bluuebunny/crossref_metadata_2025 huggingface dataset:
1150-P: Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers on Renal Outcomes in Patients with Type 2 Diabetes and Proteinuria
Authors: COLEMAN CRAIG I. , WEEDA ERIN R. , KHARAT AKSHAY A. , BOOKHART BRAHIM , BAKER WILLIAM L.
Published: June 2019

Background: The impact of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) on renal outcomes in patients with type 2 diabetes (T2D) and proteinuria remains unclear.

Methods: A search of Medline, Embase and the Cochrane Databases through 11/2/2018 was performed. We included randomized controlled trials (RCTs) of T2D patients and micro- or macroalbuminuria; comparing an ACEI or ARB with placebo, placebo+background antihypertensives or non-ACEI or ARB containing antihypertensives; randomizing ≥100 subjects; and following subjects for ≥12 months. Endpoints included doubling of serum creatinine (SCr), end-stage renal disease (ESRD), all-cause and cardiovascular (CV) mortality and progression and regression of proteinuria. A Hartung-Knapp random-effects model producing a risk ratio (RR) with 95% confidence interval (CI) was employed, with between-study variance calculated using the Paule-Mandel estimator.

Results: The use of an ACE inhibitor or ARB was not associated with a significant reduction in the risk of a doubling in SCr (n=7 trials, RR=0.77, 95% CI=0.50-1.21). ACE inhibitors or ARBs reduced the risk of progressing to ESRD (n=8, RR=0.79, 95CI=0.75-0.83). No difference in all-cause (n=11, RR=0.98, 95% CI=0.89-1.08) or CV mortality (n=6 trials, RR=1.08, 95% CI=0.92-1.28), nor the composite outcome of doubling SCr, development of ESRD or mortality (n=3 trials, RR=0.87, 95% CI=0.72-1.06) were observed. The risk of progression of patients’ proteinuria was decreased when an ACE inhibitor or ARB was used versus control (n=10, RR=0.49, 95% CI=0.33-0.74). The chance of regression of patients’ proteinuria was not significantly improved with an ACE inhibitor or ARB (n=11, RR=1.55, 95% CI=0.93-2.58).

Conclusion: ACEIs and ARBs may reduce the risk of ESRD and slow progression of nephropathy, but do not appear to decrease all-cause or CV mortality in T2D patients with proteinuria.

Disclosure

C.I. Coleman: Research Support; Self; Janssen Scientific Affairs, LLC. E.R. Weeda: None. A.A. Kharat: Consultant; Self; Janssen Scientific Affairs, LLC. B. Bookhart: Employee; Self; Janssen Pharmaceuticals, Inc. Stock/Shareholder; Self; Janssen Pharmaceuticals, Inc. W.L. Baker: None.

Funding

Janssen Scientific Affairs, LLC
1154-P: Genetic and Pharmacological Suppression of Cathepsin K Promotes Wound Healing in Diabetic Mice
Authors: GUO RUI , ZHANG LIPING , THAKAR AMIT , BROWN TRAVIS E. , REN JUN , ZGHEIB CARLOS , XU JUNWANG , LIECHTY KENNETH W. , NAIR SREEJAYAN
Published: June 2019

Background and Hypothesis: Impaired wound healing is a serious complication of diabetes and accounts for over 70,000 amputations annually in the United States. Accumulating evidence suggests that wounds with poor healing process display persistently elevated protease activity. Here we tested the hypothesis that genetic knockout or pharmacological inhibition of cathepsin K, a cysteine protease with potent collagenolytic and elastolytic activity, accelerates wound closure in diabetic mice.

Methods: Diabetes was induced in cathepsin K knockout (Ctsk-/-) and wild type litter-mates by intraperitoneal injection of streptozotocin (STZ, 120 mg/Kg). Two weeks following STZ injection, a full thickness 8-mm excisional wound was created on the dorsum of the mice. In a separate set of experiments, excisional skin wounds were created in genetically diabetic (db+/db+) and their normoglycemic litter-mates. The wounds were treated with cathepsin K inhibitor II (0.35μg/d on days 0, 3, and 5), or vehicle, given as intradermal injections along the circumference of the wound. Wound healing was evaluated by measuring the wound closure rate, CD31 expression, and histological analysis.

Results: In the STZ-induced diabetic model, wounds in the cathepsin K-knockout mice closed significantly earlier than the vehicle-treated wounds. Similarly, pharmacological inhibition of cathepsin K in db/db mice resulted in near complete resolution of the wound in 22 days compared to about 29 days in vehicle-treated mice. Histological evaluations demonstrated that topical delivery of cathepsin K inhibition resulted in higher levels of collagen deposition and increased angiogenesis. In an in vitro scratch-assay using cultured human fibroblasts, cell migration, which was significantly impaired by high-glucose concentrations, was restored by cathepsin K inhibitor-II.

Conclusion: Cathepsin K may represent a potential treatment-target to facilitate diabetic wound healing.

Disclosure

R. Guo: None. L. Zhang: None. A. Thakar: None. T.E. Brown: None. J. Ren: None. C. Zgheib: None. J. Xu: None. K.W. Liechty: Consultant; Spouse/Partner; Cell research. S. Nair: None.

Funding

National Institute of General Medical Sciences (2P20GM1034320); University of Wyoming
1156-P: Duodenal Mucosal Resurfacing (DMR) Combined with GLP-1 RA May Eliminate Insulin Therapy and Improve Metabolic Health in Type 2 Diabetes
Authors: SMEELE PAUL , VAN BAAR ANNIEKE C. , VRIEND TESSA M. , HOLLEMAN FRITS , SOETERS MAARTEN , NIEUWDORP MAX , TIJSSEN JAN , BERGMAN JACQUES J.
Published: June 2019

Background: Duodenal mucosal resurfacing (DMR) is an endoscopic intervention in which the duodenal mucosa is ablated by hydrothermal energy. DMR improves glycemic control in type 2 diabetes (T2D) through altered metabolic signaling from the duodenum causing insulin sensitization. We studied the feasibility of eliminating insulin therapy in T2D by combining DMR with GLP-1r agonism (liraglutide) and lifestyle counseling.

