bluuebunny/crossref_metadata_2025 huggingface dataset:
1176-P: Synthetic Immunomodulatory Peptoids to Control Autoimmunity in Type 1 Diabetes
Authors: RAMAKRISHNAN PARAMESWARAN , POKORSKI JON , DE JESUS TRISTAN J. , CENTORE JOSHUA
Published: June 2019

Type 1 diabetes is an autoimmune disease associated with hyperglycemia. Increased glucose flux enhances the hexosamine biosynthetic pathway and intracellular posttranslational modification of proteins by the sugar N-acetyl glucosamine (GlcNAc) in a process called O-GlcNAcylation. We discovered that hyperglycemia increases the O-GlcNAcylation of the transcription factor, nuclear factor kappaB (NF-κB) c-Rel at serine 350. O-GlcNAcylation of c-Rel activates c-Rel-dependent transcription of proautoimmune cytokines in T cells and inhibits the expression of T regulatory cell specific transcription factor FOXP3. These reciprocal effects caused by c-Rel O-GlcNAcylation may act as positive feedback accelerator of autoimmunity under hyperglycemia. Hence, blocking the function of O-GlcNAcylated c-Rel will have dual benefits in controlling autoimmune diabetes by diminishing the T cell-mediated autoimmunity and enhancing the T regulatory cell function to suppress autoimmunity. We developed a novel peptoid, called peptoid3 that specifically blocks the function of O-GlcNAcylated c-Rel. We found that peptoid3 treatment significantly decreased T cell receptor-induced, O-GlcNAcylation-dependent expression of proautoimmune cytokines and enhanced FOXP3 expression in T cells. Peptoid3 treatment selectively affected autoimmunity-associated genes and did not exhibit toxicity on survival or proliferation of T cells. Broad inhibition of hexosamine biosynthetic pathway or NF-κB will cause many side effects due to their ubiquitous importance in multiple biological functions. Therefore, inhibitors of O-GlcNAcylated NF-κB c-Rel function may prove long-sought-after specific molecular therapeutic to diminish autoimmunity in type 1 diabetes.

Disclosure

P. Ramakrishnan: None. J. Pokorski: None. T.J. de Jesus: None. J. Centore: None.

Funding

National Institute of Allergy and Infectious Diseases (R01AI116730-01A1)
1178-P: MSDC-0602 Directly Inhibits Mitochondrial Pyruvate Transport
Authors: RAUCKHORST ADAM J. , OONTHONPAN LALITA , TAYLOR ERIC B.
Published: June 2019

The mitochondrial pyruvate carrier (MPC) occupies a carbohydrate metabolism nexus and is a potential target of thiazolidinediones (TZDs) prescribed to treat the metabolic syndrome. MSDC-0602, a TZD-like, PPARγ sparing molecule, is currently in phase 2B clinical for NASH treatment following positive results in animal studies. Previous research demonstrates that MSDC-0602 inhibits mitochondrial pyruvate oxidation and physically interacts with the MPC. However, the extent to which MSDC-0602 directly inhibits mitochondrial pyruvate uptake has not been fully resolved. Here, we aimed to comprehensively test the action of MSDC-0206 as a specific MPC inhibitor. We examined MSDC-0602 treatment effects on pyruvate oxidation and pyruvate transport by isolated liver mitochondria from normal chow (NCD)- and high fat diet (HFD)-fed mice. MSDC-0602 inhibited pyruvate-driven State III and State IV+Uncoupled respiration in a dose dependent manner. MSDC-0602 reduced pyruvate-driven respiration to levels observed for liver mitochondria isolated from MPC liver knockout (MPC LivKO) mice. NCD and HFD mice showed similar response to MSDC-0602. These data confirm that MSDC-0602 inhibits pyruvate-driven respiration. However, pyruvate oxidation is an indirect measure of MPC activity because it depends upon pyruvate-oxidizing enzymes and electron transport. To directly test the action of MSDC-0602 on mitochondrial pyruvate transport, we performed isolated mitochondria 14C-pyruvate uptake assays. Pyruvate uptake was significantly decreased by MSDC-0602 to rates observed for MPC LivKO mouse liver mitochondria. Finally, we examined effects of MSDC-0602 metabolites and found them to also inhibit isolated liver mitochondria pyruvate oxidation. Together, these data demonstrate that MSDC-0602 directly and specifically inhibits MPC activity as a mechanism for impairing downstream pyruvate utilization. The therapeutic effects of MSDC-0602 may be conferred by MPC inhibition and resulting metabolic adaptations.

Disclosure

A.J. Rauckhorst: None. L. Oonthonpan: None. E.B. Taylor: Research Support; Self; Cirius Therapeutics.

Funding

American Diabetes Association (1-18-PDF-060 to A.J.R.); National Institutes of Health (DK104998); Cirius Therapeutics
1185-P: Predictive Model for Hyperglycemic Events after High Dose Corticosteroid Administration
Authors: SIMONS MORGAN G. , FUTOMA JOSEPH D. , GAO MICHAEL , COREY KRISTIN , SENDAK MARK , WHALEN KRISTA B. , DOSHI-VELEZ FINALE , MCGEE ANN S. , SETJI TRACY
Published: June 2019

Background: Patients who receive high dose corticosteroids and thereafter become hyperglycemic are at increased risk of inpatient mortality and developing diabetes. However, it is difficult to predict which patients will become hyperglycemic.

