bluuebunny/crossref_metadata_2025 huggingface dataset:
90-OR: High-Fat Diet Acutely Decreases Adipose Immunosuppressive T Regulatory Cells Leading to Insulin Resistance
Authors: BRADLEY DAVID , BLASZCZAK ALECIA M. , JALILVAND ANAHITA D. , WRIGHT VALERIE P. , NORIA SABRENA , JOSEPH JOSHUA , LIU JOEY Z. , HSUEH WILLA
Published: June 2019

Adipose resident T lymphocytes (ARTs) are known metabolic mediators in mice. In particular, immunosuppressive regulatory T cells (Tregs) protect against insulin resistance. However, little is known about ARTs in humans or the effect of human weight gain on the AT immunoenvironment. We obtained visceral AT (VAT) and subcutaneous AT (SAT) biopsies from obese (n=83, BMI 48.9±8.5 kg/m2) and lean (n=15, BMI 23.6±1.9 kg/m2) patients undergoing elective surgery. A separate group of lean metabolically healthy patients (n=15, BMI 22.4 ± 1.8 kg/m2) underwent baseline and repeat SAT biopsies and hyperinsulinemic clamps before and after 2 weeks of a high-fat diet (HFD) overfeeding protocol (additional 1,320 kcal/day:>50% total fat:>10% saturated fat). Adipocytes were isolated for gene expression and flow analysis. Tregs (CD4+CD25+FOXP3+) as percent (%) of CD4+ cells were substantially increased in lean compared to obese SAT (22.1±15.0% vs. 7.3±3.8%; p<0.001) and VAT (18.9±16.8% vs. 3.9±2.7%; p<0.001) and negatively correlated with BMI and insulin sensitivity. After HFD, there was a significant increase in BMI (p<0.001) and fasting glucose (p<0.001), but no change in fasting insulin or HOMA-IR. We noted a dramatic overall decline in SAT Tregs after HFD (7.5 ± 1.0% to 3.3 ± 0.5%, p<0.001), with all participants experiencing a decrease. The post-surgical change in SAT %Tregs positively correlated with the change in insulin sensitivity (M value) by hyperinsulinemic-euglycemic clamp (p=0.003, r=+0.797), so that those subjects with the greatest decline in Tregs had the largest decline in insulin sensitivity. This relationship persisted despite adjusting for, age, gender, pre-intervention BMI, and the change in weight from pre to post intervention (p=0.012). Our data thus demonstrates that Tregs decline in response to acute overfeeding, potentially contributing to development of insulin resistance. These results highlight a role for adipose tissue Tregs in human metabolism.

Disclosure

D. Bradley: None. A.M. Blaszczak: None. A.D. Jalilvand: None. V.P. Wright: None. S. Noria: None. J. Joseph: None. J.Z. Liu: None. W. Hsueh: None.

Funding

American Diabetes Association (1-16-ICTS-049 to W.H.); National Institutes of Health (KL2TR001068, HL135622)
901-P: Effects of Dapagliflozin, Metformin, or Exercise on Glycaemic Variability and Mean Glucose Levels in Prediabetes: The PRE-D Trial
Authors: FÆRCH KRISTINE , VISTISEN DORTE , BLOND MARTIN B. , NIELSEN LEA BRUHN , AMADID HANAN , DEJGAARD THOMAS F. , RIED-LARSEN MATHIAS , KARSTOFT KRISTIAN , PERSSON FREDERIK , JØRGENSEN MARIT E.
Published: June 2019

Introduction: We assessed the efficacy of three glucose-lowering interventions in persons with HbA1c-defined prediabetes.

Methods: 120 participants were randomised 1:1:1:1 to 13 weeks of 1) dapagliflozin (DAP, 10 m/day); 2) metformin (MET, 1700 mg/day); 3) exercise (EXE, 5 x 30 min/week); or 4) control (CON, no treatment). Continuous glucose monitor (CGM) was used for 6 days before, during (6 weeks) and after (13 weeks) the intervention. Treatments were stopped the day before the last visit (two days before in EXE). Primary outcome was 13-week change in mean amplitude of glycaemic excursions (MAGE). Intention-to-treat analysis was conducted.

Results: At baseline, median (Q1;Q3) HbA1c was 5.9 (5.7;6.1)%; BMI 30.8 (28.6;34.3) kg/m2; age 62 (54;68) years; 44% were men. No within- or between-group changes were observed for MAGE. Mean CGM glucose (MG) was slightly reduced in MET and DAP at 6 weeks (Table 1). The 6-week change in MG in DAP was different from that in CON (mean diff. (95% CI): -0.3 mM (-0.5;0.0), P=0.031). At 13 weeks, MG had increased in MET and CON, and the change in MET was different from those in EXE (0.2 mM (0.0;0.5), P=0.041) and DAP (0.2 mM (0.0;0.5), P=0.039).

Conclusion: 13 weeks of treatment with MET, DAP or EXE did not change MAGE. Treatment with DAP or MET for 6 weeks slightly reduced MG; these improvements disappeared immediately after treatments were stopped at 13 weeks.

Disclosure

K. Færch: Research Support; Self; Ascensia Diabetes Care, AstraZeneca, Unilever. Stock/Shareholder; Self; Novo Nordisk A/S. D. Vistisen: Stock/Shareholder; Self; Novo Nordisk A/S. M.B. Blond: None. L.B. Nielsen: None. H. Amadid: None. T.F. Dejgaard: Consultant; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; Boehringer Ingelheim International GmbH. M. Ried-Larsen: Other Relationship; Self; Novo Nordisk A/S. K. Karstoft: Employee; Self; Novo Nordisk A/S. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. M.E. Jørgensen: Research Support; Self; Amgen Inc., AstraZeneca, Danish Diabetes Association, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.

Funding

Novo Nordisk Foundation; AstraZeneca
909-P: Real-World Assessment of Connected Remote Continuous Glucose Monitoring Combined with Tele-consultations in a Pediatric Type 1 Diabetes Population
Authors: GIES INGE , VERMEULEN BRECHT
Published: June 2019

Objectives: To study effectiveness and predictors of tele-monitoring on metabolic outcome of T1DM CGM treated children in real world.

