bluuebunny/crossref_metadata_2025 huggingface dataset:
77-OR: Circulating MicroRNAs Predict Glycemic Improvement and Response to a Behavioral Intervention
Authors: FLOWERS ELENA , ALLEN ISABEL D. , KANAYA ALKA M. , AOUIZERAT BRADLEY
Published: June 2021

Introduction: MicroRNAs (miRs) may be important regulators of risk for type 2 diabetes (T2D). The purpose of this study was to assess whether circulating miRs predicted glycemic improvement and responses to a behavioral intervention over 12 months.

Methods: The study included 82 participants from a previously completed trial (PRYSMS study) that tested the effect of restorative yoga vs. stretching among overweight and inactive individuals with prediabetes and the metabolic syndrome, which found significant improvements in fasting blood glucose (FBG) after 12 months of yoga intervention. Circulating miRs were measured using flow cytometry. Linear models were used to determine the optimal sets of miR predictors.

Results: Subsets of miRs were significant predictors of FBG (R2=0.754, p<0.001) and change in FBG over 12 months (R2=0.731, p<0.001) in the overall sample. Three miRs (let-7c, miR-363, miR-374b) were significant among the control group only for both FBG outcomes. There was no significant interaction by intervention group. Among the identified miRs, several have previously been associated with risk for T2D and related complications.

Conclusions: This is one of the first studies to use a longitudinal design to assess whether miRs predict changes in FBG over time. Exploration of the function of the identified miRs may provide new insights about the etiology of T2D and responses to behavioral risk reduction interventions.

Disclosure

E. Flowers: None. I. D. Allen: None. A. M. Kanaya: None. B. Aouizerat: None.

Funding

National Center for Advancing Translational Sciences (KL2TR000143); National Center for Complementary and Alternative Medicine (R01AT004569); National Institute of Diabetes and Digestive and Kidney Diseases (R21DK117346); National Heart, Lung, and Blood Institute (2K24HL112827)
772-P: Portability of Nasal Glucagon for the Rescue of Severe Hypoglycemia: Stability and Performance Evaluation across a Broad Range of Temperatures
Authors: PACK BRIAN W. , MELNICK JASON , BREEN CHRISTOPHER , ALLEN ROSS
Published: June 2021

Background and Aims: Nasal glucagon is a ready-to-use, drug-device combination therapy for the treatment of severe hypoglycemia. Portability is key, as nasal glucagon should be carried by persons with diabetes at all times. In designing for portability, the medication must allow for exposure to a broad range of temperatures without significant adverse effect on product quality/performance. In this study, we evaluated the stability and performance of nasal glucagon at temperatures ranging from -20 to +30 °C (-4 to +86 °F) in order to mimic real world situations.

Methods: Testing focused on characterization of drug product (glucagon amount) and combination product performance (consistent delivery to nasal cavity). Critical quality elements, including chemical purity and content, particle size, actuation force, delivered dose, shot weight, spray pattern and plume geometry, were evaluated after being exposed to temperatures from -20 and +30 °C, a range broader than a typically controlled room temperature product [i.e., Store at Controlled Room Temperature, 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F)], such as glucagon for injection.

Results: All testing demonstrated that 100% of critical quality elements were satisfied. Nasal glucagon could be exposed to frozen (-20 °C), refrigerated (2 to 8°C), and up to 30 °C conditions for the 2-year shelf life. The degradation of glucagon followed Arrhenius kinetics (i.e., slower degradation rates at lower temperatures). Temperature cycling studies showed no significant changes in the chemical/product performance attributes.

Conclusions: These analyses indicate no adverse impact to nasal glucagon from the chemical and physical perspective when exposed to frozen, refrigerated, and up to 30 °C conditions. The stability across a broad range of temperatures facilitates the portability of nasal glucagon as a rescue medication for severe hypoglycemia.

Disclosure

B. W. Pack: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. J. Melnick: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company. C. Breen: Employee; Self; Eli Lilly and Company. R. Allen: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
774-P: Hereditary Renal Glycosuria, Diabetes, and Responses to SGLT2 Inhibitor
Authors: REN QIAN , GONG SIQIAN , HAN XUEYAO , JI LINONG
Published: June 2021

Aims: To present the clinical features of two rare cases with hereditary renal glycosuria and diabetes, and summarize the previously reported SLC5A2 mutations and the related phenotypes.

Methods: The two patients were followed up for 7 and 3 years respectively, and detailed clinical characteristics were collected. SLC5A2 and HNF1A gene were sequenced. We used flash glucose monitoring system to record the variation of glucose with and without SGLT2 inhibitor treatment. Then we retrieved all the literature from Pubmed and analyzed SLC5A2 gene mutations and the phenotypes.

Results: During regular long-time follow up, the two patients both had frequent un-proportional renal glycosuria in the morning even when their fasting serum glucose was only slightly increased above the normal range. A novel rare mutation V359G and a pathogenic rare mutation ivs7+5G>A in SLC5A2 gene were found in Case 1 and Case 2 respectively. In Case 1, the 24h glycosuria was 2.2g/d, and increased to 103g/day after dapaglifozin treatment. The average glucose (6.33±1.56 vs. 6.28±1.74mmol/L, P=0.663), and Time in Range (TIR) (95% vs. 93%) were not significantly different in metformin and dapaglifozin treatment respectively. In Case 2, the 24h glycosuria was 121.4g/d and increased to 185.8g/day after dapaglifozin add-on treatment, with a further reduction of average glucose (9.11±2.63 vs. 7.54±2.39mmol/L, P<0.001), and better TIR 70% vs. 84%. We reviewed 139 cases with hereditary renal glycosuria and SLC5A2 gene mutation. The quantity of urine glucose was highest in patients with homozygous mutation (64.0(36.6-89.6)g/24h) compared with compound heterozygous (25.9(14.4-41.2)g/24h) and heterozygous(3.45(1.41-7.50)g/24h) (P<0.001).

