bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Clinical and Economic Effects of Switching Medicare Beneficiaries with Type 2 Diabetes from Analog to Human Insulin
Authors: LUO JING , KHAN NAZLEEN F. , MANETTI THOMAS , ROSE JAMES J. , KALOGHLIAN ANI , GADHE BALU , JAIN SACHIN H. , GAGNE JOSHUA , KESSELHEIM AARON 
Published: June 2018

Objective: To evaluate the clinical and economic effects of a managed care organization’s conversion program switching Medicare beneficiaries with type 2 diabetes mellitus from analog to human insulin.
Methods: A consecutive sample of 14,635 participants who filled insulin prescriptions between January 2014 and December 2016 were identified from a Medicare Advantage and prescription drug plan operating in 4 U.S. states (CA, AZ, NV, VA). Outcomes were mean hemoglobin A1c (%), rates of severe hypoglycemia or hyperglycemia events and risk of reaching the Part D coverage gap. Data were analyzed using interrupted time series and segmented regression with cut points at the beginning and end of 2015.
Results: 14,635 members (mean age=72.5) filled 221,866 insulin prescriptions. Insulin conversion decreased the proportion of scripts filled by analog insulins from 90% to 30%. The baseline mean hemoglobin A1c was 8.46% and decreased at a rate of -0.02% per month during 2014. The beginning of the conversion program in 2015 was associated with a level change of +0.14% (p&lt;0.01) and a slope change of 0.02% (p&lt;0.01). The baseline rate of severe hypoglycemia was 4.21 per 1000-person years (py) and increased at a rate of 0.36/1000py during 2014. The baseline rate of severe hyperglycemia was 22.33/1000py and increased at a rate of 0.30/1000py. For both hypoglycemia and hyperglycemia, the level and slope changes in the 12-month intervention and post-intervention segments were not statistically significant. The intervention reduced the risk of reaching the coverage gap by 55% (HR 0.45, nominal 95% CI: 0.43-0.48, p&lt;0.001).
Conclusions: Switching Medicare beneficiaries with diabetes from analog to human insulin did not change the rates of hospitalization for hypoglycemia or hyperglycemia, slightly increased mean A1c, and reduced the risk of reaching the Part D coverage gap.

Disclosure
J. Luo: Consultant; Self; Alosa Health, Inc.. N.F. Khan: None. T. Manetti: None. J.J. Rose: None. A. Kaloghlian: None. B. Gadhe: None. S.H. Jain: Employee; Self; CareMore Health. J. Gagne: Research Support; Self; Eli Lilly and Company, Novartis Pharmaceuticals Corporation. A. Kesselheim: None.
Comparison of Peak Plantar Pressure and Peak Pressure Gradient among Patients with Prediabetes and Diabetes
Authors: IZUORA KENNETH , TRABIA MOHAMED , DEBERARDINIS JESSICA , LIDSTONE DANIEL E. , VARRE MATHEW SUNIL , TROTTER ASHLEY L. , DUFEK JANET S. 
Published: June 2018

Background: Foot ulcers are a serious complication associated with diabetes peripheral neuropathy (DPN). Diabetes foot complications associated with increased ulcer risk include: 1) decreases in plantar soft-tissue thickness, 2) increases in plantar tissue stiffness, and 3) increases in forefoot (FF) to rearfoot (RF) loading.
Aim: The purpose of this study was to determine whether patients with DPN demonstrate higher forefoot to rearfoot pressures during barefoot walking compared to diabetes patients without peripheral neuropathy (DWPN) and prediabetes patients without peripheral neuropathy (PWPN).
Methods: Eight PWPN, twenty-six DWPN and fourteen DPN patients participated in the study. Barefoot walking trials were performed while wearing Medilogic® pressure-measuring insoles. Peak plantar pressure (PPP) and peak pressure gradient (PPG) were measured on the right foot for the FF and RF regions. FF to RF PPP and PPG ratios were then calculated and normalized to body mass. Walking velocity was used as a co-variate for ANCOVAs. A priori statistical significance was set at α=0.05.
Results: No significant interactions were observed for Group*Region for PPP (F(2, 89)=1.454, p=0.239) and PPG (F(2, 89)=0.579, p=0.563). Main effects of region revealed significantly higher FF to RF loading in both PPP (F(1, 89)=6.67, p=0.011) and PPG (F(1, 89)=4.02, p=0.048) measures driven by DWPN and DPN patients. No significant differences were observed between groups for FF to RF PPP (F(2, 44)=2.624, p=0.084) or PPG (F(2, 44)=1.331, p=0.275) ratios.
Conclusion: Our findings suggest DWPN and DPN patients demonstrate a pattern of loading related to elevated foot ulcer risk. However, no significant difference was observed between groups for FF to RF PPP and PPG ratios. Inclusion of a more robust sample size will allow better testing of our hypothesis.

