bluuebunny/crossref_metadata_2025 huggingface dataset:
329-OR: Videoconferencing for Diabetes Self-Management Support—A Viable Option for Meeting the Needs of High-Risk Patients in Rural Areas?
Authors: HAMMOUDEH RAWAN , KRALL JODI S. , JOHNSON PATRICIA A. , REYNOLDS SHARI L. , RUPPERT KRISTINE , NG JASON , SIMINERIO LINDA M.
Published: May 2022

Ongoing support is critical for effective diabetes (DM) self-management, but difficult to deliver, particularly in areas with limited resources. The purpose of the study was to assess the impact of a virtual support model on DM outcomes for high-risk patients in rural underserved communities.

Methods: Patients with HbA1c>9% receiving care in federally qualified centers were referred to the Telemedicine for Reach, Education, Access, Treatment and Ongoing Support (TREAT-ON) program, where a Diabetes Care and Education Specialist (DCES) provided in person diabetes self-management education and ongoing support through videoconferencing. Participant demographics, BMI and HbA1c were collected from patient records. Participants completed the DM Summary of Self-Care Activities, Distress and Empowerment Scales and Morisky Medication Adherence Measure at baseline and 6 months, and the Telehealth Usability Questionnaire at study completion. Pre/post values were compared for HbA1c, self-care, psychosocial and process outcomes.

Results: Participants (n=37) were 84% white, mean age 46.1 years with mean BMI 37.5. Glycemia improved with a mean reduction in HbA1c from 11.2% at baseline to 9.1% at follow-up (p<.001) . There was significant improvement in self-care behaviors of general diet (p=.001) and foot care (p=.041) . DM distress was reduced significantly (p<.001) , attributed to less emotional and regimen distress. Participants also reported a high level of satisfaction with TREAT-ON and interest in future use (4.6/5 points) .

Conclusions: Findings offer evidence of significant benefits and acceptability of a video-conferencing delivery model for DM self-management support. Future research should explore additional ways to empower individuals to continue and sustain improvements.

Disclosure

R.Hammoudeh: None. J.S.Krall: Research Support; Becton, Dickinson and Company, Sanofi. P.A.Johnson: None. S.L.Reynolds: None. K.Ruppert: None. J.Ng: Research Support; Sanofi. L.M.Siminerio: Advisory Panel; Abbott, Bayer AG, Research Support; Becton, Dickinson and Company, Sanofi.

Funding

National Institute of Diabetes Digestive and Kidney Diseases of the National Institutes of Health (R34DK123370) .
330-OR: Engagement, Satisfaction, and Preliminary Impact of a Personalized Diabetes Chatbot in a Diverse Cohort of Adults with Type 2 Diabetes
Authors: MAGEE MICHELLE F. , NASSAR CARINE M. , DUNLEA ROBERT , JAMES BECKY , MONTERO ALEX R. , SACK PAUL , TWEEDT APRIL , VETAL DONALD , COBB NATHAN K.
Published: May 2022

Strategies are needed to expand diabetes education and support among persons with diabetes (PWD) . We designed a personalized conversational agent (“chatbot”) to provide diabetes education and monitoring. Feasibility and preliminary efficacy were assessed in a pilot cohort of adults with type 2 diabetes (T2DM) .

Primary care patients with T2DM and an A1C of 8.0 - 8.9% were recruited from 4 sites in a regional health care system. Patients received proactive text/email notifications from the web-based chatbot which integrated assessment of self-knowledge and self-reported care behaviors, such as medication taking and checking blood glucose, with video and written educational content. Chat frequency started at once weekly, and content was delivered up to 12 months.

Between November 2020 and October 2021, 112 (84%) of 132 invited PWD agreed to enroll. Enrollees were predominantly African American (65%) and female (60%) , with mean age 58.3 +/- 10.6. Account activation was completed by 86 enrollees (77%) . Of those, 85% (76) completed at least one subsequent education chat. Amongst those 76 enrollees, 97% were very satisfied/satisfied with the chats and 84% strongly agreed/agreed that the chats made them feel more confident in managing their health. Participants have completed 914 chats over 12 months with 10,6data points collected. Only 5% disenrolled. There were no changes in self-reported medication adherence. Follow-up A1C was available for 71 participants. Participants who completed at least one educational chat had a 0.34 percentage point decrease in mean A1C vs. a 0.2 percentage point increase for participants who did not complete any educational chats, a difference of 0.54 between the 2 groups (p=0.089) .

