Severe Hypoglycemic Events Research Articles

Multicenter Trial of a Tubeless, On-Body Automated Insulin Delivery System With Customizable Glycemic Targets in Pediatric and Adult Participants With Type 1 Diabetes.

OBJECTIVEAdvances in diabetes technology have transformed the treatment paradigm for type 1 diabetes, yet the burden of disease is significant. We report on a pivotal safety study of the first tubeless, on-body automated insulin delivery system with customizable glycemic targets.RESEARCH DESIGN AND METHODSThis single-arm, multicenter, prospective study enrolled 112 children (age 6–13.9 years) and 129 adults (age 14–70 years). A 2-week standard therapy phase (usual insulin regimen) was followed by 3 months of automated insulin delivery. Primary safety outcomes were incidence of severe hypoglycemia and diabetic ketoacidosis. Primary effectiveness outcomes were change in HbA1c and percent time in sensor glucose range 70–180 mg/dL (“time in range”).RESULTSA total of 235 participants (98% of enrolled, including 111 children and 124 adults) completed the study. HbA1c was significantly reduced in children by 0.71% (7.8 mmol/mol) (mean ± SD: 7.67 ± 0.95% to 6.99 ± 0.63% [60 ± 10.4 mmol/mol to 53 ± 6.9 mmol/mol], P < 0.0001) and in adults by 0.38% (4.2 mmol/mol) (7.16 ± 0.86% to 6.78 ± 0.68% [55 ± 9.4 mmol/mol to 51 ± 7.4 mmol/mol], P < 0.0001). Time in range was improved from standard therapy by 15.6 ± 11.5% or 3.7 h/day in children and 9.3 ± 11.8% or 2.2 h/day in adults (both P < 0.0001). This was accomplished with a reduction in time in hypoglycemia <70 mg/dL among adults (median [interquartile range]: 2.00% [0.63, 4.06] to 1.09% [0.46, 1.75], P < 0.0001), while this parameter remained the same in children. There were three severe hypoglycemia events not attributable to automated insulin delivery malfunction and one diabetic ketoacidosis event from an infusion site failure.CONCLUSIONSThis tubeless automated insulin delivery system was safe and allowed participants to significantly improve HbA1c levels and time in target glucose range with a very low occurrence of hypoglycemia.

Association of Type 1 Diabetes and Hypoglycemic and Hyperglycemic Events and Risk of Dementia.

To determine whether severe hypoglycemic and hyperglycemic events are associated with longitudinal dementia risk in older adults with type 1 diabetes. A longitudinal cohort study followed up 2,821 members of an integrated health care delivery system with type 1 diabetes from 1997 to 2015. Hypoglycemic and hyperglycemic events requiring emergency room or hospitalization were abstracted from medical records beginning January 1, 1996, through cohort entry. Participants were followed up for dementia diagnosis through September 30, 2015. Dementia risk was examined with Cox proportional hazard models adjusted for age (as time scale), sex, race/ethnicity, hemoglobin A1c, depression, stroke, and nephropathy. Among 2,821 older adults (mean age 56 years) with type 1 diabetes, 398 (14%) had a history of severe hypoglycemia, 335 (12%) had severe hyperglycemia, and 87 (3%) had both. Over a mean 6.9 years of follow-up, 153 individuals (5.4%) developed dementia. In fully adjusted models, individuals with hypoglycemic events had 66% greater risk of dementia than those without a hypoglycemic event (hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.09, 2.53), while those with hyperglycemic events had >2 times the risk (HR 2.11, 95% CI 1.24, 3.59) than those without a hyperglycemic event. There was a 6-fold greater risk of dementia in individuals with both severe hypoglycemia and hyperglycemia vs those with neither (HR 6.20, 95% CI 3.02, 12.70). For older individuals with type 1 diabetes, severe hypoglycemic and hyperglycemic events are associated with increased future risk of dementia.

Effect of Continuous Glucose Monitoring on Glycemic Control in Patients With Type 2 Diabetes Treated With Basal Insulin

