Hypoglycemic Episodes Research Articles

391-P: Individualized Optimization of Duration and Threshold of Sensor Hypoglycemia Improves Identification of Symptomatic Hypoglycemia Episodes—Hypo-METRICS Study

Current definitions of sensor detected hypoglycemia (SDH) give high levels of asymptomatic hypoglycemia on continuous glucose monitoring (CGM). We defined individually optimised thresholds and durations for sensor detected hypoglycemia (SDH) that better identify symptomatic hypoglycemia experienced by people with insulin treated diabetes. We analysed 10 weeks of blinded CGM (Libre 2) and FitBit data from 435 participants [217 type 1, 218 type 2]. They self reported symptomatic hypoglycemia on the Hypo-METRICS smartphone app. We used particle Markov chain Monte Carlo optimization to generate the threshold and duration of SDH that maximizes detection of symptomatic hypoglycemia for each individual (and by Fitbit sleep status). When using individual definitions of SDH, precision for detection of symptomatic hypoglycemia increased by 23% with 2% loss of sensitivity vs the consensus definition of Level 1 SDH (70mg/dl > 15 mins). Precision and sensitivity increased by 41% and 20% respectively vs level 2 SDH (54 mg/dl > 15 mins). Increased precision, with minimal change of sensitivity, were greatest during sleep, and irrespective of diabetes types and sleep status (Table). Optimizing SDH definitions at the individual level and by sleep status could minimize false alarms without increasing missed clinically important hypoglycemia episodes. Disclosure Z.Mahmoudi: Employee; Novo Nordisk. B.E.De galan: Research Support; Novo Nordisk. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi, Vertex Pharmaceuticals Incorporated. R.J.Mccrimmon: Advisory Panel; Sanofi, Speaker's Bureau; Novo Nordisk A/S. E.Renard: Consultant; Abbott Diabetes, Dexcom, Inc., AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Roche Diabetes Care. 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.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. J.K.Mader: Advisory Panel; Novo Nordisk A/S, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Medtronic, Becton, Dickinson and Company, Pharmasense, embecta, Research Support; A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Dexcom, Inc., Profusa, Inc., Speaker's Bureau; Novo Nordisk A/S, A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Boehringer Ingelheim Inc., Becton, Dickinson and Company, Ypsomed AG, Viatris Inc., Servier Laboratories, Medtrust, Stock/Shareholder; Decide Clinical Software GmbH. S.A.Amiel: Advisory Panel; Medtronic, Other Relationship; Sanofi, Novo Nordisk. P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. Hypo-resolve consortium: n/a. P.Divilly: None. G.Martine-edith: Other Relationship; Novo Nordisk A/S. D.Boiroux: Employee; Novo Nordisk A/S. N.Zaremba: None. U.Soeholm: Employee; Novo Nordisk A/S. M.Gomes: Employee; Novo Nordisk A/S. A.A.Vaag: None. J.Speight: Research Support; Sanofi, Medtronic, Abbott Diabetes, Lilly, Novo Nordisk A/S, Speaker's Bureau; Sanofi. Funding Innovative Medicines Initiative 2 Joint Undertaking (777460)

107-LB: Clinical Performance of Extended Mio 30 Infusion Set

Objective: Medtronic Mio™ 30 infusion set (M30IS) is a single use IS for pump users with pre-loaded inserter, a 30° insertion angle, and labeled for 3-day use. The M30IS wear duration is impacted by initial local trauma caused by insertion and sustained inflammation by cannula & insulin infusion (insulin aggregates & other impurities in the infusate), with the latter being predominant. An extended Mio™ 30 infusion set (EM30IS) was developed by improving insulin formulation stability in the fluid path. This study reports on the performance of the EM30IS in persons with T1D during an early feasibility trial (ClinicalTrials.gov: NCT05544643). Method: This is a X over study of EM30IS and M30IS on 21 subjects with type 1 diabetes. Each subject wore both sets 4-5 times each on a preferred site that was continuously infused with insulin lispro or aspart subcutaneously via a Medtronic 780G pump for 3 days (M30IS), 7 days (EM30IS) or until failure. Endpoints of safety and effectiveness (failure rate due to unexplained hyperglycemia <16%) were evaluated. Exploratory analyses related to performance and glycemic control were also evaluated. Results: The EM30IS survival rate at 6 days (70%) was comparable to M30IS survival rate at 3 days (63%). Glycemic control outcomes were equivalent (see Table 1) and there were no episodes of EM30IS-related severe hypoglycemia or DKA. Conclusion: The EM30IS was safe and its performance at 6 days was equivalent to the performance of M30IS at 3 days. Disclosure O. Cohen: Employee; Medtronic. Y. Cohen: None. S. Chattaraj: Employee; Medtronic. G. Zhang: Employee; Medtronic. E. Anselmo: Employee; Medtronic. A. Tirosh: Advisory Panel; Medtronic. Research Support; Medtronic. Speaker's Bureau; Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Funding Medtronic

