Allergan Plc Research Articles

Acellular Dermal Matrix, Smooth Tissue Expanders, and Betadine: Histologic Assessment in a Primate Model

INTRODUCTION: It is known that an overabundance of pathogens in the setting of prosthetic breast devices can lead to infection, prolonged inflammation, and capsular contracture. As such, there has been increasing emphasis on the use of aseptic techniques that include antimicrobial irrigation solutions such as Betadine. The increasing use of human acellular dermal matrices (HADM) and prosthetic devices have raised questions as to whether exposure of the implant or tissue expander (TE) to Betadine may lead to deleterious effects related to HADM incorporation. The aim of this study was to determine if exposure of HADM to a Betadine-saturated TE would affect the corresponding biological response. METHODS: Samples (1.5 × 1.5 cm) cut from custom-made smooth silicone TEs (Allergan plc) were soaked in 100% Betadine for 2 minutes, without a subsequent saline rinse, or soaked in control saline alone, and then sutured to equivalently sized HADM samples (AlloDerm, Allergan plc) to form an HADM:TE construct. Eighteen African Green monkeys were each implanted subcutaneously with a pair of Betadine and saline-treated HADM:TE constructs and evaluated for overall biologic response to Betadine treatment following implantation at 2 or 4 weeks as demonstrated by hematoxylin and eosin histologic staining and using a subjective scoring scale (0–9) inclusive of recellularization, neovascularization, and inflammatory responses. The presence of individual cell types involved in inflammation (eosinophils, lymphocytes, neutrophils, histiocytes, foreign body giant cells) and HADM remodeling (fibroblasts) was also evaluated based on hematoxylin and eosin histologic staining (0–3 scoring scale) and in some cases corroborated by immunohistochemical staining (CD-3, CD-20, CD-68). Betadine-treated constructs were compared at 2-week (n = 9) and 4-week (n = 9) implantation to saline control-treated constructs with no exposure to Betadine also at 2-week (n = 9) and 4-week (n = 9) implantation. RESULTS: Overall biologic response to the HADM in the presence of Betadine or saline control was similar at 2-week implantation, scoring 5.6 ± 0.5 and 5.3 ± 0.9, respectively (P = 0.41) and remained similar at 4 weeks, scoring 4.6 ± 1.0 and 4.2 ± 0.8, respectively (P = 0.46). Although the presence of individual inflammatory cell types appeared to trend higher in the saline control group than in the Betadine-treated group at 2 weeks, the difference was not statistically significant, and the trend did not persist at 4 weeks. Likewise, differences in HADM fibroblast infiltration were not significant between Betadine-treated and control groups. However, the presence of fibroblasts within the implanted HADM did increase over time between 2 and 4 weeks, for both the Betadine-treated (increase from 1.0 ± 0.9 to 1.8 ± 1.0) and saline control groups (increase from 1.4 ± 0.9 to 1.8 ± 0.8), indicative of ongoing HADM incorporation. CONCLUSIONS: The data suggest that exposure of the HADM to a Betadine-treated TE did not negatively impact the host response to the implanted HADM in terms of inflammation, vascularization, recellularization, or overall HADM incorporation.

1848-P: Insulin Sensitivity and Metabolic Profile of Subjects with Type 2 Diabetes and Nonalcoholic Steatohepatitis after Exposure to Cenicriviroc: A Subanalysis of the CENTAUR Study

Introduction: In mice, C-C motif chemokine receptor (CCR)5 deletion protects against insulin resistance, hepatic steatosis, and glucose intolerance. We aimed to characterize the metabolic effects of cenicriviroc (CVC), a potent CCR2/5 inhibitor, in type 2 diabetes mellitus (T2DM) patients with nonalcoholic steatohepatitis (NASH) fibrosis from the Phase 2b CENTAUR study. Methods: Subjects from CENTAUR with T2DM, biopsy-proven NASH, and fibrosis Stages F1-3 were included. CVC-exposed subjects for 1 year (Arm A) and placebo (PBO) [Arms B and C] were analyzed. Liver, metabolic, and inflammatory biomarkers were analyzed. Homeostatic model assessments (HOMA-IR and -b) were calculated. Change (from baseline to Year 1) was compared between groups using a general parametric linear model analysis of covariance (2-sided ANCOVA) based on the mITT population. Results: Of the 289 subjects in CENTAUR, 134 (46%) had T2DM and were included in this analysis. Baseline characteristics were similar for CVC (n=76) and PBO (n=58) groups (mean ±SD): age 57.5 ±7.75 years vs. 55.41 ±8.65 years, HbA1c 7.30 ±1.29 vs. 7.20 ±1.21 %, BMI 33.02 ±5.25 vs. 35.16 ±7.67 kg/m2, NAS 5.25 ±1.06 vs. 5.52 ±1.13, and fibrosis scores of F1 (31.6%), F2 (21%), and F3 (47.4%) vs. F1 (24.2%), F2 (22.4%), and F3 (53.4%), respectively. At 1 year, there was a significant decrease in HOMA-IR and interleukin (IL)-6 in the CVC group. The least squares mean changes (SE) in HOMA-IR (p=0.0159) and IL-6 (p=0.0094), respectively, were −2.75 (1.27) and −1.9 (0.35) for CVC and 1.94 (1.45) and −0.5 (0.39) for PBO. After 1-year exposure to CVC or PBO, no significant differences vs. baseline in HOMA-b, HDL cholesterol, LDL cholesterol, ALT, and AST were noted. Conclusion: CVC may improve HOMA-IR and pro-inflammatory cytokine IL-6, suggesting that CVC could potentially improve insulin resistance in NASH patients. These findings warrant further investigation. Disclosure A.D. Coviello: Consultant; Self; GI Dynamics Inc., Novo Nordisk Inc. Research Support; Self; Allergan plc., GENFIT, Orthus Health. Speaker’s Bureau; Self; Novo Nordisk Inc. G. Rodriguez: Employee; Self; Allergan plc. E.B. Martins: Employee; Self; Allergan plc. Stock/Shareholder; Self; Allergan plc. N. Alkhouri: Research Support; Self; Allergan plc. M.F. Abdelmalek: None. Funding Allergan plc

