Hypoglycemia Outcomes Research Articles

Fasting vs no fasting prior to catheterisation laboratory procedures: the SCOFF trial.

Current guidelines recommend 6 hours of solid food and 2 hours of clear liquid fasting for patients undergoing cardiac procedures with conscious sedation. There are no data to support this practice, and previous single centre studies support the safety of removing fasting requirements. The objective of this study was to determine the non-inferiority of a no fasting strategy to fasting prior to cardiac catheterisation procedures which require conscious sedation. This is a multicentre, investigator-initiated, non-inferiority randomised trial conduced in Australia with a prospective open label blinded endpoint design. Patients referred for coronary angiography, percutaneous coronary intervention or cardiac implantable electronic device (CIED) related procedures were enrolled. Patients were randomised 1:1 to fasting as normal (6 hours solid food and 2 hours clear liquid) or no fasting requirements (encouraged to have regular meals but not mandated to do so). Recruitment occurred from 2022 to 2023. The primary outcome was a composite of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia assessed with a Bayesian approach. Secondary outcomes included patient satisfaction score, new ventilation requirement (non-invasive and invasive), new intensive care unit admission, 30-day readmission, 30-day mortality, 30-day pneumonia. 716 patients were randomised with 358 in each group. Those in the fasting arm had significantly longer solid food fasting (13.2 versus 3.0 hours, Bayes factor >100 indicating extreme evidence of difference) and clear liquid fasting times (7.0 versus 2.4 hours, Bayes factor >100). The primary composite outcome occurred in 19.1% of patients in the fasting arm and 12.0% of patients in the no fasting arm. The estimate of the mean posterior difference in proportions in the primary composite outcome was -5.2% (95% CI -9.6 to -0.9, ) favouring no fasting. This result confirms non-inferiority (posterior probability >99.5%) and superiority (posterior probability 99.1%) of no fasting for the primary composite outcome. The no fasting arm had improved patient satisfaction scores with a posterior mean difference of 4.02 points (95% CI 3.36 to 4.67, Bayes factor >100). Secondary outcome events were similar. In patients undergoing cardiac catheterisation and CIED related procedures, no fasting was non-inferior and superior to fasting for the primary composite outcome of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia. Patient satisfaction scores were significantly better with no fasting. This supports removing fasting requirements for patients undergoing cardiac catheterisation laboratory procedures that require conscious sedation.

Impact of Hypoglycemia on Hospitalized Patients With Hepatocellular Carcinoma.

Aims Hepatocellular carcinoma (HCC) is one of the common liver malignancies that presents a challenge to global healthcare. The impact and outcomes of hypoglycemia in HCC have not been studied in detail before. This study aimed to investigate the outcomes and prognosis associated with hypoglycemia in patients diagnosed with HCC, utilizing a large-scale database approach. Methods Using the Nationwide Inpatient Sample (NIS) database from 2017 to 2020, we conducted a comprehensive retrospective analysis to examine the incidence, risk factors, and clinical implications of hypoglycemia on HCC patients. The patients were divided into two groups: those with hypoglycemia and those without hypoglycemia. Univariate and multivariate logistic regression were used to conduct the analysis. STATA® version 17.0 software(StataCorp LLC, College Station, TX) was used for this purpose. Results Out of a total of 343,895 patients with HCC, the prevalence of hypoglycemia was present in 1.5% of this patient population. We found that hypoglycemia was common in the male population (68%). Compared with patients without hypoglycemia, patients who had hypoglycemia with HCC had higher mortality (42%, p-value < 0.05) and higher risks of secondary outcomes such as hepatic failure, spontaneous bacterial peritonitis (SBP), ascites, and portal vein thrombosis compared to patients who did not have hypoglycemia. The multivariate-adjusted odds ratio for hepatic failure was 2.7 (2.3-3.1), for SBPwas 2.9 (1.8-3.0), for ascites was 1.6 (1.4-1.9), and for portal vein thrombosis was 1.2 (0.9-1.4). Conclusion In conclusion, hypoglycemia in HCC is associated with increased mortality and worse outcomes.