Continuous glucose monitoring (CGM) has been shown to be beneficial for adults with type 2 diabetes using intensive insulin therapy, but its use in type 2 diabetes treated with basal insulin without prandial insulin has not been well studied. To determine the effectiveness of CGM in adults with type 2 diabetes treated with basal insulin without prandial insulin in primary care practices. This randomized clinical trial was conducted at 15 centers in the US (enrollment from July 30, 2018, to October 30, 2019; follow-up completed July 7, 2020) and included adults with type 2 diabetes receiving their diabetes care from a primary care clinician and treated with 1 or 2 daily injections of long- or intermediate-acting basal insulin without prandial insulin, with or without noninsulin glucose-lowering medications. Random assignment 2:1 to CGM (n = 116) or traditional blood glucose meter (BGM) monitoring (n = 59). The primary outcome was hemoglobin A1c (HbA1c) level at 8 months. Key secondary outcomes were CGM-measured time in target glucose range of 70 to 180 mg/dL, time with glucose level at greater than 250 mg/dL, and mean glucose level at 8 months. Among 175 randomized participants (mean [SD] age, 57 [9] years; 88 women [50%]; 92 racial/ethnic minority individuals [53%]; mean [SD] baseline HbA1c level, 9.1% [0.9%]), 165 (94%) completed the trial. Mean HbA1c level decreased from 9.1% at baseline to 8.0% at 8 months in the CGM group and from 9.0% to 8.4% in the BGM group (adjusted difference, -0.4% [95% CI, -0.8% to -0.1%]; P = .02). In the CGM group, compared with the BGM group, the mean percentage of CGM-measured time in the target glucose range of 70 to 180 mg/dL was 59% vs 43% (adjusted difference, 15% [95% CI, 8% to 23%]; P < .001), the mean percentage of time at greater than 250 mg/dL was 11% vs 27% (adjusted difference, -16% [95% CI, -21% to -11%]; P < .001), and the means of the mean glucose values were 179 mg/dL vs 206 mg/dL (adjusted difference, -26 mg/dL [95% CI, -41 to -12]; P < .001). Severe hypoglycemic events occurred in 1 participant (1%) in the CGM group and in 1 (2%) in the BGM group. Among adults with poorly controlled type 2 diabetes treated with basal insulin without prandial insulin, continuous glucose monitoring, as compared with blood glucose meter monitoring, resulted in significantly lower HbA1c levels at 8 months. ClinicalTrials.gov Identifier: NCT03566693.

69-LB: Nonadjunctive Continuous Glucose Monitoring to Control Hypoglycemia (COACH)

Previous studies have been insufficiently powered to assess whether CGM can reduce severe hypoglycemia. The Continuous Monitoring and Control of Hypoglycemia study evaluated nonadjunctive use of the Dexcom CGM system for diabetes management decisions in adults new to CGM. This post-approval 12-month observational study enrolled adults with insulin-requiring diabetes who based diabetes management and insulin dosing decisions on self-monitored blood glucose (SMBG) values for 6 months and then on CGM for 6 months. Per protocol, diabetes management was per usual care. Subjects were queried monthly about hypoglycemic and diabetic ketoacidosis (DKA) events. The primary outcome was change in moderate (requiring third party assistance) and severe (seizure or loss of consciousness) hypoglycemic event frequency between SMBG and CGM phases; secondary outcomes included DKA events. The per-protocol population included all 519 adult subjects who completed the 12-month visit with mean±SD age 50.3±16.1 y, A1C 8.0±1.4%, 32.8% with impaired hypoglycemia awareness, 54.1% male, 66.5% and 33.5% with T1D/T2D, and 29.7% using pumps. Compared to the SMBG phase, the frequency of moderate and severe hypoglycemic events was significantly (p=0.0051) lower during the CGM phase; DKA frequency was also lower (Table). Compared to SMBG, nonadjunctive CGM use reduces rates of severe hypoglycemia and DKA. Disclosure S. Beck: Employee; Self; Dexcom, Inc. C. Kelly: Consultant; Self; Ajinomoto Co., Inc., Dexcom, Inc., Hitachi, Ltd., Vascular Dynamics Inc. N. Njeru: None. J. J. Gorelick: Employee; Self; Dexcom, Inc., Edwards Lifesciences. J. C. Bowers: Employee; Self; Dexcom, Inc. D. A. Price: Employee; Self; Dexcom, Inc.

1146-P: Persistent Graft Function after Islet Allotransplantation Into Prevascularized Sernova Cell Pouch Device: Preliminary Results from the University of Chicago

Introduction: Pre-vascularized Sernova Cell Pouch (SCP) device was developed to provide an optimal environment for cell/islet engraftment in the extravascular space. A first-in-human pilot study showed SCP safety/islet vascularization; however, conditions did not allow detectable islet function. We present preliminary results of phase I/II study testing safety and efficacy of modified SCPs in islet allotransplantation (ITx). Material and Methods: 6 patients with longstanding T1DM and multiple severe hypoglycemic events (SHEs) were enrolled. Immunosuppression (Thymoglobulin, Tacrolimus, and Mycophenolate) was initiated 3 weeks after abdominal wall SCP surgical implantation. ITx occurred at 3 weeks and 6 months after implantation. Sentinel SCPs were explanted for histopathological evaluation 3 months after transplant. Islet graft function was assessed based on continuous glucose monitoring (CGM), c-peptide, and insulin requirement. Results: First patient presented with persistent stimulated serum c-peptide at 6 months after 1st and 2nd ITx into SCP. After 2nd ITx, glucose control improved substantially reaching optimal target values for CGM with only 5% of Time Below Range (TBR). Second patient at 3 months after 2nd ITx had positive stimulated serum c-peptide (0.48 ng/mL) with reduction of HbA1c from 10.6% to 7.6%, decreased insulin requirement from 49 to 28 u/day, improved CGM with TBR &amp;lt;4%, and reduction in Time Above Range (from 75% to 48%). Two patients await ITx and evaluation. Conclusion: Persistent islet graft function with sustained blood levels of c-peptide, reduction of HbA1c, improved CGM parameters, reduction of SHEs, and decreased total daily insulin requirement was achieved in first 2 patients after ITx into abdominal wall SCPs. Modified approaches, including suspending islets in serum, optimizing islets/dose, and smaller pellet volumes, will likely improve engraftment and outcomes. Disclosure P. J. Bachul: None. B. Juengel: None. J. Kumar: None. C. C. Thomas: None. L. H. Philipson: Advisory Panel; Self; Nevro Corp., Research Support; Self; Provention Bio, Inc. J. Fung: None. P. Witkowski: None. G. S. Generette: None. J. S. Pyda: None. P. Borek: None. A. Perez-gutierrez: None. K. Golab: None. L. Basto: None. L. Perea: None. M. Tibudan: None. Funding JDRF; Sernova, Corp.

