bluuebunny/crossref_metadata_2025_split huggingface dataset:
2257-PUB: Evidence-Based Basal Insulin Use in T2D: Extensive Knowledge and Confidence Increases with CME
Authors: LARKIN AMY , HEALY COLLEEN S. , LE ANNE 
Published: June 2019

We assessed baseline knowledge of PCPs and diabetologists/endocrinologists (D/Es) and determine if an online continuing medical education (CME) could improve individualized treatment of patients with T2D. A 3-question knowledge and 1-question confidence linked pre-/post assessment study designed with McNemar’s chi-squared test (5% significance level P &lt;.05) and Cramer’s V (&lt;0.05 no effect; 0.06-0.15 small effect; 0.16-0.30 medium effect; &gt;0.30 large effect) assessed educational effect. The activity launched December 19, 2017 and data collected through January 19, 2018. PCPs (N=585) demonstrated a lower baseline knowledge level compared to D/Es (N=118): • 29% of PCPs compared to 81% of D/Es correctly identified which basal insulin had a lower risk for hypoglycemia • 52% of PCPs compared to 75% of D/Es correctly identified the regimen needed to decrease the risk for hypoglycemia and maintain glucose control • 42% of PCPs compared to 62% of D/Es accurately distinguished between basal insulin and longer-acting basal insulin. Overall improvements were seen after participation in the CME activity for both PCPs (N=585, P&lt;.0001, large effect V=0.343) and D/Es (N =118, P&lt;.0001, medium effect V=0.290). • 48% of PCPS (P &lt;.0001) and 15% of D/Es (P=.0008) improved related to risk of hypoglycemia with longer-acting basal insulin • 25% of PCPs (P&lt;.0001) and 20% of D/Es (P=.0011) improved on selecting a regimen to minimize hypoglycemia risk • 40% of PCPs (P&lt;.0001) and 35% of D/Es (P&lt;.0001) improved related to differences in basal versus longer-acting basal insulin • 27% of PCPs and 15% of D/Es reported increased confidence in prescribing basal insulins for patients with T2D. This study demonstrates the success of CME online activity on improving clinical knowledge and confidence of PCPs and D/Es related to evidence-based use of basal insulin for T2D. PCPs especially would benefit from further education on differences between traditional and newer, longer-acting basal insulins.

Disclosure
A. Larkin: None. C.S. Healy: None. A. Le: None.

Funding
Novo Nordisk
2258-PUB: Online CME Improves Clinical Knowledge and Confidence Related to Use of GLP-1 Receptor Agonists in Combination with Basal Insulin
Authors: LARKIN AMY , LACOUTURE MICHAEL , LE ANNE 
Published: June 2019

Introduction: We sought to assess baseline knowledge related to GLP-1 receptor agonist (GLP-1RA) use in combination with basal insulin and determine if an online, video-based, continuing medical education (CME) activity could improve the clinical knowledge of primary care physicians (PCPs) and diabetologists/endocrinologists (D/Es).
Methods: A 3-question knowledge and 1-question confidence linked pre-/post-assessment study design with McNemar’s chi-squared test (5% significance level, P &lt;.05) and Cramer’s V (&lt;0.05 no effect; 0.06-0.15 noticeable effect; 0.16-0.30 considerable effect; &gt;0.30 significant effect) assessed educational impact. The activity launched August 23, 2018, and data collected through September 19, 2018.
Results: Overall improvements were seen after participation in the CME activity for both PCPs (n = 254, P&lt;.0001, noticeable effect of V= 0.115) and D/Es (n = 95, P=.0284, noticeable effect of V= 0.091). Improvements include: 11% more PCPs (P=.013) and 5% more D/Es (P=.3597) accurately identified the profound effect of combining a GLP-1RA with basal insulin; 9% more of PCPs (P=.0327) and 14% more D/Es (P=.0311) correctly identified the effect of adding exenatide once weekly to insulin glargine in patients with T2D failing basal insulin; 14% more of PCPs (P=0.0016) and 3% more of D/Es (P=.545) accurately identified which combination of therapy resulted in significantly greater reductions in HbA1c, blood glucose (fasting and postprandial), weight, and systolic blood pressure; 28% of D/Es and 41% of PCPs reported increased confidence in recommending a GLP-1RA or SGLT2 inhibitor for a patient failing basal insulin.
Conclusion: This study demonstrates the success of online, video-based CME on improving clinical knowledge and confidence of PCPs and D/Es related to using GLP-1RA in combination with basal insulin.