Evaluation of the etiology and outcome of hypoglycemia in young children – A challenging task

Evaluation of the etiology and outcome of hypoglycemia in young children – A challenging task

Etiology and outcome of hypoglycemia in young children: A retrospective cohort study

Objectives: Hypoglycemia is one of the most common presenting complaints at a pediatric emergency department. There are many distinct causes of hypoglycemia, ranging from nutritional insufficiency to infectious origins to metabolic disorders. Full clinical assessment and appropriate investigations can help differentiate the cause of hypoglycemia with subsequent tailored management. All patients with hypoglycemia should have a full clinical assessment together with a hypoglycemia screen if appropriate. This clinical review aims to determine the investigation of hypoglycemia in young children (&lt;6 years) and whether these patients received a subsequent diagnosis and adequate follow-up plans. Material and Methods: The laboratory database searched for all children from 0 to 6 years old, with hypoglycemia defined as plasma glucose (PG) &lt;54.0 mg/dL (or &lt;3.0 mmol/L) from 2013 to 2021 at the Royal Hospital of Children, Glasgow. Cases were reviewed for the biochemistry investigations to determine if they had hypoglycemia screening requested and/or performed the presenting complaint, clinical diagnosis, and subsequent follow-up arrangements. Results: Five hundred and one children were identified with hypoglycemia (PG &lt;54.0 mg/dL) over a 9-year period. Of these patients, 28% (142/501) had a full hypoglycemia screen, 38% had a partial screen, and 34% (166/501) had no additional blood tests related to hypoglycemia screening other than a PG. The cause of hypoglycemia was identified in 15% (77/501), with gastroenteritis being the most common cause. Of those who were hypoglycemic, 48% (240/501) had an ongoing follow-up. Among those with severe hypoglycemia (PG ≤27.0 mg/dL) (86/501), causes were identified in 72% (62/86) and 63% (54/86) of this cohort which was followed up after the first presentation. Conclusion: Screening was not consistently performed for all patients presenting with hypoglycemia. A great portion of patients were not fully investigated or followed up. This could be a result of clinical judgment in the assessment of further investigation for hypoglycemia. However, moderate and severe hypoglycemia still require further investigations, which can potentially lead to long-term consequences if not managed appropriately.

Etiology and outcome of hypoglycemia in young children: Indian perspective

Etiology and outcome of hypoglycemia in young children: Indian perspective

Study of incidence, risk factors and immediate outcome of hypoglycemia in neonates admitted in NICU

Background: Hypoglycemia is the most common metabolic problem occurring in newborns which is associated with poor neurologic outcome. The present study was conducted to determine the incidence, risk factors and immediate outcome of hypoglycemia in neonates. Methods: The present study was conducted on 3776 babies born with risk factors for hypoglycemia in NICU. Screening for blood glucose level of study subjects were done at 2, 4, 6,12,24,48,78 hours of life, twice daily and whenever symptomatic by using glucometer. Babies were followed up till discharge. Incidence, risk factors and immediate outcome of hypoglycemia were assessed. Appropriate tests were applied. Results: Incidence of hypoglycemia was 9.93% among high-risk neonates and overall incidence was 5.20%. 54.13% were males. 45% were preterm, 78.7% neonates were LBW. 53.07% were born to primiparous mother, 20.5% to diabetic mothers and 28.5% to hypertensive mothers. 16.8% had perinatal asphyxia, 14.66% new-born had underlying RDS. 48.5% were symptomatic, most common being lethargy 52.75% followed by jitteriness 43.41%, convulsion in 63 (34.62%). Preterm and LBW were significantly associated with mortality. Most common underlying comorbidities associated with deaths were sepsis (59.10%), RDS (45.46%), perinatal asphyxia (13.64%) and meconium aspiration syndrome (4.55%). Conclusions: Neonates with one or more risk factors for hypoglycemia should be screened irrespective of symptoms within 72 hours of life. Focused counselling on early initiation of breast feeding will reduce the incidence of hypoglycemia and its complications.

