bluuebunny/crossref_metadata_2025 huggingface dataset:
1099-P: Effects of Empagliflozin on Glucose Metabolism and Body Fat Composition in Patients with Prediabetes: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: HUMMEL JULIA , DANNECKER CORINNA , FRITSCHE LOUISE , VOSSELER ANDREAS , KANTARTZIS KONSTANTINOS , KULLMANN STEPHANIE , MACHANN JÜRGEN , PREISSL HUBERT , HAERING HANS-ULRICH , FRITSCHE ANDREAS , WAGNER ROBERT , HENI MARTIN
Published: June 2020

Objective: In patients with diabetes, the beneficial effects of empagliflozin on glucose metabolism, body adiposity, and liver fat content are well established. As the mode of action of SGLT2 inhibitors partly depends on elevated blood glucose, we investigated if these effects also occur in prediabetes.

Methods: Forty participants with prediabetes (mean ± SD: age: 60 ± 9 years; BMI: 31.5 ± 3.8 kg/m²; FG: 5.98 ± 0.57 mmol/l) were randomized to receive 25 mg empagliflozin qd or placebo for 8 weeks. Before and after treatment, all participants underwent a 75 g oral glucose tolerance test to evaluate glucose tolerance, peripheral insulin sensitivity and insulin secretion. Body fat was assessed by whole-body MRI and intrahepatic fat by localized MR-spectroscopy. Resting energy expenditure and respiratory quotient (RQ) were assessed by indirect calorimetry at fast. “Per protocol” analysis using ANCOVA was performed.

Results: Fasting glucose, glucose tolerance, peripheral insulin sensitivity, and insulin secretion were not significantly changed by treatment. Though, after 8 weeks of treatment, total adipose tissue (mean difference between groups at the end of study ± SEM: 3.1 ± 2.3 liters; p=0.034) and intrahepatic fat (2.1 ± 2.3 %; p=0.029) were lower in patients who received empagliflozin, compared to placebo. Empagliflozin treatment resulted in a lower RQ compared to placebo (p=0.022) without differences in resting energy expenditure (p=0.2), indicating preferential lipid oxidation upon treatment.

Conclusion: In prediabetes, treatment with empagliflozin for 8 weeks has no major effects on glucose metabolism. However, this SGLT2 inhibitor reduced body adiposity and liver fat content, presumably by shifting energy metabolism towards lipid oxidation. Therefore, empagliflozin might represent a treatment option for obesity and hepatic steatosis in prediabetes, independent of drug effects on blood glucose.

Disclosure

J. Hummel: None. C. Dannecker: None. L. Fritsche: None. A. Vosseler: None. K. Kantartzis: None. S. Kullmann: None. J. Machann: None. H. Preissl: None. H. Haering: None. A. Fritsche: None. R. Wagner: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Eli Lilly and Company. M. Heni: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S.

Funding

Boehringer Ingelheim
1113-P: The Use of Empagliflozin and Dulaglutide Improves Metabolic and Glycemia Outcomes in a Real-World Primary Care Setting
Authors: SPILIOTIS IOANNIS , GALLEN IAN W.
Published: June 2020

Improving key metabolic parameters in patients with type 2 diabetes can be challenging in primary care, and integration of diabetes services within the community plays a vital role. GLP-1 receptor agonists and SGLT2 inhibitors are effective at improving glycemic control and weight, and once weekly GLP-1 receptor agonists can improve the adherence to therapy. In this retrospective observational study, we examined the outcomes in primary care practices within the West Berkshire Clinical Commissioning Group.

Methods: We identified 313 patients who had been started on a combination of dulaglutide and empagliflozin (either exclusively or as an add-on). Clinical and metabolic parameters (HbA1c, weight, blood pressure, ALT, cholesterol and eGFR) were measured prior to, and at 3, 6 and 12 months after the start of dual treatment. The study population characteristics were as follows: 57% male, age (mean +/- SD) 57 +/-9 years, HbA1c 9.5 +/- 1.6% (80 +/- 17.5 mmol/mol), weight 106.1 +/- 22 kg. Repeated measures ANOVA was used to compare values to baseline.

Results: HbA1c decreased to 8.3% (67mmol/mol) at 3 months and to 8.1% (65mmol/mol) at 12 months (p<0.001); weight decreased by 2.5kg at 3 months and by 5.7kg at 12 months (p<0.001). Blood pressure decreased from 131 to 128mmHg systolic and from 78 to 77mmHg diastolic (p<0.005) at 3 months. ALT decreased from 36.3 to 31.1mmol/L at 3 months and to 29.9mmol/L at 12 months (p<0.001), cholesterol decreased from 4.4 to 4.2mmol/L at 3 months (p=0.005), while eGFR decreased slightly from 79.9 mean to 78 at 3 months (p<0.001).

Conclusion: In this real-world, primary care study of patients with difficult to manage diabetes and increased weight, the use of empagliflozin plus once weekly dulaglutide therapy led to an improvement in glycemic control and other metabolic parameters, and a reduction in weight. These effects could be observed within 3 months of starting dual therapy, and were either maintained or further improved by 12 months.

Disclosure

I. Spiliotis: None. I.W. Gallen: None.
1115-P: Comparative Rate of Amputations among Type 2 Diabetes Patients Starting Different SGLT2 Inhibitors
Authors: HAKIMIAN STEPHANIE , WALLIA AMISHA , KANG RAYMOND , COOPER ANDREW J. , O’BRIEN MATTHEW , LISS DAVID T. , HARRIS STERLING A. , CHERUPALLY MANISHA , PARKER EMILY D. , ACKERMANN RONALD T.
Published: June 2020

