bluuebunny/crossref_metadata_2025_split huggingface dataset:
52-OR: Intrinsically Photosensitive Retinal Ganglion Cell Dysfunction in Diabetic Retinopathy Associates with Impaired Sleep and Circadian Rhythms
Authors: REUTRAKUL SIRIMON , PARK JASON C. , CHAU FELIX , BAYNARD TRACY , PRIYADARSHINI MEDHA , CROWLEY STEPHANIE , MCANANY J. JASON 
Published: June 2019

Background: Intrinsically photosensitive retinal ganglion cells (ipRGCs) control the pupillary light reflex (PLR) and synchronize sleep-wake cycles, melatonin secretion, and metabolic processes to the 24-h day. PLR abnormalities in diabetic retinopathy (DR) suggest ipRGC dysfunction. We explored whether ipRGC dysfunction in DR is associated with impaired sleep, circadian rhythms and metabolic functioning.
Methods: Healthy controls (n=6), type 2 diabetes (T2D) without DR (n=8), or T2D with at least moderate DR (n=11) participated. PLR inferred ipRGC function, HbA1c, and nocturnal urinary 6-sulfatoxymelatonin (aMT6s/creatinine ratio) were measured. Sleep was recorded by 7-day actigraphy. Dim light melatonin onset (DLMO) was assessed by sampling saliva in the 7 hours before self-reported bedtime.
Results: Mean age was 54.6±5.4 yr. The relative PLR was significantly smaller in T2D-DR (control vs. T2D-noDR vs. T2D-DR: 0.32(0.10) vs. 0.26 (0.09) vs. 0.13 (0.11), p=0.003). Nocturnal aMT6s [8.3 (3.1) vs. 14.6 (14.3) vs. 1.9 (2.1) ng/mg, p=0.001] was significantly lower in T2D-DR. Sleep was more disturbed in T2D-DR than others as reflected by higher wake time after sleep onset (p=0.024), higher fragmentation index (p=0.007) and lower sleep efficiency (p=0.030). HbA1c was similar between T2D groups. T2D-DR were more likely to have no detectable rise of salivary melatonin in the evening (normal 16% vs. DM-noDR 14% vs. DM-DR 67%, p=0.049). Smaller PLRs correlated with lower aMT6s (r=0.652, p=0.001). Among T2D, lower aMT6s and smaller PLR associated with lower sleep efficiency (p=0.029-0.046) and more fragmented sleep (p=0.028-0.066). There was no relationship between PLR or aMT6s with HbA1c in T2D. PLR was smaller in those without vs. with DMLO [0.11 (0.09) vs. 0.29 (0.09), p&lt;0.001].
Conclusion: T2D with DR had dysregulated melatonin rhythm and disrupted sleep, which significantly correlated with the degree of ipRGC dysfunction.

Disclosure
S. Reutrakul: None. J.C. Park: None. F. Chau: None. T. Baynard: None. M. Priyadarshini: None. S. Crowley: None. J. McAnany: None.

Funding
University of Illinois at Chicago
520-P: Hyperglycemia-Induced Mitochondrial Dysfunction in Diabetic Kidney Disease May Be Mediated by Crabtree Effect in Kidney Proximal Tubule Epithelial Cells
Authors: DARSHI MANJULA , KIM JIWAN JOHN , DREL VIKTOR , MURPHY ANNE N. 
Published: June 2019