557-P: Patient and Caregiver Experiences during Severe Hypoglycemia: A Qualitative Assessment

Among people with diabetes (PWD) using insulin, severe hypoglycemia (SH) can be a life threatening complication, if untreated. The personal experiences of SH from the perspective of PWD and their caregivers (CG) are not well characterized. This study assessed the perceptions of the event and decision-making processes of PWD (T1D n=36; T2D n=24) and their CGs during SH.In-depth one-on-one telephone interviews were conducted with dyads of US PWD and CGs (n=120). An initial synopsis and inductive codebook schema were used to analyze the data with 2 independent coders (kappa=0.87-0.89). Themes were developed from the codes, and codes were re-mapped to the themes.The four themes included: (1) CGs scramble to do the right thing and support PWD in treating SH. (2) Decision-making capacity is impaired during a SH event (SHE), often a panicked time. (3) Discussion with healthcare providers (HCPs) about SH, and particularly about treatment, is limited. (4) PWD and CGs learn to manage SH through their own experiences and frequently make lifestyle changes to prevent and treat future events. See Exhibit for details.This study finds that SHEs are characterized by high intensity emotions for PWD and CGs that can impair decision-making. Additionally, much of PWD and CG knowledge about SH treatment derives from prior experience rather than HCP guidance, suggesting a need for more proactive discussions with HCPs regarding SH management.View largeDownload slideView largeDownload slide DisclosureH. L. Stuckey: Consultant; Self; Eli Lilly and Company, Consultant; Spouse/Partner; Eli Lilly and Company. U. Desai: Consultant; Self; Eli Lilly and Company. S. B. King: Consultant; Self; Eli Lilly and Company. L. Popadic: Consultant; Self; Eli Lilly and Company. W. Levinson: Consultant; Self; Eli Lilly and Company. N. Kirson: Consultant; Self; Eli Lilly and Company. E. R. Hankosky: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. B. Mitchell: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company.FundingEli Lilly and Company

136-LB: Budget Impact of Adding Flash Continuous Glucose Monitoring (CGM) to Medicaid Formularies

Despite evidence pointing to clinical benefits of CGM, access has been limited by many state Medicaid plans. We assessed the budget impact of providing flash CGM to members with type 1 (T1D) or type 2 diabetes (T2D) taking multiple daily injections of insulin (MDI). We included the total US Medicaid and CHIP population. Using published data, we estimated rates of severe hypoglycemic events (SHE), diabetic ketoacidosis and other severe hyperglycemic events (DKA) as well as risk reduction from use of flash CGM for the various types of events and for reduction in HbA1c. Blood glucose monitoring (BGM) frequency was sourced from clinical trials. Costs for BGM, flash CGM, and unit costs for SHE and DKA and impact of HbA1c reductions were obtained from published literature and inflated to 2019. Increased use of the flash CGM in T1D and T2D MDI populations is almost cost-neutral from a Medicaid perspective. Increasing the population proportion using flash CGM (and the remainder using BGM) from a hypothetical share of 23% to 33% was associated with a $23 million overall decrease to the budget in one year. The analysis illustrates that although the unit cost of CGM is greater than blood glucose monitoring, cost offsets due to reductions in complications can lead to overall cost savings. This finding is important because health inequities, such as access to diabetes technology, are associated with poorer outcomes. Disclosure J. Frank: None. R. Hellmund: Employee; Self; Abbott Diabetes. N. Virdi: Employee; Self; Abbott Diabetes, Stock/Shareholder; Self; Johnson & Johnson. D. B. Blissett: Consultant; Self; Abbott Diabetes, Consultant; Spouse/Partner; Abbott Diabetes.

341-P: Effect of Pitolisant on Glucagon in Human Islets and People with Type 1 Diabetes