Intrapartum continuous subcutaneous insulin infusion vs intravenous insulin infusion among pregnant individuals with type 1 diabetes mellitus: a randomized controlled trial

Intrapartum glucose management is critical to reducing neonatal hypoglycemia shortly after birth. Although it is known that insulin is required for all pregnant individuals with type 1 diabetes mellitus, the optimal mode of intrapartum glycemic control is not known. This study aimed to compare the effect of intrapartum use of continuous subcutaneous insulin infusion with that of intravenous insulin infusion for glucose management among pregnant individuals with type 1 diabetes mellitus on neonatal blood glucose levels. This was a randomized controlled trial of pregnant participants with type 1 diabetes mellitus. After written informed consent, participants were randomly allocated to 1 of 2 intrapartum insulin administration strategies: continuation of their continuous subcutaneous insulin infusion or intravenous insulin infusion. The primary outcome was the first neonatal blood glucose level. Between March 2021 and April 2023, 76 participants were approached, and 70 participants were randomized (35 participants in the intravenous insulin infusion group and 35 participants in the continuous subcutaneous insulin infusion group). The groups were similar in terms of age, race/ethnicity, pregravid body mass index, nulliparity, and gestational age at delivery. There was no statistically significant difference in the first neonatal glucose measurement between the 2 groups (50.1±23.4 vs 49.2±22.6; P=.86). In addition, there were no statistically significant differences in any secondary neonatal outcomes. Approximately 57.1% of neonates in the continuous subcutaneous insulin infusion group required either oral, intravenous, or both treatments for hypoglycemia, whereas 51.4% of neonates in the intravenous infusion group required treatment. In both groups, 28.6% of neonates required intravenous treatment for hypoglycemia. Pregnant individuals with type 1 diabetes mellitus using either intravenous insulin infusion or continuation of their continuous subcutaneous insulin infusion for intrapartum insulin administration had no difference in the primary outcome of neonatal hypoglycemia. Patients should be given the option of both glycemic management strategies intrapartum.

904-P: 12-Month Treatment Satisfaction (TS) and Fear of Hypoglycemia (FoH) Outcomes in the ADAPT Study—A Randomized Controlled Trial Comparing an Advanced Hybrid Closed-Loop System (AHCL) to Multiple Daily Injections (MDI) with Intermittently Scanned CGM (isCGM)

Objective: To assess whether TS &amp; FoH improvements achieved with the MiniMed™ 780G AHCL system compared to MDI+isCGM therapy in adults with sub-optimally controlled type 1 diabetes participating in the ADAPT study phase (6 months) are maintained during the continuation phase (12 months) and reproduced in the MDI+isCGM control arm after cross over to AHCL. Methods: TS was measured with the Diabetes Treatment Satisfaction Questionnaire status and change (DTSQs/c) and FoH with the Hypoglycemia Fear Survey (HFS). Endpoints were within-arm changes from 6 to 12 months. Results: At 12 months, A1c (7.4%) and TS &amp; FoH scores achieved with AHCL at 6 months were maintained (Fig). In the control arm switching to AHCL, improved A1c (7.5%) was reproduced. Mean DTSQs score increased significantly (21.9 to 29.9, P&amp;lt;0.0001) with significant improvements in perceived frequency of hyper (P&amp;lt;0.001) &amp; hypoglycemia (P=0.0206). Results were consistent for DTSQc except no significant change in perceived frequency of hypo was observed. Median HFS score decreased by 6.5 points (P=0.0306). Conclusion: At 12 months, improved TS &amp; FoH observed in the AHCL arm were sustained, while substantial improvements in TS &amp; reduced FoH were seen in the MDI+isCGM arm after switching to AHCL. Disclosure O.Cohen: Employee; Medtronic. P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. J.Shin: Employee; Medtronic. R.Re: Employee; Medtronic. J.Castañeda: Employee; Medtronic. L.H.Vorrink - de groot: Employee; Medtronic. A.Ozdemir saltik: Employee; Medtronic. S.De portu: Employee; Medtronic, Stock/Shareholder; Medtronic. Funding Medtronic

