bluuebunny/crossref_metadata_2025_split huggingface dataset:
735-P: Baseline Characteristics in the REVERSE-IT Study, a 24-Week, 600-Person Randomized Placebo-Controlled Study of the Metabolic Effects of the Combination of Five Plant Extracts TOTUM-63 (T63)
Authors: OTERO YOLANDA F. , SIRVENT PASCAL , ERIK JOHANSEN ODD , CHAVANELLE VIVIEN , BARGETTO MAXIME , SAPONE VERONIQUE , BOUCHARD-MERCIER ANNIE , LE JOUBIOUX FLORIAN , BOISSEAU NATHALIE , MAUGARD THIERRY , CAZAUBIEL MURIELLE , PEREIRA BRUNO , GUIGAS BRUNO , HADJADJ SAMY , PELTIER SEBASTIEN , MARETTE ANDRE , BARD JEAN-MARIE 
Published: June 2023

The role of natural based products to support glucose control in people with prediabetes or early type 2 diabetes (T2D) (i.e. dysglycemia) is debated. T63 is a polyphenol-rich substance composed by artichoke, chrysanthellum, olive leaf, bilberry, and black pepper extracts, and studied in REVERSE-IT (NCT04423302), an ongoing 24 weeks, multi-center, multi-country clinical trial involving people with dysglycemia. It tests the hypothesis that 5 g T63 vs placebo (PBO) leads to significant reduction in fasting plasma glucose, while secondary outcomes include effects on lipids, blood pressure (BP), weight and waist circumference. The confirmatory primary analysis will compare T63 vs PBO when provided TID (double-blinded) and is powered based on minimum 174 completers in each arm. Effects of T63 BID vs PBO will be analyzed open label. A total of n=627 were recruited over 2 years from 61 sites across 7 European countries. Mean age is 57 years, BMI 32.2 kg/m2, and HbA1c 6.1% (table 1). The majority have prediabetes (78.3%), with a better glycemic profile and BP compared to those with T2D (21.7%). REVERSE-IT has enrolled an appropriate population to help inform clinical decision making on the use of plant-extract based T63 to support glucose homeostasis in people with dysglycemia. Readout is expected in the second half of 2023.

Disclosure
Y.F.Otero: Employee; Valbiotis. T.Maugard: None. M.Cazaubiel: Board Member; Valbiotis. B.Pereira: None. B.Guigas: Advisory Panel; Valbiotis, Research Support; Valbiotis. S.Hadjadj: Consultant; Bayer Inc., Novo Nordisk, Valbiotis, Research Support; AstraZeneca, Novartis, Speaker's Bureau; Abbott Diagnostics, Boehringer-Ingelheim. S.Peltier: Board Member; Valbiotis. A.Marette: Advisory Panel; Valbiotis, Amancia, Plexus, Acasti. J.Bard: Consultant; Valbiotis, Biofortis France, Stock/Shareholder; Valbiotis. P.Sirvent: Board Member; Valbiotis. O.Johansen: Employee; Nestlé Health Science. V.Chavanelle: Employee; Valbiotis. M.Bargetto: Employee; Valbiotis. V.Sapone: None. A.Bouchard-mercier: Employee; Valbiotis. F.Le joubioux: Employee; Valbiotis. N.Boisseau: None.
736-P: Projecting the Number of Type 2 Diabetes Cases and Their Complications Prevented under Different Primary Prevention Strategies
Authors: SHAO YIXUE , SHAO HUI , IMPERATORE GIUSEPPINA , HOLLIDAY CHRISTOPHER S. , ZHANG PING 
Published: June 2023

