Severe Hypoglycemia In Adults Research Articles

Population-Based Study on the Implementation of Flash Glucose Monitoring and Severe Hypoglycemia in Adults With Type 1 Diabetes.

Objective: We analyzed the effect of implementing a flash glucose monitoring (FGM) technology in a public health care system with universal coverage on the rate of severe hypoglycemia requiring urgent care in adults with type 1 diabetes mellitus (T1DM). Methods: Using a comprehensive regional dataset, we extracted emergency care codes with hypoglycemia in individuals with T1DM who initiated the use of FGM in Andalucia, Spain, from January 1, 2020, to December 31, 2021. Severe hypoglycemia was defined as a confirmed blood glucose <70 mg/dL, which required the urgent dispatch of an emergency medical service (EMS) for onsite management. We compared hypoglycemic events reported in the 12 months before and after the initiation of FGM to determine the population incidence rates. Results: A total of 13,616 participants with a mean age of 43.7 ± 13.5 years were included. The follow-up periods were 23.4 and 24.8 months before and after FGM. There were 969 and 737 cases of hypoglycemia before and after the initiation of FGM. The baseline incidence rate was 358.58 episodes per 10,000 person-years, which decreased to 260.9 at the end of the follow-up (rate-ratio 0.72 [0.66; 0.80]). The reduction in hypoglycemia was significant in individuals aged ≥60 years (rate-ratio 0.40 [0.28; 0.55]) and males (0.64 [0.56; 0.72]). In addition, there was a reduction in the overall median HbA1c of -0.35% (95% CI [-0.38; -0.33], P < 0.001). Conclusion: The implementation of FGM systems in a public health care system as a provision for adults with T1DM was associated with significant reductions in the rate of severe hypoglycemic events that required urgent EMS care.

Association of hypoglycemia problem-solving abilities with severe hypoglycemia in adults with type 1 diabetes: a Poisson regression analysis

Association of hypoglycemia problem-solving abilities with severe hypoglycemia in adults with type 1 diabetes: a Poisson regression analysis

Preventing severe hypoglycemia in adults with type 2 diabetes (PHT2): Design, delivery and evaluation framework for a randomized controlled trial

BackgroundSevere hypoglycemia is a common and feared complication of medications used to lower blood glucose levels in individuals with diabetes. Psychoeducational interventions can prevent severe hypoglycemia in individuals with type 1 diabetes (T1D). We aim to determine the effectiveness of this approach among adults with type 2 diabetes (T2D) at elevated risk for severe hypoglycemia. MethodsPreventing Hypoglycemia in Type 2 diabetes (PHT2) is a two-arm, parallel, randomized controlled trial. Participants are eligible if they are adults with T2D receiving care at an integrated group practice in Washington state and have experienced one or more episodes of severe hypoglycemia in the prior 12 months or have impaired awareness of hypoglycemia (Gold score ≥ 4). Participants are randomized to proactive nurse care management with or without my hypo compass, an evidence-based, psychoeducational intervention combining group and individual self-management training. For this study, my hypo compass was adapted to be suitable for adults with T2D and from an in-person to a virtual intervention over videoconference and telephone. The primary outcome is any self-reported severe hypoglycemia in the 12 months following the start of the intervention. Secondary outcomes include biochemical measures of hypoglycemia, self-reported hypoglycemia awareness, fear of hypoglycemia, and emergency department visits and hospitalizations for severe hypoglycemia. The study includes a process evaluation to assess implementation fidelity and clarify the causal pathway. ConclusionThe PHT2 trial will compare the effectiveness of two approaches for reducing severe hypoglycemia in adults with T2D.Trial registration: clinicaltrials.gov, # NCT04863872

Associations Between Postdischarge Care and Cognitive Impairment-Related Hospital Readmissions for Ketoacidosis and Severe Hypoglycemia in Adults With Diabetes.

