bluuebunny/crossref_metadata_2025 huggingface dataset:
270-OR: Loss of Myeloid IFNgamma Signaling Prevents Hepatic Inflammation and NASH in Obesity
Authors: FRIEDLINE RANDALL H. , ALBUSHARIF MAHAA , NOH HYE LIM , KIM ALLISON M. , KIM LAUREN H. , ZHENG DORIS X.T. , SWINAND GLENNA , BEAVERSON ANNIKA , HU XIAODI , TAUER LAUREN A. , MULLER WERNER , KIM JASON K.
Published: May 2022

Nonalcoholic steatohepatitis (NASH) is a major complication of obesity, and interferon-γ (IFNγ) is a key regulator of innate and adaptive immunity by priming macrophages and inducing an inflammatory response. We have recently generated mice with conditional deletion of IFNγ receptor in myeloid cells (Lyz-IFNγR2 KO) . After weeks of high-fat diet (HFD) , male KO and wild-type (WT) mice (n=6) developed fatty liver with a 70% increase in hepatic triglyceride levels compared to chow-fed mice (Figure 1; *P<0.vs. Chow) . Despite fatty liver, Luminex analysis found 20% to 80% decreases in intrahepatic levels of IL-1β, IL-7, IL-15, IFNγ, IL-9, KC, and MIG in KO mice (Figure 2; *P<0.vs. WT) . Next, male mice were fed with a methionine-choline deficient (MCD) diet (n=3) for NASH induction, and liver steatosis and fibrosis were noninvasively measured using Sonovol Ultrasound Imaging System. After 4 weeks of MCD diet, WT mice developed liver fibrosis, but KO mice showed significant attenuation of fibrosis, as indicated by a 20% decrease in liver stiffness (Figure 3) . Taken together, these results indicate that mice with conditional loss of IFNγ signaling in myeloid cells are protected from obesity-mediated hepatic inflammation and diet-induced NASH.

In conclusion, our findings identify myeloid IFNγ signaling as a potential therapeutic target in treating metabolic liver disease.

Disclosure

R.H.Friedline: None. L.A.Tauer: None. W.Muller: None. J.K.Kim: n/a. M.Albusharif: None. H.Noh: n/a. A.M.Kim: None. L.H.Kim: None. D.X.T.Zheng: None. G.Swinand: None. A.Beaverson: None. X.Hu: None.

Funding

National Institutes of Health (5U2CDK093000)
279-OR: Self-Efficacy, Diabetes Distress, Self-Care, and Blood Glucose: Within-Person Pathways in Adults with T1D
Authors: GONZALEZ JEFFREY S. , SPRUIJT-METZ DONNA , SCHNEIDER STEFAN , PETERS ANNE L. , CRANDALL JILL P. , CRESPO-RAMOS GLADYS , MENDEZ-RODRIGUEZ HEIDY , HOOGENDOORN CLAIRE J. , AGARWAL SHIVANI , JIN HAOMIAO , PHAM LOREE T. , ALI AINA , LEE PEY-JIUAN , RUELAS VALERIE F. , BASILE ROSE , PYATAK ELIZABETH
Published: May 2022

Introduction: Research links self-efficacy and diabetes distress to suboptimal diabetes self-care and blood glucose (BG) regulation. However, most studies rely on between-person comparisons that cannot rule out confounding by unmeasured variables or capture the dynamic interplay among these variables in real time. Pairing continuous glucose monitoring (CGM) with ecological momentary assessment, we sought to illuminate pathways of influence among these variables in a diverse sample of adults with T1D.

Methods: Participants (N=127, 41±15 yrs, 53% women, 39% Latino, 35% White, 10% Black) wore blinded CGM for 10-14 days and completed smartphone surveys 5-6 times per day. Using dynamic structural equation modeling, we evaluated within-person pathways shown in Figure 1.

Results: Hypothesized pathways were significant, as were indirect effects of:1) morning self-efficacy on that day’s mean BG via diabetes distress and self-care and2) diabetes distress on mean BG via self-care. Similar results were observed for time in range and SD of BG.

Conclusion: Our findings provide novel evidence for a sequential pathway of influence of psychological, emotional, and behavioral variables on BG regulation, observed over time and within individuals. These results provide a roadmap for interventions that target self-efficacy, diabetes distress, and self-care to improve BG regulation among adults with T1D.

Disclosure

J.S.Gonzalez: Consultant; Virta Health Corp. H.Jin: None. L.T.Pham: None. A.Ali: None. P.Lee: None. V.F.Ruelas: n/a. R.Basile: None. E.Pyatak: Research Support; Abbott Diabetes. D.Spruijt-metz: None. S.Schneider: None. A.L.Peters: Advisory Panel; Abbott Diabetes, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Shouti, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Other Relationship; Omada Health, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Stock/Shareholder; Teladoc Health. J.P.Crandall: Research Support; Abbott Diabetes. G.Crespo-ramos: None. H.Mendez-rodriguez: None. C.J.Hoogendoorn: None. S.Agarwal: Advisory Panel; Medtronic, Consultant; Beta Bionics, Inc.

Funding

National Institutes of Health (1R01DK121298-01; P30 DK111022)
28-LB: Increased Expression of Insulin Signaling Intermediates after Six Months of Metformin Medical Intervention in Women with Obesity and Polycystic Ovary Syndrome
Authors: ANDRISSE STANLEY
Published: May 2022

Objective: We hypothesize that in women experiencing obesity and PCOS, the women with higher levels of free androgen index will display more dysregulation in the insulin signaling pathway in adipose tissue. More specifically, we believe that visceral more than subcutaneous adipose tissue in the women in the study will display more dysregulation; and lastly that bariatric surgery will alleviate insulin signaling dysregulation.

Methods: Here, we performed molecular analyses (Western blots and qPRC) exploring the insulin signaling pathway in visceral and subcutaneous (SubQ) adipose tissue from women with obesity and PCOS undergoing RYGB bariatric surgery; and SubQ WAT from women with obesity and PCOS at baseline and six-months after medical intervention with metformin (MTF) .