Methods: A cohort of 19882 patients with 28845 inpatient encounters between Oct 2014 and Aug 2018 was selected to create a model to predict incident hyperglycemia. Patients in this cohort were 18 years old and had received high dose corticosteroids (20mg/day of prednisone equivalents). Patients who died during admission or were discharged to hospice were excluded. Model features included creatinine, bicarbonate, AST, ALT, and albumin results and total steroid administration dose in the prior 24 hours as continuous variables and the presence of a lactate result in this period as a binary indicator variable. The outcome of hyperglycemic events was defined as patients having a blood glucose value above 180 within 12 hours of steroid administration. A logistic regression analysis was used as the predictive method.

Results: A subset of 71837 steroid administrations were used to create the predictive model and 8278 were used to test the model’s performance (AUC of 0.737).

Conclusion: Several labs in the 24 hours prior to receipt of high dose steroids are associated with hyperglycemia. The presence of a lactate result was the most significant predictor of future hyperglycemia.

Disclosure

M.G. Simons: None. J.D. Futoma: None. M. Gao: None. K. Corey: None. M. Sendak: None. K.B. Whalen: None. F. Doshi-velez: None. A.S. McGee: None. T. Setji: None.
119-LB: Bolus Dosing Accuracy of Two Recent Insulin Pumps
Authors: ZIEGLER RALPH , WALDENMAIER DELIA , MENDE JOCHEN , HAUG CORNELIA , FRECKMANN GUIDO
Published: June 2019

In continuous subcutaneous insulin infusion (CSII) therapy, bolus doses are delivered to cover meals and to correct high blood glucose values. Data for bolus dosing accuracy were already presented for different insulin pump systems. In this study, two lately released insulin pumps were tested accordingly.

Two new insulin pumps (MiniMed® 670G and mylife™ YpsoPump®) with soft cannula were tested. In an experimental setting following EN 60601-2-24, both pumps were installed with the tip of the cannula in a water-filled beaker placed on an electronic balance. To avoid evaporation an oil film was applied. After a run-in period, 25 successive 1.0 U and 0.1 U boluses and 12 successive 10 U boluses were delivered and weighed individually. In addition, time for a bolus delivery of 10 U was recorded. Each insulin pump was tested 9 times.

While for 10 U and 1 U boluses 100% of deliveries of both pumps were within ±15% of target, only 85% (670G) and 88% (YpsoPump), respectively, of 0.1 U boluses were within these limits. Delivery time of a 10 U bolus was different between the two pumps, 6.7 min (standard speed) and 43 sec (quick) for 670G vs. 19 sec for YpsoPump, but complied with the respective manufacturer’s labeling.

These results fit to the previously tested durable insulin pumps for which similar percentages of deliveries within ±15% of target (100% for 10 and 1 U and 71% to 96% for 0.1 U) were observed. As delivery accuracy decreases with smaller bolus doses, care should be given especially when treating small children with CSII.

Disclosure

R. Ziegler: Advisory Panel; Self; Abbott, Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care. D. Waldenmaier: None. J. Mende: None. C. Haug: None. G. Freckmann: Advisory Panel; Self; Abbott, Novo Nordisk Pharma GmbH, Sensile Medical AG. Consultant; Self; Metronom Health Europe, Roche Diabetes Care, Sanofi. Speaker’s Bureau; Self; Ascensia Diabetes Care, Dexcom, Inc., Ypsomed AG.

Funding

Roche Diabetes Care GmbH
1191-P: Sotagliflozin Reduces Glucose Variability and Risk for Hyperglycemia in Adults with Type 1 Diabetes
Authors: KOVATCHEV BORIS , WANG STELLA , OLIVEIRA JULIANA H. , STEWART JOHN A. , LAPUERTA PABLO , CASTRO RITA
Published: June 2019

Individuals with type 1 diabetes (T1D) face daily challenges in achieving optimal glycemic control by reducing hyperglycemia while avoiding hypoglycemia. Optimization is reflected by the High/Low Blood Glucose Indices (HBGI/LBGI) - established metrics using self-monitored blood glucose, or continuous glucose monitoring (CGM) data, to assess glycemic variability (GV) and predict the risks of hyper- and hypoglycemia with intensification of therapy.

In the phase 3 inTandem1 and 2 studies, sotagliflozin (SOTA), a dual SGLT1 and 2 inhibitor used as adjunct to optimized insulin therapy in adults with T1D, reduced HbA1c vs. placebo. Significant improvement of glucose time in range (70-180 mg/dL) without increasing time <70 mg/dL was previously reported in the pooled CGM substudy. In this analysis (N=265), we evaluated hyper- and hypoglycemic risks with SOTA 200 mg and 400 mg, both taken once daily, using LBGI and HBGI computed from CGM data.

Compared with placebo, HBGI values were lower with SOTA 400 mg at study weeks 4, 12, and 24, and SOTA 200 mg at weeks 4 and 12 (p<0.0001) (Figure).

The percentage of adults in moderate (4.5-9) or high-risk (>9) HBGI categories was reduced with SOTA throughout the study for both dosages, and minimal changes were seen in LBGI values and risk categories.

The CGM profile showed that SOTA reduced GV through a favorable impact on HBGI without changing LBGI.

Disclosure

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. Wang: Employee; Self; Sanofi US. J.H. Oliveira: Employee; Self; Sanofi. Employee; Spouse/Partner; Sanofi. J.A. Stewart: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. R. Castro: Employee; Self; Sanofi US.

Funding

Lexicon Pharmaceuticals, Inc.; Sanofi
1195-P: Effect of Dapagliflozin on Obstructive Sleep Apnea in Patients with Type 2 Diabetes: A Randomized Controlled Trial
Authors: SUN QIN , TANG YI , ZHANG MIN
Published: June 2019

Background: Obstructive sleep apnea hypopnea syndrome (OSAHS) is closely correlated to obesity and T2DM. Lose weight is helpful for OSAHS patients. Dapagliflozin, a new hypoglycemic drug, was found to reduce weight of T2DM patients, just like metformin. Therefore, they might have potential therapeutic effects on OSAHS patients with T2DM. Aim: A randomized controlled trial was designed to observe the effects of dapagliflozin combined with metformin on body mass index (BMI), and the ventilation and sleep quality of patients with OSAHS combined with T2DM, as well as some metabolic indicators.