Preventing type 2 diabetes (T2D) involves reducing T2D risk factors at the population level (PL) and lowering the risk of developing T2D in groups at higher risk (GHR). We used the 2013-2018 National Health and Nutrition Examination Survey data to generate a nationally representative population of adults without diabetes. Using the CDC-RTI T2D Cost-Effectiveness simulation model, we estimated the number of T2D cases and their complications prevented by two hypothetical combined PL and high-risk strategies compared with no intervention over 10 years: a moderate strategy (MS) consisting of an annual T2D risk reduction (RR) of 4% at the PL and a RR of 35%, 17.5%, and 10.5% in years 1, 2, and 3 in GHR using a moderate lifestyle intervention program (LIP); an intensive strategy (IS) consisting of an annual RR of 6% at the PL and a RR of 40%, 20%, and 12% over 3 years in GHR using an intensive LIP. We assumed a 50% LIP participation rate. We also assessed % of T2D prevented by the PL strategy alone under MS or IS. The MS and IS would prevent 667,317 and 926,265 T2D cases over 10 years. Of the total cases prevented, 68.3% and 73.9% were due to PL strategy with MS and IS. The prevented complication cases increased with the number of prevented T2D cases. Curbing the national T2D epidemic, implementing both the cost-effective LIP in GHR and PL strategies is needed.

Disclosure
Y.Shao: Employee; Biogen. H.Shao: Consultant; Lilly Diabetes. G.Imperatore: None. C.S.Holliday: None. P.Zhang: None.
737-P: A Wearable Device (CGM and Activity Tracker) RCT for Postpartum Women with a History of Gestational Diabetes—Preliminary Findings on Anthropometry Measures and Self-Reported Lifestyle Behaviours
Authors: LING ELAINE QUAH PHAIK , SYAZA RAZALI NURUL , CHAI SALLY M.H. , FADZULLY FADZLYNN , RYAN LEE W.K. , WAI KU CHEE , LING LOY SEE , HIAN TAN KOK 
Published: June 2023

Background: Women with a history of gestational diabetes mellitus (GDM) have a 7-fold increased risk for subsequent development of type 2 diabetes mellitus (T2DM). Continuous glucose monitoring systems (CGMS) and exercise trackers have not been thoroughly explored in any Asian postpartum diabetes prevention studies. Objective: The Integrated Hyperglycaemia Incentivised Postnatal Surveillance (I-HIPS) study aims to investigate the efficacy of a personalized lifestyle intervention programme using wearables along with physical activity (PA) and diet modification to achieve healthy weight loss in postpartum women with history of GDM.
Methods: Women were randomized to receive the intervention or standard medical care. The intervention group received a CGM sensor and exercise tracker, along with nutrition, exercise and personalized goal-setting workshops. Anthropometric measures (weight, BMI and waist circumference (WC)) and PA assessed using the International Physical Activity Questionnaire were examined between the two arms at the 6-month follow-up. Changes in dietary behaviors in the intervention group were assessed using a validated 6P tool.
Results: Twenty-six recruited women had completed the 6-month follow-up. At 6-month, compared with the controls, women receiving intervention achieved a mean difference in the reduction of weight by 0.5 kg, BMI by 0.2 kg/m2 and WC by 0.8cm (p&gt;0.05). The intervention group had increased PA (mean difference: +990 MET mins/week), compared to the controls (mean difference: +298 MET mins/week) (p&gt;0.05) at 6-month. Between baseline and 6-month, women in the intervention group showed a reduction in the frequency of snack and beverage intakes (p=0.01).
Conclusion: Preliminary findings suggest a trend toward better health outcomes in the intervention group with improved dietary behaviour.

Disclosure
P.Quah: None. N.Razali: None. S.M.H.Chai: None. F.Fadzully: None. L.W.K.Ryan: None. C.Ku: None. S.Loy: None. K.Tan: None.

Funding
National Medical Research Council of Singapore (MOH-000504-03)
740-P: Six Subclasses with Glucose and Insulin Curves during OGTTs Capture Distinct Metabolic Characteristics and the Most Common Pathway to T2D in a Cohort of Koreans
Authors: KIM JINMI , YI WOOK , KIM DOOHWA , IM MYUNGSOO , RYANG SOREE , KIM MINSOO , JIN KIM YEONG , JOO KIM IN , JIN KIM YOUNG , KANG HYUK , CHUNG STEPHANIE T. , SHERMAN ARTHUR , SOO KIM SANG , HA JOON 
Published: June 2023

