bluuebunny/crossref_metadata_2025 huggingface dataset:
1080-P: Addressing the Safety Challenges of Aldose Reductase Inhibition: Development of AT-001 for Diabetic Cardiomyopathy, a Potent and Selective Next Generation Aldose Reductase Inhibitor
Authors: PERFETTI RICCARDO , YEPURI GAUTHAM , QUADRI NOSIRUDEEN A. , GHANNAM AMEEN F. , RAMASAMY RAVICHANDRAN , SHENDELMAN SHOSHANA
Published: June 2020

Diabetic Cardiomyopathy (DbCM) leading to overt heart failure is a common sequelae of both type 1 and type 2 diabetes. Prior attempts to develop treatments for DbCM via inhibition of Aldose Reductase (AR) were unsuccessful, due to low AR binding affinity and off-target binding with Aldehyde Reductase (AldR), an enzyme critical for detoxification of aldehydes in the liver and normal hepatocyte function. This resulted in liver-related safety and tolerability issues with first generation ARIs. We report on the selectivity and specificity of AT-001, a novel small molecule ARI with optimized affinity and specificity for AR and minimal to zero off-target AldR activity.

Methods and Results: AT-001 was evaluated for AR binding affinity vs. zopolrestat, a prior best in class ARI, which had been challenged with liver toxicity issues in clinical development. AT-001 demonstrated logarithmically improved AR inhibitory activity (IC50 of 30 pmol for AT-001 and 10 nmol for zopolrestat). Liver enzyme evaluations demonstrated that AT-001 showed no inhibition of AldR at 50x and 100x EC50 levels in assay medium, while zopolrestat inhibited AldR by 50% and 60% respectively (spec activity of 2.3 and 1.9 mmol NADPH/min/mg prot.). Additionally no elevations of ALT/AST’s were observed with AT-001 at doses up to 50x EC50, in contrast to zopolrestat which showed dose dependent release of ALT and AST (consistent with hepatocyte damage and eventual cell death). Finally, AT-001 was evaluated in a standard off-target receptor binding analysis of 87 substrates (13 enzymes, 74 binding assays); with no significant results (>50% inhibitory activity) observed.

Conclusion: The unique structure and activity of AT-001 provide potent selectivity for Aldose Reductase and lack of off-target effects. The in-vitro safety of this agent together with the positive safety data from the phase 1/2 program, supports the ongoing pivotal study in DbCM.

Disclosure

R. Perfetti: Stock/Shareholder; Self; Applied Therapeutics. G. Yepuri: None. N.A. Quadri: None. A.F. Ghannam: Employee; Self; Applied Therapeutics Inc. Stock/Shareholder; Self; Sanofi US. R. Ramasamy: Consultant; Self; Applied Therapeutics. S. Shendelman: Employee; Self; Applied Therapeutics. Stock/Shareholder; Self; Applied Therapeutics.

Funding

Applied Therapeutics (NCT04083339)
1085-P: Nasal Glucagon Was Efficacious in Reversing Insulin-Induced Hypoglycemia without Increasing Risk of Secondary Hyperglycemia
Authors: YAN YU , WANG QIANQIAN , CHILD CHRISTOPHER J. , ZHANG MICHELLE X.
Published: June 2020

Background: Nasal glucagon (NG), a ready-to-use therapy for treatment of severe hypoglycemia, contains 3 mg glucagon dry powder absorbed passively through nasal mucosa. We evaluated efficacy, pharmacodynamics (PD), and safety of NG compared to injectable glucagon (IG) in reversing insulin-induced hypoglycemia in Caucasian and Japanese adults with T1D or T2D.

Methods: Post-hoc analyses used data from 2 randomized, cross-over studies. Treatment success was defined as an increase in BG to ≥70 mg/dL or an increase of ≥20 mg/dL from nadir BG within 15 min of receiving glucagon. PD data, including area under the curve above 140 mg/dl [∆140 AUC (1-4 hr)], were used to evaluate the risk of secondary hyperglycemia. Tolerability was assessed with treatment-emergent adverse events and a symptom questionnaire.

Results: A similar proportion of NG [97.8% (131/134)] and IG patients [97.0% (130/134)] achieved treatment success. Geometric least square mean BGmax for NG and IG were 194 and 205 mg/dL (p<0.001), respectively. NG had significantly lower ∆140 AUC (1-4 hr) (p<0.001). NG had similar rates of nausea and vomiting versus IG, with higher rates of side effects related to nasal administration.

Conclusions: NG was efficacious and well-tolerated in reversing insulin-induced hypoglycemia in adults with T1D or T2D and did not increase the risk of secondary hyperglycemia compared to IG.

Disclosure

Y. Yan: Employee; Self; Eli Lilly and Company. Q. Wang: Employee; Self; Eli Lilly and Company. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. M.X. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1096-P: DPP-4 Inhibitor Teneligliptin Improves the Vascular Endothelial Function via Mechanism Different from Changes of EPCs Levels and Blood Glucose Metabolism
Authors: AKASHI NAOYUKI , UMEMOTO TOMIO , HODAKA YAMADA , FUJIWARA TAKAYUKI , YAMAMOTO KEI , TANIGUCHI YOUSUKE , SAKAKURA KENICHI , WADA HIROSHI , MOMOMURA SHIN-ICHI , FUJITA HIDEO
Published: June 2020

Background: DPP-4 inhibitors have been reported to have beneficial effects on endothelial function as sitagliptin increases circulating endothelial progenitor cells (EPCs) via inhibition of plasma stromal derived factor-1 alpha (SDF-1α). However, its mechanisms are unclear. We evaluated whether DPP-4 inhibitor teneligliptin increases the number of circulating EPCs through inhibition of SDF-1α metabolism and improves flow mediated vascular dilatation (FMD) in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) or its risk factors.