Results: Subcutaneous (SubQ) white adipose tissue (WAT) displayed a trending (p=0.2) but non-significant increase in p-ACC compared to visceral WAT from women with PCOS and obesity pre-bariatric surgery. Six months of MTF increased p-ACC in SubQ WAT by 5-fold compared to zero months (baseline) in women with PCOS and obesity. IR displayed similar expression in the visceral compared to SubQ WAT in women with PCOS and obesity pre-bariatric surgery. IR expression increased by 20-fold at 6-months of MTF compared to baseline in SubQ WAT of women with PCOS and obesity. Phosphorylated forkhead box 01 (p-FOXO1) displayed similar expression in the visceral compared to SubQ WAT in women with PCOS and obesity. However, p-FOXO1 was decreased at 6-months of MTF compared to baseline in women with PCOS and obesity. p-AKT levels were similar in visceral compared to SubQ WAT in women with PCOS and obesity pre-bariatric surgery. However, p-AKT levels were significantly increased by 4-fold at 6-months of MTF compared to 0-months in women with PCOS and obesity.

Conclusion: None of the insulin signaling intermediates measured were altered in visceral compared to SubQ in women with obesity and PCOS.

Disclosure

S. Andrisse: None.
286-OR: The CREATE Trial: Randomized Clinical Trial Comparing Open-Source Automated Insulin Delivery with Sensor Augmented Pump Therapy in Type 1 Diabetes
Authors: BURNSIDE MERCEDES J. , LEWIS DANA M. , CROCKET HAMISH , MEIER RENEE , WILLIMAN JONATHAN , SANDERS OLIVIA J. , JEFFERIES CRAIG A. , FAHERTY ANN M. , PAUL RYAN , LEVER CLAIRE S. , WHEELER BENJAMIN J. , JONES SHIRLEY , FREWEN CARLA M. , GUNN TIM , LAMPEY CHRISTINA , DE BOCK MARTIN
Published: May 2022

Objective: Open-source automated insulin delivery (AID) pre-dated the availability of commercial systems and is used by thousands of people with T1D despite no regulatory approval. Our objective was to examine efficacy and safety of open-source AID.

Methods: A 24 week, multi-center RCT in children (7-15 years) and adults (16-70 years) with T1D comparing open-source AID (using the OpenAPS algorithm from a version of AndroidAPS implemented in a smartphone with the DANA-i™ insulin pump and Dexcom G6® CGM) , to sensor augmented pump therapy (SAPT) . The primary outcome was change in the percent of time in target sensor glucose range (TIR; 3.9-10mmol/L) from run-in to the last two weeks of the RCT.

Results: Ninety-seven patients (48 children and 49 adults) were randomized. Glycemic data are shown in table 1. Mean TIR (±SD) at study end was 74.5±11.9% using AID (Δ+ 9.6±11.8% from run-in; P<0.001) for adults, and 67.5±11.5% (Δ+ 9.9±14.9% from run-in; P<0.001) for children. Mean TIR at study end for the SAPT arm was 56.5±14.2% and 52.5±17.5% for adults and children respectively, with no change from run-in. No severe hypoglycemic or DKA events occurred in either arm. Two participants withdrew from AID due to hardware issues.

Conclusion: Open-source AID using the OpenAPS algorithm within a version of AndroidAPS, a widely used open-source AID solution, appears safe and effective.

Disclosure

M.J. Burnside: None. D.M. Lewis: None. H. Crocket: None. R. Meier: None. J. Williman: None. O.J. Sanders: None. C.A. Jefferies: None. A.M. Faherty: None. R. Paul: Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. C.S. Lever: None. B.J. Wheeler: Research Support; Dexcom, Inc., i-SENS, Inc., Medtronic. T. Gunn: Other Relationship; Sooil Development Co. C. Lampey: None. M. de Bock: Research Support; Dexcom, Inc., Medtronic, Novo Nordisk, SOOIL, Ypsomed AG. Speaker's Bureau; Ypsomed AG.

Funding

Health Research Council of New Zealand (19/481 and 21/001)
287-OR: Eliminating Manual Meal Bolusing: A Feasibility Trial Using MiniMed 780G and Hand Gesture Algorithms
Authors: ROY ANIRBAN , GROSMAN BENYAMIN , MILLER DIANA , ENGEL TALY , COHEN OHAD , SHALIT ROY , SHALEM SHIRAN , HIRSH MAYA LARON , COHEN YAEL , TIROSH AMIR
Published: May 2022

Background: Carb-counting is a significant burden for persons with diabetes who require insulin to mitigate postprandial hyperglycemia. A closed-loop (CL) system with auto meal-bolus that eliminates manual mealtime bolusing was studied in adults with T1D.

Methods: The system included the MiniMed™ 780G pump and a smartphone-paired smartwatch with the KLUE application that detects eating hand-gestures using motion sensors. A smartphone algorithm converted eating hand-gestures to carb amounts that were relayed to the pump for automatic bolusing. For 6 days, participants (N=17, aged 18-75 years) with T1D used the system with the KLUE app disabled and completed traditional carb-counting and -entry (Baseline) . Thereafter, the KLUE app was enabled for 5 days and carb-counting/carb-entry was prohibited (Study) . Participants were given the same 5 test-meals (one/day) of varying caloric and carb sizes during both periods. Otherwise, they had no other meal restrictions.

Results: No significant difference in TIR was observed between periods and time spent at <70 mg/dL was significantly less during the Study period (Table) .

Conclusion: Data suggest that the novel CL system maintains glycemic control similar to that with manual meal bolusing. By eliminating the burden of carb-counting, the new CL system may improve the quality of life in persons with T1D.