1105-P: The Effect of Canagliflozin on Alanine Aminotransferase (ALT) Levels: Data from the Association of British Clinical Diabetologists (ABCD) Nationwide Audit Programme

Background: Nonalcoholic fatty liver disease (NAFLD) is common amongst those with type 2 diabetes (T2DM). Alanine aminotransferase (ALT) is known to correlate with levels of liver inflammation and fibrosis. Recent data from our audit programme showed promising reductions in ALT with dapagliflozin. Our aim was to test the same hypothesis, that canagliflozin may improve ALT levels in patients with T2DM, therefore possibly providing benefit in NAFLD. Methods: Data were extracted from the ABCD nationwide audit programme and then stratified into 4 groups based on gender and elevated or normal baseline ALT levels using gender specific references ranges (Prati et al). Baseline and follow-up ALT measurements in the 12-month (6-18months) period were required as a minimum. Data were analysed using Stata 16. Results: 730 datasets were included with mean (±SD) age 61.3yrs (±10.8), 60.1% male, 76% Caucasian (where known), BMI 32.5kg/m2 (±6.5), baseline HbA1c 8.9% (±1.6%) and weight 97.6kg (±22.2) and were broadly similar across all 4 sub-groups. For the entire population, median ALT decreased by 3U/L (95% CI -2, -3; P<0.01). Both male and female subgroups with normal ALT at baseline showed no significant change in ALT. In those with raised ALT at baseline (female ≥19U/L; male ≥30U/L) a change in ALT of -8U/L (95% CI -6, -9U/L; P<0.001) in men and -4U/L in women (95% CI -2, -5; P<0.05). Kruskal-Wallis test confirmed the difference between all groups was significant to P<0.01. No statistically significant correlation was noted between change in weight and change in ALT, which may suggest a weight-loss independent mechanism. Conclusion: Our data show that ALT decreases with canagliflozin, similar to that demonstrated with dapagliflozin. This decrease is greatest in those with elevated baseline levels. Weight-loss is not a predictor of change in ALT suggesting a potential weight-loss independent mechanism. Disclosure T.S.J. Crabtree: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. D.K. Sennik: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. A. Bickerton: None. K.H. Darzy: None. P. Winocour: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Sanofi. M.L. Cull: None. A. Strzelecka: None. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. I.W. Gallen: None. M. Yadagiri: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S.

76-LB: Differences in Time-In-Range, Glycemic Variability, and the Glucose Management Indicator in Pregnant Women with Type 1 (T1D), Type 2 (T2D), and Gestational Diabetes (GDM)

Glycemic control varies among different cohorts of pregnant women with diabetes. Most studies examining differences between groups using continuous glucose monitoring (CGM) data were performed with older CGM systems worn for 2-7 days. We examined differences in glycemic control and glycemic variability (GV) between pregnant women (n=32) with T1D (n=20), T2D (n=3), or GDM (n=9) in the 2nd and 3rd trimesters using the Dexcom G6 CGM system, worn for 10 days as part of a pregnancy CGM accuracy trial. Pair-wise comparisons were made between groups and group heterogeneity testing was performed. No adjustments were made for multiple comparisons analyses. Most women required insulin therapy (26/32, 81%). The baseline HbA1C levels were similar between groups (Table). The glucose management indicator (GMI) was numerically similar to HbA1C for the T1D and GDM cohorts. Time spent >140 mg/dL (p=0.009) was highest and time in range (63-140 mg/dL) was lowest (p=0.001) in women with T1D compared to the other groups. The coefficient of variation (CV) and mean amplitude of glycemic excursions (MAGE) were highest in the T1D group, lowest in the GDM group, and intermediate in the T2D group (p<0.0001 for each). Glycemic control was better and GV was lower for pregnant women with T2D and GDM compared to women with T1D. CGM use in pregnancy helps elucidate GV. Disclosure S. Polsky: None. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. X. Zhang: Employee; Self; Dexcom, Inc. S. Shah: Employee; Self; Dexcom, Inc. G. Haroush: None. K. Nelson: None. G. O’Malley: Research Support; Self; Abbott, Dexcom, Inc. S.J. Ogyaadu: None. S.J. Brackett: None. C. Levister: None. K.N. Castorino: Research Support; Self; Abbott, Dexcom, Inc., Medtronic, Mylan, Novo Nordisk Inc. Funding Dexcom, Inc.

17-LB: A Multicenter Study of the Burden of Hypoglycemia across Trimesters in Pregnancies Complicated by Type 1 Diabetes (LOIS-P Study)

Pregnancies in type 1 diabetes (T1D) are high-risk, and data in the U.S. are limited regarding clinical and CGM based hypoglycemia throughout pregnancy while on sensor augmented insulin pump (SAP). Pregnant women with T1D on insulin pump ≤ 16 wks gestation were enrolled at 3 U.S. centers and used study Dexcom G6. We analyzed episodes of severe hypoglycemia (SH) and days with > 20 hrs of CGM for biochemical hypoglycemia (BH) based on international consensus guidelines (<63 and <54 mg/dl) and frequency/duration of prolonged hypoglycemia (PH, ≥120 mins < 54 mg/dl) Twenty pregnant subjects, age 31 ± 4.5 yrs, 14 ± 8 yrs of T1D, baseline weight 77 ± 16 kg, BMI 28 ± 6.2 kg/m2, HbA1c 6.5 ± 0.7%, were studied. Gestational age at enrollment and delivery was 11.4 ± 4 and 37.7 ± 1.5 wks respectively. One subject experienced a single episode of SH with an overall incidence 7/100 patient years. Percentage of hypoglycemia and BH events per trimester are described in Table 1. BH was common in each trimester, but most frequent in the first. Eighteen events of PH occurred in four subjects (20%) lasting 120-410 mins with two events each in two, three events in one and 11 events in one subject respectively with 15 (83%) events occurring between 12am-6am. Our study shows pregnant women with T1D on SAP frequently experience level 1 hypoglycemia, and 20% experience prolonged hypoglycemia predominantly overnight. Disclosure R. Kaur: None. B.H. Smith: None. J.E. Pinsker: Advisory Panel; Self; Medtronic. Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. B. Ozaslan: None. G. O’Malley: Research Support; Self; Abbott, Dexcom, Inc. M. Trinidad: None. D. Desjardins: None. K.N. Castorino: Research Support; Self; Abbott, Dexcom, Inc., Medtronic, Mylan, Novo Nordisk Inc. C. Levister: None. C. Reid: None. S.K. McCrady-Spitzer: None. S.J. Ogyaadu: None. M. Church: None. M. Piper: None. W.K. Kremers: Research Support; Self; AstraZeneca. B. Rosenn: None. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. Y.C. Kudva: Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Other Relationship; Self; Abbott. Funding National Institutes of Health (122358); Dexcom, Inc. (AP-2018-016)