This pilot study demonstrates patient acceptability and satisfaction and suggests improvement in A1C and self-care confidence in a primary care population. Future research with a larger population will be needed to validate these early findings.

Disclosure

M.F.Magee: None. C.M.Nassar: None. R.Dunlea: Employee; Conversa Health / American WEll. B.James: None. A.R.Montero: None. P.Sack: None. A.Tweedt: None. D.Vetal: Employee; Conversa Health. N.K.Cobb: None.
336-OR: A First-in-Human Single- and Multiple-Ascending Dose Study Evaluating Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Novel Oral Nonpeptide GLP-1 Receptor Agonist in Healthy Subjects
Authors: PRATT EDWARD J. , MA XIAOSU , LIU RONG , ROBINS DEBORAH A. , SLOOP KYLE , BENSON CHARLES
Published: May 2022

Background: LY3502970 (LY) is a novel, highly potent, orally bioavailable nonpeptide GLP-1 receptor agonist (RA) , and a potential alternative to injectable therapies or oral peptides whose absorption is affected by food or water intake. Objectives of this study were to evaluate safety, tolerability, pharmacokinetics (PK) , and pharmacodynamics (PD) of single and multiple doses of LY in healthy subjects.

Methods: This was a multi-part, randomized, double-blind, phase 1 study (NCT03929744) . In Part A, subjects received placebo or single-dose LY with 5 cohorts receiving escalating doses. In Part B, subjects received 4 weeks of daily placebo or repeated oral LY escalating weekly to 5 different final target doses. Overtly healthy adults 18-65 yrs old with body mass index 20-40 kg/m2 and A1c <6.5% were eligible.

Results: Of 133 subjects enrolled, 32 participated in Part A (mean age 43.4 yrs) and 60 participated in Part B (mean age 42.5 yrs) . There were no deaths or serious adverse events. Most common (occurring in ≥3 subjects) treatment-emergent adverse events in Part A were vomiting, nausea, and headache, and in Part B were nausea, headache, and constipation. PK was approximately proportional; mean Cmax in Part A was 1.4-14.9 ng/mL and mean t½ was 24.6-35.3 hrs across the dose range after single dose. In Part B, mean Cmax was 11.1-99.6 ng/mL and mean t½ was 48.1-67.5 hrs on Day 28 across the dose range. Single and repeated doses of LY decreased mean fasting glucose compared to baseline across Days 1-28. In Part B, significant reductions in body weight from baseline were observed after 4 weeks in 4 cohorts (except for the lowest dose) . Gastric emptying was delayed after initial LY dose but was no longer evident at Day 28.

Conclusion: This oral nonpeptide had safety and PD marker profiles similar to injectable GLP-1 RAs and PK enabling once daily dosing. These data support further clinical development.

Disclosure

E.J.Pratt: Employee; Eli Lilly and Company. X.Ma: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. R.Liu: Employee; Eli Lilly and Company. D.A.Robins: Employee; Eli Lilly and Company. K.Sloop: Employee; Eli Lilly and Company. C.Benson: None.
343-OR: Maternal Diabetes Is Associated with Hypothalamic Gliosis in Offspring
Authors: SEWAYBRICKER LETICIA E. , OLERICH KELSEY , KEE SARAH L. , MELHORN SUSAN J. , CHANDRASEKARAN SUCHITRA , SCHUR ELLEN
Published: May 2022