Methods: Single arm, single center study in 16 insulin treated T2D patients (HbA1c ≤64 mmol/mol; basal insulin <1U/kg/day, c-peptide ≥0.5 nmol/l). Day 1, DMR is administered and insulin therapy discontinued. Day 14, liraglutide is introduced (titrated to 1.8 mg/day) and life style counseling is administered throughout. Primary endpoint: percentage of patients free of insulin and HbA1c ≤59 mmol/mol at 6 months.

Results: Enrolment has been completed and 9 patients have reached 6 months with 8/9 (89%) insulin-free and able to maintain glycemic control with improvement across multiple metabolic parameters (Table 1).

Conclusion: Single endoscopic DMR, combined with liraglutide and lifestyle counseling, may effectively eliminate the need for insulin therapy in T2D while improving overall metabolic health. This treatment approach is a promising alternative that appears to shift insulin-treated T2D patients to a state of better overall metabolic health.

Disclosure

P. Smeele: None. A.C. van Baar: None. T.M. Vriend: None. F. Holleman: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Sanofi. M. Soeters: None. M. Nieuwdorp: Advisory Panel; Self; Caelus health. J. Tijssen: None. J.J. Bergman: Research Support; Self; Fractyl Laboratories, Inc.
116-LB: New Insulin-to-Carb Ratio Formulas for Hybrid Closed-Loop Pump Use
Authors: TABATABAI IDEEN , BUCKINGHAM BRUCE A.
Published: June 2019

Objective: Formulas to determine Insulin-Carbohydrate Ratio (ICR) use total daily dose (TDD) such as the 450 Rule (450/TDD=ICR) or body weight (BW) (2.8*weight in pounds/TDD). These do not account for age differences or adjust for HCL therapy.

Methods: We analyzed data from Medtronic 670G users meeting the following criteria: Time in Range (TIR, 70-180mg/dl) >65%, Time <70mg/dl <5%, A1c <8%, HCL for >3 months. Subjects were grouped by age: pre-pubertal, pubertal, and adult (18+). Subjects’ current ICR was multiplied by TDD at each meal to determine a formula starting point.

Results: 50 subjects were included (age 6-62, mean A1c 7.2%, TDD 0.8 u/kg/day, TIR 75%, 2.5% <70mg/dl). Compared to baseline, ICRs in HCL were made 10-26% more aggressive. ICRs calculated from the 450 rule were 15-41% less aggressive compared to the ratios used by HCL subjects. BW formula ICRs were too aggressive for pre-pubertal, closely matched the pubertal subjects, and underestimated meal bolus needs in adults on HCL.

Conclusions: Our data offers new initial ICR formulas for HCL users instead of the 450/TDD rule, i.e., a 300/TDD for adults and a 350/TDD for pubertal and prepubertal children at lunch/dinner, and a breakfast 300/TDD rule. Fine-tuning is necessary for each patient, but this offers a better tuned starting point for subjects starting HCL, helping minimize HCL exits due to post-prandial hyperglycemia.

Disclosure

I. Tabatabai: None. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care.
1169-P: The Insulin Dosage Advisor Diassist Can Help Optimize Glucose Control
Authors: SVENSSON HANNA , HANAS RAGNAR
Published: June 2019

Background: The 500-rule for the insulin to carbohydrate ratio (ICR) and 100-rule for insulin sensitivity factor (ISF) are easy to use but unfortunately do not provide good ratio estimates for many patients. Analysis of downloaded CGM and pump data can give good estimates but require a lot of experience from the user and is time consuming. We have developed an algorithm (Diassist), based on clinical experience and signal processing, which automatically estimates ICR and ISF, and investigated this method in a clinical context.

Methods: Pump and CGM downloads over 2 weeks were used for analysis. The physician interpreted these and compared with the Diassist results. Diassist calculated only valid meals and corrections, i.e., when blood glucose and carbohydrates had been entered by the patient.

8 patients with poor glucose control participated with 3-5 visits over 2-8 months.

Mean (±SD) age was 12.7 ± 1.8 (range 10.4-16.5) years, diabetes duration 8.0±1.1 years. Insulin dose was 0.78±0.17 (0.6-1.1) units/kg/24 hours (% basal 40.8±13.0 (23-58)). The tool estimated ICR and ISF over 2 weeks and proposed to increase or decrease the settings based on actual glucose excursions. To validate the robustness of the method, cross validation with two data sets was used. Data was divided into 2 sets per patient; running Diassist on the two sets and comparing the results.

Results: The physician followed the Diassist recommendations for ICR titration in 73% of the time slots (4-5/day, 58 out of 79), increasing or decreasing by 10-25%. In one occasion the ICR was changed in the opposite direction to the recommendation.

In 98%, the ICR was lowered (more insulin for the meal), in 2% it was increased. HbA1c was not changed (61±4.4 vs. 57±6.3 mmol/mol, 7.7±0.4 vs. 7.4±0.6%).

The quota of carbohydrate and boluses used in analysis were 67% and 58% of the logged data.

Conclusions: Compared to methods used today, Diassist decreased both time and complexity of the estimation task. The proposed method shows promising results for usability, robustness and safety.

Disclosure

H. Svensson: Stock/Shareholder; Self; Diassist Technology AB. R. Hanas: Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; AstraZeneca.
1177-P: Discovery of New Therapeutic Antibodies to Two Metabolically Relevant Targets—GPCR CB1 and Transporter GLUT4—Using Virus-Like Particles
Authors: TUCKER DAVID , CHARPENTIER TOM , MOLINO NICHOLAS , ROSENBERG ERIN , SCRENCI BRAD , STAFFORD LEWIS J. , SULLI CHIDANANDA , CHAMBERS ROSS , DORANZ BENJAMIN J. , RUCKER JOSEPH B.
Published: June 2019

Integral membrane proteins are important drug targets, and monoclonal antibodies (mAbs) against them are highly sought for therapeutic and diagnostic purposes. However, the complex structure of multipass membrane proteins makes discovery of these mAbs particularly challenging. By employing strategies such as sequential immunization with DNA (prime) and virus-like particles (boost), and using divergent species (chickens) as immunization hosts, we routinely isolate diverse panels of mAbs against structurally complex and highly conserved membrane protein targets. Here, we report the isolation and characterization of mAbs recognizing two distinct metabolically relevant targets: the 12-transmembrane insulin-responsive glucose transporter GLUT4 and the 7-transmembrane GPCR cannabinoid receptor-1 (CB1).