Conclusions: Genetic renal glycosuria could not be translated into protecting individuals completely from developing diabetes. The response of these patients suggested that even in diabetic patients with decreased renal glucose threshold, SGLT2 inhibitor could also be effective.

Disclosure

Q. Ren: None. S. Gong: None. X. Han: None. L. Ji: None.

Funding

National Key Research and Development Program of China (2016YFC1304901); Beijing Municipal Commission of Science and Technology (Z141100007414002, D131100005313008)
78-OR: Aß Classification in Children with New-Onset Diabetes
Authors: TOSUR MUSTAFA , DEEN SAIMA , UYSAL SERIFE , ASTUDILLO MARCELA , JAHOOR FAROOK , REDONDO MARIA J. , BALASUBRAMANYAM ASHOK
Published: June 2021

The current binary classification (T1D vs. T2D) is inadequate to comprehensively dissect the heterogeneity of pediatric diabetes. The Aβ classification system, based on presence of islet autoimmunity (A+ or A-) and beta-cell functional reserve (β+ or β-), has been validated to define distinct phenotypic forms of Ketosis-Prone Diabetes in adults. Here, we aimed to study the utility of the Aβ classification system in children with new-onset diabetes. “A+” was defined as presence of ≥1 islet autoantibodies (GAD65, ICA512, insulin and ZnT8 autoantibodies) and “β+” as random C-peptide level ≥0.6 ng/mL at diagnosis. We compared the clinical characteristics at diabetes onset between the groups. The study cohort (n=67) was 46% female, 33% non-Hispanic white, 43% Hispanic, 21% non-Hispanic black and 3% Other. Mean age was 11.2 years and mean BMI was 59.3%ile. Aβ classification at diagnosis defined the following groups: A+β- (43%), A+β+ (24%) and A-β+ (33%). There were no A-β- patients. Median C-peptide levels in the three groups were 0.3, 0.7 and 3.3 ng/mL, respectively. Mean BMI %iles were 34.4 in A+β-, 53.1 in A+β+, and 96.4 in A-β+ group (p<0.001). A-β+ group were older (14 y/o) compared to A+β- (8.9 y/o) and A+β+ (11.7 y/o) (p<0.001). Diabetic ketoacidosis at diabetes onset was most frequent in A+β- (69%), intermediate in A+β+ (44%) and least in A-β+ (18%) (p<0.01). Hispanic ethnicity was more common in A-β+ (64%) compared to A+β+ (44%) and A+β- (28%) (p=0.03). There were no significant differences in sex, mean HbA1c and daily insulin dose per kg at diabetes diagnosis between the groups. The Aβ classification system provides more pathophysiologic insight and discrimination of characteristics than the current classification system. The A-β- group, which we previously reported to be 2.6% of a large pediatric diabetes cohort, was not represented in this smaller study. If prospective follow-up confirms distinct natural histories for these groups, the Aβ classification will be useful in clinical practice and for the design of intervention trials.

Disclosure

M. Tosur: Advisory Panel; Self; Provention Bio, Inc. S. Deen: None. S. Uysal: None. M. Astudillo: None. F. Jahoor: None. M. J. Redondo: Advisory Panel; Self; Provention Bio, Inc. A. Balasubramanyam: None.

Funding

Texas Children’s Hospital
79-LB: Pharmacokinetics and Pharmacodynamics of Avexitide (Exendin 9-39) in Neonates and Infants with Congenital Hyperinsulinism
Authors: CRAIG COLLEEN , DE LEON DIVA D.
Published: June 2021

Congenital hyperinsulinism (HI) is an ultra-rare pediatric disease with high unmet medical need. Avexitide, a first-in-class GLP-1 receptor antagonist, has been shown to reduce hyperinsulinemic hypoglycemia in children and adolescents with HI. Among neonates, maintenance of euglycemia often depends on high glucose infusion rates (GIR) by central lines. Those whose GIR exceeds 10 mg/kg/min frequently require subtotal pancreatectomy, leading to prolonged hospitalization, life-threatening complications, and induction of insulin-dependent diabetes. In this Phase 2 trial, 13 neonates and infants ages 11 days to 5 months with diazoxide-unresponsive HI were randomized to single ascending doses of avexitide and placebo by continuous IV infusion for up to 12 hours on two days in crossover design. Plasma glucose was monitored with GIR adjusted to maintain euglycemia. The primary endpoint was GIR. Relationships between avexitide exposure and absolute difference in GIR during avexitide vs. placebo were evaluated. A pharmacokinetic (PK) simulation of avexitide following subcutaneous (SC) injection in neonates was performed based on a modified PopPK model previously established with inclusion of weight-based allometric scaling. Relative to placebo, avexitide significantly reduced GIR when evaluated across dose levels (p=0.0087) with dose-dependent improvements observed. On average, avexitide infused at 100, 200 and 1000 pmol/kg/min demonstrated 1.3 (15%), 2.9 (24%), and 4.3 (56%) mg/kg/min reductions in GIR relative to placebo and entirely abolished glucose requirements in 50% of patients at the top dose. PK/PD analysis demonstrated an exposure-response relationship best described by an Emax model. PK simulation indicated that avexitide dosed by SC injection may achieve adequate steady-state exposure to lower GIR requirements. Subcutaneous avexitide may represent a promising therapeutic approach for treatment of neonates and infants with HI.

