bluuebunny/crossref_metadata_2025_split huggingface dataset:
1034-P: Efficacy and Safety of Fast-Acting Insulin Aspart According to Baseline HbA1c in Adults with Type 2 Diabetes Treated with a Basal-Bolus Regimen
Authors: FRANEK EDWARD , EKELUND MAGNUS , THÓRISDÓTTIR ÓLÖF , JANG HAK CHUL , LALIC KATARINA , RATHOR NAVEEN , ROSE LUDGER , GONZALEZ ALFONSO SOTO , SILVER ROBERT J. , LANE WENDY 
Published: June 2020

The impact of baseline HbA1c on the efficacy and safety of fast-acting insulin aspart (FA) was assessed in a post-hoc analysis of a 16-week, treat-to-target trial in adults with type 2 diabetes (T2D) not optimally controlled with a basal-bolus regimen (onset 9). Participants (n=1091) were randomized to FA or insulin aspart (IAsp), each with insulin degludec with or without metformin. In this analysis, participants were separated by baseline HbA1c (&lt;7.0%, [n=476] and ≥7.0% [n=615]).
Change from baseline in HbA1c was similar between treatments in the &lt;7.0% subgroup, and HbA1c improved with FA vs. IAsp in the ≥7.0% subgroup (Table). Change from baseline in 1-h postprandial glucose (PPG) increment (meal test) favored FA across subgroups. The rate of severe or blood glucose-confirmed hypoglycemia was statistically significantly lower for FA vs. IAsp in the &lt;7.0% subgroup, and was similar between treatments in the ≥7.0% subgroup. In the ≥7.0% subgroup treated with IAsp, the insulin degludec dose decreased slightly during the trial.
FA provides effective overall glycemic control with improved PPG control vs. IAsp in adults with T2D. For individuals with HbA1c &lt;7.0%, FA provides a similar reduction in HbA1c vs. IAsp, but with less hypoglycemia. For individuals with HbA1c ≥7.0%, FA may offer a greater reduction in HbA1c vs. IAsp without an increased risk of hypoglycemia.

Disclosure
E. Franek: Advisory Panel; Self; Novartis AG. Speaker’s Bureau; Self; AstraZeneca, Bioton, Eli Lilly and Company. Other Relationship; Self; Boehringer Ingelheim, Novo Nordisk. M. Ekelund: Employee; Self; Novo Nordisk. Stock/Shareholder; Self; Novo Nordisk. Stock/Shareholder; Spouse/Partner; Novo Nordisk. Ó. Thórisdóttir: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited. K. Lalic: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi. N. Rathor: Employee; Self; Novo Nordisk. L. Rose: None. A. Soto Gonzalez: Advisory Panel; Self; Novartis, Novo Nordisk. Consultant; Self; Mundipharma International, Novartis, Novo Nordisk. Speaker’s Bureau; Self; Eli Lilly and Company, Janssen/Mundipharma, Novartis, Novo Nordisk, Sanofi. R.J. Silver: Advisory Panel; Self; Medtronic, Novo Nordisk. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. W. Lane: Research Support; Self; AstraZeneca, Gilead, Mylan, Sanofi, Tolerion, vTv. Other Relationship; Self; Dexcom, Insulet, Novo Nordisk.

Funding
Novo Nordisk
1042-P: Insulin Requirement during Total Parenteral Nutrition in Patients with Diabetes Mellitus
Authors: GARG RAJESH , ARUNACHALAM AMAR , BERMUDEZ LUIS E. , RAMIREZ MARIANA 
Published: June 2020