In both cases, we isolated diverse panels of mAbs against native conformational epitopes. Affinities ranged from 2.6 nM (anti-CB1 IM-102) to 1 pM (anti-GLUT4 LM048). Two anti-GLUT4 mAbs discriminated between inward-open and outward-open conformational states, including one mAb (LM048) that inhibited transporter function. Similarly, we isolated several anti-CB1 mAbs that antagonized CB1-mediated calcium flux. Lead mAbs were confirmed to be specific for their target proteins, based on reactivity profiling in the Membrane Proteome Array of >5,600 human membrane proteins. Identified mAbs represent novel and valuable molecular tools for understanding and potentially treating common metabolic diseases, such as type 2 diabetes mellitus and nonalcoholic steatohepatitis/fatty liver disease (NASH/NAFLD). Furthermore, the technologies underpinning their discovery can be rapidly and routinely employed to facilitate discovery of mAbs against other therapeutically relevant membrane protein targets.

Disclosure

D. Tucker: None. T. Charpentier: None. N. Molino: None. E. Rosenberg: None. B. Screnci: None. L.J. Stafford: None. C. Sulli: None. R. Chambers: None. B.J. Doranz: None. J.B. Rucker: None.

Funding

National Institutes of Health
1179-P: Pharmacokinetics, Pharmacodynamics, and Safety of HD-6277, a Selective Agonist of G-Protein-Coupled Receptor 40, in Healthy Subjects as a First-in-Human Study
Authors: KIM KI-HWAN , KIM PAN-KYUNG , YANG HYE-JUNG
Published: June 2019

HD-6277 is a potent and selective G-protein-coupled receptor 40 agonist for the treatment of type 2 diabetes mellitus. Previous studies with HD-6277 showed enhanced glucose-stimulated insulin secretion and improved glycemic control in type 2 diabetic rodent models. To evaluate the potential benefits of HD-6277 on safety, tolerability, pharmacokinetics and pharmacodynamics, HD-6277 was investigated with six and four sequential cohorts in single and multiple ascending doses in healthy subjects as randomized, double-blind, placebo-controlled study, respectively. HD-6277 was well absorbed over all doses under fasting conditions and systemic exposure was increased in dose-dependent manner both in single and multiple ascending dose study. There was no severe or serious adverse events showing generally mild and transient profile, which suggested no safety concerns with the doses administered. Therefore, this study showed HD-6277 was safe and well tolerated in healthy subjects. Its exploratory efficacy on type 2 diabetes mellitus patients is currently under evaluation.

Disclosure

K. Kim: Employee; Self; Hyundai Pharmaceutical Co., Ltd. P. Kim: Employee; Self; Hyundai Pharmaceutical Co., Ltd. H. Yang: Employee; Self; Hyundai Pharmaceutical Co., Ltd.

Funding

Korean Ministry of Health and Welfare (HI17C2529)
118-LB: Glucose Variability throughout the Menstrual Cycle on Closed-Loop Control in Type 1 DM
Authors: LEVY CAROL J. , OMALLEY GRENYE , BROWN SUE A. , RAGHINARU DAN , KUDVA YOGISH C. , DASSAU EYAL , KOVATCHEV BORIS , ANDERSON STACEY
Published: June 2019

Many women with type 1 DM report change in glucose (GLU) control and insulin (INS) dosing throughout the menstrual cycle (MC). No trials have reported the effect of closed loop control (CLC) on INS delivery across the MC. Women enrolled in Phase 1 of the IDCL hybrid CLC trial logged MCs to estimate late luteal and early follicular dates. Data from 64 MC across 27 women (13 CLC), 7 using hormonal contraception, aged 28±11 years, weight 67 kg (IQR: 61-80) was analyzed for diurnal GLU control and CLC INS delivery. MC phase did not impact trends toward increased time in range with CLC. There were no differences in GLU and INS variables. While median CLC INS delivery did not change across the MC, there was intrasubject variability across the MC. CLC has the potential to elucidate individual dosing variability and may mitigate reported change in GLU control across the MC.

Disclosure

C.J. Levy: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Allergan. G. OMalley: None. S.A. Brown: Research Support; Self; Ascensia Diabetes Care, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care. D. Raghinaru: None. Y.C. Kudva: Advisory Panel; Self; Novo Nordisk Inc. Other Relationship; Self; Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care. E. Dassau: Consultant; Self; Eli Lilly and Company, Insulet Corporation. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Ltd., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; ModAGC. B. Kovatchev: Advisory Panel; Self; Sanofi. Board Member; Self; TypeZero Technologies, Inc. Consultant; Self; Sanofi, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc. Stock/Shareholder; Self; TypeZero Technologies, Inc. Other Relationship; Self; Johnson & Johnson, Sanofi. S. Anderson: Research Support; Self; Medtronic MiniMed, Inc.