Disclosure
A. Larkin: None. M. LaCouture: None. A. Le: None.

Funding
AstraZeneca
226-LB: HOMA-ß and ß-Cell Activity in Early and Late Phase during an OGTT Are Independent Risk Factors of Type 2 Diabetes in Japanese Americans
Authors: SHIMOJO TAKU , IZUMI CHIHAYA , SATO KYOKO K. , LEONETTI DONNA L. , KAHN STEVEN E. , FUJIMOTO WILFRED Y. , BOYKO EDWARD J. , HAYASHI TOMOSHIGE 
Published: June 2019

The β-cell plays a major role in type 2 diabetes (T2DM). HOMA-β reflects fasting β-cell activity. Insulin responses during an OGTT reflect β-cell activity during glucose loading, which has two phases, early and late. HOMA-β, early, and late β-cell activity have different pathophysiologies. However, no research has examined whether HOMA-β and early and late phase β-cell activity during an OGTT are independently associated with the risk of T2DM. In a prospective cohort study, 415 nondiabetic Japanese-American men and women were followed for 10-11 years. β-cell activity was assessed by HOMA-β [fasting insulin × 360/(fasting glucose − 63)] as fasting activity, the insulinogenic index (IGI) [?insulin (30-0 min)/?glucose (30-0 min)] during an OGTT as early phase activity, and (area under the curve (AUC) of insulin 60-120 min)/(AUC glucose 60-120 min) as late phase activity. Insulin sensitivity was estimated by Matsuda index [10000/square root of ((fasting glucose) × (fasting insulin) × (AUC glucose 0-120 min/120) × (AUC insulin 0-120 min/120))]. T2DM was diagnosed as fasting plasma glucose level ≥126 mg/dL, 2-hour glucose level ≥200 mg/dL, or taking glucose-lowering medications. During the 10-11 year follow-up, 95 cases of T2DM occurred. HOMA-β, IGI, and late phase β-cell activity were all independently associated with the risk of T2DM. Multiple-adjusted odds ratios of T2DM for tertile 1, 2, and 3 of HOMA-β were 1.00 (reference), 0.25 (95% CI, 0.11-0.57), and 0.14 (0.05-0.37), respectively; those of IGI were 1.00, 0.35 (0.17-0.75), and 0.19 (0.07-0.47), respectively; and those of late phase β-cell activity were 1.00, 0.34 (0.14-0.82), and 0.16 (0.05-0.53), respectively, in the model that included HOMA-β, IGI, late phase β-cell activity, Matsuda index, age, BMI, sex, and family history of T2DM.
In conclusion, higher β-cell activity while fasting and in both the early and late phase during an OGTT were all independently associated with a lower risk of T2DM.

Disclosure
T. Shimojo: None. C. Izumi: None. K.K. Sato: None. D.L. Leonetti: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. W.Y. Fujimoto: None. E.J. Boyko: None. T. Hayashi: None.
2281-PUB: Family Impact Module in NYC: Diabetes vs. Community Sample
Authors: ILKOWITZ JENIECE , ZELENIUCH-JACQUOTTE ANNE , LOIS BECKY , PREZIOSO PAULA J. , GALLAGHER MARY PAT 
Published: June 2019

Introduction: We previously reported parents of a child with diabetes (CWD) score poorly on the Pediatric Quality of Life (QoL) Family Impact Module (FIM). Use of the FIM in parents of a CWD is limited and comparison to a control group in or similar to NYC has not been explored. The objective of this study is to compare FIM scores between a PCP office and a diabetes center in NYC.
Method: Parents of children at a diabetes and PCP office in NYC completed the FIM and Holmes and Rahe Stress Scale (HRSS) to assess stressful events.
Results: Parents of 66 CWD (47% Male) and 97 of a child without (45% Male) (controls) enrolled. Compared to controls, CWD were older (median 13.7 vs. 8.3 years; p&lt;0.0001), included more white subjects (86 vs. 63%; p&lt;0.0001) and scored higher on HRSS (median 128.5 vs. 68; p&lt;0.001). Adjusting for age, sex, race, and HRSS, difference in total FIM scores between groups was statistically significant (p=0.002) with higher impact on the CWD group. Statistically significant differences were found in total Parent Health Related QoL (PHRQoL) (p=0.003), physical function (p=0.0009), cognitive function (p&lt;0.0001), communication (p=0.0003), worry (p&lt;0.0001), and daily activity (p=0.04). None were found in total Family Function, emotional or social function, and family relations.
Conclusion: Results show NYC parents of a CWD have higher levels of family impact compared to a community sample. They have worse PHRQoL stress, worry, cognitive and physical function, communication, and daily activity. It is unknown why there is no difference between the groups in all subscales. Previously we reported having a CWD has impact on, communication if CWD is male, worry if multiple CWD, and cognitive function if additional illness. HbA1c, age, and disease duration were not predictors. It should be noted, families from a diabetes clinic are given support which may buffer stress and being in NYC may increase stress regardless. Future study must recruit a larger sample, create normative data, and explore other illnesses.