In 3D human islet microtissues from nondiabetic donors, pitolisant, a histamine 3 receptor antagonist, increased glucagon secretion &amp;gt;3-fold compared to vehicle control. However, the effect of pitolisant on glucagon was diminished in islets treated with cytokines, insulin, and low glucose to mimic T1D hypoglycemia. The purpose of this study was to determine if pitolisant can restore impaired glucagon secretion response to hypoglycemia in people with T1D. The study was a double-blind randomized placebo-controlled study of five adults (3 on pitolisant and 2 on placebo), 4 men, with long-duration T1D. Patients were domiciled overnight, at baseline and after 7 days of once daily oral pitolisant (36 mg) or matching placebo. Blood glucose levels were kept at 100-120 mg/dL overnight with regular insulin infusion and an insulin tolerance test (ITT) was conducted the following morning. Glucagon was measured by the Mercodia ELISA and glucose by a YSI Glucose Analyzer. Glucose was also assessed using a blinded Dexcom G6 CGM during the trial. Safety tolerability was assessed by standard methods. Mean change (95% CI) from baseline in peak glucagon (pg/ml) was 7.5 (-2.07-17.02) for the pitolisant group and 13.1 (2.08-24.09) for the placebo group. One patient on pitolisant and no patients on placebo returned to blood glucose &amp;gt;/=70 mg/dL during the 180-minute ITT. The pitolisant group required significantly less rescue D50 on-drug vs. at baseline (5 vs. 19 grams, p=0.05), while there was no difference in the placebo group (36 vs. 25 grams). In general, patients on pitolisant had numerically higher mean glucose on CGM during the on-drug period. There were no severe hypoglycemic events and no deaths. Pitolisant was well tolerated. We conclude that pitolisant does not increase glucagon secretion during hypoglycemia in people with T1D but may mitigate hypoglycemia by a glucagon-independent mechanism. The T1D islet microtissue model better predicts the clinical effects of pitolisant on glucagon secretion compared to healthy islets. Disclosure C. A. Dehn: None. M. Fein: None. J. Hu: None. B. Yesildag: None. R. Maxwell: Other Relationship; Self; Ferox Therapeutics LLC. J. B. Harp: Other Relationship; Self; Ferox Therapeutics. Funding Ferox Therapeutics; The Leona M. and Harry B. Helmsley Charitable Trust

137-OR: Dasiglucagon Ready-to-Use Autoinjector Is More Reliably and Quickly Administered than Glucagon Emergency Kit (GEK)

Dasiglucagon is a novel glucagon analog, stable in aqueous solution and suitable for delivery in a ready-to-use autoinjector (HypoPal®) for the treatment of severe hypoglycemia. This study was performed to assess HypoPal device handling vs. GEK during simulated episodes of severe hypoglycemia. Participants included persons with diabetes (PWD) and their caregivers and untrained bystanders (UB) with no experience with diabetes. Participants had no experience with either device. PWD were trained by staff and subsequently trained caregivers (TC) on the use of devices; UB received no instruction on use prior to simulations. Primary outcome was success of TC to correctly use HypoPal vs. GEK. Secondary outcomes included success of UB, time to successful administration, and assessment of confidence in, ease of use of and preference for each device. The success rate was significantly greater for HypoPal vs. GEK in TC (p These data support that dasiglucagon HypoPal use is easier, more reliable, and faster than the use of GEK and offers the potential to improve the time to recovery from a severe hypoglycemic event. Disclosure N. Bailey: Research Support; Spouse/Partner; Zealand Pharma A/S. J. Dimsits: Employee; Self; Zealand Pharma A/S. R. Tehranchi: Employee; Self; Zealand Pharma A/S. D. M. Kendall: Employee; Self; Zealand Pharma A/S, Employee; Spouse/Partner; Amgen Inc., Stock/Shareholder; Self; Eli Lilly and Company, MannKind Corporation. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. Funding Zealand Pharma A/S

Examination of the Igls Criteria for Defining Functional Outcomes of β-cell Replacement Therapy: IPITA Symposium Report.

The Igls criteria were developed to provide a consensus definition for outcomes of β-cell replacement therapy in the treatment of diabetes during a January 2017 workshop sponsored by the International Pancreas & Islet Transplant Association (IPITA) and the European Pancreas & Islet Transplant Association. In July 2019, a symposium at the 17th IPITA World Congress was held to examine the Igls criteria after 2 years in clinical practice, including validation against continuous glucose monitoring (CGM)-derived glucose targets, and to propose future refinements that would allow for comparison of outcomes with artificial pancreas system approaches. Utilization of the criteria in various clinical and research settings was illustrated by population as well as individual outcome data of 4 islet and/or pancreas transplant centers. Validation against CGM metrics was conducted in 55 islet transplant recipients followed-up to 10 years from a fifth center. The Igls criteria provided meaningful clinical assessment on an individual patient and treatment group level, allowing for comparison both within and between different β-cell replacement modalities. Important limitations include the need to account for changes in insulin requirements and C-peptide levels relative to baseline. In islet transplant recipients, CGM glucose time in range improved with each category of increasing β-cell graft function. Future Igls 2.0 criteria should consider absolute rather than relative levels of insulin use and C-peptide as qualifiers with treatment success based on glucose assessment using CGM metrics on par with assessment of glycated hemoglobin and severe hypoglycemia events.

347-P: Why Some Americans Use Health Care following Severe Hypoglycemia, and Why Some Do Not: Baseline Results of the iNPHORM Study