In utero exposure to gestational diabetes (GDM) or hypertension (HYP) is associated with child obesity. These maternal conditions alter the in utero milieu and may predispose offspring to obesity via an effect on the brain. Cellular inflammation (gliosis) in the mediobasal hypothalamus (MBH) has been associated with child and adult obesity and type 2 diabetes in adults. We evaluated the brain MRIs of offspring exposed to GDM or HYP during gestation for evidence of MBH gliosis. This case-control study included a subsample of 3child participants (9-11y) in the NIH ABCD study. Baseline T2-weighted MRI scans were analyzed for evidence of MBH gliosis (high MBH T2 signal) based on the mean bilateral MBH/Amygdala (AMY) T2 signal ratio. Putamen (PUT) /AMY and MBH/PUT were negative and positive control ratios, respectively. Findings from 49 children exposed to GDM and 53 exposed to HYP (by pregnancy survey) were contrasted to 2age- and sex-matched controls (healthy pregnancy) . Baseline, 1y and 2y follow-up anthropometrics were available. At baseline, groups did not differ on age, sex, race, and socioeconomic status. GDM group had more Hispanic children and higher birth weight than controls and HYP. Offspring exposed to GDM or HYP had higher BMI z-score, % of BMI 95th percentile, and waist/height ratio than controls at all time points (all P<0.01) . Overall, there were significant group differences in MBH/AMY signal ratio (F (2,294) :355, P=0.03, adjusted for site, age, sex and ethnicity) . Specifically, compared to controls, GDM-exposed offspring, but not HYP, had higher MBH/AMY signal ratio (GDM β:0.05, P=0.02; HYP β:0.03, P=0.11) . The results persisted when further adjusted for baseline BMI z-score (GDM β:0.04, P=0.03) . Results were replicated with the positive control ratio, but not the negative control ratio. GDM-exposed offspring have greater evidence of MBH gliosis, independent of body adiposity. This could represent one pathway by which the in utero environment may impact offspring’s future metabolic health.

Disclosure

L.E.Sewaybricker: None. K.Olerich: None. S.L.Kee: None. S.J.Melhorn: None. S.Chandrasekaran: None. E.Schur: None.

Funding

National Institutes of Health (R01DK117623)
347-OR: Effects of a Diabetes Prevention Program among Latino Youth with Prediabetes
Authors: PENA ARMANDO , OLSON MICAH , AYERS STEPHANIE , PATRICK DONALD L. , CASTRO FELIPE G. , HOOKER ELVA , LISH ELVIA , CORRAL LIBBY , KNOWLER WILLIAM C. , SHAIBI GABRIEL Q.
Published: May 2022

Introduction: Latino youth are disproportionately impacted by prediabetes and type 2 diabetes (T2D) . Lifestyle intervention is the first line approach for preventing or delaying T2D among adults with prediabetes. We assessed the efficacy of a diabetes prevention program among Latino youth with prediabetes.

Methods: A total of 117 Latino youth (mean±SD, age 13.5±1.4) with prediabetes and obesity were randomized to lifestyle intervention (INT) or usual care (UC) . The 6-month INT (n=79) included 1 d/wk of nutrition education and training and 3 d/wk of physical activity. UC (n=38) included 2 visits with a pediatric endocrinologist and registered dietitian to discuss diabetes risks and healthy lifestyle changes. A 75-g oral glucose tolerance test was used to assess glucose tolerance (2-h glucose) , insulin sensitivity (Matsuda Index) , and β-cell function (oral disposition index, oDI) at baseline, 6 months, and 12 months. Changes in outcomes were analyzed using latent difference scores models.

Results: The INT led to significant decreases in 2-h glucose (mean±SE, from 144.5±3.4 to 132.2±3.4 mg/dL, p=0.002) and increases in insulin sensitivity (from 1.9±0.2 to 2.6±0.3, p=0.001) and oDI (from 4.5±0.3 to 5.5±0.4, p=0.035) at 6 months, but these changes were not significantly different from UC (interaction, p=0.260, p=0.79, and p=0.78, respectively) . Both INT (-15.4 mg/dL, p=0.002) and UC (-15.1 mg/dL, p=0.005) had significant 12-month reductions in 2-h glucose that did not differ significantly from each other (interaction, p=0.97) . INT led to significant increases in oDI (from 4.5±0.3 to 6.2±0.6, p=0.035) and non-significant increases in insulin sensitivity (from 1.9±0.2 to 2.3±0.2, p=0.060) at 12 months that did not differ from UC (interaction, p=0.66 and p=0.37, respectively) .

Conclusion: Both INT and UC led to similar changes in T2D risk factors among high risk Latino youth. Diabetes prevention interventions that are effective in adults also appear to be effective in high risk youth.