Disclosure

C. Craig: Consultant; Self; Eiger BioPharmaceuticals. D. D. De leon: Advisory Panel; Self; Zealand Pharma A/S, Consultant; Self; Hanmi Pharmaceutical, Heptares Therapeutics, Poxel SA, Soleno Therapeutics, Inc., Employee; Spouse/Partner; Merck & Co., Inc., Research Support; Self; Crinetics Pharmaceuticals, Tiburio, Zealand Pharma A/S.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R56DK083670); Clifford and Katherine Goldsmith Foundation; National Center for Research Resources (UL1RR024134); Eiger BioPharmaceuticals
79-OR: Butyrate Producing Bacteria and Insulin Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)
Authors: CUI JINRUI , ZHU TIANTIAN , JENSEN ELIZABETH T. , CRAGO OSA L. , RAMESH GAUTAM , SANDOW KEVIN ALBERT M. , CHEN YII-DER IDA , ROTTER JEROME I. , PETROSINO JOSEPH , GOODARZI MARK O.
Published: June 2021

Several studies have compared the stool microbiomes of people with and without type 2 diabetes (T2D), from which a pattern of depletion of butyrate producing taxa in T2D has emerged. Seventeen taxa encompass ~85% of the total butyrate producing potential in humans (mSystems 2017;2:e00130). The goal of MILES is to elucidate the effect of diet and gut microbiota on the components of insulin homeostasis (insulin sensitivity, secretion, clearance) whose dysfunction underlies T2D. MILES consists of 224 non-Hispanic Whites and 129 African Americans (mean age 59, 62% female), all of whom have completed an oral glucose tolerance test from which insulin homeostasis traits were calculated. Stool microbiome was assessed by whole metagenome shotgun sequencing (10 Gb depth), with taxonomic profiling using MetaPhlAn3. Spearman correlation was used to assess associations between the 17 dominant butyrate producing taxa (8 genera, 9 species) and insulin sensitivity, insulin secretion, disposition index (product of insulin sensitivity and insulin secretion), and insulin clearance. The Wilcoxon test was used to associate taxa with dysglycemia (prediabetes plus diabetes, 46% of cohort). Genera Coprococcus was associated with higher insulin sensitivity (ρ=0.16, P=0.003) and disposition index (ρ=0.14, P=0.009) and a lower rate of dysglycemia. Flavonifractor was associated with lower insulin sensitivity (ρ=-0.17, P=0.002) and a higher rate of dysglycemia. Eubacterium hallii was associated with insulin sensitivity (ρ=0.12, P=0.02). Analysis of 27 species from the 8 genera revealed additional associations with insulin sensitivity and disposition index, most of which displayed positive associations with these traits. These data suggest that improved insulin sensitivity and improved insulin secretion response to insulin sensitivity (i.e., disposition index) are key mechanisms whereby butyrate producing bacteria may exert metabolic protection against T2D.

Disclosure

J. Cui: None. M. O. Goodarzi: None. T. Zhu: None. E. T. Jensen: None. O. L. Crago: None. G. Ramesh: None. K. M. Sandow: None. Y. Chen: None. J. I. Rotter: None. J. Petrosino: None.

Funding

National Institutes of Health (R01DK109588)
799-P: Comparison of the Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Atrial Fibrillation among Patients with Type 2 Diabetes
Authors: LEE SEUNG EUN , KIM YOO RI , NAM HYEWON , KIM HOSEOB , KIM JAEHWAN , KIM KYOUNG-AH
Published: June 2021

Background: Type 2 diabetes is an independent risk factor for the development of atrial fibrillation (AF). However, whether reducing hyperglycemia can mitigate AF risk or not is elusive. Recently, SGLT-2i has been shown to decrease the incidence of AF through several mechanisms including reduction of atrial dilatation via diuresis and lowering body weight. On the other hand, the use of TZD was found to protect diabetic patients from new-onset AF in observational studies. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of AF development.

Methods: Using the Korean National Health Insurance Service database, we included patients with type 2 diabetes who were prescribed SGLT-2i or TZD at least once from January 2014 to December 2018. Patients were followed until the outcome event, death, or 31 December 2018. The propensity score matching method was used to balance baseline characteristics between groups. Sensitivity analysis was performed only including patients who prescribed study drugs ≥ 90 days.

Results: After propensity matching, a total of 145,378 patients were included (72,689 patients in each treatment group). Baseline characteristics were well-balanced; mean age was ~57 years and 57.4% were male; mean body mass index was ~26.3kg/m2 and ~68.3% had hypertension. During follow-up, the incidence rates of AF were 4.84 and 5.23 per 1000 person-years in SGLT-2i-treated patients and TZD-treated patients, respectively. The hazard ratio (HR) of AF was 0.99 (95% confidence interval [CI]: 0.89-1.11) in SGLT-2i-treated patients compared with TZD-treated patients. The results remained consistent after sensitivity analysis (HR, 0.92; 95% CI: 0.78-1.08).

Conclusions: In this study, the risk of AF development was comparable in patients treated with SGLT-2i versus TZD. The risk of AF development across antidiabetic drugs with little risk of hypoglycemia might be similar.

Disclosure

S. Lee: None. Y. Kim: None. H. Nam: None. H. Kim: None. J. Kim: None. K. Kim: None.
800-P: Phase 3 Results of Fixed-Dose Combination of Remogliflozin Etabonate and Vildagliptin in Indian T2DM Patients
Authors: MOHAN BRIJ , CHAWLA MANOJ S. , KODGULE RAHUL R. , TANDON MONIKA , KATARE SAGAR , SURYAWANSHI SACHIN , BARKATE HANMANT V.
Published: June 2021

Introduction: Remogliflozin Etabonate (RE) and Vildagliptin are approved in India for management of type 2 diabetes mellitus (T2DM), which were evaluated as a fixed dose combination (FDC) in this pivotal phase III study.