Disclosure

A.Roy: Employee; Medtronic. 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. B.Grosman: Employee; Medtronic. D.Miller: Employee; Medtronic. T.Engel: None. O.Cohen: Employee; Medtronic. R.Shalit: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk. S.Shalem: None. M.Laron hirsh: None. Y.Cohen: None.
288-OR: Effect of 24 Months of Optimised Glucose Control on Residual C-Peptide Secretion in Youth with New Onset Type 1 Diabetes (T1D)
Authors: BOUGHTON CHARLOTTE K. , WARE JULIA , ALLEN JANET M. , WILINSKA MALGORZATA E. , HARTNELL SARA , THANKAMONY AJAY , RANDELL TABITHA , GHATAK ATRAYEE , BESSER RACHEL , ELLERI DANIELA , TREVELYAN NICOLA , CAMPBELL FIONA , SIBAYAN JUDY , BAILEY RYAN , CALHOUN PETER , DUNSEATH GARETH J. , HOVORKA ROMAN , CONSORTIUM CLOUD
Published: May 2022

Background: We assessed whether improved glucose control with hybrid closed loop can preserve C-peptide secretion compared to standard insulin therapy in youth with T1D.

Methods: In a multicentre, randomised, parallel trial, youth aged to <17 yrs were randomised within 21 days of T1D diagnosis to hybrid closed loop using Cambridge algorithm (CL) or standard insulin therapy (control) for 24 months. Analysis was by intention to treat.

Results: We randomised 97 participants (mean±SD age 12±2 yrs) , 51 to CL and 46 to control. There was no difference in C-peptide AUC at 12 months (primary endpoint) or 24 months between groups (geometric mean [95% CI] 12 months CL: 0.35 pmol/mL [0.27, 0.43] vs. control: 0.46 pmol/mL [0.33, 0.61]; mean adjusted difference -0.[-0.14 to 0.03]; p=0. and 24 months CL: 0.17 pmol/mL [0.12, 0.23] vs. control: 0.25 pmol/mL [0.12, 0.39]; mean adjusted difference -0.[-0.14 to 0.05]; p=0.25) . Glycated haemoglobin was lower in the CL group by 4 mmol/mol [0.4%] (95% CI 0 to 8 mmol/mol [0.0 to 0.7%]) at 12 months, and mmol/mol [0.9%], (95% CI 7 to 15 mmol/mol [0.4 to 1.5%]; p<0.001) at 24 months. Five severe hypoglycaemic events occurred in CL group (3 participants) , and two in control group (2 participants) ; one DKA occurred in the CL group.

Conclusions: In new onset T1D, optimising glucose control for 24 months does not appear to prevent the decline in residual C-peptide secretion.

Disclosure

C.K. Boughton: Consultant; CamDiab Ltd. J. Ware: None. J.M. Allen: None. M.E. Wilinska: Consultant; CamDiab Ltd. S. Hartnell: Advisory Panel; Medtronic. Speaker's Bureau; Dexcom, Inc., Sanofi. Other Relationship; Ask Diabetes Ltd. A. Thankamony: None. T. Randell: Consultant; Abbott Diabetes. Speaker's Bureau; Novo Nordisk. A. Ghatak: None. D. Elleri: None. R. Bailey: None. G.J. Dunseath: None. R. Hovorka: Advisory Panel; Eli Lilly and Company. Research Support; Abbott Diabetes, Dexcom, Inc., Medtronic. Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. Other Relationship; CamDiab Ltd.

Funding

National Institute for Health Research EME Grant (14/23/09) Leona M & Harry B Helmsley Charitable Trust Grant (#2016PG-T1D046) Additional support for the artificial pancreas work is from National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z) . Medtronic and Dexcom supplied discounted CGM devices, sensors and details of communication protocol to facilitate real-time connectivity. Abbott Diabetes Care provided Libre Pro sensors.
290-OR: A Randomized Controlled Trial to Alleviate Carbohydrate Counting in Type 1 Diabetes with Automated Fiasp and Pramlintide Closed-Loop Delivery
Authors: COHEN ELISA , TSOUKAS MICHAEL , VON OETTINGEN JULIA E. , YALE JEAN-FRANÇOIS , GARFIELD NATASHA , VALLIS MICHAEL , GOUCHIE-PROVENCHER NIKITA , JAFAR ADNAN , GHANBARI MILAD , PALISAITIS EMILIE , RUTKOWSKI JOANNA , LEGAULT LAURENT , HAIDAR AHMAD
Published: May 2022

We conducted a non-inferiority randomized crossover trial to alleviate carbohydrate counting (CC) in people with diabetes using automated dual-pump delivery of faster aspart (Fiasp) and pramlintide. Adults (N=15, 9 F, 39 ± 14 years, A1c 7.2 ± 0.9%) and adolescents (N=15, 8 F, 16 ± 1 years, A1c 8.4 ± 0.9%) used (i) Fiasp and placebo with CC, (ii) Fiasp and pramlintide with meal announcement (MA) , and (iii) Fiasp and placebo with MA for 2 weeks. Fiasp and pramlintide were delivered at a fixed 1 U:µg ratio to mimic a co-formulation. MA arms delivered fixed, user-specific priming meal boluses, independent of carbohydrate content. Prior to the first arm, participants had a 1-week run-in with automated Fiasp (single pump) delivery and CC, with mean time in range (70-180 mg/dL) of 71% in adults and 64% in adolescents. In adults, mean time in range was 65% on Fiasp and placebo with CC, 71% on Fiasp and pramlintide with MA, and 64% on Fiasp and placebo with MA; non-inferiority with a pre-defined 6.25% margin was achieved in both MA arms with pramlintide and placebo (difference -6 [95% CI -12.6, 0.5]; 1 [-3.0, 4.6]) . In adolescents, mean time in range was 51%, 55%, and 46% in the three respective arms; non-inferiority was only achieved on Fiasp and pramlintide with MA (-4 [-9.0, 1.7]) . We conclude that automated Fiasp and pramlintide delivery may alleviate CC without degrading glucose control.

Disclosure

E.Cohen: None. E.Palisaitis: Other Relationship; Eli Lilly and Company. J.Rutkowski: None. L.Legault: Advisory Panel; Abbott Diabetes, Insulet Corporation, Novo Nordisk A/S, Other Relationship; Eli Lilly and Company, Research Support; AstraZeneca, Merck & Co., Inc. A.Haidar: Consultant; Eli Lilly and Company, Research Support; ADOCIA, Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. M.Tsoukas: Speaker's Bureau; AstraZeneca, Bausch Health, Canada, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Johnson & Johnson, Novo Nordisk Canada Inc. J.E.Von oettingen: None. J.Yale: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk Canada Inc., Sanofi, Research Support; Bayer AG, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Dexcom, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi. N.Garfield: None. M.Vallis: Advisory Panel; Bausch Health, Canada, Novo Nordisk Canada Inc., Consultant; Abbott Diabetes, LifeScan, Speaker's Bureau; AbbVie Inc., Bausch Health, Canada, LifeScan, Novo Nordisk, Novo Nordisk A/S. N.Gouchie-provencher: None. A.Jafar: None. M.Ghanbari: None.