148-OR: CGM Time Below Range Predicts Epinephrine Response to Hypoglycemia in Patients with Type 1 Diabetes

Identifying T1D patients with impaired awareness of hypoglycemia (IAH) is essential, as these patients are at ~10-fold risk of severe hypoglycemia. Defining IAH has relied on questionnaires such as Clarke score that are rarely used in clinical practice. Additional tools are needed to stratify hypoglycemia risk in patients with T1D. Here we show that CGM metrics correlate with physiologic response to hypoglycemia. We measured serum epinephrine levels in 22 subjects with T1D (ages 28-52, A1c 6.1-7.2, median Clarke score 3) during a hyperinsulinemic-hypoglycemic clamp. Baseline CGM data was collected for 2 weeks prior to clamp. These data show a novel, inverse relationship between CGM time below range (TBR, &amp;lt;70 mg/dL) and epinephrine response (EpiR, pg/mL/min) FIGURE. CGM TBR (ρ = -0.562, p = 0.006), Clarke score (ρ = -0.592, p = 0.03), and older age (ρ = -0.500, p = 0.015) were inversely associated with EpiR. Higher average glucose was associated with increased EpiR while time in range, coefficient of variation, BMI, and duration of T1D showed no significant association with EpiR. Our study suggests that CGM TBR predicts counterregulatory dysfunction in T1D. CGM TBR demonstrated a robust, inverse correlation with EpiR similar to the validated Clarke survey. CGM is now the gold standard for glycemic monitoring in T1D, and the percentage TBR may help identify patients at highest risk for severe hypoglycemia outcomes. Disclosure R.L.Thomas: None. J.M.Gregory: Advisory Panel; Eli Lilly and Company, vTv Therapeutics, Other Relationship; Medtronic. E.R.Giovannetti: None. S.C.Boeder: Consultant; Cecelia Health, Research Support; Dexcom, Inc., REMD Biotherapeutics, Eli Lilly and Company. J.Pettus: Advisory Panel; Sanofi, Novo Nordisk, Lilly, MannKind Corporation, Consultant; Carmot Therapeutics, Inc., Diasome. Funding JDRF (2-SRA-2018-606-M-B, 5-ECR-2020-950-A-N); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK123392)

Prevalence Risk Factors and Early Outcome of Hypoglycemia in Neonates Born at Mwananyamala and Kairuki Hospitals Dar es Salaam Tanzania

Prevalence Risk Factors and Early Outcome of Hypoglycemia in Neonates Born at Mwananyamala and Kairuki Hospitals Dar es Salaam Tanzania

Findings for iGlarLixi versus BIAsp 30 confirmed in groups of people with type 2 diabetes with different biomedical characteristics.

To report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics. SoliMix (EudraCT 2017-003370-13) compared once-daily iGlarLixi (a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide) with twice-daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function. No evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P> 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P= 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events. Treatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well-tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics.

Evaluation of Care Outcomes of Patients Receiving Hyperkalemia Treatment With Insulin in Acute Care Tertiary Hospital Emergency Department

IntroductionTreatment of hyperkalemia using intravenous insulin can result in severe hypoglycemia, but regular blood glucose monitoring is not standardized. This study aimed to (i) explore the demographics of adult patients receiving hyperkalemia treatment and (ii) identify the incidence rate of hypoglycemia and associated demographic or clinical characteristics. MethodsA descriptive design with prospective data collection was used. This study recruited 135 patients who received hyperkalemia treatment in the emergency department. Structured blood glucose monitoring was conducted at 1, 2, 4, and 6 hours after receiving intravenous insulin. Univariate analyses of association between demographic and clinical variables and hypoglycemia outcome were performed. ResultsThere were 31 hypoglycemic events, with 11.9%, 7.4%, 2.2%, and 1.5% occurring at the 1, 2, 4, and 6 hours after treatment. The logit regression showed no significantly increased risk of hypoglycemia in terms of the demographic and clinical variables. DiscussionThe variation in blood glucose response observed in this study combined with the high incidences of hypolycaemia indicated the need for frequent and longer duration of monitoring for patients who were being treated for hyperkalaemia with IDT.