Background: Individual and societal determinants can affect the need and propensity for healthcare utilization (HCU) following diabetes-related severe hypoglycemia (SH). This is the first US study to explore the real-world risk factors of HCU- versus non HCU-based SH. Methods: Data were collected online from a generalized cohort of Americans (≥18 years old) with type 1 or type 2 diabetes (T1D, T2D) on insulin and/or secretagogues. Multivariable logistic regression using backward selection was performed to identify the socio-demographic/clinical risk factors of past-year HCU- versus non HCU-based SH (daytime/nocturnal SH resulting in hospital or paramedical services). Results: Results are based on 642 (T1D: 22.7%; female: 46.3%) of 1694 baseline respondents who experienced ≥1 SH events (past year). People with T1D were 40.9 (SD:12.5) years old, while those with T2D were 45.4 (SD: 13.3) years old. Among T2D respondents, 42.5% were on insulin and secretagogues, 31.1% were on insulin alone, and 26.4% on secretagogues alone. Almost half (44.6%) of participants (T1D: 29.9%; T2D: 49.0%) reported ≥1 HCU-based SH events (past year). In the final backward logistic model, the odds of past-year HCU-based SH decreased significantly with female sex, increasing age, decreasing income, and suburban or rural (versus urban) living. Diabetes type did not have an independent effect. However, for individuals on combination insulin-secretagogue therapy, the adjusted odds of HCU-based SH were 2- and 3-times that of those on insulin alone and secretagogues alone, respectively. High A1C (versus &amp;lt;7%) also positively correlated with HCU-based SH; though, this association was marginally insignificant (p=0.065). Conclusion: Our study reveals several factors that can promote or reduce the odds of HCU-based SH. Therapeutic optimizations to mitigate non-essential HCU should prioritize patients on combination insulin-secretagogue therapy and those with poor glycemic control. Disclosure A. Ratzki-leewing: Consultant; Self; Eli Lilly and Company, Novo Nordisk, Other Relationship; Self; Sanofi. J. E. Black: None. B. L. Ryan: None. G. Zou: None. S. B. Harris: Advisory Panel; Self; Abbott Diabetes, Abvance Therapeutics, HLS Therapeutics Inc., Lilly Diabetes, Novo Nordisk A/S, Consultant; Self; Boehringer Ingelheim (Canada) Ltd., mdBriefCase, Other Relationship; Self; American Diabetes Association, AstraZeneca, Novo Nordisk Canada Inc., Sanofi. Funding Sanofi Global

308-OR: Effectiveness of Telemedicine Intervention on Improving Glycemia and Reducing Pharmacologic Therapy in Older Adults with Type 2 Diabetes

Background: We previously demonstrated that carbohydrate restricted nutrition therapy delivered virtually resulted in safe and sustained reduced blood glucose (BG), resulting in deprescription of antihyperglycemic medications in patients with T2D ≤65 years. Given concerns regarding polypharmacy and risk of hypoglycemia (HYPO) in older adults with T2D, this treatment approach may confer benefit. Methods: At the time of analysis, 279 adults aged ≥65 years at enrollment (27% female, 69±1.6 years, HbA1c: 7.5±1.5%) enrolled in our clinic at least 1 year prior. Data were obtained from medical records to assess changes in BG and medication use among patients retained 1 year and incidence of HYPO in all patients enrolled. Patients provided &amp;gt;1 BG per day on average. Glucose values and patient-reported events were used to identify level 1 (54-69 mg/dL), level 2 (&amp;lt;54 mg/dL), and level 3 (severe requiring third-party assistance) HYPO events. Results: Among 201 (72%) patients treated 1 year, mean glucose declined (-18.8±3.7 from 147.3±3.8 mg/dL, p&amp;lt;0.001). Among 144 patients taking 231 medications other than metformin at enrollment, 141/231 (61%) of medications were deprescribed, including 45% of insulins and 85% of sulfonylureas. Among the 38 patients still prescribed insulin at 1 year, the average dosage decreased from 98.5±66.0 to 36.2±29.2 IU/day (p&amp;lt;0.001). The average number of diabetes prescriptions per patient declined from 1.2±0.9 to 0.5±0.7 (p&amp;lt;0.001). There were 149 level 1 HYPO events per 100 person-years (p-y), 28 level 2 events per 100 p-y, and no level 3 events reported. Discussion: The majority of older adults continued treatment for at least 1 year. Improved glycemia concurrent with discontinuation of many high-risk medications and no known severe HYPO events in older adults with T2D suggests this treatment approach may reduce risk and cost associated with polypharmacy and HYPO in older adults with T2D. Disclosure R. N. Adams: Employee; Self; Virta Health Corp., Stock/Shareholder; Self; Virta Health Corp. S. J. Athinarayanan: Employee; Self; Virta Health Corp. C. G. P. Roberts: Employee; Self; Virta Health Corp., Stock/Shareholder; Self; Virta Health Corp. B. M. Volk: Employee; Self; Virta Health Corp., Virta Health Corp. B. Fell: None. A. L. Mckenzie: Employee; Self; Virta Health Corp., Stock/Shareholder; Self; Virta Health Corp.

ATTD 2021 Invited Speaker Abstracts.

ATTD 2021 Invited Speaker Abstracts.