Methods: This study was a prospective, single-center, open-label, randomized controlled trial. A total of 16 patients with present or past history of ACS or multiple cardiovascular risk factors were enrolled, and who take any medicine for diabetes, whose HbA1c > 7.5% and/or peak CPK > 2000 IU/ml, were excluded. Variable of glucose and lipids, the number of EPCs, activity levels of DPP-4 and SDF-1α and FMD were evaluated at baseline and at 28±4 weeks after enrollment in all patients. They were randomly assigned into 2 groups either 20mg per day teneligliptin or control. Finally, 8 patients were included in teneligliptin group and 8 in control. All data were analyzed by paired t-test, and p < 0.05 was considered statistically significant.

Results: DPP-4 activity (∆-509.5±105.7 vs. ∆32.8±53.4 μU/ml) and SDF-1α levels (∆-695.6±443.2 vs. ∆11.1±193.7 pg/ml) were significantly decreased after 28 weeks in teneligliptin group compared to control, respectively. Number of EPCs, and variables of glucose and lipids were not significantly different between two groups before and after 28 weeks. However, FMD was significantly improved in the teneligliptin group compared to control (∆3.8±2.1 vs. ∆-0.3±2.9%, p = 0.006) after 28 weeks treatment.

Conclusion: These results indicate that teneligliptin improves FMD by different mechanisms from the increase of blood EPC number via SDF-1α.

Disclosure

N. Akashi: None. T. Umemoto: None. Y. Hodaka: None. T. Fujiwara: None. K. Yamamoto: None. Y. Taniguchi: None. K. Sakakura: None. H. Wada: None. S. Momomura: None. H. Fujita: None.
1117-P: Cardiovascular and Glycemic Benefits of Bexagliflozin as an Adjunct to Metformin for the Treatment of Type 2 Diabetes in Adults: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: HALVORSEN YUAN-DI C. , LOCK JOHN P. , FREEMAN MASON W.
Published: June 2020

Bexagliflozin is a potent and selective sodium glucose co-transporter 2 inhibitor. To evaluate the safety and effectiveness of bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes mellitus, participants (317) were randomized to receive bexagliflozin or placebo in addition to ongoing treatment with metformin. The primary endpoint was the placebo-adjusted change in HbA1c from baseline to week 24. Changes in systolic blood pressure (SBP), fasting plasma glucose (FPG) and body mass were secondary endpoints. The study also enrolled an open label arm of participants with elevated HbA1c. Including post-rescue observations, the mean change in HbA1c was 1.09% (95% CI 1.24%, 0.94%) in the bexagliflozin arm and 0.56% ( 0.71%, 0.41%) in the placebo arm, for a difference of -0.53% ( 0.74%, 0.32%; p < 0.0001). By the last-observation-carried-forward method, the intergroup difference was -0.70% ( 0.92, 0.48; p < 0.0001). The open label cohort experienced a mean change in HbA1c of 2.82% ( 3.23%, -2.41%). The placebo-adjusted changes from baseline SBP, FPG and body mass and SBP were 7.07 mm Hg ( 9.83, -4.32; p < 0.0001), -1.35 mmol L-1 (-1.83, -0.86; p < 0.0001) and 2.51 kg (-3.45, -1.57; p < 0.0001). Adverse events were experienced by 42.4% and 47.2% of subjects in the bexagliflozin and placebo arms, respectively, and fewer subjects in the bexagliflozin arm experienced serious adverse events. Bexagliflozin produced clinically meaningful and statistically significant improvement in measures of cardiovascular health and glycemic control in a population of diabetic adults inadequately controlled by metformin alone. ClinicalTrials.gov Identifier: NCT03259789.

Disclosure

Y.C. Halvorsen: Research Support; Self; Theracos, Inc. J.P. Lock: None. M.W. Freeman: Research Support; Self; Theracos, Inc.
1156-P: Correlates of Analog vs. Human Basal Insulin Use and Glycemic Control among Adults with Type 2 Diabetes in the United States
Authors: CROMER SARA , WEXLER DEBORAH J. , KAZEMIAN POOYAN
Published: June 2020

There has been a shift from use of less expensive human basal insulins to costlier analog basal insulins for type 2 diabetes since the early 2000s. It is not known whether this trend has been uniform across patient groups or if these newer insulins are associated with improved outcomes in a nationwide sample. We performed statistical analyses using six consecutive cross-sectional National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2016 to determine patient characteristics and glycemic management associated with use of analog compared to human basal insulin. NHANES respondents were included if they had a diagnosis of diabetes, reported currently taking basal insulin, and did not meet criteria for type 1 diabetes. Demographic factors (age, sex, race), socioeconomic factors (educational attainment, health insurance status), and NHANES cycle were included in a logistic regression model predicting use of analog versus human basal insulin; subsequently all variables were included in models predicting HbA1c. Between NHANES cycles 2005-2006 and 2015-2016, 723 participants met inclusion criteria. Basal insulin use increased from 9.6% to 17.2% among respondents with type 2 diabetes. Among basal insulin users, analog basal insulin use rose from 58% in 2005-2006 to 88% in 2015-2016. Compared to non-Hispanic white respondents, African American respondents were less likely to report use of analog basal insulin (aOR 0.42, 95% CI 0.24-0.74), as were Hispanic respondents (aOR 0.54, 95% CI 0.30-0.96), after adjusting for age, sex, education, and health insurance status. Older age and having health insurance, but not type of basal insulin, correlated with achievement of HbA1c goals. The use of analog or human basal insulin is associated with race and ethnicity, but not with other demographic and socioeconomic measures. Increased use of analog basal insulins in the United States between 2005-2016 was not associated with improved glycemic control.