101-LB: Eighteen-Month Use of Closed-Loop Control (CLC): A Randomized, Controlled Trial

While the use of CLC systems is increasing, data on durable use for >1 year are limited. We present 18-month data on a recently approved CLC system (Control-IQ, Tandem Diabetes Care) in a randomized controlled trial with follow-up extension phase. The study had 164 participants with T1D (14-71 years old) who for this analysis were divided in 3 groups: Group 1: CLC for 6 months, then continued CLC to study end; Group 2: CLC for 6 months, then PLGS (Basal-IQ) for 3 months, then CLC to study end; and Group 3: SAP for 6 months, then CLC to study end. Data were evaluated in 3-month intervals for the primary outcome of time in range (TIR, 70-180mg/dL) and secondary outcomes of hypoglycemia, hyperglycemia and HbA1c. Participants in Group 1 maintained significant improvements in TIR over 18 months with overall mean of 69.9% and sustained reductions in HbA1c. TIR improvement was seen within one month of initiation of CLC and retained its durability over 18 months of use. Group 2 had deterioration in time in range and HbA1c when placed on PLGS for 3 months and restored TIR and HbA1c once resuming CLC. Group 3 had persistent improvements in TIR and HbA1c after transitioning from SAP to CLC. There were 4 severe hypoglycemic events (all after month 9) and 4 DKA events. CLC use was generally 90% or higher with no trend toward decreased use over time. Sustained use of CLC over 18 months demonstrated rapid and consistent improvements in TIR, HbA1c, and hypoglycemia. Disclosure S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. D. Raghinaru: None. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. Y.C. Kudva: Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Other Relationship; Self; Abbott. L.M. Laffel: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Insulogic LLC, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. J.E. Pinsker: Advisory Panel; Self; Medtronic. Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. R. Wadwa: Advisory Panel; Self; Eli Lilly and Company, Medtronic. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, MannKind Corporation, Medtronic, Novo Nordisk Inc., Tandem Diabetes Care. J. Lum: None. C. Kollman: Other Relationship; Self; Dexcom, Inc., Tandem Diabetes Care. R. Beck: None. B. Kovatchev: Advisory Panel; Self; Dexcom, Inc. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc., Sanofi, Tandem Diabetes Care. Other Relationship; Self; Dexcom, Inc., Johnson & Johnson, Sanofi. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UC4108483); University of Virginia Strategic Investment Fund (Project 88); Tandem Diabetes Care

2224-PUB: The Effect of Diabetes Duration on Response to Empagliflozin: Data from the Association of British Clinical Diabetologists (ABCD) Audit Programme

Background: Data previously presented from our audit programme showed that sodium-glucose co-transporter 2 inhibitors (SGLT2s) remain equally effective at reducing HbA1c irrespective of duration of diabetes. This analysis was performed to establish if the same held true for empagliflozin. Methods: Data extracted from the ABCD nationwide empagliflozin audit was stratified into groups based on duration of diabetes: group 1 (<5yrs; n=2320), group 2 (≥5yrs, <10yrs; n=1516), group 3 (≥10yrs; n=2224). Data was analysed using paired t-tests and ANOVA in Stata 16. Results: 6060 datasets were included with mean (±SD) age 59.5yrs (±10.4), 61.1% male, 86% Caucasian (where known), BMI 33.2kg/m2 (±7.2), baseline HbA1c 9.2% (±1.6%) and weight 98.1kg (±21.0). These were broadly similar across all 3 sub-groups apart from age, which understandably increased with duration of diabetes (group 1 57.7yrs±10.8 v group 3 62.0yrs±9.7). Decreases in HbA1c (%) from baseline were observed in all groups, greatest in group 1 (-1.27%; 95% CI -1.19%, -1.35%) and least pronounced in group 3 (-0.9%; 95% CI -0.83%, -0.97%). ANOVA showed significant differences amongst the groups for HbA1c change (P<0.001) but not for weight, BMI or blood pressure. Further analysis has demonstrated no significant difference between HbA1c reductions in group 1 and 2 (P=0.79) but very significant differences (P<0.001) between both groups 1 and 2 and group 3, suggesting the change in response occurs at around the 10 year mark. Conclusions: This analysis demonstrates statistically significant differences in the magnitude of HbA1c change (due to empagliflozin use) in those with shorter v longer durations of diabetes, appearing to occur after 10 years. Although the pattern is generally comparable to other SGLT2s the statistical significance is likely to have been increased from previous data due to a larger sample. The clinical significance of such minor differences in effect is not clear. Disclosure T.S.J. Crabtree: None. K. Adamson: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. A.M. Robinson: None. M. Atkin: Speaker’s Bureau; Self; AstraZeneca, Napp Pharmaceuticals. D.S. Morris: None. D.M. Williams: None. J.W. Stephens: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Napp Pharmaceuticals, Novo Nordisk A/S. D.K. Sennik: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. M.L. Cull: None. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S.

