Insulin-treated Diabetes Research Articles

Development of a requirement for exogenous insulin treatment in dogs with hyperglycemia.

It has been suggested that overt diabetes mellitus in dogs be defined based on a persistent fasting blood glucose concentration (BGC) >144 mg/dL. Determine the number of dogs with randomly identified hyperglycemia without insulin-treated diabetes mellitus (ITDM) that later develop a need for exogenous insulin treatment. A total of 1318 dogs examined at a university teaching hospital without ITDM and with randomly identified hyperglycemia. Retrospective longitudinal study. Hyperglycemia was defined as randomly identified BGC above >112 mg/dL, moderate hyperglycemia as BGC >144 mg/dL but <200 mg/dL and pronounced hyperglycemia as BGC ≥200 mg/dL. Dogs were defined as having ITDM if they were treated with insulin. Follow-up was attempted 7 to 12 years after hyperglycemia was documented to determine if over time dogs developed a need for exogenous insulin treatment. Twenty-nine of 824 dogs (3.5%) with hyperglycemia and follow-up information developed ITDM, including 3/824 dogs (0.4%) with moderate hyperglycemia, and 2/824 dogs (0.2%) with pronounced hyperglycemia. Most dogs with hyperglycemia that developed ITDM (24/29, 83%) had BGC ≤144 mg/dL. Among dogs that eventually developed a need for exogenous insulin treatment, no association was found between the degree of hyperglycemia and the time interval between documentation of hyperglycemia and diagnosis of ITDM. Logistic regression determined that BGC is not significantly associated with ITDM. Most dogs with randomly identified hyperglycemia did not develop a need for exogenous insulin treatment. Other criteria could be required to augment the definition of overt DM in non-insulin treated dogs.

High Risk of Stroke in Patients With Worsening Heart Failure, Reduced Ejection Fraction, Coronary Heart Disease and Sinus Rhythm: Risk Prediction Score Analysis From the COMMANDER-HF Trial

BackgroundPatients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm have a heightened risk of stroke. Whether anticoagulation benefits these patients is uncertain. In this post hoc analysis of the A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER-HF) trial we evaluated how a previously validated risk model consisting of 3 variables (history of prior stroke, insulin-treated diabetes, and N-terminal pro-B-type natriuretic peptide level) would perform, compared with plasma d-dimer, for stroke prediction and estimation of the benefit of low-dose rivaroxaban. Methods and ResultsStroke risk and treatment effect were computed across risk score and plasma d-dimer tertiles. Risk score was available in 58% of the COMMANDER-HF population (n = 2928). Over a median follow-up of 512 days (range 342–747 days), 60 patients experienced a stroke (14.6 per 1000 patient-years). The risk model did not identify patients at higher risk of stroke and showed a low overall prognostic performance (C-index = 0.53). The effect of rivaroxaban on stroke was homogeneous across risk score tertiles (P-interaction = .67). Among patients in whom the risk score was estimated, d-dimer was available in 2343 (80%). d-dimer had an acceptable discrimination performance for stroke prediction (C-index = 0.66) and higher plasma d-dimer concentrations were associated with higher rates of stroke (ie, tertile 3 vs tertile 1, hazard ratio 3.65, 95% confidence interval 1.59–8.39, P = .002). Treatment with low-dose rivaroxaban reduced the incidence of stroke in patients at highest risk by d-dimer levels (ie, >515 ng/mL, hazard ratio 0.42, 95% confidence interval 0.18–0.95, P-interaction = .074), without any safety concerns. ConclusionsIn our analysis, plasma d-dimer concentrations performed better than a previously described 3-variable risk score for stroke prediction in patients with heart failure with reduced ejection fraction, a recent clinical worsening and sinus rhythm as enrolled in the COMMANDER-HF trial. In these patients, a raised plasma d-dimer concentration identified patients who might benefit most from rivaroxaban.

What difference does sleep make? Continuous glucose monitoring metrics during fixed-overnight time versus sleep periods among older adults with type 1 diabetes.