Glycemic control in patients with diabetes mellitus receiving total parenteral nutrition (TPN) can be challenging due to multiple factors. These patients often have a high burden of illness and receive medications that raise blood glucose (BG) levels. Moreover, TPN delivers a large amount of glucose directly into the systemic circulation without the benefit of incretin effect. Therefore, relatively large amounts of insulin are expected to be required for glycemic control. However, there are no studies to guide insulin dosing in patients with diabetes being started on TPN. We conducted a retrospective study including all patients with diabetes admitted to our hospital over a 1-year period who received TPN for ≥ 3 days. The goal of this study was to estimate a safe starting dose of insulin for TPN. Patients receiving enteral nutrition along with TPN were excluded. Insulin doses and blood glucose levels on the last day of TPN were used for data analysis. We found 25 patients who fulfilled our inclusion/exclusion criteria. All patients had type 2 diabetes and were receiving antidiabetic drugs before hospitalization. Mean age was 68 ± 7 years, 56% were men, 80% were White, 44% had microvascular and 44% had macrovascular complications. Mean BMI was 26.7 ± 6.7 kg/m2, systolic BP 131 ± 27 mmHg, diastolic BP 65 ± 15 mmHg, HbA1c 7.7 ± 2.3% and serum creatinine 2.7 ± 3.3 mg/dl. The mean daily BG on TPN was 212 ± 47 mg/dl. Out of 171 BG values available on the last day of TPN, 116 (68%) were &gt;180 mg/dl, 4 (2%) were &lt;70 mg/dl and 0 were &lt;40 mg/dl. Only two patients suffered mild hypoglycemic episodes while all others remained hyperglycemic. Average total daily insulin dose was 17 ± 20 units before starting TPN and 53 ± 54 units on the last day of TPN. Patients received an average of 0.7 Units/kg total daily dose of insulin on the last day of TPN. With this dose, they had minimal risk of hypoglycemia but the glucose levels were often high. Our study shows that the majority of patients with diabetes need more than 0.7 units/kg insulin when receiving TPN.

Disclosure
R. Garg: None. A. Arunachalam: None. L.E. Bermudez: None. M. Ramirez: None.
105-OR: Trends in Complications in Type 1 and Type 2 Diabetes in Denmark, 1996-2016
Authors: CARSTENSEN BENDIX , AMADID HANAN , JØRGENSEN MARIT E. 
Published: June 2020

Background and aim: Both micro- and macro vascular complications represent major problems for diabetes patients and monitoring of the extent of these among diabetes patients is essential. Several studies have reported decreasing complications rates. We describe the burden and trend in 18 groups of complications in persons with diabetes in Denmark 1996-2016.
Methods: We compiled a diabetes register for the entire Danish population, including reliable classification of type of diabetes. From the National Patient Register we extracted dates of recorded complications in 18 classes. Binomial regression was used to describe the prevalence of complications at diagnosis and change in these over time. Rate models based on Poisson likelihood were used to describe the incidence rates and changes in these. Analyses were conducted separately for T1D and T2D, and controlled for sex, age, duration of diabetes and including a linear term to describe the calendar time effect (date of diagnosis).
Results: The prevalence at diagnosis of previous CVD was 10% in T1D and 37% in T2D, with annual relative changes of 3% in T1D and 5% in T2D. Retinopathy prevalence at diagnosis was 4.3% in T1D and 1.7% in T2D with no change in T1D, but a relative decrease of 6% in T2D. We found similar decreases in rates of complications in T1D and T2D; decrease of 2%/year in rates of CVD, 5%/year in amputations, while there were no changes in the incidence rates of retinopathy and renal disease over the period 1996-2016. For most complications we found a very high incidence during the first year after diagnosis, most likely reflecting a diagnostic catch-up and not any biological phenomenon.
Conclusions: A steady decrease in incidence rates of most complications was seen, but not for microvascular complications. The pattern of complications at diagnosis was more mixed, influenced by fluctuations in diagnostic activity over the period. In general an encouraging trend in complication occurrence was seen in Denmark in the period 1996-2016.

Disclosure
B. Carstensen: Stock/Shareholder; Self; Novo Nordisk A/S. H. Amadid: None. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.
1050-P: Enhanced Release of Glucose into the Intraluminal Space of the Intestine Associated with Metformin Treatment as Revealed by 18F FDG-Based PET-MRI
Authors: SAKAGUCHI KAZUHIKO , MORITA YASUKO , NOGAMI MUNENOBU , OKADA YUKO , HIROTA YUSHI , SUGAWARA KENJI , TAMORI YOSHIKAZU , MURAKAMI TAKAMICHI , OGAWA WATARU 
Published: June 2020

Objective: In addition to the inhibition of gluconeogenesis in the liver, metformin exerts various effects on the gut that likely contribute to the lowering of blood glucose levels. Positron emission tomography (PET)-computed tomography recently has revealed that metformin promotes the intestinal accumulation of [18F]fluorodeoxyglucose (FDG), a nonmetabolizable glucose derivative, indicating that the drug affects glucose handling in the intestine. It has remained unknown, however, whether this accumulation occurs in the wall or intraluminal space of the intestine. We here addressed this question with the use of [18F]FDG-based PET-magnetic resonance imaging (MRI), a recently developed imaging modality with increased accuracy of registration and high soft-tissue contrast.
Methods: Among 244 individuals with type 2 diabetes who underwent PET-MRI, we extracted 24 pairs of subjects matched for age, BMI, and HbA1c level who were (metformin group) or were not (control group) receiving treatment with metformin. We evaluated accumulation of [18F]FDG in different portions of the intestine with both a visual scale and measurement of maximum standardized uptake value (SUVmax), and such accumulation within the intestinal wall or lumen was discriminated on the basis of SUVmax.
Results: SUVmax of the jejunum, ileum, and right or left hemicolon was greater in the metformin group than in the control group. [18F]FDG accumulation in the ileum and right or left hemicolon as assessed with the visual scale was also greater in the metformin group. SUVmax for the intraluminal space of the ileum and right or left hemicolon, but not that for the intestinal wall, was greater in the metformin group than in the control group.
Conclusions: Metformin treatment was associated with increased accumulation of [18F]FDG in the intraluminal space of the intestine, suggesting that this drug promotes the transport of glucose from the circulation into stool.