Disclosure
K. Izuora: None. M. Trabia: None. J. DeBerardinis: None. D.E. Lidstone: None. M. Varre: None. A.L. Trotter: None. J.S. Dufek: None.
Pathophysiology of Remission in Type 2 Diabetes—The Diabetes Remission Clinical Trial (DiRECT)
Authors: TAYLOR ROY , AL-MRABEH AHMAD , ZHYZHNEUSKAYA SVIATLANA V. , PETERS CARL , BARNES ALISON C. , ARIBISALA BENJAMIN , HOLLINGSWORTH KIEREN G. , SATTAR NAVEED , LEAN MICHAEL E. 
Published: June 2018

DiRECT is a prospective, randomised study of type 2 diabetes of &lt;6 years duration. In the intervention group, weight loss was induced using a liquid diet replacement (825-853 kcal/day) for 3-5 months with withdrawal of all antidiabetic drugs on day 1. A subgroup underwent 3-point Dixon MRI of liver and pancreas fat and measurement of hepatic very low density lipoprotein triglyceride (VLDL1-TG) metabolism and first phase insulin secretion, before and after 3-5 months. Those with HbA1c &lt;48mmol/mol (&lt;6.5%) after weight loss (n=37; responders) were compared with those remaining &gt;48mmol/mol (n=16; non-responders). At baseline, the two groups were similar (age 53.3±1.2 vs. 53.6±2.2 years, weight 100.3±2.8 vs. 98.2 ±3.9kg, BMI 34.9±0.7 vs. 34.9±1.2kg/m2) but not duration of diabetes (2.7±0.3 vs. 3.8±0.4 years, p=0.04) nor HbA1c 57.1±1.8 vs. 62.5±2.3 mmol/mol; p&lt;0.07). Weight decreased similarly in responders (100.3±2.8 vs. 84.2±2.3kg; p&lt;0.0001) and in non-responders (98.2 ±3.2 vs. 84.3 ±3.6kg (p&lt;0.0001). HbA1c changed only in responders (57.1±1.8 to 41.2±0.6 mmol/mol, p&lt;0.0001; 62.5±2.3 to 63.8±4.7 mmol/mol, p=0.77, respectively). Decreases occurred in liver fat in responders and non-responders (16.7±1.6 to 3.4±0.7%, p&lt;0.0001 and 15.0±2.7 to 2.4±0.5%, p&lt;0.0001), plasma VLDL1-TG concentration (0.69±0.07 to 0.44±0.mmol/l, p=0.001 and 0.64±0.10 to 0.46±0.11 mmol/l, p=0.15), and intra-pancreatic fat (8.7±0.4 to 7.8±0.4%, p&lt;0.0001 and from 7.6±0.5 to 6.7±0.4%, p=0.001). In contrast, first phase insulin secretion increased in responders only (0.05±0.01 to 0.12±0.02, p&lt;0.0001 vs. 0.02± 0.01 to 0.02±0.01, p=0.98, respectively). Failure of first phase insulin secretion response but not differential lipid or hepatic responses characterises non-responders. De-differentiation of beta cells in early type 2 diabetes is not reversible in all, despite removal of the metabolic stress. Such individuals are characterised by longer duration of diabetes even in early type 2 diabetes.