Methods: This 16 week, multi-centric, prospective, double blind, double dummy, parallel group, randomized controlled study compared efficacy and safety of FDC of RE 100mg + Vildagliptin 50mg (RV) given twice daily to active comparator of Empagliflozin 25mg + Linagliptin 5mg (EL) given once daily. Adult T2DM patients with HbA1c 8-11% on Metformin stable dose of ≥1500mg for ≥8 weeks before screening were randomized to either of treatment arms. The study endpoints were mean changes from baseline (CFB) in HbA1c (primary), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), body weight (BW) and blood pressure (BP) for efficacy and adverse events (AE) monitoring for safety assessments.

Results: Of 182 eligible subjects (91 in each arm), 157 (86.3%) subjects completed the study. The baseline demographic characteristics were well balanced between 2 treatment arms. Adjusted mean (SE) change from baseline in HbA1c (%) at week 16 viz. EL arm -1.36 (0.15) vs. RV arm -1.41(0.16); (mITT population; p<0.001 in each arm) was comparable between the two treatment arms (p=0.82). The mean difference of -0.05% (95%CI: -0.46, 0.36) in HbA1c demonstrated non-inferiority (NI) of RV compared to EL (p=0.016 for NI test). Similarly, significant reduction was observed in FPG, PPG, BW and BP which was found to be comparable between the two treatment arms. Drug related AEs were observed in 8.8% and 6.6% subjects of EL and RV arm respectively, with low incidence of hypoglycemia, genital and urinary tract infections (1-3%).

Conclusion: Overall, FDC of Remogliflozin Etabonate + Vildagliptin was found to be efficacious, safe and well tolerated in the treatment of patients with T2DM, and demonstrated non-inferiority to Empagliflozin 25mg + Linagliptin 5mg treatment.

Disclosure

B. Mohan: None. M. S. Chawla: Speaker’s Bureau; Self; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals, Inc., Colgate-Palmolive, Eli Lilly and Company, Glenmark Pharmaceuticals Limited, Novo Nordisk. R. R. Kodgule: Employee; Self; Glenmark Pharmaceuticals Limited. M. Tandon: Employee; Self; Glenmark Pharmaceuticals Limited. S. Katare: Employee; Self; Glenmark Pharmaceuticals Limited. S. Suryawanshi: Employee; Self; Glenmark Pharmaceuticals Limited. H. V. Barkate: None.
818-P: Barriers to Metformin Initiation and Adherence following a New Diagnosis of Type 2 Diabetes
Authors: GONG CHELSEA , GU KRISTINE , BLATCHINS MARUTA A. , MISHRA PRANITA , GRANT RICHARD W. , GOPALAN ANJALI
Published: June 2021

Metformin is the first line treatment for type 2 diabetes (T2D). While earlier initiation is associated with achievement of glycemic targets and a delayed need for treatment escalation, metformin initiation and adherence remain suboptimal. We explored contributors to suboptimal metformin initiation and adherence during the year following a T2D diagnosis. From a population of adults diagnosed with T2D between 2014-2018, we randomly identified 100 individuals who were prescribed metformin during the year after diagnosis (starters) and 100 who were not (non-starters). Through physician review of electronic health record (EHR) notes from the year following diagnosis, we explored patient-provider discussions about metformin, reasons metformin was or was not ordered, and reasons for discontinuation. Metformin starters were younger (mean age 53.8 vs. 60.0 years, p<0.001), more likely to be men (64% vs. 50%, p=0.046), and had higher initial HbA1c values (9.1% vs. 7.0%, p<0.001). Though 94/100 starters filled the initial prescription, only 71 were still taking metformin at one year. The most common documented reason for stopping was side effects. Only 18/100 non-starters had a documented patient-provider discussion about metformin, with a desire to try lifestyle modification as the primary reason for not starting metformin. Among the 18 non-starters who discussed metformin, metformin treatment was only revisited with 3. Though our findings are limited by a small sample and the extent of clinical documentation in the EHR, we still captured aspects of metformin treatment not available using structured EHR variables.

In conclusion, among metformin starters, efforts to mitigate side effects, including titration strategies or long-acting formulations, may improve metformin adherence. For most non-starters, there was no documented discussion regarding metformin. Strategies that prompt providers to have this important discussion may increase early initiation of this critical medication.

Disclosure

C. Gong: None. K. Gu: None. M. A. Blatchins: None. P. Mishra: None. R. W. Grant: None. A. Gopalan: None.

Funding

Kaiser Permanente Northern California
819-P: Comparison of Two Nurse-Driven Adult Diabetic Ketoacidosis (DKA) Treatment Protocols Using a Single Bag vs. Simultaneous Two-Bag Maintenance Intravenous Fluids
Authors: HALFON REBECA , DREUCEAN DIANE , SIRIMATUROS MICHAEL , SADHU ARCHANA R.
Published: June 2021

Objective: Evaluate safety and efficacy of a novel, simultaneous 2-bag (2B) maintenance intravenous fluid (IVF) DKA protocol compared with a conventional, single 1-bag (1B) protocol in adults.

Methods: Retrospective, observational review of patients treated with a DKA protocol from March-June 2017 (1B group) and March-June 2019 (2B group). One bag (1B) protocol: individual infusion of 1B IVF of ½ NS, ½ NS + KCL, D5W, OR D5W + KCL. Two bag (2B) protocol: simultaneous IVF infusion of 2B of D10W + KCL AND ½ NS + KCL. Safety endpoints of hypoglycemia, hyperkalemia, hypokalemia as well as efficacy endpoints of DKA resolution, incidence of rebound hyperglycemia, and hospital length of stay (LOS) were evaluated.

