Late Breaking Abstracts June 2015 | Volume 64 | Suppl. 1A | www.diabetes.org/diabetes Late Breaking Abstracts LB1 Subject Index LB85 Abstract Author Index LB88 Abstract Author Disclosure Information LB98 scientificsessions.diabetes.org COMLatePLI catBREAIOKINGNS—Hy ABSTRACTSPOGLYCEMIA COMplIcatIONS—HYpoGLYceMIA 3‑LB Coordination of Inpatient Food Delivery and Mealtime Insulin Administration Improves On‑Time Insulin Dosing and Reduces Hypo‑ 1‑LB glycemia The Effect of Hypoglycemia on Progression of Atherosclerosis in MICHAEL G. JAKOBY, SWATHI BEERAVOLU, SU AH BAE, SUMMI PARGAL, AMINA VA Diabetes Trial (VADT) JAFFAR, VEENA KESIREDDY, SHWETHA MALLIKARJUNA, LINDA READ, CHERYL ARAMESH SAREMI, GIDEON BAHN, PETER D. REAVEN, Phoenix, AZ, Hines, IL BURNS, Springfield, IL, Cincinnati, OH, Milwaukee, WI, San Leandro, CA We examined whether hypoglycemia predicted the progression of Basal/bolus insulin is the best approach for hospitalized patients with atherosclerosis in a substudy of the VADT. The effect of hypoglycemia (severe POSTERS diabetes mellitus, but little is published on strategies to synchronize delivery Complications episodes with loss of consciousness/requiring assistance, or documented of food and mealtime insulin. The SIU Hospital Diabetes Team implemented Acute and Chronic glucose <50 mg/dl) on progression of coronary artery calcium (CAC) was and evaluated a program to link food delivery and prandial insulin at St. determined in 197 participants with baseline and follow-up CT scans. During an John’s Hospital (Springfield, IL). Food Service personnel were equipped with average follow-up time of 4.5 years between scans, a total of 97 participants wireless phones and trained to contact nurses of tray drops during a three reported severe hypoglycemia (n=23) or glucose <50 (n=74). Frequency of month run in period. Primary study endpoint was proportion of insulin lispro hypoglycemia was higher in the intensive compared to the standard treatment doses administered within 20 minutes of food delivery. Secondary endpoints group (77% vs. 24%, P <0.01). Hypoglycemia did not predict progression of were frequency of insulin dosing errors, defined as a meal without insulin or CAC in the entire group. However, there was a significant hypoglycemia by insulin without food, glycemic control measured by median capillary blood treatment interaction (P=0.08 for hypoglycemia x treatment and P=0.01 for glucose (CBG), and frequency of CBG below the diabetes team target of 80- severe hypoglycemia x treatment, respectively). People with hypoglycemia 140 mg/dL. A prospective study with historical controls was performed, with in the standard group had significantly higher progression of CAC (Figure). intervention data collected June 2014-January 2015 and June 2013-January Age adjusted hypoglycemia predicted progression of CAC only in the 2014 serving as a historical control. All patients were managed by the standard group ( =3.51 ± 1.71, P=0.04 and = 6.46 ±2.71, P=0.01 for severe β β diabetes team. Nurses were notified at 96.1% of tray deliveries. Time hypoglycemia, respectively). Adjustment for all baseline differences including between meal and insulin was evaluated for 2,199 meals, 1,318 in the control baseline CAC, or on trial risk factors did not change the results. In conclusion, period and 881 after intervention. Mealtime insulin administered on time although hypoglycemic episodes were more frequent in the intensive group, increased from 49.7% to 57.7% for all meals (P = 0.0002), with significant they were associated with progression of CAC in the standard group only. improvements at breakfast (58.8% vs. 44.0%, P < 0.0001) and lunch (60.9% vs. 51.5%, P = 0.012). Insulin errors were reduced two-fold (2.4% to 1.2%), a clinically meaningful result that was not quite statistically significant (P = 0.06). Median CBG was equivalent before and after the notification system (159 mg/dL vs. 163 mg/dL, P = 0.46), but frequency of CBG < 80 mg/dL was reduced two-fold (9.8% vs. 4.9%, P < 0.0001). A program to coordinate food and prandial insulin improved diabetes management and patient safety in hospital by increasing on time insulin administration, decreasing insulin errors, and decreasing hypoglycemia rate. Supported By: Friends of St. John’s Hospital 2‑LB Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of 4‑LB BIOD‑961 Compared with Marketed Glucagons Unreported Therapeutic Effect of Liraglutide in Dumping Syndrome LILIANA URIBE-BRUCE, LINDA MORROW, LORI CANNEY, PHILIP PICHOTTA, CHRISTINE K. STIER, Frankfurt, Germany MARCUS HOMPESCH, ALAN KRASNER, ERROL DE SOUZA, Chula Vista, CA, 7 patients with a new onset of a hyperinsulinemic hypoglycemia after Danbury, CT Roux-en-y gastric bypass were treated with Liraglutide to improve their Multiple glucagon formulations for use in user-friendly devices are severe dumping symptoms. Liraglutide is an anti-diabetic GLP-1 (Glucagon currently in development for the treatment of severe hypoglycemia; like peptide 1) mimetic, which modulates pancreatic insulin production. Its