HYPOGLYCEMIA IS ASSOCIATED WITH INCREASED IN-HOSPITAL MORTALITY IN PATIENTS WITH ACUTE PANCREATITIS ADMITTED TO THE ICU: A NATIONWIDE STUDY

HYPOGLYCEMIA IS ASSOCIATED WITH INCREASED IN-HOSPITAL MORTALITY IN PATIENTS WITH ACUTE PANCREATITIS ADMITTED TO THE ICU: A NATIONWIDE STUDY

Glycemic Outcomes of Hospitalized Patients on Ambulatory Humulin-R U-500 Insulin

ObjectiveManaging hospitalized patients on ambulatory U-500 insulin is challenging because of limited guidance on how to safely adjust insulin doses during admission. We sought to evaluate glycemic outcomes in relation to inpatient insulin doses in patients receiving U-500 prior to hospitalization. MethodsRetrospective study of hospitalized patients on ambulatory U-500 seen consecutively from January 2015 to December 2019. Primary outcomes were inpatient hypoglycemia, hyperglycemia, and normoglycemia at different insulin dosages expressed as weight-based (unit/kg/d) inpatient total daily dose (TDD) and ratio of inpatient to outpatient TDD. ResultsWe identified 66 admissions of 46 unique patients. The median (interquartile range) body mass index was 41.0 kg/m2 (35.1, 46.8), home TDD 212 units (120, 300), and home insulin dose 1.6 units/kg/d (1.1, 2.2). The median (interquartile range) inpatient insulin dose was 0.7 unit/kg/d (0.3, 1.0) and the ratio of inpatient to outpatient TDD was 0.4 (0.2, 0.8). Hyperglycemia persisted throughout the hospitalization. For the outcomes of hyperglycemia and normoglycemia, we found no association between increased levels of insulin dosages. For the outcome of hypoglycemia, significantly higher odds were observed when non-fasting patients received an inpatient TDD that was either > 40% of their home TDD or > 0.6 unit/kg/d of insulin. ConclusionPatients on ambulatory U-500 have significant hyperglycemia during admission. Inpatient insulin doses of 40% of home TDD or ≤ 0.6 unit/kg were not associated with increased hypoglycemia risk. Further prospective studies are needed to determine effective doses in these high-risk patients.

Improved patient-reported outcomes with iGlarLixi versus premix BIAsp 30 in people with type 2 diabetes in the SoliMix trial.

To assess patient-reported outcomes (PROs) in the SoliMix trial, which compared the efficacy and safety of iGlarLixi versus BIAsp 30 in people with type 2 diabetes (T2D). SoliMix (EudraCT: 2017-003370-13), a 26-week, open-label study, randomized (1:1) 887 adults with T2D and HbA1c≥7.5%-≤10.0% (≥58-≤86 mmol/mol) on basal insulin plus oral antihyperglycaemic drugs (OADs) to once-daily iGlarLixi or twice-daily premix insulin, BIAsp 30. PROs were assessed using the Treatment-Related Impact Measure Diabetes (TRIM-D) and Global Treatment Effectiveness Evaluation (GTEE) questionnaires. Over 26 weeks, iGlarLixi showed greater improvement from baseline versus BIAsp 30 in total TRIM-D score (least squares mean difference [95% confidence interval]: 5.08 [3.69, 6.47]; effect size: 0.32) and in each TRIM-D domain, with the greatest differences seen in diabetes management (8.47 [6.11, 10.84]) and treatment burden (6.95 [4.83, 9.07]). GTEE scores showed a greater proportion of participants and physicians rated a complete or marked improvement of diabetes control with iGlarLixi (80.5%, 82.8%) versus BIAsp 30 (63.3%, 65.1%) at week 26. Post hoc analyses showed that after adjusting for HbA1c, body weight and hypoglycaemia outcomes, iGlarLixi continued to show greater improvements in TRIM-D total scores versus BIAsp 30. In addition to better glycaemic control, weight benefit and less hypoglycaemia, once-daily iGlarLixi provided improved diabetes management, treatment burden and perceived effectiveness versus twice-daily premix BIAsp 30, further supporting iGlarLixi as an advanced treatment option in people with suboptimally controlled T2D on basal insulin plus OADs.