Results: A total of 605 patients were included (1B: n=204; 2B: n=401). Both groups had similar baseline characteristics except a higher baseline beta-hydroxybutyrate level in the 2B group than 1B (3.2 vs. 2.4; P=0.02) and differences in distribution of Body Mass Index (BMI) categories. Safety: Significantly fewer patients had hypoglycemia (BG <70 mg/dL) in the 2B group than 1B (15% vs. 22%, P=0.04), but severe hypoglycemia (BG < 40 mg/dL) was not different (0.5% vs. 1.5%, P=0.3). Incidence of hyperkalemia (K > 5.2 mEq/L) was significantly lower in the 2B group than 1B (10% vs. 21%, P<0.01), but hypokalemia (K < 3.3 mEq/L) was not different (21% vs. 24%, P=0.4). Efficacy: Median time to DKA resolution was similar between the 2B and 1B (15.0 vs. 15.6 hours, P=0.6). Rebound hyperglycemia (BG > 250 mg/dL) was less in 2B than 1B (29% vs. 44%, P<0.01). The 2B group had a trend of decreased LOS, but the difference was not statically significant (3.7 vs. 4.3 days, P=0.06).

Conclusion: In adult patients with DKA, a 2-bag protocol performed better in hypoglycemia, hyperkalemia, and rebound hyperglycemia without changing time to DKA resolution or LOS. In addition, the 2-bag protocol offered simplicity by decreasing the number of IVF bag options for the nurse.

Disclosure

R. Halfon: Stock/Shareholder; Spouse/Partner; Pfizer Inc. D. Dreucean: None. M. Sirimaturos: None. A. R. Sadhu: None.
827-P: Pioneering a Novel Inpatient Diabetes Consult Service in the COVID Era
Authors: RIZVI ALI A. , RICH ANITA O. , ELDRIDGE RITA
Published: June 2021

Hospitalized patients often do not reach the ADA-recommended glucose targets, which in turn increases complications, costs, length of stay, and readmission rate. The ADA supports the availability of trained specialists and teams to improve outcomes. Partly in response to the SARS CoV-2 pandemic, we instituted an inpatient “virtual care” initiative by electronic medical record (EMR) review. The ProActive Glucose Advice Team (pGAT) utilizes specialist expertise, automated computerized detection of hyperglycemia, and feedback to the primary service. The pGAT team members consist of an endocrinologist, a nurse diabetes care and education specialist, and a clinical dietician. The team reviewed a computer-generated report of inpatients with either 2 or more blood glucose values ≥180 mg/dl within the last 24 hours, and/or a hemoglobin A1c (A1c) ≥8%. We proposed to enter a brief, structured “pGAT Note” in the EMR, followed by a “gentle reminder” note the next day, including advice for a formal diabetes education and an endocrinology consultation. This proactive approach to the management of hyperglycemia would provide a summary review of the patient’s glucose state, determine the level of patient’s self-care skills, and steps to improve inpatient glycemic control. For preliminary data during the first 4-month phase after implementation of the pGAT initiative, we examined individualized discharge management and timely outpatient follow-up with endocrinology. Of 37 patients (28 males, 9 females; average age 60.4 years), 34 were treated with intensive insulin therapy with multiple daily insulin injections, 31 were seen in f/u within 2 weeks of discharge, and 25 were begun on Continuous Glucose Monitoring. The average A1c fell from an inpatient value of 11.6% to 8.4% measured between 2-4 months later. During the next pGAT phase, we intend to study inpatient therapy parameters, notably appropriate use of computerized insulin order sets, titration of basal insulin, and prandial-correction bolus insulin use.

Disclosure

A. A. Rizvi: None. A. O. Rich: None. R. Eldridge: None.
828-P: Inpatient Provider Experience with Diabetes Technology Use on General Medicine Wards: Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitors (CGM)
Authors: MADHUN NABIL Z. , GALINDO RODOLFO J. , DONATO JESSICA , HWANG PATRICIA , SHABBIR HASAN F. , FOWLER MICHAEL , MOLITCH-HOU ETHAN , UMPIERREZ GUILLERMO E. , LANSANG M. CECILIA
Published: June 2021

In the advent of increased use of technology in diabetes care, the management of CSII and CGM devices in the inpatient setting has not been well described. We conducted a non-incentivized survey among inpatient licensed independent practitioners (LIP) at 4 large US hospital systems to assess their knowledge, comfort, and behaviors related to the use of CSII and CGM in the inpatient setting. Of 128 respondents, 83% were day and night hospitalists, 10% advanced practice providers, and 7% primary care physicians. Most LIPs worked in academic centers (68%), 18% at community teaching hospitals, with 93% having diabetes consult service, and 55% having dedicated teams to assist with use of CSII and CGM.

Most respondents (96%) rated inpatient hyperglycemia treatment as important, and 93% of LIPs agreed that CSII should be continued in the inpatient setting in the absence of contraindication. However, only half (49%) reported reviewing CSII settings on admission, and of those, only 50% were confident with interpreting those parameters to guide therapy. Almost two-thirds (64% ) of providers reported knowledge of a CSII policy at their institution. The most common barriers to continuing CSII included lack of LIP knowledge and perceived lack of nursing knowledge regarding CSII.

LIPs were less familiar with the use of CGM, with 72% being unaware or not at all familiar with their institution’s policy. Of 64 respondents who cared for a patient with CGM in the preceding 6 months, 56% reported not reviewing CGM data to guide therapy.

Most inpatient providers value glycemic control and use of DM technology; however, many reported limited in-depth knowledge of CSII and CGM devices for optimal use to guide clinical care in the inpatient setting. Educational programs and collaboration between LIPs and endocrinologists are needed to safely optimize the use of CSII and CGM in the hospital setting.