345-OR: First Home Evaluation of the Omnipod Horizon Automated Glucose Control System at Specific Glucose Targets in Children with Type 1 Diabetes

The Omnipod Horizon™ System is a hybrid closed-loop system (HCL) consisting of a tubeless insulin pump and Dexcom G6 sensor which provides automated insulin delivery with customizable glucose targets from 110-150mg/dL, adjustable by time of day to allow therapy personalization. This outpatient study assessed the safety and effectiveness of HCL use at higher targets of 130-150mg/dL. Participants aged 6-13.9y with T1D>6mo and A1C<10.0% used the HCL system at home for 14 days (first 2 days hotel, n=8) over winter holidays with unrestricted eating and exercise. The target was 130, 140, and 150mg/dL for 3 days each, followed by 5 days of free choice of 110-150mg/dL. Primary outcomes were safety measures and percent time 70-180mg/dL over the first 9 days of HCL use, stratified by target glucose. Participants thus far (n=15) had a mean±SD age of 11±2y, T1D duration 5±3y, and A1C 7.7±0.9%. At the 130, 140, and 150mg/dL targets, percent time from 70-180mg/dL was 63.4±7.9%, 64.2±11.6%, and 52.1±11.7%, respectively (Table). Percent time <54 and <70mg/dL was low, and tended to decrease with increased target. There were no severe adverse events. The HCL system was safe and performed well in children with T1D when used at home with higher glucose targets. Participants were invited to continue in a 3mo outpatient study of the system, which is currently underway. Disclosure G.P. Forlenza: Advisory Panel; Self; Medtronic. Consultant; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A.B. Criego: Other Relationship; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Omnipod. S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B.W. Bode: Advisory Panel; Self; InPen, Medtronic. Consultant; Self; ADOCIA, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Pfizer Inc. Research Support; Self; Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Medtronic, Novo Nordisk A/S, Provention Bio, Inc., Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., InPen, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Glytec. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation. Funding Insulet Corporation

100-LB: Closed-Loop Control Reduces Hypoglycemia without Increased Hyperglycemia in Subjects with Increased Prestudy Hypoglycemia: Results from the iDCL DCLP3 Randomized Trial

Closed Loop Control (CLC) has the ability to reduce both hypoglycemia and hyperglycemia. We conducted a post-hoc analysis of data from the iDCL DCLP3 randomized trial comparing CLC with Control-IQ versus sensor augmented pump therapy (SAP) for 6 months in participants who had baseline CGM below 70mg/dL ≥4.0% of the time (N= 41 CLC, 14 SAP, mean±SD age of 33±16yrs, 49% female). CLC use led to a greater reduction in time below 70mg/dL (least square mean change from baseline of -4.6% in CLC vs. -3.1% in SAP, mean-adjusted treatment difference -1.5% or 22 min/d, 95% CI -2.2% to -0.9%, P<0.0001), increased time in range 70-180 mg/dL (mean-adjusted difference +10.4% or 2.5 hr/d, P<0.0001), decreased time above 180mg/dL (mean-adjusted difference -8.5% or 2.0 hr/d, P=0.0001), decreased mean glucose (mean-adjusted difference -10.4 mg/dL, P=0.005), and lower HbA1C (mean-adjusted difference -0.28%, P=0.06). CLC improves HbA1C and reduces both hypoglycemia and hyperglycemia in people with T1D with elevated levels of hypoglycemia prior to starting CLC. Disclosure C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. G. O’Malley: Research Support; Self; Abbott, Dexcom, Inc. S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. G.P. Forlenza: Advisory Panel; Self; Medtronic. Consultant; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. Y.C. Kudva: Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Other Relationship; Self; Abbott. R. Beck: None. C. Kollman: Other Relationship; Self; Dexcom, Inc., Tandem Diabetes Care. J. Lum: None. D. Raghinaru: None. B. Kovatchev: Advisory Panel; Self; Dexcom, Inc. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc., Sanofi, Tandem Diabetes Care. Other Relationship; Self; Dexcom, Inc., Johnson & Johnson, Sanofi. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UC4108483); University of Virginia Strategic Investment Fund (Project 88); Tandem Diabetes Care

983-P: First Home Evaluation of the Omnipod Horizon Automated Glucose Control System at Specific Glucose Targets in Adults with Type 1 Diabetes

The Omnipod Horizon™ System is a hybrid closed-loop system (HCL) consisting of a tubeless insulin pump and Dexcom G6 sensor which provides automated insulin delivery with customizable glucose targets from 110-150mg/dL, adjustable by time of day to allow therapy personalization. This outpatient study assessed the safety and effectiveness of HCL use at higher targets of 130-150mg/dL. Participants aged 14-70y with T1D>6mo and A1C<10.0% used the HCL system at home for 14 days (first 2 days hotel, n=8) over winter holidays with unrestricted eating and exercise. The target was 130, 140, and 150mg/dL for 3 days each, followed by 5 days of free choice of 110-150mg/dL. Primary outcomes were safety measures and percent time 70-180mg/dL over the first 9 days of HCL, stratified by target glucose. Participants thus far (n=13) had a mean±SD age of 35±13y, T1D duration 16±13y, and A1C 6.9±0.8%. At the 130, 140, and 150mg/dL targets, percent time from 70-180mg/dL was 75.6±11.6%, 66.5±8.9%, and 63.7±7.9%, respectively (Table). Percent time <54 and <70mg/dL decreased with increasing target, without a corresponding increase in time ≥250 mg/dL. There were no serious adverse events. The HCL system was safe and performed well in adults with T1D when used at home with higher glucose targets. Participants were invited to continue in a 3mo outpatient study of the system, which is currently underway. Disclosure S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B.W. Bode: Advisory Panel; Self; InPen, Medtronic. Consultant; Self; ADOCIA, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Pfizer Inc. Research Support; Self; Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Medtronic, Novo Nordisk A/S, Provention Bio, Inc., Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., InPen, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Glytec. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. G.P. Forlenza: Advisory Panel; Self; Medtronic. Consultant; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A.B. Criego: Other Relationship; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Omnipod. T.T. Ly: Employee; Self; Insulet Corporation. Funding Insulet Corporation