Disclosure

A. Pena: None. M. Olson: None. S. Ayers: None. D.L. Patrick: Consultant; Allakos, Bristol-Myers Squibb Company, Grail, Philip Morris. F.G. Castro: None. E. Lish: None. W.C. Knowler: None. G.Q. Shaibi: None.

Funding

R01DK107579F31DK125037
349-OR: ADA President's Select Abstract: Circulating Level of DNA Methylation Near CPT1A and Long-Term Changes in Triglycerides in Response to Diet Interventions: The POUNDS Lost Trial
Authors: LI XIANG , SHAO XIAOJIAN , XUE QIAOCHU , GRUNDBERG ELIN , BRAY GEORGE , SACKS FRANK , QI LU
Published: May 2022

Background: Epigenome-wide association studies identified DNA methylation (DNAm) at several CpG sites of the carnitine palmitoyltransferase-1A (CPT1A) gene to be associated with triglycerides (TG) . However, little is known about whether the pre-treatment DNAm level at CPT1A is associated with changes in TG in response to weight-loss diet interventions.

Methods: We included 673 white participants with overweight or obesity, who were randomly assigned to 1 of 4 diets varying in macronutrients components. Blood DNAm levels were profiled by a high-resolution methyl-capture sequencing at baseline. We defined the regional DNAm at CPT1A as the average methylation level over CpGs within 500 bp of the 3 TG-related DNAm sites (cg00574958, cg09737197, and cg17058475) , which were closely located. Two-year changes in TG were calculated. Linear regression models were used to examine the associations between baseline DNAm at CPT1A and 2-year changes in TG.

Results: Higher regional DNAm level at CPT1A was associated with lower TG at baseline (β=-2.21, SE=1.01, p=0.029) . We found that dietary fat intake significantly modified the association between baseline DNAm at CPT1A and 2-year changes in TG, independent of concurrent weight-loss (p-int=0.018) . In the low-fat diet group, a higher regional DNAm level was associated with a greater reduction in TG at 2 years, after adjustment for age, sex, baseline body mass index, use of lipid-lowering medication, baseline TG level, and concurrent weight-loss (p=0.01) , whereas no such association was observed in the high-fat diet group (p=0.64) . A similar interaction pattern was also found between dietary fat and baseline DNAm at CPT1A on 2-year changes of TG in very-low-density lipoprotein without apolipoprotein C-III (p-int=0.01) .

Conclusion: Our data indicate that participants with a higher regional DNAm level at CPT1A benefited more in long-term improvement in TG when assigned a low-fat weight-loss diet.

Disclosure

X.Li: None. X.Shao: None. Q.Xue: None. E.Grundberg: None. G.Bray: None. F.Sacks: None. L.Qi: None.

Funding

The study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024) , the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383) , the Fogarty International Center (TW010790) , and Tulane Research Centers of Excellence Awards. Xiang Li was the recipient of the American Heart Association Predoctoral Fellowship Award (19PRE34380036) .
351-OR: Investigation of Novel Vitamin D Metabolites and Risk of Islet Autoimmunity and Progression to Type 1 Diabetes
Authors: KIM SOOJEONG , ZWICK NICOLE L. , CARRY PATRICK M. , DEFELICE BRIAN C. , JOHNSON RANDI K. , DONG FRAN , BUCKNER TERESA , VANDERLINDEN LAUREN A. , FROHNERT BRIGITTE I. , KECHRIS KATERINA , FIEHN OLIVER , REWERS MARIAN , NORRIS JILL M.
Published: May 2022