Disclosure

S. Cromer: Employee; Spouse/Partner; Johnson & Johnson. D.J. Wexler: Other Relationship; Self; Novo Nordisk A/S. P. Kazemian: None.

Funding

National Institutes of Health (T32DK007028)
1158-P: Cost-Effectiveness of Empagliflozin vs. Liraglutide as Second-Line Therapy for Type 2 Diabetes in the United States
Authors: REIFSNIDER ODETTE , PIMPLE PRATIK , STARGARDTER MATTHEW J.D. , BRAND SARAH , DESAI NIHAR , SHETTY SHARASH
Published: June 2020

Background: The ADA’s “Standards of Medical Care in Diabetes” recommends use of an SGLT2 inhibitor or GLP-1 receptor agonist as one of the six drug classes after metformin (MET) in T2D patients. These therapies are preferred among T2D patients with cardiovascular disease (CVD) based on clinical trial results demonstrating significant improvement in clinical outcomes. We sought to examine the economic implications of sequential use of these therapies.

Methods: An economic simulation model evaluating treatment in U.S. T2D patients after MET with empagliflozin (EMPA) as 2nd line and liraglutide (LIRA) as 3rd line vs. LIRA as 2nd line and EMPA as 3rd line was used to estimate the lifetime health and cost outcomes of T2D-related complications and adverse events (AEs). Complications, including CV death, myocardial infarction, stroke, and renal outcomes, were predicted using United Kingdom Prospective Diabetes Study risk equations and EMPA-REG OUTCOME data. A meta-analysis informed treatment-induced changes in HbA1c, SBP, and weight in patients without CVD. For each complication in patients with CVD, an indirectly estimated hazard ratio of LIRA vs. EMPA was applied. Costs ($2019), AE rates, and utilities were sourced from published literature.

Results: Compared with LIRA as 2nd line, use of EMPA added 0.32 quality-adjusted life-years (QALYs) and led to lower lifetime costs (by $11,422/patient), suggesting dominance over 2nd line LIRA (improved health outcomes at lower cost). These results were similar across CVD subgroups. Patients with CVD at baseline compared to those without CVD showed larger gains in incremental QALYs (0.42 with CVD, 0.29 without CVD) with somewhat lower cost savings (by $9,550, $12,392, respectively) for 2nd line EMPA vs. LIRA, showing dominance in both subpopulations.

Conclusion: For T2D patients with and without CVD, the use of EMPA on background MET was a dominant strategy for U.S. payers, associated with improved outcomes and lower costs as compared with LIRA.

Disclosure

O. Reifsnider: Consultant; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharmaceuticals, Inc. P. Pimple: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Employee; Spouse/Partner; CVS Caremark. M.J.D. Stargardter: Consultant; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharmaceuticals, Inc. S. Brand: Consultant; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharmaceuticals, Inc. N. Desai: None. S. Shetty: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.
1170-P: Provider Response to Critical Action Hypoglycemia in the Ambulatory Setting
Authors: ASHOK ADITYA , ABUSAMAAN MOHAMMED S. , MATHIOUDAKIS NESTORAS
Published: June 2020

Objective: There is no standardized defined threshold for outpatient critical action value (CAV) hypoglycemia and a scarcity of literature on provider responses to it. The aim of this study was to characterize patient demographics of, provider/patient responses to, and clinical sequelae of CAV hypoglycemia.

Methods: This was a retrospective EMR-based cohort study of all ambulatory patients with a serum glucose <50 mg/dL measured at the clinical laboratories of Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center between April 1, 2013 and January 31, 2017. Manual chart review was conducted using an electronic questionnaire.

Results: Two hundred nine CAV hypoglycemic episodes from 106 unique patients were identified. The median (IQR) hypoglycemic BG value was 43 (37.0, 47.0) mg/dL, and the median time from BG specimen collection to result was 158.0 min. The majority (72.2%) of patients had diabetes mellitus. The next 3 most common comorbidities were CHF (29.2%), HIV (19.6%), and ESRD (8.6%). The median age was 58 yrs and the majority (67.0%) were black; there was roughly equal gender distribution (53.6% male). Providers contacted patients in 128 (61.2%) of these episodes, and most commonly no hypoglycemic etiology (63.3%) and no signs or symptoms of hypoglycemia (80.5%) were documented. The most common documented symptoms were weakness/fatigue (32.0%), dizziness (16.0%), and tremor (12.0%). Only 4 serious adverse events were found, 3 of which had a related ED visit within 24 hrs of CAV, 1 of which involved loss of consciousness, and 2 of which involved glucagon administration.

Conclusion: Though CAV hypoglycemia tended to occur in individuals over 50 with common comorbidities and without documented hypoglycemic signs/symptoms, providers inconsistently reached out to patients and there were few serious adverse events. Further research is needed to identify optimal CAV glucose thresholds and responses, especially considering the delay between lab draw and provider/patient communication.

Disclosure

A. Ashok: None. M.S. Abusamaan: None. N. Mathioudakis: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK111986-01)
1171-P: Endocrine Final Recommendation Note (EFR) Embedded in the Electronic Medical Record (EMR) Improves the Discharge Process for Hospitalized Patients with Diabetes (DM)
Authors: PINKHASOVA DIANA , DONIHI AMY , FETERIK KRISTIAN , KORYTKOWSKI MARY T. , FRENCH ESRA KARSLIOGLU
Published: June 2020

Hospitalized patients with DM represent a group at high risk for readmission. Variability in how instructions for home DM management are provided at discharge can contribute to this risk.

At our institution, recommendations made by the endocrine consult service were not always accurately translated into patient discharge orders by the primary service.