Funding

Juvenile Diabetes Research Foundation International (2-SRA-2018-654-M-B) , Canada Research Chairs
315-OR: The Membrane Protease Prostasin Promotes Insulin Secretion by Regulating the Epidermal Growth Factor Receptor Pathway
Authors: ISHII TOSHIHISA , UCHIMURA KOHEI , FURUYA FUMIHIKO
Published: May 2022

Prostasin (PRSS8) is a serine protease that cleaves and regulates the activity of specific substrates. Epidermal growth factor receptor (EGFR) , which regulates insulin secretion and pancreatic β-cell proliferation, is activated via proteolytic shedding by PRSS8. In this study, we first found that PRSS8 is expressed in β-cells of mouse pancreatic islets. To clarify the molecular mechanisms of PRSS8-associated insulin secretion, we generated pancreatic β-cell-specific PRSS8 knockout (βKO) and PRSS8-overexpressing (βTG) mice. Overall, we observed glucose intolerance and decreased glucose-stimulated insulin secretion in the βKO mice compared to controls, whereas an increased response to glucose was observed in isolated islets from βTG mice. In vitro studies using MIN6 cells, we demonstrated that erlotinib, a specific inhibitor of EGFR, inhibits both EGF- and glucose-stimulated insulin secretion, and that glucose increases EGF secretion from β-cells. Following silencing of PRSS8, MIN6 cells showed lower levels of insulin secretion upon glucose stimulation, impaired EGFR signaling and lower expression levels of SNARE proteins. On the other hand, MIN6 cells overexpressing PRSS8 showed higher levels of insulin secretion at both the basal and glucose-stimulated insulin secretion, and higher phospho-EGFR levels. Furthermore, short-term exposure to glucose increased the expression level of endogenous PRSS8 protein in MIN6 cells, by blocking intracellular degradation. Our findings suggested that PRSS8 might be a blood glucose-dependent physiological modulator of insulin secretion via EGF-EGFR signaling in pancreatic β-cells.

Disclosure

T. Ishii: None. K. Uchimura: None. F. Furuya: None.

Funding

KAKENHI (19K17958 and 21K16367)
318-OR: Intermittent Fasting Improves ß-cell Function in Nonobese KATP-Induced Neonatal Diabetes through Reduction of Cellular Stress and Enhanced Autophagy
Authors: CASTELBLANCO ESMERALDA , SHYR ZEENAT A. , YAN ZIHAN , DIWAN ABHINAV , REMEDI MARIA S.
Published: May 2022

Diabetes progression is characterized by loss of functional β-cell mass. Non-obese KATP-GOF mouse models of human neonatal diabetes developed severe diabetes due to lack of insulin secretion; with a marked loss of β-cell mass/identity and dedifferentiation as diabetes progresses. Intermittent fasting (IF) reduces body weight, improves diabetes and autophagy in humans and obese mice, but the mechanisms underlying this in lean individuals remains elusive. Upon diabetes development, non-obese KATP-GOF mice were divided in two groups: i) fed chow diet ad libitum (AL) , ii) subjected to IF (24h fast/24hr feed cycles) . IF-KATP-GOF mice showed reduced blood glucose without changes in body weight or lean-fat mass compared to AL-KATP-GOF mice. The markedly reduced insulin and increased proinsulin levels in islets from AL-KATP-GOF mice were restored to normal levels in IF-KATP-GOF islets. IF-KATP-GOF islets showed reduced ATF6 and sXBP1 message levels and decreased sXBP1 and TXNIP protein levels compared to AL-KATP-GOF islets, suggesting reduced oxidative and ER stress. Strikingly, the markedly increased autophagy markers LC3II and P62 in AL-KATP-GOF islets were reduced to control levels in IF-KATP-GOF, suggesting improved autophagy. Electron microscopy confirmed increased insulin granules, reduced mitochondrial and ER damage, and decreased autophagosome accumulation in IF-KATP-GOF. While liver G6PC and PCK1 (gluconeogenesis) , FAS (lypogenesis/lipolysis) , and CPT1 and ATGL (β-oxidation/lipolysis) messages were increased, CRCT2 and FOXO1 (gluconeogenesis) , GCK (glycolysis) and PPARα (β-oxidation) were decreased. PPARγ and PPARα were decreased in brown adipose tissue.

In conclusion, our studies in KATP-GOF mice indicate the beneficial effects of IF not only on improving functional β-cell mass through decreasing oxidative and ER stress and enhancing autophagy, but also improving liver and adipose tissue function.

Disclosure

E.Castelblanco: None. Z.A.Shyr: None. Z.Yan: None. A.Diwan: Consultant; Biomedical systems (ERT) , Dewpoint Therapeutics. M.S.Remedi: None.