Hypoglycaemia during sleep is a common and clinically important issue for people living with insulin-treated diabetes. Continuous glucose monitoring devices can help to identify nocturnal hypoglycaemia and inform treatment strategies. However, sleep is generally inferred, with diabetes researchers and physicians using a fixed-overnight period as a proxy for sleep-wake status when analysing and interpretating continuous glucose monitoring data. No study to date has validated such an approach with established sleep measures. Continuous glucose monitoring and research-grade actigraphy devices were worn and sleep diaries completed for 2 weeks by 28 older adults (mean age 67 years [SD 5]; 17 (59%) women) with type 1 diabetes. Using continuous glucose monitoring data from a total of 356 nights, fixed-overnight (using the recommended period of 00:00 hours-06:00 hours) and objectively-measured sleep periods were compared. The fixed-overnight period approach missed a median 57 min per night (interquartile range: 49-64) of sleep for each participant, including five continuous glucose monitoring-detected hypoglycaemia episodes during objectively-measured sleep. Twenty-seven participants (96%) had at least 1 night with continuous glucose monitoring time-in-range and time-above-range discrepancies both ≥ 10 percentage points, a clinically significant discrepancy. The utility of fixed-overnight time continuous glucose monitoring as a proxy for sleep-awake continuous glucose monitoring is inadequate as it consistently excludes actual sleep time, obscures glycaemic patterns, and misses sensor hypoglycaemia episodes during sleep. The use of validated measures of sleep to aid interpretation of continuous glucose monitoring data is encouraged.

Influence of sex on the functional assessment of myocardial ischemia.

Fractional flow reserve (FFR) and non-hyperemic resting pressure ratios, such as instantaneous wave-free ratio (iFR) and resting full-cycle ratio (RFR), are recommended for evaluating the significance of angiographically intermediate coronary stenoses. Despite their usefulness, approximately 20% of assessed lesions exhibit discordance between FFR and iFR/RFR. The role of sex in this discrepancy remains uncertain; thus, we aimed to investigate its impact on the discordance between FFR and iFR/RFR. We reviewed 417 consecutive intermediate stenotic lesions from 381 patients, stratified by sex and assessed with both FFR and iFR/RFR. FFR≤0.80 and iFR/RFR ≤0.89 were considered positive for ischemia. Among the 381 patients, 92 (24.1%) were women. Women were older, had lower estimated glomerular filtration rate (eGFR), a higher ejection fraction, and were more likely to have peripheral artery disease than men. Median FFR and iFR/RFR values were lower in men than in women (FFR 0.86 vs. 0.80; P < 0.001; iFR 0.92 vs. 0.90; P = 0.049). However, overall discordance prevalence was similar for both sexes (20.6% vs. 15.1%; P = 0.22). In men, eGFR, insulin-treated diabetes mellitus, and arterial hypertension were predictors of positive FFR | negative iFR/RFR discordance, while eGFR, insulin-treated diabetes mellitus, atrial fibrillation, and chronic obstructive pulmonary disease were predictors of negative FFR | positive iFR/RFR discordance. No factors associated with either discordance were identified in women. FFR and iFR/RFR results indicating significant ischemia were more common in men than women when assessing intermediate coronary stenoses. Nevertheless, sex did not predict discordant results.

DIAGNOSTIC VALUE OF NITROGEN METABOLISM DISORDERS IN NON-ALCOHOLIC FATTY LIVER DISEASE IN COMORBID PATIENTS WITH METABOLIC SYNDROME AND STRATIFICATION OF DISEASE STAGES

