bluuebunny/crossref_metadata_2025_split huggingface dataset:
1451-P: Risk of Progression to Clinical Type 1 Diabetes in Older Adolescents Positive for Islet Autoantibodies
Authors: WAUGH KATHLEEN , GENO RASMUSSEN CRISTY , DONG FRAN , GESUALDO PATRICIA D. , FROHNERT BRIGITTE I. , REWERS MARIAN 
Published: June 2023

Objective: Evaluate progression to type 1 diabetes (T1D) among adolescents with persistent islet autoimmunity.
Background: Few studies have continued to follow adolescents with islet autoimmunity through to young adulthood. With the emergence of treatments to delay clinical diabetes and general population screening, there is need to accurately predict and communicate risk for progression to T1D in autoantibody positive persons.
Methods: Included in this analysis were 203 participants of prospective studies (DAISY, TEDDY Graduates, ASK) who were persistently positive for islet autoantibodies and free of diabetes between 13-15 y of age. Of those, 51% were female, 52% non-Hispanic white, and 32% had a first-degree T1D relative. Autoantibodies to insulin, GAD, IA-2, and ZnT8 were measured using standard radio-binding assays.
Results: During the median 3.0 y (IQR 1.2-5.2) follow-up, 14.8% (n=30) of the participants progressed to T1D. The 5-year risk of progression to clinical diabetes was 33.1% (95%CI 20.0-51.7%) among adolescents with multiple autoantibodies vs 7.8% (95%CI 3.9-15.2%) in those with a single persistent autoantibody. Independent predictors of progression to diabetes included: multiple autoantibodies (HR=3.2, 95%CI 1.4-7.5, p=0.008) and higher baseline HbA1c (HR=1.7 per 0.5%, 95%CI 1.2-2.2. p=001). A receiver operating characteristic based on autoantibody status and HbA1c (AUC 0.78) did not improve significantly with addition of sex, ethnicity, and family history of T1D (AUC 0.81).
Conclusion: One third of adolescents with multiple islet autoantibodies progress to clinical diabetes within 5 years, with baseline HbA1c being highly predictive of progression.

Disclosure
K.Waugh: None. C.Geno rasmussen: None. F.Dong: None. P.D.Gesualdo: None. B.I.Frohnert: Advisory Panel; Provention Bio, Inc. M.Rewers: Research Support; Provention Bio, Juvenile Diabetes Research Foundation (JDRF), Hemsley Charitable Trust, Dexcom, Inc., Janssen Research & Development, LLC.

Funding
National Institutes of Health (5R01DK032493-36); JDRF (2-SRA-2022-1270-S-B)
1491-P: ER Stress Drives the VEGF Expression in Monocytic Cells by Mechanisms Involving CHOP/ROS/HIF-1alpha/NRF2 and NF-kappaB/p38 MAPK Pathways
Authors: SINDHU SARDAR A.K. , AKHTER NADEEM , WILSON AJIT , AREFANIAN HOSSEIN , AL MADHOUN ASHRAF , THOMAS REEBY S. , KOCHUMON SHIHAB P. , ALRASHED FATEMA , BAHMAN FATEMAH , ALZAID FAWAZ , ALMULLA FAHD , AHMAD RASHEED 
Published: June 2023

Obesity is marked by metabolic inflammation and by metabolic impairment caused by increased endotoxin, free fatty acids, and vascular endothelial growth factor (VEGF) levels; and involves the endoplasmic reticulum (ER) stress as well. However, it remains unclear whether the ER stress can induce/amplify VEGF expression in metabolically-stressed monocytic cells; and if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treating cells separately with lipopolysaccharide (LPS), palmitic acid (PA), and oleic acid (OA), in presence/absence of ER stressor thapsigargin (TG). Gene expression of VEGF/ER stress markers was assessed by qRT-PCR, protein expression by ELISA, ROS by DCFH-DA assay, phosphorylation of HIF-1α, NF-κB, ERK1/2, and p38 MAPK by immunoblotting, and the insulin response in stressed cells by glucose-uptake assay. Regarding clinical analyses, adipose VEGF gene and protein expression was detected using qRT-PCR and IHC, respectively, while plasma hs-CRP, TNF-α, MDA, and OX-LDL levels were measured by ELISA. The experimental data show that a cooperative interaction between the metabolic and ER stresses led to the expression of VEGF, ROS, CHOP, ATF6, SOD2, and NRF2 (P˂0.05), as well as stimulated the CHOP and NRF2 promoter activities in reporter cells (P˂0.05). However, the glucose uptake was not impaired. The VEGF expression was dependent on phosphorylation of HIF-1α, NF-κB, and p38 MAPK; and the inhibitors of NF-κB/MAPK pathways as well as antioxidants or ROS scavengers suppressed the VEGF production. Further, individuals with obesity showed increased VEGF expression which associated positively with plasma levels of hs-CRP, TNF-α, MDA, and OX-LDL (P≤0.05). Overall, our findings support a cooperativity model in which the ER and metabolic stresses interact to augment VEGF expression in monocytic cells via the mechanisms involving CHOP/ROS/HIF-1α/NRF2 and NF-κB/p38 MAPK pathways.