Background: Recent studies indicate mitochondrial dysfunction is a dominant pathway in diabetic kidney disease (DKD), however underlying mechanisms are unclear. Here we examined if Crabtree effect by glucose is a cause of mitochondrial dysfunction in kidney.
Methods: Lactate was measured by by YSI biochemistry analyzer. TCA cycle metabolites were measured by gas chromatography mass spectroscopy in urine samples of type 1 and type 2 DKD mouse models. Changes in oxygen consumption (OCR) and extracellular acidification i(ECAR) were analyzed on a Seahorse extracellular flux analyzer. Immunohistochemical analysis was performed on FFPE-embedded mouse kidney sections. Western blot analysis was performed on kidney cortical sections and HK2 cells.
Results: Significantly increased urine and plasma lactate along with a decrease in several TCA cycle metabolites were observed in both type 1 and type 2 diabetic mice. Mitochondrial functional analysis in different kidney cells showed a profound respiratory inhibition and stimulation of lactate by glucose in proximal tubules, but not in mesangial cells and podocytes. Pyruvate at above physiological concentration reversed the glucose-induced inhibition of OCR. Western blotting of kidney cortical tissue sections showed a significant increase in phospho PDH in diabetic kidney tissues and in HK2 cells treated with high glucose. In normal conditions, phospho PDH was predominantly on distal tubules, however in diabetic conditions a significant increase in phospho PDH was noted in proximal tubule cells. Dichloroacetate, an inhibitor of PDK completely reversed the glucose induced respiratory inhibition in proximal tubule epithelial cells.
Conclusions: Mitochondrial dysfunction in proximal tubule epithelial cells may potentially be due to high-glucose induced PDH phosphorylation resulting in limited pyruvate oxidation into mitochondria and enhanced lactate production.

Disclosure
M. Darshi: None. J.J. Kim: None. V. Drel: None. A.N. Murphy: Advisory Panel; Self; Cytokinetics Inc. Consultant; Self; Agilent Technologies.

Funding
JDRF; U.S. Department of Veterans Affairs
521-P: Sodium Butyrate Alleviates High-Glucose-Induced Renal Glomerular Endothelial Cells Pyroptosis
Authors: GU JUNLING , HUANG WEI , XU YOUHUA , XU YONG 
Published: June 2019

Caspase1-GSDMD canonical pyroptosis pathway is associated with pathogenesis of chronic inflammatory diseases. As the first layer of renal filtration barrier, whether high glucose triggers glomerular endothelial cells (GECs) pyroptosis in the pathogenesis of diabetic nephropathy (DN) is unclear. Previous research showed that the gut microbiota metabolites-butyrate, reversed high glucose induced IL-1β release in mesangial cells. However, the effects of butyrate on pyroptosis in GECs remain indistinct. Therefore, we hypothesized that high glucose may induce GECs pyroptosis and then trigger inflammatory, but sodium butyrate may alleviate it. In this study, human renal glomerular endothelial cells (HRGECs) were exposed to high glucose in vitro, exogenous sodium butyrate was used as an intervention reagent, and then caspase 1 inhibitor Ac-YVAD-CMK pre-treated or silencing GSDMD by siRNA on HRGECs. The expression of Caspase1-GSDMD signaling molecule were observed by confocal microscopy and western blotting. Propidium iodide (PI) staining-positive cells were determined using a flow cytometer. The release of IL-1β was detected and the release of lactate dehydrogenase (LDH) was assayed. Our results showed that high glucose increased the protein level of GSDMD, GSDMD-N and cleaved-caspase-1, and induced the release of IL-1β and LDH, PI positive staining cells also increased synchronously. Sodium butyrate co-treated, pretreatment with caspase-1 inhibitor or GSDMD siRNA alleviated high glucose-induced pyroptosis in HRGECs, respectively. Moreover, sodium butyrate-mediated anti-pyroptosis effect was facilitated by si-GSDMD. Overall, this is the first observation of the potential relationship between sodium butyrate and pyroptosis in the pathogenesis of DN, proved that sodium butyrate could inhibit high glucose-induced Caspase1-GSDMD canonical pyroptosis pathway, which may act as new therapeutic targets of DN.