however, formulations that are not reconstituted immediately prior to use spectrum of activity embraces neuro- and cardio protection, a decrease of have been associated with impaired absorption from the subcutaneous stomach emptying, glucagon secretion, hepatic glucose production, and (SC) space. BIOD-961 is a lyophilized glucagon formulation developed β-cell apoptosis and an increase of β-cell proliferation, insulin secretion and for use in an auto-reconstitution device. The PK and PD profiles of BIOD- biosynthesis, as well as glucose uptake and storage. Against doctrine, the 961 were compared to those of two marketed glucagon formulations in use of Liraglutide in these patients showed a remarkable decrease in insulin a Phase 1 randomized, six-period crossover study. On separate dosing secretion together with a better synchronization of corresponding plasma days, each subject received 1 mg of BIOD-961, Lilly glucagon, and Novo glucose levels as measured by repeated oral glucose tolerance tests (OGTT). glucagon delivered either SC or intramuscularly (IM). Fifteen normal, healthy subjects were randomized into the study and 10 completed all dosings. There were no statistically significant differences in maximal glucose concentration (BGmax), area under the glucose concentration vs. time curve (BGAUC0-240min), maximal glucagon concentration (Cmax) or area under the curve for glucagon concentration vs. time curve (AUC0-240min) (Table). Furthermore, standard criteria for PK and PD bioequivalence were met when comparing BIOD-961 to Lilly glucagon (IM) and to Novo glucagon (SC). The incidence of adverse events was similar among treatments. In summary, BIOD-961 PK and PD profiles are substantially similar to both comparator glucagons and likely to also show BE in a pivotal trial. Table. Pharmacokinetic and Pharmacodynamic Parameters. Parameter SC BIOD-961 SC Lilly SC Novo IM BIOD-961 IM Lilly IM Novo (n=12) (n=11) (n=12) (n=11) (n=11) (n=12) Cmax (µg/L) 9.01 ± 0.75 7.87 ± 0.79 9.16 ± 0.59 6.80 ± 0.52 6.75 ± 0.31 7.22 ± 0.44 AUC0-240 min 559.5 ± 28.7 520.8 ± 29.8 570.5 ± 26.8 409.5 ± 39.2 402.6 ± 27.8 441.4 ± 42.7 (µg*min/L) Tmax (min) 26.7 ± 3.76 23.2 ± 1.82 20.8 ± 1.83 15.5 ± 2.07 17.7 ± 4.39 14.6 ± 2.64 BGmax (mg/dL) 178.2 ± 7.3 170.9 ± 5.3 175.3 ± 5.9 182.9 ± 6.5 171.1 ± 6.7 174.8 ± 5.5 BGAUC0-240 min 26118 ± 630 25915 ± 685 25240 ± 424 26184 ± 607 24960 ± 568 25274 ± 485 (mg*min/dL) Time to BGmax 41.7 ± 4.1 43.6 ± 4.2 34.6 ± 3.2 40.5 ± 2.5 40.5 ± 3.4 44.6 ± 3.8 (min) ADA-Funded Research For author disclosure information, see page LB98. LB1 COMPLIcatIONS—Macrovascular—ATHEROSCLEROTIC CARDIovascular DISEASE AND HUMAN DIABETES The SHARE system was able to identify and quantify the frequency of RH in a real-life use environment. Cloud based health information provides the opportunity for learning about actual diabetes management practices and facilitate prompt actions on appropriate hypoglycemia treatment. POSTERS Complications Acute and Chronic COMplIcatIONS—Macrovascular— AtherosclerotIC CardIovascular DIsease AND HUMAN DIabetes 6‑LB The Cardiac Deficiency of Pyruvate Dehydrogenase Complex Alters Cardiac Glucose Oxidation and Sensitizes Heart to Ischemic Insults WANQING SUN, QUAN LIU, JIYAN LENG, YANG ZHENG, JI LI, Changchun, China, Buffalo, NY Pyruvate Dehydrogenase Complex (PDH), plays a key role in aerobic energy metabolism. We found that cardiac PDH deficiency mice easily die and the PDH deficiency heart demonstrate significant hypertrophy phenotype. We hypothesized that glucose oxidation regulated by PDH is critical for the heart’s energy metabolism. The objectives of this study is to characterize the signaling mechanisms by which PDH deficiency sensitizes heart to myocardial infarction. The myocardial infarction was conducted by ligation of left anterior descending coronary artery (LAD) in mice. The results showed that PDH deficiency significantly increased myocardial infarct area (p<0.01 versus WT groups), and the immunohistochemistry data showed that cardiac PDH deficiency increased macrophage infiltration (p<0.01 vs. WT groups). The staining of wheat germ agglutinin (WGA) and Masson trichrome revealed greater hypertrophy and fibrosis in the PDH deficiency than WT hearts (p<0.05). It indicated the importance of PDH’s modulation of glucose metabolism in response to ischemic insults. Furthermore, we measured the substrate metabolism of hearts in a working heart perfusion system. The glucose oxidation rate was impaired in the cardiac PDH deficiency hearts as compared to WT hearts during ischemia and reperfusion (I/R), while the PDH activator, dichloroacetate (DCA), can augment glucose oxidation in WT hearts during I/R. The AMP-activated protein kinase (AMPK) signaling can lead to an increased glucose metabolism under ischemic stress in the heart. Intriguingly. The immunoblotting data demonstrated that cardiac 5‑LB PDH deficiency attenuates ischemic AMPK activation while DCA treatment Incidence of Hypoglycemia Overtreatment in the SHARE Real Life enhances the ischemic AMPK activation.