Methods: 36 enrolled OSAHS patients with newly-diagnosed T2DM were randomly assigned to two groups (dapagliflozin group and control group). These patients in dapagliflozin group were given dapagliflozin and metformin for 24 weeks, while controls were given glimepiride and metformin for 24 weeks. apnea-hypopnea index (AHI), minimum oxygen saturation (LSpO2), Epworth somnolence scale (ESS) score and some metabolic indicators were measured before and at 24 weeks after the initiation of treatment.

Results and Conclusion: Our study indicate that dapagliflozin can significantly reduce glucose, BMI, blood pressure and AHI, and improve hypoxemia during sleep and excessive daytime sleepiness (Table 1), which thereby has potential as an effective treatment approach for OSAHS.

Disclosure

Q. Sun: None. Y. Tang: None. M. Zhang: None.
121-OR: Insulin Clearance Is an Independent Determinant of ß-Cell Cell Function in Obese Youths
Authors: GALDERISI ALFONSO , TRICO DOMENICO , GIANNINI COSIMO , SANTORO NICOLA , CAPRIO SONIA , WEISS RAM
Published: June 2019

Background: Hyperinsulinemia results from β-cell ompensatory adaptation to insulin resistance and reduced insulin clearance. We examined the relationship between hepatic/peripheral insulin clearance and β-cell function in lean and obese insulin sensitive (IS) and insulin resistant (IR) adolescents.

Methods: A 2-step euglycemic hyperinsulinemic clamp and an hyperglycemic clamp were performed in 153 youths (73F, 14.4±3.3y) to evaluate hepatic (MCR1) and peripheral (MCR2) insulin clearance, β-cell function (DIcpep) and insulin sensitivity. Participants were grouped as:non-Obese NGT (nOb-NGT, n=23), obese NGT-IS (Ob-NGT-IS, n=47), obese NGT-IR (Ob-NGT-IR, n=47), and obese IGT (Ob-IGT, n=36). IS and IR were defined according to the median M (glucose disposal) from euglycemic clamp. Effect of MCR1-2, sex, age, BMI, Tanner stage, fasting/2h-glucose, ethnicity on DIcpepwas estimated by multivariate regression model.

Results: IS, MCR1/MCR2 did not differ between nOb-NGT and Ob-NGT-IS. MCR1 was lower in Ob-NGT-IR and Ob-IGT than nOb-NGT, while MCR2 only declined in the Ob-IGT. (upper panels) MCR1 and MCR2 were the sole determinants of DIcpep (p0.006 and p0.015), as confirmed by ~50% reduction in DIcpep of the lowest tertiles of MCR1 and MCR2. (lower panels).

Conclusion: In obese adolescents, lower MCR1 and MCR2 are independently associated with a blunted β-cell function thus playing a key role in youth onset T2D.

Disclosure

A. Galderisi: None. D. Trico: None. C. Giannini: None. N. Santoro: None. S. Caprio: None. R. Weiss: Consultant; Self; Medtronic MiniMed, Inc.

Funding

National Institutes of Health (R01DK085577-01, R01HD40787, R01HD28016, P30DK045735, K12DK094714-02, R01DK111038-01A1); Robert E. Leet and Clara Guthrie Patterson Trust; European Medical International Framework (EMIF115372)
1212-P: Sotagliflozin Reduces Markers of Arterial Stiffness in T1D: Pooled Analysis from inTandem 1 and inTandem 2 Clinical Trials
Authors: RODBARD HELENA W. , GIACCARI ANDREA , DAVIES MICHAEL J. , SAWHNEY SANGEETA , WANG STELLA , GARG SATISH K. , CARIOU BERTRAND
Published: June 2019

Cardiovascular (CV) disease is a major cause of mortality in type 1 diabetes (T1D). Elevated blood pressure, including both systolic blood pressure (SBP) and diastolic blood pressure (DBP), and increased arterial stiffness are linked to CV events. While SGLT2 inhibitors have shown positive outcomes pertaining to BP and markers of arterial stiffness and vascular resistance in adults with type 2 diabetes, such effects have not been reported previously in T1D. When added as an adjunct to insulin therapy, sotagliflozin (SOTA), a dual SGLT1 and SGLT2 inhibitor, has previously demonstrated significant SBP reduction vs. placebo in adults with T1D. In this post hoc analysis, several indirect markers of arterial stiffness including pulse pressure (PP), mean arterial pressure (MAP), and double product (DP), were calculated using observed SBP, DBP or pulse rate at 24 weeks using pooled data (n=1,575) from the inTandem 1 and 2 studies. Baseline characteristics were similar among groups. Significant placebo-adjusted reductions were observed at week 24 for SOTA 200 and 400 mg in SBP, DBP, MAP, and DP, and in PP for SOTA 400 mg [Table]. The reductions in BP were not associated with increases in heart rate.

In conclusion, treatment with SOTA in adults with T1D resulted in significant reduction in BP and several markers of arterial stiffness and vascular resistance.