Funding

National Institutes of Health
1193-P: Health-Care Costs and Medication Burden in Routine Care Initiators of Empagliflozin: A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study
Authors: PAWAR AJINKYA , PATORNO ELISABETTA , DERUAZ-LUYET ANOUK , BRODOVICZ KIMBERLY , USTYUGOVA ANASTASIA V. , GAUTAM NILEESA , BESSETTE LILY G. , SCHNEEWEISS SEBASTIAN , NAJAFZADEH MEHDI
Published: June 2019

EMPRISE studies the comparative effectiveness, safety and health care resource utilization of empagliflozin (EMPA) in Medicare and 2 U.S. commercial claims datasets (2014-2019). In this first analysis, we evaluated healthcare costs and medications burden associated with EMPA vs. dipeptidyl peptidase 4 inhibitors (DPP-4i) use in routine care patients with type 2 diabetes (T2D). We identified a 1:1 propensity-score-matched cohort of T2D patients ≥18 years initiating either EMPA or DPP-4i between 08/2014-09/2016. Total (inpatient, outpatient, pharmacy) cost and medication burden were compared for EMPA vs. DPP-4i. We identified 17,549 matched pairs with balanced baseline characteristics (Table 1) with mean follow-up of 5.4 months. Per member per year (PMPY) total cost was similar among EMPA vs. DDP4i initiators ($17,771 vs. $17,814; Diff= -$43, 95% CI: -1,380─1,295). Medical costs tended to be lower and pharmacy costs were higher in EMPA initiators. Distinct medication prescriptions were slightly lower among EMPA initiators [Incidence rate ratio 0.97, 95% CI: 0.96─0.98]. Results stratified by history of CV disease were consistent. Within the first two years of EMPRISE, we observed similar total cost, driven by trend towards lower medical and higher pharmacy costs, and lower medication burden in EMPA vs. DDP4i initiators.

Disclosure

A. Pawar: None. E. Patorno: Research Support; Self; National Institute on Aging. Other Relationship; Self; Boehringer Ingelheim International GmbH. A. Deruaz-Luyet: Employee; Self; Boehringer Ingelheim International GmbH. Employee; Spouse/Partner; Medtronic, Sanofi. K. Brodovicz: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. A.V. Ustyugova: Employee; Self; Boehringer Ingelheim International GmbH. N. Gautam: None. L.G. Bessette: None. S. Schneeweiss: Consultant; Self; Aetion, WHISCON, LLC. M. Najafzadeh: Consultant; Self; Epigenomics.

Funding

Boehringer Ingelheim
1197-P: Two-Year Effects of Ertugliflozin on Renal Function
Authors: CHERNEY DAVID , HEERSPINK HIDDO L. , FREDERICH ROBERT , MALDONADO MARIO , PONG ANNPEY , XU ZHI JIN , LIU JIE , MANCUSO JAMES P. , GANTZ IRA , TERRA STEVEN G.
Published: June 2019

2 RCT evaluating ertugliflozin 5 mg (E5, n=652), 15 mg (E15, n=640) vs. non-ertugliflozin (NE, glimepiride or placebo, n=644) in T2D patients were pooled to evaluate effects on eGFR (MDRD) and albuminuria (UACR, geometric mean of % change from baseline). eGFR and UACR were analyzed by mixed model repeated measures with treatment, time, trial, baseline measures [A1C, SBP, eGFR/UACR] as covariates in overall population and by presence of UACR >30 mg/g. Baseline characteristics in the treatment groups were balanced. Overall, mean baseline eGFR was 88.2 ml/min/1.73m2 and geometric mean baseline UACR was 11.6 mg/g. At week 6, changes in eGFR were: -2.3, -2.7 and -0.7 ml/min/1.73m2, for the E5, E15 and NE groups, respectively. Mean eGFR with ertugliflozin increased over time, while it decreased in the NE group. The week 104 ΔeGFR [95% CI] compared to NE was 1.81 ([0.13, 3.49]; p=0.04) and 2.10 ml/min/1.73m2 ([0.42, 3.78]; p=0.01) for E5 and E15, respectively. In patients with baseline UACR > 30 mg/g (n=415) the ertugliflozin groups had greater UACR reductions. The week 104 ΔUACR [95% CI] compared to NE was -29.0% ([-47.0, -4.5]; p=0.02) for E5 and -32.7% ([-50.4, -8.6]; p=0.01) for E15. Ertugliflozin acutely reduced eGFR in an expected fashion, possibly based of known hemodynamic effects. Over 104 weeks, eGFR values were higher with ertugliflozin than control, suggestive of renal function preservation. Ertugliflozin reduced UACR in subjects with baseline albuminuria.

Disclosure

D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi. H.L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation. R. Frederich: Employee; Self; Pfizer Inc. Stock/Shareholder; Self; Bristol-Myers Squibb Company, Pfizer Inc. M. Maldonado: Employee; Self; Merck Sharp & Dohme Corp. A. Pong: None. Z. Xu: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. J. Liu: Employee; Self; Merck & Co., Inc. J.P. Mancuso: Employee; Self; Pfizer Inc. Employee; Spouse/Partner; Pfizer Inc. Stock/Shareholder; Spouse/Partner; Pfizer Inc. Stock/Shareholder; Self; Pfizer Inc. I. Gantz: Employee; Self; Merck & Co., Inc. S.G. Terra: Employee; Self; Pfizer Inc.

Funding

Pfizer Inc.; Merck & Co., Inc.
1200-P: Predictors of Glycaemic and Weight Response to Empagliflozin Treatment: The ABCD Nationwide Empagliflozin Audit
Authors: THONG KEN , CHUNG-WAH-CHEONG JONATHAN , YADAGIRI MAHENDER , CULL MELISSA L. , BICKERTON ALEX , PHILLIPS SUZANNE M. , EVANS ALISON , SENNIK DEVESH K. , ROHILLA ANURITA , REID HAZEL , MORRIS DAVID S. , ATKIN MARC , ROBINSON ANTHONY M. , WILLIAMS DAVID M. , STEPHENS JEFFREY W. , GALLEN IAN W. , ADAMSON KAREN , RYDER ROBERT E.
Published: June 2019

Introduction: We investigated clinical parameters that are potentially associated with improved empagliflozin treatment response.

Methods: We obtained data from a large-scale audit of empagliflozin use in the UK. We analyzed the association between patients’ baseline age, HbA1c, weight, diabetes duration, alanine aminotransferase (ALT), sex, chronic kidney disease (CKD) stage, empagliflozin dose (25 vs. 10mg), use of GLP-1RAs and use of insulin with HbA1c and weight changes at 26 weeks of treatment.