Heterogeneity of glucose abnormalities makes prevention and treatment of diabetes challenging. Subclasses of people at high risk have been identified based on glucose profiles during OGTTs. However, previous work on subclasses lacks longitudinal confirmation. Here, we used glucose and insulin during OGTTs and k-means clustering to classify subclasses of people without diabetes and then determined the model-derived beta-cell function (BCF) and insulin sensitivity (IS) within each subclass. We identified metabolic risk and the most common pathway to T2D by tracking transitions of subclasses over the 16-year Korean Genome Epi. Study. Participants underwent OGTTs every 2 years for up to 16 years or until diabetes (N=2682, BMI=24.4±2.9 kg/m2, age 49.8±7.6 y). 1) 6 subclasses: Cluster A: Normal BCF, Normal IS, B: Mildly impaired BCF and IS, C: Impaired BCF, mildly impaired IS, D: Strong BCF, impaired IS, E: Mildly impaired BCF, impaired IS, F: Strong BCF, severely impaired IS; 2) Cluster C had the highest risk for T2D, HR: 10.7 (8.0, 14.1), compared to cluster A, followed by Clusters E, B, F, and D; Transition from A to B and C was the most common pathway; A, B, and C together comprised 86% of the cohort. Clustering using glucose and insulin classified 6 subgroups showing distinct metabolic parameters and identified the most common pathway to T2D in Koreans.

Disclosure
J.Kim: None. H.Kang: None. S.T.Chung: None. A.Sherman: None. S.Kim: None. J.Ha: None. W.Yi: None. D.Kim: None. M.Im: None. S.Ryang: None. M.Kim: None. Y.Kim: None. I.Kim: None. Y.Kim: None.

Funding
Busan Economic Promotion Agency; National Research Foundation of Korea (2022H1D3A2A01063552); Korea Health Industry Development Institute (HI18C2383); dkNET New Investigator Pilot Program in Bioinformatics; National Institute of Diabetes and Digestive and Kidney Diseases
744-P: Reach and Effectiveness of the University of California Diabetes Prevention Program Initiative
Authors: GHOLAMI MARYAM , JACKSON NICHOLAS , LOEB TAMRA B. , YOUNG CHUNG UN , RAMM KATE , SHEDD KELLY , SOETENGA SAMANTHA , HAMILTON ALISON B. , ELASHOFF DAVID , MANGIONE CAROL , KENRIK DURU O. , MOIN TANNAZ 
Published: June 2023

The University of California (UC) system implemented the Diabetes Prevention Program (DPP) across UC campuses to address diabetes and obesity risk. We examined the reach and effectiveness of this novel, university-based DPP delivery approach. We compared weight change at 12-mo follow-up among 3 groups of overweight/obese UC beneficiaries: 1) those who reported receiving DPP invitation letters and enrolled in DPP (DPP enrollees), 2) those who were sent DPP invitation letters but did not enroll (DPP aware non-enrollees), and those who were not sent letters and did not enroll (controls). Using EHR, administrative and UC DPP cohort data, we conducted an interrupted time series to compare differences in the rate of weight change 12-mo after DPP enrollment for enrollees, receipt of DPP letters for non-enrollees or proxy enrollment date for controls. Our analysis included 7,465 UC beneficiaries (142 DPP enrollees, 2,494 DPP aware non-enrollees, 4,829 controls). UC beneficiaries had a mean age of 42 (SD 13), 51% were female, 26% Asian, 6% Black, 16% Hispanic, 6% Multi/Other, 1% Native American, 34% White, and 12% Unknown. DPP enrollees were older (mean age 49 [SD 11]), mostly women (75%), and more diverse (32% Asian, 7% Black, 21% Hispanic, 4% Multi/Other and 1% Native American). During the 12-mo follow-up, the rate of weight change was -0.60 lbs/mo among DPP enrollees. The within-person change in rate of weight loss was significantly greater among DPP enrollees compared to DPP aware non-enrollees (Δ-0.93 vs Δ-0.03 lbs/mo, difference = -0.90, p &lt;.001). We found no difference in weight loss among DPP enrollees and DPP aware non-enrollees compared to controls. We found that the UC DPP Initiative reached a diverse group of UC beneficiaries and was effective for weight loss among enrollees. However, UC DPP invitation letters to raise DPP awareness were not associated with weight change in the absence of DPP enrollment. University based approaches to DPP delivery may help enhance reach of DPP among at risk adults.