Lower blood 25 (OH) D concentration is associated with increased risk of islet autoimmunity (IA) in some cohorts; it is not known if 25 (OH) D metabolites are important after the onset of IA. We investigated novel vitamin D metabolites in development of IA and progression from IA to T1D in the Diabetes Autoimmunity Study in the Young (DAISY) . IA was defined as two or more consecutive visits positive for ≥ 1 autoantibody (IAA, IA-2A, GAD, ZnT8) . In a nested case-control study, we examined plasma vitamin D metabolites at a pre-seroconversion visit in 114 IA cases and 116 controls. We then followed 144 IA-positive children, of whom 46 developed T1D during a mean follow-up of 8.4 years. Plasma was quantified for 25 (OH) D3, 3-epi-25 (OH) D3, 25 (OH) D2, 24,25 (OH) 2D3, and 1,25 (OH) 2D3, using targeted LC-MS/MS. Logistic regression was used to examine pre-seroconversion metabolites and IA, and Cox regression was used to examine metabolites at seroconversion and progression to T1D. Both models adjusted for age, ethnicity, T1D family history and HLA-DR3/4. Higher pre-seroconversion level of 24,25 (OH) 2D3, an inactive catabolite of 25 (OH) D3, was associated with increased odds of IA (OR: 1.35; 95%CI: 1.03,1.78 per SD of 24,25 (OH) 2D3; p=0.031) . The association between 3-epi-25 (OH) D3 at seroconversion and progression from IA to T1D was modified by age at seroconversion. Higher 3-epi-25 (OH) D3 level was more protective against progression to T1D among children who seroconverted at an older age (HR: 0.47; 95%CI: 0.26, 0.85 for children at the 75th percentile of age at seroconversion (ie years)) compared to children who seroconverted at a younger age (HR: 0.88; 95%CI: 0.63, 1.24 for children at the 25th percentile (ie 3 years)) . Neither IA nor progression to T1D was associated with 25 (OH) D3, 25 (OH) D2 or 1,25 (OH) 2D3.Increased 24,25 (OH) 2D3 may play a role in IA development. The age-related heterogeneity of the relationship between 3-epi-25 (OH) D3 and T1D progression requires further investigation.

Disclosure

S.Kim: None. K.Kechris: None. O.Fiehn: None. M.Rewers: Consultant; Janssen Research & Development, LLC, Medscape, Provention Bio, Inc., Research Support; Dexcom, Inc., JDRF, Roche Diagnostics USA. J.M.Norris: None. N.L.Zwick: None. P.M.Carry: None. B.C.Defelice: None. R.K.Johnson: None. F.Dong: None. T.Buckner: None. L.A.Vanderlinden: None. B.I.Frohnert: Advisory Panel; Provention Bio, Inc.

Funding

National Institutes of Health (R01-DK104351, R01-DK32493, RI142483)
352-OR: Proteomics of Incident Diabetes in Midlife: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: ROONEY MARY R. , CHEN JINGSHA , TANG OLIVE , BALLANTYNE CHRISTIE M. , BOERWINKLE ERIC , TCHEUGUI JUSTIN ECHOUFFO , NDUMELE CHIADI E. , DEMMER RYAN , PANKOW JAMES S. , LUTSEY PAMELA , WAGENKNECHT LYNNE E. , GRAMS MORGAN , SELVIN ELIZABETH , CORESH JOSEF
Published: May 2022

Introduction: Proteomics could improve our understanding of the etiology of diabetes. We sought to identify proteomic signatures associated with incident diabetes.

Method: We used data from the Atherosclerosis Risk in Communities (ARIC) Study (visit 2, 1990-92) in midlife (ages 47-70y) . We examined associations of 4955 plasma proteins measured using an aptamer-based platform in 11341 participants (∼50% women, ∼25% Black) without prevalent diabetes. We divided the data into discovery (2/3) and validation (1/3) sets. We used multivariable Cox regression to examine protein associations with incident diabetes (diagnosis or medication) . Statistical tests were based on Bonferroni corrected p-values.

Results: In the discovery set (n=7907) , 1443 diabetes events accrued over a median (IQR 12, 21) years. We identified 568 proteins associated (p<0.05/4955) with incident diabetes after demographic adjustment and 162 proteins after additional adjustment for lifestyle and cardiometabolic risk factors (Figure) . In the validation set (n=3434, 723 events) , 78 of the 162 proteins were statistically significantly (p<0.05/162) associated with incident diabetes, including established (e.g. adiponectin, growth hormone receptor) and novel hits (e.g. apoplipoprotein F, carboxypeptidase M) .

Conclusions: We identified multiple established and novel proteins associated with incident diabetes in midlife.