Results: Among 1436 patients, HbA1c reduced by, mean[95% CI], 1.35%[1.27,1.42] (p<0.0001) from a baseline of, mean±SD, 9.41±1.41%. Among 1381 patients, weight reduced by 3.6 kg[3.3,3.9] (p<0.0001) from a baseline of 100.2±20.7 kg. Results of univariate analyses are shown in Table 1. In multivariate analysis, higher baseline HbA1c (p<0.0001), lower CKD stage (p=0.002) and higher ALT (log transformed)(p=0.02) were associated with greater HbA1c reduction. Higher baseline weight (p<0.001) and non-insulin use (p<0.0001) were associated with greater weight reduction.

Conclusion: As expected, HbA1c reduction was associated with baseline HbA1c and background renal function, while weight reduction was associated with baseline weight. The interactions between HbA1c reduction and ALT levels, and weight reduction with insulin treatment status warrant further investigations.

Disclosure

K. Thong: None. J. Chung-Wah-Cheong: None. M. Yadagiri: None. M.L. Cull: None. A. Bickerton: Employee; Self; MyWay Digital Health. S.M. Phillips: None. A. Evans: None. D.K. Sennik: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. A. Rohilla: None. H. Reid: None. D.S. Morris: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., NAPP Pharmaceuticals Limited, Novo Nordisk A/S, Sanofi-Aventis. M. Atkin: Advisory Panel; Self; NAPP Pharmaceuticals Limited. Consultant; Self; My mHealth. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. A.M. Robinson: Advisory Panel; Self; Takeda UK. D.M. Williams: None. J.W. Stephens: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, NAPP Pharmaceuticals Limited. I.W. Gallen: None. K. Adamson: None. R.E. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest.

Funding

Association of British Clinical Diabetologists
1204-P: The Effects of Insulin Treatment on Circulating Ketone Levels in Patients with Type 2 Diabetes on Sodium-Glucose Cotransporter 2 Inhibitors
Authors: LEE CHI HO , LAM JOANNE K. , LEE ALAN C. , LUI DAVID T.W. , CAROL FONG HO YI , WOO YU CHO , LAM KAREN S. , TAN KATHRYN C.
Published: June 2019

Objective: Use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) is associated with ketosis. On the other hand, insulin treatment inhibits lipolysis, hepatic ketogenesis, and promotes ketone oxidation in the peripheral tissues. Here, we investigated the effects of insulin therapy on circulating ketone levels in patients with type 2 diabetes (T2DM) receiving SGLT2i.

Research Design and Methods: 150 patients with T2DM on SGLT2i (51.3% on concomitant insulin therapy) and 100 not on SGLT2i were recruited from Diabetes Clinic. Fasting serum levels of β-hydroxybutyrate (βOHB)and free fatty acids (FFA) were measured by colorimetric assays.

Results: Participants on SGLT2i had significantly better glycemic control than those not on SGLT2i (HbA1c 7.7±1.2% and 8.8±1.5%, respectively; p <0.001). However, serum βOHBlevels were significantly higher in participants on SGLT2i compared with those who were not (347 uM [228-507] vs. 196 [151-274], respectively, p <0.001), despite similar age, body mass index (BMI), duration of diabetes and serum FFA levels (111 uM [81-148] vs. 108 [88-143]). In the group of participants on SGLT2i, those on insulin therapy had significantly higher BMI and HbA1c than those not on insulin therapy (BMI: 30.3±5.5 kg/m2vs. 27.5±5.5, respectively, p=0.002; HbA1c: 8.1±1.3% vs. 7.4±1.0%, respectively, p=0.001) but the duration of diabetes was similar. The median total daily dose of insulin was 50 units. Despite the concomitant use of insulin, serum βOHBlevels were comparable between participants on SGLT2i with or without insulin therapy (347 uM [220-485] vs. 347 [230-523], respectively), and were similar even after adjustments for BMI and HbA1c levels.

Conclusions: Serum ketone levels were increased in patients with T2DM on SGLT2i, and concomitant insulin therapy did not suppress the increase in circulating ketone levels. Further prospective studies or randomized controlled trials are required to confirm the above findings.

Disclosure

C. Lee: None. J.K. Lam: None. A.C. Lee: None. D.T. Lui: None. H. Fong: None. Y. Woo: None. K.S. Lam: None. K.C. Tan: None.
1209-P: Relationship between Canagliflozin Treatment Response and Duration of Diabetes: The Association of British Clinical Diabetologists (ABCD) Nationwide Canagliflozin Audit
Authors: RYDER ROBERT E.J. , PHILLIPS SUZANNE M. , EVANS ALISON , SENNIK DEVESH K. , ROHILLA ANURITA , BICKERTON ALEX , THONG KEN , YADAGIRI MAHENDER , CULL MELISSA L. , WYRES MELANIE C. , WINOCOUR PETER , DARZY KEN H. , STRZELECKA ANNA , GOHIL SHAILESH G. , GALLAGHER ALISON , GALLEN IAN W.
Published: June 2019

In the ABCD nationwide liraglutide audit the impact of liraglutide on HbA1c was found to lessen with increasing duration of diabetes (abstract 1038-P, ADA 2012). We were interested to examine the relationship between change in HbA1c and duration of diabetes in response to canagliflozin in real clinical use in the ABCD nationwide canagliflozin audit. By December 2018 the audit had accumulated data on 972 canagliflozin treated patients of whom there were 604 with baseline HbA1c ≥ 7% and follow-up HbA1c (mean ± SD age 60.3 ± 11.1 year, BMI 33.7 ± 6.7 kg/m2, 62% male, median (IQR) diabetes duration 6.0 (2.6-11) year). By 1st return to clinic after commencing canagliflozin at median (IQR) 4.1 (3.0-6.1) months, mean ± SD HbA1c fell by 0.91 ± 1.2%, from 9.2 ± 1.5 to 8.3 ± 1.3% (p<0.001). Patients with duration of diabetes data (n=434) were divided into 3 groups: 0-5, 6-10, >10 years with mean ± SD baseline HbA1c 9.1 ± 1.6, 9.2 ± 1.5 and 9.3 ± 1.3% respectively (p=0.62). The mean ± SD falls in HbA1c for the 3 groups were 0.87 ± 1.3%, 0.88 ± 1.2%, and 0.86 ± 1.2%, respectfully (p=0.99) (Figure). There was thus no relationship between duration of diabetes and fall in HbA1c in this audit of canagliflozin in real clinical use in the UK. This result contrasts with that from the ABCD liraglutide audit and is in keeping with the differing modes of action of liraglutide and canagliflozin.