1383-P: Longitudinal Observation of Insulin Use and Glucose Time-in-Range in T1D Pregnancy

The target time in range (TIR) for pregnant women with type 1 diabetes (T1D) by the International Consensus on TIR is 70% between 63-140 mg/dL. This is difficult to achieve and is rarely met in the literature. Insulin use increases during pregnancy, but prospective data and guidance on pump setting adjustments are limited. Insulin pump delivery and CGM data for 17 T1D women from 3 U.S. sites were prospectively collected every 2 weeks as part of the LOIS-P trial. Subjects enrolled before 17 weeks gestational age (GA) and wore personal pumps and study Dexcom G6 CGM. Changes in mean daily total, basal and bolus doses per kilogram, and TIR for every 2 weeks GA are reported, and linear mixed effects regression models are used for evaluation across trimesters. Enrollment HbA1C was 6.4±0.8%. Total daily dose increased from 0.68 to 0.73 to 0.98 U/kg during the first, second and third trimesters, respectively (p<0.01). Basal dose increased from 0.31 to 0.36 to 0.44 (p<0.01). Bolus dose increased from 0.37 to 0.37 to 0.54 (p<0.01). Daily TIR was 68%, 60% and 63% (p=0.9), with 29% of subjects achieving >70% TIR during pregnancy. Time below target was 5%, 4% and 2%. Doses trended upwards around 24 weeks GA. Postpartum doses decreased significantly. While insulin doses were increased significantly across pregnancy, most subjects did not achieve > 70% TIR. Systems that are customized to this population’s targets with changing insulin sensitivity are needed. Disclosure G. O’Malley: Research Support; Self; Abbott, Dexcom, Inc. B. Ozaslan: None. C. Levister: None. M. Trinidad: None. K.N. Castorino: Research Support; Self; Abbott, Dexcom, Inc., Medtronic, Mylan, Novo Nordisk Inc. D. Desjardins: None. M. Church: None. B.H. Smith: None. S.J. Ogyaadu: None. M. Piper: None. C. Reid: None. S.K. McCrady-Spitzer: None. R. Kaur: None. W.K. Kremers: Research Support; Self; AstraZeneca. F.J. Doyle: Research Support; Self; DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Mode AGC. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. J.E. Pinsker: Advisory Panel; Self; Medtronic. Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. B. Rosenn: None. Y.C. Kudva: Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Other Relationship; Self; Abbott. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. Funding National Institutes of Health (R01DK120358); Dexcom, Inc. (AP-2018-016)

1104-P: Many Benefits of Empagliflozin Persist in Those with Reduced Renal Function: Updated Data from the Association of British Clinical Diabetologists (ABCD) Audit Programme

Background: Sodium-glucose linked transporter 2 inhibitors (SGLT2s) are currently favoured for their tolerability, cardiovascular benefit and renal protective effects. However, due to their mechanism of action, they are only licensed for use in those with preserved renal function at baseline. Previous analyses with other drugs in the class showed potential benefits even when used in those with estimated glomerular filtration rate (eGFR) below licensed level. Methods: Data was extracted from the ABCD nationwide empagliflozin audit and then stratified into groups, as follows, based on baseline eGFR (mL/min/1.73m2): CKD1 (n=2900, eGFR≥90), CKD2 (n=2753, eGFR<90, eGFR≥60), CKD3a (n=210, eGFR<60, eGFR≥45) and CKD3b+ (n=17, eGFR<45). Data was analysed using paired t-tests and ANOVA in Stata 16. Results: 5880 datasets were included with mean (±SD) age 59.5yrs (±10.4), 61.1% male, 86% Caucasian (where known), BMI 33.1kg/m2 (±6.6), HbA1c 9.17% (±1.61) and median duration diabetes 7.3 years (2.2-12.1 IQR) and were broadly similar across groups apart from age: those with more impaired renal function being generally older (CKD1 55.4yrs±9.5 v CKD3b+ 69.6yrs±8.5) with a longer duration diabetes with median (IQR) in CKD1 6.6yrs (1.8-10.9) v CKD3b+ 14.5yrs (8.9-17.3). Reductions in HbA1c, weight and BMI occurred in all groups (P<0.005); reductions in HbA1c were of a smaller magnitude as eGFR declined (ANOVA P<0.01). Changes in systolic (SBP) and diastolic blood pressure (DBP) were significant in those in CKD1- CKD3a but not in CKD3b+ (SBP +2.6mmHg, 95% CI +14.9, -9.6). eGFR was observed to decrease in CKD1 and CKD2 (CKD1 eGFR -2.1mL/min/1.73m2, CI 95% -1.8, -2.3). Conclusion: The use of empagliflozin at eGFR<45mL/min/1.73m2 may still confer HbA1c improvement (although perhaps of lower magnitude) and weight loss, though SBP and DBP reduction may be limited. More evidence is needed regarding its use at lower levels of eGFR. Disclosure T.S.J. Crabtree: None. K. Adamson: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. A.M. Robinson: None. M. Atkin: Speaker’s Bureau; Self; AstraZeneca, Napp Pharmaceuticals. D.S. Morris: None. D.M. Williams: None. J.W. Stephens: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Napp Pharmaceuticals, Novo Nordisk A/S. D.K. Sennik: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. M.L. Cull: None. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S.