Therefore, the EFR embedded within the EMR was developed. We investigated its effectiveness by reviewing the EMR of 48 patients discharged with insulin prior to (group 1) and following implementation (group 2) for fidelity of recommendations carried out by the primary service. Accuracy of the diabetes-related discharge regimen was defined as correct type and dose of insulin, correct administration supplies (syringes vs. pen needles), and provision of appropriate glucose monitoring supplies by the primary team.

About 50% of patients had a change in their DM regimen at discharge. Insulin was added as a new medication in 29% vs. 44% of patients in groups 1 and 2 respectively.

There was significant improvement in the accuracy of the diabetes-related discharge regimen (68% vs. 96%, p = 0.001).

These results demonstrate that deficiencies in the discharge process can be ameliorated by EMR tools which facilitate a safer transition of care from inpatient to outpatient settings for patients with DM.

Disclosure

D. Pinkhasova: None. A. Donihi: None. K. Feterik: None. M.T. Korytkowski: None. E. Karslioglu French: None.
1180-P: Better Care Strategies Are Necessary to Address Poor Medication Adherence
Authors: SPERL-HILLEN JOANN M. , ANDERSON JEFFREY P. , HAAPALA JACOB , CHUMBA LILIAN , EKSTROM HEIDI , APPANA DEEPIKA , DESILVA MALINI B. , O’CONNOR PATRICK J.
Published: June 2020

Background: As part of a clinical decision support (CDS) and pharmacist outreach interventional study to improve medication adherence, we analyzed rates and clinical implications of poor adherence for diabetes (DM), hypertension (HTN) and lipid control.

Methods: In two high performing care delivery systems in MN, 28 clinics were randomized to an adherence CDS intervention or control. The CDS uses web-based algorithms to assess clinical data and objectively capture poor adherence using an Epic based measurement of Proportion of Days Covered (ePDC) calculated using SureScripts dispense data with a moderate or high confidence rating. For 16 weeks in 2019, the CDS ran silently in all primary care encounters of patients age 18-75 to determine how many patients qualified for study eligibility using the following criteria: 1.DM cohort: A1c ≥8% with a non-insulin glycemic medication ePDC < 80%.

2. HTN cohort: BP ≥140/90 on two separate consecutive dates with a BP medication ePDC < 80%.

3. Lipid cohort: ACC/AHA criteria for statin use, on a statin with ePDC < 80%, excluding for LDL < 70 mg/dl.

Results: Of 142,879 patients, 138,252 remained after excluding for cancer, pregnancy, hospice or nursing home. A non-insulin DM medication was identified in 15,546 (11%). Of these, 3890 (25%) had A1C ≥ 8%, and of these 1467 (59%) had poor adherence. Among the DM cohort, the mean A1C was 9.6% and 30% had A1C ≥10%. Of patients identified with DM in the HTN cohort (494/1711, 29%), 60% had a systolic blood pressure ≥ 150 mm Hg. Of patients identified with DM in the lipid cohort (2298/4564, 50%), 19% had an LDL ≥130 mg/dl.

Conclusion: Over 14 weeks, large numbers of DM patients were identified at primary care encounters with difficulty achieving A1C, BP and lipid goals in association with poor medication adherence, which was often unrecognized. Based on extremely high A1C, BP and LDL levels in these patients, there is a tremendous clinical opportunity to identify and address poor adherence using CDS and/or pharmacist care team involvement.

Disclosure

J.M. Sperl-Hillen: None. J.P. Anderson: None. J. Haapala: None. L. Chumba: None. H. Ekstrom: None. D. Appana: None. M.B. DeSilva: None. P.J. O’Connor: None.
1200-P: Use of SGLT2 Inhibitors in Hospitalized Patients in an Academic Center
Authors: PALERMO NADINE E. , GOODBERLET MELANIE , CROMWELL GRACE , SMITH COLLEEN M. , BILODEAU AMY , SZUMITA PAUL M. , MCDONNELL MARIE E.
Published: June 2020

Recent data shows significant cardiovascular and renal benefit due to SGLT2 inhibitor (SGLT2i) therapy. However, use in the acute setting is limited and deferred due to concern of ketoacidosis especially in the setting of decreased nutrition intake and illness. Between 5/1/19 and 11/25/19 in one hospital, the inpatient formulary allowed the use of SGLT2i in patients with diabetes on the cardiology service as part of a supervised pilot program. As a result, 94 hospitalized patients were exposed to at least one dose of SGLT2i, 24 (25%) directed by the pilot program (PILOT), and 70 (75%) undirected (UND). In the UND group, 12 (13%) were newly started on SGLT2i and 58 (62%) were continued from home. Among all patients, 29.8 % were women, mean age 65, A1c 8.3% and GFR 67 mL/min. 17 patients (18%) had GFR ≤ 45, who were 5 years older on average (p= 0.04). In hospital there was no incident metabolic acidosis or clinically significant hypoglycemia. 79.8% of patients remained on SGLT2i at 1 month. 55 patients had data within 3 months post discharge. Of those still taking SGLT2i at 1 month, there was no significant change in systolic BP (SBP) at 1 or 3 months across all groups. In the UND group, there was no significant change in GFR. By comparison, in the PILOT group there was both a significant decrease in estimated GFR at 1 month (-6.95 mL/min, p= <0.01) and in SBP of -4.62 mmHg (p=0.04). Of all those newly started on SGLT2i, 6 had ≥ 25% reduction in GFR and moved up one CKD stage by 3 months; one moved from CKD stage 4 to 5. Among the patients with 3 month data, 40% were readmitted within 90 days, 0.3% for CHF, 36% other cardiac and 6% infection. Baseline GFR did not affect readmission risk.