Disclosure

R.E.J. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest. S.M. Phillips: None. A. Evans: None. D.K. Sennik: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. A. Rohilla: None. A. Bickerton: Employee; Self; MyWay Digital Health. K. Thong: None. M. Yadagiri: None. M.L. Cull: None. M.C. Wyres: None. P. Winocour: None. K.H. Darzy: None. A. Strzelecka: None. S.G. Gohil: None. A. Gallagher: Speaker's Bureau; Self; Novo Nordisk A/S. I.W. Gallen: None.

Funding

Association of British Clinical Diabetologists
1224-P: Improving Compliance with SGLT2 Inhibitors by Reducing the Risk of Genital Mycotic Infections: The Outcomes of Personal Hygiene Advice
Authors: WILLIAMS SCOTT M. , AHMED SYED HARIS
Published: June 2019

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have now become established as important second line agents for the management of type 2 diabetes, and are known to have clinical glycaemic, renal and cardiovascular benefits. The development of genital mycotic infections is more common with SGLT2 inhibitors (overall incidence in clinical trials of 4% to 6%) compared to other oral hypoglycaemic agents, and can dissuade patients from persisting with treatment.

Aims: To determine whether the provision of hygiene advice is beneficial in the prevention of genital mycotic infections in patients commenced on SGLT2 inhibitors.

Methods: Patients in an outpatient setting were provided with hygiene advice to rinse the genital area with water after every void and before going to bed, when commencing an SGLT2 inhibitor including dapagliflozin, empagliflozin and canagliflozin. The incidence of genital mycotic infections in these patients was compared to patients who were not given hygiene advice whilst receiving an SGLT2 inhibitor during a three-year period (2015 to 2018) using a linear regression analysis considering the confounding factors of age, sex, glycaemic control (HbA1c) and previous genital mycotic infection.

Results: Of the 125 patients who received hygiene advice, 6 (4.8%) developed a genital mycotic infection, whereas 51 of the 125 patients (40.8%) who were not given hygiene advice developed a genital mycotic infection within the first 6 months. 15 of the 51 patients had mild infection and continued an SGLT2 inhibitor with antifungal treatment, and 36 stopped due to severe infection. There was a significant reduction in the risk of these infections (p = 0.015) in patients given hygiene advice, and compliance was significantly higher in this group (p = 0.012).

Conclusion: Personal hygiene advice should be provided for all patients commenced on SGLT2 inhibitor therapy to improve compliance with this clinically beneficial treatment.

Disclosure

S.M. Williams: None. S.H. Ahmed: None.
123-OR: Effect of Surgical vs. Medical Therapy on Diabetic Kidney Disease (DKD) in Severely Obese Adolescents with Type 2 Diabetes (T2D)
Authors: BJORNSTAD PETTER , HUGHAN KARA S. , KELSEY MEGAN M. , SHAH AMY , LYNCH JANE L. , NEHUS EDWARD , MITSNEFES MARK , JENKINS TODD M. , XU PEIXIN , XIE CHANGCHUN , INGE THOMAS H. , NADEAU KRISTEN J.
Published: June 2019

To compare DKD rates over 5-years of follow-up in two cohorts of severely obese adolescents with T2D undergoing medical vs. surgical interventions.

A secondary analysis of data collected by the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and Treatment Options of type 2 diabetes in Adolescents and Youth (TODAY) studies was performed. Teen-LABS participants underwent bariatric surgery; TODAY participants were randomized to metformin alone or in combination with rosiglitazone or intensive lifestyle intervention, and insulin therapy was given when there was loss of glycemic control. TODAY participants (irrespective of treatment group assignment) were frequency matched to the 30 Teen-LABS participants with T2D by baseline age (13-18 years), ethnicity, sex, and baseline BMI (>35 kg/m2). Urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR) by creatinine and cystatin C equation, and prevalence of elevated UAE (≥ 30mg/g) and hyperfiltration (eGFR ≥ 135ml/min/1.73m2) were assessed.

Thirty Teen-LABS participants with T2D (mean±SD age, 16.9±1.3 years; 70% female; 66% white; BMI 54.4 kg/m2) and 63 TODAY participants (15.3±1.3 years; 44% female; 71% white; BMI 40.5 kg/m2) were compared. During 5-years of follow-up, hyperfiltration decreased from 20% to 13% in Teen-LABS and increased from 5% to 37% in TODAY. Elevated UAE decreased from 27% to 5% in Teen-LABS and increased from 21% to 43% in TODAY. Adjusting for baseline age, sex, BMI and HbA1c, Teen-LABS participants had 15-fold lower odds of hyperfiltration (OR: 0.06, 95% CI 0.01-0.38) and 27-fold lower odds of elevated UAE (OR: 0.04, 95% 0.01-0.20) at 5-years of follow-up. Decreases in HbA1c and BMI showed the strongest associations with attenuation of hyperfiltration and elevated UAE, respectively.

Compared with medical treatment, bariatric surgery of severely obese youth with T2D was associated with significantly lower odds of DKD over 5-years of follow-up.

Disclosure

P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. K.S. Hughan: None. M.M. Kelsey: None. A. Shah: None. J.L. Lynch: Board Member; Self; American Academy of Pediatrics. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Daiichi Sankyo Company, Limited, National Institutes of Health, Novo Nordisk Inc., Pediatric Diabetes Consortium. E. Nehus: Other Relationship; Self; Certara. M. Mitsnefes: None. T.M. Jenkins: None. P. Xu: None. C. Xie: None. T.H. Inge: Other Relationship; Self; Independent Medical Expert Consulting Services, Standard Bariatrics, UpToDate. K.J. Nadeau: None.