984-P: First Home Evaluation of the Omnipod Horizon Automated Glucose Control System in Adults with Type 1 Diabetes

The Omnipod Horizon™ System is a hybrid closed-loop system (HCL) consisting of a tubeless insulin pump and Dexcom G6 sensor which provides automated insulin delivery with glucose targets from 110-150mg/dL, adjustable by time of day to allow therapy personalization. This study is the first outpatient safety and effectiveness evaluation of the system. Participants aged 14-70y with T1D>6mo and A1C<10.0% used the HCL system at home for 14 days (first 2 days hotel, n=8) over winter holidays with unrestricted eating and exercise. Participants set protocol-determined higher targets of 130-150mg/dL for 9 days, then could freely choose their targets from 110-150mg/dL for the last 5 days. Primary outcomes were safety measures and percent time 70-180mg/dL for the 5 days of HCL use with free choice of target. Participants thus far (n=12) had a mean±SD age of 34±13y, T1D duration 15±12y, and A1C 6.9±0.8%. Participants primarily chose the 110 (59% of study time) and 120mg/dL (41%) targets. For 53 patient-days of HCL use, percent time from 70-180mg/dL was 74.3±7.6% (Table). Percent time <70mg/dL was low: 0.9±1.3% overall and 0.9±2.2% overnight. There were no serious adverse events. The HCL system was safe and performed well in adults with T1D when used at home for 5 days with free choice of target glucose. Participants were invited to continue in a 3mo outpatient study of the system, which is currently underway. Disclosure S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B.W. Bode: Advisory Panel; Self; InPen, Medtronic. Consultant; Self; ADOCIA, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Pfizer Inc. Research Support; Self; Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Medtronic, Novo Nordisk A/S, Provention Bio, Inc., Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., InPen, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Glytec. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. G.P. Forlenza: Advisory Panel; Self; Medtronic. Consultant; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A.B. Criego: Other Relationship; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Omnipod. T.T. Ly: Employee; Self; Insulet Corporation. Funding Insulet Corporation

184-OR: Liver Fibrosis Scores Do Not Predict Response to Therapy in T2DM

Patients with NAFLD and T2DM are at high risk of liver fibrosis. Pioglitazone(Pio) and GLP-1RAs have shown efficacy against NAFLD. The EDICT trial assessed Triple (pio/exenatide/metformin(met)) vs. Conventional(Conv) (met/SU/insulin) Therapy. Aim: Evaluate the effect of these approaches on liver fibrosis scores and hepatic fibrosis, steatosis (FibroScan). Methods: 144 newly diagnosed T2DM were randomized to receive Triple or Conv Therapy to maintain HbA1c <6.5%. After 2 yrs baseline measurements were repeated and liver fibrosis scores (AST/ALT ratio, APRI, FIB-4, NFS) were calculated. Results: Patients were well matched for age, BMI, HbA1c (8.8%), LFTs. Neither therapy reduced any liver fibrosis score. Triple, but not Conv, reduced AST/ALT (p<0.001). The greatest AST/ALT reductions with Triple Therapy occurred in subjects in highest AST/ALT tertile at baseline. Only 1 subject receiving Triple Therapy had fibrosis score >0, while 43% of Conv Therapy subjects had fibrosis score of F3/F4 (p<0.0001). 87% of Conv Therapy subjects had steatosis score of S2/S3 vs. to 38% of Triple Therapy (p<0.001) (Table). Conclusion: Both Triple (6.0%) and Conventional Therapy (6.7%) markedly reduced HbA1c after 2 yrs, but only Triple Therapy reduced AST/ALT. Fibrosis scores did not change in either group and are not useful in predicting response to therapy. Triple Therapy completely prevented fibrosis and reduced steatosis by >50 % vs. Conventional Therapy. Disclosure O. Lavrynenko: None. M. Alatrach: None. M. Abdul-Ghani: None. E. Cersosimo: None. N. Alkhouri: Research Support; Self; Allergan plc. C.L. Puckett: None. R.A. DeFronzo: None. J.M. Adams: None. J.A. Vasquez: None. G.D. Clarke: None.

1276-P: First Home Evaluation of the Omnipod Horizon Automated Glucose Control System in Children with Type 1 Diabetes

The Omnipod Horizon™ System is a hybrid closed-loop system (HCL) consisting of a tubeless insulin pump and Dexcom G6 sensor which provides automated insulin delivery with glucose targets from 110-150mg/dL, adjustable by time of day to allow therapy personalization. This study is the first outpatient safety and effectiveness evaluation of the system. Participants aged 6-13.9y with T1D>6mo and A1C<10.0% used the HCL system at home for 14 days (first 2 days hotel, n=8) over winter holidays with unrestricted eating and exercise. Participants set protocol-determined higher targets of 130-150mg/dL for 9 days, then could freely choose their targets from 110-150mg/dL for the last 5 days. Primary outcomes were safety measures and percent time 70-180mg/dL for the 5 days of HCL use with free choice of target. Children thus far (n=15) had a mean±SD age of 11±2y, T1D duration 5±3y, and A1C 7.7±0.9%. Participants primarily chose the 110 (69% of study time), 120 (10%), and 130mg/dL (21%) targets. For 72 patient-days of HCL use, percent time from 70-180mg/dL was 64.1±10.0% (Table). Percent time <70mg/dL was low: 0.9±1.2% overall and 0.5±0.5% overnight. There were no serious adverse events. The HCL system was safe and performed well in children with T1D when used at home for 5 days with free choice of target glucose. Participants were invited to continue in a 3mo outpatient study of the system which is currently underway. Disclosure B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. G.P. Forlenza: Advisory Panel; Self; Medtronic. Consultant; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A.B. Criego: Other Relationship; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Omnipod. S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B.W. Bode: Advisory Panel; Self; InPen, Medtronic. Consultant; Self; ADOCIA, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Pfizer Inc. Research Support; Self; Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Medtronic, Novo Nordisk A/S, Provention Bio, Inc., Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., InPen, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Glytec. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation. Funding Insulet Corporation

1363-P: Continuous Glucose Monitoring (CGM) of Postprandial (PP) Glycemic Responses in Pregnancies Complicated by Diabetes