Patients with severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) experience high hospital readmission after being discharged. Cognitive impairment (CI) may further increase the risk, especially in those experiencing an interruption of medical care after discharge. This study examined the effect modification role of postdischarge care (PDC) on CI-associated readmission risk among U.S. adults with diabetes initially admitted for DKA or SH. We used the Nationwide Readmissions Database (NRD) (2016-2018) to identify individuals hospitalized with a diagnosis of DKA or SH. Multivariate Cox regression was used to compare the all-cause readmission risk at 30 days between those with and without CI identified during the initial hospitalization. We assessed the CI-associated readmission risk in the patients with and without PDC, an effect modifier with the CI status. We identified 23,775 SH patients (53.3% women, mean age 65.9 ± 15.3 years) and 140,490 DKA patients (45.8% women, mean age 40.3 ± 15.4 years), and 2,675 (11.2%) and 1,261 (0.9%), respectively, had a CI diagnosis during their index hospitalization. For SH and DKA patients discharged without PDC, CI was associated with a higher readmission risk of 23% (adjusted hazard ratio [aHR] 1.23, 95% confidence interval 1.08-1.40) and 35% (aHR 1.35, 95% confidence interval 1.08-1.70), respectively. However, when patients were discharged with PDC, we found PDC was an effect modifier to mitigate CI-associated readmission risk for both SH and DKA patients (P < 0.05 for all). Our results suggest that PDC can potentially mitigate the excessive readmission risk associated with CI, emphasizing the importance of postdischarge continuity of care for medically complex patients with comorbid diabetes and CI.

390-P: Improving Quality of Life and Self-Efficacy through a Hypoglycemia Management Program—The HARPdoc Randomised Controlled Trial

Background: A significant minority (15-18%) of adults with type 1 diabetes (T1D) continue to experience problematic hypoglycemia despite access to structured education in flexible insulin therapy and advanced technologies. Many have impaired awareness of hypoglycemia, now recognised to be associated with significant mental health burden. The HARPdoc trial (Hypoglycemia Awareness Restoration Program for people with problematic hypoglycemia Despite Optimised Care) showed that a group programme focused on cognitions and motivation improved scores for diabetes distress, anxiety and depression compared to BGAT (blood glucose awareness training, which addresses education and behaviours), with similarly reduced rates of severe hypoglycaemia. Methods: This exploratory study addresses the further impact of these programmes on quality of life and mental health. Quality of life was measured at baseline with EQ-5D-5L and it and service use (Adult Service Utilisation Schedule) were measured at 12 and 24 months after randomised participation to either HARPdoc or BGAT. Results: Mean EQ-5D scores rose by 14%, +0.1 HRQoL utility score (HUS), over 24 months in HARPdoc and fell by 1%, -0.007 HUS in BGAT. Use of mental health services after HARPdoc or BGAT was 26 vs 56 contacts with a psychiatrist, psychologist or counsellor in months 0-12 and 1 vs 17 contacts in months 13 - 24 respectively. Conclusions: We conclude that HARPdoc reduces previously treatment-resistant severe hypoglycaemia in adults with type 1 diabetes but also enhances quality of life, whilst reducing use of mental health services. We hypothesise that the psychosocial aspects of HARPdoc increase self-efficacy and coping skills, thereby reducing disease burden and the need to access general and mental healthcare provision. Disclosure S.A.Amiel: Advisory Panel; Medtronic, Other Relationship; Sanofi, Novo Nordisk. E.Toschi: Advisory Panel; Eli Lilly and Company. S.R.Heller: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Other Relationship; Eli Lilly and Company, Research Support; Dexcom, Inc., Speaker's Bureau; Novo Nordisk, Medtronic. M.A.Stadler: None. P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. N.De zoysa: None. Funding JDRF (4-SRA-2017-266-M-N); National Institute of Health Research UK

139-LB: Use of Digital Diabetes Solution Is Associated with Improved Glycemic Control without Increased Risk of Severe Hypoglycemia in Adults with Type 2 Diabetes Mellitus in the United States—Retrospective Cohort Study

