bluuebunny/crossref_metadata_2025_split huggingface dataset:
1334-P: Hepatocyte D-ß-Hydroxybutyrate Dehydrogenase Deficiency Improves Glucose Homeostasis and Prevents Diet-Induced Liver Fibrosis
Authors: STAGG DAVID B. , SEAY ALISHA R. , NELSON ALISA B. , D’AVIGNON DANA ANDRE A. , HUGHEY CURTIS C. , PUCHALSKA PATRYCJA , CRAWFORD PETER A. 
Published: May 2022

Interest in intermittent fasting, ketogenic diets, and exogenous ketone therapies for prediabetes, diabetes, and nonalcoholic fatty liver disease (NAFLD) is increasing, with numerous studies showing connectivity between ketone body metabolism and NAFLD progression. Previous studies from our group showed that exogenously administered ketone bodies have divergent effects on liver health: acetoacetate (AcAc) ameliorated, while its reduced redox partner D-B-hydroxybutyrate (D-BOHB) exacerbated lobular fibrosis. Here, we study the role of hepatic redox dependent interconversion of AcAc and D-BOHB in the setting of obesity and insulin resistance. Mice deficient in hepatocyte D-BOHB dehydrogenase (BDH1) and their littermate controls were maintained on high fat western diet (WD) for 18 weeks. Post WD challenge, these mice showed similar body weight, glucose, insulin, and circulating lipids in comparison to littermate controls. While livers of hepatocyte-specific BDH1-deficient mice lost the ability to generate D-BOHB, these mice remained capable to interconvert ketone bodies in extrahepatic tissues, leading to substantial circulating D-BOHB. Hepatocyte-specific BDH1 deficient mice maintained on WD displayed diminished glucose production and hepatic oxidative fluxes. Surprisingly, BDH1 deficient mice maintained normal static energy charge and NAD+/NADH ratios. Although insulin signaling in the liver and muscle was comparable between genotypes, knockout mice exhibited improved insulin sensitivity after acute insulin challenge. In addition, livers of knockout mice showed diminished liver fibrosis and oxidative stress. Taken together, these data support the notion for salutary roles of local AcAc, but detrimental roles of local D-BOHB on liver health and suggest that hepatic BDH1-dependent ketone body interconversion is a significant contributor to liver physiology in the setting of obese insulin resistance.

Disclosure
D.B.Stagg: None. A.R.Seay: None. A.B.Nelson: None. D.A.D’avignon: None. C.C.Hughey: None. P.Puchalska: None. P.A.Crawford: Advisory Panel; Abbott Diabetes, Johnson & Johnson Global Services.

Funding
NIH DK091538, and NIH AG069781
1336-P: FoxO1-ATGL-Sirt1-FoxO1 Feed Forward Signaling Mediates Effects on Hepatic Gene Expression and Glucose Homeostasis in LIRKO Mice
Authors: O-SULLIVAN IN SUG , BHATTACHARYYA SUMIT , LIEW CHONG WEE , LEE SAM M. , CORDOBA-CHACON JOSE , PERRY RACHEL J. , SHULMAN GERALD I. , UNTERMAN TERRY 
Published: May 2022

FoxO1 is a major target of insulin action and regulates expression of ATGL and its inhibitor, G0S2, in the liver (Cell Rep 15:349, 2016) . Here, we asked whether ATGL mediates effects of FoxO1 in liver-specific insulin receptor knockout (LIRKO) mice. Studies in LIRKO and IR/FoxO1 double knockout (LIRFKO) mice show ATGL expression is increased and G0S2 is suppressed in a FoxO1-dependent fashion when insulin signaling is disrupted in the liver. ATGL knockdown (KD) reduces high plasma glucose and insulin concentrations, HOMA-IR and fatty acid oxidation, and improves glucose tolerance in LIRKO mice. Hyperinsulinemic-euglycemic clamp studies show ATGL KD improves insulin sensitivity due to effects on both HGP and glucose utilization, reflecting changes in WAT lipolysis, BAT metabolism and hepatic gene expression. The expression of FoxO1-regulated gluconeogenic genes (PEPCK, G6Pase, PCO, PGC-1α) , hepatokines (e.g., follistatin) and IGFBP-1 is increased in LIRKO mice and reduced by ATGL KD, reflecting changes in acetylation of FoxO1 and its co-activator, PGC-1α (decreased in LIRKO, increased by ATGL KD) . Rictor acetylation, which promotes activation of Akt and phosphorylation of FoxO1, also is increased by ATGL KD in LIRKO mice and isolated hepatocytes. Since ATGL promotes activation of Sirt1 (Mol Cell 77:810, 2020) and Sirt1 deacetylates FoxO1, PGC-1α and rictor, these studies suggest FoxO1 promotes increased ATGL and Sirt1 activity, and that Sirt1 activation enhances the effects of FoxO1 on gene expression and glucose homeostasis in a feed forward fashion (FoxO1 -&gt; ATGL -&gt; Sirt1 -&gt; FoxO1) . Targeting the FoxO1/ATGL/Sirt1 pathway may provide a useful strategy for improving glucose homeostasis when insulin signaling is impaired in the liver.