Background: Diabetes in pregnancy portends increased maternal and fetal morbidity and mortality. Glucose testing is advised at 1 or 2 hours Pp. CGM during pregnancy may improve meal-time glycemic monitoring. Limited Pp CGM data exist for gestational diabetes (GDM), type 1 diabetes (T1D), or type 2 diabetes (T2D). Methods: We report prospective Pp glycemic data for 32 pregnant women collected during a 6-hour YSI clinic session for a 10-day Dexcom G6 CGM accuracy trial. Each subject wore 2 sensors. During the session, food consumption was recorded and analyzed if >5g. Meals were not standardized. CGM and YSI Pp responses within 2 hours of meals and carbohydrate content were evaluated. Results: Most women had T1D (n=20) (See table). Subjects consumed 1 (n=6), 2 (n=13) or 3 (n=13) meals for a total 71 meals. Mean carbohydrate intake per meal was 29 ± 19 g (range 6-101). Peak CGM values were recorded for 32 morning and 31 afternoon meals in 2 sensors/subject (n=139 values). Pp CGM values peaked at 136 ± 32 mg/dL (range 78-233) at median 60 minutes (interquartile range: 44, 99). Conclusions: Eating patterns are heterogeneous among pregnant women. These data support 1 hour Pp testing, and CGM use allows more detailed glycemic evaluations around meals. Our YSI results support CGM reliability. Timing of Pp peak glucose levels related to nutrient content in pregnancy needs further evaluation. Disclosure E.V. Nosova: None. K.N. Castorino: Research Support; Self; Abbott, Dexcom, Inc., Medtronic, Mylan, Novo Nordisk Inc. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. T. Johnson: Employee; Self; Dexcom, Inc. S. Shah: Employee; Self; Dexcom, Inc. G. Haroush: None. K. Nelson: None. G. O’Malley: Research Support; Self; Abbott, Dexcom, Inc. S.J. Ogyaadu: None. C. Levister: None. S.J. Brackett: None. S. Polsky: None.

1456-P: Identifying Diabetic and Prediabetic Patients Who Require Pharmacotherapy for Nonalcoholic Steatohepatitis Using the FAST Score

New pharmacologic agents to treat fatty liver in diabetics are expected to be approved in 2020 and will target those with nonalcoholic steatohepatitis (NASH) and significant fibrosis (NASH-F). The FAST (Fibroscan + AST) score was recently developed to predict the presence of (NASH-F) based on measuring controlled attenuation parameter (CAP) for steatosis, liver stiffness measurement (LSM) for fibrosis, and AST for inflammation. The aim of this study was to assess the utility of FAST score in patients with T2DM and prediabetes to identify those that require NASH pharmacotherapy. Methods: Consecutive patients with T2DM or A1c ≥5.7% who presented for evaluation of fatty liver were included. All had Fibroscan to measure CAP and LSM + AST within 6 months. Based on published data, FAST ≥0.75 was used to rule in the presence of NASH-F and therefore as an indication for pharmacotherapy. FAST < 0.40 was used to rule out NASH-F. Nominal and continuous variables were analyzed with chi-squared and 2-sided T-tests, respectively. Results: 90 patients were identified; average age 56 (13.55) years, BMI was 35.06 (6.29) kg/m2, and 58 (64.4%) were female. A total of 11 (12.3%) patients had a FAST ≥0.75 indicating that they qualify for pharmacotherapy once available. Patients with FAST ≥0.75 were older (57.3 years vs. 47; p=0.01), had higher ALT (139.63 u/L vs. 57.06; p <0.01), and triglycerides (234.87 mg/dL vs. 162.44; p =0.02). Patients with FAST ≥0.75 were not more likely to have higher A1c, hypertension, or metabolic syndrome. 34 patients (37.7%) had FAST <0.4 indicating the absence of significant disease and 45 patients (50%) had FAST between 0.4 and 0.75. Conclusion: Using a high cutoff value of 0.75, the FAST score identified 12% of patients with T2DM/prediabetes that will qualify for NASH pharmacotherapy. While 38% of patients can be stratified as low risk by using a cutoff value of 0.40, 50% of patients had intermediate FAST score values indicating the need for further workup. Disclosure P. Aggarwal: None. N. Alkhouri: Research Support; Self; Allergan plc.

1388-P: Maternal and Neonatal Outcomes in Pregnancies with Preexisting Type 1 Diabetes and Controls

Background: There are limited contemporaneous data about outcomes in pregnancies with pre-existing type 1 diabetes (T1D) in the U.S. Objective: To determine maternal and neonatal outcomes in pregnancies with preexisting T1D and pregnancies in age, parity and BMI matched healthy subjects. Methods: We retrospectively studied 32 pregnancies in patients with preexisting T1D matched for age (mean 25.83 years), gravidity/parity {G1P1 (66), G2P1 (19), G3P1 (9) and G4P1 (6) % respectively} and BMI with controls (n=32) during a 5 year period from 01/01/2015 at Mayo Clinic, Rochester. Results: In 32 T1D pregnancies, 4 (12.5%) congenital defects (CD) were observed in neonates, 1-dysplastic ribs with thumb hypoplasia and 3-congentinal heart defects leading to death in one in comparison to no congenital defect or death in controls. CD pregnancies were complicated by severe pre-eclampsia in all 4 and poor glycemic control (HbA1c >8) in 3. There was a significant difference in Apgar score at 1 min between T1D pregnancies and controls (p=<0.001). Significant respiratory distress was observed in neonates with T1D pregnancies (p=0.011) compared to control group. Significant difference was observed in gestational age b/w two groups (35.9 ± 3.1 vs. 39.4 ± 1.4, p=<0.001). More severe eclampsia was observed in T1D subjects (11 vs. 2, p=0.005) along with pre-term deliveries (12 vs. 1, p=<0.001) compared to controls. Frequency of C-sections was increased in T1D subjects (19 vs.3, p=<0.001) compared to controls. Smoking had a significant effect on Apgar score at 5 min (p=0.014) when compared with current smokers or former smokers. Hypothyroidism (being on T4) during pregnancy had an effect on Apgar score both at 1 min (p=0.003) as well as at 5 min (p=0.004). Conclusion: Pregnancies in T1D continue to be high risk pregnancies and need tight glycemic control with a more advanced system such as closed loop insulin delivery during pregnancy to improve maternal and neonatal outcomes. Disclosure R. Kaur: None. S. Rizvi: None. M. Trinidad: None. B.H. Smith: None. S. Batthula: None. S.K. McCrady-Spitzer: None. C. Reid: None. D. Desjardins: None. G. O’Malley: Research Support; Self; Abbott, Dexcom, Inc. K.N. Castorino: Research Support; Self; Abbott, Dexcom, Inc., Medtronic, Mylan, Novo Nordisk Inc. J.E. Pinsker: Advisory Panel; Self; Medtronic. Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. W.K. Kremers: Research Support; Self; AstraZeneca. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. Y.C. Kudva: Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Other Relationship; Self; Abbott.