Background: Dario Diabetes Solution (DDS) is a digital health application (app) that combines blood glucose (BG) monitoring system with a smartphone app, allowing tracking of BG levels in real time. This study assessed effects of DDS on HbA1c levels in adults with type 2 diabetes mellitus (T2DM) with baseline (BL) HbA1c ≥8% and on severe hypoglycemia (SH). Methods: This retrospective cohort analysis included adults with T2DM who used DDS (users) and nonusers from 1JAN2017 to 31OCT2021. BL period was 1 year before index date (users, first DDS registration; nonusers, first claim date in the quarter); follow up was 6 months. DDS users and nonusers were sequentially matched 1:3 using exact and propensity score matching. Secondary endpoints included SH (event requiring medical intervention) rates for all patients (pts) and for pts with BL HbA1c ≥8% who achieved predefined target HbA1c &amp;lt;8%. SH incidence in users vs nonusers was examined. Results: Overall cohort included 568 DDS users and 1699 nonusers: mean age, 57.5±11.3 years; mean BL HbA1c, 9.14±1.83%; oral antidiabetic drugs, 51%; insulin, 6%. BL SH was rare (users, 7/568; nonusers, 12/1699). There were 387 users and 1089 nonusers with BL HbA1c ≥8% (mean BL HbA1c, 10.0±1.7%). In this subgroup, HbA1c &amp;lt;8% was achieved by 9% more DDS users (174/387 [45%]) vs nonusers (393/1089 [36%]) at 6 months; P=0.002. At 6 months, overall SH rate was 38.8 (users) vs 10.6 (nonusers) events/1000 pts per year (incidence rate ratio, 0.9; P=0.9). No observed increase in SH risk was associated with DDS in this population. SH was rare in pts who achieved HbA1c &amp;lt;8% (users, 1/174; nonusers, 3/393). Conclusions: In this retrospective study, a larger proportion of adults with uncontrolled T2DM (BL HbA1c ≥8%) achieved HbA1c &amp;lt;8% after using DDS vs nonusers, with no increased risk of SH. Disclosure N. Thingalaya: None. F. Lee: Employee; Sanofi, Stock/Shareholder; Sanofi. D. Kerr: Consultant; Sanofi-Aventis U. S. P. Potukuchi: None. L. Wilson: Employee; Sanofi. K. C. Lee: Employee; Sanofi. E. K. Han-burgess: Employee; Sanofi. A. Edwards: Employee; Symphony Health, an ICON plc company, Other Relationship; Sanofi. X. Yu: None. A. Kennedy: None. Funding Sanofi

Severe hypoglycaemia in adults presenting to a hospital emergency department: Clinical characteristics, comorbidities, and mortality outcomes.

To determine the clinical characteristics, risk factors and mortality outcomes associated with severe hypoglycaemia (SH) treated at a hospital emergency department. Adult patients presenting with SH to the Northern General Hospital, Sheffield, UK over a 44-month period were assessed for clinical characteristics, coexisting comorbidities and mortality outcomes, including cause of death, and analysed by age of diabetes onset, below and above age 40 years. Factors that predicted mortality were determined. A total of 619 episodes of SH occurred in 506 individuals. Most had type 1 (T1D; n = 172 [34.0%]) or type 2 diabetes (T2D; n = 216 [42.7%]), but several attendees did not have diabetes (non-DM; n = 110 [21.7%]). Irrespective of age of diabetes onset, patients with T2D had more socioeconomic deprivation and comorbidities (P < 0.005). SH was uncommon in those with young-onset T2D, who constituted 7.2% of all episodes in diabetes. Hospital admission was high (60%-75%). The T2D cohort had the longest inpatient stay (median 5 days, vs. 2 and 3 days for the T1D and non-DM cohorts, respectively). Survival after the index SH episode was lower and mortality was higher in the non-DM (39.1%) and T2D (38.0%) cohorts than the T1D cohort (13.3%; all P < 0.05), with a median time to death of 13, 113 and 465 days, respectively. Most deaths (78%-86%) were from non-cardiovascular causes. Charlson index predicted mortality and poor survival in T1D and T2D (both P < 0.05). Severe hypoglycaemia requiring emergency hospital treatment is associated with non-cardiovascular deaths and exerts a disproportionately greater impact on mortality in people with T2D and those without diabetes. Multimorbidity is an important risk factor for SH and increases mortality risk.