Disclosure
J. Gu: None. W. Huang: None. Y. Xu: None. Y. Xu: None.
522-P: Long-Term Renal Outcomes in Young Onset Type 2 Diabetes
Authors: MIDDLETON TIMOTHY , CHADBAN STEVE , MOLYNEAUX LYNDA M. , D'SOUZA MARIO I. , CONSTANTINO MARIA I. , YUE DENNIS , MCGILL MARGARET , WU TED , TWIGG STEPHEN M. , WONG JENCIA 
Published: June 2019

Young adult onset type 2 diabetes (YT2DM) is an aggressive disease. Cross-sectional studies have shown a higher prevalence of albuminuria in YT2DM compared to age-matched young adults with T1DM (YT1DM). Whether this translates to poorer long-term renal outcomes has not been widely studied. We aimed (i) to examine progression to renal replacement therapy (RRT) and renal-related death (RRD) in our young adult population, and (ii) to examine survival on RRT for those individuals who reached end stage renal disease. We performed probabilistic linkage of prospectively collected data from the RPA Diabetes Centre eMR to the Australian National Death Index and the Australian and New Zealand Dialysis and Transplant Registry up to 31/12/2015. In our patient cohort diagnosed between the ages of 15 and 35 years, 1,248 had YT1DM and 1,534 had YT2DM. After a median (IQR) observation of 13.6 (6.9-20.7) years, 56 (4.5%) of YT1DM vs. 98 (6.4%) of YT2DM reached the combined renal end-point of RRT/RRD. Analysis of Kaplan-Meier survival curves demonstrated a greater rate of progression of renal disease in YT2DM (Log-rank p=0.003). Cox proportional hazard modelling of RRT/RRD with adjustment for gender, ethnicity and duration of diabetes exposure was undertaken. The HR (95% CI) for an adverse renal outcome in YT2DM relative to YT1DM was 2.0 (1.4-2.9), p&lt;0.001. This HR was attenuated when further adjustments were made for HbA1c, blood pressure, BMI and cholesterol. Similar results were obtained after multiple imputation for missing data. For the 80 young adults who commenced RRT, there were 19 deaths (70%) in the YT1DM subgroup and 26 deaths (49%) in the YT2DM subgroup after a median (IQR) observation time of 4.2 (2.2-9.1) years. KM survival analysis demonstrated equally poor survival in YT1DM and YT2DM. Cox regression with transplant as a time-varying covariate also showed non-significance. These data highlight the more rapidly progressive renal disease seen in YT2DM compared to YT1DM; however, survival on RRT appears to be equally poor for both diabetes types.

Disclosure
T. Middleton: Other Relationship; Self; AstraZeneca. S. Chadban: None. L.M. Molyneaux: None. M.I. D'Souza: None. M.I. Constantino: None. D. Yue: None. M. McGill: None. T. Wu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. S.M. Twigg: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; AstraZeneca. Research Support; Self; Abbott. Speaker's Bureau; Self; Abbott, AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. J. Wong: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; AstraZeneca, Lilly Diabetes.
523-P: Axon Guidance Pathway (AGP) Proteins Associate with ESKD and Kidney Lesions in Type 2 Diabetes
Authors: SAULNIER PIERRE , SATAKE EIICHIRO , LOOKER HELEN C. , SKUPIEN JAN , KROLEWSKI ANDRZEJ , NELSON ROBERT 
Published: June 2019

Seven AGP proteins associate with ESKD in Caucasians with diabetes. We explored the association of these proteins with ESKD and kidney lesions in Pima Indians with type 2 diabetes. EPHA1, EPHA2, EPHB6, EFNA4, EFNA5, UNC5Cand UNC5D were measured in serum of 162 Pimason a SOMAscan platform. Hazard ratio (HR) for ESKD for a 1 SD increase of each protein was computed by Cox regression after adjustment for age, sex, A1c, iothalamate glomerular filtration rate (GFR), and albumin:creatinine ratio (ACR). Serum samples obtained a median of 2.5 years later were measured in a subset of 67 Pimas who underwent kidney biopsy. Relationships between changes in protein concentrations and kidney lesions were explored by Spearman correlations. Baseline, mean age was 45±10 years, diabetes duration 15±6 years, GFR 155±53 ml/minute, and median ACR 54 (13-250) mg/g. During median follow-up of 12.5 years, 54 participants developed ESKD. Higher concentrations of 6 proteins (UNC5C HR1.51 [95CI 1.07-2.13]; EPHB6 1.67 [1.15-2.41]; EFNA4 1.72 [1.29-2.31]; UNC5D 1.73 [1.12-2.69] EFNA5 1.99 [1.36-2.91] and EPHA2 2.15[1.46-3.17]) were associated with ESKD. Increasing concentrations of these proteins were associated with structural lesions of diabetes (Figure). Proteins related to cell surface molecules of the Ephrin family were associated with kidney lesions and with progression to ESKD in Pima Indians with type 2 diabetes.

