase II trial in adults with longstanding T1D has followed all patients in the BCG-treated (n=100) and placebo groups (n=50) for five years and is pending read-out. The primary outcome of all the trials is HbA1c lowering. Two new, randomized, double-blinded pediatric trials are testing the potential benefits of BCG vaccination with active enrollment ongoing. One is testing BCG in children ages 12 to 18 with more than 2 years since T1D diagnosis. The other is enrolling children ages 8 to 18 with less than 1 year since T1D diagnosis. BCG vaccine therapy may provide a safe and affordable medical intervention in individuals with longstanding T1D and works decades after disease onset by changing glucose metabolism within lymphocytes, independently of the pancreas. Presentation: 6/3/2024

5120 Contribution Of Proximal Femur Geometry And Bone Density Distribution To Hip Fragility In Adults ≥ 50yrs With Longstanding Type 1 Diabetes

Abstract Disclosure: F. Johannesdottir: None. C. D’Mello: None. A.B. Murthy: None. B. Zahedi: None. K. Engelke: None. M.L. Bouxsein: None. E.W. Yu: Grant Recipient; Self; Amgen Inc. Introduction: Adults with type 1 diabetes (T1D) have a 6-fold increased risk of hip fracture, which is explained only in part by lower areal bone mineral density (aBMD) by DXA. We hypothesize that femoral geometry and regional bone deficits at the proximal femur contribute to higher hip fracture risk in older adults with T1D. Further, we determine the influence of age at T1D diagnosis on femoral bone density and structure. Methods: We enrolled 97 individuals with T1D and 53 non-diabetic controls (CON) as part of the T1D Bone Health Connection (BEACON) Study, an ongoing prospective study of adults aged ≥50 years. We obtained computed tomography (CT) scans of the proximal femur (in-plane pixel size 0.98x0.98 mm, 1.25 mm slice thickness) to measure total (Tt), trabecular (Tb) and cortical (Ct) volumetric BMD (vBMD); and volume (Vol) and Ct thickness (Th) in several regions, including total hip, femoral neck (FN), trochanter (TR) and intertrochanter (IT) (Medical Image Analysis Framework, University of Erlangen, Germany). We also assessed total hip and FN aBMD by DXA. We employed ANCOVA models to compare bone outcomes between T1D and controls with adjustment for age, height, and weight, stratified by sex. When comparing bone outcomes within T1D, we adjusted for age, height, weight, and sex. Differences are reported as % difference between the least-square means for the groups. Results: The average age of participants was 64±7 yrs, and similar between T1D and CON (p=0.21). Male T1D were shorter than male CON (173 cm vs 176 cm, p=0.05), but with similar weight (p=0.73). Female T1D were heavier than female CON (71 kg vs 64 kg, p=0.03). The T1D cohort included 50 men and 47 women with mean diabetes duration of 46±10 yrs, mean A1c 7.1±1.0%, and median age at onset 17 yrs (IQR:10-25). Among T1D, 31 (52% female) were diagnosed ≤ age 12. Among men, total hip and FN aBMD did not differ by group, but T1D had smaller FN Tt.Vol (9%) and FN width (8%) (p&amp;lt;0.05 for all). In contrast, there were no differences between T1D and CON in the female cohort, neither by DXA nor CT (p≥0.13). Of note, T1D men appeared to have more poorly controlled diabetes than women (29% of men vs 11% women had A1c ≥8%, p=0.03). Within T1D, those who were diagnosed ≤ age 12 had lower Tb.vBMD (16-18%) at the total hip, TR and IT regions (p&amp;lt;0.05) and tended to have lower Tb.vBMD (16%, p=0.06) at the neck compared to those diagnosed at a later age, but no differences in DXA aBMD (p&amp;gt;0.31). Conclusion: In sum, older men, but not women, with T1D showed some deficits in bone structure at the proximal femur. Adults with T1D who were diagnosed ≤ age 12 had trabecular bone deficits within the proximal femur. Additional studies are needed to identify mechanisms underlying the high hip fracture risk in T1D. Presentation: 6/1/2024

6870 Cardiac Imaging And Metabolomics Studies Suggest Differential Risk And Protective Biomarkers For Cardiovascular Disease In Renoprotected, Long-Duration Type 1 Diabetes