Identification of predictors of severe hypoglycemia in adults with type 1 diabetes in andalusia (Spain): results of the multicenter study "Sehypan"

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Real-Time Continuous Glucose Monitoring for People Living With Type 1 Diabetes

&#x0D; Continuous glucose monitoring (CGM) is a method of glucose testing in which a sensor is inserted into the skin and continuously monitors interstitial glucose concentrations. Real-time continuous glucose monitoring (rtCGM) systems automatically measure glucose and display a recent glucose value.&#x0D; Evidence suggests that rtCGM may improve hemoglobin A1C and time in range in adults and pediatric patients with type 1 diabetes, but this is uncertain.&#x0D; Limited evidence suggests that in people with type 1 diabetes, there is little to no difference between rtCGM and self-monitoring of blood glucose (SMBG) on quality of life, diabetic ketoacidosis, and severe adverse events.&#x0D; Safety evidence suggests that rtCGM may decrease severe hypoglycemia in adults and pediatric patients with type 1 diabetes, but this is uncertain.&#x0D; rtCGM may be more cost-effective in the long term than SMBG in adults with type 1 diabetes.&#x0D;

375-P: Indirect Treatment Comparison (ITC) of Three Ready-to-Use Glucagon Treatments for Severe Hypoglycemia: Baqsimi, Gvoke, and Zegalogue

Objective: To evaluate and compare the efficacy and safety of 3 ready-to-use glucagon treatments for severe hypoglycemia in adults and children with diabetes: Baqsimi (nasal glucagon) , Gvoke (glucagon injection) , and Zegalogue (dasiglucagon injection) . Methods: A systematic literature review was conducted to identify randomized clinical trials assessing the efficacy and safety of ready-to-use glucagon vs. reconstituted injectable glucagon. Bayesian fixed-effect network meta-analysis was used to perform the ITC of Gvoke and Zegalogue vs. Baqsimi. Endpoints included the proportion of participants achieving treatment success, maximum blood glucose, and treatment-emergent adverse events. Mean time to treatment success and to maximum blood glucose were also analyzed for Gvoke vs. Baqsimi, but not for Zegalogue due to reporting differences (mean vs. median) . Results and Conclusion: Ten trials were included in the ITC, including 4 for Baqsimi, 3 for Gvoke, and 3 for Zegalogue. Baqsimi had comparable efficacy with Gvoke and with Zegalogue (Table) , and all 3 treatments achieved high treatment success (&amp;gt;98%) in adults and children with diabetes. In adults, results from the combined T1D and T2D analysis were consistent with the T1D analysis, except a statistically significant faster time achieving treatment success observed for Baqsimi vs. Gvoke in the combined analysis. Disclosure M. Gimenez: Advisory Panel; Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi. Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi. K. Khunti: Consultant; Abbott, Amgen Inc., AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Lilly, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals Limited, Novartis AG, Novo Nordisk, Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Servier Laboratories. Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. K. Syring: Employee; Eli Lilly and Company. L.A. Baker: None. R.J. Threlkeld: Employee; Lilly Diabetes. Y. Yan: Employee; Eli Lilly and Company. M. Matsuhisa: Research Support; Nissui, Sysmex Corp. Speaker's Bureau; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Funded by Eli Lilly and Company.

173-OR: Associations between Post-Discharge Care (PDC) and Cognitive Impairment-Related Hospital Readmissions for Ketoacidosis and Severe Hypoglycemia in Adults with Diabetes

Cognitive Impairment (CI) is associated with an increased risk of ketoacidosis (DKA) and severe hypoglycemia (SH) in persons with diabetes (DM) . Post-discharge Care (PDC) in nursing homes and home care facilities provides continuous medical care after hospital discharges. This study examined whether PDC is associated with lower CI-related hospital readmission for DKA and SH in US adults with DM (age &amp;gt;18) . Our study population includes 43,467 and 166,221 adults admitted for DKA and SH from the 2016-2018 National Readmission Database, among which 1492 (3.43%) and 822 (0.49%) had CI, respectively. Readmission was defined as hospitalization for all causes within 30 days after discharge. CI-related readmission risk was estimated by comparing those with and without CI using a multiple logistic regression model, adjusting for age, sex, primary payer, income level, disease severity, mortality risk at the index discharge, and PDC status. PDC as an effect modulator was tested as an interaction term of PDC and CI. For patients initially admitted for DKA, CI was associated with 62% (adjusted odds ratio (aOR) =1.62, 1.25-2.11) higher odds of readmission among those who were discharged to home. The CI-related increase in readmission risk disappeared if patients received PDC (aOR=1.05, 0.88-1.26) . For patients initially admitted for SH, CI was associated with 34% (aOR=1.34, 95% CI 1.08-1.66) higher odds of readmission among those discharged to home and a 32% lower odds of readmission if patients received PDC (aOR=0.68, 0.59-0.81) . CI was associated with increased readmission risks for SH and DKA among adults with DM discharged to home. This CI-related readmission risk was substantially lower in patients who received PDC, indicating the importance of PDC for people with DM and CI. Disclosure Y.Wang: None. P.Zhang: None. R.R.Fang: None. J.D.Brown: None. T.Jiao: None. J.Guo: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.