101-LB: Phase 3 Trial to Evaluate Efficacy and Safety of Gemigliptin and Dapagliflozin Dual Add-on Therapy to Metformin—SOLUTION 2 Study

Background: Type 2 diabetes mellitus (T2DM) patients inadequately controlled with metformin alone require an addition of other medications with complementary mechanism of action. Gemigliptin, a dipeptidyl peptidase-4 inhibitor, and Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, can be considered as additional options. In this clinical trial, efficacy and safety of treatment of gemigliptin and dapagliflozin were evaluated in T2DM patients inadequately controlled with metformin monotherapy. Method: Total 469 T2DM patients receiving treatment with stable metformin for ≥ 8 weeks before screening were randomized to gemigliptin and dapagliflozin (n=157) or gemigliptin (n =156) or dapagliflozin (n =156), respectively. The primary endpoint was the change in HbA1c at 24 weeks from baseline. Results: At 24-week treatment, the HbA1c change from baseline in dual add-on of gemigliptin and dapagliflozin showed a significant reduction (LS Mean -1.34%) compared to gemigliptin add on (-0.90%; difference -0.44% [95% CI -0.58% to -0.31%]) and dapagliflozin add on (-0.78%; difference -0.56% [95% CI -0.69% to -0.42%]). Most of the reported adverse events were mild with no episodes of severe hypoglycemia. Conclusion: This study demonstrated that triple therapy of gemigliptin and dapagliflozin dual add-on to metformin was effective and well tolerated in T2DM patients. Disclosure K. Park: None. K. Han: None. Y. Hwang: None. S. Moon: None. H. Cho: None. H. Yoo: None. S. Choi: None. S. Chon: None. K. Kim: None. T. Kim: None. J. Kang: None. C. Park: None. J. Won: None. S. Lee: Advisory Panel; LG Chem. Speaker's Bureau; Dong-A Pharm. Advisory Panel; CKD Pharm. Speaker's Bureau; Novo Nordisk, Lilly. Advisory Panel; Daiichi Sankyo. Speaker's Bureau; Boehringer Ingelheim Inc. N. Kim: None. E. Kang: None. D. Kim: None. S. Kim: None.

175-OR: Pregnancy Intervention with a Closed-Loop System (PICLS) Study

We performed a parallel, two-site, randomized controlled trial of a commercially available hybrid closed-loop (HCL) system compared to sensor augmented pump therapy (SAPT) in pregnant women with type 1 diabetes (T1D). Participants started SAPT (Medtronic 670G) by 11 weeks gestation, were randomized at 14-18 weeks, and continued therapy until 6 weeks postpartum. The HCL group used assistive techniques, “fake carbohydrate” boluses, to optimize therapy. We performed linear mixed model regression to compare outcomes between groups, adjusted for clinic. There were 24 women randomized and 23 completers. At baseline there were no significant differences between groups (mean baseline A1C 6.8% at 8w5d [SAPT]/9w0d [HCL] enrollment). There were no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization. Adverse skin reactions occurred in 6 participants (5 SAPT vs 1 HCL, p=0.1550) with a median (IQR) number of 1 (1-2) SAPT vs 4 (4-4) HCL (p=0.8774). A1C significantly decreased from baseline to 2nd trimester, and was different between groups in the 3rd trimester (Table 1). There were no differences in time below, within, or above range between groups during the study (Table 1) or in gestational health outcomes (Table 2). In a pilot cohort of pregnant women with T1D, assisted HCL therapy did not increase risk to mothers or fetuses compared to SAPT despite lack of a pregnancy-specific algorithm in the HCL system. Disclosure E.Buschur: Consultant; Beta Bionics, Inc., Research Support; Dexcom, Inc., JDRF, Leona M. and Harry B. Helmsley Charitable Trust. E.R.Nease: None. S.Polsky: Other Relationship; diaTribe, Research Support; Dexcom, Inc., Medtronic, Hemsley Charitable Trust, JDRF, NIH - National Institutes of Health. J.K.Snell-bergeon: None. L.Pyle: None. R.Garcetti: None. K.M.Dungan: Board Member; Elsevier, Consultant; Eli Lilly and Company, Dexcom, Inc., Other Relationship; UpToDate, Research Support; Dexcom, Inc., Abbott, ViaCyte, Inc., Sanofi, Speaker's Bureau; Academy for Continued Healthcare Learning, Cardiometabolic Health Congress, Medscape, Integritas. S.F.Thung: None. A.Bartholomew: None. T.Summerfield: None. T.Bloks: None. Funding JDRF (2-SRA-2018-666-M-R); Colorado Clinical and Translational Sciences Institute; Children’s Diabetes Foundation; National Center for Research Resources (UL1RR02578)