Disclosure
S.A.K.Sindhu: None. F.Alzaid: None. F.Almulla: None. R.Ahmad: None. N.Akhter: None. A.Wilson: None. H.Arefanian: None. A.Al madhoun: None. R.S.Thomas: None. S.P.Kochumon: None. F.Alrashed: None. F.Bahman: None.

Funding
Kuwait Foundation for the Advancement of Sciences (RA2015-027, RA2010-003, RAHM-2019-022)
1497-P: Comprehensive Metabolic Assessment Reveals Excellent and Stable Glucose Control during First Year after Pancreas Transplantation
Authors: JEET KAUR RAVINDER , RAZA RIZVI SHAFAQ , REID COREY , SMITH BYRON H. , KUKLA ALEKSANDRA , STEGALL MARK D. , KUDVA YOGISH C. 
Published: June 2023

Introduction: Limited data are available regarding comprehensive metabolic evaluation after Pancreas transplantation (PT) for T1DM.
Methods: We prospectively studied 15 PT recipients at baseline, 4 months & 1 year after PT. Subjects used Dexcom G4/G6 CGM for 1 week & a standard Mixed Meal Test (MMT) was performed.
Results: PT recipient were 45.1 ± 11.9 years old, F 10, BMI (Kg/m2) 24.4 ± 3.6 & mean duration diabetes 26.8 ± 14.3 years. Seven patients received pancreas alone, five simultaneous pancreas kidney & three pancreas after kidney transplants. Baseline values were Hb 10.4 ± 1.2 (g/dl), HbA1c 6.6 ± 1.1 %, Albumin 4.0 ± 0.4 g/dl, Fructosamine 245.7 ± 37.2 (µmol/L), Fasting glucose 94.9 ± 20.6 mg/dl, C-peptide 4.4 ± 2.8 (ng/ml), eGFR 64.7 ± 17.6 ml/min and AST 18.5 ± 6.7 U/L. Two participants developed partial graft failure: one due to a peri-pancreatic abscess requiring long term drainage & the second patient had nonadherence issues. MMT after adjusting for eGFR revealed excellent glucose concentration & C-peptide/insulin concentrations at all 3 visits. On CGM analysis, mean CGM was similar at V1, V2 and V3 & overall glucose control was excellent with &gt; 89 % of readings within 70-180mg/dL on all visits (Table).
Conclusion: PT recipients demonstrate excellent glucose control on comprehensive assessment at multiple time points in the first year after PT.

Disclosure
R.Kaur: None. S.Rizvi: None. C.Reid: None. B.H.Smith: None. A.Kukla: Advisory Panel; Novo Nordisk, Other Relationship; Dexcom, Inc. M.D.Stegall: None. Y.C.Kudva: Advisory Panel; Novo Nordisk, Research Support; Dexcom, Inc.
1515-P: Effect of Aging on Insulin Clearance in Mice
Authors: NIAZUR RAHMAN S.M. , ZAIDI SOBIA , MUTURI HARRISON T. , NAJJAR SONIA M. , GIACCA ADRIA 
Published: June 2023