New Fast Acting Glucagon for Recovery from Hypoglycemia, a Life-Threatening Situation: Nasal Powder and Injected Stable Solutions.

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989–1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.

Aging and comorbidities influence the risk of hospitalization and mortality in diabetic patients experiencing severe hypoglycemia

Background and aimsTo assess the risk of hospitalization and mortality within 1 year of severe hypoglycaemia and theirs clinical predictors. Methods and resultsWe retrospectively examined 399 admissions for severe hypoglycemia in adults with DM at the Emergency Department (ED) of the University Hospital of Novara (Italy) between 2012–2017, and we compared the clinical differences between older (aged ≥65 years) and younger individuals (aged 18–64 years). A logistic regression model was used to explore predictors of hospitalization following ED access and 1-year later, according to cardiovascular (CV) or not (no-CV) reasons; 1-year all-cause mortality was also detected.The study cohort comprised 302 patients (median [IQR] age 75 [17] years, 50.3% females, 93.4% white, HbA1c level 7.6% [1.0%]). Hospitalization following ED access occurred in 16.2% of patients and kidney failure (OR 0.50 [95% CI 1.29–5.03]) was the only predictor of no-CV specific hospitalization; 1-year hospitalization occurred in 24.5% of patients and obesity (OR 3.17 [95% CI 1.20–8.12]) and pre-existing heart disease (OR 3.20 [95% 1.20–9.39]) were associated with CV specific hospitalization; 1-year all-cause mortality occurred in 14.9% of patients and was associated with older age (OR 1.12 [95% CI 1.07–1.18]) and pre-existing heart disease (OR 2.63 [95% CI 1.19–6.14]) ConclusionsSevere hypoglycemia is associated with risk of hospitalization and mortality mainly in elderly patients and it may be predictive of future cardiovascular events in diabetic patients with pre-existing heart disease and obesity.

Trends in Glucose-Lowering Drug Use, Glycemic Control, and Severe Hypoglycemia in Adults With Diabetes in Hong Kong, 2002-2016.

There has been a shift toward new classes of glucose-lowering drugs (GLDs) in the past decade but no improvements in glycemic control or hospitalization rates due to severe hypoglycemia (SH) in previous surveys. We examined trends in GLDs use, glycemic control, and SH rate among patients with diabetes in Hong Kong, which introduced a territory-wide, team-based diabetes care model since 2000. Using population-based data from the Hong Kong Diabetes Surveillance Database, we estimated age- and sex-standardized proportion of GLD classes, mean hemoglobin A1c (HbA1c) levels, and SH rates in 763,809 patients with diabetes aged ≥20 years between 2002 and 2016. Between 2002 and 2016, use declined for sulfonylureas (62.9% to 35.3%) but increased for metformin (48.4% to 61.4%) and dipeptidyl peptidase 4 inhibitors (DPP-4is) (0.01% in 2007 to 8.3%). The proportion of patients with HbA1c of 6.0-7.0% (42-53 mmol/mol) increased from 28.6% to 43.4%, while the SH rate declined from 4.2/100 person-years to 1.3/100 person-years. The main improvement in HbA1c occurred between 2007 and 2014, decreasing from mean (SD) 7.6% (1.6) (59.5 [19.0] mmol/mol) to 7.2% (1.7) (54.8 [18.9] mmol/mol) (P < 0.001). The 20-44 years age-group had the highest proportion of HbA1c ≥9% (75 mmol/mol) and rising proportions not on GLDs (from 2.0% to 7.7%). In this 15-year survey, the modest but important improvement in HbA1c since 2007 coincided with diabetes service reforms, increase in metformin, decrease in sulfonylureas, and modest rise in DPP-4i use. Persistently poor glycemic control and underuse of GLDs in the youngest group calls for targeted action.