Disclosure
J. Ilkowitz: None. A. Zeleniuch-Jacquotte: None. B. Lois: None. P.J. Prezioso: None. M. Gallagher: Consultant; Self; Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc.
229-OR: GLP-1 Infusions during Postprandial Insulin Clamps Enhance Muscle Microvascular Flow, Glucose Uptake, and Protein Anabolism in Older Men
Authors: ABDULLA HAITHAM , PHILLIPS BETHAN E. , LIMB MARIE C. , WILKINSON DANIEL J. , JANDOVA TEREZA , CEGIELSKI JESSICA , BASS JOSEPH J. , RANKIN DEBBIE , LEWIS JONATHAN S. , WILLIAMS JOHN , SMITH KEN , IDRIS ISKANDAR RAUF , ATHERTON PHILIP J. 
Published: June 2019

Introduction: Ageing skeletal muscle becomes insulin resistant and atrophic. This is largely due to a failure in sequestering of amino acids and glucose from dietary intake into muscle protein and glycogen. GLP-1 possesses pleiotropic multi-organ properties and its receptor is expressed and exert effects in muscle tissue(s) e.g., endothelium. We hypothesized GLP-1 infusion would enhance muscle glucose uptake and bolster the trophic effects of an anabolic stimulus i.e., feeding.
Methods: Eight men (71±1y) were studied in a cross-over trial. Basal measures were taken (first 3 h) prior to insulin (i.e., postprandial (fed-state)) and glucose (euglycaemic) clamps. Participants received I.V co-infusions of octreotide, Vamin 14-EF ±GLP-1. Four muscle biopsies were taken at 90-120 min intervals. Muscle protein turnover was quantified via A-V balance and direct incorporation of 13C6 phenylalanine via mass spectrometric techniques. GLP-1 and insulin were measured using Milliplex Map, ELISA kits. Muscle microvascular blood flow (MBF) was assessed via contrast enhanced ultrasound. Glucose handling was assayed by infusion rates and leg A-V balance.
Results: GLP-1 (vs. -GLP-1 condition) augmented muscle protein synthesis (basal: 0.058±0.004%.h-1 vs. fed: 0.102±0.005%.h-1, p&lt;0.01), net protein balance (p&lt;0.0001 and p=0.03 vs. basal at 1.5h and 3h postprandial, respectively) and MBF (5±2 vs. 1.9±0.7 fold-change from basal respectively, p&lt;0.01) - while increasing whole-body glucose uptake (AUC 17.0±1.7 vs. 11.4±1.8 mg.kg-1.180 min-1, p=0.02 with and without GLP, respectively). Muscle protein breakdown was equally suppressed with and without GLP-1. Leg glucose uptake was unchanged by GLP-1.
Conclusions: The beneficial effects of GLP-1 upon whole-body glycaemic control are seemingly independent of muscle under fed-conditions. The pro-anabolic effect of GLP-1 in ageing is striking and requires further clinical and mechanistic research.

Disclosure
H. Abdulla: None. B.E. Phillips: None. M.C. Limb: None. D.J. Wilkinson: None. T. Jandova: None. J. Cegielski: None. J.J. Bass: None. D. Rankin: None. J.S. Lewis: None. J. Williams: None. K. Smith: None. I.R. Idris: None. P.J. Atherton: None.