The aim of the study is to determine the significance of hyperammonemia for the diagnosis of non-alcoholic fatty liver disease (NAFLD) in patients with metabolically associated comorbid pathology.&#x0D; Materials and Methods. A single-stage cohort randomized study was conducted to examine NAFLD in patients with metabolically associated pathology – type 2 diabetes, obesity, hypertension, coronary artery disease, and dyslipidemia. The study included 96 patients, who were divided into 3 groups: patients with steatotic liver disease (n=33), patients with non-alcoholic steatohepatitis (n=47) and patients with newly diagnosed liver cirrhosis (n=16). For NAFLD diagnosis, non-invasive methods were also applied (APRI, FIB4, NAFLD fibrosis score). To diagnose hepatocellular insufficiency, the authors evaluated ammonia level in capillary blood. Statistical processing was carried out by parametric and nonparametric methods, correlation and cluster analysis (Statistica 10.0). We also calculated odds ratio.&#x0D; Results. Metabolic syndrome in patients aged 64.2±0.85 (64.9 % females and 35.1 % males, Charleson comorbidity index 4.57±0.12) was represented by type 2 diabetes (100 %), insulin-treated diabetes (2/3 of patients), hypertension (1/3 of patients, stage 3 of NAFLD), obesity (87.5 %), coronary heart disease (90.6 %), steatotic liver disease (34.4 %), non-alcoholic steatohepatitis (49 %) and asymptomatic liver cirrhosis (16,6 %). According to NFS results, stage F3–F4 fibrosis was diagnosed in 52.1 % of patients, F2 fibrosis in 47.9 %; hyperammonemia was found in 91.7 % (up to 111.1±4.86 (101.3–120.7) µmol/l). Hyperammonemia developed from steatosis to non-alcoholic steatohepatitis and liver cirrhosis and correlated with the stage of liver fibrosis, hepatitis activity, and metabolic syndrome key criteria. NFS calculator and hyperammonemia diagnosis made it possible to stratify the stages of non-alcoholic fatty liver disease.

Continuous glucose monitoring metrics and pregnancy outcomes in insulin-treated diabetes: A post-hoc analysis of the GlucoMOMS trial.

To investigate the association between continuous glucose monitoring (CGM) metrics and perinatal outcomes in insulin-treated diabetes mellitus in pregnancy. In a post-hoc analysis of the GlucoMOMS randomized controlled trial, we investigated the association between the metrics of an offline, intermittent CGM, glycated haemoglobin (HbA1c) and perinatal outcomes per trimester in different types of diabetes (type 1, 2 or insulin-treated gestational diabetes mellitus [GDM]). Data were analysed using multivariable binary logistic regression. Outcomes of interest were neonatal hypoglycaemia, pre-eclampsia, preterm birth, large for gestational age (LGA) and Neonatal Intensive Care Unit (NICU) admission. The glucose target range was defined as 3.5-7.8 mmol/L (63-140 mg/dL). Of the 147 participants (N = 50 type 1 diabetes, N = 94 type 2 diabetes/insulin-treated GDM) randomized to the CGM group of the GlucoMOMS trial, 115 participants had CGM metrics available and were included in the current study. We found that, in pregnancies with type 1 diabetes, a higher second trimester mean glucose was associated with LGA (odds ratio 2.6 [95% confidence interval 1.1-6.2]). In type 2 and insulin-treated gestational diabetes, an increased area under the curve above limit was associated with LGA (odds ratio 10.0 [95% confidence interval 1.4-72.8]). None of the CGM metrics were associated with neonatal hypoglycaemia, pre-eclampsia, shoulder dystocia, preterm birth and NICU admission rates for pregnancies complicated by any type of diabetes. In this study, in type 2 diabetes or insulin-treated GDM, the glucose increased area under the curve above limit was associated with increased LGA. In type 1 diabetes, the mean glucose was the major determinant of LGA. Our study found no evidence that other CGM metrics determined adverse pregnancy outcomes.

Diagnosis and treatment of anti-insulin antibody-mediated labile glycaemia in insulin-treated diabetes.

Anti-insulin antibodies in insulin-treated diabetes can derange glycaemia, but are under-recognised. Detection of significant antibodies is complicated by antigenically distinct insulin analogues. We evaluated a pragmatic biochemical approach to identifying actionable antibodies, and assessed its utility in therapeutic decision making. Forty people with insulin-treated diabetes and combinations of insulin resistance, nocturnal/matutinal hypoglycaemia, and unexplained ketoacidosis were studied using broad-specificity insulin immunoassays, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) with or without ex vivo insulin preincubation. Twenty-seven people had insulin immunoreactivity (IIR) below 3000 pmol/L that fell less than 50% after PEG precipitation. Insulin binding by antibodies in this group was low and judged insignificant. In 8 people IIR was above 3000 pmol/L and fell by more than 50% after PEG precipitation. GFC demonstrated substantial high molecular weight (HMW) IIR in 7 of these 8. In this group antibodies were judged likely significant. In 2 people immunosuppression was introduced, with a good clinical result in one but only a biochemical response in another. In 6 people adjustment of insulin delivery was subsequently informed by knowledge of underlying antibody. In a final group of 5 participants IIR was below 3000 pmol/L but fell by more than 50% after PEG precipitation. In 4 of these GFC demonstrated low levels of HMW IIR and antibody significance was judged indeterminate. Anti-insulin antibodies should be considered in insulin-treated diabetes with unexplained glycaemic lability. Combining immunoassays with PEG precipitation can stratify their significance. Antibody depletion may be beneficial, but conservative measures often suffice.