39-OR: Secular Trends in Glucose-Lowering Drug Utilization, Glycemic Control, and Severe Hypoglycemia in Adults with Diabetes between 2002 and 2016 in Hong Kong

Introduction: There has been a shift towards new classes of glucose lowering drugs (GLDs) in the past decade but no improvements in glycemic control or hospitalization rates due to severe hypoglycemia (SH) in previous surveys. We examined secular trends in GLDs utilization, glycemic control and rate of SH among people with diabetes, mainly type 2 diabetes, in Hong Kong which introduced a territory-wide, team-based diabetes care model since 2000. Methods: Using population-based data from the Hong Kong Diabetes Surveillance Database consisting mainly of Chinese living a westernized lifestyle, we estimated the annual age- and sex-standardized proportion of GLDs classes, mean hemoglobin A1c (HbA1c) levels and SH rates in 763,809 diabetes patients aged ≥20 years between 2002-2016. We used Joinpoint regression to examine secular trends over time. Results: In 2002-2016, use declined for sulfonylureas (50.7% to 28.9%) but increased for metformin (47.8% to 57.3%) and dipeptidyl peptidase-4 inhibitors (DPP-4i) (0.01% in 2007 to 7.0%). The proportion of patients with HbA1c of 6.0-7.0% increased from 25.6% to 37.2% while the rate of SH declined from 4.4 to 1.7 per 100 person-years. The main improvement in annual mean HbA1c occurred between 2007 and 2014, decreasing from mean (SD) 7.8 (1.6)% to 7.4 (1.7)% (p&amp;lt;0·001). The 20-44 age group had the highest proportion of HbA1c&amp;gt;9% with rising proportions not treated with any GLDs (from 4.3% to 10.5%). Conclusion: Prescription of GLDs has changed dramatically in Hong Kong in the past 15 years in line with treatment guidelines and introduction of new drugs. The modest but important improvement in HbA1c since 2007 coincided with widening reform of diabetes services in primary care and introduction of DPP-4i. Poor glycemic control and low utilization of GLDs in the youngest age group calls for targeted treatment strategies and ongoing surveillance. Disclosure A. Yang: None. H. Wu: None. E.S. Lau: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. A.P. Kong: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Sanofi. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. W. So: None. A. Luk: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Roche Pharma. Other Relationship; Self; Merck Sharp &amp; Dohme Corp. J.C. Chan: None. E. Chow: None. Funding Chinese University of Hong Kong

1103-P: Balancing the Risk of DKA and Severe Hypoglycemia with Sotagliflozin in Adults with Type 1 Diabetes

Background: DKA and severe hypoglycemia (SH) are the 2 most important acute complications of type 1 diabetes (T1D). SGLT inhibitors are associated with an increased risk of ketosis and DKA. Sotagliflozin (SOTA), a dual SGLT 1 and 2 inhibitor, has been shown to reduce the incidence of documented hypoglycemia and SH as adjunct to insulin therapy in T1D. The objective was to determine if the increased risk of DKA with SOTA was offset by the reduction of SH. Methods: Data were pooled from the inTandem 1 and 2, 52-week, placebo (PBO)-controlled studies in adults with T1D (N=1575). Events of DKA and SH were adjudicated by an IRC. Incidence and exposure-adjusted incidence rates (EAIR) were calculated along with numbers needed to treat or harm (NNT/NNH). Results: A higher incidence of adjudicated DKA was seen with SOTA 200 and 400 mg (2.9 and 3.8%) compared to PBO (0.2%). However, SOTA was associated with a lower rate of hypoglycemia events with blood glucose levels ≤55 mg/dL and a lower incidence of adjudicated SH with SOTA 200 and 400 mg (5.7 and 4.4%) compared with PBO (7.4%). The absolute risk difference in EAIR between SOTA and PBO was 2.9 to 4.0 events per 100 patient-yr for DKA and -1.9 to -3.4 events per 100 patient-yr for SH (Figure). NNH for DKA (28) was similar to the NNT for SH (33) with SOTA 400 mg. Conclusions: With SOTA added to insulin, the increase in DKA was similar in magnitude to the decrease in SH in adults with T1D. Disclosure J. Pettus: Consultant; Self; Diasome Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk Inc., Sanofi. B. Cariou: Advisory Panel; Self; Bristol-Myers Squibb, Gilead Sciences, Inc., Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; GENFIT. Research Support; Self; Amgen, Regeneron Pharmaceuticals. Speaker’s Bureau; Self; Abbott, AstraZeneca. S. Sawhney: None. P.L. Banks: Employee; Self; Lexicon Pharmaceuticals, Inc. M.J. Davies: Employee; Self; Lexicon Pharmaceuticals, Inc. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc.