Disclosure
P. Saulnier: None. E. Satake: None. H.C. Looker: None. J. Skupien: None. A. Krolewski: None. R. Nelson: None.

Funding
American Diabetes Association (1-08-CR-42 to R.N.)
53-OR: Efficacy of Efpeglenatide in Patients with Obesity and Prediabetes: A Subanalysis of the BALANCE 205 Study
Authors: PRATLEY RICHARD E. , JACOB STEPHAN , KANG JAHOON , TRAUTMANN MICHAEL E. , HOMPESCH MARCUS , HAN OAKPIL , STEWART JOHN A. , OGBAA IKE , SORLI CHRISTOPHER H. , YOON KUN-HO 
Published: June 2019

Once-weekly (QW), subcutaneous efpeglenatide (efpeg) is a long-acting GLP-1 RA being developed to improve glycemic control in T2D. In the 20-week BALANCE 205 study (NCT02075281), all doses of efpeg led to significant reductions in body weight (BW) vs. placebo (PBO) in patients with obesity without diabetes (p&lt;0.0001; primary endpoint). This exploratory analysis investigated the effects of efpeg on glycemic, BW, BMI, waist circumference (WC) and cholesterol parameters in patients from BALANCE with prediabetes (HbA1c 5.7−6.4% or FPG 100−125 mg/dL) at baseline (n=140/295). At study end, percentages of patients with normoglycemia (i.e., no longer prediabetic) were higher with efpeg (4 mg QW, 64.3%; 6 mg QW, 46.2%; 6 mg once every 2 weeks [Q2W], 40.6%; 8 mg Q2W, 41.7%; pooled efpeg, 48.2%) than with PBO (10.0%; Table). All efpeg doses led to significant reductions vs. PBO in BW and HbA1c (p&lt;0.0001 for all comparisons; −6.6 kg and −0.4%, respectively for pooled group), BMI, total cholesterol, FPG and WC (p&lt;0.05 for all), except the 4 mg QW dose for WC. Adverse events (AEs) mirrored those known for GLP-1 RAs, with higher rates of gastrointestinal AEs vs. PBO, with no incidences of severe hypoglycemia.
In conclusion, treatment with efpeg led to significant improvements vs. PBO in HbA1c, BW, BMI, FPG, WC and cholesterol, and greater proportions of patients achieving normoglycemia, in patients with obesity and prediabetes.

Disclosure
R.E. Pratley: Consultant; Self; Sanofi US. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Janssen Global Services, LLC., Janssen Research & Development, Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk Inc., Pfizer Inc., Sanofi, Takeda Development Center Americas, Inc. S. Jacob: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novartis AG, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. J. Kang: Employee; Self; Hanmi Pharm. Co., Ltd. M.E. Trautmann: Consultant; Self; CeQur Corporation, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Oramed Pharmaceuticals, ProSciento, Servier. Stock/Shareholder; Self; Lilly Diabetes. M. Hompesch: Stock/Shareholder; Self; ProSciento. O. Han: None. J.A. Stewart: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. I. Ogbaa: Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. Other Relationship; Self; Sanofi. C.H. Sorli: Employee; Self; Sanofi. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. Speaker's Bureau; Self; Takeda Pharmaceutical Company Limited.