Disclosure
M.Gholami: None. C.Mangione: None. O.Duru: None. T.Moin: None. N.Jackson: None. T.B.Loeb: None. U.Chung: None. K.Ramm: None. K.Shedd: None. S.Soetenga: None. A.B.Hamilton: None. D.Elashoff: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK124503–02)
75-OR: Cold-Responsive Proteolytic Rewiring of Mitochondria Safeguards White Fat Thermogenic Remodeling
Authors: FU TINGTING , SUN WANPING , ZHOU ZHENG , XU ZHISHENG , YAN MAO , YANG LIKUN , YIN YUJING , GAN ZHENJI 
Published: June 2023

Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity acting both as protein quality surveillance and regulatory enzymes. It remains unclear, however, whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switch such as white-to-beige conversion of adipocytes. Here we report that cold-responsive mitochondrial proteolysis is a prerequisite for conversion from white-to-beige adipocytes during white adipose tissue (WAT) browning. MitoTimer reporter and chemical thiol probe analysis reveal that thermogenic stimulation selectively promotes mitochondrial proteostasis in WAT via mitochondrial protease LONP1 both in vivo and in vitro. Disruption of LONP1-dependent proteolysis substantially impairs cold or b3-AR agonist induced adipocyte identity programming, evidenced by the remarkably attenuated formation of UCP1+ multilocular adipocytes in IWAT from Lonp1 f/f/Adipoq-Cre (LONP1 AKO) mice. LONP1 AKO mice exposed to cold had lower body temperature, elevated serum TG and FFA levels. Chow-fed LONP1 AKO mice also developed glucose intolerance. “AdipoChaser” system “pulse-chase” lineage tracing experiments confirm that LONP1 ablation markedly blocks the direct cell fate programming of pre-existing mature adipocytes. Importantly, augmented LONP1 expression corrects aging-related impairments in white-to-beige adipocytes conversion. 10-month-old adipocyte-specific Lonp1 overexpression mice had significantly lower body weight and fat mass as a result of elevated energy expenditure. Thus, the identification of LONP1 as a critical safeguard of WAT beiging holds promise for translational applications in enhancing white-to-beige adipocytes conversion capacity relevant to a variety of metabolic disease states and during aging.

Disclosure
T.Fu: None. W.Sun: None. Z.Zhou: None. Z.Xu: None. M.Yan: None. L.Yang: None. Y.Yin: None. Z.Gan: None.
758-P: Changes in Liver and Abdominal Fat in Tirzepatide-Treated Patients Achieving Normoglycemia in the SURPASS-3 MRI Substudy
Authors: RODRÍGUEZ ÁNGEL , CUSI KENNETH , GASTALDELLI AMALIA , NICOLAY CLAUDIA , TORCELLO-GOMEZ AMELIA , FERNANDEZ LANDO LAURA 
Published: June 2023

Tirzepatide (TZP), a novel, once-weekly GIP/GLP-1 receptor agonist, significantly reduced liver fat content (LFC) and volumes of visceral and abdominal subcutaneous adipose tissue (VAT and ASAT) vs insulin degludec in a subpopulation of patients in the SURPASS-3 phase 3 trial. This post-hoc analysis evaluated changes from baseline to Week 52 in these outcomes and other clinical and laboratory parameters in TZP-treated patients achieving or not achieving normoglycemia (HbA1c &lt;5.7%) at Week 52.
LFC, VAT and ASAT volumes were assessed with MRI prior to randomization and at Week 52 in insulin-naïve patients with type 2 diabetes inadequately controlled on metformin with/without SGLT-2i and fatty liver index ≥60 at baseline. Analyses used pooled data from all TZP arms (5, 10, and 15 mg).
Patients achieving HbA1c &lt;5.7% were slightly younger and had lower baseline HbA1c and VAT vs those not achieving HbA1c &lt;5.7%. Substantial reductions in LFC, VAT and ASAT volumes, weight, HbA1c, and overall improvement in lipids profile were observed in both subsets of patients (Table). Among patients achieving HbA1c &lt;5.7% and ≥5.7%, respectively, 56% and 27% achieved LFC &lt;6%, and 91% and 64% achieved ≥30% reduction in LFC.
In summary, in TZP-treated patients, changes in LFC, VAT and ASAT, and lipids were more pronounced in those achieving normoglycemia.