Glutamate Infusion Reduces Myocardial Dysfunction after Coronary Artery Bypass Grafting According to NT-proBNP: Summary of 2 Randomized Controlled Trials (GLUTAmate for Metabolic Intervention in Coronary Surgery [GLUTAMICS I-II

BackgroundGlutamate is reported to enhance the recovery of oxidative metabolism and contractile function of the heart after ischemia. The effect appears to be blunted in diabetic hearts. Elevated plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction. In the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) II trial, the proportion of patients with diabetes had nearly doubled to 47% compared with the cohort used for sample size estimation, and a significant effect on the postoperative rise in NT-proBNP was only observed in patients without diabetes. ObjectiveWe aimed to summarize the pooled NT-proBNP results from both GLUTAMICS trials and address the impact of diabetes. MethodsData from 2 prospective, randomized, double-blind multicenter trials with similar inclusion criteria and endpoints were pooled. Patients underwent a coronary artery bypass grafting (CABG) ± valve procedure and had a left-ventricular ejection fraction of ≤0.30 or a European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) of ≥3.0 with at least 1 cardiac risk factor. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was started 10–20 min before reperfusion and continued for 150 min. The primary endpoint was the difference between preoperative and day 3 postoperative NT-proBNP levels. ResultsA total of 451 patients, 224 receiving glutamate and 227 controls, fulfilled the inclusion criteria. Glutamate was associated with a reduced primary endpoint (5344 ± 5104 ng/L and 6662 ± 5606 ng/L in glutamate and control groups, respectively; P = 0.01). Postoperative mortality at ≤30 d was 0.9% and 3.5% (P = 0.11), whereas stroke at ≤24 h was 0.4% and 2.6% in glutamate and control groups, respectively (P = 0.12). No adverse events related to glutamate were observed. A significant interaction regarding the primary endpoint was only detected between glutamate and insulin-treated diabetes groups (P = 0.04). Among patients without insulin-treated diabetes, the primary endpoint was 5047 ± 4705 ng/L and 7001 ± 5830 ng/L in the glutamate and control groups, respectively (P = 0.001). ConclusionsInfusion of glutamate reduced the postoperative rise in NT-proBNP after CABG in medium- to high-risk patients. A significantly blunted effect was observed only in insulin-treated patients with diabetes. Clinical trial detailsThis trial was registered at www.clinicaltrials.gov as NCT02592824.

Exposures during pregnancy and at birth are associated with the risk of offspring eating disorders.

Eating disorders (ED) are severe psychiatric disorders, commonly debuting early. Aberrances in the intrauterine environment and at birth have been associated with risk of ED. Here, we explore if, and at what effect size, a variety of such exposures associate with offspring ED, that is, anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS). This population-based cohort study, conducted from September 2021 to August 2023, used Finnish national registries of all live births in 1996-2014 (N = 1,097,753). Cox proportional hazards modeling was used to compare ED risk in exposed versus unexposed offspring, adjusting for potential confounders and performing sex-stratified analyses. A total of 6614 offspring were diagnosed with an ED; 3668 AN, 666 BN, and 4248 EDNOS. Lower risk of offspring AN was seen with young mothers, continued smoking, and instrumental delivery, while higher risk was seen with older mothers, inflammatory disorders, prematurity, small for gestational age, and low Apgar. Offspring risk of BN was higher with continued smoking and prematurity, while lower with postmature birth. Offspring risk of EDNOS was lower with instrumental delivery, higher for older mothers, polycystic ovary syndrome, insulin-treated pregestational diabetes, antibacterial treatment, prematurity, and small for gestational age. Sex-specific associations were found. Several prenatal and at birth exposures are associated with offspring ED; however, we cannot exclude confounding by maternal BMI. Nevertheless, several exposures selectively associate with risk of either AN, BN, or EDNOS, and some are sex-specific, emphasizing the importance of subtype- and sex-stratified analyses of ED. We define environmental factors involved in the development of different ED, of importance as preventive measure, but also in order to aid in defining the molecular pathways involved and thus in the longer perspective contribute to the development of pharmacological treatment of ED.