Methods: CGM data of 47 T1DM patients (3-18 years) were studied during two years (October 2016 - September 2018): 6 months without bi-weekly tele-consultations (T0), 6 months with connected CGM and tele-consultations (T1-2), 6 months washout period and 6 months without tele-consultations (T3). HbA1C, time-in-hypo, and days-in-hospital were measured. Relationship between metabolic outcome and age, gender, baseline HbA1C, insulin regimen (pen vs. pump), puberty and compliance towards the tele-consultations, was studied.

Results: 2.836.322 CGM values (16.479 total days) were analysed. Baseline HbA1C (±SD) for the total group was 7.7±1% and did not change significantly; time-in-hypo decreased from 8±5% (T0) to 5±3% (T2) (p=0.002) and increased to 6±4% (T3) (p=0.143). HbA1C of patients with HbA1C > 7.5% at T0 decreased significantly from 8.3±0.6% to 8±0.7% at T1 (p=0.024), to 8.1±1% at T2 (p=0.176) and stabilized at 8.1±1 at T3 (p=0.742). During 6 months of tele-monitoring, 352 therapy adjustments were proposed during 585 tele-consultations. In compliant patients (n=8) with baseline HbA1C >7.5%, HbA1C changed from 8.1±0.5% (T0) to 7.6±0.4% (T1) (p=0.029), to 7.3±0.3% (T2) (p=0.001), and to 7.9±0.9% at T3 (p=0.035) while time in hypo was on average 6% and 7% before and after the tele-consultations and 4% during tele-consultations. Time-in-range with this group improved by 6% during 6 months of tele-consultations, and number of serious hypos decreased from 9 (T0) to 1 (T2) and 1 (T3); days-in-hospital from 7 (T0) to 0 (T2). No effect of age, gender, insulin regimen or puberty was found on HbA1C or time-in-hypo.

Conclusions: A benefit of tele-consultations in pediatric CGM patients was seen only in compliant patients with HbA1C > 7.5%. Targeted use of tele-consultations can increase CGM benefits.

Disclosure

I. Gies: None. B. Vermeulen: None.

Funding

Belgian National Institute for Health and Disability Insurance
914-P: Connected Glucose Meter plus CDE Coaching Improves Diabetes Patient Empowerment and Distress in Real-World Outcomes Setting
Authors: BOLLYKY JENNIFER , LU WEI , PAINTER STEFANIE L. , POON JIAT LING , PEREZ-NIEVES MAGALY
Published: June 2019

Background: Diabetes-related distress contributes to poor self-management and glycemic control over time. Empowering diabetes patients with health literacy and self-management skills improves self-management behaviors. The Livongo Diabetes Program offers a cellular-enabled, two-way messaging device that measures blood glucose, free unlimited blood glucose test strips; and access to CDE for real-time support and goal setting. We investigated the impact of the Livongo program on diabetes distress and empowerment over 12 months and characterized members with improved responses.

Methods: The Diabetes Distress Survey (DDS2) and Diabetes Empowerment Survey (DES-SF) were administered to 957 Livongo members via email at baseline and month 12. Demographic, clinical and medical spending characteristics of Responders (with improved DDS2 and DES-SF scores or high levels of empowerment and low levels of distress), were compared to Non-responders using student t-tests and Chi-square. Patient characteristics predicting Responder status were determined using logistic regression.

Results: Mean DES-SF improved from 3.9 (pre) to 4.3 (post) (p<0.001). Mean DDS2 improved from 2.4 to 2.2 (p<0.001). Sixty-one percent of members had an improvement in both DDS2 and DES-SF and 94% had improved scores in at least one. A greater proportion of Responders used oral medications only (64% vs. 55%, p=0.01) and had increased number of days with program activities (54% vs. 50%, p=0.02), while a smaller proportion had BG>180 mg/dL (66% vs. 87%, p=0.04). Responders also had lower mean BG (139 vs. 147 mg/dL, p<0.001). Upon multivariable adjustment, Responders were less likely to be Asian, more likely to be younger, have a lower BMI and diabetes duration of 5-10 years. Medical spending was not significantly different between the groups.

Conclusions: Significant improvements in both diabetes distress and empowerment were experienced by members of the Livongo program over 12 months.

Disclosure

J. Bollyky: Employee; Self; Livongo Health. Stock/Shareholder; Self; Livongo Health. W. Lu: None. S.L. Painter: Employee; Self; Livongo Health. J. Poon: Employee; Self; Eli Lilly and Company. M. Perez-Nieves: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.
92-LB: Real-World, Chart Review Study to Determine the Effectiveness of FreeStyle Libre Flash Glucose Monitoring System, in Adults with Type 2 Diabetes in France
Authors: HANAIRE HELENE , BENHAMOU PIERRE Y. , BURES CLEMENCE , FAVRE SANDRINE , FENDRI SALHA , JOUBERT MICHAEL
Published: June 2019

This retrospective, real-world, chart review study determined the effectiveness of the FreeStyle Libre Flash Glucose Monitoring SystemTM on HbA1c when used by adults with type 2 diabetes (T2DM) as their standard of care in a real-world setting for between 3 months to 6 months. The study population included adults on a basal-bolus insulin regimen for at least 1 year, with HbA1c between 8.0 and 12.0% (64 to 108 mmol/mol), who had been prescribed and using FreeStyle Libre regularly for at least 3 months. Pregnant patients were excluded, as were patients on dialysis. A total of 88 records from insulin using patients with T2DM from 6 hospital sites in France were included in this chart review. On average, HbA1c was 9.0±0.9% (74.7±9.7 mmol/mol), prior to FreeStyle Libre use, age was 64.4±10.6 years, BMI was 32.9±5.5 kg/m2 and average duration of insulin use 9.9±6.4 years (mean±SD), 24.1% were CSII users, 58.0% of patients were on oral antidiabetic medications (metformin, SU or DPP-4) in addition to basal-bolus and 56.8% were male. CVD, renal and retinopathy complications were reported by 40.9%, 37.5% and 37.5% of patients, respectively. HbA1c results were recorded between 91 to 183 days from the start of use of FreeStyle Libre, between May 2017 and July 2018. To minimise selection bias records were selected on a systematic basis. After at least 3 months of using FreeStyle Libre, HbA1c (primary outcome) was significantly reduced by 0.8±1.1% (mean±SD); p<0.0001. Sub-group analysis by insulin administration method showed HbA1c significantly reduced for both people using multiple daily injections and CSII; with reductions of 0.7±1.1%, p<0.0001 and 1.0±1.0% (mean±SD), p=0.0001, respectively. This real-world, chart review study concluded that people with T2DM on insulin therapy, using FreeStyle Libre for between 3 to 6 months significantly reduced HbA1c.