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. Y. Morita: None. M. Nogami: None. Y. Okada: None. Y. Hirota: Other Relationship; Self; Sanofi. K. Sugawara: None. Y. Tamori: None. T. Murakami: 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.
1051-P: Selective Targeting of Angiopoietin-Like 3 (ANGPTL3) via the Second-Generation Antisense Oligonucleotide (ASO) ISIS-703802 (AKCEA-ANGPTL3-LRx) in Subjects with Familial Partial Lipodystrophy (FPLD)
Authors: FOSS-FREITAS MARIA CRISTINA , AKINCI BARIS , NEIDERT ADAM H. , HENCH RITA P. , SWAIDAN MARIO , ORAL ELIF A. 
Published: June 2020

FPLD is an extreme form of metabolic dyslipidemia and diabetes caused by selective loss of peripheral subcutaneous fat. Currently, there are no approved therapies for this rare cause of diabetes in the U.S. Reductions in circulating levels of the hepatokine ANGPTL3 either by mutations in humans or by targeted drugs in rodents are associated with reductions in triglyceride levels and provide protection from atherosclerosis, making it an attractive target for patients with FPLD and metabolic dyslipidemia. The objective of this proof-of concept, Phase 2, open-label study was to assess the early efficacy and safety of a strategy that targets ANGPTL3 via ISIS-703802 (AKCEA-ANGPTL3-LRx) in patients with FPLD. Four patients with FPLD (3F/1M; age range: 38-47; 1 with LMNA R482Q, 1 with LMNA R584H, and 2 with no causative genetic variant) with diabetes (HbA1c&gt;6.5%) and hypertriglyceridemia (≥ 500 mg/dL or ≥ 200 mg/dL for patients meeting genetic or family history criteria) were included. Patients received the study drug at a subcutaneous dose of 20 mg weekly for 26 weeks. Primary endpoint was the percent change in serum triglycerides from baseline to week 27. All other endpoints were also analyzed at week 27. Treatment resulted in a 60±26 (mean±SD) % reduction in triglycerides from a baseline of 818±432 mg/dL. Consistent with antisense reduction of ANGPTL3 mRNA, circulating ANGPTL3 levels were lowered by 55±10%. Treatment was also associated with 51±27% reduction in circulating apoC3 levels, 64±24% reduction in total VLDL and chylomicron triglycerides, and 18±15% reduction in total cholesterol. In addition, HbA1c showed a modest mean absolute reduction of 0.2±1.0 % The drug was well tolerated and there were no new safety signals observed. Although a small study, these results suggest that targeting ANGPTL3 in patients with FPLD could successfully address metabolic dyslipidemia.

Disclosure
M. Foss-Freitas: None. B. Akinci: Advisory Panel; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals. Research Support; Self; Gemphire Therapeutics Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Servier. A.H. Neidert: None. R.P. Hench: None. M. Swaidan: None. E.A. Oral: Consultant; Self; Aegerion Pharmaceuticals, Akcea Therapeutics, Regeneron Pharmaceuticals. Research Support; Self; Aegerion Pharmaceuticals, Akcea Therapeutics, Gemphire Therapeutics Inc., GI Dynamics Inc., Regeneron Pharmaceuticals.