In conclusion, permitting use of SGLT2i in the acute setting to select populations is likely to increase overall exposure of the drug to the general inpatient diabetes population. While we did not identify ketoacidosis, which is rare, reduction in GFR is common. Substantial education and direction is needed for inpatient clinicians in both the inadvertent and intended use of SGLT2is.

Disclosure

N.E. Palermo: None. M. Goodberlet: None. G. Cromwell: None. C.M. Smith: None. A. Bilodeau: None. P.M. Szumita: None. M.E. McDonnell: None.
1203-P: Safety Implications of Insulin Prescribing in the Emergency Department
Authors: PATTERSON SIMONE L. , EKINCI ELIF I. , DRISCOLL ANDREA , RASMUSSEN BODIL
Published: June 2020

Background: Despite being a common comorbidity, diabetes is often overlooked when patients present to the emergency department (ED) with nondiabetic emergencies.

Aims: To examine the associations between insulin treated patients presenting to the ED with nondiabetic emergencies and;

(i) adverse glycaemia (AG); including hypoglycaemia (< 70 mg/dL) and hyperglycaemia (< 180 mg/dL) and insulin prescribing errors,

(ii) glycaemic variability and AG following ED evaluation and ward diabetes management.

Methods: A two-year retrospective medical record audit of discharged insulin treated adult patients (≥ 18 years) was conducted at a quaternary hospital. All patients presented to the ED with nondiabetic emergencies and admitted to general wards for > 24 hours and < 30 days.

Results: Of the 103 patients (Table), 25 (24%) had one or more prescribing errors charted in the ED. Thirty-nine (37.8%) patients experienced hypoglycaemia. Of these, 21 (53.8%) were prescribed sliding scale insulin (SSI) in the ED (p = 0.05). Despite uncontrolled hyperglycaemia, 40 (47.6%) patients had no change to their diabetes treatment during admission (p = 0.04).

Conclusions: Half of insulin treated patients experienced uncontrolled hyperglycaemia. Use of SSI regimens prescribed in the ED were associated with higher risk of AG. Safety for insulin treated patients should be prioritised from the time the hospital journey begins in ED to after discharge.

Disclosure

S.L. Patterson: None. E.I. Ekinci: None. A. Driscoll: None. B. Rasmussen: None.
1209-P: A Quality Improvement Initiative to Increase Utilization of Continuous Glucose Monitors Results in Improved Glycemic Outcomes in a Pediatric Diabetes Clinic
Authors: OBRYNBA KATHRYN , INDYK JUSTIN A. , GANDHI KAJAL , BUCKINGHAM DON A. , WELLS TRAVIS , WAYNE WYNOLA N. , KAMBOJ MANMOHAN K.
Published: June 2020

A minority of youth with type 1 diabetes (T1D) achieve HbA1c goals recommended by the ADA. Continuous glucose monitoring (CGM) is shown to improve glycemic control and reduce complications of disease. Despite this evidence, CGM utilization is low among youth with T1D. In this quality improvement project, we aimed to increase percentage utilization of CGM amongst our pediatric T1D clinic population from a baseline mean of 9% in 2017. Targeted interventions to achieve this goal included identification and tracking of utilizers vs. non-utilizers, creation of a standardized clinic workflow to initiate a new CGM device within the EMR, and identification of barriers to insurance coverage. CGM utilization in our pediatric T1D clinic increased from a mean 9% in 2017 to 53% in 2019. Over this same period, our clinic observed a 7% increase in patients who achieved goal HbA1c. Targeted interventions to increase CGM utilization in a pediatric T1D clinic secondarily led to improved glycemic outcomes.

Disclosure

K. Obrynba: None. J.A. Indyk: None. K. Gandhi: None. D.A. Buckingham: None. T. Wells: None. W.N. Wayne: None. M.K. Kamboj: Research Support; Self; Type 1 Diabetes TrialNet, Unitio, Inc.
1226-P: Effectiveness of Frequency of Visits in the Internet plus Diabetes Shared Care Clinic on Glucose Improvement in Patients with Type 2 Diabetes: A Real-World Analysis
Authors: LI ANG , ZHANG WENFEI , GUO XIAOHUI , ZHANG JUNQING
Published: June 2020

Background: Patients with diabetes need DSMS on the basis of systematic comprehensive management. However, there is no recommendation on how often regular follow-up visits patients should receive in China.

Objectives: To explore the effectiveness of frequency of visits in the Internet plus Diabetes Shared Care (IDSC) clinic on glycemic control among patients with type 2 diabetes followed-up more than 2 years.

Design: A retrospective single-center hospital-based propensity scores weighting (PSW) real-world analysis.

Methods: IDSC in Peking University First Hospital (PKUFH) provided individualized, systematic and continuous management with off-line and on-line support. Adult patients with type 2 diabetes who received at least second follow-up visit in IDSC clinic in the first semester of 2018 were eligible. All subjects were divided into three groups by actual follow-up visit times within 2018 Jan to 2019 Jan. Age, gender, diabetes duration, baseline metabolic profiles (BMI, HbA1c, LDL-c, BP), baseline Insulin usage and baseline costs of antidiabetic drugs were used as covariates for three-group PSW analysis to compare the average treatment effect in the population (ATE) of HbA1c in each group at 1-year and 2-year follow up.

Result: A total of 496 eligible subjects were included [Fv group (Four visits/y) n=330, Tv group (Three visits/y) n=128, TLv group (Two or Less visits/y) n=38]. After PSW, HbA1c of Fv group was improved in trend at 1-year follow up compared with Tv group (-0.25%, p=0.05) and TLv group (-0.34%, p=0.06) but was significantly improved at 2-year follow up (-0.34%, p=0.01 for Tv group; -0.55%, p=0.008 for TLv group). There was no significant difference in HbA1c between the Tv group and TLv groups at neither 1-year and 2-year follow-up.