Disclosure

H. Hanaire: Research Support; Self; Abbott, Eli Lilly and Company, LifeScan, Inc., Novo Nordisk A/S. Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S. P.Y. Benhamou: Board Member; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi. Consultant; Self; Abbott. C. Bures: Employee; Self; Abbott Laboratories. Employee; Spouse/Partner; Alere Inc. S. Favre: None. S. Fendri: None. M. Joubert: Board Member; Self; Abbott, Air Liquide, AstraZeneca, Lilly Diabetes, Medtronic, Novo Nordisk A/S. Consultant; Self; Voluntis France. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Amgen Inc., LifeScan, Inc., Merck Sharp & Dohme Corp., Sanofi.
942-P: Caregivers of Children with Type 1 Diabetes Value Real-Time Functions of Continuous Glucose Monitoring
Authors: WONG JENISE C. , ABDULHUSSEIN FATEMA , YEUNG BRITTANY J. , VELAZQUEZ EDGAR J.
Published: June 2019

Continuous glucose monitoring (CGM) improves glycemic outcomes in children with type 1 diabetes (T1D) and is recommended for regular use. However, it is unclear how families use CGM and if they are using it to its greatest potential. In this study, 193 caregivers of children with T1D using CGM (mean age 9.3±2.8 years, 44% female, 10% ethnic minority, 92% using insulin pump) were recruited throughout the United States by social media to complete a cross-sectional survey about their real-time CGM use. Many children (70%) wore the sensor “all of the time,” with 77% using CGM ≥22 of the last 30 days. Most caregivers (93%) had a CGM feature to see their child’s data remotely in real time; 87% of those who used this feature viewed their child’s data at least once a day when their child was not with them. Though nearly all knew about CGM alert functions, only 73% set alerts for hyperglycemia and 80% for hypoglycemia “all the time.” Frequent retrospective review of CGM data was less common, with only 64% uploading and reviewing data at least monthly. Since starting CGM, most caregivers reported a decrease in their child’s glycated hemoglobin (A1c) (64%) and reduced frequency and severity of hypoglycemia (78%) and hyperglycemia (72%). In regression analysis (adjusted for age, duration of T1D, gender, minority status, caregiver education, geographic region, and pump use), younger age was associated with decrease in A1c (OR 0.78, 95% CI 0.67, 0.92) and decrease in hyperglycemia (OR 0.70, 95% CI 0.58, 0.84). Longer duration of CGM use was associated with decrease in hypoglycemia (OR 2.0, 95% CI 1.0, 4.1). Seventy-two percent reported CGM is “essential,” and 53% felt the greatest benefit is seeing data in real time.

In summary, caregivers utilize real-time CGM functions (remote monitoring, alerts) more frequently than they retrospectively review data. Future studies should focus on how caregivers use real-time and retrospective CGM data to make T1D management decisions in order to optimize use of the technology.

Disclosure

J.C. Wong: Advisory Panel; Self; Tidepool Project. Research Support; Self; Dexcom, Inc. F. Abdulhussein: None. B.J. Yeung: None. E.J. Velazquez: None.

Funding

Dexcom, Inc.
945-P: The Characteristics of Patients with Intermittent Large Positive Spikes in the Morning Fasting Glucose (FG), “Hyper-Spikers”
Authors: KING ALLEN B.
Published: June 2019

Basal insulin is titrated upward whenever the average of several days’ FG exceeds a goal. It is assumed that averaging better reflects the ‘true’ FG (Central Limit Theorem) but this is true only if they are normatively distributed. There are a large subgroup of patients with diabetes in which their day-to-day FG variation is not normative but characterized by intermittent large positive spikes, the “Hyper-Spikers,” and large coefficient of variability (CV). We report their prevalence and characteristics in a large clinical practice. From 2000+ clinic charts, the data from 200 charts were consecutively selected if the patients had T2DM and were on basal insulin ± non-insulin but no bolus insulin. Only those with ≥ 3 consecutive daily FG readings were selected. CV = (SD/mean)*100. Hyper-Spikers were arbitrarily defined as a day to day FG CV ≥ 20%. CV distribution of the FG sets for all patients was not normative distributed but positive skewed with a mean CV of 17.8% and median, 15.9%. CV sets were divided into those ≤ 10% (LoVar) vs. those, ≥20% (Hyper-Spikers), 29 and 32% of patients, respectively. Age, gender, DM duration and weight were not different between groups (p > 0.20). The mean basal doses were 23.1 vs. 30.0 U/d (p=0.0157) and 0.247 vs. 0.327 U/kg (p=0.00153) yet the A1c was higher, 8.06 vs. 8.47% (p = 0.0951) in Hyper-Spikers. The correlation coefficient of all individual’s CV at baseline vs. a mean follow-up of 4.1 m was 0.197 (p = 0.0166). From these observations, the Hyper-Spikers are not significantly different in age, gender, diabetes duration and weight from LoVar. The Hyper-Spikers were treated to a significantly higher basal insulin dose yet had a more elevated A1c. We conclude that the traditional method of averaging FGs to determine dosage increase is misleading in a significant (1/3) portion of patients and may lead to excessive basal insulin. We recommend that Hyper-Spikers be identified and the cause of the spikes determined before the dosage is increased.

Disclosure

A.B. King: None.
95-LB: Utility of Continuous Glucose Monitoring in Pediatric Diabetic Ketoacidosis
Authors: POTT THOMAS R. , JIMENEZ VEGA JOSE M. , PARKER JESSICA L. , FITZGERALD ROBERT
Published: June 2019

Continuous glucose monitoring (CGM) commonly used in the outpatient setting is yet to be implemented in the pediatric intensive care unit (PICU) setting. The purpose of this study was to evaluate the feasibility, reliability and accuracy of the system in pediatric patients with DKA.