Prescribing of SGLT2 inhibitors (SGLT2i) has been on the rise. A 2016 FDA safety alert raised concerns of a possible risk for lower extremity amputations for patients initiating treatment with SGLT2i. We used a large national claims database to compare amputation events among patients newly prescribed one of 3 different SGLT2is: Canagliflozin (Cana), Dapagliflozin (Dapa), Empagliflozin (Empa). Study included adults with a first prescription fill for a SGLT2i between January 2014 and May 2017. We estimated adjusted incident rate ratios for any subsequent non-traumatic amputation over a mean of about 16.7 months of follow up using a multi-variable Poisson regression model adjusting for demographics, insurance, year of start, and clinical covariates (prior non-traumatic amputation and Diabetes Complication Severity Index (DCSI)). Among 43017 new SGLT2i starts, 64% (N=27528) were Cana, 22% (N=9487) were Empa and 14% (N=6002) were Dapa. Mean age was 58.0 ± 11.4 years and 42% were women. Use of Empa increased over time (1.3% of new starts in 2014 to 45.3% in 2017). 14% of Dapa patients had Medicare, compared with 32% of Cana and 35% of Empa. Unadjusted event rates (per 1000 patient years) were 2.81 for Cana, 2.71 for Dapa, and 2.43 for Empa. In the adjusted model, no differences in amputation rates for Cana (IRR 1.26 CI [0.81, 1.97]) or Dapa (IRR 1.31 CI [0.72, 2.36]) when compared to Empa. Significant predictors were prior amputation (IRR 21.44 CI [11.88-36.69]) and DCSI score of 3 or higher (IRR 8.44 CI [5.55-12.82]). Non-traumatic amputation rates for patients on SGLT2is were low and did not differ among Cana, Dapa or Empa. Limitations include short follow-up and non-randomized study design. Understanding the risk of amputation in patients with diabetes related complications, who may otherwise benefit from SGLT2i use, is needed especially given benefit in cardiovascular outcomes and mortality. More research should investigate if patients’ risk of amputation can be predicted prior to initiation.

Disclosure

S. Hakimian: None. A. Wallia: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., UnitedHealth Group. R. Kang: Research Support; Self; UnitedHealth Group. A.J. Cooper: None. M. O’Brien: Research Support; Self; UnitedHealth Group. D.T. Liss: None. S.A. Harris: None. M. Cherupally: None. E.D. Parker: None. R.T. Ackermann: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, UnitedHealth Group.

Funding

UnitedHealth Group (SP0036847)
112-LB: ADO09, a Coformulation of Pramlintide (PRAM) and Insulin A21G, Improves Postprandial Glucose vs. Novolog in Type 1 Diabetes (T1D)
Authors: MEIFFREN GRÉGORY , ANDERSEN GRIT , ELOY ROSY , SEROUSSI CYRIL , MÉGRET CLAIRE , FAMULLA SUSANNE , CHAN YOU-PING , GAUDIER MARTIN , SOULA OLIVIER , DEVRIES J. HANS , HEISE TIM
Published: June 2020

ADO09 is a co-formulation of PRAM and insulin A21G developed to leverage the beneficial effects of PRAM on post-prandial glucose without additional injections. This double-blind randomized cross-over trial studied pre-meal ADO09 vs. Novolog® over 24 days with degludec as basal insulin. Mixed meal tolerance test data (MMTTs) and CGM metrics of 21 T1D subjects were analyzed. Incremental plasma glucose MMTT-AUCs with ADO09 on day 24 were reduced by >100% after 1h and 2h (both p<0.001) and by 39% after 4h (not significant) vs. Novolog. Similarly, ∆PGmax was reduced by 19 mg/dL (p=0.01) and ∆PG_1h by 70 mg/dL (p<0.001)(Fig. 1). ADO09 showed improved CGM-metrics with higher 24h-time in range (TIR 70-180 mg/dL, + 51 min, p=0.01), time in tight range (80-140mg/dL, +70 min, p=0.002). Time <70 mg/dL was slightly higher (+9.6 min, p=0.046) as were hypoglycemic events (142 vs. 115) in the outpatient period. ADO09 significantly reduced body weight (-0.7kg vs. baseline, p=0.01). On the last outpatient day, mean daily bolus doses were 4 U lower with ADO09 (-21%, p=0.05). Both treatments were well tolerated with more gastrointestinal adverse events (24 vs. 6) observed with ADO09, consistent with typical effect of PRAM.

In conclusion, ADO09 significantly improved CGM metrics including TIR, weight control and bolus insulin needs vs. Novolog over 24 days of use.

Disclosure

G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. G. Andersen: Employee; Self; Profil Institute for Clinical Research. R. Eloy: Employee; Self; ADOCIA. C. Seroussi: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. C. Mégret: None. S. Famulla: None. Y. Chan: Employee; Self; ADOCIA. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Employee; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. Stock/Shareholder; Spouse/Partner; ADOCIA. Stock/Shareholder; Self; ADOCIA. J. DeVries: Advisory Panel; Self; Novo Nordisk A/S, Zealand Pharma A/S. Consultant; Self; Metronom Health. Employee; Self; Profil Institute for Clinical Research. T. Heise: Advisory Panel; Self; Mylan, Novo Nordisk A/S. Research Support; Self; ADOCIA, Aerami, Becton, Dickinson and Company, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Merck KGaA, Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S.
1122-P: Sodium–Glucose Transporter 2 Inhibitor Delays Progression of Diabetic Kidney Disease in Japanese Patients with Type 2 Diabetes: Retrospective Slope Analysis of Renal Function
Authors: KASHIMA KOJI , SHIMIZU HIROYUKI , YAMADA MASANOBU
Published: June 2020

Objective: Prevention of end stage kidney disease is one of the priorities in diabetes management. But very few data are available in using sodium glucose transporter 2 inhibitor (SGLT2i) at advanced chronic kidney disease (CKD). We assessed annual eGFR decline rate (slope) in patients with type 2 diabetes with diabetic kidney disease (DKD) treated by SGLT2i.

Methods: A total of 75 patients with DKD, treated by SGLT2i (on empagliflozin 64% and others), were analyzed. Average age was 70.7±12.2 year-old and duration of diabetes was 15.0±9.3 years. Initial eGFR slopes were calculated from 46±21 months period, and slopes after adding SGLT2i were calculated from 21±8 months. Efficacy was compared by each CKD stage: stage 3A; eGFR 45-59 (n=29), stage 3B; eGFR 30-44 (n=28) and stage 4; eGFR<30ml/min/1.73m2 (n=18) at the time of recruitment (middle in 2019).