Lipohypertrophy and Insulin: An Update From the Diabetes Technology Society.

Lipohypertrophy is a common skin complication associated with insulin-treated diabetes. The impact of lipohypertrophy as a contributing factor to suboptimal glycemic control, glucose variability, and hypoglycemia is often under-recognized by health care professionals. In a recent Webinar on April 26, 2023, Diabetes Technology Society asked international experts to provide updates on the latest knowledge related to lipohypertrophy for practicing clinicians and educators, researchers, and industries involved in insulin delivery. A recording of the Webinar is freely available on the Diabetes Technology Society Web site (https://www.diabetestechnology.org/).

Lipid abnormalities in pediatric kidney transplant recipients on steroid withdrawal maintenance immunosuppression.

Dyslipidemia is a modifiable risk factor for cardiovascular disease. The prevalence of dyslipidemia in pKTR (pediatric kidney transplant recipients) under modern immunosuppression remains unknown. We determined the prevalence, risk factors, co-morbidities, and treatment patterns of lipid abnormalities in pediatric kidney transplant recipients on steroid withdrawal immunosuppression. pKTR (age ≤ 21years) at a single center on steroid withdrawal immunosuppression underwent lipid screening between January 1, 2020, and September 30, 2022. Continuous and categorical variables were compared using the Wilcoxon rank-sum and chi-square or Fisher's exact tests, respectively. The correlation between total cholesterol and BMI (body mass index) was assessed using Pearson's product-moment correlation, and predictors of lipid abnormalities were evaluated using the multivariable logistic regression. A total of 96 patients were included, with a median post-transplant time of 2.5years (IQR: 1.3-5.4). Of the total, 64.6% (n = 62) of patients had a fasting lipid abnormality. We found a significant linear correlation between total cholesterol and BMI (r = 0.38, p = 0.0022). After multivariable adjustment, every 1ml/min/1.73 m2 increase in eGFR was associated with a 2% lower odds of a lipid abnormality (OR 0.979, p = 0.026). Obesity, hypertension, and left ventricular hypertrophy were similar between those with and without lipid abnormalities, while insulin-treated diabetes was more prevalent in recipients with lipid abnormalities (12.9% vs. 0%, p = 0.047). Only 36.5% of patients (n = 19) were referred to a dietician and/or lipid specialist; one received statin therapy. Lipid abnormalities are highly prevalent in pKTR, but therapeutic intervention is infrequent. Calcineurin inhibition without corticosteroids may not be protective; however, higher eGFR is associated with a lower prevalence of lipid abnormalities. A higher resolution version of the Graphical abstract is available as Supplementary information.

Assessing Quality of Life in Patients With Chronic Urticaria Through Comparisons With Patients Having Other Common Chronic Diseases.

Chronic urticaria (CU) is a common chronic inflammatory disease, but the burden on quality of life (QOL) has been underestimated. To compare QOL among patients with CU and those with other chronic diseases. Adult patients who visited a referral hospital for CU were enrolled. Patients completed self-reported questionnaires including clinical characteristics of chronic urticaria and the short form 36 health survey. As a comparative group, patients with rheumatoid arthritis, patients with diabetes treated with insulin, patients on maintenance hemodialysis, and healthy controls were enrolled and completed the short form 36 health survey. In all, 119 patients with CU were enrolled and their short form 36 scores were not significantly different from those of healthy controls. However, patients with CU with poor responses to treatment showed impaired QOL to a degree similar to that of patients with rheumatoid arthritis or insulin-treated diabetes. The patients with CU showed various clinical characteristics with respect to treatment response, accompanying symptoms, and aggravating factors. Among these factors, pain at the urticarial lesion and symptom aggravation during exercise and after the consumption of certain foods were related with lower QOL. Patients with CU with an incomplete response to treatment had significantly low QOL, comparable to that of patients with rheumatoid arthritis or insulin-treated diabetes. To minimize this effect, clinicians should aim to control symptoms and aggravating factors.

Continuous Glucose Monitoring by Insulin-Treated Pilots Flying Commercial Aircraft Within the ARA.MED.330 Diabetes Protocol: A Preliminary Feasibility Study.