Objective: Determine the accuracy of CGM Dexcom G6™ in the setting of pediatric DKA compared to point of care capillary (POC) and serum glucose testing. Secondly, determine if the degree of acidosis impacts CGM when compared to POC and serum glucose testing.

Methods: Single institution IRB approved prospective trial. PICU patients that met inclusion criteria receiving standard DKA therapy were enrolled. CGM Dexcom G6™ sensors was applied to the patient’s abdomen on admission. Hourly POC and every 6 hour serum basic metabolic panels were obtained. CGM data was obtained every 5 minutes and matched to the nearest POC capillary and serum glucose levels ± 3 minutes. Reliability and feasibility analysis included frequency of data display, data gaps and any reasons for sensor removal.

Results: 35 pediatric patients, 11.9 ± 4.1 years old were enrolled. 51.4% were known diabetics and were older compared to the new onset diabetics, mean age 13.9 vs. 9.7 years respectively (p= 0.001). Clark Error grid of serum glucose versus CGM reveals 95.6% of readings within zones A and B, the Clark Error grid for POC versus CGM reveals 95.4% of readings within A and B zones. There was a negative correlation (-0.27) between the serum glucose and CGM delta when compared to serum bicarbonate level (p=0.007), while a positive correlation (0.24) between the POC and CGM delta when compared to serum bicarbonate level (p = 0.056). There were no sensors removed or adverse events that occurred during the study.

Conclusion: CGM use in patients with DKA seems both feasible and accurate. Serum bicarbonate level does not appear to impact the accuracy of CGM in the setting of DKA. Further studies examining the use and cost effectiveness of CGM in treatment decisions in DKA are warranted.

Disclosure

T.R. Pott: None. J.M. Jimenez Vega: Consultant; Self; Dexcom, Inc. J.L. Parker: None. R. Fitzgerald: None.
960-P: Personalized Diabetes Management Using Data from Continuous Glucose Monitors
Authors: MILLER DANIEL R. , WARD ANDREW T. , MAAHS DAVID M. , SCHEINKER DAVID
Published: June 2019

Expansion of continuous glucose monitor (CGM) use in type 1 diabetes (T1D) patients has not fully translated into personalized, timely glucose management. We propose a standardized approach based on individual CGM data to set patient-specific disease-management targets and monitor progress. We developed tools to measure daily mean glucose (MG), time-in-range between 70-180 mg/dL (TIR), and glucose variability (GV); set patient-specific targets for these metrics; and detect deviation from these targets. We simulate the proposed approach on 2,668,063 hours of CGM data from 299 T1D patients.

To simulate a patient’s clinic visit after CGM use, their first 90 days of CGM data were used to generate personalized targets. To simulate patient disease management post-visit, the subsequent 14 days of data were used to generate alerts on each day which deviated from their target. The number of daily alerts for static targets (>65% TIR) vs. personalized targets (at least 5% improvement over the preceding 90-day average TIR) were compared.

The evaluation included all 248 patients with at least 104 days of data. Patient-specific personalized glucose targets varied significantly. Of these 248 patients, 150 had a historical mean TIR higher than the static target of 65%. For the 98 patients with TIR <65%, the number of alerts for deviations from target TIR were fewer for personalized than for static targets (7.14 vs. 8.42 during the 14-day window.

Personalized glucose targets based on each patient’s CGM history offer several advantages over static targets set without knowledge of the patient history. Personalized targets may be more achievable; for patients with high TIR targets to maintain performance may be more appropriate than lower static targets; and personalized targets may be set to produce fewer unnecessary alarms. Automated analyses of CGM data may empower care teams to support personalized, timely disease management.

Disclosure

D.R. Miller: None. A.T. Ward: None. D.M. Maahs: Advisory Panel; Self; Novo Nordisk Inc. Consultant; Self; Abbott, Sanofi. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. D. Scheinker: Advisory Panel; Self; Carta Healthcare.
964-P: CGM-Tele Monitoring in Older Adults with T1D: Results of a Pilot Study
Authors: HARMEL MARK D. , RUELAS VALERIE F. , NYKAZA EDWARD T. , PETERS ANNE L.
Published: June 2019

T1D management in older individuals can be difficult due to an increased risk for hypoglycemia and other co-morbidities. CGM can help lower rates of hypoglycemia; however, in practice, patient data is only reviewed at clinic visits, rather than in near real-time by the diabetes care team. This pilot study tested if patients could be remotely monitored daily through a CGM system (Dexcom G5/6) that communicated via smart phone to a Tidepool designed dashboard. Alerts were set for: ≥4 hours without CGM signal, ≥2 hours 54-70 mg/dl, and 15 mins <54 mg/dl. If alerts occurred, the CDE performed telemedicine outreach following a protocol. Ten individuals with T1D ≥65 years were enrolled. Patients were 72+5.3 years; duration of diabetes 39.1+16.5 years; 50% were on CSII. At baseline, the CGM was connected to the monitoring system, followed by 2 weeks of system checks. Remote monitoring was activated at week 2 continuing to week 14. Three patients didn’t complete the study. One had connection issues, one didn't want to wear the CGM; the third had spousal health issues. The CDE/system was capable of identifying the desired findings (Table). An A1C was measured at baseline and 14 weeks. The A1C didn’t change, 7.2% +0.95 vs. 7.3% +0.99. This trial proved it was possible to monitor well-controlled seniors with T1D using an automated system with daily alerts to identify episodes of hypoglycemia and time off CGM. Further research is needed to assess the alert system efficacy.