Abstract Disclosure: M. Yu: None. S. Jangolla: None. N. Ziemniak: None. E. Viebranz: None. T. Chokshi: None. K. Park: None. I. Wu: None. H. Shah: None. G.L. King: None. Cardiovascular disease (CVD) is a major cause of mortality in people with Type 1 diabetes (T1D), especially in those with nephropathy (DN). However, in long-duration T1D, a substantial proportion of individuals without DN still exhibit excessive CVD risks. The Joslin 50-Year “Medalist” Study (n=1043), composed of people with T1D≥50 years, are ideal for studying CVD in a renoprotected T1D cohort, as only 13% have DN, and yet 40% have CVD, despite excellent control of lipids and blood pressure. Stratifying the Medalists by DN revealed that exercise was cardioprotective in the group with DN (OR 0.60, p=0.04); while age at T1D diagnosis (OR 1.03, p=0.01), HbA1c (OR 1.25, p=0.01), C-reactive protein (OR 1.14, p=0.01), and interleukin-6 (OR 1.13, p=0.01) all increased CVD risk in Medalists without DN. A subset of Medalists also underwent coronary artery calcification scans (CAC; n=153) and cardiac magnetic resonance imaging of left ventricular (LV) structure and function (CMR; n=111). The majority of these Medalists (97.8%) had detectable CAC&amp;gt;0; furthermore, the median CAC score of 1000 was higher at any cutoff compared to similar age-matched T1D and Type 2 diabetes (T2D) populations with higher DN prevalence. In contrast, mean CMR values in this Medalist subset were comparable to other cohorts. Continuous glucose monitoring (CGM) metrics for hyperglycemia (mean glucose, β=0.002, p=0.03; glucose management indicator, β=0.09, p=0.03; and time above range&amp;gt;180 mg/dL, β=0.003, p=0.02), but not glucose variability or hypoglycemia, were associated with LV remodeling in the Medalists, even after adjusting for eGFR. Likewise, plasma levels of advanced glycation end-products (AGEs) N-carboxyethyl-lysine (CEL), N-carboxymethyl-lysine (CML), and methylglyoxal-derived hydroimidazolone (MGH1) were associated with CAC (β=16.22, p=0.05; β=15.21, p=0.01; and β=10.18, p=0.01, respectively) and LV remodeling (β=0.001, p=0.09; β=0.001, p=0.05; and β=0.001, p=0.04, respectively) in the Medalists. The association of CEL with CVD replicated in a separate Medalist subset (n=311) with self-reported CVD data (OR 1.26, p=0.01). Plasma global metabolomics studies (n=140) revealed that amino acid activation pathways, with lower levels of branched chain amino acids, were associated with CAC (FDR=0.002); while amino acid metabolism pathways were associated with less favorable LV volumes (FDR=0.03). In this comprehensive study of aging T1D people with no substantial DN, hyperlipidemia, or hypertension, cardiac imaging and metabolomics studies suggest disproportionate advanced CAC, as compared to subclinical LV remodeling or dysfunction, and highlight the importance of targeting hyperglycemia for CVD risk reduction. Plasma metabolites associated with CVD in T1D are different from those in T2D, and may provide novel information on potential therapeutic targets for CVD in T1D. Presentation: 6/1/2024