Funding

National Institutes of Health (GDK123163)
325-OR: Associations of Systolic Blood Pressure (SBP) with the Incidence of Heart Failure (HF) According to Glucose Tolerance Status (GTS)
Authors: FUJIHARA KAZUYA , YAMADA MAYUKO H. , YAMAMOTO MASAHIKO , OE MOMOKO , OSAWA TAEKO , IWANAGA MIDORI , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO
Published: May 2022

Although a linear relationship between SBP and risk of coronary artery disease or cerebrovascular disease was observed regardless of GTS, this association in HF is little known. We analyzed data from a nationwide claims database from 20to 20on 589,621 individuals. A Cox proportional hazards model identified risks of HF among 5 levels of SBP according to GTS [i.e. normal glucose tolerance (NGT) , prediabetes, diabetes (DM) ]. Incidence of HF per 1,000 person-years was 0.for NGT, 0.18 for prediabetes, and 0.80 for DM. Compared with SBP <1mmHg, hazard ratios (HR) (95% CI) for HF in the 4 higher NGT levels (120-129, 130-139, 140-149, ≥150 mmHg) increased from 1.93 (1.30-2.85) in the second level to 8.66 (5.44-13.39) in the fifth level. For prediabetes or DM, HF risk was significantly increased in the ≥150 mmHg group compared with the ≤1mmHg group. Compared with NGT and SBP ≤1mmHg, prediabetes or DM patients with SBP ≤1mmHg had approximately 2-fold or 5-fold risks of HF, respectively (Table) . Association of SBP with HF differs according to GTS. BP control is essential in those with NGT. The impact of risk factors other than SBP, such as poor glycemic control and physical inactivity, on the development of HF may increase with worsening of glucose status, suggesting that comprehensive management of risk factors other than BP is essential in those with prediabetes and DM to prevent HF.

Disclosure

K.Fujihara: None. M.H.Yamada: None. M.Yamamoto: None. M.Oe: None. T.Osawa: None. M.Iwanaga: None. T.Yamada: None. S.Kodama: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding

JSPS (21K11569)
33-LB: Using Telehealth to Deliver Diabetes Self-Management Education and Support (DSMES) In Rural Communities
Authors: SAHASRANAM PREM , GAVINI FRANK , SODHI SANDEEP , GARNERO THERESA , THOMPSON JACQUELINE , SALINAS CAROLYN M. , BAXTER STORMIE S.
Published: May 2022

The Centers for Disease Control and Prevention (CDC) National Diabetes Statistics Report 2020 emphasized that diabetes is an overwhelming national problem and especially prevalent in rural areas. Of the 12.3 million Californians with diabetes or prediabetes, only 1.23 million have been diagnosed, and 45% of those haven’t received diabetes education. Rural Californians have lower per capita income compared to urban Californians, equating to higher poverty rates (U.S. Department of Agriculture, 2021) , and they often face social service inaccessibility. Studies show that populations with low income have higher rates of unhealthy behaviors and are more likely to develop diabetes (Hsu et. al, 2012) . Revamping standardized diabetes prevention and education via a telehealth model to reach those in rural California has shown significant results. My Diabetes Tutor (MDT) , as part of a DSMES telehealth program, has provided a convenient and effective way to access diabetes education (DE) in rural areas and beyond. MDT delivers education for diabetes, gestational diabetes, prediabetes, and obesity in several languages from Certified Diabetes Care and Education Specialists. People have direct access to DE from home or a kiosk at their provider/health plan offices. Topics range from diabetes basics, nutrition, medication comprehension, emotional well-being, and reducing the risk of possible complications to understanding the use of insulin pumps and continuous glucose monitoring. People using MDT have shown an average A1C reduction of 1.2%, LDL decrease of 9.4 points, and improvements in blood pressure, weight, and self-care behaviors. The technology to deliver MDT DSMES was developed in collaboration with CharmHealth. MDT satisfies a great need to make DE accessible in rural California, which sets the stage for MDT’s planned national expansion, and to replicate this model to increase access to DE for people hospitalized with diabetes via virtual inpatient DE services.

Disclosure

P. Sahasranam: None. F. Gavini: None. S. Sodhi: None. T. Garnero: None. J. Thompson: Employee; Vida Health. Other Relationship; DayTwo Inc. C. M. Salinas: None. S. S. Baxter: None.
333-OR: Oxyntomodulin Analog LY3305677 (LY) Improves Glycemic Control and Weight Loss in Healthy Volunteers and Subjects with Type 2 Diabetes (T2D)
Authors: BENSON CHARLES , THAM LAI-SAN , DU YU , GURBUZ SIREL , ROBINS DEBORAH A. , MATHER KIEREN J. , TANG CHENG CAI , THOMAS MELISSA K.
Published: May 2022

LY is an acylated peptide analog of oxyntomodulin, a dual glucagon and GLP-1 receptor agonist. We conducted 2 randomized, double-blind, phase 1 multiple ascending subcutaneous dosing studies in healthy subjects (S1, NCT03325387) and in T2D patients (S2, NCT03928379) to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics. In S1, 4 cohorts of healthy subjects received placebo or LY once-weekly (QW) for 4 weeks. In S2, T2D subjects received placebo or LY QW in 2 cohorts with doses escalated over 12 or 16 weeks. A total of 54 subjects completed S1 and 24 patients completed S2. The most common treatment-emergent adverse events in both studies (decreased appetite, nausea, and diarrhea) were mostly mild in severity, and no deaths or serious adverse events were reported. Pharmacokinetic results were consistent between healthy subjects and T2D patients and supported weekly dosing. In healthy subjects, fasting glucose levels were decreased from baseline with increasing LY doses, and reductions in mean body weight from baseline were generally seen with increasing doses, with the largest change observed on Day 29. In T2D subjects during weeks 12-16, preliminary results of mean HbA1c changes from baseline ranged from -1.56% to -2.16% in LY-treated vs. -0.43% to -0.70% in placebo subjects, and mean body weight changes from baseline ranged from -2.30 kg to -11.24 kg in LY-treated vs. -0.35 kg to -2.03 kg in placebo subjects. Fasting glucose, triglycerides, cholesterol, and glucagon levels were decreased from baseline with LY vs. placebo at weeks 12-16. We conclude that LY was well tolerated in both studies, with a safety profile similar to selective GLP-1 receptor agonists. LY has a promising pharmacodynamic profile with potential for therapeutic benefit in T2D, obesity, or other metabolic diseases.

Disclosure

C.Benson: None. L.Tham: Employee; Eli Lilly and Company. Y.Du: None. S.Gurbuz: Employee; Eli Lilly and Company. D.A.Robins: Employee; Eli Lilly and Company. K.J.Mather: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. C.Tang: Employee; Eli Lilly and Company. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.
34-LB: Feasibility of Onboarding and Supporting Diabetes Technologies in Youth with Type 1 Diabetes during the COVID-19 Pandemic and Beyond
Authors: PELLIZZARI MARGARET , FISHBEIN JOANNA , FRANK GRAEME , NWOSU BENJAMIN U.
Published: May 2022

Background: Prior to COVID-19 lockdown, all new insulin pump training was done in house with the patient and families in attendance. However, the pandemic lockdown made it difficult for in-person education. Therefore, we embarked on virtual trainings as well as in-person training for new insulin pump starts.