Disclosure

M.D. Harmel: Advisory Panel; Spouse/Partner; Abbott, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., MannKind Corporation, Merck & Co., Inc., Novo Nordisk Inc., Omada Health, Inc., OptumRx, Inc., Sanofi, Zafgen, Inc. Consultant; Self; MannKind Corporation. Research Support; Spouse/Partner; AstraZeneca, Dexcom, Inc., MannKind Corporation. Speaker's Bureau; Spouse/Partner; Novo Nordisk Inc. V.F. Ruelas: None. E.T. Nykaza: None. A.L. Peters: Advisory Panel; Self; Abbott, Becton, Dickinson and Company, Bigfoot Biomedical, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Livongo Health, MannKind Corporation, Medscape, Merck & Co., Inc., Omada Health, Inc., OptumRx, Inc., Sanofi US, Zafgen, Inc. Research Support; Self; AstraZeneca, Dexcom, Inc., Jaeb Center for Health Research, MannKind Corporation, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc.
97-OR: Leptin's Hunger-Suppressing Effects Are Mediated by the Hypothalamic-Pituitary-Adrenocortical Axis
Authors: PERRY RACHEL J. , RESCH JON , DOUGLASS AMELIA M. , MADARA JOSEPH , SONG JOONGYU D. , WU CHEN , LOWELL BRADFORD , SHULMAN GERALD I.
Published: June 2019

Leptin deficiency is known to promote hyperphagia, but the mechanism for this is unknown. Here we show that hypoleptinemia-driven hypercorticosteronemia promotes hyperphagia in fasting (40.3±4.9 kcal consumed in 2 hour after a 48 hour fast vs. 2.4±1.0 kcal after a 6 hour fast, P<0.0001) and poorly-controlled type 1 diabetes (T1D) (28.4±2.5 vs. 13.3±2.9 kcal, P<0.01) in rats. Correcting hypoleptinemia with a 6 hour leptin infusion reversed hypercorticosteronemia and reduced food intake to control rates in both models (48 hour fast+leptin 5.2±2.2 kcal, P<0.0001; T1D+leptin 8.1±1.9 kcal, P<0.0001), while restoring hypercorticosteronemia abrogated the anorexic effect of leptin (48 hour fast+leptin+corticosterone 29.5±3.1 kcal, T1D+leptin+corticosterone 30.0±2.7 kcal, both P<0.001 vs. leptin-treated). Treatment with a glucocorticoid receptor antagonist, mifepristone, reversed hyperphagia (48 hour fast 8.8±4.3 kcal, T1D 15.0±2.3 kcal; both P<0.05). In adrenalectomized mice treated with low-dose corticosterone, food intake following a fast was markedly reduced, whereas high-dose corticosterone restored hyperphagia. Hypercorticosteronemia induced by hypoglycemia drove hyperphagia independent of leptin and insulin (hypoglycemic-hyperinsulinemic: 42.5±2.3 kcal, euglycemic-hyperinsulinemic: 1.8±1.9 kcal, euglycemic-hyperinsulinemic-corticosterone-treated: 32.0±4.6 kcal; both P<0.001 vs. euglycemic) which was reversed by mifepristone (14.6±2.3 kcal, P<0.0001 vs. hypoglycemic).

Finally, we show that hypercorticosteronemia increases feeding behavior through corticosterone-mediated stimulation of AgRP neuron activity: overexpression of 11β-hydroxysteroid dehydrogenase 2 in AgRP neurons abrogated the hyperphagic effect of corticosterone. Together these data provide new insights into hypoleptinemia-induced hyperphagia and reveal that corticosterone-driven AgRP neuron activity drives hyperphagia during starvation, T1D, and hypoglycemia.

Disclosure

R.J. Perry: Research Support; Self; AstraZeneca. J. Resch: None. A.M. Douglass: None. J. Madara: None. J.D. Song: None. C. Wu: None. B. Lowell: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, Merck & Co., Inc. Advisory Panel; Spouse/Partner; Merck & Co., Inc. Board Member; Self; Novo Nordisk A/S. Consultant; Self; Aegerion Pharmaceuticals, IMetabolic BioPharma Corporation, Longitude Capital, Nimbus Discovery, Inc., Staten Biotechnology B.V.

Funding

National Institutes of Health (R01DK113984, P30DK059635, T32DK101019, K99/R00CA215315, R01NS087568, UL1TR000142, T32DK007058, R01DK075632, R01DK089044, R01DK096010, R01DK111401)
970-P: The Clinical Accuracy Evaluation of Noninvasive Glucometer Based on Metabolic Heat Conformation Method: A Multicenter Study
Authors: LI ANG , GENG ZHANXIAO , LI SHUZHE , GUO XIAOHUI , ZHANG JUNQING , TANG FEI
Published: June 2019

Objective: To evaluate the accuracy of noninvasive glucometer based on metabolic heat conformation (MHC) method by multicenter clinical trial.

Methods: This study was a multi-center, open, self-controlled trial. Venous plasma glucose measured by the hexokinase method was taken as reference level. The screening period was 1 to 7 days before the test, and a fasting blood glucose of the subjects who enrolled to this study was recorded as a calibration value. Subjects were tested at 3 time points successively on experimental day: fasting, 2-hour and 4-hour postprandial. On each time point, the noninvasive glucose measurement was performed at first, and followed by venous blood sample collection within 5 minutes. The subjects ate the 80 g standard noodle meal after the fasting test. The meal should be finished within 15 minutes.

Results: 3 centers participated with 210 subjects (M/F=98/112, average age is 61.2 year-old, 200 with T2DM, 7 with T1DM, 3 with prediabetes) were enrolled. The correlation coefficient of noninvasive glucose value and the serum glucose value in fasting, 2h and 4h postprandial status was 0.79, 0.61, 0.63 respectively.

Conclusion: The noninvasive glucometer based on MHC method showed a good correlation with the venous plasma glucose, especially in fasting state.

Disclosure

A. Li: None. Z. Geng: None. S. Li: None. X. Guo: None. J. Zhang: None. F. Tang: None.
987-P: Real-World Weight Change, Adherence, and Discontinuation among Type 2 Diabetes (T2D) Patients Initiating GLP-1 Receptor Agonists (GLP-1RAs) in the UK
Authors: WEISS TRACEY , IGLAY KRISTY , CARR RICHARD D. , MISHRA AJAY PRATAP , YANG LINGFENG , RAJPATHAK SWAPNIL
Published: June 2019

Background: GLP-1 RAs are an injectable class of medications with demonstrated weight loss in clinical trials. However, weight changes related to GLP-1RA use have not been well-characterized in a real-world setting. Further, there are limited real-world data on patient adherence to and discontinuation of GLP-1RAs.