Disclosure
I.O-sullivan: None. S.Bhattacharyya: None. C.Liew: None. S.M.Lee: None. J.Cordoba-chacon: None. R.J.Perry: None. G.I.Shulman: Advisory Panel; 89bio, Inc., AstraZeneca, Equator Therapeutics, Inc., Janssen Research & Development, LLC, Merck & Co., Inc., Consultant; DiCerna Pharmaceuticals, Inc., Novo Nordisk, Other Relationship; Generian Pharmaceuticals, iMetabolic Biopharma Corporation, Maze Therapeutics, The Liver Company, Stock/Shareholder; Levels Health, Inc. . T.Unterman: None.

Funding
Department of Veterans Affairs (5I01BX001968)
1343-P: The Acute Effects of Glucagon on Glucose Dynamics Are Not Impaired in Individuals with Nonalcoholic Fatty Liver Disease
Authors: KJELDSEN SASHA , JENSEN NICOLE J. , NILSSON MALIN , HEINZ NIKLAS , NYBING JANUS D. , LINDEN FREDERIK H. , HØGH-SCHMIDT ERIK , BOESEN MIKAEL P. , MADSBAD STEN , VILSTRUP HENDRIK , SCHIØDT FRANK V. , MØLLER ANDREAS , RASHU ELIAS B. , GLUUD LISE , HAUGAARD STEEN B. , HOLST JENS J. , RUNGBY JOERGEN , WEWER ALBRECHTSEN NICOLAI J. 
Published: May 2022

Glucagon is essential for glucose control and increased levels of glucagon (hyperglucagonemia) observed in patients with type 2 diabetes contribute to their hyperglycemia. Recently, hyperglucagonemia has also been found in individuals with non-alcoholic fatty liver disease (NAFLD) as well as impaired actions of glucagon on amino acid catabolism. Whether glucagon actions on hepatic glucose production are impaired is unknown. We investigated the acute effects of a single bolus of glucagon (0.2mg) on glucose dynamics in 18 normoglycemic individuals (age: 51±3 years, BMI; 31± 0.8kg/m2, hepatic fat content: 20±2%, fasting glucose: 5.5±0.1mM) with magnetic resonance imaging verified NAFLD and 22 controls (age: 38±3 years, BMI; 24± 0.8kg/m2, hepatic fat content: 4±0.1%, fasting glucose: 5.0±0.1mM) . On a separate day, a mixture of amino acids (14 g/L; 331 mg/min/kg body weight) was infused intravenously for 45min to evaluate the actions of endogenous glucagon on glucose dynamics. Glucose levels (see figure) were significantly increased in individuals with NAFLD 60min after the glucagon bolus and during the amino acid infusion with a maximal difference of 0.5mM 30min into the infusion. These data suggest that the actions of glucagon on hepatic glucose production are not impaired by NAFLD. Therefore, the hyperglucagonemia in patients with NAFLD may constitute a diabetogenic risk factor.