Funding
Ionis Pharmaceuticals, Inc.; Akcea Therapeutics
1056-P: Effect of Dulaglutide on Glycemic Variability: Post Hoc Analysis of the AWARD Studies
Authors: JODAR ESTEBAN , WANG QIANQIAN , ROMERA IRENE , CAVEDA ELENA , GARCIA LUIS EMILIO 
Published: June 2020

Glycemic variability (GV) may contribute to the development and progression of cardiovascular complications. This post-hoc analysis assessed GV in people with type 2 diabetes, treated with once-weekly dulaglutide (DU), and not receiving any concomitant insulin treatment. Analysis included pooled data from 5 randomized, parallel-arm, phase 3 studies (AWARD 1,2,3,6 and 8). The participants (N=1114, 48% male) received DU 1.5 mg without any concomitant insulin for 26 weeks and with evaluable GV measurements at baseline and study endpoint (week 26). The measurements included within-day and between-day GV calculated by standard deviation (SD) and coefficient of variation (CV) from self-monitored plasma glucose (SMPG), and between-day fasting self-monitored plasma glucose (FSMPG) values. At baseline, the mean (SD) age was 55.9 (9.7) years, BMI 32.7 (5.2) kg/m2, HbA1c 8.0 (0.9) % and fasting plasma glucose 166.5 (47.8) mg/dL. At 26 weeks, DU significantly reduced within-day and between-day GV from SMPG values (SD values, p&lt;0.001, Figure) and between-day GV from FSMPG (p&lt;0.001). SMPG GV changes were significant and consistent across studies. Analysis by CV gave consistent results (Figure). Overall, the analysis suggests that treatment with once-weekly DU 1.5 mg reduces within-day and between-day GV from SMPG and between-day GV from FSMPG.

Disclosure
E. Jodar: Other Relationship; Self; Elli Lilly & Co, Novo Nordisk, MSD, Lilly, Janssen, Pfizer, AstraZeneca, Sanofi, UCB, Amgen, FAES, Shire, Mundipharma, Novartis. Q. Wang: Employee; Self; Eli Lilly and Company. I. Romera: Employee; Self; Eli Lilly and Company. E. Caveda: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L. Garcia: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

Funding
Eli Lilly and Company
1059-P: Additive Manufactured Macroencapsulation Devices for Islet Cell Replacement Therapy
Authors: LEVEY RUTH E. , COULTER FERGAL B. , ROBINSON SCOTT T. , MCDONOUGH LIAM , DEOTTI STEFANO , DOLAN EIMEAR B. , DOCKERY PETER , KELLY HELENA , OCEARBHAILL EOIN D. , DUFFY GARRY P. 
Published: June 2020

Islet encapsulation devices can induce a Foreign Body Response (FBR) and the formation of a dense avascular fibrotic capsule. This FBR is heightened when the device has a smooth surface as fibrous tissue is unable to adhere, instigating a substantial immunological reaction, islet death and ultimately implant failure. In this study, we examine whether additive manufactured multiscale porous devices promote optimal tissue integration and vascularisation for long-term functional islet encapsulation. Furthermore, we examine the potential for this method to be scaled for functional use in a large diabetic animal model. Silicone devices exhibiting progressively more complex surface architectures (quantity of macro- and micro-pores), were implanted submuscularly in rodents. Upon explant, analysis of fibrous capsule, angiogenic and macrophage response were performed. To determine its potential as an encapsulation device, multiscale porosity devices were used for intra-peritoneal syngeneic islet transplantation in 8 diabetic rats. Circulating blood glucose levels were monitored for 8 weeks. To validate scalability and functionality, devices were implanted submuscularly in an STZ-induced diabetes pig model for 2 weeks before blood glucose levels were measured in response to the infusion of insulin through the device. Degree of tissue integration and vascularity in proximity to the implant was shown to increase 2.5 fold with precisely controlled multiscale device topography. Moreover, encapsulated islets maintain glucose responsiveness and function for 8 weeks. Bioavailability was equal when the same dose of insulin is delivered via the device vs. subcutaneously in diabetic pig model. The use of additive manufactured multiscale porous coatings on macroencapsulation devices can increase tissue integration and vascularity. These findings demonstrate functionality, scalability and could help to resolve the immunological and diffusion limitations of current encapsulation devices.

Disclosure
R.E. Levey: None. F.B. Coulter: None. S.T. Robinson: None. L. McDonough: None. S. Deotti: None. E.B. Dolan: None. P. Dockery: None. H. Kelly: None. E.D. OCearbhaill: None. G.P. Duffy: None.