6719 Sex Differences In Lipoproteins And Excess Risk Of Coronary Heart Disease In Women With Type 2 Diabetes

Abstract Disclosure: Y. Yoshida: None. D. Li: None. X. Li: None. V.A. Fonseca: None. L. Qi: None. F. Mauvais-Jarvis: None. Background: Women with type 2 diabetes (T2D) have a greater risk of coronary heart disease (CHD) than men with T2D. We compared levels of lipoproteins and their associations with CHD in women and men with new-onset T2D, pre-diabetes (PDM), and euglycemia. Method: We obtained circulating metabolomic data, including lipoprotein classes, apolipoproteins, total triglycerides (TG), and TG in very large LDL (VLDL), LDL, and HDL by nuclear magnetic resonance for 95,108 CHD-free people at baseline and incident CHD from the national health registers of the UK Biobank study. We used multivariable linear regressions to examine the association between sex and lipoprotein markers (log(x)) in groups of new-onset T2D (new T2D diagnosis or diabetes medication use within two years from the baseline), PDM (HbA1c 5.7-6.5%), and euglycemia, accounting for age, race, Townsend Deprivation Index, income, smoking, obesity, medications for hypertension, hyperlipidemia, and diabetes. We used Cox proportional hazard models to evaluate the association between lipoproteins and CHD risk in men and women separately, adjusting the same covariates. We performed sensitivity analyses using the assay-measured lipoproteins of the same participants and accounted for menopausal status. False discovery rate adjusted for multiple comparisons. Results: 1328 individuals with newly diagnosed T2D, 6204 with PDM, and 87,576 with euglycemia were included in the analysis. In adjusted linear regressions, atherogenic lipoproteins, including total cholesterol (c), non-HDL-c, remnant-c, and LDL-c were significantly higher in women than in men across glycemic status, and this sex difference was the most striking in the T2D group (β 0.5, 0.3, 0.15, and 0.23 in T2D vs. 0.44, 0.16, 0.09, and 0.12 in PDM vs. 0.37, 0.08, 0.04, and 0.08 in euglycemia). In euglycemic individuals, levels of Apo B and VLDL were higher in men than in women (β -0.01 and -0.05); however, in T2D individuals, women had higher levels of VLDL(β 0.05 and 0.05). Total TG and TG in VLDL were significantly higher in men with euglycemia (β -0.22 and -0.23) and PDM (β -0.15 and -0.16), but the sex differences were not significant in the T2D group (β -0.01 and -0.04). During the median 10-year follow-up, one SD increase in total TG (women HR 2.5, 95% 1.3-4.9 vs. men 1.07, 0.7-1.7 P-interaction=0.03), TG in VLDL (W 2.1, 1.2-3.7 vs. M 1.06 0.7-1.6 P=0.03), TG in LDL (W 3.2, 1.2-8.8 vs. M 1.3, 0.7-2.6, P=0.1), and TG in HDL (W 3.7, 1.4-9.5 vs. M 0.9, 0.5-1.7, P=0.008) was significantly associated with increased risk of CHD in women with T2D, but the associations were not significant in male patients. Results from available assay-measured markers and menopausal stratification were generally consistent with the main results. Conclusions: Women had higher levels of atherogenic lipids than men with advancing glycemic status. Women with T2D are at a higher risk of CHD associated with TG than men with T2D. Presentation: 6/3/2024

6971 Effects of the Hybrid Closed-loop System in Pediatric-Onset Type 1 Diabetes

Abstract Disclosure: H. Woo: None. J. Yoo: None. S. Shin: None. Y. Lee: None. H. Kim: None. M. Gu: None. J. Kim: None. J. Kim: None. C. Shin: None. Y. Lee: None. Purpose: We evaluated the effectiveness and limitations of the MiniMedTM 770G, a hybrid closed-loop (HCL) system which adjusts basal insulin every five minutes using continuous glucose monitoring (CGM) data, for glycemic control in pediatric-onset type 1 diabetes (T1D) in South Korea. Methods: We enrolled 20 patients (10 boys and 10 girls) who had been using the 770G pump for over three months, initiating its use between February 2022 and May 2023. Prior to this, they were CGM users and were followed for over a year post T1D diagnosis. Clinical and biochemical data, along with CGM metrics such as time in range (TIR), time below range (TBR), time above range (TAR), and coefficient of variation (CV), were analyzed. Additionally, the percentage of SmartGuard Auto Mode system usage was collected. Results: The median age at the start of 770G was 13.97 years (IQR 11.24–17.86), with a median of 6.5 years of duration of type 1 diabetes. After utilizing the 770G pump (n=20), TIR, TAR, and CV improved over the year (P&amp;lt;0.05). Patients utilizing Auto Mode over 85% of the time exhibited significant improvements in HbA1c (P=0.02), TIR (P=0.04), CV (P&amp;lt;0.01), and TAR 250 (P=0.02), in contrast to those who used Auto Mode 85% or less. Hyperglycemia and lack of calibration contributed to over 50% of the exits from Auto Mode. Conclusions: The implementation of HCL in adolescents and young adults with T1D enhanced glycemic control over one year. Educating patients on sustained Auto Mode use without interruptions is crucial. Presentation: 6/2/2024

Exploring the association of social connections and food security among adults with uncontrolled type 2 diabetes: a population-based study