98-LB: Diabeloop DBL4K Hybrid Closed-Loop System Improves Time-in-Range without Increasing Time-in-Hypoglycemia in Children Aged 6–12 Years

Introduction: The DBLG1 Hybrid Closed-Loop system improves time in range and glycemic control in adults. However, the efficacy and safety of the system had not yet been evaluated in children. Objective: of this study is to evaluate the non-inferiority of the DBL4K (Diabeloop for Kids) hybrid closed-loop system (Kaleido pump + Dexcom G6 = CL) compared to a Dexcom G6 sensor augmented pump (open loop = OL) in prepubescent children. Materials and Methods: Multicenter open-label randomized controlled trial in 3 pediatric diabetology centers, 2 of which are French. The CL and OL are allocated for 4 days in hospital, followed by 6 weeks at home for the French centers. Results: Seventeen patients (mean age: 8.3+/- 1.6 years) were included for evaluation at 6 weeks at home between March and December 2019. The percentage of time spent in range (0.7-1.8 g/L) was significantly higher in the CL group during the 6 weeks at home (66.19% in CL vs. 58.68% in OL, p&amp;lt;0.001). The percentage of time spent in hypoglycemia (&amp;lt;0.7 g/L) was significantly lower in the CL group (2.62% in CL vs. 5.24% in OL, p&amp;lt;0.0001) as well as the number of hypoglycemic episodes (25.51 in CL vs. 48.16 in OL, p&amp;lt;0.0001). The coefficient of variation of blood glucose is significantly lower in CL group (31.85% in CL vs. 36.36% in OL, p&amp;lt;0.001). No events of ketoacidosis or severe hypoglycemia were recorded. Conclusions: The DBL4K Closed-Loop System is suitable for prepubescent children. It is not inferior to sensor augmented pump therapy in children. Just as in adults it improves the time in range while decreasing the time spent in hypoglycemia. It could allow for better long-term glucose control in children with diabetes. Disclosure D. Kariyawasam: None. C. Morin: None. K. Casteels: None. C. Le Tallec: None. C. Godot: None. A. Sfez: None. N. Garrec: None. M. Polak: Other Relationship; Self; AMMTeK. G. Charpentier: Other Relationship; Self; Diabeloop. S. Franc: Advisory Panel; Self; Diabeloop SA. Board Member; Self; Novo Nordisk. Research Support; Self; Merck Sharp &amp; Dohme Corp. Stock/Shareholder; Self; Diabeloop SA. Other Relationship; Self; Abbott Diabetes. J. Beltrand: None.

95-OR: Safety and Feasibility Evaluation of Closed-Loop Glycemic Management in Pregnant Women with Type 1 Diabetes

Pregnancy complicated by type 1 diabetes (T1D) is associated with increased maternal and fetal morbidity and mortality. We report results from the first clinical trial testing a closed-loop control (CLC) system specifically designed for pregnant women with T1D in the United States. Eight pregnant women with T1D participated in a 48-hour clinical trial at three US sites (NCT04492566). Women were enrolled in the second trimester after organogenesis was completed. CLC sessions used the interoperable artificial pancreas system (iAPS) running a Zone-Model Predictive Control algorithm designed for stricter glycemic targets for pregnancy. Glycemic target zones were 80-110 mg/dL during the day and 80-100 mg/dL overnight, with assertive insulin delivery in the postprandial period. The primary outcome was sensor glucose time in range (TIR) for pregnancy 63-140 mg/dL as per international consensus guidelines. All enrolled subjects completed the trial. Participants had a mean age of 29.3±3.5 years, gestational age of 22.2±3.6 weeks, weight of 77±12.2 kg, and HbA1c of 5.7±0.5%. Mean sensor TIR 63-140 mg/dL was 79.3±12.8% during CLC, compared to 60.8±18.8% for the week prior in open loop at home (p=0.03, Table 1). Unrestricted carbohydrate intake at meals ranged from 7 to 78 grams during the CLC sessions. No severe hypoglycemia or adverse events occurred. CLC in pregnant women with T1D is safe and effective. Disclosure B. Ozaslan: None. M. Church: None. M. Plesser: None. S. K. Mccrady-spitzer: None. C. Bakus: None. S. J. Ogyaadu: None. K. Nelson: None. C. Reid: None. S. Deshpande: None. W. K. Kremers: Research Support; Self; AstraZeneca, Biogen, Roche Pharma. F. J. Doyle: Advisory Panel; Self; Mode AGC, Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. C. J. Levy: Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Employee; Spouse/Partner; AbbVie Inc., Other Relationship; Self; Dexcom, Inc., Research Support; Self; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. B. Rosenn: None. Y. C. Kudva: Research Support; Self; Dexcom, Inc. E. Dassau: Consultant; Self; Eli Lilly and Company, Employee; Self; Eli Lilly and Company, Research Support; Self; Dexcom, Inc., Tandem Diabetes Care, Speaker’s Bureau; Self; Dexcom, Inc., Roche Diabetes Care, Stock/Shareholder; Self; Eli Lilly and Company. J. E. Pinsker: Advisory Panel; Self; Medtronic, Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. G. O’malley: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Horizon Therapeutics plc, Tandem Diabetes Care. R. Kaur: None. K. N. Castorino: Consultant; Self; Dexcom, Inc., Research Support; Self; Abbott Diabetes, Abbott Laboratories, Dexcom, Inc., Drawbridge Health, Inc., Lilly Diabetes, Medtronic, Novo Nordisk Inc. C. Levister: Research Support; Self; Abbott Diabetes, Insulet Corporation. M. Trinidad: None. D. Desjardins: None. Funding National Institutes of Health (R01DK120358); Dexcom, Inc. (AP-2020-014)

2-LB: Flash Glucose Monitoring in the Reduction of Hypoglycemia in Diabetic Kidney Disease: A Randomised Controlled Trial