Funding
European Union (645991)
106-LB: Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1092 in Subjects with T1DM and T2DM
Authors: MORROW LINDA , GRIMM MICHAEL , BEYSEN CARINE , WALFORD GEOFFREY , DUNCAN KELLY , MITRA PRANAB K. , VADDADY PAVAN , HOMPESCH MARCUS 
Published: June 2020

Background: MK-1092, a first-in-class insulin receptor partial agonist, is being developed as a novel basal insulin to treat diabetes. Primary objectives were to assess safety and tolerability of single subcutaneous (SC) doses of MK-1092 in T1DM and T2DM and to determine safe single SC doses of MK-1092 in T1DM with a maximum glucose infusion rate (GIRmax) between 1.5 and 4.5 mg/kg/min. Secondary objectives were to estimate PK profiles in T1DM and T2DM and to determine the GIRmax in T2DM.
Methods: All subjects received blinded treatments of MK-1092 or glargine and placebo matched to the alternative active treatment under euglycemic clamp conditions. T1DM: 2 cohorts (n=8/cohort) were each randomized (3:1) to receive MK-1092 (8 nmol/kg in cohort 1 or 32 nmol/kg in cohort 2) or glargine (3 nmol/kg [0.5 units/kg]). T2DM: 1 cohort (n=9) was randomized to receive either MK-1092 (n=6) or glargine (n=3). Each subject underwent 3 dosing periods. MK-1092 was dosed at 32, 16 and 64 nmol/kg in periods 1, 2, and 3, respectively and glargine was dosed at 3 nmol/kg in all periods.
Results: All doses tested were safe and well tolerated. There were no SAEs or discontinuations due to AEs. AEs were mild or moderate and resolved spontaneously. No anti-MK-1092 or anti-insulin antibodies were observed. In T1DM, the geometric mean of apparent terminal t1/2 was 8.54 and 6.70 hr; Tmax was 15.00 and 15.04 hr; AUC0-∞ was 21.5 and 74.9 nM*hr and Cmax was 0.79 and 3.43 nM for 8 and 32 nmol/kg MK-1092, respectively. PK parameters for 32 nmol/kg MK-1092 were comparable for T1DM and T2DM except for a ~40-50% lower AUC0-∞ and Cmax in T2DM. In T1DM, the mean GIRmax was 1.33 and 2.74 mg/kg/min for 8 and 32 nmol/kg MK-1092, respectively and 2.32 mg/kg/min for glargine. In T2DM, the mean GIRmax was 1.90, 1.40 and 2.83 mg/kg/min for 32, 16 and 64 nmol/kg MK-1092, respectively and ~ 1.2 mg/kg/min for glargine.
Conclusion: Single doses of MK-1092 are well-tolerated and lower glucose in patients with diabetes.

Disclosure
L. Morrow: Employee; Spouse/Partner; Lilly Diabetes. Employee; Self; ProSciento. M. Grimm: None. C. Beysen: Employee; Self; ProSciento. G. Walford: Employee; Self; Merck & Co., Inc. K. Duncan: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. P.K. Mitra: Employee; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Self; Bristol-Myers Squibb. P. Vaddady: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. M. Hompesch: Board Member; Self; ProSciento. Employee; Self; ProSciento. Stock/Shareholder; Self; ProSciento.
106-OR: National Trends in Lower Extremity Amputation among U.S. Medicare Beneficiaries with Diabetes, 2000-2017
Authors: HARDING JESSICA , ANDES LINDA J. , ROLKA DEBORAH B. , IMPERATORE GIUSEPPINA , LI YANFENG , GREGG ED , ALBRIGHT ANN L. 
Published: June 2020

Diabetes is the leading cause of non-traumatic lower extremity amputation (NLEA) in the United States. After a period of decline, some U.S. data show that diabetes-related NLEA has recently increased, particularly among young and middle-aged adults. However, the trend for older adults is less clear. To examine NLEA trends among older adults with diabetes (≥67 years), we used 100% Medicare claims for beneficiaries enrolled in Parts A and B during 2000-2017. NLEA was defined as the highest-level amputation per patient per calendar year. NLEA rates were stratified by sex, race and ethnicity, and NLEA level. All rates were age-sex standardized to the 2000 Medicare population. Trends over time were assessed using Joinpoint regression and annual percent change (APC) reported. NLEA rates (per 1,000 persons) halved from 8.5 in 2000 to 4.4 in 2009 (APC -7.9, p value&lt;0.001). However, from 2009 to 2017 NLEA rates increased slightly to 4.8 (APC 1.2, p-value&lt;0.001). Trends were similar across most sex and race/ethnic groups, however absolute rates were highest in blacks and men (Figure A). By NLEA level, overall increases were driven by increases in rates of toe and foot NLEAs. This study of the U.S. Medicare population shows that recent increases in diabetes-related NLEA are also occurring in the older population but at a less severe rate.

Disclosure
J. Harding: None. L.J. Andes: None. D.B. Rolka: None. G. Imperatore: None. Y. Li: None. E. Gregg: None. A.L. Albright: None.