282-OR: Closed-Loop Insulin Delivery Postpartum in Type 1 Diabetes

Background: Postpartum demands of caring for a newborn, breastfeeding, and sleep deprivation result in little time for self care of type 1 diabetes (T1D). Data are limited on the efficacy, safety and feasibility of closed loop insulin delivery postpartum. Methods: We performed an open label, controlled pilot trial randomizing women to hybrid closed loop insulin delivery Medtronic MiniMed™ 670G/770G in auto mode or sensor augmented insulin pump (SAP) therapy in the first 12 twelve postpartum weeks. The primary outcome was the percent time in target glucose range of 70-180 mg/dL (3.9-10.0 mmol/L). Mixed models analysis assessed between group differences in glucose measures from median start time of closed loop (8 days) to 12wks postpartum. Results: Twenty women were recruited. Two withdrew prior to randomization. The remaining 18 women completed 12 weeks of postpartum follow up in their assigned randomization group. Overall baseline mean age, duration of T1D and first pregnancy A1c was 32 years, 22 years and 6.9% respectively. Analyses adjusted for first pregnancy A1c and was intention to treat. Time in range did not differ between groups (79 ± 8.0% versus 80 ± 6.4% p =.079). Time below 70mg/dL (3.9 mmol/L) and 54mg/dL (3.0 mmol/L) was less for women randomized to closed loop versus SAP (1.6 ± .72 % vs 5.3 ± 3.3 % p <0.001 and .23 ± .16 % vs .95 ± .82 % p = 0.002 respectively). Time above 180 mg/dL (10 mmol/L) was not different between groups 19.5 ±8.7% vs 15.9 ±7.8% p = .823. Mean glucose was 146 ± 13 and 133 ± 14 mg/dL p <.001 for closed loop and SAP groups respectively. No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either group. Conclusions: Closed loop insulin delivery postpartum was associated with less hypoglycemia than SAP and slightly higher mean glucose. There were no safety concerns. Time in target glucose range was high, minimizing the potential for further improvement with closed loop. These findings are reassuring for the use of closed loop insulin delivery postpartum because of its’ potential to reduce hypoglycemia. Disclosure L.E.Donovan: Research Support; Dexcom, Inc., Medtronic, Tandem Diabetes Care, Inc., Inner Analytics. D.Feig: Advisory Panel; Novo Nordisk Canada Inc., Speaker's Bureau; Sanofi, Novo Nordisk Canada Inc. P.Lemieux: Other Relationship; Dexcom, Inc. H.R.Murphy: Advisory Panel; Medtronic, Research Support; Dexcom, Inc. R.C.Bell: None. R.J.Sigal: Research Support; Novo Nordisk. J.Ho: None. J.M.Yamamoto: None. Funding Calgary Health Trust

386-P: Inpatient Hypoglycemic Rate Reduction through the Implementation of Prescriber Targeted Decision Support Tools

Introduction: Hypoglycemia has been shown to increase mortality and length of hospital stay in patients with and without diabetes. The purpose of this study is to determine if the implementation of prescriber targeted decision support tools reduces the incidence of inpatient hypoglycemic events. Methods: This pre-post intervention study included adult patients who experienced an inpatient hypoglycemic event within 24 hours of insulin administration from October 2018 to December 2019. Pregnant women and patients receiving insulin infusions were excluded. Best Practice Alerts (BPAs) and banners were implemented in January 2019 to alert providers of patients at risk for hypoglycemia. Triggers for the BPAs and banners include use of sulfonylureas with reduced renal function, high weight-based basal doses, a previous episode of hypoglycemia during the admission, or concomitant use of fluoroquinolones and scheduled insulin. The primary outcome was to measure the incidence of hypoglycemia per 1000 patient days in pre- vs. post-intervention groups. Results: In total, 1186 hypoglycemic events in the pre-intervention group were compared to 5260 events in the post-intervention group. The implementation of EMR alerts significantly decreased hypoglycemia (glucose ≤ 70 mg/dL) from 22.91 events/1000 patient days to 18.27 events/1000 patient days (p<0.001). Severe hypoglycemia (glucose < 54 mg/dL) was not significantly reduced (1.65 events/1000 patient days vs. 1.79 events/1000 patient days (p=0.453)). The use of high weight-based basal insulin doses was reduced in the post-intervention patients with normal renal function, 23.0% vs. 16.7% (p<0.001), and patients with impaired renal function, 7.1% vs. 4.9% (p=0.017). Conclusion: The implementation of prescriber targeted decision support tools was successful in reducing the overall incidence of inpatient hypoglycemia. Disclosure R.Goldstein: None. J.M.Odom: None.