Aging is commonly linked with hyperinsulinemia and insulin resistance. Age-related hyperinsulinemia results from increased insulin secretion and/or decreased insulin clearance as compensatory mechanisms to peripheral insulin resistance. Several studies have reported reduced β-cell function in elderly rodents and humans. Earlier reports on decreased insulin clearance due to aging suggest that hyperinsulinemia in elderly could be explained predominantly by a reduction in insulin clearance. Hence, we aim to better understand the role of aging on insulin clearance following fat infusion. To investigate the aging effect, 3 months and 10-14 months old C57BL6 mice were infused with ethylpalmitate for 48h (hydrolyzed to palmitate and ethanol in plasma), to achieve elevated circulating FFA in a non-toxic manner. Mice were then subjected to hyperglycemic clamp, and during the clamp plasma C-peptide and insulin were measured to evaluate insulin clearance. Glucose infusion rate (GINF), insulin sensitivity index (SI) and disposition index (DI) were also assessed during clamp analysis. GINF is a measure of glucose tolerance whereas DI evaluates β-cell function. Whereas insulin secretion did not increase, insulin clearance was reduced in the aging mice, as indicated by the lower C-peptide/insulin molar ratio, observed during hyperglycemic clamp. No significant changes were observed in GINF between old and young mice; however, SI and DI were lower in elderly group. These results collectively suggest that with advancing age, β-cells may lose their ability to maintain a higher insulin secretion and that reduced hepatic insulin clearance plays a more dominant role to compensate for age-related decline in insulin sensitivity.

Disclosure
S.Rahman: None. S.Zaidi: Other Relationship; BullFrog AI. H.T.Muturi: None. S.M.Najjar: None. A.Giacca: None.
1607-P: FGF1 Induces Glucokinase Upregulation and Increased Lactate Export in Mouse Hepatocytes
Authors: KABIR MORVARID , ADER MARILYN , THOMAS NAREG , SEKI EKIHIRO , BERGMAN RICHARD N. 
Published: June 2023

Rodent studies performed in Dr. Schwartz's lab showed that a single injection of fibroblast growth factor 1 (FGF1) has glucose-lowering activity in diabetic animals and induces concomitant increases in glucokinase (GCK) activity and plasma lactate (Scarlett, JM, Nat Med, 2016). In addition, in vivo experiments performed by our group demonstrated that hepatic lactate export is a surrogate for GCK activity. The mechanism by which FGF1 exerts these effects at cellular level in hepatocytes is unknown. In this study, we treated C57BL/6 mouse hepatocytes with different concentrations of FGF1 (100, 200, or 400 ng/ml) and evaluated GCK gene expression and lactate export from hepatocytes into the medium after 24 h of treatment. FGF1 increased lactate export with 200 to 400 ng/ml FGF1 increased lactate export by 1.5-fold (P&lt;0.05). FGF1 concentration from 100-400 ng/ml did not change cell proliferation, and 200 to 400 ng/ml FGF1 upregulated the expression of GCK by 2.3 and 3-fold (P&lt;0.05), respectively. Thus, these data provide a possible mechanism by which of FGF1 upregulates GCK and, consequently, increases lactate export by hepatocytes.

Disclosure
M.Kabir: None. M.Ader: None. N.Thomas: None. E.Seki: Research Support; Nippon Zoki Ltd, Jubilant. R.N.Bergman: Consultant; Lilly, ReCor Medical, Inc., Research Support; AstraZeneca.

Funding
National Institutes of Health (R01DK027619-33A1)
164-OR: Factors Influencing Young Adults Rationing Insulin and Diabetes Supplies
Authors: NORIEGA KIMBERLY , MONZON ALEXANDRA , CORRY JOLINDA , PATTON SUSANA R. , CARAKUSHANSKY MAURI , WASSERMAN RACHEL M. 
Published: June 2023

Background: Despite known risks, young adults (YAs) may ration insulin and type 1 diabetes (T1D) supplies past their recommended use for many reasons, such as changes in health insurance, increased insulin costs, and gaps in health care. In this study, we examined the frequency with which YAs ration insulin and T1D supplies, and related individual and social factors.
Methods: We surveyed 203 YAs with T1D (age 18-25; 54% Female, 1.5% Transgender, 82% Non-Hispanic White, 9% Hispanic/Latino, 11% Non-Hispanic Black, 46% in college, 63% pump-users, and mean HbA1c = 7.69 ± 1.61%.) in a cross-sectional design. Participants completed a validated risk questionnaire including a question about how often they “tried to make insulin or diabetes supplies last longer than recommended” (Likert scale: Never to Daily), and the Diabetes Distress Scale. Participants also reported on social factors including race/ethnicity, insurance status, frequency of T1D appointments, and living with parents (Yes or No). We examined bivariate correlation between diabetes distress (DD) and frequency of rationing insulin/supplies and performed independent samples t-tests comparing groups based on social factors.
Results: Sixty percent of the sample reported rationing insulin/supplies at least once in the last year. Frequency of rationing insulin/supplies correlated with diabetes distress (r= 0.24). Independent samples t-test revealed that participants who lived with a parent or other family member were less likely to ration insulin/supplies t(201) = 2.34, p&lt; 0.05. No other social factors were significant.
Conclusion: Rationing insulin/supplies is common in YAs. YAs who live away from their parents may be at greater risk for rationing, though the relation is not causal. Similarly, YAs who ration insulin/supplies may report higher DD. Clinicians may consider assessing for rationing supplies and its potential detrimental effect on glycemic control. Additional research is needed to examine why YAs might ration insulin/supplies.