Management and Outcomes of Severe Hypoglycemia Treated by Emergency Medical Services in the U.S. Upper Midwest.

To examine factors associated with emergency department (ED) transport after hypoglycemia treated by emergency medical services (EMS) and assess the impact of ED transport on severe hypoglycemia recurrence. We retrospectively analyzed electronic health records of a multistate advanced life support EMS provider and an integrated healthcare delivery system serving an overlapping geographic area in the upper Midwest. For adults with diabetes treated by EMS for hypoglycemia between 2013 and 2019, we examined rates of ED transport, factors associated with it, and its impact on rates of recurrent hypoglycemia requiring EMS, ED, or hospital care within 3, 7, and 30 days. We identified 1,977 hypoglycemia-related EMS encounters among 1,028 adults with diabetes (mean age 63.5 years [SD 17.7], 55.2% male, 87.4% non-Hispanic White, 42.4% rural residents, and 25.6% with type 1 diabetes), of which 46.4% resulted in ED transport (31.1% of calls by patients with type 1 diabetes and 58.0% of calls by patients with type 2 diabetes). Odds of ED transport were lower in patients with type 1 diabetes (odds ratio [OR] 0.44 [95% CI 0.31-0.62] vs. type 2 diabetes) and higher in patients with prior ED visits (OR 1.38 [95% CI 1.03-1.85]). Within 3, 7, and 30 days, transported patients experienced recurrent severe hypoglycemia 2.8, 5.2, and 10.6% of the time, respectively, compared with 7.4, 11.2, and 22.8% of the time among nontransported patients (all P < 0.001). This corresponds to OR 0.58 (95% CI 0.42-0.80) for recurrent severe hypoglycemia within 30 days for transported versus nontransported patients. When subset by diabetes type, odds of recurrent severe hypoglycemia among transported patients were 0.64 (95% CI 0.43-0.96) and 0.42 (95% CI 0.24-0.75) in type 1 and type 2 diabetes, respectively. Transported patients experienced recurrent hypoglycemia requiring medical attention approximately half as often as nontransported patients, reinforcing the importance of engaging patients in follow-up to prevent recurrent events.

808-P: Association between Analogue Compared with Human Insulin and the Outcomes of Mortality, Hospitalization, MACE, and Hypoglycemia in Hemodialysis Patients with Type 2 Diabetes: The ARO Research Initiative