Disclosure

N. Z. Madhun: None. R. J. Galindo: Consultant; Self; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi US, Valeritas, Inc., Research Support; Self; Dexcom, Inc., Novo Nordisk. J. Donato: None. P. Hwang: None. H. F. Shabbir: None. M. Fowler: Other Relationship; Self; AstraZeneca. E. Molitch-hou: None. G. E. Umpierrez: Research Support; Self; AstraZeneca, Dexcom, Inc., Novo Nordisk. M. Lansang: Consultant; Self; Sanofi, Research Support; Self; Dexcom, Inc.
836-P: Models to Predict Initial Insulin Requirements in Hospitalized Patients with Diabetes
Authors: CHIANG HOU-HSIEN , SURAMPUDI PRASANTH , SOOD AJAY
Published: June 2021

Background: The quality of inpatient glycemic control is limited by unknown starting dose of insulin at hospital admission.

Aim: To evaluate and estimate the first day insulin dose requirement in hospitalized patients with diabetes mellitus.

Methods: In this retrospective cohort study, patients with previous history of diabetes mellitus, aged ≥ 18 years, and admitted to UC Davis Medical Center from January 1, 2017 to December 31, 2018 were randomly recruited. Independent factors that may affect the insulin requirement were collected. The dependent factor is corrected insulin total daily dose (CxTDD) during the first 24 hours of hospitalization, which is defined as the insulin dose actually given plus calculated correction dose to target average blood glucose 180 mg/dL. Multivariable regression analyses are used to build models to predict CxTDD.

Results: The 144 patients who were prescribed insulin before admission had higher average blood glucose and higher CxTDD during the first 24 hours of hospitalization, compared to the 97 patients who were not prescribed insulin before admission (median 201.7 vs. 171 mg/dL, 25 vs. 5 units, respectively]. The adjusted R squares of the multivariable regression models are 58.6% in patients who were on insulin before admission, and 35.5% in those who were not, with common significant independent factors including first blood glucose upon presentation, body weight, oral intake, and new glucocorticoid use. Opiate/IV pain medication and home insulin daily dose are significant predictive factors (SIRS shows trend toward significance) only in patients who were prescribed insulin before admission.

Conclusion: Models to predict the first day insulin dose requirement shows clear differences between patients who were prescribed insulin versus not prescribed insulin before admission. First blood glucose upon presentation is a strong predictor of first day insulin dose requirement after hospitalization and this has not been emphasized previously in the literature.

Disclosure

H. Chiang: None. P. Surampudi: Research Support; Self; Viacyte, Inc. A. Sood: None.
838-P: Current Provision and HCP Experiences of Remote Care Delivery and Diabetes Technology Training for People with Type 1 Diabetes in the UK during the COVID-19 Pandemic
Authors: FORDE HANNAH E. , CHOUDHARY PRATIK , HUSSAIN SUFYAN
Published: June 2021

The covid-19 pandemic has led to rapid implementation of remote care delivery in type 1 diabetes (T1D). An understanding of current modes of care delivery and HCP experiences is required to improve care. The UK Diabetes Technology Network undertook an online survey aimed at members providing care in T1D. One hundred and forty three HCPs (47.6% diabetes physicians, 51.8% diabetes educators) from 105 UK NHS centers (51.7% university hospitals, 45.8% general/community hospitals), responded. Median (IQR) percentage of consultations and time taken via face-to-face, telephone and video were 20%(5-30), 30 minutes (20-34); 50% (30-80), 20 minutes (15-30) and 10% (0-35), 30 minutes (20-30), respectively. Sixty four percent responded that remote consultations offered an effective strategy for care delivery. Common barriers were patient familiarity with technology (72%) and access to patient device data (67.1%). Devices with smartphone based automated cloud uploads made consultations easier (73.4%), more effective (84.6%) and facilitated hospital discharges (60.9%). Median (IQR) responses on a 7-point scale for effectiveness of remote training, compared to face-to face, for new CSII starts, CSII renewals and CGM starts, were reported as 5 (4-6), 5.5 (5-6) and 6 (5-6), respectively. Common barriers included patient digital literacy (60.8%), limited HCP experience (46.2%) and time required per patient (43.6%). A reduction in new starts (72.8%) and renewals (60.9%) for CSII was highlighted by most. Variation was noted in proportion of new CSII starts being done virtually (53.9% respondents reporting <20% and 32.9% reporting >60%). Most (92.4%) responded that remote consultations and technology training are likely to continue post-Covid19. This survey highlights the impact of COVID-19 on access to diabetes technology and demonstrates how HCP’s have embraced remote care delivery, but digital literacy remains a barrier.

Disclosure

H. E. Forde: Consultant; Self; Dexcom, Inc. P. Choudhary: Advisory Panel; Self; Abbott Diabetes, Insulet Corporation, Lilly Diabetes, Medtronic, Sanofi-Aventis, Speaker’s Bureau; Self; Dexcom, Inc., Novo Nordisk. S. Hussain: Speaker’s Bureau; Self; Novo Nordisk.
841-P: Racial and Ethnic Disparities in Pregnant Women with Diabetes: A Review of Literature
Authors: PHONYIAM RATCHANOK , BERRY DIANE C.
Published: June 2021

Purpose: To examine the state of the science concerning racial and ethnic disparities and social determinants of health, perinatal care, and maternal and infant health outcomes in pregnant women with diabetes.

Method: PubMed, Scopus, CINAHL, and EMBASE databases were searched using the PRISMA guidelines. The inclusion criteria were original qualitative or quantitative manuscripts published in English from January 1, 2009, to May 31, 2020. Consensus statements were excluded.

Results: This review included 16 manuscripts of women with gestational diabetes mellitus and pregestational diabetes mellitus living in the United States. This synthesis demonstrated the differences in maternal economic stability, education, and health and health care. Non-Hispanic Black, Hispanic, and Asian women had significantly higher odds of experiencing preeclampsia, spontaneous preterm, and postpartum readmission than non-Hispanic White women. Non-Hispanic Black infants had the highest hypoglycemia and intensive care unit admission rates, while Hispanic infants were more likely to have macrosomia than non-Hispanic White infants.