Disclosure
S.Kjeldsen: None. H.Vilstrup: None. F.V.Schiødt: Advisory Panel; Novo Nordisk. A.Møller: None. E.B.Rashu: None. L.Gluud: Advisory Panel; Novo Nordisk, Consultant; Pfizer Inc., Research Support; Alexion Pharmaceuticals, Inc., Gilead Sciences, Inc., Novo Nordisk, Sobi. S.B.Haugaard: None. J.J.Holst: Advisory Panel; Novo Nordisk, Board Member; Antag Therapeutics, Bainan Biotech. J.Rungby: Advisory Panel; Abbott, Boehringer Ingelheim International GmbH, Speaker’s Bureau; AstraZeneca, Bayer AG, Novo Nordisk, Pfizer Inc. N.J.Wewer albrechtsen: Research Support; Mercodia AB, Novo Nordisk, Regeneron Pharmaceuticals Inc., Speaker’s Bureau; Merck & Co., Inc., Mercodia AB. N.J.Jensen: None. M.Nilsson: None. N.Heinz: None. J.D.Nybing: None. F.H.Linden: None. E.Høgh-schmidt: n/a. M.P.Boesen: None. S.Madsbad: None.

Funding
NNF Excellence Emerging Investigator Grant – Endocrinology and Metabolism (Application No. NNF19OC0055001) , EFSD Future Leader Award (NNF21SA0072746) and DFF Sapere Aude.
1344-P: Engineering Physiologically Relevant Models of Hepatic Insulin Resistance
Authors: TEVONIAN ERIN , JEPPESEN JACOB F. , LAUFFENBURGER DOUGLAS , GRIFFITH LINDA G. 
Published: May 2022

An estimated 70% of individuals with type 2 diabetes also suffer from nonalcoholic fatty liver disease (NAFLD) . Insulin resistance is pathologically fundamental to both NAFLD and T2D, however the mechanisms of insulin resistance linking these complex diseases remains incompletely understood. Microphysiological systems provide an avenue to simulate disease parameters in the context of human biology, however current in vitro models of hepatic insulin resistance often include nutrient and insulin concentrations orders of magnitude above in vivo levels. Here, we established an in vitro 3D model culturing primary human hepatocytes and non-parenchymal cells in physiologically relevant media conditions simulating both baseline physiological and T2D conditions. Albumin secretion and cytochrome p450 assays indicate hepatocytes remain functional over two weeks in culture for both physiological and T2D conditions. Results further show hepatocytes cultured in physiological conditions maintain insulin responsiveness after 12 days in culture, measured by glucose output following dose response of insulin stimulation. Conversely, cells cultured in T2D media conditions have significantly attenuated response to insulin stimulation compared to the physiological condition. Measuring insulin clearance from the media also showed reduced clearance over time for the T2D conditions. Together, these results demonstrate the induction of hepatic insulin resistance through culture with insulin concentrations found in the portal vein of T2D patients. Studies further applying this in vitro model to understand insulin resistance mechanisms are ongoing.

Disclosure
E.Tevonian: Research Support; Novo Nordisk. J.F.Jeppesen: Employee; Novo Nordisk A/S. D.Lauffenburger: None. L.G.Griffith: Research Support; Novo Nordisk A/S, Novo Nordisk A/S, Novo Nordisk A/S, Novo Nordisk A/S, Novo Nordisk A/S, Novo Nordisk A/S, Novo Nordisk A/S.
1354-P: Alternate-Day Intermittent Fasting Improves Diabetes and Protects Beta-Cell Function in Polygenic Mouse Models of T2DM
Authors: PATEL SUMIT , YAN ZIHAN , REMEDI MARIA S. 
Published: May 2022

Type 2 diabetes (T2DM) , caused by the interaction of multiple genes and environmental factors, is characterized by hyperglycemia, insulin secretion deficiency and insulin resistance. Chronic hyperglycemia induces β-cell dysfunction and loss of β-cell mass/identity, increased apoptosis and β-cell dedifferentiation. Intermittent fasting (IF) , either alternate-day fasting (ADF) or time-restricted feeding, commonly used regimens for weight-loss, also induces metabolic benefits including reduced blood glucose, improved insulin sensitivity, reduced adiposity, inflammation and oxidative-stress, and increased fatty-acid oxidation; however, the mechanisms underlying these effects remain elusive. KK and KKAy, mouse models of polygenic T2DM spontaneously develop hyperglycemia, glucose intolerance, glucosuria, impaired insulin secretion and insulin resistance. To determine the long-term effects of IF on T2DM, 6-weeks old KK and KKAy mice were subjected to ADF for 16-weeks. While KKAy mice fed ad-libitum demonstrated severe hyperglycemia (˜500mg/dL) , increased plasma insulin, impaired glucose tolerance and insulin resistance at 8 weeks of age, KK mice showed blood glucose levels of ˜200mg/dL, but progressively became as severely diabetic as KKAy mice by 22-weeks. Strikingly, both KK and KKAy mice subjected to ADF showed reduced blood glucose and plasma insulin levels, decreased body weight gain despite increased food intake, reduced plasma triglycerides and cholesterol, and improved insulin sensitivity. They also demonstrated enhanced expression of the β-cell transcription factors PDX1 and NKX6.1, suggesting protection from loss of β-cell identity/dedifferentiation by IF. In addition, respiratory exchange ratio (RER) and movement were significantly enhanced in the ADF group, indicating peripheral benefits of IF. These results have important implications as an optional intervention for preservation of β-cell mass and function in T2DM.