Results: 1) Average of initial (first month) eGFR changes (drops) are as follows; stage 3A; 57.8±10.5 to 54.9±10.3 ml/min/1.73m2 (P<0.05), stage 3B; 43.2±7.1 to 40.9±6.5 ml/min/1.73m2 (P<0.01), stage 4; 30.6±10.2 to 28.7±9.4ml/min/1.73m2 (P<0.01). The start of SGLT2i treatment decreased eGFR 1.9-2.9ml/min/1.73m2 on initial month. However, annual mean eGFR slopes were improved in all stages; stage 3A: -4.2±3.7 to -1.8±4.4ml/min/1.73m2/year (P<0.02), stage 3B; -4.8±3.7 to -1.7±2.7ml/min/1.73m2/year (P<0.001), stage 4; -12.3±16.3 to -1.9±4.6ml/min/1.73m2/year (P=0.01). 2) The proportion of showing reduction of eGFR slopes after the start of SGLT2i (responder) are similar in all stages: stage 3A; 66% (19/29), stage 3B; 75% (21/28), stage 4; 78%; (14/18). Changes of mean eGFR slopes in those responders were as follows, -8.1±10.3 to -0.6±3.3ml/min/1.73m2/year (P<0.0001).

Conclusion: SGLT2i treatment could have a favorable benefit on renal function even in advanced stage of DKD. Slope analysis might be useful for safety and individualized therapy.

Disclosure

K. Kashima: None. H. Shimizu: None. M. Yamada: None.
113-OR: Circular RNAs: Promising Biomarkers for Type 1 Diabetes
Authors: YIN CONGCONG , MI QING-SHENG
Published: June 2020

Aims/Hypothesis: Circular RNAs (circRNAs), a class of endogenous RNAs, have emerged as an enigmatic class of RNAs. Little is known about their value in diagnosis of type 1 diabetes. We aimed to explore circRNA profiles for risk T1D in both mouse and human serum, and studied the interplay between microRNA and circular RNAs in human serum.

Methods: We examined circRNA expression profiles during T1D development in nine NOD mice using Arraystar circRNA microarray. Human serum samples from 107 new onset T1D patients and 40 healthy control (HC) were used to profile miRNA expression. Furthermore, 50 T1D and 50 HC were randomly selected from this cohort for circRNA profiling using circRNA microarray.

Results: 134 circRNAs in NOD mice were significantly different in T1D mice compared to normal control or insulitis (FDR<0.10029. In human serum, we identified 50 circRNAs differentially expressed between T1D and HC. By comparing circRNAs in NOD mouse model that might be homologous to human circRNA, two of the circRNAs showed suggestive evidence for differential expression between normal control, insulitis and T1D (FDR<0.2). Furthermore, 87 human serum miRNAs were significantly regulated in T1D compared to HC, 23 among those were highly negatively associated with the 50 differentially expressed circRNAs.

Conclusions: We have identified a serum circRNA and miRNA pattern of T1D, and they may be a potential novel and stable biomarker for the diagnosis of T1D.

Disclosure

C. Yin: None. Q. Mi: None.

Funding

National Institute of Allergy and Infectious Diseases (R01AI119041, R01AI108612)
114-LB: An Exploratory Study to Evaluate the Glycemic Variability by Continuous Glucose Monitoring (CGM) with Insulin Glargine 300 U/mL vs. Glargine 100 U/mL in Patients with Type 2 Diabetes
Authors: FRANCO DENISE R. , VISCONTI GUILHERME D. , FEDER CECILIA , BAPTISTA JULIANA , VIANNA ANDRE G. , GUIMARÃES MARIANA T. , SOUZA FLÁVIA V. , TAGATA LUCIANA A. , ELIASCHEWITZ FREDDY
Published: June 2020

Decreasing glycemic variability (GV) is become a criterion of glycemic control and important goal in the treatment of diabetes. Despite this importance there are only a few reports on GV using continuous glucose monitoring (CGM) patients with T2D on basal insulin.

The aim of this exploratory study was to compare the GV after 12 weeks of treatment on Glargine-100U (Glar-100) or Glargine-300U (Glar-300) in T2D patients.

Methods: This is 12-week, randomized with parallel arms. Ninety-four T2D subjects >18 y old with HbA1c between 7.5% -11% (9.2±0.9%) on NPH insulin ÷ OAD, were randomized to Glar-100 or Glar-300. A blinded CGM was inserted in a baseline (run-in) and after 12-week patient- driven titration period. The CGM parameter included TIR (70-180mg/dl), MAGE, CV, time in hypoglycemia and in hyperglycemia ranges were uploaded by carelink software and the GV parameters were analyzed by Glyculator software.

Results: No differences between groups was found in any analysed GV parameter. The final HbA1c were similar to Glar-100 and Glar-300(8.0±1.12 and 8.15±1.04), however there were a significant difference regarding on total hypoglycemic events verified by self-monitoring blood glucose (SMBG) Glar-100 and Glar-300 groups (0.44±0.43 vs. 0.25± 0.42 episodes/patient/year respectively, p= 0.007). In exploratory analysis in the quartile that reached the HbA1c <7.4% TIR for Glar-300 group was 75.43% and 65.62% for Glar-100 (NS).

Conclusion: In this exploratory study, even when we could not detect differences between GV parameters (probably due to not reaching target glycemic control), the lower risk of hypoglycemia with Glar-300 compared to Glar-100 can still be clearly shown. A tendency for longer TIR stay in the Glar-300 group vs. in the Glar-100 group was seen in the subgroup of those who reached close-to-target A1c values.