Funding
Medical Research Council UK; Arthritis Research UK
2295-PUB: Novel Use of Continuous Glucose Monitoring in Transitioning a Patient with Suspected Monogenic Diabetes from Insulin to Oral Antidiabetic Agent
Authors: NAJERA OMAR , WISSE BRENT E. , TRENCE DACE 
Published: June 2019

37-year-old Hispanic female with diagnosis of T1DM at age 18, uncontrolled on MDI with complications of mild non-proliferative diabetic retinopathy and CKD V presented giving additional history of a son just diagnosed with MODY 3. Multiple other family members were reported as having diabetes- diagnosed as both type 1 and type 2. Patient’s GAD 65 antibodies previously checked were negative. A sulfonylurea challenge test was performed. Baseline labs obtained included insulin 18.7 u(IU)/dL, C-peptide 1.9 ng/dL, glucose of 98 ml/dL. Patient was then advised to hold her morning insulin doses. One and a half hours after receiving glipizide and ingesting a meal, insulin level was 18.7 u(IU)/dL, C-peptide 10.3 ng/dL, glucose 141 ml/dL. MODY 3 was strongly suspected and decision made to transition from insulin to sulfonylurea. Given her advanced renal disease, there was significant concern with the potential of hypoglycemia despite cautious initiation of low dose glipizide. A continuous glucose monitoring system- the Freestyle Libre- was procured to allow for the close monitoring of glucose trends, to both guide ability to reduce insulin doses, as well as to judge sulfonylurea dosing in the setting of significant renal disease. The patient was able to decrease insulin doses and transition to sulfonylurea without hypoglycemia. MODY 3 is a form of monogoneic diabetes, and is a rare form of diabetes that should be suspected in patients diagnosed with diabetes mellitus in their early years along with a strong family history and negative GAD65 antibodies. Although not traditionally described in Hispanic populations, MODY3 has been reported in various minority populations. Continuous glucose monitoring should be considered in MODY 3, to aid in the safety of transitioning patients from multiple dose insulin regimens to sulfonylurea therapy, especially in the setting of severe renal disease.

Disclosure
O. Najera: None. B.E. Wisse: None. D. Trence: Stock/Shareholder; Self; Medtronic, Sanofi-Aventis.
2307-PUB: VN-B101: A New, Promising Drug Candidate for the Treatment of Diabetes
Authors: CHEN HUI-LING , WANG PEI-RAN 
Published: June 2019

HC-N2, an active ingredient from ethanol extracts of a Chinese herbal medicine Hedychium coronarium Koenig (Zingiberaceae), has demonstrated excellent efficacy and safety profiles in diabetic animal models. Four weeks treatment with HC-N2 at 60 mg/kg significantly reduced fasting blood glucose and OGTT incremental glucose AUC by 43% (p&lt;0.01) and 62% (p&lt;0.001); respectively. In addition, preclinical repeat-dose toxicity study in rat and in dog both revealed NOAEL to be 972 mg/kg/day which provided a safety margin of 10 folds over the maximal recommended starting dose in phase 1 clinical study.
VN-B101, a 500 mg tablet contains 165mg active ingredient HC-N2 with 335 mg of inactive excipients, would be used in the clinical trials. The clinical study protocol of VN-B101 tablet received the IND approval from USFDA and TFDA in 2012 and 2016; respectively.
One of the major objectives of this study was to evaluate effects of VN-B101 as an adjuvant to metformin (MET) in patients with uncontrolled type 2 diabetes mellitus (T2DM). This trial was a single center, open-label, phase-I study (NCT03033433) consisting of two stages: Stage 1 was a dose-escalation study to assess the safety and tolerability profile of three escalating doses of VN-B101 (1, 2, and 4 tablets; qd; for 7 days) in healthy subjects, while Stage 2 applied VN-B101 as add-on treatment to MET in T2DM. There was no AEs or SAE found in stage 1 and stage 2 subjects. In addition, the combination treatment significantly reduced OGTT incremental glucose AUC by additional 35% (p&lt;0.05) compared to MET monotherapy.
In summary, VN-B101 as add-on therapy to MET is safe and efficacious in T2DM inadequately controlled by MET alone. The inspiring study results encourage further clinical studies to be conducted.

Disclosure
H. Chen: None. P. Wang: None.
2308-PUB: Liraglutide 3 mg for Weight Loss in a Real-World Setting: Clinical Outcomes after 56 Weeks
Authors: BUCKLEY ADAM J. , SULIMAN MOHAMED , TIKRITI ALIA AL , LESSAN NADER , ROUX CAREL LE , TAN TRICIA M. , BARAKAT MAHA T. 
Published: June 2019