Funding

National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
1231-P: Dapagliflozin (DAPA) in Type 1 Diabetes (T1D): Pooled Outcomes from DEPICT-1 and -2
Authors: DANDONA PARESH , MATHIEU CHANTAL , PHILLIP MOSHE , HANSEN LARS , THOREN FREDRIK A. , SCHEERER MARKUS F. , XU JOHN , LANGKILDE ANNA MARIA
Published: June 2019

DEPICT-1 and -2 (NCT02268214, NCT02460978) were near identical studies assessing DAPA 5 and 10 mg as add-on to insulin (INS) in T1D. Here we present an analysis of the pooled population from the two studies. Safety data were available for 548, 566 and 532 patients (pts) in the DAPA 5 mg, 10 mg and placebo (PBO) groups, respectively and efficacy data for 530, 529 and 532 pts in each group, respectively. Baseline characteristics were similar between groups. Overall mean (SD) age was 43 (14) years, BMI 28 (5) kg/m2, duration of T1D 20 (12) years and HbA1c 8.5 (0.7)%. At week (week) 24 and 52 DAPA decreased HbA1c, systolic blood pressure (BP) and weight vs. PBO (Table). At week 24, INS dose was decreased with DAPA 5 mg (−8.3%) and 10 mg (−10.5%) but increased with PBO (+1.4%); this pattern was also seen up to week 52. More DAPA vs. PBO pts achieved HbA1c reduction ≥0.5% without severe hypoglycemia (hypo; Table). Safety of DAPA was consistent with previous observations in T1D and T2D. Severe hypo was balanced across groups. Events adjudicated as definite diabetic ketoacidosis (DKA) occurred more frequently with DAPA vs. PBO (in 3.8 vs. 1.1% of pts after 52 weeks); most were of mild or moderate intensity.

In conclusion, over 52 weeks in this large group of pts with T1D, DAPA provided glycemic, weight and BP benefits along with reductions in INS, increased DKA events, but with a low frequency of severe hypo.

Disclosure

P. Dandona: Advisory Panel; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. C. Mathieu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Speaker's Bureau; Self; AstraZeneca, Novartis AG, Novo Nordisk A/S, Sanofi. M. Phillip: Consultant; Self; Qulab Medical, RSP Systems A/S. Research Support; Self; Bristol-Myers Squibb Company, Dexcom, Inc., JDRF, Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., OPKO. Stock/Shareholder; Self; DreaMed Diabetes, Ltd., NG Solutions Ltd., Nutriteen Professional Ltd. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Insulet Corporation, Medtronic MiniMed, Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. L. Hansen: Employee; Self; AstraZeneca, MedImmune. Stock/Shareholder; Self; Bristol-Myers Squibb Company, Novo Nordisk A/S. F.A. Thoren: Employee; Self; AstraZeneca. M.F. Scheerer: Employee; Self; AstraZeneca. J. Xu: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca.

Funding

AstraZeneca
1234-P: Cost-Coping Behaviors Differ between Patients With and Without Diabetes Mellitus
Authors: HOLLAR LAURA , HUMBLE SARAH , HERRICK CYNTHIA J. , JAMES AIMEE S.
Published: June 2019

Background: Cost-coping behaviors, including skipping doses or borrowing money, are a recognized consequence of rising medication costs. Patients with diabetes mellitus (DM) have higher annual healthcare costs; however, there is limited data comparing cost-coping decisions in patients with and without DM.

Methods: We recruited 270 adults aged 35-80 with at least one chronic health condition, one medication and concern about cost. Participants were enrolled from academic multispecialty and community primary care clinics and newspaper ads. Individual hour-long surveys covered demographics, healthcare utilization and literacy, insurance, medications and diagnoses, financial strain, and provider communication. We compared survey data from patients with (n=81) and without (n=189) DM.

Results: The sample was 59% female and 83% African American. The majority had a high school education or less and 47% made less than $800 monthly. In patients with DM, monthly self-reported medication cost was higher ($92 vs. $42, p=0.001) and more variable month to month (25% vs. 15%, p=0.05). Those with DM were less likely to have never skipped doses to cut cost (44% vs. 59%, p=0.02) and were more likely to ask for and receive free samples (52% vs. 29%, p=0.0004). They were more likely to have filed for bankruptcy (38% vs. 22%, p=0.005) and reported spending less on basic needs to pay for medications (58% vs. 42%, p=0.01). These patients spent less on food/groceries first, followed by utilities, transport, and housing. More patients with DM had ever talked with a doctor about affordability of healthcare or medications (67% vs. 49%, p=0.008) and 86% were comfortable with the discussion.

Conclusion: Patients with DM are vulnerable to rising healthcare cost and utilize cost-coping strategies that could negatively affect health; however, most report being comfortable talking to a doctor about cost. Interventions that acknowledge and address cost-coping must be incorporated in practice to improve medication adherence.

Disclosure

L. Hollar: None. S. Humble: None. C.J. Herrick: Stock/Shareholder; Spouse/Partner; Cardinal Health. A.S. James: None.

Funding

National Institutes of Health (R01MD010445 to A.S.J.)
1241-P: Understanding Patients through Their Own Lens: The Lives of Individuals with Complex Diabetes as Revealed through Photo-Elicitation Interviews
Authors: PAUL MARGARET M. , SAAD ANDREA DAVILA , TAGLIAFERRO M. BARBARA , BILLINGS JOHN , BLECKER SAUL , BERRY CAROLYN
Published: June 2019

Background: Individuals living with complex diabetes in medically underserved areas face additional barriers to accessing needed services and support. This study used photo elicitation interviews (PEI) to develop a rich understanding of everyday life among individuals with complex diabetes living in such areas of New Mexico (NM).