Disclosure

H.W. Rodbard: Advisory Panel; Self; Bayer US, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Spouse/Partner; Eli Lilly and Company. Consultant; Self; Gan & Lee Pharmaceuticals. Research Support; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Merck & Co., Inc., Novo Nordisk Inc. A. Giaccari: Advisory Panel; Self; Sanofi. Board Member; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Merck Sharp & Dohme Corp., Sanofi. M.J. Davies: Employee; Self; Lexicon Pharmaceuticals, Inc. S. Sawhney: Stock/Shareholder; Spouse/Partner; AstraZeneca, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck & Co., Inc., Pfizer Inc. S. Wang: Employee; Self; Sanofi US. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. B. Cariou: Board Member; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals. Consultant; Self; GENFIT, Sanofi-Aventis. Research Support; Self; Amgen Inc., Pfizer Inc. Speaker's Bureau; Self; Abbott, Akcea Therapeutics, Merck Sharp & Dohme Corp.

Funding

Lexicon Pharmaceuticals, Inc.; Sanofi
1213-P: Assessing the Performance of Cardiovascular Risk Equations in the DECLARE-TIMI 58 Population
Authors: MCEWAN PHILIP , FOOS VOLKER , BENNETT HAYLEY , KARTMAN BERNT , EDMONDS CHRISTOPHER , GAUSE-NILSSON INGRID ANNA
Published: June 2019

Sodium-glucose co-transporter inhibitors have demonstrated reduced incidence of cardiovascular (CV) events, which cannot be fully explained by effects on HbA1c, body weight or blood pressure. Type 2 diabetes mellitus (T2DM) economic models link treatment-related changes in risk factor levels to long-term incidence of CV events via risk equations (RE). This study assessed the performance of commonly used CV RE in T2DM to the CV outcomes trial DECLARE-TIMI 58. Ten sets of RE were coded in MS-Excel (ADVANCE, ARIC, BRAVO, Framingham, Fremantle, New Zealand CVD, QRisk3, Swedish NDR, UKPDS 68 and 82) to predict annual probabilities of CV events and applied to baseline characteristics and 1-year treatment effects (HbA1c, weight and blood pressure) for dapagliflozin (DAPA) versus placebo (PLA) from DECLARE-TIMI 58. Predicted event rates for myocardial infarction (MI), heart failure (HF) and stroke and the relative risks (RR) associated with DAPA versus PLA were estimated and compared to the closest reported trial outcome. Of the ten sets of RE, seven predicted composite CV outcomes, demanding assumptions to predict risk of individual events; only UKPDS and BRAVO predicted all three events. When comparing trial observations against predictions averaged across RE, correlation was greater for absolute event rates (R2: 0.92) than RRs (R2: 0.42). ARIC, Fremantle and New Zealand RE considerably overpredicted risk of MI and stroke compared to the trial. RE typically underpredicted the effect of DAPA on HF (average predicted RR: 0.89 versus reported hazard ratio 0.73, CI: 0.61 to 0.88) and MI (average predicted RR: 0.93 versus reported hazard ratio 0.89, CI: 0.77 to 1.01). Existing methods of CV risk prediction evaluated in this study did not accurately predict the treatment benefits observed in DECLARE-TIMI 58. The development of DECLARE-TIMI 58-specific risk equations may be required to robustly evaluate the long-term clinical and economic impact of DAPA in T2DM.

Disclosure

P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. V. Foos: Employee; Self; Health Economics and Outcomes Research Ltd., IQVIA. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca.

Funding

AstraZeneca
1217-P: The Kidney Effects of the SGLT2 Inhibitors on the Japanese Type 2 Diabetes Mellitus Patients with Chronic Kidney Disease
Authors: KOBAYASHI KAZUO , TOYODA MASAO , HATORI NOBUO , SAKAI HIROYUKI , FURUKI TAKAYUKI , TAMURA KOUICHI , MIYAKAWA MASAAKI
Published: June 2019

Background: In some large-scale clinical trials, the administration of sodium glucose co-transporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) has revealed pronounced and consistently beneficial renal outcome. However, it is unclear whether long term SGLT2i administration led to similar results in Japanese T2DM patients. Objective: To elucidate the renal effects of long term SGLT2i administration in Japanese T2DM patients with chronic kidney disease (CKD).

Method: Data from T2DM patients with CKD who were visiting members of Kanagawa Physicians Association and being administered SGLT2i for more than 1 year were used.

Result: We analyzed 753 patients. Six SGLT2i types were used with median administration period of 33.0 months. The mean albumin-to-creatinine ratio (ACR) significantly decreased from 36.0 to 27.5 (mg/gCr, p<0.01). Based on intensity, the mean ACR value significantly decreased from 72.1 to 54.8 in microalbuminuric patients (n=288) and from 625.1 to 414.1 in macroalbuminuric patients (n=58) (p<0.01); however, it did not change in normoalbuminuric patients (n=275). Multiple linear regression analysis revealed that the localized ACR baseline value, change (Δ) in systolic and diastolic BP, and ΔHbA1c were independently correlated with ΔACR; values of these regression coefficients were -0.21, 0.01, 0.01, and 0.08, respectively (p<0.01). The eGFR decreased from 77.5±22.2 to 72.7±22.4 mL/min/1.73 m2 (p<0.01). The localized ACR baseline value, ΔBW, age, baseline eGFR, treatment duration, and baseline diastolic BP were independently correlated with ΔeGFR; the regression coefficients were -1.35, -0.42, -0.24, -0.23,-0.11, and -0.08, respectively (p<0.01).

Conclusion: This study confirmed that the improvement of ACR was also observed in the real world; however, eGFR gradually decreased after long term SGLT2i administration. The relationship between background factors should be further discussed in future.