Conclusions: Our findings indicate that regularly followed-up in IDSC clinic at least 4 times/year could efficiently improve glycemic control of among patients with type 2 diabetes.

Disclosure

A. Li: None. W. Zhang: Employee; Self; iHealth Labs. X. Guo: None. J. Zhang: None.
1227-P: Importance of Awareness and Treatment for Diabetes in Influenza Vaccination Coverage in Patients with Diabetes
Authors: KO SEUNG-HYUN , AHN YU-BAE , SONG KI-HO , LEE JUNG-MIN , KIM SUNG-KYOUNG , HAN KYUNGDO
Published: June 2020

Influenza is a global public health problem causing considerable morbidity and mortality. Although vaccination is the most effective way to prevent infection, vaccination coverage is insufficient in people with chronic disease under 65 years, especially diabetes. The purpose of this study was to evaluate influenza vaccination coverage and identify factors associated with influenza vaccination in Korean diabetic adults under 65 years. Data were obtained from 24,821 subjects in the Korea National Health and Nutrition Examination Survey (2014-2017). Socioeconomic, health-related, and diabetic factors were investigated for their relations with influenza vaccination in diabetic patients under 65 years using univariate and multivariate analyses. Among 24,821 subjects, 1,185 were diabetic patients under 65 years and their influenza vaccination rate was 36.5%. Socioeconomic (older age, female gender, non-smoker, light alcohol drinker, lower educational level, and employed status), health-related factors (lower fasting glucose and HbA1c level, good self-perceived health status, recent health screening, and diet therapy), and diabetic factors (more awareness and getting treated) were associated with influenza vaccination. In multivariate analysis, more awareness and getting treated for diabetes were associated with influenza vaccination in diabetic patients under 65 years (odds ratio: 1.553 and 1.495; 95% confidence interval: 1.080-2.233 and 1.057-2.115, respectively). Influenza vaccination rate was low in diabetic patients under 65 years, especially in those with unawareness and not getting treated for diabetes. Active screening and treatment for diabetes may be helpful to improve the influenza vaccination rate in these patients.

Disclosure

S. Ko: None. Y. Ahn: None. K. Song: None. J. Lee: None. S. Kim: None. K. Han: None.

Funding

Korean Ministry of Health and Welfare (HI18C0275)
123-LB: The Simplici-T1 Trial: Relationship between Glycemic Control and Insulin Dose
Authors: VALCARCE CARMEN , FREEMAN JENNIFER L. , DUNN IMOGENE , KLEIN KLARA , BUSE JOHN B.
Published: June 2020

The Simplici-T1 trial (NCT03335371), designed to explore the safety and efficacy of TTP399 as an oral adjunctive therapy for T1DM, showed that addition of TTP399 to an optimized insulin regimen produced a statistically significant improvement in HbA1c (-0.32%, p<0.01) and Daytime Time In Range (8%, p<0.05) relative to placebo. The treat-to-target (FPG: ~80-130mg/dL; post meal glucose: <180-200 mg/dL) design of the study allowed changes in insulin dose after the insulin-optimization period. To evaluate the effect that these changes could have on A1c, several pre-planned analyses were performed. A positive correlation was observed between reduction in A1c and both reduction in total insulin (p=0.008) (Figure 1) and bolus insulin dose (p=0.004) in the TTP399-treated group but not in the PBO group. A subgroup analysis, matching on changes in insulin use reveals that, relative to PBO, those treated with TTP399 who maintained the optimized insulin regimen improved A1c by -0.35%, p=0.04 (41%TTP399; 36% PBO). The group that reduced their total insulin dose by more than 0.06U/Kg (i.e.,>10% reduction in total and >20% reduction in bolus insulin dose; 47% TTP399; 33% PBO) improved A1c by -0.41%, p=0.013. These improvements occurred without increasing ketones in plasma or hypoglycemic events. During the 12-week treatment period, 12% of the TTP399 group and 31%of the PBO increased their insulin dose.

Disclosure

C. Valcarce: Employee; Self; vTv Therapeutics. J.L. Freeman: Employee; Self; vTv Therapeutics. Stock/Shareholder; Self; vTv Therapeutics. Stock/Shareholder; Spouse/Partner; vTv Therapeutics. I. Dunn: None. K. Klein: None. J.B. Buse: Consultant; Self; Cirius Therapeutics, CSL Behring, Neurimmune. Research Support; Self; American Diabetes Association, National Institutes of Health, Novo Nordisk A/S, Patient-Centered Outcomes Research Institute, Sanofi, Tolerion, Inc., vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings, Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg Therapeutics, Novo Nordisk A/S, Senseonics, Inc, vTv Therapeutics, Zafgen, Inc.

Funding

JDRF; vTv Therapeutics; National Institutes of Health (UL1TR002489)
123-OR: Short-Term Hyperglycemia Causes a Paradoxical Reduction in Sensory Neuron Excitability
Authors: CAMPANUCCI VERONICA A. , BAUTISTA MARICRIS , NEAPETUNG JOSEPH T.
Published: June 2020

