bluuebunny/crossref_metadata_2025_split huggingface dataset:
1097-P: Disposition Index Is a Predictor of Urinary Glucose Excretion in Subjects Treated with SGLT2 Inhibitors
Authors: SAKAGUCHI KAZUHIKO , SO ANNA , ITO JUN , KANEKO AKIHIRO , MORITA YASUKO , YAMADA TOMOKO , MIURA HIROSHI , OTOWA-SUEMATSU NATSU , NAKAMURA TOMOAKI , KOMADA HISAKO , OKADA YUKO , HIROTA YUSHI , TAMORI YOSHIKAZU , OGAWA WATARU 
Published: June 2020

Aims: Urinary glucose excretion (UGE) induced by SGLT2 inhibitors (SGLT2i) varies considerably by individual, and is influenced by blood glucose level and glomerular filtration rate (GFR). It is however unknown what other factors are involved in this process. We have now investigated the relation between various physiological parameters and UGE in patients treated with an SGLT2i.
Methods: To minimize the influence of glycemic variability, we analyzed SGLT2i-induced UGE during a hyperinsulinemic-euglycemic clamp. OGTT and a 120 min-hyperinsulinemic-euglycemic clamp, during which plasma glucose (PG) were maintained at 90 mg/dl, were performed with type 2 diabetes subjects (n=45) within 6 days after the start of dapagliflozin (5mg/day). Relationships between UGE during the clamp and various indexes for insulin secretion/sensitivity were analyzed. Disposition index (DI) was calculated as the product of insulinogenic index (II) and insulin sensitivity index (ISI) determined by the clamp.
Results: During the clamp, UGE considerably varied from 28.2 to 176.9 (mean ± SD, 87.1 ± 32.8) mg/kg/120min. In univariate analysis, UGE was not correlated with PG before the clamp, mean PG during the clamp or any indexes for insulin secretion/sensitivity determined by OGTT or the clamp (HOMA-β, II, OGTT AUCIRI/AUCPG, HOMA-IR, composite index, QUICKI and ISI). However, UGE was correlated with log-transformed DI (r = -0.338, p = 0.023) as was eGFR (r = 0.418, p = 0.004). Multivariate analysis revealed that eGFR and log-transformed DI were independent predictors of UGE (R2 = 0.267, β = 0.332, p = 0.045, and β = -0.315, p = 0.031, respectively).
Conclusion: Even in euglycemic conditions, SGLT2i-induced UGE considerably varied by individuals and was correlated with DI, which represents individual capacity of glucose disposal. The present results thus suggest that SGLT2i-induced UGE is regulated by an unidentified physiological process that is related to glucose tolerance in living body.

Disclosure
K. Sakaguchi: Other Relationship; Self; AstraZeneca, Novartis AG, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. A. So: None. J. Ito: None. A. Kaneko: None. Y. Morita: None. T. Yamada: None. H. Miura: None. N. Otowa-Suematsu: None. T. Nakamura: None. H. Komada: None. Y. Okada: None. Y. Hirota: Other Relationship; Self; Sanofi. Y. Tamori: None. W. Ogawa: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharma GmbH & Co.KG, Eli Lilly Japan K.K., Kowa Company, Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.
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&lt;0.001); weight decreased by 2.5kg at 3 months and by 5.7kg at 12 months (p&lt;0.001). Blood pressure decreased from 131 to 128mmHg systolic and from 78 to 77mmHg diastolic (p&lt;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&lt;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&lt;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 &gt;100% after 1h and 2h (both p&lt;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&lt;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 &lt;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&lt;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&lt;0.05), stage 3B; 43.2±7.1 to 40.9±6.5 ml/min/1.73m2 (P&lt;0.01), stage 4; 30.6±10.2 to 28.7±9.4ml/min/1.73m2 (P&lt;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&lt;0.02), stage 3B; -4.8±3.7 to -1.7±2.7ml/min/1.73m2/year (P&lt;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&lt;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&lt;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&lt;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 &gt;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 &lt;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&lt;.05). db/db mice on canagliflozin diet had even worse appearance and use compared to db/db mice on a regular diet (p&lt;.05), and +/+ mice on canagliflozin diet (p&lt;.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&lt;.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)