Disclosure

K. Kobayashi: None. M. Toyoda: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Medtronic Japan Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. N. Hatori: None. H. Sakai: None. T. Furuki: None. K. Tamura: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca, Ono Pharmaceutical Co., Ltd. Speaker's Bureau; Self; AstraZeneca, Ono Pharmaceutical Co., Ltd. M. Miyakawa: None.
1239-P: Trend in Total Payment and Out-of-Pocket Payment on a Yearly Supply of Oral Antidiabetic Drug Types among U.S. Adults with Private Health Insurance from 2003 to 2016
Authors: SHAO HUI , LAXY MICHAEL , BENOIT STEPHEN R. , CHENG YILING J. , GREGG EDWARD , ZHANG PING
Published: June 2019

Increases in the number of new oral antidiabetic medications in the last decade have resulted in a change in payments. We examined the trends in total payment and patients’ out-of-pocket (OOP) payments on a yearly supply of various oral antidiabetic drug types from 2003 to 2016. We analyzed 1,803,427 adults with diabetes under fee for service plans from the 2003-2016 MarketScan commercial claims database. Antidiabetic drugs were grouped using National Drug Codes. Total and OOP payment for each drug type were modelled at a 30-day supply level, and later multiplied by 12 to obtain yearly estimates. Joinpoint regression was applied to identify the inflection point for trend changes and to estimate the magnitude of change in each defined segment. Payments were standardized to 2016 USD. Total payment for a yearly supply of newer drug types grew sharply after 2012, with an increasing rate of $334 (11%), $598 (10%), and $414 (11%) per year for DPP-4, GLP-1 and SGLT2, respectively (all p< 0.01). For older drugs, a decrease in total payment for a yearly supply was observed among Sulfonylurea (-$9,-6%), Meglitinide (-$595,-34%), AGI (-$71.41, -10%) and TZD (-$721,-48%) per year after 2012 (all p <0.01). Metformin is the only exception, which was found to have sharply increased at annual rate of $75 (32%, p<0.01) for a yearly supply. Although total payment escalated over time, OOP payment on most drug types remained during the study periods (all p-values >0.05). Only OOP payments on DPP-4, GLP-1, SGLT2 increased after 2010, but all below 5% per year and with p-values >0.05. Patterns of changes in payment on a yearly supply of drugs varied by drug type. Payment on older drugs tended to decline with exception of an increase for Metfomin. Payment increases on newer oral drugs tended to accelerate over time. OPP payments also varied by drug types but mostly declined over time, implying that the increase in payment for the newer drugs was mainly borne by payers.

Disclosure

H. Shao: None. M. Laxy: None. S.R. Benoit: None. Y.J. Cheng: None. E. Gregg: None. P. Zhang: None.
124-LB: Patients’ Experiences with a Do-It-Yourself Artificial Pancreas and Perspectives of the Endocrinologist’s Role in Supporting Their Use
Authors: PALMER WALTER , GREELEY SIRI ATMA W. , LETOURNEAU LISA R. , NAYLOR ROCHELLE N.
Published: June 2019

While commercial manufacturers push toward developing closed-loop insulin delivery systems, some type 1 diabetes patients are implementing self-built versions of such systems already. Use of these “do-it-yourself” (DIY) systems is increasing, but without standard regulatory oversight or clinical trial data.

The purpose of this study was to understand: 1) patients’ experiences with DIY systems and 2) their perspectives of how diabetes care providers have supported their use of such systems. We developed a survey through an iterative process and distributed via Twitter and Facebook to patients in the U.S. The survey was open for 2 weeks.

Respondents (n=101) were 2-72 years of age, from 34 states. A majority reported positive clinical outcomes, such as increased time in range (94%), less frequent sleep interruptions (93%), less frequent hyperglycemia (92%), less frequent hypoglycemia (89%), and lower HbA1c (74%).

Most respondents (89%) described DIY systems as “Safe” or “Very Safe,” whereas only 21% chose the same for traditional continuous glucose monitor and insulin pump combinations.

The majority of respondents were the only patient in their endocrinology practice on a DIY system (73%). Most reported their providers were “supportive” of their continued use (80%), but only 20% reported that their endocrinologist “understands the system well.”

Our results suggest that patients are adopting DIY systems with positive reported outcomes, and that endocrinologists are generally supportive despite limited experience with this technology. This study had limitations, including sample size, reliance on self-reported data, lack of a control group, and lack of data from endocrinology providers. Until commercially available closed-loop systems improve, the number of patients using DIY systems is likely to increase. Our research suggests that endocrinology providers may benefit from more exposure to such systems and education regarding their use.

Disclosure

W. Palmer: None. S.W. Greeley: None. L.R. Letourneau: None. R.N. Naylor: None.
1242-P: The Impact of Telehealth on the Management of Diabetes in Rural/Remote North Queensland, Australia: A Retrospective Cohort Study
Authors: NANGRANI NISHA , MALABU USMAN , VANGAVETI VENKAT
Published: June 2019

Background: The prevalence of diabetes in rural and remote North Queensland is twice that of the general Australian population. The vast geographical distances in North Queensland prevent patients from accessing specialist diabetes care in tertiary hospitals. Telehealth (TH) presents a unique opportunity to overcome this barrier. However, the ability of TH to improve glycaemic control and vascular risk factors (blood pressure, body mass index, lipid profile) in comparison to traditional face-to-face (FTF) care in this population remains unknown.

Methods: This was a retrospective cohort study of all diabetes-related telehealth consultations conducted at the Townsville Hospital from January 2016 to March 2018. The primary outcome was the change in HbA1c post-FTF (face-to-face) care versus post-TH care. Secondary outcomes included change in blood pressure, body mass index and lipid profile. We conducted a preliminary economic analysis to determine patient cost-savings from the tele-diabetes model of care.

Results: 330 patients were included in the study. The majority (71%) had a diagnosis of type 2 diabetes. The median baseline HbA1c was 9.1% (8.0-10.8). HbA1c improved from 9.1% (post-FTF) to 8.1% post-TH intervention (z = -9.184, p<0.001). We observed a reduction in total cholesterol levels (4.15 mmol/L to 4.00 mmol/L; z = -3.198, p<0.001) and LDL-cholesterol (2.00 mmol/L to 1.80 mmol/L; z = -4.209, p<0.001). The tele-diabetes model was associated with a total patient cost-savings of $131,710 (equating to $390 in cost-savings per patient per trip).