Peripheral neuropathy in diabetes is characterized by a constellation of sensory abnormalities, including numbness, tingling, as well as exacerbated responses to painful and non-painful stimuli. Particular interest has concentrated on voltage-gated sodium (Nav) channels since they play central roles in painful forms of neuropathy in long-term diabetes. However, their possible contributions to the onset of neuropathy are still under investigation. In the current study, we aimed at elucidating the contribution of Nav channels during early hyperglycemia in sensory neurons from the Dorsal Root Ganglion (DRG). We used cultured DRG neurons, maintained in either control (5 mM glucose) or in high glucose media (25 mM) for up to 14 days, and intact DRG tissues from streptozotocin (STZ)-induced hyperglycemic mice (at 1 and 3 months after induction). To study Nav channel function we used whole-cell patch-clamp electrophysiology and biochemical analysis by Western blotting for the detection of Nav subunit expression. Our results indicate that DRG neurons maintained in high glucose showed reduced action potential firing frequency and reduced inward currents. The later was consistent with the downregulation of the tetrodotoxin sensitive (TTX-S) Nav1.3, Nav1.6, and Nav1.7 subunits in intact DRG tissues from one-month STZ-hyperglycemic mice. The Navβ2 subunit, which has been shown to regulate the cell surface expressions of TTX-S Nav channels, also shows reduced expression levels. Interestingly, after three months of STZ-induced hyperglycemia, there was a significant upregulation in the expression level of the TTX-S Nav1.7 subunit, which has been linked to painful forms of neuropathy. Taken together, our data revealed that changes in expression and function of TTX-S Nav subunits take place from the early stage of pathologic hyperglycemia. Therefore, our data suggest that Nav channel may be involved in the development of positive and negative sensory symptoms in diabetic neuropathy.

Disclosure

V.A. Campanucci: None. M. Bautista: None. J.T. Neapetung: None.

Funding

Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-03958)
1231-P: Type 2 Diabetes Care and Management: A Comparison of German and American Approaches
Authors: DINEGAR SARAH
Published: June 2020

Within their multi-payer healthcare system, Germany has employed Disease Management Programs (“DMP”s) nationwide to manage T2D since 2002. Studies have suggested T2D financial burden reduction and improved health outcomes since DMP implementation. No such standardized programs exist in the fragmented U.S. healthcare-system. This study evaluated German and American primary care physicians’ opinions of efficacy of their nation’s respective T2D management methods in improving health outcomes, healthcare costs, and quality of care. German physicians reported consistent protocol and resource availability for T2D management, while American physicians’ responses varied widely by their clinical network and their patients’ insurers. Strengths of Germany’s T2D DMPs included lack of financial barrier to care and increased frequency of diabetic visits and patient accountability. Weaknesses included bureaucratic documentation and lack of customization. Strengths of American methods revolved around opportunity for innovation, resulting in increasing utilization of technological tools and motivational interviewing techniques. Weaknesses stemmed from systematic inequality of access, including lack of insurance-covered diabetes education, prohibitively high costs of medication, and lack of affordable preventive care. Despite these differences between German and American T2D care, both nations struggle with imperfect patient compliance and difficulty of achieving sustainable lifestyle changes. This study provides primary care physicians’ opinions on best directions forward for chronic disease management, particularly addressing these universal challenges. Recommendations included widespread insurance coverage of dieticians, intensive diabetes education courses, and mental health counselors, as well as increased use of team-based care, telemedicine and apps to improve patient accountability, and value-based reimbursement.

Disclosure

S. Dinegar: None.

Funding

Northwestern University
124-OR: Progressive Loss of Corneal Nerve Fibers and Sensitivity with Duration of Obesity Type 2 Diabetes in Sprague-Dawley Rats: Valid Marker for Peripheral Neuropathy and Treatment
Authors: YOREK MARK A.
Published: June 2020

Purpose: Determine whether density of nerve fibers in the cornea and corneal function are valid markers for early detection and treatment of peripheral neuropathy in rat models of prediabetes and type 2 diabetes.

Methods: Rat models for prediabetes and type 2 diabetes were created and longitudinally studied for loss of structure and function of sensory nerves in the cornea and skin as well as nerve conduction velocity and vascular reactivity of epineurial arterioles. Reversibility of neuro and vascular pathology was also examined in these models following chronic obesity or type 2 diabetes after dietary intervention with menhaden oil a natural source of long chain omega-3 polyunsaturated fatty acids.

Results and Conclusions: Our longitudinal study demonstrated that vascular and neural dysfunction associated with obesity or type 2 diabetes occur early and are progressive. Decrease in cornea nerve fiber length and function were valid markers of disease in both the prediabetic and diabetic rat models and were more sensitive than decrease in intraepidermal nerve fiber density of the skin and thermal nociception of the hindpaw. Late intervention with menhaden oil reversed both vascular and peripheral damage induced by chronic obesity or type 2 diabetes. These studies provide support for examination of corneal structure and function as an early marker of peripheral neuropathy in prediabetes and diabetes. Furthermore, we demonstrate that omega-3 polyunsaturated fatty acids derived from fish oil as an effective treatment for peripheral neuropathy that occurs with chronic obesity or type 2 diabetes.

Disclosure

M.A. Yorek: Consultant; Self; Novo Nordisk Inc.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (DK107339); U.S. Department of Veterans Affairs (RX000889)
1242-P: Response Heterogeneity to Lifestyle Intervention in Latino Adolescents with Obesity
Authors: PENA ARMANDO , MCNEISH DANIEL , AYERS STEPHANIE , OLSON MICAH , VANDER WYST KILEY B. , WILLIAMS ALLISON , KONOPKEN YOLANDA P. , KELLER COLLEEN , CASTRO FELIPE GONZÁLEZ , PATRICK DONALD L. , SHAIBI GABRIEL Q.
Published: June 2020

Background: Lifestyle change is the cornerstone for preventing type 2 diabetes (T2D) in high risk populations. However, there is significant biological variability in how individuals respond. The purpose of this secondary analysis is to characterize response heterogeneity in high-risk youth after a lifestyle intervention that led to significant increases in insulin sensitivity.

Methods: Latino adolescents with obesity (N=90, age 15.4±0.9 y, BMI% 98.0±1.5) were enrolled in a 3-month lifestyle intervention and followed for 1 year. Insulin sensitivity (IS) was estimated by glucose and insulin response to OGTT at 0, 3, 6, and 12 months. Covariance pattern mixture models identified response phenotypes. Baseline T2D risk factors were compared among response phenotypes using one-way ANOVA.