1110-P: Effect of Raised Alanine Transaminase (ALT) Levels on HbA1c in the Association of British Clinical Diabetologists (ABCD) Nationwide Audits of SGLT2 Inhibitors (SGLT2i)

Introduction: Alanine transaminase (ALT) is an important marker for Nonalcoholic Fatty Liver Disease (NAFLD), and its levels are reduced following treatment with SGLT2i. However, how raised ALT levels and hence NAFLD affects HbA1c response to SGLT2i is not known. Methods: Data for this study was obtained from the ABCD nationwide audits of patients with type 2 diabetes started on SGLT2i. We used a gradient boosting machine learning algorithm (GBM) to identify if ALT is an important predictor of glycaemic response to SGLT2i. The results of the GBM model were confirmed using linear regression analysis where the absolute drop in HbA1c was modelled as a dependent variable with baseline ALT as independent variable adjusted for relevant covariates. Results: We studied 9,609 patients initiated on Empagliflozin (n=5061), Dapagliflozin (n=3711) or Canagliflozin (n=837). The mean age of the study population was 59(±10.3), 62% male with a mean weight of 96.6(±18.8), baseline eGFR 81(±11) and baseline HbA1c 9.06% (±1.62). At a median 5.8 months follow-up, the mean HbA1c drop was 0.81% and was similar in all three types of SGLT2i. The drop in HbA1c was 0.62%, 0.78% and 1.01% in 1st 2nd and 3rd quartiles of baseline ALT, respectively (P-Anova <0.0001). In the GBM analysis the important predictors of glycaemic response were baseline weight (relative influence (RI)=71%), and baseline HbA1c (RI= 7.2%), baseline ALT (RI= 5.6%) baseline creatinine (RI= 4.9%). The model accuracy was 0.73 (0.71-0.75) and area under the curve was 0.83. In the linear regression model, higher baseline ALT was associated with a larger drop in HbA1c (beta=0.007, P<0.0001) after adjustments for baseline weight, weight loss, baseline HbA1c, and duration of diabetes. Conclusion: Higher baseline ALT levels are associated with a more significant SGLT2 induced HbA1c drop and SGLT2 inhibitors and are likely to be more effective in those with NAFLD. Disclosure H. Deshmukh: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. D.K. Sennik: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. K. Adamson: None. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. T. Sathyapalan: Research Support; Self; Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; Ipsen Biopharmaceuticals.

MP31-07 POST VOID RESIDUAL VOLUME AND RATES OF CLEAN INTERMITTENT CATHETERIZATION WITH SPONTANEOUS AND NON-SPONTANEOUS VOIDING AFTER ONABOTULINUMTOXINA TREATMENT

INTRODUCTION AND OBJECTIVE: OnabotulinumtoxinA (onabotA) is a well-tolerated, effective treatment for overactive bladder (OAB); transient increases in post void residual volume (PVR) have been reported following treatment with some cases requiring clean intermittent catheterization (CIC). Increases in PVR may be a driver for follow-up and CIC initiation in real-world practice. The rate of the complete inability to void has not previously been reported. This analysis evaluated maximum PVR (maxPVR) after onabotA 100U treatment, CIC use, and rates of spontaneous/non-spontaneous voiding. METHODS: This was a pooled post hoc analysis of two phase 3 studies. Patients were stratified based on maxPVR measured during the 12 weeks after initial onabotA 100U treatment into groups of 100 mL increments (0-100 mL, 101-200 mL, 201-300 mL, 301-400 mL, 401-500 mL, 501-600 mL, and ≥601 mL). Rates of clean intermittent catheterization (CIC) were assessed at each maxPVR category and rates of spontaneous and non-spontaneous voiding were calculated in patients who initiated CIC. Per phase 3 protocols, CIC was initiated if PVR was ≥200 to <350 mL with relevant associated symptoms assessed by the investigator, or if PVR was ≥350 mL regardless of symptoms. RESULTS: This analysis included 551 onabotA-treated patients. Most patients had a maxPVR ≤200 mL (494/551, 89.7%) and few patients had a maxPVR ≥201 mL (57/551, 10.3%). Most episodes of significantly raised PVR occurred within the first 6 weeks. In total, 36/551 (6.5%) patients receiving onabotA required CIC throughout the study and was highest in patients with maxPVR >300 mL (25/30, 83.3%) versus ≤300 mL (11/521, 2.1%). No consistent trend in mean CIC duration was observed across the maxPVR subgroups (39-106 days). Only one patient (0.2%) with a maxPVR in the ≥601 mL category was unable to spontaneously void (Figure). CONCLUSIONS: This analysis suggests the vast majority of onabotA-treated patients (99.8%) do not develop a complete inability to void; seen here in only one patient. All other patients that initiated CIC were able to spontaneously void and so did not meet the International Continence Society’s definition of urinary retention (inability to pass urine despite persistent effort).Source of Funding: Allergan plc.