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

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

152-LB: Implementing a Pilot Clinic for Steroid-Induced Hyperglycemia in Graft vs. Host Disease

Introduction: Malignant hematologic disorders are often treated with hematopoietic stem cell transplantation. This can be complicated by graft versus host disease (GVHD). Treatment is high dose corticosteroids, which often leads to steroid induced hyperglycemia (SIH). Uncontrolled hyperglycemia is associated with increased morbidity and mortality. Despite evidence favoring glycemic control in this population, there are no formal protocols or clinics in place to achieve this. Methods: The University of Kansas Blood and Marrow Transplant Program collaborated with the Department of Endocrinology to establish a pilot clinic for patients with GVHD who have SIH. Over 12 months, patients were referred to a physician assistant specializing in diabetes. They were seen at 1-4 week intervals based on acuity and glycemic control. Data was collected on blood glucose, hemoglobin A1c, fructosamine, steroid doses, insulin doses, hospitalizations, infections, and death. Results: 64 patients were referred to this clinic. 24 were excluded due to lack of hyperglycemia or declined being seen. Median time to index visit from referral was 20.5 days (IQR 8.25-29). Median A1c at index visit was 5.9 (IQR 5.4-7.2) and at 3 months was 5.3 (IQR 4.6-6.3). Median highest glucose within the first 3 months was 230 mg/dL (IQR 183-362) and at 3-6 months was 161 mg/dL (IQR 119.8-247, p-value = 0.0025). Median lowest glucose at 3 months was 86 mg/dL (IQR 78.5-103) and at 6 months was 87 mg/dL (IQR 75-115.8). There were 20 patients who were hospitalized and 9 patient deaths. Conclusions: Managing SIH is complex and requires a multidisciplinary approach. Patients who were seen had reduced episodes of hyperglycemia without increased episodes of hypoglycemia. A1c is an unreliable measurement in this patient population due to high cell turnover and frequent transfusions. Future studies using continuous glucose monitors could be investigated to assess the efficacy and feasibility of this pilot clinic. Disclosure D. Pham: None. K. Grdinovac: None. J. Leal: None. L. Rodriguez: None. A. Salva: None. W. Wesson: None. J. McGuirk: None.

804-P: Similar Hypoglycemia Duration with Once-Weekly Icodec vs. Degludec or Glargine U100 in Insulin-Treated T2D—A Post Hoc CGM Analysis from ONWARDS 2 and 4

Once weekly (OW) icodec is a basal insulin in development. Hypoglycemia duration during the switch (weeks 0-4) and steady state (weeks 22-26) periods from two phase 3, randomized, treat-to-target trials in T2D was investigated, using double-blinded Dexcom G6 CGM. Insulin-treated individuals were randomized to OW icodec or once-daily (OD) degludec (ONWARDS 2), or OW icodec or OD glargine U100 with mealtime insulin aspart (ONWARDS 4). When switching, a one-time only additional 50% icodec dose was administered. Basal insulins were titrated weekly. Median hypoglycemia <70 mg/dL duration for episodes lasting ≥ 15 minutes and the proportion of such episodes spent <54 mg/dL were assessed. Median duration of hypoglycemia <70 mg/dL was similar between icodec and comparators during switch and at steady state (Figure), with no apparent clustering in either time-period. At steady state (icodec/degludec and icodec/glargine U100), of the episodes <70 mg/dL, 66.6/63.9% and 60.4/60.0% spent no time <54 mg/dL; 23.2/26.6% and 29.2/28.8% included episodes <54 mg/dL for ≥15 minutes; and 10.2/9.5% and 10.4/11.2% included episodes <54 mg/dL for <15 minutes, respectively. In insulin-treated T2D, the duration of hypoglycemic episodes <70 mg/dL was similar, with no apparent clustering, during switch and at steady state for OW icodec versus OD degludec or glargine U100. Disclosure H.S.Bajaj: Research Support; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Anji Pharmaceuticals, Eli Lilly and Company, Kowa Company, Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Tricida, Inc. B.Ásbjörnsdóttir: Employee; Novo Nordisk. L.Carstensen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. L.Lang lehrskov: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. C.Mathieu: Advisory Panel; Novo Nordisk A/S, Boehringer Ingelheim Inc., Eli Lilly and Company, Medtronic, Vertex Pharmaceuticals Incorporated, Roche Diabetes Care, Imcyse, Speaker's Bureau; Novo Nordisk A/S, AstraZeneca, Boehringer Ingelheim Inc., Eli Lilly and Company, Medtronic, Vertex Pharmaceuticals Incorporated. A.Philis-tsimikas: Advisory Panel; Dexcom, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Medtronic, Research Support; Novo Nordisk A/S, Lilly, Viking Therapeutics, NIH - National Institutes of Health. T.Battelino: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Medtronic, Abbott Diabetes, Consultant; Indigo Diabetes, Research Support; Novo Nordisk, Sanofi, Medtronic, Novartis, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, Sanofi, Medtronic, Abbott Diabetes, Dexcom, Inc. Funding Novo Nordisk A/S