Disclosure
Á.Rodríguez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. A.Gastaldelli: Advisory Panel; Pfizer Inc., Novo Nordisk, Merck Sharp & Dohme Corp., Boehringer Ingelheim International GmbH, Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Fractyl Health, Inc., Merck Sharp & Dohme Corp., Other Relationship; Pfizer Inc., Speaker's Bureau; Eli Lilly and Company. C.Nicolay: Employee; Eli Lilly and Company. A.Torcello-gomez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.Fernandez lando: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding
Eli Lilly and Company
76-OR: Axon Guidance Molecule Slit3 Is Essential for Cold-Induced Remodeling of BAT Neurovasculature and Thermogenesis
Authors: DUARTE AFONSO SERDAN TAMIRES , CERVANTES HEIDI E. , NETO FELIPPE M. , TSENG YU-HUA , SHAMSI FARNAZ 
Published: June 2023

Brown adipose tissue (BAT) is primarily responsible for regulating body temperature through adaptive thermogenesis. Enhancing energy expenditure through the activation of BAT thermogenesis is a promising strategy to prevent and reverse obesity and its cardiometabolic sequelae. Brown adipocytes are embedded in a dense network of blood vessels and sympathetic nerves that supports their thermogenic activity. Increasing the density of blood vessels and sympathetic innervation is essential for enhanced thermogenesis in cold. However, how these distinct processes are spatiotemporally regulated is not clear. To define the mediators of intercellular crosstalk in the BAT, we used single-cell transcriptomic analysis of BAT to build a network of ligand-receptor interactions. We identified Slit guidance ligand 3 (Slit3) as a new adipokine that mediates the crosstalk among adipocyte progenitors, endothelial cells, and sympathetic nerves. Using a combination of in vivo gain and loss of function studies, we showed that Slit3 is essential for cold-induced angiogenesis and sympathetic innervation in BAT. Loss of Slit3 reduced the density of blood vessels and sympathetic neurites in BAT. Consequently, mice lacking Slit3 expression in BAT exhibited severe cold intolerance, increased lipid accumulation and whitening of BAT, and reduced expression of thermogenic and mitochondrial genes in BAT. Conversely, the overexpression of Slit3 enhanced cold-induced BAT thermogenesis. Our mechanistic studies identified the key regulatory events that control Slit3 signaling in BAT. Collectively, these findings established the essential role of Slit3 signaling in regulation of BAT thermogenesis and introduced Slit3 as a new niche factor that promotes adipose tissue health. These studies introduced a potential node of intervention for improving systemic metabolism through the expansion of thermogenic fat.

Disclosure
T.Duarte afonso serdan: None. H.E.Cervantes: None. F.M.Neto: None. Y.Tseng: Consultant; Cellarity, LyGenesis. F.Shamsi: None.

Funding
National Institutes of Health (K01DK125608)
764-P: Time in Range and Time in Tight Range in Tirzepatide-Treated Patients Achieving Normoglycemia in the SURPASS-3 CGM Substudy
Authors: BERGENSTAL RICHARD M. , RODRÍGUEZ ÁNGEL , BENNEYWORTH BRIAN D. , NICOLAY CLAUDIA , BROWN KATELYN 
Published: June 2023