Disclosure

M.R. Rooney: None. J. Chen: None. O. Tang: None. C.M. Ballantyne: Consultant; Abbott Diagnostics, Althera Pharmaceuticals, Amarin Corporation, Amgen Inc., Arrowhead Pharmaceuticals, Inc., AstraZeneca, Corvidia Therapeutics, Denka Seiken, ESPERION Therapeutics, Inc., Genentech, Inc., Gilead Sciences, Inc., Illumina, Matinas BioPharma Inc, Merck & Co., Inc., New Amsterdam, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Regeneron Pharmaceuticals Inc., Roche Diagnostics, Sanofi. Research Support; Abbott Diagnostics, Akcea Therapeutics, Amgen Inc., Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Ionis Pharmaceuticals, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals Inc., Roche Diagnostics. E. Boerwinkle: None. J. Echouffo Tcheugui: None. C.E. Ndumele: None. J.S. Pankow: None. P. Lutsey: None. L.E. Wagenknecht: None. M. Grams: None. E. Selvin: Other Relationship; Wolters Kluwer. J. Coresh: Consultant; Healthy.io Ltd. Research Support; National Institutes of Health.
362-OR: The Role of Intraislet Glucagon in Pulsatile Insulin Secretion
Authors: SUBA KINGA , PATEL YATEEN S. , ROBERTS ANNA , SHREWSBURY JED V. , CHEN SHIQIAN , KWOK RACHEL , KALOGIANNI VASILIKI , LIU XIAOXUAN , RUTTER GUY A. , JONES BEN , TAN TRICIA M. , OWEN BRYN , DRUCKER DANIEL J. , BLOOM STEPHEN , MURPHY KEVIN , SALEM VICTORIA
Published: May 2022

Background: Type 2 diabetes (T2D) is characterised by the loss of pulsatile insulin secretion. We studied mice with β-cell specific loss of the glucagon receptor (GCGRflox/flox X Ins-1 cre) , to investigate the role of intra-islet glucagon signalling on pan-islet calcium oscillations and islet pulsatility.

Methods: Frequently sampled intravenous glucose tolerance tests were conducted on GCGRKOβ-cells-/-and littermate controls. Crossing with GCaMP6f (STOP flox) animals allowed for β-cell specific expression of a fluorescent calcium indicator. These islets were functionally imaged in vitro and in vivo. Wild-type mice were transplanted with islets expressing GCaMP6f in β-cells into the anterior eye chamber and placed on a high fat diet. Half of the cohort received a glucagon analogue (GCG-analogue) for 40 days and the control group were fed to achieve weight matching. Calcium imaging was performed regularly during the development of hyperglycaemia and in response to GCG-analogue treatment.

Results: GCGRKOβ-cells-/- mice had poorer glucose tolerance in an intraperitoneal glucose tolerance test (control 12.7mmol/L ±0.6 vs. GCGRKOβ-cells-/- 15.4mmol/L ±0.0 at 15 min, p=0.002) ; fasting glycaemia was not different to controls. In vitro, GCGRKOβ-cells-/- islets showed profound loss of synchronised calcium waves in response to glucose which is only partially rescued in vivo. First-phase insulin pulsatility on peripheral blood sampling (n=5) was significantly disordered in GCGRKOβ-cells-/- mice (burst mass GCGRKOβ-cells-/- 0.30 ±0.03 versus 0.84 ±0.23 for controls p=0.04) . Diet induced obesity and hyperglycaemia resulted in a loss of co-ordinated calcium waves in transplanted islets. This was reversed with GCG-analogue treatment, independently of weight-loss (n=8) .

Conclusion: These data provide novel evidence for the role of intra-islet glucagon in sustaining synchronised calcium oscillations and support a possible therapeutic role for glucagonergic agents to restore the insulin pulsatility lost in T2D.