Aims: Poor glycemic control may contribute to the very high mortality rate in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) . Whether analogue compared to human insulin therapy associates with different outcomes is unknown. Methods: Incident HD patients with T2D on insulin treatment enrolled at one of the 288 Fresenius Medical Care facilities across 7 European countries between 2007-20were identified using an established administrative data algorithm. All patients were censored after 3 years of observation. Following multiple imputation, inverse probably weighting (IPW) and instrumental variable (IV; using country) analyses were used to generate Cox-proportional hazards to estimate analogue compared to human insulin hazard ratios for all-cause mortality (ACM) , MACE, hospitalization, and confirmed hypoglycemia (&amp;lt;3.0 mmol/L during a dialysis session) . Results: About 713 analogue users were compared to 733 subjects treated with human insulin. Significant variation in prescription by country was observed. IPW hazard ratios [95% confidence intervals] for patients on analogue compared to human insulin were 0.8[0.659-0.991] for ACM (p=0.042) , 0.817 [0.679-0.983] for MACE (p=0.033) , 0.757 [0.665-0.861] for hospitalization (p&amp;lt;0.001) , and 1.6[1.1419-2.268] for hypoglycemia (p=0.008) . Consistent strength and direction of the associations were observed in the IV analysis and across sensitivity analyses. Conclusions: In this large, multinational cohort of patients with T2D on HD, compared to human insulins, analogue insulins were associated with better clinical outcomes, although hypoglycemia rates were increased. Whether analogue insulins represent the preferred therapy in this group requires confirmatory evidence from a clinical trial. Disclosure T. Ebert: Consultant; Sanofi, Santis. Research Support; AstraZeneca, Novo Nordisk. N. Sattar: None. M. Greig: None. C. Lamina: None. K. Eckardt: Consultant; Akebia Therapeutics, Inc. Research Support; Bayer AG, Evotec International GmbH, Fresenius Medical Care. Speaker's Bureau; AstraZeneca, Bayer AG, Otsuka Pharmaceutical Co., Ltd. J. Floege: Other Relationship; Novo Nordisk A/S. F. Kronenberg: Advisory Panel; Amgen Inc., Novartis AG. P. Stenvinkel: Advisory Panel; AstraZeneca, Baxter, Fresenius Medical Care, Reata Pharmaceuticals, Inc., Vifor Pharma Management Ltd. Speaker's Bureau; Astellas Pharma Inc., Bayer AG, Novo Nordisk. D.C. Wheeler: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Global Services, LLC, Merck Sharp &amp; Dohme Corp., Mundipharma, Tricida, Inc., Vifor Pharma Management Ltd. Consultant; AstraZeneca. Speaker's Bureau; Amgen Inc., Astellas Pharma Inc. J. Fotheringham: Advisory Panel; Novartis Pharmaceuticals Corporation. Speaker's Bureau; Fresenius Medical Care, Novartis Pharmaceuticals Corporation, Vifor Pharma Management Ltd. Funding Amgen (Europe) GmbH- Rotkreuz, Switzerland- Swedish Research Council (grant 2009-1068) - Swedish Heart and Lung Foundation (20160384) - Njurfonden- Westmans Foundation- Novo Nordisk (Postdoctoral fellowship program run inpartnership with Karolinska Institutet, Stockholm,Sweden) - Karolinska Institutet Research Foundation - EFSD (EFSD Mentorship Programme supported by AstraZeneca) - German Research Foundation (SFB TRR 219, projects C1 and M1) - National Institute for Health Research (UK) (Clinician Scientist Award)

231-OR: Antecedent Hypoglycemia Increases Damage Due to a Subsequent Myocardial Infarction in Rats

Several clinical trials have noted an association between hypoglycemia and major cardiovascular events; however, a direct link between antecedent hypoglycemia and worse cardiac outcomes has not been established. We hypothesized that antecedent recurrent hypoglycemia predisposes the heart to increased damage following a subsequent myocardial infarction. To test this hypothesis, adult Sprague Dawley rats were subjected to 3 days of recurrent insulin-induced hypoglycemia (25-30 mg/dl, 90 minutes each day; n = 6) or saline (control, n = 6) . On the following day, all rats underwent a myocardial infarction (MI) induced by occlusion of the left anterior descending artery for 30 minutes followed by reperfusion for 60 minutes. Electrocardiograms indicated ST elevation during the MI, which returned to normal sinus rhythm upon reperfusion. Hearts were removed immediately and analyzed for damage. MI induced ventricular damage from rats that underwent antecedent recurrent hypoglycemia (39 ± 5%) was significantly higher than control rats (16 ± 4%; p&amp;lt;0.001, Figure) . Additionally, plasma norepinephrine levels were elevated 14-fold in rats that underwent recurrent hypoglycemia. These studies indicate that antecedent hypoglycemia directly contributes to worse outcomes following an MI and that increased norepinephrine is associated with this damage. Disclosure C.G.Christensen: None. S.Fisher: None. C.M.Reno: None. Funding University of Utah’s Driving Out Diabetes, a Larry H. Miller Family Wellness InitiativeNational Institutes of Health (P30 DK020579) Juvenile Diabetes Research Foundation (1-FAC-2020-984-A-N)