Predictors of Recurrent Severe Hypoglycemia in Adults With Type 1 Diabetes and Impaired Awareness of Hypoglycemia During the HypoCOMPaSS Study.

The HypoCOMPaSS study was designed to test the hypothesis that successful avoidance of biochemical hypoglycemia without compromising overall glycemic control would restore sufficient hypoglycemia awareness to prevent recurrent severe hypoglycemia in the majority of participants with established type 1 diabetes. Before starting the study, we planned to investigate associations between baseline characteristics and recurrent severe hypoglycemia over 2 years' follow-up. A total of 96 adults with type 1 diabetes and impaired awareness of hypoglycemia participated in a 24-week 2 × 2 factorial randomized controlled trial comparing insulin delivery and glucose monitoring modalities, with the goal of rigorous biochemical hypoglycemia avoidance. The analysis included 71 participants who had experienced severe hypoglycemia in the 12-month prestudy with confirmed absence (complete responder) or presence (incomplete responder) of severe hypoglycemia over 24 months' follow-up. There were 43 (61%) complete responders and 28 (39%) incomplete responders experiencing mean ± SD 1.5 ± 1.0 severe hypoglycemia events/person-year. At 24 months, incomplete responders spent no more time with glucose ≤3 mmol/L (1.4 ± 2.1% vs. 3.0 ± 4.8% for complete responders; P = 0.26), with lower total daily insulin dose (0.45 vs. 0.58 units/24 h; P = 0.01) and greater impairment of hypoglycemia awareness (Clarke score: 3.8 ± 2.2 vs. 2.0 ± 1.9; P = 0.01). Baseline severe hypoglycemia rate (16.9 ± 16.3 vs. 6.4 ± 10.8 events/person-year; P = 0.002) and fear of hypoglycemia were higher in incomplete responders. Peripheral neuropathy was more prevalent in incomplete responders (11 [39%] vs. 2 [4.7%]; P < 0.001) with a trend toward increased autonomic neuropathy. Recurrent severe hypoglycemia was associated with higher preintervention severe hypoglycemia rate, fear of hypoglycemia, and concomitant neuropathy.

Impact of severe hypoglycaemia on psychological outcomes in adults with Type 2 diabetes: a systematic review.

Hypoglycaemia affects many people with Type 2 diabetes using insulin and other glucose-lowering therapies. This systematic review examined the impact of severe hypoglycaemia (episodes requiring external assistance) on psychological outcomes (e.g. emotional well-being, health status and quality of life) in adults with Type 2 diabetes. MEDLINE Complete, PsycINFO and CINAHL databases were searched for peer-reviewed empirical studies, published in English, reporting the occurrence and severity of hypoglycaemia and its relationship with patient-reported outcomes (PROs) in adults with Type 2 diabetes. Data were extracted from published reports and analysed. Of 3756 potentially relevant abstracts, 29 studies met the inclusion criteria. Most reported cross-sectional data and sample sizes varied widely (N=71 to 17563). Although definitions of mild and severe hypoglycaemia were largely consistent between studies, additional non-standard categorizations (e.g. moderate, very severe) were apparent and recall periods varied. Overall, severe hypoglycaemia was associated with increased fear of hypoglycaemia and decreased emotional well-being, health status and diabetes-specific quality of life. Effect sizes show that the association with fear of hypoglycaemia was stronger than with general health status. Notwithstanding the limitations of the empirical studies, these findings indicate that severe hypoglycaemia in adults with Type 2 diabetes (insulin- and non-insulin-treated) is associated with impaired psychological outcomes. Healthcare professionals should address the psychological impact of severe hypoglycaemia during clinical consultations, to support individuals to minimize exposure to, and the psychological consequences of, severe hypoglycaemia.