Background: Liraglutide 3 mg was approved in the UAE for the treatment of obesity in residents with BMI &gt;30 kg/m2 or BMI &gt;27 kg/m2 with obesity-related complications and clinical use started in January 2017 at the Imperial College London Diabetes Centre (ICLDC). The proportions of participants achieving weight loss of ≥5%, ≥10% and ≥15% at 16 weeks were 60%, 23% and 6%.
Methods: Retrospective review of clinical data from a cohort of patients treated at ICLDC in Abu Dhabi and Al Ain, UAE. Inclusion criteria were treatment with Liraglutide 3 mg for weight loss and follow-up of ≥ 56 weeks (4 weeks dose escalation plus 52 weeks treatment). 93% of participants were Emirati.
Results: 322 individuals were included. Median follow-up was 485 (433-551) days and treatment was stopped in 75 individuals before end of follow-up. 91 received treatment ≥ 365 days, and 27 had no gaps in treatment &gt; 30 days during follow-up, with a median of 265 (151-381) days of treatment. Eight participants had T2DM and 190 had IFG or IGT. 28 had prior history of bariatric surgery (18 sleeve, 8 RYGB, 2 other). Intentional to treat analysis suggested that after a year, ≥ 5% weight loss was achieved in 51%, ≥ 10% in 25% and ≥ 15% in 9%. Per protocol analysis suggested completing 1 year of treatment resulted in ≥ 5% in 83.5%, ≥ 10% in 52.7% and ≥ 15% in 22.2% of patients.
Conclusion: Weight loss continued between 16 and 56 weeks, but gaps in treatment may have impaired effectiveness.

Disclosure
A.J. Buckley: None. M. Suliman: None. A. Al Tikriti: None. N. Lessan: None. C. le Roux: Advisory Panel; Self; GI Dynamics, Inc., Herbalife International of America, Inc., Janssen Pharmaceuticals, Inc., Johnson & Johnson, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp. T.M. Tan: Other Relationship; Self; Novo Nordisk A/S. M.T. Barakat: None.
2309-PUB: The Effect of Linagliptin on the Microbiome of Diabetic ZDF Rats
Authors: SAYOLS SERGI , SIMON ERIC , KLEIN HOLGER , LEPARC GERMAN G. , MARK MICHAEL , LUIPPOLD GERD , KLEIN THOMAS 
Published: June 2019

Recent data suggest that the individual microbiome influences the pathology of type 2 diabetes (T2D). Linagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor used for the treatment of T2D, which is excreted mainly via the bile. We investigated the microbiome of diabetic ZDF vs. normal rats and the effect of linagliptin on the gut bacterial composition over time.
Diabetic ZDF and normal rats (two groups each, of six biological replicates) were treated with linagliptin 7.2 mg/kg qd or vehicle, in 5 ml/kg Natrosol 0.5%; faeces were collected at days 0, 3 and 7. The sequencing of microbial 16S rRNA amplicons was performed at CeMeT GmbH in Tübingen, to produce between 50000 and 75000 raw reads per library, at a read length of 2x250 bp. Preprocessing, import QC and quantification of reads assigned to specific operational taxonomic units (OTUs) were carried out using the MEGAN 6 toolbox. Between 14 k and 37 k raw reads were assigned to different bacterial phyla. We then used the Phyloseq package coupled with DESeq2 to determine significant changes in the abundance of OTUs between diabetic ZDF and normal animals, and changes over time in animals treated with linagliptin vs. vehicle.
Between 20 and 27 OTUs (quantified at family level) significantly changed in untreated diabetic vs. healthy rats, in agreement with previously published studies. However, we found only weak to moderate changes in the linagliptin treated vs. untreated ZDF rats (i.e., 3 different bacterial families with significant changes in abundance after 7 days). No systematic changes in the biodiversity of the gut phyla could be attributed to linagliptin.
This study provides new knowledge on how linagliptin affects the microbiome of diabetic ZDF vs. healthy rats. Some of the changes attributable to linagliptin agree with published studies on the beneficial effect of probiotics in diabetes. However, the observed changes in the microbiota after a short treatment with linagliptin are rather weak compared with the important differences seen in diabetic vs. nondiabetic animals.

Disclosure
S. Sayols: Employee; Self; Boehringer Ingelheim International GmbH. E. Simon: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. H. Klein: Employee; Self; Boehringer Ingelheim International GmbH. G.G. Leparc: Employee; Self; Boehringer Ingelheim International GmbH. M. Mark: Employee; Self; Boehringer Ingelheim International GmbH. G. Luippold: Employee; Self; Boehringer Ingelheim International GmbH. T. Klein: Employee; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH.

Funding
Boehringer Ingelheim; Eli Lilly and Company