Methods: Using the UK Clinical Practice Research Datalink (CPRD) database (2010-2016), we conducted a retrospective cohort study of UK T2D patients ≥ 18 years of age initiating GLP-1RAs to evaluate one-year weight change, as well as GLP-1 RA adherence and discontinuation. Included patients initiated GLP-1RA as monotherapy or as dual therapy with metformin. GLP-1 RA adherence was assessed using the proportion of days covered (PDC) among all GLP-1 RA initiators with two or more prescriptions. Discontinuation was defined as any GLP-1 RA therapy gap >90 days during follow-up.

Results: 589 patients met the study criteria; Female: 56.4%, median age: 54 years, and median BMI: 41.2 kg/m2. The median one-year weight change was -3.1 kg; 72.1% of patients experienced weight loss while the rest of patients reported weight gain. Furthermore, only 32.6% of patients had a weight loss that is typically considered clinically-meaningful (≥5%). In terms of adherence, 64.5% of patients were considered adherent (PDC ≥80%) while 45.2% of patients discontinued GLP-1RA by 1 year.

Conclusion: Less than one-third of patients initiating GLP-1RA achieved ≥5% weight loss. Further, approximately one-third of patients were non-adherent to therapy and nearly half discontinued treatment within a year. Further investigation on the impact of GLP-1 RA adherence and discontinuation on real-world effectiveness is warranted.

Disclosure

T. Weiss: Employee; Self; Merck & Co., Inc. K. Iglay: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R.D. Carr: Employee; Self; Merck & Co., Inc. Speaker's Bureau; Spouse/Partner; Eli Lilly and Company, Merck & Co., Inc. A.P. Mishra: None. L. Yang: Employee; Self; Bristol-Myers Squibb Company, Merck & Co., Inc. S. Rajpathak: None.
989-P: MEDI0382, an Oxyntomodulin-Like Peptide with Targeted GLP-1/Glucagon Receptor Activity: Safety Study in Subjects of Japanese and Chinese Descent
Authors: ROBERTSON DARREN , PETRONE MARCELLA , TSAI LAN-FENG , GASSER ROBERT A.
Published: June 2019

Background: MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1/glucagon receptor activity that is under development for type 2 diabetes mellitus. This study was conducted in subjects of Japanese and Chinese descent to facilitate expansion of its global clinical development in Japan and China.

Methods: This phase 1, randomized, blinded study evaluated the safety, tolerability, pharmacokinetics, and immunogenicity of single subcutaneous (SC) doses of MEDI0382. In part A, 24 subjects of Japanese descent across 3 cohorts (8 per cohort) received single SC doses of MEDI0382 at a dose of 50 µg (cohort 1), 100 µg (cohort 2), or 150 µg (cohort 3) or placebo in a 3:1 ratio. In part B, 8 subjects of Chinese descent received a single SC dose of MEDI0382 at 100 µg or placebo in a 3:1 ratio (cohort 4).

Results: In part A, the incidence of treatment-emergent adverse events (TEAEs) was highest in the 150-μg group (5 of 6 subjects). In part B, 2 of 6 subjects in the MEDI0382 group reported TEAEs. Nausea, headache, and vomiting were most common. A trend of increased pulse rate post-dose was seen in subjects of Japanese descent in the MEDI0382 100- and 150-µg groups. No clinically meaningful changes from baseline in vital signs were observed in part B. Median tmax values were 6.15-8.16 h at doses of 50-150 μg, both in subjects of Japanese and Chinese descent. In part A subjects receiving MEDI0382 100 and 150 µg, postprandial mean glucose levels remained closer to baseline levels as compared with changes seen with MEDI0382 50 µg or placebo.

Discussion: The safety profile of single doses of MEDI0382 at doses of 50, 100, and 150 µg supports its further development in subjects of Japanese and Chinese descent. The pharmacokinetic data for MEDI0382 in the range of 50-150 µg also support its further clinical development in subjects of Japanese and Chinese descent.

Disclosure

D. Robertson: Employee; Self; AstraZeneca. Employee; Spouse/Partner; GlaxoSmithKline plc. Stock/Shareholder; Self; AstraZeneca. M. Petrone: Employee; Self; MedImmune. L. Tsai: Employee; Self; MedImmune. Other Relationship; Self; AstraZeneca. R.A. Gasser: Employee; Self; AstraZeneca, MedImmune.

Funding

AstraZeneca
996-P: Therapeutic Effect of a Novel Long-Acting GLP-1/GIP/Glucagon Triple Agonist (HM15211) in a Dyslipidemia Animal Model
Authors: CHOI JAEHYUK , JO HYOSANG , KIM JUNG KUK , LEE SANG DON , LEE SANG HYUN , CHOI IN YOUNG
Published: June 2019

Dyslipidemia is a well-established risk factor for cardiovascular disease. Although an efficacy has been demonstrated for several drugs including HMGCR inhibitor and PCSK9 inhibitor, overall outcome was still in doubt due to heterogeneity of this disease. Thus, targeting multiple pathways may provide promising efficacy in broad patient population. Previously, we showed that a long-acting GLP-1/GIP/Glucagon triple agonist, HM15211, not only provided efficient weight loss, but also improved lipid profiles in DIO mice. Of note, unlike current drugs possessing a single target, HM15211 could affect multiple pathways in lipid metabolism, suggesting HM15211 as a potential therapeutic option for dyslipidemia. Here, we investigated the effect of HM15211 on dyslipidemia and its mode of action (MoA). In high fructose-fed hamsters, HM15211 showed greater LDL lowering (-69.3% vs. Veh.) than evolocumab, PCSK9 Ab (-17.9% vs. Veh.). To elucidate the responsible MoA, HepG2 cells were treated with HM15211, and significantly increased LDLR expression (4.1-fold for HM15211, 2.3-fold for evolocumab vs. CTL) was observed. Consistently, the amount of LDL uptake (3.6-fold for HM15211, 2.8-fold for evolocumab vs. CTL) indicated enhanced LDL clearance by HM15211 via increasing LDLR expression even greater than evolocumab. To further identify the HM15211 target, the activity status of HMGCR, the key enzyme for cholesterol synthesis, was evaluated. Surprisingly, HM15211 progressively induced phosphorylation and degradation of HMGCR, thereby inhibiting its enzymatic activity. In case of free fatty acid (FFA) metabolism, HM15211 led to a favorable gene expression signature associated with β-oxidation and enhanced β-oxidation. Increased ApoA1 may explain, at least in part, the increase of HDL by HM15211.