55-LB: “Older patients manifest it differently”—HCP Perspectives of People Aging with Type 1 Diabetes

In the last decade, people with type 1 diabetes (T1D) are living longer due to advancements in diabetes technology. However, there is little research on treating this population. This study examined health care professionals’ (HCPs) experiences in treating older adults with T1D to identify clinical and practical differences. Participants were recruited from T1D Exchange (an online diabetes community) and 11 HCPs (average time in practice: 21.5 years) were interviewed. Interview questions focused on their clinical experiences, challenges that older people experienced, and needs of this aging population that might be different from other age groups. The interviews were recorded, transcribed, independently coded by 2 coders and thematically analyzed. Themes included treatment recommendations for older adults with T1D, diabetes education, post-severe hypoglycemic event recommendations, fear of hypoglycemia, insurance, and polypharmacy. As older adults with diabetes continue to live longer, new recommendations for this age group should be considered. Specifically, treatment recommendations amongst older adults differ in glycemic target goals and HbA1c range. These recommendations are made to combat any severe hypoglycemic episodes prone to this population. There is a greater degree of neurocognitive decline which poses a greater risk for life threatening emergencies, not only in older adults but also older adults with T1D. It is the HCPs duty to prepare this population for the risks of developing certain complications associated with T1D as well as the possible dangers if the more emergent situations are not addressed promptly. Disclosure K. Uddin: None. H. L. Stuckey: Consultant; Eli Lilly and Company. A. Hughes: None.

147-OR: Revisiting the Impact of Opioid Receptor Blockade on Hypoglycemia-Associated Autonomic Failure (HAAF)

HAAF, which has been defined as >20% reduction in average epinephrine (Epi) levels following recurrent hypoglycemia (PMID: 28911152), complicates insulin therapy in T1D. We previously showed that activation of opioid receptors induces HAAF, while intravenous (IV) administration of the opioid receptor antagonist naloxone prevents HAAF. Because of its wide clinical use and possible direct CNS effects, we examined the effects of intranasal naloxone (IN) on hypoglycemia and HAAF. Seventeen (15M, age 43.8±8.7) healthy adults were enrolled in a randomized, placebo-controlled, cross-over, double-blinded study in which they underwent three hyperinsulinemic hypoglycemic clamp studies (duration 2h, glucose nadir 54 mg/dL), with administration of IN (4mg) or placebo during the first two clamps. Two subjects were excluded for lack of Epi response to hypoglycemia. Nine of the remaining 15 subjects developed HAAF, confirming inter-individual variability in susceptibility to HAAF (PMID: 32915987, 35475026). Among the 15 subjects included in the analysis, Epi levels trended downward between the 1st and 3rd clamps in placebo studies (mean ± SEM: 677 ± 114 vs. 512 ± 78 pg/mL, p=0.054), whereas Epi levels remained stable in IN studies (1st vs. 3rd: 519 ± 70 vs. 487 ± 77 pg/mL, p= 0.69). Among the 9 subjects who developed HAAF, Epi levels during the 1st clamp were significantly lower with IN vs. placebo (493 ± 102 vs. 858 ± 161 pg/mL, p=0.03), but there was no further reduction in Epi with IN (1st vs. 3rd: 493±102 vs. 539±101 pg/ml, p=0.67). In summary, these studies suggest differential effects of intranasal naloxone on initial vs. repeated hypoglycemic episodes. Specifically, IN may be effective in preventing Epi blunting during repeated exposure to hypoglycemia. In subjects susceptible to HAAF, IN may paradoxically blunt the Epi response to initial hypoglycemic exposure. Future studies should investigate the clinical significance of initial vs. ongoing epinephrine responses to hypoglycemia. Disclosure C.E.Boyle: None. M.Hawkins: None. E.Lontchi yimagou: Employee; Sanofi. S.Aleksic: None. P.M.Mathias: None. M.Nogueira cordeiro: None. A.Manavalan: None. M.Carey: None. N.Jiang: None. O.Sandu: None. I.Gabriely: None. K.Zhang: None. Funding National Institutes of Health (R01DK079974)

1157-P: Diabetic Ketoacidosis (DKA) Rates Do Not Differ by Insulin Pump Use vs. Nonuse in Teens with Type 1 Diabetes (T1D) and Executive Function (EF) Problems