Conclusions: Telehealth consultations improved glycaemic control and lipid levels more effectively than traditional face-to-face care with significant cost savings for a rural and remote population in North Queensland, Australia.

Disclosure

N. Nangrani: None. U. Malabu: None. V. Vangaveti: None.
1245-P: The Association of Glucose Variability during the Last Day of Hospitalization and 30-Day Readmission in Adults with Diabetes
Authors: SPANAKIS ELIAS , SINGH LAKSHMI G. , SIDDIQUI TARIQ , SORKIN JOHN D. , NOTAS GEORGE , MAGEE MICHELLE F. , FINK JEFFREY C. , ZHAN MIN , UMPIERREZ GUILLERMO E.
Published: June 2019

Objective: Thirty-day hospital readmission (30-day RA) rates are a metric of healthcare quality. Limited data is available, whether increased glucose variability (GV) during the last day of hospital stay is associated with an increased risk of 30-day RA.

Design: Nationwide cohort of 1,042,859 admissions of patients with diabetes in the non-critical care setting in 129 Veteran Affairs hospitals, between 2001-2014. Coefficient of Variation (CV) was measured using point of care- glucometer values and was used as measurement of GV, divided into ten equal categories (tentiles). Covariates, including demographics, socio-economic and hospital related factors and up to 30 comorbidities were collected. Poisson regression was used to determine if CV during the last stay day of the hospitalization was associated with 30-day RA.

Results: After adjusting for age, gender and race (Model 1), there was a gradual increase in 30-day RA ratio among admissions with higher CV. Following adjusting for all the covariates collected (Model 2), only admissions with the highest CV demonstrated an increased 30-day RA. The rate ratios and 95% CIs were 1.049 (1.026, 1.073, p<0.0001), 1.038 (1.015,1.061, p=0.0011), 1.065 (1.042,1.089, p<0.0001), for the 8th, 9th and the 10th tentiles respectively, compared to those with CV in the 1st tentile. In Model 3, after adjusting for covariates used in Model 2 and for hypoglycemia, results remained statistically significant for those admissions with the highest CV [rate ratios and 95% CIs are 1.044 (1.021,1.068, p=0.0001), 1.028 (1.006,1.052, p=0.014), 1.042 (1.018,1.067, p=0.0005) for the 8th, 9th and the 10th tentiles].

Conclusions: Higher glucose variability during the last day of hospitalization was associated with increased 30-day RA rates after adjustment for multiple covariates and hypoglycemia.

Disclosure

E. Spanakis: None. L.G. Singh: None. T. Siddiqui: None. J.D. Sorkin: None. G. Notas: None. M.F. Magee: Consultant; Self; Mytonomy. Research Support; Self; Lilly Diabetes, Mytonomy, Sanofi. Speaker's Bureau; Self; PRIMED. J.C. Fink: None. M. Zhan: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc., Sanofi US.

Funding

U.S. Department of Veterans Affairs (1I01CX001825-01)
127-LB: Longevity of the Coated ConvaTec Infusion Set with Lantern Technology
Authors: LAL RAYHAN , SCHøNDORFF PERNELLE K. , HSU LIANA , HESCHEL MATTHIAS , BUCKINGHAM BRUCE A.
Published: June 2019

Objective: Current insulin infusion sets are approved for 2-3 days of wear; however, glucose sensors are approved for 7-14 days of wear. A commonly reported reason for discontinuing use of CGM within 1 year is not wanting to wear devices on two sites of the body. Any attempt to create a combined glucose sensor and infusion set for closed-loop control requires a set with greater longevity. The coated ConvaTec Infusion Set with Lantern Technology is a new infusion set with multiple slits and coating intended to reduce foreign body response and occlusion from bending or kinking.

Methods: A pilot safety and extended wear tolerability study is being performed at Stanford University. To date, 15 adult subjects on tethered insulin pump therapy using insulin aspart or lispro have completed the study. Each participant places the set and wears it for 10 days or until set failure to establish a maximum length of infusion set wear when 80% of sets are still functional (excluding accidental “pull-outs”). Infusion set failures are based on: (1) Presence of serum ketones with hyperglycemia; (2) Unexplained hyperglycemia, unresolved with correction dose; (3) Signs of infection at the infusion site; (4) Pump occlusion alarm; and (5) Adhesive failure.

Results: Two subjects did not meet failure criteria and were excluded. Of the remaining, 6 (46%) wore the novel infusion set the full 10 days and all sets lasted 7 days or more (mean 8.8 days). 3 premature set failures were associated with persistent hyperglycemia unresponsive to correction boluses on days 7-8, 3 with adhesive failure on days 7-9, and 1 with infection on day 9.

Conclusions: In our previous studies assessing 353 infusion set insertions for 7 days, average length of wear was 5.1 ± 1.7 days. Thus far, the novel set has demonstrated increased longevity. The duration of wear established in this pilot study will be used to perform a masked, randomized controlled crossover study comparing the coated ConvaTec Infusion Set with Lantern Technology against standard infusion sets.