Discussion: Evidence highlights disproportion in maternal social determinants of health and health outcomes. Additional research is needed in disadvantaged groups who are less likely to utilize perinatal care services and be screened for type 2 diabetes after pregnancy. Little is known about the direct and indirect pathway between racial discrimination and maternal and infant health, specifically through chronic stress to glycemic control. Infants exposed to hyperglycemia in pregnancy need closer attention from infancy in assessment and management to prevent diabetes later in life.

Conclusion: There is an urgent need to improve the quality of care for women with diabetes. Health care providers should implement tailored interventions that target racial and ethnic disparities and promote health equity in pregnant women with diabetes and their offspring.

Disclosure

R. Phonyiam: None. D. C. Berry: None.
856-P: Long-Term Benefits of Multicomponent Integrated Care Program Participation on Diabetes Care Goals: The DIABEMPIC Program
Authors: SILVA-TINOCO RUBÉN , DELATORRE-SALDAÑA VIRIDIANA , CUATECONTZI-XOCHITIOTZI TERESA , GONZALEZ-CANTU ARNULFO , CASTILLO-GALINDO CARMEN , PIMENTEL-HERNÁNDEZ BLANCA , ROMERO-IBARGUENGOITIA MARIA ELENA , NÚÑEZ-RODRÍGUEZ ADRIÁN , OROZCO-GUTIÉRREZ FRANCISCO , GALLARDO-HERNÁNDEZ ALBERTO , OCHOA-MORENO JORGE
Published: June 2021

Diabetes burden is greater in low- middle-income countries, where large gaps exist in achieving diabetes care goals. We examined a quality initiative multicomponent integrated care (MIC) program (DIABEMPIC, DIABetes EMPowerment and Improvement of Care) on diabetes care goals in adults with type 2 diabetes (T2D) implemented in a public primary care specialized diabetes clinic in Mexico City/Iztapalapa. DIABEMPIC is a 5-month empowerment-based program that includes an interdisciplinary case management team, diabetes self-management education, shared medical appointments, a patient-centered approach, and audit and feedback. At the end of the program patients continue routine care in public primary care units. We report the effect of the intervention on diabetes care goals at the end of the program and 18 months after the initial recruitment (long-term evaluation). Results: 704 patients with T2D completed the program, and 182 already have a long-term evaluation. The mean (SD) age of this subgroup was 57 (10.9) years, 67% female, 61% had elementary or less education, 68% had medium-low or lower socioeconomic status, mean diabetes duration was 13 (8) years, and mean A1c was 9.5% (2.2). After the program (n=182) systolic and diastolic blood pressure (-11, -4 mmHg respectively), A1c (-2.6%), and non-HDL cholesterol (-29 mg/dl) decreased significantly (p<0.0001). Clinical benefits persisted in long-term evaluation in systolic and diastolic blood pressure (-9, -3 mmHg respectively, p<0.0001), A1c (-1.4%, p<0.0001), and non-HDL cholesterol (-11 mg/dl, p=0.018). Conclusions: This quality-of-care initiative had valuable short and long-term effects on diabetes care goals in a real-world setting. The long-term impact is smaller than the impact observed at the end of the intervention. This work suggests further replication of the intervention and enhances the need to improve routine follow-up in primary health units after the participation in MIC programs.

Disclosure

R. Silva-tinoco: None. A. Gallardo-hernández: None. J. Ochoa-moreno: None. V. Delatorre-saldaña: None. T. Cuatecontzi-xochitiotzi: None. A. Gonzalez-cantu: None. C. Castillo-galindo: None. B. Pimentel-hernández: None. M. Romero-ibarguengoitia: None. A. Núñez-rodríguez: None. F. Orozco-gutiérrez: None.
859-P: Impact of a Prediabetes Clinical Decision Support System on CV Risk Factor Control in Primary Care: Randomized Trial
Authors: DESAI JAY R. , CRAIN A. LAUREN , SAMAN DANIEL , SPERL-HILLEN JOANN M. , ALLEN CLAYTON , WARING STEPHEN , OHNSORG KRIS , APPANA DEEPIKA , DEHMER STEVEN P. , EKSTROM HEIDI , O’CONNOR PATRICK J.
Published: June 2021

Purpose: We designed, implemented, and evaluated impact of a prediabetes clinical decision support system on identification of prediabetes and control of major cardiovascular (CV) risk factors in adults with prediabetes receiving care in primary care clinics.

Methods: We randomized 34 primary care clinics with 18,229 study-eligible patients age 40-75 years at index encounter with laboratory evidence of prediabetes to usual care (UC) or a prediabetes clinical decision support (PreD-CDS) intervention condition. Study-eligible patients and their primary care clinician (PCC) were given patient-specific treatment suggestions to support diagnosis of PreD and control of systolic BP (SBP), low-density lipoprotein cholesterol (LDL), smoking, and Body Mass Index (BMI, Kg/m2). Electronic medical record (EHR) and other data were analyzed using linear and logistic mixed models to account for nested data structures.

Results: At index visit study subjects were 50.7% female, 97.1% white, mean age 60.9 years, 56.7% not diagnosed with PreD, 17.2% current tobacco smokers, and mean age 60.9 years, BMI 33.6 Kg/m2, SBP of 151 mmHg, and LDL 118 mg/dl. Compared to UC clinics, those receiving care at PreD-CDS clinics had no significant change in likelihood of PreD diagnosis, mean SBP, mean LDL, mean BMI, or smoking (all p >.05).

Conclusions: This point-of-care EHR-linked web-based clinical decision support system had no statistically significant impact on diagnosis of prediabetes or CV risk factor control. Alternative methods of improving care for these vulnerable patients are needed.