Aim: Providers may resist offering pump therapy to teens with T1D who have challenges with EF (planning, organization) due to concerns for DKA. We evaluated rates of DKA and severe hypoglycemia according to pump use in teens with and without EF problems. Methods: Parents of teens aged 13-17 years with T1D provided proxy reports of teen EF using the Behavior Rating Inventory of Executive Function (BRIEF). Global Executive Composite (GEC) t-score ≥60 defined risk of executive dysfunction. Families reported severe hypoglycemic episodes and ER visits/hospitalizations for hyperglycemia (including DKA) every 3 months for 18 months. Incidence rates (IR) were calculated as events/100 person-years. DKA IR includes ER visits/hospitalizations for either hyperglycemia or DKA. Poisson regressions evaluated differences in IR by pump use, CGM use, and BRIEF score. Results: 169 teens (54% male) had baseline age 14.9±1.3 years, T1D duration 7.4±3.7 years, A1c 8.5±1.0%; 69% were pump users, 41% used CGM some time during follow-up, and 31% had GEC ≥60. During 297 person-years, severe hypoglycemia IR was 38.3/100 person-years and DKA IR was 7.7/100 person-years. There were no differences in hypoglycemia IR by pump or CGM use or GEC score. There was no difference in DKA IR by CGM use while DKA IR was lower in pump users vs non-users (4.9 vs 14.0, p=.01) and in those with GEC <60 vs ≥60 (4.9 vs 14.0, p=.01). Among those with GEC <60, DKA IR was lower in pump users vs non-users (2.0 vs 13.7, p=.003); in those with GEC ≥60, DKA IR was similar in pump users and non-users (13.7 vs 14.4, p=.94). Conclusion: In this sample of teens with T1D, hypoglycemia IR did not differ by pump or CGM use or EF status; in the teens with EF challenges, DKA IR was not higher in pump users vs non-users. These observations suggest that hesitation by clinicians to offer insulin pump therapy to teens with clinical suspicion of executive dysfunction due to concerns for increased DKA risk may not be warranted. Disclosure R.J.Vitale: None. L.K.Volkening: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. Funding National Institutes of Health (P30DK036836, R01DK095273); JDRF (2-SRA-2014-253-M-B); Iacocca Family Foundation

Expanding the Role of Continuous Glucose Monitoring in Modern Diabetes Care Beyond Type1 Disease.

Application of continuous glucose monitoring (CGM) has moved diabetes care from a reactive to a proactive process, in which a person with diabetes can prevent episodes of hypoglycemia or hyperglycemia, rather than taking action only once low and high glucose are detected. Consequently, CGM devices are now seen as the standard of care for people with type1 diabetes mellitus (T1DM). Evidence now supports the use of CGM in people with type2 diabetes mellitus (T2DM) on any treatment regimen, not just for those on insulin therapy. Expanding the application of CGM to include all people with T1DM or T2DM can support effective intensification of therapies to reduce glucose exposure and lower the risk of complications and hospital admissions, which are associated with high healthcare costs. All of this can be achieved while minimizing the risk of hypoglycemia and improving quality of life for people with diabetes. Wider application of CGM can also bring considerable benefits for women with diabetes during pregnancy and their children, as well as providing support for acute care of hospital inpatients who experience the adverse effects of hyperglycemia following admission and surgical procedures, as a consequence of treatment-related insulin resistance or reduced insulin secretion. By tailoring the application of CGM for daily or intermittent use, depending on the patient profile and their needs, one can ensure the cost-effectiveness of CGM in each setting. In this article we discuss the evidence-based benefits of expanding the use of CGM technology to include all people with diabetes, along with a diverse population of people with non-diabetic glycemic dysregulation.

Insulinoma with peripheral neuropathy: a case report

BackgroundInsulinomas are rare neuroendocrine tumors that typically present with hypoglycemic crises. Peripheral neuropathy is an uncommon complication of insulinoma. Most clinicians expect peripheral neuropathy symptoms to reverse completely after the insulin-secreting tumor is resected, but this may be a misassumption.Case reportWe report a case of a 16-year-old Brazilian boy with clonic muscle spasms of the lower limbs for almost one year. Disabling paraparesis and confusional episodes had progressively set in as well. There were no sensorial abnormalities in the lower limbs, upper limbs or cranial nerves. An electromyography revealed a motor neuropathy of the lower limbs. The diagnosis of insulinoma was established as serum insulin and C-peptide concentrations were inappropriately normal during spontaneous episodes of hypoglycemia. Following a normal abdominal magnetic resonance scan, the imaging work-up continued with an endoscopic ultrasound, which localized the tumor at the pancreatic body-tail transition. Once localized, a prompt surgical removal (enucleation) of the tumor was undertaken, leading to an immediate and complete resolution of hypoglycemia. The time length between the onset of symptoms and tumor resection was 15 months. After surgery, the symptoms of peripheral neuropathy of the lower limbs showed a slow and only partial improvement. At a two-year follow-up after surgery, although being able to lead a normal and productive life, the patient still reported symptoms of reduced muscular strength in the lower limbs and a new electroneuromyography analysis showed chronic denervation and reinnervation in the legs’ muscles—indicating chronic neuropathic injury.ConclusionThe events of this case reinforce the importance of an agile diagnostic work-up and spry definitive treatment for patients with this uncommon disease, enabling the cure of neuroglycopenia before permanent bothersome complications ensue.