In conclusion, we propose that by targeting multiple steps essential for LDL and FFA metabolism, HM15211 could provide therapeutic benefits for dyslipidemia patients.

Disclosure

J. Choi: None. H. Jo: None. J. Kim: None. S. Lee: Employee; Self; Hanmi Pharm. Co., Ltd. S. Lee: Employee; Self; Hanmi Pharm. Co., Ltd. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd.
Koordinatorordninger som samordningstiltak – tre mulige paradokser
Authors: Vik Erlend , Aarseth Turid
Published: June 2019

Koordinatorordninger i helsetjenesten er temaet for dette kapittelet, der vi undersøker både bakgrunnen for og spesielle utfordringer ved denne typen samordningstiltak. Det teoretiske utgangspunktet er Luhmanns systemteori og en forståelse av helsetjenesten som funksjonelt differensiert. Samordning handler her om å kunne få til kobling mellom ulike delsystemer.

Vi ser samhandlingsreformen som et tidsskille, og har gjennomført en dokument­analyse av nasjonale styringsdokumenter i perioden 2008–2018. Gjennomgangen avdekket 14 ulike koordinatorordninger, hvorav åtte var spesifikt rettet mot pasienter med sammensatte behov. Problembeskrivelsene i styringsdokumentene og trekk ved utformingen av koordinatorordningene danner grunnlag for å identifisere tre mulige paradokser. Det første handler om at koordinatorordningene – gjennom å være opptatt av å håndtere grenser mellom delsystemer – kan bidra til å bevare den funksjonelle differensieringen heller enn å redusere den. Det andre viser til at selve organiseringen av koordinatorordningene kan forsterke den funksjonelle differensieringen, mens det tredje synliggjør at ordningene i seg selv bidrar til økt kompleksitet, ved at det oppstår behov for å koordinere koordinatorene.
KOMITMEN ORGANISASIONAL, MOTIVASI LAYANAN PUBLIK DAN KINERJA LAYANAN DALAM SEKTOR PUBLIK
Authors: Nainggolan Arison , Ginting Mitha C.
Published: June 2019

Penelitian ini bertujuan untuk membangun satu model manajemen kinerja Sektor Publik. Dalam melaksanakan penelitian ini, peneliti menggunakan metode penelitian kuantitatif dengan menggunakan alat analisis statistik SmartPLS 2.0.M3. Penelitian ini dilakukan pada dinas dan badan yang ada dilingkungan pemerintah kota medan dengan menggunakan 162 sampel. Dari analisis data yang dilakukan, diketahui bahwa terdapat hubungan signifikan antara hubungan kerja dengan atasan (HKDA) terhadap komitmen organisasional (KO) dan motivasi layanan publik (MLP). Sementara itu, tidak terdapat hubungan signifikan antara organisasional tenure terhadap komitmen organisasional dan motivasi layanan publik. Terlihat signifikan hubungan antara pengembangan karir (PK) terhadap komitmen organisasional (KO) namun tidak signifikan terhadap motivasi layanan publik (MLP). Persepsi Pegawai mengenai Organisasi (PPO) memengaruhi signifikan Komitmen Organisasional (KO) dan juga terhadap Motivasi Layanan Publik (MLP). Tuntutan akuntabilitas (TA) tidak berpengaruh signifikan terhadap komitmen organisasional (KO), namun berpengaruh terhadap motivasi layanan publik (MLP). Tingkat pendidikan tidak berpengaruh terhadap komitmen (KO) dan motivasi layanan publik (MLP). Tidak terdapat hubungan signifikan antara komitmen organisasional terhadap kinerja (K). Terdapat hubungan signifikan motivasi layanan publik (MLP) terhadap kinerja (K). Terakhir, bahwa komitmen organisasional tidak memediasi hubungan antara motivasi layanan publik terhadap kinerja.
PELUANG IKATAN DAI MUDA INDONESIA (IDMI) DALAM MEMBINA MASYARAKAT MUSLIM DI KOTA PALU
Authors: Mahmud Muchlis A
Published: June 2019

This article discusses the dakwah method of the Indonesian Young Dai Association (IDMI) of Palu in fostering and developing the religiosity aspects of the community of Palu. Coaching is carried out to its members as well as to the general public. In carrying out its missionary activities, IDMI applied a variety of methods in fostering Muslim communities through recitation groups that were held regularly, ta’līm assemblies for women, as well as recitals held at the commemoration of Islamic holidays. Observation of da`wah activities and interviews with the preachers affiliated with IDMI showed that this institution had an excellent opportunity in carrying out community religious development in Palu. The enthusiasm of the community to take part in the recitations organized by IDMI and the dakwah material that is inclusive provides the possibility for this institution to act as a unifying node in the heterogeneous community of Palu.
THE USE OF SIMULATION MODELING FOR OPTIMIZATION THE DAILY ACTIVITIES OF THE EMERGENCY DEPARTMENT
Authors: Teplov V. M. , Tsebrovskaya E. A. , Karpova E. A. , Minnullin I. P. , Bagnenko S. F.
Published: June 2019

This article presents the first experience of computer modeling, performed as a result of the construction of the model of the emergency department (ED). A number of experiments were conducted aimed at determining the admissible flow of patients’ arrival per day for a given staffing table, determining the necessary conditions for the department’s readiness for mass one-stage entry, and conducting research in the context of expanding the job responsibilities of the doctor of the ED.
MÍDIA E AUTORITARISMO: OS (DES)CAMINHOS DA CONCENTRAÇÃO DO PODER COMUNICATIVO NA DEMOCRACIA CONSTITUCIONAL BRASILEIRA
Authors: Gonçalves Fábio Marques , Lima Danilo Pereira
Published: June 2019