Disclosure

R. Lal: Consultant; Self; Abbott. P.K. Schøndorff: Employee; Self; ConvaTec Inc. L. Hsu: None. M. Heschel: Employee; Self; Unomedical a/s. 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.
1271-P: Impact of Physician-Pharmacist Collaboration on A1C in an Interprofessional Endocrinology Clinic
Authors: ISAACS DIANA , ZIMMERMAN ROBERT S. , LANSANG M. CECILIA
Published: June 2019

Background: Comprehensive medication management (CMM) ensures an individualized plan for medication appropriateness, effectiveness, safety, and adherence. It is most often performed by pharmacists within a pharmacist-physician collaborative agreement. Published studies on CMM are few and mostly conducted in primary care settings. The aim of our study was to determine the impact of CMM on the proportion of patients that achieve ≥ 1% A1c reduction in an interprofessional specialty clinic.

Methods: This is a retrospective study comparing 2 groups: group 1-without pharmacist collaboration, group 2-with pharmacist collaboration. Subjects were adults with diabetes and most recent A1c ≥ 8.5% with at least one visit in the interprofessional endocrinology clinic between 1/2016-12/2017. Exclusion criteria were pregnancy, no A1c within 6 weeks of initial visit, and no follow-up A1c. The 2 groups were matched for initial A1c, type of diabetes, age, and BMI.

Results: A total of 162 participants were included. Baseline characteristics were similar between groups: Group 1: (mean age: 57.6 ± 15.8 years, BMI: 34.3 ± 8.1 kg/m2, A1c: 10.2 ± 1.2%, T1DM: 26%), Group 2 (mean age: 56.0 ±16.4 years, BMI: 32.6 ± 8.1 kg/m2, A1c: 10.1± 1.3%, T1DM: 26%). The percentage of subjects achieving ≥1% A1c reduction at 6 months was 58.0% in Group 2 compared to 40.7% in Group 1, p=0.041. More subjects achieved A1c < 8% in group 2 (32.1%) vs. Group 1 (18.5%), p=0.047. The frequency of endocrinologist visits was more in group 1 (2.37/patient) vs. group 2 (1.89/patient), p=0.01. Group 2 averaged 3.0 pharmacist visits per patient.

Discussion: Physician-pharmacist collaboration led to greater A1c reduction compared to usual endocrinologist care in patients with uncontrolled A1c. However, frequency of total provider visits may account for some differences. Overall, utilizing pharmacists within diabetes health care models may reduce frequency of endocrinologist visits while improving glycemic control.

Disclosure

D. Isaacs: Advisory Panel; Self; BD, Sanofi-Aventis. R.S. Zimmerman: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. Speaker's Bureau; Self; Johnson & Johnson Diabetes Institute, Merck & Co., Inc. M. Lansang: None.
1280-P: Effect of Professional CGM (pCGM) on Glucose Management in Type 2 Diabetes Patients in Primary Care
Authors: MARTENS THOMAS W. , BERGENSTAL RICHARD M. , JOHNSON MARY L. , DAVIDSON JANET L. , SIMONSON GREGG
Published: June 2019

Background: Very little data exists regarding the impact of CGM in the primary care management of type 2 diabetes (T2D). We initiated a QI project in a large health care system to determine the effect of pCGM on glucose management. We evaluated a MD model, and an RN/Certified Diabetes Educator (CDE) model.

Methods: Patients (pts) with T2D for >1 year, A1C ≥7.0 and <11.0%, managed with any T2D regimen, and willing to use pCGM were included. Baseline A1C was collected and pts wore a pCGM (Libre Pro) up to 2 weeks followed by a visit with MD or RN/CDE (MD consultation if needed) to review CGM data including Ambulatory Glucose Profile (AGP). Shared decision making was used to modify lifestyle and medication regimen. Clinic follow-up in 3-6 months included an A1C and in a subset a repeat CGM.

Results: Sixty-eight pts average age 61.6 years, average duration of T2D 15 years, mean A1C 8.8%, were identified. Pre to post pCGM lowered A1C from 8.8 ± 1.2% to 8.2 ± 1.3% (n=68, p=0.006). The time in range (TIR) and time in hyperglycemia improved along with slightly more hypoglycemia in the subset of 37 pts who wore a second pCGM (Table). Glycemic improvement was largely due to lifestyle counseling (68% of pts) and intensification of current therapy (65% of pts), and not due to addition of medications.

Conclusion: Using pCGM in a primary care setting, with an MD or RN/CDE model, is effective at lowering A1C, increasing TIR and reducing time in hyperglycemia.

Disclosure

T.W. Martens: Research Support; Self; Abbott Laboratories, Dexcom, Inc., Medtronic, Novo Nordisk Inc. R.M. Bergenstal: Research Support; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Glooko, Inc., Hygieia, JDRF, Johnson & Johnson Medical Devices Companies, Lilly Diabetes, Medtronic MiniMed, Inc., Merck & Co., Inc., National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc., Roche Diabetes Care, Sanofi. Other Relationship; Self; Abbott, Helmsley Charitable Trust, Hygieia, Lilly Diabetes, Novo Nordisk Inc., Onduo LLC, Sanofi, UnitedHealth Group Inc. M.L. Johnson: Research Support; Self; Abbott, Calibra Medical, CeQur Corporation, Dexcom, Inc., Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc., Sanofi. J.L. Davidson: None. G. Simonson: Advisory Panel; Self; Merck & Co., Inc. Research Support; Self; Abbott.