Background and Aims: A preliminary study compared the use of continuous glucose monitoring (CGM) with the use of self-monitored blood glucose (SMBG) by aircraft pilots with insulin-treated diabetes in the United Kingdom, Ireland, and Austria, certified to fly commercial aircraft within the European Aviation Safety Agency ARA.MED.330 protocol. Methods: SMBG and simultaneous interstitial glucose measurements using CGM (Dexcom G6®) were recorded during pre- and in-flight periods. Results: Eight male pilots (seven with type 1 diabetes and one with type 3c diabetes), median age of 48.5 years and median diabetes duration of 11.5 years, participated. The correlation coefficient (R) between 874 contemporaneously recorded SMBG and CGM values was 0.843, P < 0.001. The mean glucose concentration was 8.78 mmol/L (standard deviation [SD] 0.67) using SMBG compared with 8.71 mmol/L (SD 0.85) recorded using CGM. The mean absolute relative difference was 9.39% (SD 3.12). Conclusions: CGM using Dexcom G6 systems is a credible alternative to SMBG for monitoring glucose levels when insulin-treated pilots fly commercial aircraft. The study was registered with Clinical Trials.gov NCT04395378.

Predicting Stroke in Heart Failure and Preserved Ejection Fraction Without Atrial Fibrillation.

The rate of stroke in patients with heart failure (HF) and preserved ejection fraction but without atrial fibrillation (AF), is uncertain as is whether it is possible to reliably predict the risk of stroke in these patients. We validated a previously developed simple risk model for stroke among patients enrolled in the I-Preserve trial (Irbesartan in Heart Failure With Preserved Systolic Function) and PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The risk model consisted of 3 variables: history of previous stroke, insulin-treated diabetes, and plasma N-terminal pro-B-type natriuretic peptide level. Of the 8924 patients included in the pooled trial dataset, 5126 patients did not have AF at baseline. Among patients without AF, 190 (3.7%) experienced a stroke over a median follow-up of 3.6 years (rate 10.5 per 1000 patient-years). The risk for stroke increased with increasing risk score: second tertile hazard ratio, 1.78 (95% CI, 1.17-2.71); third tertile hazard ratio, 3.03 (95% CI, 2.06-4.47), with the first tertile as reference. For patients in the third tertile, the occurrence rate of stroke was 17.7 per 1000 patient-years, similar to that in patients with AF not receiving anticoagulation (20.7 per 1000 patient-years), and those with AF who were receiving anticoagulation (14.5 per 1000 patient-years). Model discrimination was good with a C index of 0.81 (0.68-0.91) and a simple score could be created from the model. A simple risk model can detect a subset of HF and preserved ejection fraction patients without AF who have a higher risk for stroke. The balance of risk-to-benefit in these individuals may justify the use of prophylactic anticoagulation, but this hypothesis needs to be prospectively evaluated. URL: https://www. gov; Unique identifiers: NCT00095238 and NCT01920711.

Impact of Intensive Glycemic Treatment on Diabetes Complications-A Systematic Review.

Diabetes complications can be related to the long duration of the disease or chronic hyperglycemia. The follow-up of diabetic patients is based on the control of chronic hyperglycemia, although this correction, if obtained rapidly in people living with severe chronic hyperglycemia, can paradoxically interfere with the disease or even induce complications. We reviewed the literature describing the impact of the rapid and intense treatment of hyperglycemia on diabetic complications. The literature review showed that worsening complications occurred significantly in diabetic microangiopathy with the onset of specific neuropathy induced by the correction of diabetes. The results for macroangiopathy were somewhat mixed with the intensive and rapid correction of chronic hyperglycemia having a neutral impact on stroke and myocardial infarction but a significant increase in cardiovascular mortality. The management of diabetes has now entered a new era with new therapeutic molecules, such as gliflozin for patients living with type 2 diabetes, or hybrid insulin delivery systems for patients with insulin-treated diabetes. Our manuscript provides evidence in support of these personalized and progressive algorithms for the control of chronic hyperglycemia.