Disclosure

D.R. Franco: Advisory Panel; Self; Abbott, Medtronic, Novo Nordisk A/S, Sanofi. Research Support; Self; Sanofi. Speaker’s Bureau; Self; Abbott, AstraZeneca, Medtronic. G.D. Visconti: None. C. Feder: None. J. Baptista: None. A.G. Vianna: Board Member; Self; Abbott, Medtronic, Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker’s Bureau; Self; Lilly Diabetes. M.T. Guimarães: None. F.V. Souza: None. L.A. Tagata: None. F. Eliaschewitz: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Bayer AG, GlaxoSmithKline plc., Novo Nordisk A/S, Sanofi-Aventis. Speaker’s Bureau; Self; Eli Lilly and Company.

Funding

Sanofi
1147-P: Canagliflozin Decreases Ischemic Limb Perfusion and Angiogenesis in Diabetic Mice
Authors: NALUGO MARGARET , HARROUN NIKOLAI , BELAYGOROD LARISA , JIN XIAOHUA , SEMENKOVICH CLAY F. , ZAYED MOHAMED A.
Published: June 2020

Objectives: Amputation rates appear to be increased in people with diabetes taking canagliflozin, an SGLT2 inhibitor. The mechanism underlying this observation is unknown. To better understand the negative consequences of canagliflozin on limb salvage, we evaluated the effects of canagliflozin on ischemic hindlimb perfusion and angiogenesis in db/db mice (a murine model for type 2 diabetes).

Methods: Adult wild type (+/+) and db/db mice were maintained on 8 weeks of regular chow diet or chow diet containing canagliflozin (200mg/kg chow). All mice underwent unilateral hindlimb ischemia via femoral artery ligation.

The appearance, use, and Doppler perfusion of hindlimbs were evaluated post-ischemia. Hindlimb gastrocnemius muscle fiber size and microvessel density were evaluated 21 days post-ischemia. One-way ANOVA was used to evaluate differences in the study endpoints between mouse genotypes and diets.

Results: db/db mice ischemic hindlimbs demonstrated significantly worse appearance and use than +/+ mice on regular and canagliflozin diets (p<.05). db/db mice on canagliflozin diet had even worse appearance and use compared to db/db mice on a regular diet (p<.05), and +/+ mice on canagliflozin diet (p<.01). At day 21 following hindlimb ischemia, db/db mice on canagliflozin diet demonstrated decreased Doppler perfusion and gastrocnemius muscle fiber size compared to db/db mice on a regular diet as well as +/+ mice on canagliflozin diet (p=.04, p=.02 and p=.04, respectively). db/db mice had significantly decreased microvessel density compared to +/+ mice on canagliflozin diet (p<.001).

Conclusions: Canagliflozin significantly decreases perfusion and muscle angiogenesis in ischemic hind-limbs, and these deleterious effects are higher in the setting of diabetes. These findings may have direct clinical relevance, and suggest that this model will be useful for identifying additional mechanisms underlying the effects of canagliflozin in peripheral arterial disease.

Disclosure

M. Nalugo: None. N. Harroun: None. L. Belaygorod: None. X. Jin: None. C.F. Semenkovich: None. M.A. Zayed: None.

Funding

National Institutes of Health (K08HL132060)
1150-P: Empagliflozin Decreases the Plasma Concentration of Plasminogen Activator Inhibitor-1 (PAI-1) in Patients with Type 2 Diabetes: Association with Improvement of Fibrinolysis
Authors: NIITANI TAKAFUMI , SAKURAI SHINTARO , JOJIMA TERUO , IIJIMA TOSHIE , TOMARU TAKUYA , USUI ISAO , ASO YOSHIMASA
Published: June 2020

Objectives: Elevation of the plasma concentration of plasminogen activator inhibitor-1 (PAI-1), a rapid-acting inhibitor of fibrinolysis, is associated with development of cardiovascular diseases. We investigate the effects of empagliflozin, an SGLT2 inhibitor, on the plasma concentration of PAI-1 and fibrinolytic activity in patients with type 2 diabetes.

Methods: In a randomized, active-controlled, open-label trial, 51 patients with type 2 diabetes were randomly allocated at a 2:1 ratio to receive empagliflozin (10 mg/day, n=31) or standard therapy (n=18) for 12 weeks. We measured the plasma concentrations of PAI-1 and plasmin-α2-antiplasmin complex (PAP) as indicators of fibrinolytic activity. Serum leptin and HMW adiponectin were also measured.

Results: Body weight and visceral fat decreased in the empagliflozin group, but not in the control group. The serum level of γ-GTP showed a significant decrease at 12 weeks in the empagliflozin group, while it was unchanged in the control group. Serum HMW adiponectin increased significantly in the empagliflozin group. Plasma PAI-1 decreased significantly by 25% in the empagliflozin group, but not in the control group. In the empagliflozin group, the change of plasma PAI-1 was positively correlated with the changes of body weight and leptin, but was negatively correlated with the change of PAP.

Conclusions: Empagliflozin reduced the plasma PAI-1 concentration through its synergistic actions of a glucose-lowering effect, weight loss, and restoring the adipokine balance. The beneficial effects of empagliflozin on fibrinolysis by decreasing circulating PAI-1 may be associated with improvement of vascular thrombotic outcomes in patients with type 2 diabetes. (Clinical trial registry: UMIN000025418).

Disclosure

T. Niitani: None. S. Sakurai: None. T. Jojima: None. T. Iijima: None. T. Tomaru: Research Support; Self; Merck & Co., Inc., Teijin Pharma Limited. I. Usui: None. Y. Aso: None.
1151-P: A Cost-Effectiveness Analysis of Charcot Reconstruction, Transtibial Amputation, and Lifetime Bracing for Adults with Midfoot Charcot Arthropathy
Authors: FLEISCHER ADAM E. , ALBRIGHT RACHEL H. , ARMSTRONG DAVID G. , WUKICH DANE
Published: June 2020

Background: The optimal therapeutic approach for people suffering with unstable Charcot arthropathy of the midfoot is unclear. The purpose of this study was to examine the cost-effectiveness of three competing treatment strategies for adults suffering with unstable, midfoot Charcot arthropathy.