Aim: To evaluate the feasibility and effectiveness of remote and in-person trainings by comparing management metrics in the years of 2020 and 2021.

Methods: We compared the age, race, sex, glycemic control at 6 months post insulin pump initiation, incidence of severe hypoglycemic episodes, and diabetic ketoacidosis (DKA) among the two training models.

Results: There were 118 insulin pump starts during the study period, of which 73 (62%) were in-person: (49 (67%) male, mean ± SD age was 10.6 ± 4.0 years, and 40 (55%) White, 11 (15%) Black and 22 (30%) other; and 39 (33%) were remote: (19 (49%) male, mean ± SD age: 11.6 ± 4.0 years, and 26 (67%) White, 4 (10%) Black, and 9 (23%) other race. There were no cases of severe hypoglycemia requiring a third-party assistance, hospitalizations, or DKA in the first 6 months after insulin pump initiation in either group. The proportion of subjects with optimal glycemic control (A1c of ≤7%) at 6 months following pump initiation was similar between the two training groups after adjusting for baseline A1c and BMI percentile group (p=0.35) .

Conclusion: This study found no evidence that remote pump training was less safe than in-person training. Therefore, remote training could be an alternative method to promote health equity by increasing access to diabetes technology for youth with type 1 diabetes in whom in-person training may be a challenge. A larger study is warranted to further evaluate the safety and effectiveness of this alternative method.

Disclosure

M. Pellizzari: None. J. Fishbein: None. G. Frank: None. B. U. Nwosu: None.
387-P: Novel Mitochondrial Complex I Modulator Reduces Diabetes-Associated Expression of Inflammation and Fibrosis Markers in Human Proximal Tubular Epithelial Cells
Authors: ABOOLIAN ARA , URNER SOFIA , RODEN MICHAEL , JANDELEIT-DAHM KARIN
Published: May 2022

Diabetic kidney disease (DKD) is a chronic microvascular complication of diabetes and accounts for 30-40% of all diabetic patients. Patients with DKD experience a progressive and irreversible decline of renal function until dialysis and kidney transplantation become the last line of intervention. Renal loss of function is driven by the diabetic milieu causing an imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defense mechanisms. The excessive amounts of ROS, driven either by mitochondria or by NADPH oxidases (NOXs) , cause inflammation and eventually lead to fibrosis and kidney failure. Methods: To address this problem, we cultivated healthy primary human renal cells (renal proximal tubular epithelial cells) under diabetic conditions. The cells were treated either with 5mM normal glucose (NG) , or 25mM high glucose with 10ng/ml TNF-α or TGF-β (HG) for 24h. In addition, a novel mitochondrial complex I modulator (BIM, 250nM) that has been designed to interfere with the ROS production at mitochondrial complex I has been tested in combination with the treatments. We analyzed the gene expression of different oxidative stress, inflammation as well as fibrosis markers. Results: On the transcriptional level, a treatment with BIM resulted in a significant downregulation of the HG treatment-induced expression of the oxidative stress markers SOD2 (by 40%) , NOX4 (by 61%) and NOX5 (by 34%) , the inflammation markers IL1B (by 29%) and TNFA (by 22%) , as well as the fibrosis markers TGFB1 (by 23%) , COL4A1 (by 50%) and CTGF (by 43%) , as determined by a two-way ANOVA and Tukey’s multiple comparison. Conclusion: The reduction of these markers after treatment with the complex I modulator suggests renoprotective properties in vitro. Further in vivo experiments in diabetic db/db mice will reveal whether the novel mitochondrial complex I modulator can attenuate renal injury in DKD.

Disclosure

A.Aboolian: None. S.Urner: None. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. K.Jandeleit-dahm: None.
399-P: Associations among Biomarkers of Inflammation, Tubular Injury, and Lipid Metabolism with Gestational Diabetes Mellitus (GDM) Status, Microalbuminuria, and Retinopathy in the MARIGOLD Study
Authors: LIU HONGYAN , SRIDHAR VIKAS S. , LOVBLOM LEIF ERIK , FEIG DENICE , HERER ELAINE , KISS ALEX , LIPSCOMBE LORRAINE , YIP PAUL M. , CHERNEY DAVID , SHAH BAIJU R.
Published: May 2022

Levels of hyperglycemia below those for diagnosis of diabetes are associated with microvascular injury, though the duration required to induce these complications remains poorly understood. This is especially relevant in patients with GDM due to its transient nature, which can nevertheless predispose to microvascular disease. Our aim was to assess whether mechanistic pathways associated with microvascular complications are upregulated in pregnant women with GDM or microvascular disease.

In this analysis, urinary albumin excretion and biomarkers of inflammation, lipoprotein metabolism, and tubular injury were quantified in 355 women at 32-40 weeks of gestation, with and without GDM. Adjusted associations between all biomarkers and each outcome variable - GDM status, microalbuminuria, and retinopathy - were performed using logistic regression.

Significant associations between GDM status and ApoA1, Il-6, IL-8, sTNFR I/II, NGAL, VEGF and vWF were observed (Figure 1A) . Increased CRP and sTNFR-II were associated with higher levels of albuminuria (Figure 1B) . CRP (Figure 1C) and previous GDM were associated with retinopathy.

In conclusion, GDM and its relatively short-term exposure to hyperglycemia are associated with pathways involved in diabetes and microvascular complications.