122-OR: What Are the Barriers and Facilitators of Resistance Training in Mildly Frail Older Adults with Insulin-Treated Diabetes? A Qualitative Analysis Using the Capability, Opportunity, Motivation, and Behaviour (COM-B) Behavioural Science Model

Background: Resistance exercise offers many benefits for those with frailty and sarcopenia and may carry less risk of exercise induced hypoglycaemia. However most older adults do not meet recommended levels of exercise. Little is known about why, especially for mildly frail older adults with insulin treated diabetes. Our aim was to investigate behavioural related influences to undertaking resistance exercise in this vulnerable group. Methods: A phenomenological qualitative study using semi structured interviews with mildly frail adults aged ≥60 with insulin-treated diabetes (Type 1 (n=12); Type 2 (n=3)) recruited via online advert, in the UK. Frailty was assessed using the Rockwood Clinical Frailty Scale. Those with a history of myocardial infarction, stroke, renal failure, severe hypertension or liver disease in the last 12 months were excluded. Data were analysed inductively using thematic analysis, then aligned to the COM-B. Results: Barriers to exercise centred on the physical capability, opportunity, and reflective motivation COM-B domains. Primary barriers included exacerbating existing fatigue or diabetes-related complications, exercise induced hypoglycaemia and injury, and inability to use resistance equipment. Most were unaware of the benefits of exercise on diabetes and muscle health. Many with a decades-long diagnosis were initially told that exercise was unsafe. Facilitators included an informative and flexible training environment, clarity on potential diabetes specific benefits, and having a supportive partner ideally also capable of exercise. Conclusion: Older, mildly frail adults with insulin-treated diabetes are a vulnerable group whose beliefs may prevent them from undertaking regular exercise. They may benefit from a specific programme of awareness raising and a tailored, flexible exercise environment. Disclosure R.Stocker: None. J.A.Shaw: Advisory Panel; Betalin Therapeutics, Provention Bio, Inc., Consultant; Mogrify. M.D.Witham: None. G.Taylor: None. D.J.West: None. Funding UK Wellcome Trust

1047-P: Evaluating Discharge Prescription Errors and the Clinical Impacts in Patients with Insulin-Treated Diabetes Mellitus in a Community Hospital

Introduction: Transitioning patients with insulin treated diabetes (ITDM) at time of hospital discharge is identified as a source of error in how information for home management is provided that can contribute to significant adverse health outcomes. To address this, we conducted a quality improvement project investigating the safety of current discharge procedures in our hospital and the impact on glycemic control at 3 months and diabetes related readmissions at 3 and 6 months. Methods: We retrospectively analyzed discharge prescription errors in patients with ITDM in a community hospital between January 2020 and December 2021. Errors were defined as being discharged on the wrong form of insulin (pen vs vial), and/or not being provided appropriate insulin administration devices (i.e., pen needles or syringes). Data was collected by reviewing discharge summaries, discharge medication reconciliations and pharmacy records. Results: Among 75 patients with ITDM (62 (82%) T2DM, 12 (16%) T1DM, 1 (1%) ketosis-prone DM), errors were noted in 73 (97%) patients. 46 (63%) were discharged on wrong form of insulin and 67 (91%) were discharged without appropriate insulin administration devices. Among those 73 patients, 19 (26%) patients had an increase in HbA1c at 3 months (8.7 vs 10.03, p=0.001); 5 (25%) and 8 (24%) had 30-day and 90-day diabetes-related hospital readmissions, respectively. In 2 patients with appropriate discharge, there were no 30-day or 90-day hospital readmissions. Conclusion: Prescription errors in patients with ITDM at discharge are common and potentially remediable and lead to hospital readmissions and poor glycemic control. These results demonstrate the need for increased awareness among providers through adoption of standardized discharge insulin order sets in EMR system including the form of insulin, insulin administration devices and supplies as well as for early post-discharge follow up with endocrinology. Disclosure A.N.Keskinkilic: None. M.T.Korytkowski: None. S.Mon: None.