Funding

Abbott Laboratories
1300-P: Hyperglycemia Is Associated with Worse Outcomes in Neurosurgery Only in Patients without Diabetes
Authors: GRECO GIAMPAOLO , MOSKOWITZ ALAN J. , LAM DAVID W.
Published: June 2019

Hyperglycemia is associated with adverse outcomes in critically ill surgical patients with increasing recognition that those without preexisting DM (NODM) are more affected. As the brain acts as a major regulator of glucose and exclusively depends on it for its high energy needs, we examined the association between hyperglycemia and outcomes in ICU patients undergoing elective or emergent neurosurgery (NSGY) with and without DM. Patients (N 864) were grouped as NODM, pre-existing DM on (DMTR) and not on medications (DMNT) (NODM 637 DMNT 80 DMTR 147). Postop glucose (BG) and time weighted average BG (TWAg) 24 hours postop, postop length of stay (pLOS), hospitalization cost and adverse outcomes (death, respiratory failure, infection, stroke, MI) were obtained retrospectively from admissions between May 2011 - January 2015. Those in DMTR had higher TWAg than in DMNT and NODM (188 vs. 166, 145 mg/dL p<0.005). After adjustment for demographics, comorbidities and surgical characteristics, NODM patients with hyperglycemia (mean of 2 consecutive BG > 180 mg/dL) had higher costs and pLOS while those in DMTR had lower cost and shorter pLOS. Those in NODM with hyperglycemia had more adverse events than those without; this was not seen in DMNT and DMTR (Figure). We found in NSGY patients, hyperglycemia’s association with adverse events depends on DM status and stresses the need to understand underlying mechanisms.

Disclosure

G. Greco: None. A.J. Moskowitz: None. D.W. Lam: Research Support; Self; Novo Nordisk A/S.
1313-P: Comparison of Diabetes Health-Care Quality between Endo ECHO and the Academic Medical Center
Authors: PAUL MARGARET M. , SAAD ANDREA DAVILA , BILLINGS JOHN , BLECKER SAUL , BOUCHONVILLE MATTHEW F. , HAGER BRANT , ARORA SANJEEV , BERRY CAROLYN
Published: June 2019

Background: Patients receiving diabetes specialty care experience higher quality care, fewer complications and improved survival; however, access to specialists is limited in medically underserved areas. The Endo ECHO program connects specialists at academic medical centers with PCPs through virtual clinics. We report the comparability of quality measures between Endo ECHO patients and those receiving diabetes specialty care.

Methods: Patients with complex diabetes from 10 Endo ECHO clinics in NM completed surveys assessing healthcare quality one year after program enrollment. Patients at the University of New Mexico Diabetes Comprehensive Care Center (DCCC) served as a comparison group and completed the same survey.

Results: Five hundred thirty-three ECHO patients and 139 DCCC patients completed surveys. ECHO patients were much less likely to identify English as their primary language (69% ECHO vs. 91% DCCC, p<0.0001) and reported lower levels of educational attainment (40% ECHO with at least some college vs. 60% DCCC, p<0.0001). DCCC patients were more likely to report a positive overall health status (42% ECHO vs. 68% DCCC, p<0.0001), yet there was no difference in overall concern about health across groups. ECHO patients reported more frequent visits to their usual source of diabetes care (72% ECHO with 4 or more annual visits vs. 58% DCCC, p<0.0001). There were no differences in the frequency of A1C testing or feet checks by a provider; however, more DCCC patients reported regular eye exams (69% ECHO vs. 87% DCCC, p<0.0001) and that their provider had assessed smoking status (70% ECHO vs. 82% DCCC, p<0.0001).

Conclusions: Endo ECHO patients faced greater medical literacy barriers yet reported similar outcomes for several, but not all, diabetes care quality measures as compared to those reported by patients at the DCCC. Endo ECHO may be a suitable alternative to specialty care for patients in medically underserved areas; ongoing evaluation will determine its impact on clinical outcomes.

Disclosure

M.M. Paul: None. A. Davila Saad: None. J. Billings: None. S. Blecker: Advisory Panel; Self; Medtronic. M.F. Bouchonville: None. B. Hager: None. S. Arora: None. C. Berry: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
1314-P: Co-creating Gestational Diabetes Education: Using Web Analytics to Assess Learning Interests
Authors: BOISVENUE JAMIE , GHNAIM SARAH A. , KAUL PADMA , RYAN EDMOND A. , YEUNG ROSEANNE O.
Published: June 2019

Objectives: Gestational diabetes mellitus (GDM) education is the foundation for self-care management. This study aims to improve the GDM learning experience using the narrative and care experiences of women with GDM and their healthcare providers.

Methods: A working group of women with GDM and their health care providers used iterative dialogic priming (key quotes from previous sessions) to frame five sessions. Through a deliberative priority-setting process, participants decided to update www.diabetes-pregnancy.ca, an existing website that addresses GDM education priorities of the group. Participants contributed to the website organization, videos, and text content. Google analytics was used to evaluate site uptake.

Results: Five women with GDM and 7 diabetes healthcare providers were involved in updating the content of the website. Following the website re-launch, an analytics assessment of a 50-day average (Nov 14/18 - Jan 3/19) was compared to a previous period with its earlier design (Sept 24 - Nov 13/2018). A total of 490 users visited the site and the majority (n=224) resided in Alberta compared to 546 users (200 from Alberta) in the previous 50-day period. Amongst the recent users with an identified gender (n=166), there were 133 females and 33 males. Bounce rate (visitors immediately leaving website) decreased from 78.4% to 42.4% post-redesign. The pages viewed per user session increased from 1.86 to 3.91, and the average duration of sessions increased by 30.6% (7:23 to 9:39 minutes). Behavior flow of the site showed user navigation to the “GDM” homepage (n=382), followed by the “For Providers” page (n=122), and “Additional Resources” (n=112).

Conclusions: Co-creation of online education materials informed uptake of the website. Web analytics suggest that although the audience is more likely female, there are males seeking information. An online GDM resource provides a novel method to support continuous improvement of GDM education.

Disclosure

J. Boisvenue: None. S.A. Ghnaim: None. P. Kaul: None. E.A. Ryan: None. R.O. Yeung: Advisory Panel; Self; Sanofi. Consultant; Self; Novo Nordisk Inc. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi.

Funding

AstraZeneca Canada