Patients with moderate-to-advanced diabetic kidney disease (DKD) are at high risk of hypoglycemia. There are few studies evaluating personal continuous glucose monitoring (CGM) use in this group. We investigated whether flash glucose monitoring (FGM) was effective in reducing hypoglycemia compared with standard self-monitoring of blood glucose (SMBG) in individuals with chronic kidney disease (CKD) stages 3b-5 (non-dialysis). This was a single-centre, parallel-group randomised clinical trial of 94 adults with diabetes and CKD [G3b (n=36), G4 (n=44) and G5 (n=14)] and a history of hypoglycemia. Patients were randomly assigned 1:1 to FGM or SMBG for 16 weeks. Both groups received structured education on hypoglycemia and monthly reviews by healthcare professionals. Blinded CGM was performed at baseline and end of study in both groups. Patients were aged (mean±SD) 65.4±9.0 years with estimated glomerular filtration rate (eGFR) 26.1±9.6 ml/min/1.73m2, HbA1c 7.4±0.8% and median duration of diabetes for 20 years. 93 patients had type 2 diabetes and 99% were on insulin. After 16 weeks, percentage time &amp;lt;70mg/dL (3.9 mmol/L) decreased significantly from 4.0% to 2.5% in FGM group (- 1.7%; 95% CI -3.4 to -0.01%) but not in SMBG group (-1.1%; 95% CI -2.6 to 0.4%; between-group difference, p=0.73). Mean HbA1c improved significantly in both FGM (-0.33%, 95% CI -0.52 to -0.1) and SMBG groups (-0.36%, 95% CI -0.52 to -0.21; between-group difference p=0.08). One severe hypoglycemic event occurred in the FGM and none in SMBG group. The acceptability of FGM was high with overall 87% mean sensor use and average 8 scans per day. FGM was effective in reducing hypoglycemia and improving HbA1c in moderate-to-advanced DKD, but not significantly different from SMBG. Future studies are needed to assess whether real-time CGM with alerts would further reduce hypoglycemic episodes in this high-risk group. Disclosure J. Ling: None. J. K. Ng: None. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. A. Luk: None. C. Szeto: None. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. Funding Hong Kong College of Physicians; University Grants Committee Research Matching Grant Scheme

110-LB: Efficacy, Safety, and Appropriateness of iGlarLixi, a Fixed-Ratio Combination (FRC) in Type 2 Diabetes (T2D) in Real-World Settings: Results from the ENSURE Study

Randomized clinical trials (RCT) showed benefits of FRC of basal insulin (BI) and GLP1-RAs in terms of glycemic target, no weight gain, low risk of hypoglycemia, and gastrointestinal side effects. Real-world evidence (RWE) complements RCT to assess effectiveness and safety of drugs in clinical practice. The study evaluated the impact of iGlarLixi [once-daily FRC of basal insulin glargine 100 U/mL and GLP1-RA lixisenatide] in T2D. This was a retrospective, multicenter study, based on electronic medical records. All subjects initiating iGlarLixi in May 2018-July 2020 were analyzed. Overall, 25 centers provided data on 675 subjects with the following baseline characteristics (mean and standard deviation or proportion): age: 66.4±10.1 years, 54.2% men, T2DM duration 15.5±11.5 years, HbA1c 8.6±1.4%, and BMI 30.8±5.3 Kg/m2. Before starting iGlarLixi, 67.3% of subjects were treated with BI and 9.9% with GLP1-RA (5.5% as free combinations). Drugs associated with iGlarLixi were not only metformin and SGLT2 inhibitors, as by summary of product characteristics (SmPC); off-label combinations were found in 32.4% of patients (21.4% sulphonylureas). Effectiveness data (N=184) showed that HbA1c decreased by -0.77% [95%CI -1.00;-0.54] after 6 months and by -0.92% [95%CI -1.22;-0.62] in patients treated as by SmPC. Weight significantly decreased by 1.21 Kg. iGlarLixi dose increased by 5.14 U. Rates of blood glucose ≤70 and &amp;lt;54 mg/ml (N=171) were 0.26 and 0.05 events per person-month, respectively. No severe hypoglycemic events occurred. Participants discontinuing iGlarLixi within 6 months were 122 (18.1%). After discontinuation, 45.1% of patients started BI plus short acting insulin. In predominantly overweight/obese T2D people with poor metabolic control and long-lasting disease, effectiveness and safety of iGlarLixi are documented in real life, but improvements in treatment appropriateness are required. Disclosure R. Candido: None. M. Modugno: None. E. Gabellieri: None. A. Nicolucci: Advisory Panel; Self; AstraZeneca, Research Support; Self; Novo Nordisk, Pikdare, Sanofi, Shionogi &amp; Co., Ltd., SOBI. M. Rossi: Research Support; Self; Novo Nordisk, Sanofi, Shionogi &amp; Co., Ltd., Swedish Orphan Biovitrum AB. M. Larosa: Employee; Self; Sanofi. On behalf of ensure study group: n/a. Funding Sanofi

51-LB: Emotional Impact of Hypoglycemia and Use of Glucagon: Perspectives of People with T1D