Disclosure
R. Taylor: None. A. Al-Mrabeh: None. S.V. Zhyzhneuskaya: None. C. Peters: None. A.C. Barnes: None. B. Aribisala: None. K.G. Hollingsworth: None. N. Sattar: Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Mitsubishi Tanabe Pharma Corporation, Medscape, Sanofi-Aventis Deutschland GmbH. M.E. Lean: Advisory Panel; Self; Novo Nordisk Inc., Orexigen Therapeutics, Inc.. Research Support; Self; Cambridge Weight Plan. Consultant; Self; Counterweight Ltd. Stock/Shareholder; Self; Eat Balanced.
Clinical Outcomes and Mortality among Patients Hospitalized with Hypoglycemia and End-Stage Renal Disease in the U.S.
Authors: GALINDO RODOLFO J. , HURTADO CAROLINA R. , PASQUEL FRANCISCO J. , VELLANKI PRIYATHAMA , UMPIERREZ GUILLERMO E. 
Published: June 2018

Patients with diabetes and end stage renal disease (ESRD) are at high risk of hypoglycemia. The prevalence and outcomes among hospitalized patients with hypoglycemia and ESRD in the U.S. is not known. Accordingly, we compared the outcomes of patients hospitalized for hypoglycemia with and without ESRD in a U.S. nationwide cohort. We searched the National Inpatient Sample (largest public inpatient database in the U.S.), for adult patients (&gt;18 years) in 2014. We used ICD9 codes to identify admissions for hypoglycemia (primary diagnosis) and ESRD (secondary diagnosis), defined as stage 5 chronic kidney disease, with or without dialysis. Among 97,445 patients admitted for hypoglycemia, 11,285 (11.6%) had ESRD. Patients with ESRD were more likely of African-American and Hispanic race, and had a higher mortality rate, longer length-of-stay (LOS) and higher hospitalization costs compared to those without ESRD (Table). In multivariate analysis, ESRD was significantly associated with an increased odds for mortality (OR 2.92, 95% CI 1.98, 4.29, p&lt;0.01), longer LOS (p&lt;0.001) and higher hospitalization costs (p&lt;0.001). Among patients with hypoglycemia, ESRD is common (11.5%) and is associated with a 3-fold increase in mortality, longer LOS and higher hospitalization costs. Further research on treatment strategies to decrease the burden of hypoglycemia in this population is needed.
CharacteristicsHypoglycemia with ESRD n: 11,285 (11.6%)Hypoglycemia without ESRD n: 89,160 (88.4%)p-valueAge, mean years (±SD)60.5 (30.8)63.4 (41.8)&lt;0.001Female, n (%)4,695 (41.6)35,940 (40.3)0.9Race, Caucasian, n (%)4,294 (39)51,000 (57)&lt;0.001Race, African-American, n (%)4,090 (38)18,000 (20)&lt;0.001Ethnicity, Hispanics, n (%)1,725 (16)10,000 (11)&lt;0.001Hospital Mortality, n (%)220 (1.95)590 (0.67)&lt;0.001LOS, mean days (±SD)6.4 (18.5)5.1 (11.9)&lt;0.001Costs, mean US$ (±SD)13,810 (43,448)9,859 (34,040)&lt;0.001

Disclosure
R.J. Galindo: None. C.R. Hurtado: None. F.J. Pasquel: Consultant; Self; Merck Sharp & Dohme Corp., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..
Intensive Hypoglycemia Avoidance and Improved Awareness of Hypoglycemia Associated with Partial Recovery Activation Lost in Hypoglycemia Unaware Patients with Type 1 Diabetes
Authors: CHOUDHARY PRATIK , NWOKOLO MUNACHISO , O'DALY OWEN , AMIEL STEPHANIE A. , ZELAYA FERNANDO O. 
Published: June 2018