Disclosure

H.Liu: None. B.R.Shah: None. V.S.Sridhar: None. L.Lovblom: None. D.Feig: Advisory Panel; Novo Nordisk, Research Support; Apotex. E.Herer: None. A.Kiss: None. L.Lipscombe: n/a. P.M.Yip: None. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk.
4-OR: IL6R Signaling in Adipogenesis Mediates GLP-1 Analog Effects on Adipose Tissue Beiging
Authors: GUTIERREZ ABSALON D. , GAO ZHANGUO , YU YONGMEI , KOLONIN MIKHAIL
Published: May 2022

Mechanisms underlying antidiabetes effects of GLP-1 analogs such as liraglutide, collectively termed incretins, remain incompletely understood. While incretins boost insulin secretion, they also modulate the immune system and have anti-obesity effects. We discovered that prediabetic patients treated with incretins have increased thermogenic gene expression in supraclavicular adipose tissue (AT) . Interestingly, incretin-treated patients were found to have elevated levels of IL6 plasma, consistent with the observation that incretin treatment induces IL6 secretion by human monocytes. We hypothesized that incretins induce adipocyte browning via IL6 and used the mouse model to test if IL6 receptor (IL6Ra) signaling underlies the effects of the incretin-IL6 axis. We show that liraglutide transiently increases IL6 in circulation and ILRa signaling in AT while metronomic liraglutide treatment results in AT browning and improved glucose clearance in mice. IL6-blocking antibody treatment inhibited the thermogenic and antidiabetes effects of liraglutide. Based on the observation that IL6 induces thermogenic gene expression in cultured adipocytes, we hypothesized that the incretin-IL6 axis directly induces adipocyte browning. To test this, we generated mice with IL6Ra knockout in Pdgfrb-positive adipocyte progenitors (APC-KO) and in adipocytes (AD-KO) . We show that liraglutide-induced weight loss does not depend on IL6 signaling in the adipocyte lineage. However, both IL6Ra APC-KO and AD-KO mice failed to undergo thermogenic adipocyte browning and glucose utilization increase in response to liraglutide treatment. We conclude that the antidiabetes effects of metronomically administered incretins are mediated by transient upregulation of IL6, which activates canonical ILRa signaling and thermogenesis in adipocytes.

Disclosure

A.D.Gutierrez: None. Z.Gao: None. Y.Yu: None. M.Kolonin: n/a.

Funding

National Institutes of Health (NIDDK 5R21DK122234)
401-P: Development of Predictive Models for Health Care Outcomes of Patients with Chronic Kidney Disease and Type 2 Diabetes
Authors: SHEER RICHARD , NAIR RADHIKA , PASQUALE MARGARET K. , EVERS THOMAS , COCKRELL MEGHAN M. , GAY ALAIN , SINGH RAKESH , SCHMEDT NIKLAS
Published: May 2022

Progression of chronic kidney disease (CKD) is associated with increased risk of cardiovascular or renal events that contribute to increasing healthcare costs. The purpose of this study was to develop predictive models for rapid progression of CKD, days out of the home, and high costs for patients with both CKD and type 2 diabetes (T2D) . This retrospective observational cohort study used administrative claims data for patients with CKD (stage 3-4) and T2D aged 65-89 years enrolled in a Humana Medicare Advantage Prescription Drug plan 1/1/2012-12/31/2017. Patients were enrolled ≥1 year pre-index and followed up to one year post-index. Outcomes included rapid progression of CKD (>1 decrease in estimated glomerular filtration rate [eGFR] >5 mL/min/1.73m2 per year) , days out of the home (days spent out of their residence [e.g., hospital]; ≥2% days out of the home) and high costs (75-90th and >90th percentiles) post-index. Pre-index demographic and clinical characteristics, selected based on the LASSO technique, were included in logistic regression models to generate parameter estimates and model performance statistics. We identified 169,876 patients with CKD stage 3-4 and T2D. The C-statistics for the models ranged from 0.694 to 0.745. Lower initial eGFR led to incrementally higher risk for more days out of the home and high costs. Patients with urinary albumin to creatinine ratio (UACR) ≥300 mg/g had three times increased risk for rapid progression of CKD, 57% higher risk of more days out of the home, and, among those in the 75-90th cost percentile, had 38% higher costs than patients with UACR<30 mg/g. The presence of congestive heart failure, anemia, or higher pre-index utilization (≥5 physician visits) increased the risk for all outcomes. The predictive models developed in this study can be potentially used as decision support tools for clinicians and payers, and the risk scores from these models can be applied to future outcomes studies focused on patients with T2D and CKD.

Disclosure

R. Nair: None. M.K. Pasquale: Consultant; Bayer AG. T. Evers: Employee; Bayer AG. M.M. Cockrell: Employee; Humana. Stock/Shareholder; Humana. A. Gay: Employee; Bayer AG. R. Singh: None. N. Schmedt: Employee; Bayer AG.

Funding

This study was funded by Bayer.
405-P: Glycemic Control Impacts Renal Function Decline among People with Type 1 Diabetes after the Onset of Diabetic Kidney Disease
Authors: SHAH HETAL , MCGILL JANET B. , HIRSCH IRL B. , WU CHUN-YI , GALECKI ANDRZEJ , MAUER MICHAEL , DORIA ALESSANDRO , CONSORTIUM PERL
Published: May 2022

While poor glycemic control increases the risk of diabetic kidney disease (DKD) , its impact on renal function decline among those with established DKD is unclear. To examine this, we tested the relationship between baseline HbA1c and renal outcomes in the 3-year Preventing Early Renal Loss (PERL) trial (n=530) , which included persons with type 1 diabetes (T1D) and early-to-moderate DKD (eGFR 40-100 ml/min/1.73m2 and persistent albuminuria and/or ongoing GFR decline) . In Cox regression models, baseline HbA1c was associated (p<0.0001) with a higher risk of progression to ESKD or serum creatinine doubling (HR 1.87 per HbA1c unit increment, 95% CI 1.42-2.47) , and in mixed-effects linear regression models, with 0.87 and 0.51 ml/min/1.73m2/year higher rates of estimated glomerular filtration rate (eGFR) and iohexol GFR decline (p<0.00for both) . Baseline albumin excretion rate (AER) was a modifier of the HbA1c-GFR slope relationships (p for interaction <0.05) , such that HbA1c was associated with a higher rate of GFR decline among those with AER≥200 μg/min than among those with AER<20 or 20≤AER<200 (Fig.1) . Thus, worse glycemic control in PERL was a major determinant of GFR decline and ESKD risk after DKD onset, especially in persons with overt proteinuria. Efforts to normalize HbA1c should continue among such persons.