Introduction: Severe hypoglycemia is an ongoing barrier to achieving glycemic targets. Glucagon is an effective, yet underutilized treatment for severe hypoglycemia. This study characterized the emotional impact of severe hypoglycemia, glucagon perceptions, and barriers to glucagon use for people with T1D. Methods: Participants included individuals recruited from the T1D Exchange online community. The current study conducted 7 focus groups consisting of adults with T1D (n = 38, average age 49.4, SD = 16.11 years). Average duration of diabetes was 34.4 years (SD = 17.3) and average self-reported A1c was 6.8% (SD = 0.7). Focus groups were recorded, transcribed, and thematically analyzed. Results: A range of emotions was expressed about severe hypoglycemia including fear, anxiety, stress, frustration, shame, and embarrassment. Due to hypoglycemia unawareness, participants discussed relying on CGM to make hypoglycemia treatment decisions. Multiple participants self-administered glucagon to prevent or treat a severe hypoglycemic event. Although overnight hypoglycemia and CGM alarms were described as important, some participants also viewed them as sleep disruptors for themselves and their partners. Participants frequently identified prescription cost and insurance deductibles as barriers to glucagon use. Participants were also concerned about ease of administration—how difficult it is to prepare the glucagon in an emergency situation. Many participants expressed a preference for auto-injectables over nasal administration. Timing of glucagon action and time to recovery were high priorities. Some participants, while they had not self-administered glucagon, were interested in a mini-dose glucagon they could self-administer. Conclusions: These results provide insight into the real-world impact of diabetes management in persons with T1D and highlight the attitudes about severe hypoglycemia and emergency glucagon treatment. Disclosure A. Hughes: None. K. S. M. Chapman: None. J. Bispham: None. N. M. Heydarian: None. J. Dimsits: Employee; Self; Zealand Pharma A/S. S. A. Weinzimer: Advisory Panel; Self; Dompe, Zealand Pharma A/S, Speaker’s Bureau; Self; Medtronic. W. Wolf: None.

1120-P: Sex Differences in the Burden of Diabetes-Related Complications among Older Adults with Type 1 Diabetes

Background: A growing number of older adults with type 1 diabetes (T1D) live into old age, yet, little is known about the burden of and sex differences in diabetes-related complications in this unique group. Methods: We examined the prevalence of diabetes-related complications in 780 adults aged ≥60 with T1D from the Study of Longevity in Diabetes (SOLID) overall and by sex across categories of T1D duration ( Results: Average (SD) age at baseline and duration of T1D were 67.3 (6.4) and 39.5 (14.9). Among those with T1D ≥50 years (Figure), prevalence of retinopathy, neuropathy and lifetime severe hypoglycemic event were all >60%. Women were more likely to report retinopathy (OR=1.49; 95% CI: 1.09, 2.03) and DKA (OR=1.92; 1.39, 2.66); no other sex differences were observed. Conclusions: Results quantify the burden of complications across a range of T1D duration and report key sex differences. Findings underscore how widespread diabetes-related complications are in those with longer T1D duration and highlight complications that disproportionately impact women. Disclosure M. L. Leigh: None. P. Gilsanz: None. C. Moran: None. A. J. Karter: Research Support; Self; Dexcom, Inc. R. A. Whitmer: None. Funding National Institute on Aging (R01AG047500); National Center for Advancing Translational Sciences (KL2TR001996)

352-P: Assessment of a Deep Learning Model Based on Three-Year Longitudinal Electronic Health Record Data for Predicting Severe Hypoglycemia in Patients with Type 2 Diabetes

Background: This study aimed to investigate the ability of a deep learning model to predict the outcome of severe hypoglycemia (SH) using longitudinal electronic medical records data. Methods: Structured data were extracted from the clinical data warehouse, including demographics, laboratory, medications, and diagnostic information. Between January 2010 and December 2012, 17,670 adult patients were enrolled; participants had type 2 diabetes, were aged over 30 years, and visited the diabetes centers of two hospitals. The primary outcome was SH, defined as diagnostic codes for hypoglycemia (E16.x, E11.63, E13.63, E14.63) in hospitalization or emergency room records. The performance of the longitudinal deep learning model (gated recurrent units) in predicting SH was quantified using the area under the receiver operating characteristic curve (AUROC) and evaluated in terms of net reclassification improvement (NRI) versus a traditional logistic regression model. Based on predicted risk of SH, we stratified patients into four risk groups: low (&amp;lt;1.0%), intermediate (1.0% to &amp;lt;2.0%), high (2.0% to &amp;lt;5.0%), and very high (≥5.0%). Results: Of 17,670 patients, 528 patients developed SH events during the follow-up period (mean of 6.4 years). The performance of the longitudinal deep learning model was superior to the logistic model for predicting SH (AUROC of logistic model, 0.788 [95% CI 0.781-0.793] vs. longitudinal deep learning model, 0.858 [0.853-0.863]). The very high-risk group of SH categorized using the deep learning model had 73 times higher risk of SH than the low-risk group. The deep learning model improved case reclassification (NRI, 13.4%). Conclusion: We found that the longitudinal deep learning model showed better performance and classification ability for predicting than the conventional logistic model. Disclosure G. Lee: None. S. Ko: None. Y. Ahn: None. E. Lee: None. S. Cha: None. D. Kim: None. J. Yun: None. Funding Korean Diabetes Association (2018-F to J-S.Y.)