Disclosure
K.Noriega: None. A.Monzon: None. J.Corry: None. S.R.Patton: None. M.Carakushansky: None. R.M.Wasserman: None.

Funding
Society of Pediatric Psychology
165-OR: Early Electronic Consultation Reduces Glucose and Health Care–Associated Infection in Hospital—The STOIC-D Surgery Randomised Controlled Trial
Authors: BARMANRAY RAHUL , KYI MERVYN , COLMAN PETER G. , ROWAN LOIS M. , COLLINS LUCY , DONALDSON LAURA E. , MONTALTO STEPHANIE , SUN EMILY , LE MINH V.H. , WORTH LEON J. , FOURLANOS SPIROS 
Published: June 2023

Aims: To assess the effect of early intervention with electronic-based proactive specialist diabetes care in surgical inpatients on glycaemia and clinical outcomes.
Methods: The Specialist Treatment of Inpatients: Caring for Diabetes (STOIC-D) Surgery randomised controlled trial (RCT) recruited consecutive adults admitted to surgical units of the Royal Melbourne Hospital (Australia) in 2021 with diabetes or blood glucose ≥200 mg/dL and length of stay (LOS) ≥24 hours. Intervention arm patients received remote proactive consultation by the inpatient diabetes service (IDS) in the electronic medical record (Epic®) within 24 hours of admission and, if escalation criteria were met, received a bedside consultation. Patients receiving standard care were reviewed by the IDS at the bedside only following referral. Insulin and non-insulin agents were used to target glucose 90-180 mg/dL. Outcomes included glucometrics, healthcare-associated infection (HAI), and mortality. Registration: ACTRN12620001303932.
Results: 1,383 admissions met inclusion criteria; 689 received the intervention. The primary outcome of mean patient-day mean glucose was lower in the active (158.4 mg/dL, standard deviation [SD] 48.6) vs. control arm (162.0 mg/dL, SD 46.8, p&lt;0.001). HAI (most commonly pneumonia) was lower in the active vs. control arm (11% vs. 16%, p=0.02). Mortality (2.4% vs. 4.2%, p=0.08) and LOS (10.7 vs. 10.0 days, p=0.26) were no different. The number needed to treat for HAI prevention was 22. Hypoglycaemia &lt;72 mg/dL was not increased (1.0% active vs. 0.9% control, p=0.23). The IDS performed a bedside consultation in 333 (49%) of the active vs. 93 (14%) of the control arm.
Conclusion: The STOIC-D Surgery trial is the largest RCT of a diabetes model-of-care intervention in non-critical care. Early, electronic-based specialist diabetes intervention significantly reduced patient-day mean glucose and HAIs in a surgical population.

Disclosure
R.Barmanray: None. L.J.Worth: None. S.Fourlanos: Advisory Panel; Viatris Inc., Pfizer Inc., Speaker's Bureau; Novo Nordisk, AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance. M.Kyi: None. P.G.Colman: None. L.M.Rowan: None. L.Collins: None. L.E.Donaldson: Stock/Shareholder; Medtronic, Novo Nordisk. S.Montalto: None. E.Sun: None. M.V.H.Le: None.
1657-P: Post–Mixed Meal Glucagon Secretion Is Not Influenced by Residual Beta-Cell Function in Type 1 Diabetes
Authors: TAYLOR GUY , SMITH KIERAN , BASHIR AYAT , MCDONALD TIMOTHY J. , STEVENSON EMMA J. , SHAW JAMES A. , WEST DANIEL J. 
Published: June 2023