Methods: A Markov model was utilized to compare Charcot reconstruction (CR), primary transtibial amputation (TTA) and lifetime bracing in three progressively worsening clinical scenarios: no foot ulcer, uncomplicated ulcer, and infected ulcer. Data regarding costs and probabilities were obtained from available literature. Primary outcomes included long-term costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Willingness-to-pay was set at $100,000 USD.

Results: TTA failed to show cost-effectiveness in comparison to other strategies available. Lifetime bracing was cost-effective in all clinical scenarios, with ICERs ranging from $6,970 to $15,010. CR was also cost-effective in the non-ulcerated and ulcerated scenarios, and offered the greatest potential for maximal QALYs gained, but failed to show value in the infected ulcer scenario. For CR to be cost-effective in the infected ulcer scenario, costs of surgery would need to lessen to $40,000 or complication rates would need to remain under 50%. The results in the non-ulcerated and ulcerated cohorts were robust to multiple sensitivity analyses.

Conclusion: Bracing is a cost-effective option in all stages of Charcot arthropathy while CR appears to be only cost-effective when performed early (i.e., in the non-ulcerated and uncomplicated ulcerated patient). An opportunity for shared-decision making exists in the early stages of Charcot arthropathy, where patient goals and expectations may be assessed while multiple cost-effective options are still available.

Disclosure

A.E. Fleischer: None. R.H. Albright: None. D.G. Armstrong: None. D. Wukich: Consultant; Self; Orthofix, Wright Medical. Other Relationship; Self; Arthrex.
1153-P: National Trend in Out-of-Pocket Burden in Adults Aged 18–64 Years with Diabetes: 2001-2017
Authors: WANG YU , PARK JOOHYUN , LI RUI , LUMAN ELIZABETH , ZHANG PING
Published: June 2020

Recent changes in health coverage benefits and increases in diabetes medication prices may have affected out-of-pocket (OOP) expenditures for people with diabetes. High OOP expenditures is a barrier to get adequate medical care. We assessed national trends in OOP expenditures overall and by OOP-component among adults aged 18-64 years with diabetes from 2001 to 2017 using data from the U.S. Medical Expenditure Panel Survey. OOP expenditures were defined as the amount paid by a family with one or more members with diabetes, including insurance premiums, deductions, copays, coinsurance and payments not covered by insurance. High OOP burden was defined as spending >10% of the family’s pretax income on OOP expenditures. We examined trends overall as well as by insurance type, income (as a ratio of federal poverty level, FPL), type of service, and whether patients used insulin. We tested for changes in trends using joinpoint analysis. OOP expenditures were adjusted to 2017 U.S. dollars. From 2001 to 2017, OOP expenditures decreased 4.3%, from $4328 to $4139, and the percentage of persons with high OOP burden fell 32%, from 28% to 19% (P<0.001). No significant changes in trends were identified for either measure. Both OOP expenditures and percentages with high OOP burden declined for those with public or no insurance and those with family income < 200% of FPL (P<0.001). There were increases in OOP expenditures (P<0.001) but no significant changes in percentages with high OOP burden for those with private insurance and those with income ≥ 400% of FPL. OOP expenditures on prescriptions decreased for all insurance types and income subgroups (P<0.001). Decreases in total (-$58 vs. -$37, P<0.001) and prescription (-$79 vs. -$68, P<0.001) OOP expenditures were larger for insulin users than non-users. These most recent data show that OOP expenditures for U.S. adults with diabetes are steadily declining, especially for those least able to afford them. Future studies are needed to explain these patterns.

Disclosure

Y. Wang: None. J. Park: None. R. Li: None. E. Luman: None. P. Zhang: None.
1159-P: Cost of Achieving A1C Treatment Goals in Patients with Type 2 Diabetes: Results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
Authors: ZHANG PING , SHAO HUI , BERTONI ALAIN , LOVATO LAURA , CHEN HAIYING
Published: June 2020

American Diabetes Association (ADA) guideline on glycemic control recommends an A1c <7% in most adults with diabetes and 7-8% for those with history of hypoglycemia, limited life expectancy, or comorbid conditions. From 2013-2016, 64% of U.S. adults with diabetes met ADA A1c goals. Using data from the ACCORD trial, we estimated the cost of achieving the two A1c goals, defined as reaching the goal for two consecutive follow-up visits. Costs of the diabetes drugs were estimated from Marketscan data. Costs by baseline A1c levels were estimated using a generalized linear model with Gamma distribution and log link. 3698 participants in the control arm achieved the goal of 7-7.9%, and 4135 in the intervention arm achieved the goal of <7%. Estimated monthly cost increased by baseline A1c level and was higher for achieving A1c<7% than 7-7.9% (Figure). In patients with a baseline A1c of 11%, the estimated cost was $610 per month ($7320 per year) for achieving <7% and $413 per month ($4956 per year) for achieving 7-7.9%. In patients with a baseline A1c level of 9%, the corresponding estimates were $430 per month ($5160 per year) and $266 per month ($3192 per year). Our study provides critical cost estimates needed for assessing the cost-effectiveness of tighter glucose control in the U.S.

Disclosure

P. Zhang: None. H. Shao: None. A. Bertoni: None. L. Lovato: None. H. Chen: None.
116-LB: Evaluating the Impact of Glucommander on Improvement in Time-in-Range (TIR) in Type 2 Diabetes Using Continuous Glucose Monitoring
Authors: BODE BRUCE W. , CLARKE JOHN G.
Published: June 2020

A proof of concept single center prospective study aimed at evaluating the safety and efficacy of utilizing Glucommander outpatient insulin dosing software to assist providers in titrating basal bolus insulin doses, using Abbott Freestyle Libre 14-day glucose monitoring system. A total of 25 adults (18-80), having T2D and an A1C > 8%, were enrolled. A nurse educator provided patient education on insulin administration, meal planning and use of the glucose sensor. Baseline CGM data was collected during week 1, after which time participants insulin doses were titrated weekly for the next 4 weeks. Data was collected on initial HbA1C, days of CGM wear, time in range (TIR), and time in hypoglycemia. Use of Glucommander significantly improved TIR from a baseline of 48.02% during the initial week to 73.84% during the final week of treatment (p<0.00001). Time in hypoglycemia (BG < 54 mg/dl) decreased from 0.37% during the initial week to 0.33% during the final week of treatment (p>0.557). % Changes in insulin: %Change(Basal) = 10.5%, %Change(Total Boluses)= 19.7%, %Change(TDD)= 15.1%.