O objetivo da pesquisa é traçar o histórico de modernização autoritária da sociedade brasileira, contexto no qual surgem os meios de comunicação social, para que se possa delimitar e enfrentar o problema da concentração proprietária dos meios de comunicação, analisando-se as consequências desse modelo para a (não) consolidação do Estado Democrático de Direito. Assim, a partir da Crítica Hermenêutica do Direito é realizada uma análise do papel da comunicação social para o aprofundamento da democracia. Em diálogo com as obras de Robert Dahl, Guillermo O’Donnell e Alexis de Tocqueville é colocado o problema da “nova poliarquia” brasileira, na qual o poder da mídia ainda se mantém concentrado com poucos grupos, reforçando uma situação de baixa constitucionalidade, em um país onde pouco se manifesta a ideia de Constituição normativa.
DISCRIMINATION IN THE WORKPLACE RELIGIOUS: NOTES FOR A CRITICAL REFLECTION
Authors: Delgado Joedson De Souza , Kölling Gabrielle Jacobi
Published: June 2019

The purpose of this study is to analyze religious discrimination in work environments under the aegis of freedom as worthy of protection as opposed to the right to business freedom. With the scope of religious freedom and its limitation parametrized, the article determines in which cases and conditions conduct can be characterized as intolerance or be considered by the employer as reasonable accommodation of religion in the scope of work. To perform this analysis, a qualitative approach was used, with bibliographic and descriptive methodological procedures. It is concluded that, to protect freedom of belief and religion, liberal theory (legal policy) is used for the promotion of individual autonomy and human dignity.
REFORMAS JUDICIÁRIAS NA AMÉRICA LATINA E REFLEXÕES SOBRE MODIFICAÇÕES EM PROCESSOS DE IMPROBIDADE ADMINISTRATIVA
Authors: Ramos Edith Maria Barbosa , Pinheiro Heron De Jesus Garcez
Published: June 2019

O presente artigo tem por escopo compreender e analisar os impactos da agenda neoliberal, forjada no âmbito do Consenso de Washington (1989), nas estruturas dos Estados Nacionais da América Latina, para tanto põem-se em relevo a desarticulação e o esvaziamento das funções públicas administrativa, legislativa e judiciária. Pontuam-se elementos caracterizadores das reformas judiciais da região, orientadas por organismos financeiros internacionais com o argumento de imprimir segurança jurídica às transações negociais, mediante previsibilidade e estabilidade das decisões judiciais, opção política que acabou olvidando as demandas locais pela afirmação de direitos fundamentais e promoção da cidadania social. Por derradeiro, examina-se a repercussão de reformas legais em processos de improbidade administrativa no Brasil, identificando a matriz patrimonialista, consentânea com a tradição caudilhista latino-americana, e apontando as tentativas de institucionalização da não-incidência da Lei nº 8.429/1992 em desfavor de agentes políticos pertencentes à elite dirigente nacional.
Time Dependent Density Functional Theory Calculations of 4-Thiothymidine-containing DNA Dinucleotides
Authors: Luong Dawn , Ortiz-Rodríguez Luis A. , Crespo-Hernández Carlos
Published: June 2019

Preliminary research report.
The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells
Authors: Gao Yankun , Dutta Banik Debarghya , Muna Mutia M , Roberts Stefan GE , Medler Kathryn F
Published: June 2019

WT1 is a transcriptional activator that controls the boundary between
multipotency and differentiation. The transcriptional cofactor BASP1 binds to
WT1, forming a transcriptional repressor complex that drives differentiation in
cultured cells; however, this proposed mechanism has not been demonstrated in
vivo. We used the peripheral taste system as a model to determine how BASP1
regulates the function of WT1. During development, WT1 is highly expressed in
the developing taste cells while BASP1 is absent. By the end of development,
BASP1 and WT1 are co-expressed in taste cells, where they both occupy the
promoter of WT1 target genes. Using a conditional BASP1 mouse, we demonstrate
that BASP1 is critical to maintain the differentiated state of adult taste cells
and that loss of BASP1 expression significantly alters the composition and
function of these cells. This includes the de-repression of WT1-dependent target
genes from the Wnt and Shh pathways that are normally only transcriptionally
activated by WT1 in the undifferentiated taste cells. Our results uncover a
central role for the WT1–BASP1 complex in maintaining cell
differentiation in vivo.
Percursos mentirosos para utopias construtivas
Authors: Cruz Cecilia Mori
Published: June 2019

O proposto texto parte de conceitos ambivalentes, de proposições fugidias e de noções de atravessamento para pensar o processo de criação da obra de arte. Apresentaremos fronteiras, ilusões, trapaças e idiotices como táticas operativas do Bobo da Corte, que realiza utopias por construções artísticas. Articulando pares opostos como alto e baixo, passado e futuro e verdade e mentira, o pensamento utópico é aqui valorizado como aquele que está voltado para o tempo presente ao invés da infinita projeção para o futuro. Assim, pretendemos situar a utopia na suspensão do presente para garantirmos a mentira como verdade poética e, com isso, a construção de percursos improváveis como prática artística.
Mira Schendel
Authors: Barbosa Iracema
Published: June 2019

A poética de Mira Schendel se constrói através da repetição de gestos sensíveis que, de acordo com a artista, funcionam apenas para ativar o vazio. A partir da observação de algumas de suas obras, este artigo procura pontos de contato com o pensamento Oriental sobre tal noção de vazio, e cria vínculos com certas reflexões do músico John Cage e do escritor Jorge Luis Borges.
Sobre cair (ou voar) – inconstância material, arte contemporânea e vontade de sublime
Authors: Tamayo Yana
Published: June 2019

Este artigo visa apontar para a existência de uma tendência presente na arte desde os primórdios da modernidade e, essencialmente, acentuada após o Romantismo. A vontade de alcançar o sublime, de ultrapassar fronteiras delimitadas, se relacionaria com as instâncias que modelam a cultura ocidental do excesso e as estruturas do capital, processo iniciado com a conquista da navegação. Assim, abordamos um imaginário de queda no qual se insere o sujeito da arte, como uma abordagem possível do percurso da subjetividade e estética contemporâneas.
Grand-tour
Authors: Dias Karina
Published: June 2019

Grand-Tour foi um trabalho coletivo desenvolvido gradualmente por nove artistas a partir de uma residência na Alfinete Galeria durante os meses de julho, agosto e setembro de 2014. Através da experiência dos artistas no espaço onde se situa a galeria em Brasília, Grand-Tour é o resultado de um trabalho pensado coletivamente, em que as noções de curadoria e autoria das obras foram embaralhadas, gerando uma exposição-obra, uma geografia imaginada.