Aims: Postprandial glucose excursions contribute to dysglycemia in type 1 diabetes (T1D). Hyperglucagonaemia may play a role but the relationship between beta and alpha-cell dysfunction together with incretin response remains unclear. We sought to elucidate this in people with established T1D with and without C-peptide.
Methods: Participants (n=29, age 38 ± 12 years, HbA1c 57 ± 9 mmol/mol, T1D duration 20 ± 13 years) with a range of postprandial urine C-peptide were recruited. A Meal Tolerance Test (MTT, 240 mL Fortisip: 360kcal, 14.4g protein, 13.92g fat, 44.16g carbohydrate) was completed after an overnight fast, maintaining normal basal insulin, without an insulin bolus. Blood samples were taken pre and 30min intervals for 180 minutes post-drink and analysed for glucose, C-peptide, glucagon, proinsulin, GLP-1 and GIP. Participants were grouped by peak C-peptide (high &gt;200 pmol/L, low 3-200pmol/L, undetectable). [Incremental] area under the curves ([i]AUC) were compared by one way ANOVA, Spearman's correlation and multiple regression with significance accepted p≤0.05.
Results: Ten participants had high peak C-peptide (680 ± 426 pmol/L), 8 low (39 ± 34 pmol/L), and 11 undetectable. Glucagon was comparable in all groups with mean AUC 1721 ± 890 pmol/L*180min (p=0.84). Glucagon correlated with GLP-1 (r=0.81, p&lt;0.01) and GIP (r=0.43, p=0.02) response, but not C-peptide (R=-0.10, p=0.61), proinsulin (r=-0.18, p=0.35) or proinsulin/C-peptide ratio (r=0.04, p=0.85). C-peptide predicted glucose AUC using multiple regression (R2 = 44.3%, F(1, 27) = 21.4, p&lt;0.01). C-peptide in combination with glucagon predicted glucose iAUC (R2 = 41.1% F(2, 26) = 9.1, p&lt;0.01).
Conclusion: Residual C-peptide is a predictor of MTT glucose excursions but not glucagon response in established T1D. Postprandial glucagon contributed to glucose excursion as well as correlating with incretin response. This supports altered alpha-cell phenotype in T1D, aberrantly responding to or secreting incretin.

Disclosure
G.Taylor: None. K.Smith: None. A.Bashir: None. T.J.Mcdonald: None. E.J.Stevenson: None. J.A.Shaw: Advisory Panel; Betalin Therapeutics, Provention Bio, Inc., Consultant; Mogrify. D.J.West: None.

Funding
Diabetes Research and Wellness Foundation (SCA/OF/12/15); Francis James Bell Endowment Fund; Country Durham Community Foundation
1753-P: Islet GLP-1R Protein Expression Is Reduced in Humans with Cystic Fibrosis–Related Diabetes
Authors: VEMIREDDY RACHNA , CASTILLO JOSEPH J. , FOUNTAINE BRENDY S. , BAMMLER THEO K. , MACDONALD JAMES , HULL-MEICHLE REBECCA L. , GHARIB SINA , ZRAIKA SAKENEH 
Published: June 2023

Impaired insulin secretion underlies the development of cystic fibrosis-related diabetes (CFRD). Glucagon like peptide-1 (GLP-1) is produced in islet α cells, and potentiates insulin secretion by binding GLP-1 receptors (GLP-1Rs) on β cells. In CFRD, α-cell mass is increased. Despite this, we hypothesized that levels of GLP-1 and/or its signaling components are reduced in CFRD, thereby contributing to deficits in insulin secretion. To address our hypothesis, paraffin-embedded pancreas sections from humans with CFRD and age-matched nondiabetic controls (from nPOD) underwent immunohistochemistry to quantify protein levels of active GLP-1 and GLP-1R (n=5-6/group). Spatial transcriptomics (NanoString) was also performed to assess differentially expressed α- and/or β-cell genes between CFRD and control pancreas (n=3/group; 15 CFRD + 9 control islets). GLP-1 immunoreactivity was unchanged between CFRD and control pancreas (0.33±0.15 vs 0.51±0.15, % GLP-1 area/pancreas area; p=0.4), however islet GLP-1R immunoreactivity was significantly reduced (4.35±1.21 vs 18.70±0.50, % GLP-1R area/islet area; p=0.004). Surprisingly, few α- or β-cell genes were differentially expressed between CFRD and control islets. However, a gene set test (ROAST) to assess transcripts involved in GLP-1 production/signaling revealed that those in α cells (GCG, PCSK1, PCSK2, DPP-4) significantly changed in mixed directions (up- or down-regulated; p=0.001). No such perturbation was seen in the β-cell gene set (INS, GLP1R, DPP-4, PLCG1, PIP4P2, ITPR3, ADCY1, ADCY6, PRKACA, RAPGEF4; p=0.4). In sum, our data suggest CFRD is not associated with altered intra-islet GLP-1 levels, however α-cell genes that modulate GLP-1 levels are dysregulated. Also, islet GLP-1R protein levels are reduced, though expression of genes downstream of GLP-1R is unchanged. Thus, interventions to restore protein levels of islet GLP-1R and/or promote intracellular signaling beyond GLP-1R may improve β-cell function in CFRD.