Doege-Potter Syndrome Secondary to a Solitary Fibrous Tumor of the Abdominopelvic Cavity: A Case Report

Solitary fibrous tumors (SFTs) are rare neoplasms initially identified as "localized fibrous mesothelioma" predominantly found in the pleural cavity. Common clinical manifestations include pain, the presence of a palpablemass, as well as neurological or vascular symptoms. Tumors located in the abdomen or pelvis can exert pressure on adjacent structures, leading to symptoms such as urinary obstruction or retention, bowel obstruction or constipation, and abdominal distention. Doege-Potter syndrome is characterized by hypoglycemia resulting from excessive production of insulin-like growth factors by the tumor. We report the case of a 54-year-old male patient, diagnosed with type II diabetes 8 years ago, currently not undergoing any treatment, Admitted for investigation of recurrent episodes of hypoglycemia.

Dementia in Diabetes: The Role of Hypoglycemia.

Hypoglycemia, a common consequence of diabetes treatment, is associated with severe morbidity and mortality and has become a major barrier to intensifying antidiabetic therapy. Severe hypoglycemia, defined as abnormally low blood glucose requiring the assistance of another person, is associated with seizures and comas, but even mild hypoglycemia can cause troubling symptoms such as anxiety, palpitations, and confusion. Dementia generally refers to the loss of memory, language, problem-solving, and other cognitive functions, which can interfere with daily life, and there is growing evidence that diabetes is associated with an increased risk of both vascular and non-vascular dementia. Neuroglycopenia resulting from a hypoglycemic episode in diabetic patients can lead to the degeneration of brain cells, with a resultant cognitive decline, leading to dementia. In light of new evidence, a deeper understating of the relationship between hypoglycemia and dementia can help to inform and guide preventative strategies. In this review, we discuss the epidemiology of dementia among patients with diabetes, and the emerging mechanisms thought to underlie the association between hypoglycemia and dementia. Furthermore, we discuss the risks of various pharmacological therapies, emerging therapies to combat hypoglycemia-induced dementia, as well as risk minimization strategies.

Real-World User and Clinician Perspective and Experience with MiniMed™ 780G Advanced Hybrid Closed Loop System.

The advanced hybrid closed loop (AHCL) MiniMed™ 780G system changes basal insulin delivery every 5min and auto bolus in response to sensor glucose values. We assessed the performance of the AHCL system in real-world settings for individuals with type 1 diabetes (T1DM) as well as user and clinician perspectives and satisfaction. We held two peer group discussions: one having adults with T1DM/parents of children and adolescents with T1DM to understand their experiences with the AHCL system and another with healthcare providers (HCPs). Responses from the discussions were analyzed and categorized into themes by two independent researchers, with any inconsistencies resolved by consensus. We also analyzed data from the system uploaded to CareLink personal software. Glycemic outcomes, including time in range (TIR), time below range (TBR), time above range (TAR), mean sensor glucose (SG) levels, glucose management indicator (GMI), sensor use, and percentage of time spent in AHCL, were determined. The peer group discussions revealed numerous key themes and issues for each group, such as the significance of setting reasonable expectations, carbohydrate counting and bolus dosing, technical difficulties, and overall user experience. The users (n = 25; T1DM; 17 female; age 13.8 ± 7.49years; A1C 6.54 ± 0.45%; duration of diabetes 6 ± 6.78years) were very satisfied with the system. Most users experienced consistent blood glucose values with very few hypoglycemic episodes. However, there were a few limitations reported, such as hyperglycemic episodes caused by inaccuracies in carb counting, issues with sensor connectivity, and cannula blockages or kinking for those using insulin Fiasp. Users achieved a mean GMI of 6.4 ± 0.26%, TIR of 83.0 ± 8.12%, TBR (54-70mg/dL) of 2.0 ± 0.81%, TBR* (< 54mg/dL) of 0%. All of the users achieved a TIR of > 70%. The use of the AHCL system in T1DM resulted in robust glycemic control, minimizing hypoglycemia. Providing training to both users and HCPs can help them use the system effectively.

Ghrelin does not impact the blunted counterregulatory response to recurrent hypoglycemia in mice.