Disclosure
S.Patel: None. Z.Yan: None. M.S.Remedi: None.

Funding
National Institutes of Health (R01DK123163)
1364-P: Low-Dose Whey Protein (WP) Microgel Improves Preprandial Satiety in People with Type 2 Diabetes (T2D) and Prediabetes
Authors: JOHANSEN ODD ERIK , SAVANT LOTIKA , MAGOS ZOLTAN , PHILIPPE DAVID , APRIKIAN OLIVIER 
Published: May 2022

Whey proteins (WP) , found in dairy products, are rich in branched chain aminoacids that may stimulate mediators of satiety (anorexigenic hormones, gastric emptying [GE]) . We recently reported that a low-dose (10g, 40 Cal) pre-meal drink (125 mL) , generated with novel micelle-technology (WP microgel [WPM]) , ingested 15 min before lunch increased GLP-1 and delayed early GE in people with T2D, while lowering glucose. We wanted to quantify the effect of WPM on self-reported hunger/fullness on a 1-9 likert scale (1: “Ravenously hungry”, 9: “Stuffed”) in people with T2D, or prediabetes, before and 15 min after WPM-drink consumption, ahead of lunch. “Hungry” was defined with scores 1-3, “satisfied” with 4-6, and “full” with 7-9. Categorical change, and the overall numbers of participants that improved/reduced their satiety by 1 or 2 units, were analyzed with sign tests. A total of 102 (40 males) people, aged 30-70 (71% 50-70 yrs) , with T2D (61%) , or prediabetes (39%) , were involved. A higher number of participants reported to be less hungry or more satisfied (Fig) 15 min after WPM-consumption, and a significantly larger proportion experienced a ≥ 1 unit increase (n=44/50) relative to a comparable negative change (p&lt;0.0001) , as well as a ≥ 2 unit increase (n=15/17, p=0.002) . These data suggest that low-dose, low-caloric, pre-meal WPM might improve satiety/reduce hunger, but further studies are needed.

Disclosure
O.Johansen: Employee; Boehringer Ingelheim International GmbH, Nestlé Health Science. L.Savant: None. Z.Magos: Consultant; Nestlé Health Science. D.Philippe: Employee; Nestlé Health Science. O.Aprikian: None.

Funding
Nestlé Health Science
139-OR: Large-Scale Sex-Stratified Additive and Recessive GWAS Identifies Novel Large-Effect Variants and Improves Polygenic Prediction for Type 2 Diabetes
Authors: SCHROEDER PHILIP H. , COLE JOANNE B. , LEONG AARON , FLOREZ JOSE C. , MERCADER JOSEP M. 
Published: May 2022

Introduction: Most genome-wide association studies (GWAS) of type 2 diabetes (T2D) assume an additive mode of inheritance and equal effects in men and women. These assumptions can preclude the discovery of variants with effects that are non-additive and/or sex-specific. Focused exploration of these effects may reveal novel genetic variation associated with T2D and improve the predictive performance of polygenic risk scores (PRS) .
Methods: We performed a sex-stratified GWAS, using additive and recessive models for T2D, in individuals of European ancestry in the UK Biobank (UKBB) and Genetic Epidemiology Research on Aging cohort. We also generated sex-specific and non-sex-specific T2D PRSs, using PRS-CS, and assessed their performance in Mass General Brigham Biobank (MGBB) .
Results: As the largest sex-stratified additive and recessive GWAS of T2D performed to date, this study included 30,625 cases and 223,442 controls. In the recessive analysis, we identified 7 novel variants, of which 1 was female-specific and 1 was male-specific. Among these variants, 4 were associated with over 10-fold increase in risk for T2D. The male-specific variant, rs35725476 (OR = 1.49, p = 3×10- 9) , is associated with higher expression of a long non-coding RNA in pancreatic islets (p = 3×10- 14) . In the additive analysis, we identified a novel female-specific protective variant, rs12109272 (OR = 0.91, p = 3×10-8) , which is associated with lower PCSK1 expression, lower risk of gestational diabetes (p = 1×10- 6) and lower fasting glucose (p = 6×10- 32) in independent cohorts. Finally, the sex-specific PRS outperformed the non-sex-specific PRS at predicting T2D in MGBB (AUC of 0.653 versus 0.643, p [of difference] = 2×10-4 in males; AUC of 0.674 versus 0.656, p [of difference] = 3×10-4 in females) .
Conclusions: These findings demonstrate the value of non-additive and sex-stratified analyses for both variant discovery and improving polygenic prediction for T2D.