Methods: Five individuals with T1DM and 3 with complex T2DM receiving care through Endo ECHO in NM received digital cameras and the task of taking photographs about their experience of living with diabetes, and then participated in interviews with our team, during which they selected 10 photos from their collections to discuss. Interviews were recorded and transcribed, and then coded using Grounded Theory in an iterative process.

Results: Six family-codes emerged: Self-management, health care, support, complications, food, and coping strategies. Three overarching axial codes were identified: Rural living, body self-knowledge, and diabetes burden. A picture of the relentless and never-ending nature of managing diabetes emerged in the analysis. Over half of the photos were of food, both healthy and forbidden; food is an overriding concern, and participants’ understanding of healthy food varied greatly. Participants noted important sources of support and optimism, and the joy of activities beyond diabetes care such as online gaming, raising chickens, or hiking.

Conclusions: Participants shared their unique perspectives; however, regardless of participants’ age, diabetes diagnosis, and gender, they uniformly expressed acute awareness of the permanent burden of their condition, the challenges of self-management, and the need to overcome the barriers of living in medically underserved areas. PEI proved to be a valuable method for ascertaining a deep understanding of individuals’ daily experience of living with complex diabetes.

Disclosure

M.M. Paul: None. A. Davila Saad: None. M. Tagliaferro: None. J. Billings: None. S. Blecker: Advisory Panel; Self; Medtronic. C. Berry: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
1247-P: Anticipating the Impact of 2019 Guidelines: Use of SGLT2i and GLP-1RA in Patients with Diabetes and Cardiovascular Disease
Authors: RATTELMAN CORI R. , CIEMINS ELIZABETH L. , CUDDEBACK JOHN K.
Published: June 2019

Objective: To describe use of GLP-1 RA and SGLT2i in the treatment of patients with diabetes and cardiovascular disease (CVD) using a large, clinical database.

Study Design: A retrospective descriptive analysis in a clinical database with 22 million longitudinal patient records across 22 health care organizations (HCOs).

Population Studied: A total of 2.6 million patients aged 18-75 with ≥ 2 ambulatory visits with primary care, endocrinology, cardiology, or nephrology in the past 18 months were included from 1/2013 to 3/2018. A subset of 350,000 patients with a type 2 diabetes (DM) diagnosis was observed during the 36 months ending 2016 Q1, 2017 Q1, 2018 Q1 for existing or new prescriptions of novel antidiabetic agents: GLP-1, SGLT2, or DPP-4. Patients were stratified by presence of cardiovascular disease (CVD), baseline DM medication regimen, and HbA1c ≥ 8.0, indicating need for advancing therapy.

Principal Findings: In 2018 Q1, the prevalence of CVD among patients with type 2 DM was 31%. Among patients with type 2 DM, a baseline oral antidiabetic regimen, and HbA1c ≥ 8.0, those with CVD were more likely to have any new DM medication class added (51% vs. 44%, p < 0.001), but no more likely than those without CVD to have a GLP-1 or SGLT2 added (p = 0.70). Patients with CVD were more likely to be prescribed insulin than those without evidence of CVD (20.2% vs. 10.3%, p < 0.001). From the 3-year period ending 2016 Q1 to that ending 2018 Q1, GLP-1 and SGLT2 prescriptions increased 3% and 4%, respectively, among all patients with type 2 DM.

Conclusions: Overall prescriptions of GLP-1 and SGLT2 are increasing but represent only 12% and 13%, respectively, of prescriptions for patients with type 2 DM (vs. 20% for DPP-4). Among patients with type 2 DM, these agents were prescribed no more frequently to those with established CVD than to those without CVD. Prescribing behavior complied with the new guidelines in only 14% of patients with both type 2 diabetes and CVD (range 8-31% across 20 HCOs).

Disclosure

C.R. Rattelman: None. E.L. Ciemins: None. J.K. Cuddeback: None.

Funding

Novo Nordisk
1252-P: Readmission Risk and Risk Factors of Hospitalizations with a Primary Diagnosis of Diabetes Differ from Discharges with a Secondary Diagnosis of Diabetes
Authors: RUBIN DANIEL J. , ZHAO HUAQING , MILLER ELI
Published: June 2019

Whether the risk of hospital readmission within 30 days of discharge (early readmission, ER) varies by primary or secondary discharge diagnosis of diabetes (DcDxDM) is unknown.

In a retrospective cohort study of adults with diabetes discharged from an academic medical center, we analyzed 4,027 discharges with a primary DcDxDM and 4,027 discharges with a secondary DcDxDM. A total of 49 characteristics were evaluated for association with ER by multivariable logistic regression models.

The ER rate of discharges with a primary DcDxDM was significantly higher than the ER rate of discharges with a secondary DcDxDM (22.2% vs. 16.2%, p<0.01). Discharges with a primary DcDxDM were significantly different from discharges with a secondary DcDxDM in 44 characteristics (all p<0.04). Among both primary and secondary DcDxDM discharges, lack of an outpatient visit within 30 days of discharge, length of stay, being unemployed, being discharged within 90 days before admission, and anemia were associated with higher ER risk, and being uninsured was associated with lower ER risk (all p<0.05). Among only primary DcDxDM discharges, lower education, gastroparesis, and higher serum creatinine were associated with higher ER risk, and inpatient diabetes consultation, thiazolidinedione use, and higher hematocrit were associated with lower ER risk (all p<0.02). Among only secondary DcDxDM discharges, urgent/emergent admission, abnormal serum sodium or albumin, discharge against medical advice, and pancreatitis were associated with higher ER risk (all p<0.05). C-statistics for the multivariable models of ER were similar between primary and secondary DcDxDM discharges (0.834 vs. 0.822, p=0.15).

Risk factors for ER after a primary DcDxDM discharge differ from risk factors after a secondary DcDxDM discharge. Patients with a primary DcDxDM are at a higher risk of ER and may benefit from dedicated effort to reduce their ER risk.

Disclosure

D.J. Rubin: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. H. Zhao: None. E. Miller: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K23DK102963 to D.J.R.)