Disclosure

B.W. Bode: Advisory Panel; Self; Medtronic, Novo Nordisk A/S. Consultant; Self; Eli Lilly and Company, Medtronic, Novo Nordisk A/S. Research Support; Self; Abbott, Advance, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, National Institutes of Health, Nova Biomedical, Novo Nordisk A/S, Provention Bio, Inc., Sanofi, Senseonics. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Senseonics. Stock/Shareholder; Self; Aseko. J.G. Clarke: Employee; Self; Glytec. Stock/Shareholder; Self; Glytec.

Funding

Glytec, LLC
1160-P: Impact of Reduced Medication Out-of-Pocket Costs on Acute Diabetes Complications and High-Acuity Outcomes: A Natural Experiment for Translation in Diabetes (NEXT-D2) Study
Authors: WHARAM J. FRANK , LAKOMA MATTHEW , ZHANG FANG , WALLACE JAMIE , GARABEDIAN LAURA F. , SOUMERAI STEPHEN B. , ROSS-DEGNAN DENNIS
Published: June 2020

In an attempt to improve diabetes outcomes, some employers and insurers have adopted Preventive Drug Lists (PDLs) that reduce out-of-pocket costs for antidiabetic and cardioprotective medications to $0. We sought to determine whether shifts to PDL coverage reduce acute diabetes complications and high-acuity outcomes among commercially insured patients with diabetes. Our study design was a natural experiment comparing changes in outcomes 1 year before and after the PDL switch in matched study groups. The Intervention group included 16,174 commercially-insured diabetes patients age 12-64 switched by their employers to PDL coverage; the Control group included 711,085 coarsened exact-matched contemporaneous patients whose employers offered no PDL. We conducted similar analyses in a subset of low-income members switched to PDL plans and their matched controls. Outcomes were acute diabetes complication visits, high-severity emergency department visits, and hospitalization days. Transition to the PDL was associated with a relative pre-post change of 1.6% (95% confidence interval, -7.2% to 10.3%) in acute diabetes complication visits, -3.2% (-14.4% to 8.1%) in high-severity emergency department visits, and 2.2% (-9.8% to 14.1%) in hospitalization days. Findings were similar in the low-income subgroup. We did not find detectable changes in acute diabetes complication visits and high-acuity outcomes among diabetes patients switched to low drug cost sharing health plans. Further research should assess longer-term outcomes and examine effects of reducing financial barriers to outpatient and emergency department care.

Disclosure

J. Wharam: None. M. Lakoma: None. F. Zhang: None. J. Wallace: None. L.F. Garabedian: None. S.B. Soumerai: None. D. Ross-Degnan: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases; Centers for Disease Control and Prevention (5U18DP006122-05)
1161-P: Differences in U.S. Health Care Costs for Patients with Type 2 Diabetes: A Comparison Based upon HbA1c Thresholds
Authors: BOYE KRISTINA , LAGE MAUREEN J. , RAIBULET NEDINA K. , YU MARIA
Published: June 2020

Objective: The ADA defines normoglycemia as HbA1c < 5.7% and glycemic control for most adults with diabetes as HbA1c < 7%. This research examined U.S. healthcare costs for patients with type 2 diabetes (T2D) with index HbA1c < 5.7% (normoglycemia) compared to HbA1c ≥ 7% (above target).

Methods: The IBM® MarketScan® Commercial and Medicare databases (2013-2017) were used to identify adults with T2D, a recorded HbA1c result (first such date = index date), and continuous insurance coverage from 1 year prior through a 1 year post index date (post-period). Patients with normoglycemia were matched to patients with HbA1c above target without replacement. Using the propensity-score matched cohort, multivariable analyses examined the association between index HbA1c and healthcare costs.

Results: In the 1:1 matched cohort (7,567 normoglycemia; 7,567 above target), multivariable analyses showed that patients with normoglycemia had significantly lower post-period all-cause and diabetes-related drug costs, acute care costs, and outpatient costs compared to patients above target. Total diabetes-related costs were 25% lower (Figure 1) and all-cause total costs were 4% lower (both P<0.0001) for patients with normoglycemia compared to those with index HbA1c above target.

Conclusion: Results suggest significant economic benefits associated with normoglycemia compared to HbA1c ≥ 7%.

Disclosure

K. Boye: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Eli Lilly and Company. M.J. Lage: Consultant; Self; Eli Lilly and Company. Consultant; Spouse/Partner; Eli Lilly and Company. N.K. Raibulet: Employee; Self; Eli Lilly and Company. M. Yu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; LifeLabs. Stock/Shareholder; Self; Eli Lilly and Company.
1167-P: CSII and Insulin: Does Extending the Wear Duration of Infusion Sets Save Expensive Insulin?
Authors: CHATTARAJ SARNATH , FIENUP MARISA , ZHANG GINA , TIECK MARIE
Published: June 2020

Objective: Patients using continuous subcutaneous insulin infusion (CSII) as a means of insulin delivery are advised to replace their infusion set every 2-3 days, as the probability of adverse events related to insertion increases after 72 hours, according to labeling and manufacturer’s instructions. When the infusion set is changed the remaining unused insulin in the reservoir and infusion set tubing are usually thrown away. The potential savings associated with extending the duration of infusion set wear from 2-3 days to 7 days was determined from the perspective of insulin pump users.

Method: The discarded insulin volume in the reservoir and infusion set under a current-wear scenario of 2-3 days versus 7 days was modeled. A mix of best-case (use for a 3-day set/reservoir with the shortest length of tubing) and worst-case (normal use for a 3-day set/reservoir with longest tubing) scenarios was used. Insulin cost savings were computed for the 3-day scenario assuming a complete infusion set and reservoir change every 3 days. Under the 7-day scenario, a complete infusion set change occurred every 7 days, while the reservoir was changed midway between complete changes. Under the best-case scenario, reservoirs were discarded by the end of 7 days.