Aim: The brain senses hypoglycemia and governs symptomatic, hormonal and behavioral responses to it. This study aimed to understand the differences in regional brain responses to experimental hypoglycemia between adults with type 1 diabetes (T1D) with intact hypoglycemia awareness [HA] and impaired awareness of hypoglycemia [IAH] and evaluate the impact of intensive hypoglycemia avoidance on these responses.
Methods: We performed ASL fMRI scans to measure global and regional cerebral blood flow [CBF and rCBF] and measured symptomatic and hormonal responses to experimental hypoglycemia [47 mg/dl] in 15 HA T1D subjects and 22 subjects with IAH matched for age, HbA1c and duration of diabetes. Those with IAH underwent a hypoglycemia avoidance program including education, frequent contact and additional technology where required, including sensor augmented pump therapy with predictive low glucose suspend before being restudied with ASL FMRI at hypoglycemia.
Results: Baseline scans: Global CBF increased in response to hypoglycemia in HA and IAH [HA 6.3% p=0.01; IAH 8.0%, p=0.03; HA vs. IAH p=NS]. There was greater increase in rCBF in thalamus, prefrontal cortex and orbitofrontal cortex in HA vs. IAH and greater reduction in rCBF in the hippocampus. Repeat scans: The hypoglycemia avoidance program improved subjective awareness [Gold score 6 ±1 vs. 4.2±1.9; p = 0.001] in the 12 completers. Compared to baseline scans, there was a trend to greater increase in rCBF in the anterior cingulate cortex in response to hypoglycemia [p=0.058], but no changes in the thalamus, prefrontal or orbitofrontal cortices.
Conclusion: Intensive education and support can improve hypoglycemia awareness with some restoration of activation in the anterior cingulate cortex, but frontal changes are not restored suggesting cognitive responses to hypoglycemia may not be changed by these interventions.

Disclosure
P. Choudhary: Speaker's Bureau; Self; Medtronic MiniMed, Inc., Novo Nordisk Inc.. Advisory Panel; Self; Becton, Dickinson and Company, Sanofi-Aventis, Roche Diabetes Care Health and Digital Solutions, Lilly. M. Nwokolo: None. O. O'Daly: None. S.A. Amiel: Advisory Panel; Self; Medtronic MiniMed, Inc., Novo Nordisk A/S, Roche Diabetes Care Health and Digital Solutions. F.O. Zelaya: None.
A Risk Prediction Model for Heart Failure Hospitalization among Patients with Type 2 Diabetes
Authors: WILLIAMS BRENT , GANDHI PRANAV 
Published: June 2018

Type 2 diabetes mellitus (T2DM) is strongly associated with future cardiovascular (CV) events, including heart failure (HF) and its sequelae such as hospitalization (HFH) and death. Identifying T2DM patients at highest risk of HFH may be clinically valuable so therapeutic regimens can be optimized.
Accordingly, this study aimed to develop and validate a risk prediction model for HFH among patients with T2DM. This electronic medical record- (EMR-) based, retrospective cohort study included patients with new or preexisting diagnoses of T2DM receiving health care services longitudinally through the Geisinger Health System. Study patients were assigned an index date at an office visit at least two years following their first EMR-documented encounter between 1/1/03 and 11/10/15. Candidate predictors of HFH were defined according to EMR documentation in the 2-year period prior to the index date from demographics, vital signs, medical history including diagnoses and procedures, CV-related symptoms, and laboratory tests. Cox proportional hazards regression with stepwise variable selection identified the strongest predictors of HFH. Internal validation was performed by randomly splitting the sample 1:1. Among 77,385 T2DM patients meeting study criteria, median (IQR) age of patients at the index date was 62 (52, 72) years and 49% were male. Over a mean (SD) follow-up of 5.8 (4.2) years, 2903 (3.8%) HFH occurred, and estimated HFH incidence rates at 1, 3, and 5 years after the index date were 0.5%, 1.8%, and 3.0%. The development set model containing the 15 strongest HFH predictors had a c-statistic of 0.833, and the validation set c-statistic was 0.824. The five strongest predictors were age, a history of HF, coronary artery disease, blood urea nitrogen, and HbA1c. The patients with 10% highest risk based on the model had ≥2.0% annual risk of HFH. This proposed model for HFH among T2DM demonstrated strong predictive capability and may be valuable in guiding therapeutic decision making.

Disclosure
B. Williams: None. P. Gandhi: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc..
Electrophysiological Assessment of Cardiac Complication in Chronic Diabetic Minipigs
Authors: STRICKER-KRONGRAD ALAIN , LIU JASON , BOUCHARD GUY 
Published: June 2018