Insulin Dosing and Glycemic Outcomes Among Steroid-treated Hospitalized Patients

ObjectiveTo determine the optimal insulin-to-steroid dose ratio for the attainment of glycemic control in hospitalized patients. MethodsWe retrospectively studied data collected from the electronic health records within an academic medical center from 18 599 patient-days where patients were treated concurrently with insulin and steroids. Multivariate logistic regression analyses, which included demographic and clinical variables, were performed to assess the relationships between the exposures of total and basal insulin-to-steroid ratios and the outcomes of glycemic control (all blood glucose readings on the following patient-day were >70 and ≤180 mg/dL) and hypoglycemia within 3 subgroups of steroid dosing: low (≤10-mg prednisone equivalent dose [PED]), medium (from >10-mg to ≤40-mg PED), and high (>40-mg PED). ResultsIncreased insulin-to-steroid ratio was associated with increased odds of both glycemic control and hypoglycemia. The optimal total insulin-to-steroid ratio for attaining glycemic control was 0.294 U/kg/10-mg PED in the low-dose subgroup, 0.257 U/kg/10-mg PED in the medium-dose subgroup, and 0.085 U/kg/10-mg PED in the high-dose subgroup. The optimal basal insulin-to-steroid ratio was 0.215 U/kg/10-mg PED in the low-dose subgroup, 0.126 U/kg/10-mg PED in the medium-dose subgroup, and 0.036 U/kg/10-mg PED in the high-dose subgroup. ConclusionIncreasing insulin-to-steroid ratios are positively associated with glycemic control and hypoglycemia. Our study suggests that approximately 0.3 U/kg/10-mg PED is an optimal dose for low- and medium-dose steroids, whereas approximately 0.1 U/kg/10-mg PED is an optimal dose for high-dose steroids. Further prospective studies are needed to identify insulin regimens that will optimize glycemic control in steroid-treated patients while minimizing the risk of hypoglycemia.

Safety, efficacy, and cost-effectiveness of insulin degludec U100 versus insulin glargine U300 in adults with type 1 diabetes: a systematic review and indirect treatment comparison.

Clinical differences between degludec U100 (Deg-100) and glargine U300 (Gla-300) in type 1 diabetes (T1D) were unknown. To indirectly compare the safety, efficacy, and cost-effectiveness between Deg-100 and Gla-300 in T1D adults via systematic review. Medline, the Cochrane Library, ClinicalTrials.gov, and Google Scholar were searched (October 2021). Randomized controlled trials comparing Deg-100 or Gla-300 vs. glargine U100 in T1D adults (follow-up ≥ 12weeks) were selected and analyzed using a frequentist network meta-analysis. Cost-effectiveness analysis (CEA) was conducted over a 1-year time horizon from societal perspectives. Nine trials were included. Efficacy analysis suggested that Deg-100 was non-inferior to Gla-300 in reducing HbA1c (MD 0.03 [95%CI - 0.09 to 0.15];P = 0.60), FPG (MD - 1.12 [- 2.19 to - 0.04];P = 0.04), and pre-breakfast SMBG (MD - 0.71 [- 1.46 to 0.03];P = 0.06). Safety analysis suggested that Deg-100 appeared to have lower rates of both severe (HR 0.44 [0.25-0.78]; P = 0.005) and nocturnal severe (HR 0.19 [0.08-0.44]; P < 0.001) hypoglycemia, with lower total (MD - 0.07 [- 0.13 to - 0.01];P = 0.02) and basal (MD - 0.08 [- 0.12 to - 0.04];P < 0.001) insulin doses compared with Gla-300. No significant differences were observed for other hypoglycemia outcomes, adverse events, serious adverse events, bolus insulin dose, and body weight. The CEA showed that Deg-100 appeared to be a dominant treatment in Japan (+ 0.0283 QALYs, ¥26,266 [$228] per patient) and the United States (+ 0.0267 QALYs, $986 per patient). Low-certainty indirect evidence suggested that Deg-100 appeared to have a favorable reduction in rates of severe hypoglycemia and more cost-effective compared with Gla-300 in T1D adults.