Funding
Hanmi Pharmaceutical, Co., Ltd.; Sanofi
536-P: Association between Uric Acid Level and Incidence of Macroalbuminuria in People with Type 2 Diabetes Mellitus: A 4.5-Year Cohort Study
Authors: LAI YUN-JU 
Published: June 2019

Background: Using animal models and molecular biology researches, hyperuricemia has been shown to instruct renal arteriolopathy, arterial hypertension, and microvascular injury involving the renin-angiotensin system and resulting in renal function impairment. Nevertheless, the association between uric acid levels and the development of macroalbuminuria has been under-investigated in people with type 2 diabetes mellitus.
Methods: Patients with type 2 diabetes and regular outpatient visits were recruited from the Puli Branch of the Taichung Veterans General Hospital in Taiwan since January 2014. Demographics, lifestyle features, and medical history were gathered by well-trained interviewers. All participants underwent comprehensive physical examinations, including a biochemical assay of venous blood specimens and urine samples after an 8-hour overnight fast. Participants were followed until June 2018. The primary outcome was the macroalbuminuria incidence. Univariate and multivariate Cox regression analysis were employed to explore the relation between uric acid and incident macroalbuminuria. Uric acid cutoffs for incident macroalbuminuria were determined with the receiver operator characteristic curve.
Results: We included 247 qualified subjects (mean age: 64.78 years old [standard deviation=11.29 years]; 138 [55.87%] men). During a 4.5-year follow-up duration, 20 subjects with incident macroalbuminuria were recognized. Serum uric acid was significantly associated with an increased risk of incident macroalbuminuria (adjusted hazard ratio=2.39; 95% confidence interval: 1.53-3.75; p&lt;0.001) with potential confounders adjustment. The uric acid cutoff point was 6.9 mg/dL (area under the curve 0.708, sensitivity 60.0%, specificity 84.58%) for incident macroalbuminuria.
Conclusions: Serum uric acid was associated with incident macroalbuminuria among people with type 2 diabetes.

Disclosure
Y. Lai: None.
542-P: One-Year eGFR Decline Rate Predicts Renal Outcome in High-Risk Japanese Patients with Hypercholesterolemia and Diabetic Retinopathy
Authors: MEGURO SHU , SATO YASUNORI , ITOH HIROSHI 
Published: June 2019

Objective: The slope of eGFR decline is collecting attentions for earlier recognition of eGFR decliner. We analyzed the predictive value of maximum 1-year eGFR decline rate for the renal endpoint in prospective cohort.
Research Design and Methods: We analyzed the data from EMPATHY trial which was the multicenter randomized control trial to assess the benefits of intensive statin therapy for patients with hypercholesterolemia and diabetic retinopathy. We calculated 1-year eGFR decline rate in every 6 months and analyzed its relation to the renal endpoint defined as initiation of chronic dialysis or increase in serum creatinine level by at least twofold.
Results: The renal endpoint developed in 101 subjects out of 5,042 patients in mean follow-up 37 ± 13 months. The AUC of maximum 1-year eGFR decline rate by ROC was 0.960, that of albuminuria at baseline was 0.913, and that of eGFR at baseline was 0.809. When we defined the cut-off value of maximum 1-year eGFR decline rate as 20%, its sensitivity was 97.8% and its specificity was 80.2%. Time until the renal endpoint from the first demonstration of 1-year eGFR decline rate more than 20% was 353.1 ± 31.9 days.
Conclusions: One-year eGFR decline more than 20% was highly associated with the renal endpoint. The renal endpoint was predominantly observed in the subjects with albuminuria.

Disclosure
S. Meguro: Research Support; Self; Novartis Pharmaceuticals Corporation. Speaker's Bureau; Self; Abbott, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., NIPRO Medical Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Y. Sato: None. H. Itoh: None.
547-P: Utility of Galectin-3 as a Biomarker of Prediabetes and Complications of Type 2 Diabetes Mellitus
Authors: ABDELLA NABILA A. , MOJIMINIYI OLUSEGUN A. 
Published: June 2019