Disclosure

J. R. Desai: None. H. Ekstrom: None. P. J. O’connor: None. A. Crain: None. D. Saman: None. J. M. Sperl-hillen: None. C. Allen: None. S. Waring: None. K. Ohnsorg: None. D. Appana: None. S. P. Dehmer: None.

Funding

National Heart, Lung, and Blood Institute (R01HL128201)
879-P: Dropout Risk and Effectiveness of Retention Strategies: A Substudy of the Memory Advancement by Intranasal Insulin (INI) in Type 2 Diabetes (MemAID)
Authors: KHAN FAIZAN , ISAZA-PIEROTTI DANIEL F. , NOVAK PETER , MANTZOROS CHRISTOS , NGO LONG H. , NOVAK VERA
Published: June 2021

Effective recruitment and retention strategies in clinical trials are essential to achieve the enrollment goals. We aimed to identify baseline characteristics predicting dropouts and analyze the effect of retention strategies within the MemAID elderly cohort. The trial consisted of 12 visits during 24 weeks of INI/placebo treatment and 24 weeks of follow-up. Retention strategies were implemented 2 years after the beginning of the study and included incentives (meals, stipend, transportation), revised eligibility criteria, and flexibility in scheduling. A total of 244 participants (122 female; 65.8 ± 9.1 years old, 115 diabetes (DM)) were randomized, and completed baseline (223), treatment (174), and follow-up (156). After randomization, 65 participants (27%, 30 DM [46%]) dropped out. Dropouts occurred earlier in the study (19.6% cumulative failure at 100 days) as compared to later (25.3% cumulative failure at 300 days). Cox models showed no risk of dropout with DM diagnosis, but increased risk (p<0.05) with less education, unmarried status, longer DM duration, higher HbA1c, and no antidiabetic drugs. After retention strategies, the dropout rate per month decreased from 4.1 to 1.8% (p=0.04). These strategies attenuated the risk of dropping out of unmarried status and higher HbA1c. Baseline characteristics allow to predict a risk for dropping out in elderly participants. Retention strategies that increase incentives and lessen the study burden on older participants may be effective to minimize the impact of dropout-related risk factors. Further research into efficacy of retention strategies in elderly DM population is needed (NCT02415556).

Disclosure

F. Khan: None. D. F. Isaza-pierotti: None. P. Novak: Other Relationship; Self; Dysimmune Foundation, Endonovo Therapeutics, Oxford Press. C. Mantzoros: Advisory Panel; Self; Amgen Inc., GENFIT, Intercept Pharmaceuticals, Inc., Novo Nordisk, Regeneron Pharmaceuticals Inc. L. H. Ngo: Consultant; Self; Five Islands Consulting, Other Relationship; Self; Radiological Society of America. V. Novak: Advisory Panel; Spouse/Partner; Endonovo Therapeutics, Inc., Consultant; Spouse/Partner; Dysimmune Foundtation, Other Relationship; Spouse/Partner; Oxford University Press.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK103902); U.S. Food and Drug Administration (IND107690); Novo Nordisk (ISS-001063), Medtronic (NERP15-0310); World Health Organization (UTN-U111-1175-1588)
88-OR: Evaluation of a New Neural Network Classifier for Diabetic Retinopathy
Authors: KATZ OR , PRESIL DAN , COHEN LIZ , NACHMANI ROI , KIRSHNER NAOMI , OWENS DAVID R. , LEV TSVI H. , HADAD AVIEL
Published: June 2021

Background: Medical image segmentation is a well-studied subject within the field of image processing. The goal of this research is to create an AI retinal screening grading system that is both accurate and fast. We introduce a new segmentation network which achieves state-of-the-art results on semantic segmentation of colour fundus photographs. By applying the network to identify anatomical markers of diabetic retinopathy (DR) and diabetic macular edema (DME) including: micro-aneurysms, haemorrhages, etc., we collect sufficient information to classify patients into R0 (no DR) and R1 or above (DR), as well as M0 (no DME) and M1 (DME).

Methods: The AI grading system was trained on public and private screening data to evaluate the presence of DR and DME. The system’s core algorithm is a novel deep learning segmentation network (W-net) that locates and segments relevant anatomical features in a retinal image. Both eyes of the patients are graded individually, based on the detected features and classified according to the standard feature-based grading protocol used in the NHS Diabetic Eye Screening Programme.

Results: The algorithm performance was evaluated with a series of patient retinal images from routine diabetic eye screenings and achieved state-of-the-art results. It correctly predicted 98% of retinopathy events (95% confidence interval [CI], 97.1-98.8) and 68.9% of maculopathy events (95% CI, 58.1-79.7). Non-disease events prediction rate was 68.6% for retinopathy and 81.3% for maculopathy.

Conclusion: This novel deep learning segmentation model trained on a colour fundus photograph data set and tested on patient data from annual diabetic retinopathy screenings can detect and classify with high accuracy the DR and DME status of a person with diabetes. The system can be easily reconfigured according to any grading protocol, without starting a long AI training procedure. The incorporation of the AI grading system can increase the graders’ productivity and improve the final outcome of the screening process.

Disclosure

O. Katz: Employee; Self; NECAM, Research Support; Self; Northgate Public Services. D. Presil: Employee; Self; NECAM, Research Support; Self; Northgate Public Services. L. Cohen: Employee; Self; NECAM, Research Support; Self; Northgate Public Services. R. Nachmani: Employee; Self; NECAM, Research Support; Self; Northgate Public Services. N. Kirshner: Employee; Self; NEC, Research Support; Self; Northgate Public Service. D. R. Owens: Advisory Panel; Self; 360 Consulting. T. H. Lev: Employee; Self; NECAM (NEC Corporation of America), Research Support; Self; Northgate Public Services. A. Hadad: Consultant; Self; Necam.