BackgroundPrimary health care professionals are held accountable for various quality measures in the treatment of patients with chronic diseases such as diabetes. Uncontrolled type 2 diabetes (T2D) remains a considerable health problem; thus, further studying patients with this condition is important for delivering effective interventions. Social determinants of health (SDoH) have been shown to affect various aspects of diabetes care in different subpopulations. We studied the association of SDoH with uncontrolled T2D in a population of adult primary care patients.MethodsWe retrospectively searched our electronic health record for adult patients (≥18 years) with a diagnosis of T2D and a hemoglobin A1c (HbA1c) level of 8% or higher. Patients were empaneled to 2 primary care clinic sites between January 1, 2021, and January 31, 2022. Patients were grouped by HbA1c level to stratify patients according to the extent of uncontrolled T2D. Patient characteristics were compared among groups. Unadjusted and adjusted multinomial logistic regression analysis was used to estimate the odds of various SDoH factors among patient groups with different levels of uncontrolled T2D.ResultsThe study cohort included 1,596 patients. Most patients were White (79%), and the median age was 58.8 years. The median HbA1c level was 8.9%, and approximately 68% of patients were obese (body mass index [BMI] ≥30). When the study population was grouped by HbA1c level (8% to < 9% [n = 806], ≥9% to < 12% [n = 684], and ≥12% [n = 106]), significant differences among groups were observed in age group (P < .001), marital status (P < .001), race (P < .001), ethnicity (P = .001), and BMI category (P = .01). In groups with higher HbA1c levels, we noticed a higher percentage of patients who were aged 51 to 65 years or single. Among patients with uncontrolled HbA1c levels, more patients were obese than overweight. Patients in the intermediate HbA1c group had increased odds of food insecurity and some decreased social connections, even after adjusting for age, sex, race, ethnicity, and marital status.ConclusionsAmong patients with uncontrolled T2D, higher HbA1c levels were associated with decreased social connections and increased food insecurity. Our findings provide insight into the role of these SDoH in managing T2D and have important implications for primary care practice.

Impact of continuous glucose monitoring on emergency department visits and all-cause hospitalization rates among Medicaid beneficiaries with type 2 diabetes treated with multiple daily insulin or basal insulin therapy.

The increasing prevalence of diabetes in the United States continues to drive a steady rise in health care resource utilization, especially emergency department visits and all-cause hospitalizations, and the associated costs. To investigate the impact of continuous glucose monitoring (CGM) on emergency department visits and all-cause hospitalizations among Medicaid beneficiaries with type 2 diabetes (T2D) treated with multiple daily insulin injections (MDIs) or basal insulin therapy (BIT) in a real-world setting. In this retrospective, 12-month analysis, we used the Inovalon Insights claims dataset to evaluate the effects of CGM acquisition on emergency department visits and all-cause hospitalizations in the Managed Medicaid population. The analysis included 44,941 beneficiaries with T2D who were treated with MDIs (n = 35,367) or BIT (n = 9,574). Primary outcomes were changes in the number of emergency department visits and all-cause hospitalizations following 6 months after acquisition of CGM (post-index period) compared with 6 month prior to CGM acquisition (pre-index period). The first claim for CGM was the index date. Inclusion criteria were as follows: aged younger than 65 years, diagnosis of T2D, claims for short- or rapid-acting insulin (MDI group) or basal insulin (not rapid-acting) (BIT group), acquisition of a CGM device between January 1, 2017, and September 30, 2022, and continuous enrollment in their health plan throughout the pre-index and post-index periods. In the MDI group, all-cause inpatient hospitalization rates decreased from 3.25 to 2.29 events/patient-year (hazard ratio = 0.12; 95% CI = 0.11-0.13; P < 0.001) and emergency department visit rates decreased from 2.15 to 1.86 events/patient-year (hazard ratio = 0.52; 95% CI = 0.50-0.53; P < 0.001). In the BIT group, all-cause inpatient hospitalization rates decreased from 1.63 to 1.39 events/patient-year (hazard ratio = 0.11; 95% CI = 0.09-0.12; P < 0.001) and emergency department visit rates decreased from 1.60 to 1.43 events/patient-year (hazard ratio = 0.47; 95% CI = 0.44-0.50; P < 0.001). Acquisition of CGM is associated with significant reductions in emergency department visits and all-cause hospitalizations among people with T2D treated with MDIs or BIT.