Introduction: To determine its utility as a biomarker, this study explores the diagnostic usefulness of Galectin-3 (Gal3), in subjects with type 2 diabetes mellitus (T2D) and their first-degree relatives (FDR).
Methods: Gal3, glucose (FPG) and high-sensitivity C-reactive protein(hs-CRP) were measured in 217 T2D patients and 226 FDR. Clinical data were recorded and subjects were classified using homeostasis model assessment of insulin resistance (HOMA-IR). FDR were classified as normal, prediabetes or diabetic using HbA1c. T2D were classified by presence or absence of retinopathy, neuropathy (autonomic (AN) and sensory (SN) and as normo- (NAO) or micro-albuminuric (MIA)) using urine microalbumin to creatinine ratio. Binary logistic regression with determination of the Odds Ratio (OR) analyses were used to evaluate associations with T2D complications. Receiver-Operating Characteristic Curve (ROC) analysis was used to evaluate diagnostic utility of Gal3.
Results: Gal3 showed significant (p&lt;0.05) correlations with waist circumference (r=0.21), HbA1c (r= 0.33); glucose (r=0.21) and hs-CRP (r=0.2). In FDR, mean Gal3 levels increased stepwise with worsening glucose tolerance - normal (7.6ng/ml); prediabetes (8.1ng/ml) and diabetes (9.1 ng/ml) and subjects with HOMA-IR &gt;2 had significantly higher mean Gal 3 than subjects with HOMA-IR &lt; 2 (10.2 vs. 9.3 ng/ml). In FDR, ROC analysis showed that Gal3 cut-off value of 8.7 ng/ml has 77% sensitivity and 67% specificity for detection of diabetes. In T2D, binary logistic regression analysis showed Gal3 was significantly associated with hypertension (HT), MIA, AN, SN and retinopathy. ROC analysis showed that Gal3 significantly detects HT, MIA, AS and SN. Gal3 &gt;9.7 ng/ml was associated with presence of T2D complications with sensitivity and specificity &gt;70%.
Conclusions: Gal3 is significantly associated with diabetes in FDR and is a strong predictor of associated complications in subjects with T2D.

Disclosure
N.A. Abdella: None. O.A. Mojiminiyi: None.

Funding
Kuwait Foundation for the Advancement of Science (2011-1302-01)
56-OR: Liraglutide for Perioperative Management of Hyperglycaemia in Cardiac Surgery Patients (GLOBE): A Multicentre, Prospective, Superiority Randomised Trial
Authors: HULST ABRAHAM H. , PRECKEL BENEDIKT , HOLLMANN MARKUS W. , DEVRIES J. HANS , HERMANIDES JEROEN 
Published: June 2019

Background: Most cardiac surgery patients develop perioperative hyperglycaemia requiring intravenous insulin therapy. This is labour-intensive and carries a risk of hypoglycaemia. We hypothesised that preoperative administration of the GLP-1 receptor agonist liraglutide would reduce the number of patients requiring insulin during cardiac surgery.
Methods: In this randomised, blinded, placebo-controlled, parallel-group, balanced (1:1), superiority, multicentre randomised trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomised to receive 0·6 mg subcutaneous liraglutide on the evening before surgery and 1·2 mg after induction of anaesthesia, or matching placebo. Blood glucose was measured hourly and controlled using an insulin-bolus-algorithm. The primary outcome was insulin administration for blood glucose above 8·0 mmol/L in the operating theatre. Research pharmacists used centralised, stratified, variable-block, randomisation software. Patients, care providers, and study personnel were blinded to treatment allocation.
Findings: Between June 2017 and August 2018, 278 patients were randomised to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention-to-treat analyses (liraglutide: 129, placebo: 132). In the liraglutide group, 55 patients (43%) required additional insulin compared to 80 patients (61%) in the placebo group, absolute difference: 18% (95% CI 5·9-30·0, p=0·003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality, or postoperative complications.
Interpretation: Preoperative liraglutide reduces insulin requirements while improving peri-operative glycaemic control during cardiac surgery.

Disclosure
A.H. Hulst: Research Support; Self; Novo Nordisk A/S. B. Preckel: Research Support; Self; Novo Nordisk Inc. M.W. Hollmann: Consultant; Self; Eurocept BV. Other Relationship; Self; CSL Behring. J. DeVries: Advisory Panel; Self; Novo Nordisk A/S. Employee; Self; Profil Institute for Metabolic Research. Speaker's Bureau; Self; Novo Nordisk A/S. J. Hermanides: Consultant; Self; Julius Clinical (CRO). Research Support; Self; Novo Nordisk A/S.

Funding
Novo Nordisk A/S