392-P: Optimizing Duration and Threshold of Sensor Glucose for Identifying Symptomatic Hypoglycemia in Insulin-Treated Diabetes—Hypo-METRICS Study

Many episodes of hypoglycemia defined by the ATTD consensus are asymptomatic. We investigated if optimizing the glucose threshold and duration for sensor detected hypoglycemia (SDH) improves precision and sensitivity for identifying symptomatic hypoglycaemia from continuous glucose monitoring (CGM) data. We analysed 10 weeks of blinded CGM (Libre 2) and FitBit data from 435 participants [217 type 1, 218 type 2] with intact hypoglycemic awareness (Gold score &amp;lt;4). They self-reported symptomatic hypoglycemia on the Hypo-METRICS smartphone app. We used particle Markov chain Monte Carlo optimisation to generate the threshold and duration of SDH that maximizes detection of symptomatic hypoglycemia across our population and assessed impact of sleep status and diabetes type. The optimized threshold and duration were 70mg/dl for 27 min, with 2% gain of precision but 8% loss of sensitivity vs level 1 SDH (70mg/dl &amp;gt;15 min). Both level 1 SDH and our optimized definition had 3-fold increased sensitivity vs level 2 SDH (54mg/dl &amp;gt;15 min), with minimal loss of precision (Table). Our data validate ATTD level 1 hypoglycemia. Overall precision for detection of symptomatic hypoglycemia remains low despite optimization. Disclosure P.Divilly: None. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi, Vertex Pharmaceuticals Incorporated. R.J.Mccrimmon: Advisory Panel; Sanofi, Speaker's Bureau; Novo Nordisk A/S. J.K.Mader: Advisory Panel; Novo Nordisk A/S, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Medtronic, Becton, Dickinson and Company, Pharmasense, embecta, Research Support; A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Dexcom, Inc., Profusa, Inc., Speaker's Bureau; Novo Nordisk A/S, A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Boehringer Ingelheim Inc., Becton, Dickinson and Company, Ypsomed AG, Viatris Inc., Servier Laboratories, Medtrust, Stock/Shareholder; Decide Clinical Software GmbH. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. S.A.Amiel: Advisory Panel; Medtronic, Other Relationship; Sanofi, Novo Nordisk. P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. Hypo-resolve consortium: n/a. Z.Mahmoudi: Employee; Novo Nordisk. G.Martine-edith: Other Relationship; Novo Nordisk A/S. D.Boiroux: Employee; Novo Nordisk A/S. N.Zaremba: None. U.Soeholm: Employee; Novo Nordisk A/S. M.Gomes: Employee; Novo Nordisk A/S. A.A.Vaag: None. B.E.De galan: Research Support; Novo Nordisk. Funding Innovative Medicines Initiative 2 Joint Undertaking (777460)

Cancer incidence and mortality in 23 000 patients with type 1 diabetes in the UK: Long-term follow-up.

Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23 473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30 years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio = 1.58; 95% confidence interval 1.16-2.11; P < .01) and vulval (3.55; 1.94-5.96; P < .001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P < .001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.

Accuracy of Continuous Glucose Monitoring in an Insulin-Treated Population Requiring Haemodialysis.

Continuous glucose monitoring (CGM) is revolutionizing diabetes care by giving both patients and the healthcare professionals unprecedented insights into glucose variability and patterns. It is established in National Institute for Health and Care Excellence (NICE) guidance as a standard of care for type 1 diabetes and diabetes in pregnancy under certain conditions. Diabetes mellitus (DM) is recognized as an important risk factor for chronic kidney disease (CKD). Around a third of patients receiving in-center haemodialysis as renal replacement therapy (RRT) have diabetes, either as a direct cause of renal failure or as an additional co-morbidity. Evidence of poor compliance with the current standard of care (self-monitoring of blood glucose [SMBG]) and overall greater morbidity and mortality, suggests this patient population as an ideal target group for CGM. However, there exists no strong published evidence showing the validity of CGM devices in insulin-treated diabetes patients requiring haemodialysis. We applied a Freestyle Libre Pro sensor to 69 insulin-treated diabetes haemodialysis (HD) patients on a dialysis day. Interstitial glucose levels were obtained, and time matched within 7 minutes to capillary blood glucose testing and any plasma blood glucose levels sent. Data cleansing techniques were applied to account for rapidly correcting hypoglycaemia and poor SMBG technique. Clarke-error grid analysis showed 97.9% of glucose values in an acceptable range of agreement (97.3% on dialysis days and 99.1% on non-dialysis days). We conclude that the Freestyle Libre sensor is accurate in measuring glucose levels when compared to glucose as measured by capillary SMBG testing and laboratory obtained serum glucose in patients on HD.