Abundant evidence shows that patients with type 1 diabetes are at high risk for several cardiovascular disorders. Our objective was to assess cardiac electro-pathophysiology changes linked to chronic insulin-dependent diabetes in the Yucatan miniature swine (total N = 22). Diabetic animals were divided into different groups based on duration of diabetes (Group 1: normal; Groups 2, 3, 4 and 5: diabetes duration of 3-4, 4-5, 5-6 and &gt;6 years). Cardiac electrophysiological parameters were acquired in conscious diabetic and normal control animals using a standard lead II configuration. Routine measurements of electrocardiograms, including HR (bpm), RR, PR, QRS, QT and QTc, were done (all in msec). A heart rate correction for the QT interval (QTc) was calculated using the Fridericia method [QTc=QT/(cubed root of RR)]. Mean heart rate was decreased for the diabetic Groups 2, 4, and 5 compared to the mean heart rate for normal animals (52, 54 and 54 vs. 75 bpm, respectively). The mean PR interval was increased in all diabetic animals compared to normal animals and the effect increase with the duration of diabetes (132 vs. 138, 140, 152 and 172 msec for Groups 1, 2, 3, 4 and 5, respectively). The mean QRS interval was increased for all of the diabetic animals compared to normal animals (47 vs. 56, 66, 52 and 64 msec for Groups 1, 2, 3, 4 and 5, respectively). There were no pronounced QTc abnormalities in this study when comparing diabetic to the normal animals although one animal in Group 3 did have a QTc prolongation of 43 msec. In addition, one animal in Group 5 had a prolonged PR segment (224 msec) associated with frequent ventricular escape complexes.
In conclusion, chronic diabetes in Yucatan miniature swine manifests with progressive effects on heart rate, PR interval, and QRS duration. This indicates that the diabetic minipig could provide a good model to test preventative approaches for progressive cardiac therapies in diabetes, using electrocardiography segments as markers of early heart damage.

Disclosure
A. Stricker-Krongrad: None. J. Liu: None. G. Bouchard: None.
Update in Cardiovascular Safety of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes—A Mixed Treatment Comparison Meta-analysis of Randomized Controlled Trials
Authors: ALFAYEZ OSAMAH , YAMI MAJED S. AL , ALSHEIKH RAZAN 
Published: June 2018

Background: The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) was recently published. Thus, we here present a mixed treatment comparison meta-analysis (MTC) of major randomized clinical trials to determine Glucagon like peptide 1 (GLP-1) receptor agonists’ effects on CV outcomes in patients with T2DM.
Methods: A comprehensive, systematic review was conducted using Embase and MEDLINE databases. Studies were included in the MTC meta-analysis if they were (1) RCTs and (2) evaluated the effects of one of the GLP-1 agonists vs. placebo on CV outcomes as their primary endpoint. The primary outcomes were CV death, nonfatal MI, and nonfatal stroke. Hospitalization for HF was evaluated as a secondary endpoint.
Results: A total of 202 publications were identified and reviewed, of which 198 were excluded based on study design or relevance to the research question. A total of 4 trials, including 33,457 patients, met the eligibility criteria and were retained analysis. The pairwise meta-analysis showed a 13% reduction in death from cardiovascular causes in patients who received GLP-1 agonists vs. those who received placebo (RR 0.87, 95% CI: 0.78-0.96, I2=0%, P=0.592). The NMA showed no differences among all the interventions, with liraglutide the preferred agent (53%) followed by semaglutide (18%). The pairwise meta-analysis showed no significant reduction in non-fatal MI events between the two groups (RR 0.95, 95% CI: 0.86-1.04, I2=19.5%, P=0.293). Like the pairwise meta-analysis, the NMA results showed no reduction in non-fatal MI events with semaglutide as the preferred agent (66%), followed by liraglutide (19%).
Conclusion: GLP-1 therapy was associated with a significant reduction in CV death. However, GLP-1 agonists seem to have a safety profile comparable to placebo in terms of reducing non-fatal MI, non-fatal stroke events, and rates of HF hospitalization.