Disclosure
P.H.Schroeder: None. J.B.Cole: None. A.Leong: None. J.C.Florez: Consultant; AstraZeneca, Goldfinch Bio, Inc., Other Relationship; AstraZeneca, Merck & Co., Inc., Novo Nordisk. J.M.Mercader: None.

Funding
American Diabetes Association (1-19-ICTS-068) ; National Human Genome Research Institute (U01HG011723)
1395-P: The Role of Adipocyte Connexin-43 in Mediating Adipose Tissue Inflammation and Dysfunction in Obesity
Authors: RON SOPHIE , RON IDIT , RATHAUS MORAN , LIVNE RINAT , TIROSH AMIR 
Published: May 2022

Obesity is a leading global health concern and a major risk factor for type-2 diabetes. Thus, identifying mechanisms linking obesity to insulin resistance is of great importance. Chronic low-grade inflammation of the adipose tissue (AT) observed in obesity has been shown as an important pathophysiological link between obesity and the development of systemic insulin resistance, by various mechanisms. Gap junction (GJ) intercellular-communication, primarily composed of connexin- (Cx) 43, has been recently reported to have immunomodulatory roles in various tissues, and increased Cx43 expression and GJ activity have been implicated in the response of various tissues to chronic stress conditions. We have therefore aimed to study the role of Cx43 in shaping the AT adaptive or maladaptive response to these cellular insults of obesity. In a diet-induced obesity mouse model we demonstrated an increase in Cx43 expression in the intact AT, which could be primarily attributed to increased Cx43 expression in adipocytes. In high fat diet-fed adipocyte-specific Cx43 knock-out mice (AdCx43KO) , we observed increased infiltration of macrophages to the AT as compared to wild-type (WT) mice. This was accompanied by morphologic changes in the AT, with increased variability in adipocyte size. While AdCx43KO mice did not significantly differ from WT mice in body weight, adiposity or food intake, the AdCx43KO mice demonstrated reduced whole-body insulin sensitivity assessed by insulin tolerance test. Mechanistically, we observed that adipocytes can interact directly with neighboring adipocytes as well as with macrophages via Cx43-composed gap junctions, an interaction that is likely to be key in attenuation of the tissue inflammatory response. Our results suggest an immunomodulatory and metabolic role for adipocyte-Cx43 in obesity.

Disclosure
S.Ron: None. I.Ron: None. M.Rathaus: None. R.Livne: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company.

Funding
Israel Science Foundation (922/17)
1413-P: Semaglutide 2.4 mg Improved Glucose Metabolism and Reverted Prediabetes to Normoglycemia in Adults with Overweight/Obesity vs. Liraglutide 3.0 mg (STEP 8)
Authors: ROSENSTOCK JULIO , GARVEY W. TIMOTHY , GOLDMAN BRYAN , KHALID USMAN , SØRRIG RASMUS , RUBINO DOMENICA 
Published: May 2022