Results: For the insulin pump users, the average annual reduction in discarded insulin volume was calculated to save about 5-10 vials of insulin per year per pump user. The corresponding cost reduction per user due to insulin savings was ∼$1,500 to $3,000 per year per pump user (based on ∼ $300/insulin vial; IBM Micromedex Red Book).

Conclusion: Using infusion sets that last for 7 days can yield substantial savings to patients, private health plans, and other payers (e.g., Centers for Medicare and Medicaid Services). Work is in progress to assess environmental impact cost savings due to reduction in material waste when extending the duration of infusion set wear from 2-3 days to 7 days.

Disclosure

S. Chattaraj: Employee; Self; Medtronic. M. Fienup: Employee; Self; Medtronic. G. Zhang: None. M. Tieck: None.
1168-P: Effectiveness of a Comprehensive Diabetes Program for Patients with Poorly Controlled Diabetes in an Academic Health Care System: The Emory Diabetes Management Program
Authors: GALINDO RODOLFO J. , PENG LIMIN , SMITH ZIRKA T. , JACOBS SOL , KHOSRAVANIPOUR MARJAN K. , TURTON FREDERICK E. , MASI CHRISTOPHER M. , ESPER GREGORY J. , WYLDE BJAY , CASTELLANO PENNY A. , UMPIERREZ GUILLERMO E.
Published: June 2020

The Emory Diabetes Management Program (DMP) is a four-core chronic care management model including 1) specialized ambulatory program led by educators and advanced practitioners, 2) inpatient care protocols, 3) education of healthcare professionals through webinars, live sessions and “train-the-trainer” program, and 4) surveillance and data sharing/monitoring. The DMP goal is to reduce the percentage of patients within the Emory Healthcare System with A1c >9% to <15%. We report our results from 02/01/18 to 01/31/2019. Among 27,061 patients, the overall % of patients with A1c >9% reduced from 20.5% to 17.2%, with improvement observed in all clinic operating units-- primary care (19.4 to 16.2%), family medicine (24.2% to 21.9%) and endocrinology (23.3 to 18.8%). Among 922 patients referred to the specialized ambulatory program (core 1), 644 participated (DMP) and 278 declined participation (No-DMP). DMP participants had greater improvement in A1c from baseline (-1.3%±2.5 vs. -0.5%±2.1, p<0.01), and a reduction in % of patients with A1c >9% by 26% (from 64% to 38%) vs. 12% (from 61% to 49%) compared to No-DMP group, p<0.01. The Emory-DMP, is an effective population management program for improving diabetes care, with significant reduction in the number of patients with poor control diabetes.

Disclosure

R.J. Galindo: Advisory Panel; Self; Lilly Diabetes. Consultant; Self; Valeritas, Inc. Research Support; Self; Novo Nordisk Inc. Other Relationship; Self; UpToDate. L. Peng: None. Z.T. Smith: None. S. Jacobs: None. M.K. Khosravanipour: None. F.E. Turton: None. C.M. Masi: None. G.J. Esper: None. B. Wylde: None. P.A. Castellano: Advisory Panel; Self; American Association of Medical Colleges. Board Member; Self; Vizient Inc. G.E. Umpierrez: None.
117-LB: Nonviral Direct Reprogramming of Human Skin Fibroblasts into Hormone-Expressing ß-Like Cell Clusters
Authors: LEMMERMAN LUKE R. , RINCON-BENAVIDES MARIA ANGELICA , TERSEY SARAH A. , BLACKSTONE BRITANI N. , POWELL HEATHER M. , HIGUITA-CASTRO NATALIA , MIRMIRA RAGHAVENDRA , GALLEGO-PEREZ DANIEL
Published: June 2020

While allogenic islet grafting has shown significant promise for the treatment of T1D, donor tissue scarcity and the need for aggressive immunosuppression has limited widespread use of this therapy. Consequently, recent studies have focused on deriving β-like cells from autologoussources (e.g., exocrine pancreas, iPSCs) via reprogramming and/or lengthy differentiation protocols. However, current approaches to β-cell derivation face several hurdles, including limited and/or functionally impaired cell sources, tedious pre-processing steps, and heavy reliance on viral vectors (i.e., for cell transformations), among others. Here we report on the development ofa non-viral approach to β-cell derivation from human skin fibroblasts via direct reprogramming.Human fibroblasts were isolated from surgical discard tissue. Electroporation was then used to screen a pool of transcription factor genes that included Pdx1, Ngn3, MafA, Pax4, and Tcf3, to identify optimum permutations that can drive β-cell-directed conversions in human skin fibroblast cultures. Transfection extent, efficiencies, and transcriptive activity, were evaluated by qRT-PCR,fluorescence microscopy, and RNA sequencing. Transfected fibroblasts were maintained indifferentiation media for ~3 weeks. β-cell-directed transformations were evaluated in terms of morphology and C-peptide expression. Our results indicate that while transfection with Tcf3 alone did not lead to significant changes in cell morphology and phenotype compared to sham, co-transfection of Tcf3 with Pdx1+Ngn3+MafA (PNM) or Pdx1+Ngn3+MafA+Pax4 (PNMP) led to cell clustering, as well as C-peptide expression as early as day 15 post-transfection, which was absent in fibroblasts transfected only with PNM or PNMP. Altogether, our findings indicate that Tcf3 maybe a key factor in enabling direct conversion of human dermal fibroblasts into hormone-expressingβ-like cells for potential applications in β-cell replacement therapies.