Recurrent episodes of insulin-induced hypoglycemia in patients with diabetes mellitus can result in hypoglycemia-associated autonomic failure (HAAF), which is characterized by a compromised response to hypoglycemia by counterregulatory hormones (counterregulatory response; CRR) and hypoglycemia unawareness. HAAF is a leading cause of morbidity in diabetes and often hinders optimal regulation of blood glucose levels. Yet, the molecular pathways underlying HAAF remain incompletely described. We previously reported that in mice, ghrelin is permissive for the usual CRR to insulin-induced hypoglycemia. Here, we tested the hypothesis that attenuated release of ghrelin both results from HAAF and contributes to HAAF. C57BL/6N mice, ghrelin-knockout (KO) + control mice, and GhIRKO (ghrelin cell-selective insulin receptor knockout) + control mice were randomized to one of three treatment groups: a "Euglycemia" group was injected with saline and remained euglycemic; a 1X hypoglycemia ("1X Hypo") group underwent a single episode of insulin-induced hypoglycemia; a recurrent hypoglycemia ("Recurrent Hypo") group underwent repeated episodes of insulin-induced hypoglycemia over five successive days. Recurrent hypoglycemia exaggerated the reduction in blood glucose (by ~30%) and attenuated the elevations in plasma levels of the CRR hormones glucagon (by 64.5%) and epinephrine (by 52.9%) in C57BL/6N mice compared to a single hypoglycemic episode. Yet, plasma ghrelin was equivalently reduced in "1X Hypo" and "Recurrent Hypo" C57BL/6N mice. Ghrelin-KO mice exhibited neither exaggerated hypoglycemia in response to recurrent hypoglycemia, nor any additional attenuation in CRR hormone levels compared to wild-type littermates. Also, in response to recurrent hypoglycemia, GhIRKO mice exhibited nearly identical blood glucose and plasma CRR hormone levels as littermates with intact insulin receptor expression (floxed-IR mice), despite higher plasma ghrelin in GhIRKO mice. These data suggest that the usual reduction of plasma ghrelin due to insulin-induced hypoglycemia is unaltered by recurrent hypoglycemia and that ghrelin does not impact blood glucose or the blunted CRR hormone responses during recurrent hypoglycemia.

Ramadan fasting in people with diabetes and chronic kidney disease (CKD) during the COVID-19 pandemic: The DaR global survey

Background and aimsThe DaR Global survey was conducted to observe the impact of the COVID-19 pandemic on the intentions to fast and the outcomes of fasting in people with diabetes and chronic kidney disease (CKD). MethodsMuslim people with diabetes and CKD were surveyed in 13 countries shortly after the end of Ramadan 2020, using a simple Survey Monkey questionnaire. ResultsThis survey recruited 6736 people with diabetes, of which 707 (10.49%) had CKD. There were 118 (16.69%) people with type1 diabetes (T1D), and 589 (83.31%) were with type2 diabetes (T2D). 62 (65.24%) people with T1D and 448 (76.06%) people with T2D had fasted with CKD. Episodes of hypoglycaemia and hyperglycaemia were more frequent among people with T1D compared to T2D, 64.52% and 43.54% vs 25.22% and 22.32% respectively. Visits to the emergency department and hospitalization were more frequent among people with CKD, however no significant difference was found between people with T1D and T2D. ConclusionThe COVID-19 pandemic had only a minor effect on the intention to fast during Ramadan in people with diabetes and CKD. However, hypoglycaemia and hyperglycaemia were found to be more frequent, as well as emergency visits and hospital admissions among people with diabetic kidney disease. Prospective studies are needed in future to evaluate the risk indicators of hypoglycaemia and hyperglycaemia among fasting people with CKD, especially in the context of different stages of kidney disease.

Fetal Bowel Dilatation Associated With LCHAD Deficiency: A New Sonographic Finding

A long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency constitutes a very rare autosomal recessive disease, affecting long fatty acids’ metabolism. In the prenatal period, it is difficult to suspect this diagnosis in the absence of family history, as there are no specific sonographic signs of this disease. A 32-year-old pregnant woman was receiving follow-up care, as she was a carrier for Duchenne muscular dystrophy (DMD). The fetus was female, and the pregnancy progressed normally until 29th week of gestation. At that time, the fetal bowel had noted dilatation with mild hyperechogenicity. Fetal surveillance was conducted with sequential sonograms. Labor was induced at 36 weeks, due to pre-eclampsia. The newborn presented with poor weight gain and hypoglycemic episodes. Neonatal screening revealed the diagnosis of an LCHAD deficiency. Prenatal diagnosis of LCHAD is usually performed by genetic testing when there is a family history. However, only a few sonographic signs have been described in association with this disease, such as fetal bowel hyperechogenicity or cardiomyopathy. This is the first case study to report a prenatal sonographic finding of bowel dilatation in a fetus with LCHAD deficiency, and one of the few to report fetal bowel hyperechogenicity.