Disclosure

K.Suba: n/a. B.Jones: None. T.M.Tan: Consultant; Zihipp Ltd. B.Owen: None. D.J.Drucker: Consultant; Kallyope, Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Other Relationship; Eli Lilly and Company. S.Bloom: None. K.Murphy: None. V.Salem: None. Y.S.Patel: Employee; PerkinElmer. A.Roberts: None. J.V.Shrewsbury: None. S.Chen: None. R.Kwok: None. V.Kalogianni: None. X.Liu: None. G.A.Rutter: Advisory Panel; Sun Pharmaceutical Industries Ltd., Research Support; Sun Pharmaceutical Industries Ltd.
367-OR: Elucidating Mechanisms of α-Cell Dysfunction in T1D
Authors: PETTWAY YASMINYE D. , DAI CHUNHUA , RICHARDSON TIFFANY M. , WALKER JOHN T. , ARAMANDLA RADHIKA , POFFENBERGER GREG , BRADLEY AMBER , POWERS ALVIN C. , BRISSOVA MARCELA
Published: May 2022

We previously showed that α cell function and gene expression in islets from donors with type 1 diabetes (T1D) was significantly compromised. The reason (s) for these intrinsic α cell changes are unknown but may include loss of α-to-β cell contact, chronic hyperglycemia, and/or repeated hypoglycemic events. To test these concurrent hypotheses, we modeled human T1D islets using α cell-enriched (“T1D-like") human pseudoislets. The synchronous acquisition of intracellular Ca2+ and hormone response showed impaired intracellular Ca2+ signaling and glucagon secretion in T1D-like pseudoislets compared to controls containing both α and β cells. For modeling of chronic hyperglycemia, we transplanted pseudoislets into Nod-SCID-IL2Rγnull; RIP-Diphtheria Toxin Receptor mice made diabetic by diphtheria toxin (DT) -induced β cell depletion. In DT-treated mice, α cells in T1D-like pseudoislets maintained expression of MAFB and ARX but began to express the β cell-enriched transcription factor NKX6.1 (control vs. T1D-like, 3.43±2.49 vs. 54.8±20.8% NKX6.1+ α cells; P=0.046, N=3-5 mice, 2 donors/group) . To mimic repeated hypoglycemic events, we intermittently exposed T1D-like pseudoislets to low glucose (1.7 mM) (3 events x 3hr each) in vitro, using those remaining in basal glucose (5 mM) as control. Following multiple low glucose (MLG) exposures, T1D-like pseudoislets had reduced glucagon secretion in the presence of both 1.7 mM (control vs. MLG, 1.51±0.18 vs. 0.79±0.13 % glucagon content; P=0.011, N=4 donors) and 16.7 mM glucose (control vs. MLG, 0.79±0.13 vs. 0.39±0.% glucagon content; P=0.023, N=4) . Native human islets exposed to MLG had similar changes in glucagon response (control vs. MLG, 1.7mM: 0.63±0.vs. 0.22±0.% glucagon content, P=0.007; 16.7mM: 0.18±0.vs. 0.05±0.% glucagon content, P=0.029; N=4 donors) . These data suggest that loss of α-to-β cell contact and repeated exposure to low glucose impair α cell function. Further, exposure to chronic hyperglycemia may lead to changes in α cell identity state after β cell loss.

Disclosure

Y.D.Pettway: None. C.Dai: None. T.M.Richardson: None. J.T.Walker: None. R.Aramandla: None. G.Poffenberger: None. A.Bradley: None. A.C.Powers: None. M.Brissova: None.
371-P: Predicting Real-World Nonsevere Hypoglycemia in Americans with Diabetes (iNPHORM)
Authors: RATZKI-LEEWING ALEXANDRIA , HARRIS STEWART B. , BLACK JASON E. , ZOU GUANGYONG , WEBSTER-BOGAERT SUSAN , RYAN BRIDGET L.
Published: May 2022

Iatrogenic non-severe hypoglycemia (NSH) is a common and known precursor of severe hypoglycemia. Still, virtually no valid risk estimators exist to predict daytime and nocturnal NSH (NSDH, NSNH) in the general US population with diabetes. To redress this gap, we analyzed primary, self-reported data from the 1-year, prospective iNPHORM study.

Adults (18-90 years old) with insulin- and/or secretagogue-treated type 1 or 2 diabetes (T1D, T2D) were recruited from a US-wide probability-based internet panel. Twelve monthly emailed questionnaires assessed NSH risk. Prognostic models were built for recurrent 30-day NSDH and NSNH using negative binomial and machine learning penalized regression with lasso. Missing data were multiply imputed with chained equations.