Disclosure

L.R. Lemmerman: None. M. Rincon-Benavides: None. S.A. Tersey: None. B.N. Blackstone: None. H.M. Powell: None. N. Higuita-Castro: None. R. Mirmira: Advisory Panel; Self; Hibercell, Sigilon Therapeutics, Veralox Therapeutics. Employee; Spouse/Partner; Eli Lilly and Company. D. Gallego-Perez: None.
1172-P: Impact of Telemedicine Clinics in the Management of Type 1 Diabetes
Authors: EILAND LESLIE A. , SIAHPUSH MOHAMMAD , AKKIREDDY PADMAJA , KUECHENMEISTER LISA
Published: June 2020

Background: Our institution began telemedicine clinics at rural hospitals in 2013, with standard office visits delivered synchronously via video conferencing. This project aims to assess the impact of telemedicine clinics in T1D care at our institution.

Methods: IRB approval was obtained to access records of people with T1D with three or more telemedicine visits from Nov 2013 to Oct 2019. To assess change in A1c, we used a random coefficient regression model and estimated the effect of time on A1c, controlling for gender and age at start of treatment. Data were collected on change in treatment and prior provider (PCP, outside/academic endocrinologist).

Results: The 139 patients evaluated (average age 45 y (range 16-94), 58% F) had an average of 8 A1c values (2-23) over an average duration of 32 mos (4-69). The scatterplot and fitted regression line show a temporal A1c decline. Similarly, random coefficient regression analysis provided overwhelming evidence for an A1c decline (P< 0.001). Each year in telemedicine care was associated with a decline of 0.13 in A1c (95% CI: -0.20, -0.06). Age and gender were not associated with A1c. A1c decline was noted irrespective of prior provider or treatment change (ie, starting CGM/pump therapy).

Conclusions: Our data supports the concept that T1D can be effectively managed via telemedicine. Declines in A1c were seen in all groups, irrespective of age, prior provider and additions of diabetes technology.

Disclosure

L.A. Eiland: None. M. Siahpush: None. P. Akkireddy: None. L. Kuechenmeister: None.
1173-P: Use of Patient-Centered Medical Homes (PCMH)–Related Care Management Processes to Improve Glycemic Control in Medicaid Patients and Non-Medicaid Patients
Authors: FU HELEN N. , WOLFSON JULIAN , SOLBERG LEIF , GREY MARGARET , PETERSON KEVIN A.
Published: June 2020

Background: Care management processes are meant to improve care quality, but there is little information about their effectiveness in socioeconomically disadvantaged individuals. This study was aimed to test if systematic care management processes are as effective in controlling diabetes among Medicaid as in non-Medicaid patients.

Methods: This cross-sectional study used standardized performance measures (glycemic control, BP control, statin drug use, aspirin use, smoking cessation) matched to a 2017- clinic survey on the use of diabetes-related care management processes (62 items in Physician Practice Connections-Research Survey). A mixed effect multi-level regression model with fixed clinic- and patient-level independent variables and random clinic-level intercepts was used to test the association between clinic use of care management processes (index of 0-100%) and glycemic control of glycated hemoglobin (A1C) level while adjusting for patient covariates (age, sex, comorbid conditions, diabetes type 1 or 2, residence rurality) and clinic covariates (PCMH certification, medical group size, federally qualified health center).

Results: The overall mean index of care-management processes usage was 86% (IQR of 76-97%). Every 10% increase in the use of care management processes was associated with a decrease of 0.57 in A1C (p<.001). Among Medicaid patients, every 10% increase in the use of care-management was associated with a decrease of 0.72 in A1C (p<.001), while for non-Medicaid patients the associated decrease was 0.53 (p<.001). The 0.2 difference between Medicaid and non-Medicaid groups was also statistically significant (p<.001).

Conclusions: Clinic utilization of PCMH care management processes had a larger effect on diabetes control for patients on Medicaid than for other patients. Improving and implementing these processes may be an important strategy for reducing disparities in diabetes outcomes.

Disclosure

H.N. Fu: None. J. Wolfson: None. L. Solberg: None. M. Grey: None. K.A. Peterson: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R18DK110732)
1174-P: Reducing Lost to Follow-Up Rates in the T1D Exchange Quality Improvement Collaborative (T1DX-QI)
Authors: MCDONOUGH RYAN , THOMAS SARAH , RIOLES NICOLE , EBEKOZIEN OSAGIE , CLEMENTS MARK A. , CORATHERS SARAH , LEE JOYCE M. , GARRITY ASHLEY , PRAHALAD PRIYA , KAMBOJ MANMOHAN K. , BUCKINGHAM DON A. , ALONSO GUY T.
Published: June 2020

The ADA recommends quarterly follow-up for routine diabetes care, however, this is not consistently achieved. This gap represents an opportunity to improve care. The T1D Exchange Quality Improvement Collaborative (T1DX-QI) aims to improve T1D care in the U.S. through structured sharing of best practices. To reduce the lost to follow-up (LTFU) rate, five pediatric centers identified key change concepts, designed iterative testing cycles, and used data visualization to inform future interventions. Patients <18 years were considered LTFU if their last visit was 180-365 days ago without a future visit scheduled. The following interventions were developed during monthly workgroup calls: establishing standard work, outreach between visits, offering patient portal self-scheduling, scheduling future visits at registration, scheduling multiple follow-ups, and improving adult care transition. Analysis included 14,790 patients across the five sites. Successful application of QI methodologies resulted in improvement across all ages. With a reduction to < 4%, 156 youth were proactively reengaged with diabetes care. Continued follow-up of this population will focus on identifying and overcoming barriers to LTFU and assess which interventions had the biggest impact. We are developing a “Change Package” with successful interventions to share with other diabetes centers.

Disclosure

R. McDonough: None. S. Thomas: None. N. Rioles: None. O. Ebekozien: None. M.A. Clements: Consultant; Self; Glooko, Inc. Other Relationship; Self; Glooko, Inc. S. Corathers: None. J.M. Lee: Advisory Panel; Self; Goodrx. Consultant; Self; T1D Exchange. Research Support; Self; Lenovo. A. Garrity: None. P. Prahalad: None. M.K. Kamboj: Research Support; Self; Type 1 Diabetes TrialNet, Unitio, Inc. D.A. Buckingham: None. G.T. Alonso: None.