Disclosure

H.Shah: None. J.B.Mcgill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; Dexcom, Inc., Novo Nordisk. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. C.Wu: None. A.Galecki: None. M.Mauer: None. A.Doria: Research Support; Novo Nordisk Foundation. Perl consortium: n/a.

Funding

National Institutes of Health UC4DK101108Juvenile Diabetes Research Foundation 17-2012-377The Leona M. and Harry B. Helmsley Charitable Trust 2018PG-T1D014
41-LB: A Randomized, Placebo-Controlled Crossover Study to Evaluate the Effect of a Natural Powder Blend (Mulberry Leaf Extract [MLE], Vitamin D, Chromium, and Fiber) on Postprandial (PP) Metabolic Response in Type 2 Diabetes (T2D)
Authors: MOHAMED MAFAUZY , ZAGURY ROBERTO , BHASKARAN KALPANA , NEUTEL JOEL M. , MOHD YUSOF BARAKATUN-NISAK , MOONEY LINDA , PERRIN EMILIE , SMITH ALEX D. , APRIKIAN OLIVIER , VON EYNATTEN MAXIMILIAN , JOHANSEN ODD ERIK
Published: May 2022

MLE contains iminosugar alkaloids (of which 1-deoxynojirimycin [DNJ] is most abundant) , and phenolic and flavonoid functional ingredients, which can modulate PP metabolism. We tested a 2 g powder blend of 250 mg MLE (containing 12.5 mg DNJ) combined with fibre (1.75 g) , vit D (0.75 μg) , and chromium (75 μg) , versus placebo (PBO) , in a double-blind RCT. In this two-center (US, Singapore) , single-intervention study, in people with T2D (drug-naïve or on metformin) with Asian race, the powder was sprinkled over a 350 kcal breakfast meal (white bread, cheese, apple juice [55.4 g carbs]) , consumed after a 10h fast. PP blood glucose and insulin were assessed over 3h. Thirty individuals (mean age 59 years, HbA1c 7.1%, BMI 26.5 kg/m2) were enrolled. Compared to PBO, the MLE-blend significantly reduced PP incremental area under the glucose curve (iAUC) , at 1h (-20%, p<0.0001) , 2h (-17%, p=0.0001) , and 3h (-15%, p=0.0032) (Figure) . A significant 1h-reduction in insulin iAUC (-24%, p=0.0236) was also observed, but not at 2h, or 3h (Figure) . Compared to PBO, a 2 g natural powder blend of MLE, fibre, Vit D and chromium significantly reduced the overall glycemic burden and early insulin response of a carbohydrate-rich breakfast in T2D, suggesting its use as a convenient dietary adjuvant to improve PP metabolic response.

Disclosure

M. Mohamed: None. M. Von eynatten: Employee; Nestlé Health Science. O. Johansen: Employee; Boehringer Ingelheim International GmbH, Nestlé Health Science. R. Zagury: Consultant; Nestlé Health Science, Speaker’s Bureau; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Servier Laboratories. K. Bhaskaran: None. J. M. Neutel: None. B. Mohd yusof: Advisory Panel; Abbott, Merck & Co., Inc., Research Support; Nestlé Health Science, Speaker’s Bureau; Abbott, Boehringer Ingelheim International GmbH, Nestlé Health Science, Novo Nordisk. L. Mooney: None. E. Perrin: Other Relationship; Nestlé. A. D. Smith: Employee; Nestlé Health Science. O. Aprikian: None.

Funding

Nestlé Health Science
423-P: Predictors of Epicardial Adipose Thickness in Overweight and Obese Youth with Type 1 Diabetes
Authors: CIELONKO LUKE , SABATI ARASH A. , CHAMBERS MELISSA , NEWBERN DOROTHEE , CHAKRAVARTHY VARSHINI , SCHMIDT JACLYN , MULLEN JOHN , LUTZ NATALIE , SHAIBI GABRIEL Q. , OLSON MICAH
Published: May 2022

Objectives: Cardiovascular disease (CVD) is the leading cause of death in adults with type 1 diabetes mellitus (T1D) and risk factors for CVD are present early in the disease course. Epicardial adipose thickness (EAT) , a novel independent marker of CVD, is significantly increased in children with T1D compared to healthy controls. Obesity, a known CVD risk factor, is increasingly prevalent in the pediatric population and may confer additional risk in youth with T1D. The purpose of this study was to examine EAT in overweight/obese pediatric patients with T1D.

Methods: This was a single-center, cross-sectional study of 37 youth with T1D and BMI > 85th percentile (BMI percentile=93.1±4.3, age 13.5y±3.4, 62.1% female) . Waist circumference, blood pressure, HbA1C and a 2D echocardiogram measuring EAT were obtained. Insulin resistance was calculated via estimated glucose disposal rate (eGDR) .

Results: EAT was correlated with age (r=0.45, P=0.006) , BMI (r=0.58, P=0.0001) , waist circumference (r=0.64, P=0.0001) , and diastolic BP (r=0.37, P=0.023) , while inversely correlated with eGDR (r=-0.49, P 0.002) and most recent HDL level (r=-0.43, P=0.027) . There were no significant correlations between EAT and HbA1C (r=-0.01, P=0.9) or duration of diabetes (r=0.16, P=0.4) . After multivariate regression analysis, age and BMI were independent predictors explaining 43.7% of the variance in EAT (P=0.001) .

Conclusions: EAT is associated with measures of adiposity and CVD risk, however, only age and BMI were independent predictors of EAT among overweight and obese youth with T1D. In addition to a focus on tight glycemic control to prevent CVD in overweight and obese youth with T1D, further studies are needed to investigate the impact of BMI lowering interventions on EAT.

Disclosure

L.Cielonko: None. M.Olson: None. A.A.Sabati: None. M.Chambers: None. D.Newbern: None. V.Chakravarthy: None. J.Schmidt: None. J.Mullen: None. N.Lutz: None. G.Q.Shaibi: None.