Disclosure
O. Alfayez: None. M.S. Al Yami: None. R. Alsheikh: None.
A Novel Therapeutic Approach to Intensive Statin Therapy–Resistant Vulnerable Plaque of Coronary Artery in Diabetic Patients by Use of Anti-PCSK9 Antibody and Coronary CT Angiography (CCTA)
Authors: HIRAI AIZAN , FUJIMURA KOJI , KONDO SEIYA , SAKAI TAKENORI , IKEJIMA SHIN , TANIAI HISANORI , HIRAI KEIJI , MURATA KAZUYA , SHIRAKAMI ATSUSHI , OKUZAKI KAZUTOSHI , KAGEYAMA TAKAHIRO 
Published: June 2018

Purpose: Coronary plaque progression despite very low levels of LDL-C has been reported in the patients with coronary artery disease (CAD) who received intensive statin therapy (IST). CCTA has been applied to detect vulnerable coronary plaques having low attenuation of CT value. The best characterized function of PCSK9 is the binding to hepatic LDL receptors, leading to their degradation. PCSK9 is produced also in vascular smooth muscle cells constituting the atheriosclerotic lesion in addition to hepatocytes. PCSK9 promotes foam cell formation by suppressing the excretion of cholesterol from macrophages. Recently, statin is demonstrated to promote PCSK9 production. PCSK9 has been proposed to play a crucial role in the pathogenesis of IST resistance. The present study was performed to establish a novel therapeutic approach to IST resistant vulnerable plaque of coronary artery in diabetic patients.
Methods: The present study included 1T2DM patients with non-FHC asymptomatic CAD who developed vulnerable plaques in coronary artery despite IST over 1 year. CCTA by use of 320-slice CT was applied to evaluate vulnerable plaques in coronary artery. During the administration of anti-PCSK9 antibody, changes in serum lipids and CT value of vulnerable coronary plaques were determined.
Results: After the administration of anti-PCSK9 antibody, 72% decrease in serum LDL-C was observed. Also, improvement of vulnerable coronary plaque e.g., rise in the CT value of plaque (from 45.2 ± 12.0 HU to 107.5 ± 42.3 HU, p&lt;0.0001) was observed in 6 months after administration of the drug.
Conclusion: A significant improvement in vulnerable coronary plaques was observed in the patients with asymptomatic CAD who are resistant to IST after 6 months administration of anti-PCSK9 antibody. An analysis of the plaque quality by CCTA is useful method for the evaluation of the effect of the drug on vulnerable coronary plaques.

Disclosure
A. Hirai: None. K. Fujimura: None. S. Kondo: None. T. Sakai: None. S. Ikejima: None. H. Taniai: None. K. Hirai: None. K. Murata: None. A. Shirakami: None. K. Okuzaki: None. T. Kageyama: None.
Specific Deletion of PKC Delta in Endothelial Cells Restores VEGF Action in Diabetes
Authors: GERALDES PEDRO 
Published: June 2018

Introduction: Ischemia due to narrowing of the femoral artery and distal vessels is also a major cause of peripheral arterial disease and morbidity affecting patients with diabetes. Our laboratory has previously shown that hyperglycemia reduced vascular endothelial growth factor receptor (VEGFR2) activity in ischemic muscle of diabetic mice, which was not observed in protein kinase C (PKC)-Δ deficient mice. The objective of this study is to evaluate the impact of a specific deletion of PKC-Δ in endothelial cells in diabetic mice.
Methods: Nondiabetic (NDM) and 3 months diabetic (DM) mice with deletion of PKC-Δ specifically in endothelial cells (PrckdEC-) were used. Ligation of the femoral artery was performed and blood flow reperfusion was measured by laser Doppler for 4 weeks. Primary lung endothelial cells (EC) isolated from each group of mice were exposed to normal (5.6mM; NG) or high glucose concentrations (25mM; HG) for 48 hours, in normoxia (20% oxygen) or hypoxia (1%) for the last 24 hour in presence of VEGF, a pro-angiogenic factor.
Results: Blood flow was recovered to 43% in DM mice compared to 78% in NDM mice. Specific EC deletion of PKC-Δ enhanced reperfusion in NDM and DM mice up to 88% and 71%, respectively. Expression of VEGFR2 was decreased in ischemic muscle of DM mice, but not in DM-PrkcdEC- mice. In vitro, VEGF-induced Akt phosphorylation was reduced by 40% in EC isolated from DM mice compared to NDM mice, which was prevented in EC isolated from DM-PrkcdEC- exposed to HG+hypoxia.
Conclusion: Diabetes induced PKC-Δ activity and caused inhibition of VEGF actions in EC, whereas the deletion of PKC-Δ specifically in EC restored VEGF action, VEGFR2 expression and blood flow reperfusion in diabetic mice.

Disclosure
P. Geraldes: None.