384-P: An Integrated Summary of Safety and Efficacy of a Ready-to-Use Liquid Glucagon Rescue Pen for the Treatment of Severe Hypoglycemia in Adults

Objective: To prevent medical complications of severe hypoglycemic emergencies, prompt and reliable rescue intervention is critically important. A ready-to-use stable liquid Glucagon Rescue Pen (GRP; Xeris Pharmaceuticals) auto-injector was evaluated for the rescue treatment of severe hypoglycemia. Method: Two Phase 3 randomized, controlled, blinded, crossover studies were conducted in 161 adults with T1D to compare 1 mg doses of GRP versus Glucagon Emergency Kit (GEK; Eli Lilly) for the treatment of insulin-induced severe hypoglycemia. Efficacy was evaluated as either a return of plasma glucose (PG) to &amp;gt;70 mg/dL or increase in PG ≥20 mg/dL from a baseline PG &amp;lt;50 mg/dL, within 30 min of dosing. Result: Subjects treated with GRP (98.7%) achieved successful PG recovery within 30 minutes, and (99.4%) had a PG &amp;gt; 70 mg/dL or neuroglycopenic symptom relief within 30 minutes, both comparable to GEK. From glucagon dosing, the mean time to achieve PG &amp;gt;70 mg/dL or increase in PG ≥20 mg/dL was 13.8±5.6 min for GRP and 10.0±3.6 min for GEK. This mean time does not account for the significantly shorter (p&amp;lt;0.0001) drug preparation and administration time for GRP (27.3±19.7 seconds) vs. GEK (97.2±45.1 seconds). The GRP was similar to GEK in terms of glucose Cmax, Tmax, and AUC(0-90min). The overall incidence of treatment emergent adverse events (TEAEs) was comparable in both groups; the most commonly reported TEAEs were nausea (GRP 29.9%, GEK 22.9%) and vomiting (GRP 16.1%, GEK 9.6%). One SAE was reported in these studies (GEK). Conclusion: A ready-to-use, easy two-step administration GRP achieved plasma glucose recovery reliably, was therapeutically equivalent to GEK, and had an incidence of nausea and vomiting comparable to GEK. There was a significant difference in drug preparation time in favor of the GRP. These results demonstrate that GRP is an effective, safe, and well tolerated rescue treatment for severe hypoglycemia and is a viable alternative to GEK. Disclosure M.P. Christiansen: Research Support; Self; Abbott, Biolinq, Dexcom, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk A/S, Sanofi-Aventis, Xeris Pharmaceuticals, Inc. M.J. Cummins: Employee; Self; Xeris Pharmaceuticals, Inc. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc. M.K. Junaidi: None.

Association of Depressive Symptoms and Diabetes Distress With Severe Hypoglycemia in Adults With Type 2 Diabetes.

To examine the association of depressive symptoms (DS) and diabetes-related distress (DD) with severe hypoglycemia (SH) in adults with type 2 diabetes. Baseline data from a cohort study of adults with type 2 diabetes (N=2,040) were used. The Patient Health Questionnaire 8-items and Problem Areas in Diabetes 5-items questionnaires were used to assess DS and DD, respectively. SH was defined as a positive report of "calling an ambulance or visiting an emergency department because of hypoglycemia in the past year." Composite dummy variables for the 2 stratification levels of DS and DD were computed and used in multivariable logistic regression analyses. Participants had a mean (± SD) age of 64±11years, and 45% were female. The average duration of diabetes was 12±9years; 3% had moderate to severe DS, 8% had moderate to severe DD and 5% had moderate to severe levels of both symptoms. Only 4.2% of participants reported experiencing SH in the past year. The presence of any level of DD (adjusted OR 2.3; 95% CI 1.3, 3.9) or moderate to severe DD (2.2; 1.1, 4.2) was associated with increased risk for SH. Combinations of any levels of DD and DS (4.3; 2.5, 7.3) and moderate to severe DD and DS (2.3; 1.1, 4.8) were associated with increased risk for SH. The presence of any level of DS alone (1.2; 0.3, 4.9) or moderate to severe DS (1.7; 0.6, 5.1) was not associated with increased risk for SH. Patients with type 2 diabetes and symptoms of depression, but not diabetes-related distress alone, were more likely to experience SH than those without either of these symptoms.