Results: Four distinct response phenotypes were identified: Long-Term Responders (LTR, N=13), Short-Term Responders (STR, N=29), Slow Responders (SR, N=30), and Non-Responders (NR, N=18). LTRs exhibited the greatest increase in IS (β±SE linear, 0.51±0.2, p=0.002), STR exhibited early, non-significant increases in IS (-0.08±0.3, p=0.5), SRs exhibited a slow increase (0.09±0.03, p=0.002), and NR did not change over time (0.002±0.02, p=0.9). Attendance during the intervention was not different across response phenotypes (p=0.1) and groups did not differ by age (p=0.9) sex (p=0.5), or prediabetes status (p=0.2). Comparing baseline characteristics between the most extreme response phenotypes (NR vs. LTR), NR exhibited significantly lower IS (p<0.001) and higher BMI% (p=0.001), waist circumference (p=0.001), TRGs (p=0.006), fasting and 2-hr insulin (p<0.001), and 2-hr glucose (p=0.009) compared to LTR.

Conclusion: Results highlight the heterogeneous response to lifestyle intervention in Latino youth and suggest that the highest risk youth require more aggressive efforts to improve insulin sensitivity. Precision approaches are warranted to meet the T2D prevention needs in this population.

Disclosure

A. Pena: None. D. McNeish: None. S. Ayers: None. M. Olson: None. K.B. Vander Wyst: None. A. Williams: None. Y.P. Konopken: None. C. Keller: None. F. González Castro: None. D.L. Patrick: None. G.Q. Shaibi: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK10757901, 3R01DK107579-03S1); National Institute on Minority Health and Health Disparities (P20MD002316, U54MD002316)
1244-P: Impact of Maternal Fasting Glucose in Pregnancy on Excess Weight at Preschool Age in the Offspring
Authors: KAUL PADMA , SAVU ANAMARIA , MOORE LINN E. , YEUNG ROSEANNE O. , RYAN EDMOND A.
Published: June 2020

Aim: To examine the association between elevated maternal fasting plasma glucose (FPG) during pregnancy and obesity in the offspring.

Methods: For women without pre-existing diabetes in 2 zones in Alberta, Canada with births between 2005 - 2013, maternal data were linked to offspring’s birth registry and preschool immunization records (w/height, weight) between 2009-2017. A 50-g glucose challenge test (GCT) followed by a 75-g OGTT was used to diagnose GDM. Pregnancies were grouped as follows: 1) GCT negative; 2) OGTT negative; 3) elevated FPG on the OGTT; and 4) elevated 1-hour and/or 2-hour OGTT only. WHO criteria were used to identify children who were overweight, obese, or extremely obese.

Results: Of 79,156 pregnancies, 80.3% were GCT negative, 14.7% were OGTT negative, 1.3% had elevated FPG, and 3.7% had elevated post-load glucose only. Both LGA and pre-school obesity rates were highest in pregnancies with abnormal FPG (Figure). Relative to children of GCT negative pregnancies, children of pregnancies with elevated maternal FPG had adjusted odds ratio (aOR, 95% CI) 3.0, (2.6-3.6) for LGA; and aOR 1.3 (1.1 - 1.6) for overweight, aOR 2.4 (1.9 - 3.0) for obesity, aOR 3.5 (2.7 - 4.7) for extreme obesity at preschool age.

Conclusion: The effect of elevated maternal FPG in pregnancy on offspring weight extends to early childhood. These children may be candidates for early pediatric weight and health interventions.

Disclosure

P. Kaul: None. A. Savu: None. L.E. Moore: None. R.O. Yeung: Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker’s Bureau; Self; Merck & Co., Inc. E.A. Ryan: None.

Funding

Canadian Institutes of Health Research; University Hospital Foundation
1255-P: Parental Socioeconomic Status and Risk of Impaired Fasting Glucose and Obesity of Children by Sex in Korea
Authors: LEE SOMIN , HAN KYUNGDO
Published: June 2020

Objective: To assess relations between parental socioeconomic status (SES) and impaired fasting glucose (IFG) and obesity of children by sex in Korea population.

Method: This study was based on the data from the Korean National Health and Nutrition Examination Survey, conducted by the Korean Ministry of Health and Welfare from 2007 to 2017. Data of 28747 participants (6605 children, 4969 fathers, and 6387 mothers) were analyzed. The SES was assessed with household income level and education level. The household income level was categorized into three groups: high, middle, and low. The education level was categorized into two groups: graduated post-secondary school or not. The prevalence of IFG was defined as >=100 fasting blood sugar. The prevalence of obesity was defined with the Korean Pediatrics Growth Chart from 2017. The relationship of SES to the risk of IFG and obesity was assessed with multivariate logistic regression analysis.

Result: In female children participants, a higher risk of IFG was associated with 1) low household income level (OR: 2.874, 95% CI:1.315, 6.279) and 2) low education level of mother (OR: 1.923, 95% CI: 1.062, 3.744), while the risk was not associated with low education level of father (OR: 1.395, 95% CI: 0.893, 2.18). Risk of obesity of female children was also associated with these two factors: low household income level (OR: 2.262, 95% CI: 1.182, 4.328) and education level of mother (OR: 1.484, 95% CI: 1.081, 2.036). Unlike female, in male children participants, risk of IFG and obesity was not associated with either factors.

Conclusions: For girls, low household income and low mothers’ education level may increase the incidence of IFG and obesity while boys are not affected by either factors. These differences should be considered when raising children and managing risk of diabetes and obesity of children to ultimately prevent risk of diabetes.

Disclosure

S. Lee: None. K. Han: None.