Tirzepatide (TZP), a novel once-weekly GIP/GLP-1 receptor agonist, demonstrated superior glycemic control vs insulin degludec (IDeg) in SURPASS-3 CGM. This post-hoc analysis evaluated changes from baseline to Week (Wk) 52 in Time in Range (TIR) (71-180 mg/dL), Time in Tight Range (TITR) (71-140 mg/dL), and glycemic variation (within-day coefficient of variation (CV) and Mean Amplitude of Glycemic Excursions (MAGE)) in TZP-treated patients achieving or not achieving HbA1c &lt;5.7% at Wk 52. Interstitial glucose values were collected by CGM at 5-minute intervals for 7 days at baseline, Wk 24, and Wk 52 in a subset of patients in the SURPASS-3 trial. Analyses used pooled data from all TZP arms (5, 10, 15 mg) only due to limited sample size for IDeg patients achieving HbA1c &lt;5.7% at Wk 52. Patients achieving HbA1c &lt;5.7% were slightly younger, had lower HbA1c and FSG, and higher TITR and TIR vs those not achieving HbA1c &lt;5.7% at baseline (Table). Increases in daily TITR and TIR from baseline (61.02% and 41.12% respectively) were seen in patients achieving HbA1c &lt;5.7% while those not achieving HbA1c &lt;5.7% had increased daily TITR and TIR of 36.62% and 32.40% (Table). Within-day CV and MAGE were reduced in both patient groups but more apparent in those achieving HbA1c &lt;5.7%. In TZP-treated patients, improvements in TIR, TITR, and glycemic variability were more pronounced in those achieving HbA1c &lt;5.7%.

Disclosure
R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. Á.Rodríguez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. B.D.Benneyworth: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. C.Nicolay: Employee; Eli Lilly and Company. K.Brown: Employee; Eli Lilly and Company.

Funding
Eli Lilly and Company
765-P: A Single Ascending Dose Study of the Novel GLP-1 Receptor Agonist GL0034 (Utreglutide) in Obese Individuals without Diabetes
Authors: THENNATI RAJAMANNAR , BURADE VINOD S. , NATARAJAN MUTHUKUMARAN , SHAHI PRADEEP , NAGARAJA RAVISHANKARA , PANCHAL SATISH T. , AGRAWAL SUDEEP K. , JANDRAIN BERNARD , DUVAUCHELLE THIERRY , GARCIA-OCANA ADOLFO , RUTTER GUY A. , PRATLEY RICHARD E. , THORENS BERNARD , VILSBØLL TINA 
Published: June 2023

The novel incretin analogue, GL0034 (GL), has potent agonist activity at glucagon-like peptide 1 (GLP-1RA) receptor. The primary objective of this phase 1 study in people with obesity was to assess the safety and tolerability of single-ascending doses of GL. Healthy individuals (N=24) with BMI ≥30 kg/m2 were randomized (6:2) to increasing doses of subcutaneous GL (1,520, 2,000 and 2,520 μg) or placebo once-weekly during four weeks. GL pharmacokinetics and key exploratory pharmacodynamic parameters (triglyceride, leptin levels and body weight) were assessed (Table). Most common GL-related adverse events were gastrointestinal with dose-dependent nausea, decreased appetite and vomiting. No injection site reactions or any other adverse events were noted. GL maximum concentrations ranged from 227 to 367 ng/mL, and mean half-life ranged from 99 to 118 h. Triglyceride levels were reduced from baseline following treatment with GL 2,000 and 2,520 μg dose at day 8. Decreases in leptin levels were dose-dependent. Reduction in body weight versus baseline reached a maximum of 3.3 kg with the 2,520 μg dose at day 8 and this effect was sustained through day 22 at every GL dose (Table). In conclusion, once-weekly GL demonstrated clinically relevant reductions in body weight in obese individuals and was well tolerated.

Disclosure
R.Thennati: None. A.Garcia-ocana: Consultant; Sun Pharmaceutical Industries Ltd. G.A.Rutter: Consultant; Sun Pharmaceutical Industries Ltd. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. B.Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd. 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. V.S.Burade: None. M.Natarajan: None. P.Shahi: None. R.Nagaraja: None. S.T.Panchal: None. S.K.Agrawal: None. B.Jandrain: None. T.Duvauchelle: None.