The STEP 8 trial randomized 338 adults with overweight/obesity to weekly semaglutide 2.4 mg or placebo (PBO) , or daily liraglutide 3.0 mg or PBO, plus lifestyle intervention for 68 wks (3:1:3:1) ; PBO data not shown. Body weight (BW) change was greater with semaglutide vs. liraglutide (-15.8% vs. -6.4%, respectively; p&lt;0.0001) . This exploratory analysis assessed effects on glucose metabolism and glycemic status (normoglycemia; prediabetes; T2D) at wk 68 in participants (pts) with prediabetes at baseline (BL; 43 semaglutide/45 liraglutide; mean HbA1c 5.9/5.8%; fasting plasma glucose [FPG] 102/100 mg/dL; HOMA-IR 4.9/3.7; BW 104/1kg) . Analyses were not adjusted for multiplicity. At wk 68, 89.5% of pts were normoglycemic with semaglutide vs. 64.9% with liraglutide (p=0.01) (Figure) ; in these pts, 76.5% had weight loss ≥10% with semaglutide vs. 33.3% with liraglutide. One pt in each group developed T2D (Figure) . From BL to wk 68, semaglutide led to greater reductions vs. liraglutide in HbA1c (difference: -0.22 %; p=0.0002) , FPG (difference: -6.2 mg/dL; p=0.02) , and HOMA-IR (relative % difference: -28%; p=0.02) .
In conclusion, both semaglutide 2.4 mg and liraglutide 3.0 mg had clinically beneficial effects on glucose metabolism and glycemic status in pts with overweight/obesity and prediabetes, though the effect of semaglutide was greater vs. liraglutide.

Disclosure
J.Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck & Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. W.Garvey: Other Relationship; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Epitomee, JAZZ Pharmaceuticals, Novo Nordisk, Novo Nordisk, Pfizer Inc., Pfizer Inc. B.Goldman: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. U.Khalid: None. R.Sørrig: Employee; Novo Nordisk A/S. D.Rubino: Advisory Panel; Novo Nordisk, Other Relationship; Endocrine Society, PeerView, WebMD LLC, Research Support; Boehringer Ingelheim International GmbH, Novo Nordisk, Obesinov, SARL, Speaker's Bureau; Novo Nordisk, Stock/Shareholder; Novo Nordisk.

Funding
Funded by Novo Nordisk A/S
1416-P: UK First National Health Service (NHS) Endobarrier (EB) Service for Uncontrolled Diabesity: Four-Year Outcomes for All 62 Treated Patients
Authors: RYDER ROBERT E.J. , GUPTA PIYA SEN , YADAGIRI MAHENDER , BURBRIDGE WINNIFRED (WYN) , IRWIN SUSAN P. , BASHIR TAHIRA , GANDHI HARDEEP , WYRES MELANIE C. , ALLDEN RACHAEL , BLEASDALE JOHN , FOGDEN EDWARD , ANDERSON MARK 
Published: May 2022

EB, a 60cm endoscopically inserted proximal intestinal liner, reduces weight and HbA1c over 1 year. In the 1st NHS EB service, we provided EB to patients with sub optimally controlled diabesity and monitored outcomes in a registry. 44/62 (71%) completing 3 years post EB removal (age 51.3±7.8 years, 54% male, diabetes duration 14.56 (8-21) years, BMI 41.7±7.2 kg/m2) attended follow-up. During EB treatment, mean ± SD HbA1c fell by 1.9±1.8 %, from 9.1±1.8 to 7.2±1.0 % (p&lt;0.001) , weight by 17.3±9.0 kg from 122.8 ± 29.8 to 105.4±30.6 kg (&lt;0.001) , systolic BP from 138.8±14.3 to 125.9±14.9 mmHg (&lt;0.001) , serum alanine aminotransferase (liver fat marker) from 30.4±17.2 to 19.1±11.2 U/L (p&lt;0.001) . Median (IQR) total daily insulin dose reduced from 1 (50-171) to 30 (0-63) units (n=29, p&lt;0.001) ; 10/29 (34%) insulin treated patients discontinued insulin. 3-years post EB removal 33/44 (75%) maintained most of the improvement achieved with EB whilst 11/44 (25%) reverted to baseline (figure) . Of those deteriorating, all had depression and/or bereavement and/or major health problems/disability. 10/62 (16%) had early EB removal for adverse events or symptoms; all fully recovered after removal and most derived significant benefit. Our data demonstrates EB as highly effective in patients with refractory diabesity, with maintenance of significant improvement 3 years after removal in 75%

Disclosure
R.E.J. Ryder: None. P. Sen Gupta: None. M. Yadagiri: None. W. Burbridge: None. S.P. Irwin: None. H. Gandhi: None. M.C. Wyres: None. J. Bleasdale: None. E. Fogden: None. M. Anderson: None.