Disclosure
R. Vemireddy: None. J.J. Castillo: None. B.S. Fountaine: None. T.K. Bammler: None. J. MacDonald: None. R.L. Hull-Meichle: Research Support; Casma Therapeutics, Cystic Fibrosis Foundation, NIH - National Institutes of Health. Employee; Veterans Administration. Research Support; Veterans Administration. S. Gharib: None. S. Zraika: None.

Funding
National Institutes of Health (P30DK089507, P30DK017047)
178-OR: Better Glycemic Control with Once-Weekly Insulin Icodec vs. Once-Daily Insulin Degludec in Insulin-Naïve Type 2 Diabetes (ONWARDS 3)
Authors: LINGVAY ILDIKO , ASONG MARISSE , DESOUZA CYRUS , GOURDY PIERRE , KAR SOUMITRA , VIANNA ANDRE G. , VILSBØLL TINA , VINTHER SIRI M. , MU YIMING 
Published: June 2023

Efficacy and safety of once-weekly insulin icodec (icodec) vs once-daily insulin degludec (degludec) in insulin-naïve adults with T2D were examined in ONWARDS 3 (NCT04795531), a 26-week, randomized, double blind, double dummy, treat-to-target, phase 3a trial. Participants (n=588) were randomized 1:1 to icodec or degludec. Key outcomes are shown in the table. The primary endpoint was A1C change from baseline (BL) to week 26. Estimated mean A1C change was greater with icodec (−1.57%; BL: 8.55%) vs degludec (−1.36%; BL: 8.48%); estimated treatment difference −0.21%-points (95% CI −0.34, −0.08), confirming non-inferiority (p&lt;0.0001) and superiority (p=0.0016). Level 2 or 3 hypoglycemia rates were numerically but not statistically significantly higher with icodec vs degludec in the on-treatment period. Odds of achieving A1C &lt;7% without level 2 or 3 hypoglycemia were statistically significantly higher with icodec vs degludec. There were no significant differences in weekly insulin dose from week 24 to 26 or body weight change from BL to week 26 between arms. No unexpected safety findings were observed. Overall, once-weekly icodec demonstrated superior A1C reduction vs once-daily degludec with low level 2 or 3 hypoglycemia rates in both arms. Icodec may facilitate insulin treatment acceptance and adherence by reducing basal insulin injections from ≥365 to 52 per year.

Disclosure
I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp & Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. M.Asong: Employee; Novo Nordisk. C.Desouza: Advisory Panel; Novo Nordisk A/S, Bayer Inc., Consultant; Asahi Kasei Corporation, Research Support; Eli Lilly and Company. P.Gourdy: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Sanofi, Bayer Inc., Merck Sharp & Dohme Corp., Novartis, Intercept Pharmaceuticals, Inc., Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Sanofi, Abbott, AstraZeneca, Boehringer-Ingelheim. S.Kar: None. A.G.Vianna: Advisory Panel; AstraZeneca, Board Member; Abbott Diabetes, Novo Nordisk, Medtronic, Research Support; Novo Nordisk, Anji Pharmaceuticals, Lilly, Speaker's Bureau; AstraZeneca, Novo Nordisk, Medtronic. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck & Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. S.M.Vinther: Employee; Novo Nordisk. Y.Mu: Speaker's Bureau; Abbott Diabetes, Boehringer Ingelheim Inc., Novo Nordisk (China), Sanifit.

Funding
Novo Nordisk A/S