N=986 were analyzed (T1D: 17%; age: 51 [SD: 14.3] years; male: 49.6%; T1D/T2D duration: 12 [IQR: 14] years; retention rate: 86.2%) . Among T2D respondents, 38% were on insulin alone, 38% secretagogues alone, and 24% insulin plus secretagogues. Follow-up incidence proportions and 30-day rates of NSDH and NSNH were 79.6% (95% CI: 77.0-82.0%) and 1.70 (95% CI: 1.59-1.82) , and 53.7% (95% CI: 50.5-56.7%) and 0.69 (95% CI: 0.64-0.75) , respectively. Risks of 30-day NSDH and NSNH increased with insulin+secretagogue therapy; A1C≤7%; insulin pump, continuous glucose monitoring, beta blockers, and antibiotics use; decreased number of medications; T1D and diabetes education; increased past severe hypoglycemia requiring healthcare; chronic kidney disease; depression; food insecurity; lack of insurance; younger age; female sex; and White race; risks decreased with A1C≥7.1%, cognitive impairment, hypoglycemia unawareness, and insurance. As well, higher income predicted NSNH risk. The optimism adjusted c-statistics for NSDH and NSNH risks were 0.78 and 0.77, respectively.

As the first US study to prospectively estimate real-world NSDH and NSNH risk, iNPHORM provides important insight into individual-level event detection and prevention.

Disclosure

A.Ratzki-leewing: Consultant; Eli Lilly and Company, Other Relationship; Sanofi. S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation. J.E.Black: None. G.Zou: None. S.Webster-bogaert: None. B.L.Ryan: None.

Funding

Sanofi Global
381-P: Recurrent Hypoglycemia Alters Endocrine Counterregulation during Insulin-Induced Hypoglycemia in Healthy and Diabetic Göttingen Minipigs
Authors: LYHNE MILLE KRONBORG , HINZ KATHRIN , VEGGE ANDREAS , STURIS JEPPE , KILDEGAARD JONAS , PEDERSEN-BJERGAARD ULRIK , OLSEN LISBETH HØIER
Published: May 2022

Hypoglycemia is a common adverse effect of insulin treatment in people with diabetes and recurrent episodes can alter counter regulation, ultimately increasing the risk of severe hypoglycemic episodes. The aim of this study was to investigate the effect of recurrent hypoglycemia on endocrine counter regulation during insulin-induced hypoglycemia in healthy and diabetic Göttingen Minipigs.

Twelve adult, female, intact Göttingen Minipigs with (n=6) and without (n=6) streptozotocin-induced diabetes were included. Three pigs in each group were preconditioned with either hypoglycemia (RH) or normoglycemia (RN) on three consecutive days using a three-hour hyperinsulinemic clamp procedure (16 pmol/kg/min human insulin and variable glucose infusion) targeted a fasted minipig euglycemic level of 63 mg/dL plasma glucose in RN and 27 mg/dL in RH. On day four, all groups were subjected to a four-hour hypoglycemic clamp with 18 mg/dL target. Samples for plasma glucose, glucagon and epinephrine were collected at predefined time points. Influence of diabetes status and preconditioning on endocrine counter regulation during the final clamp were investigated using a repeated measures linear mixed model.

Clamp glucose targets were reached in all groups. A blunted glucagon response was seen during the final hypoglycemic clamp in the RH groups (median 26.7 pM (IQR 21.6-33.2)) compared to RN groups (56.3 pM (46.3-63.5) , P=0.008) . Diabetes status did not influence the findings and no significant differences in plasma epinephrine were found between groups.

Göttingen Minipigs with and without streptozotocin induced diabetes exhibit blunted glucagon response to hypoglycemia after recurrent hypoglycemia similar to humans, indicating impaired counter regulatory response. Epinephrine response was not significantly affected. Further studies are needed to investigate the effect of RH on epinephrine counter regulation in the Göttingen Minipig.

Disclosure

M.Lyhne: None. K.Hinz: Employee; Antag Therapeutics, Novo Nordisk. A.Vegge: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. J.Sturis: Employee; Novo Nordisk A/S. J.Kildegaard: Employee; Novo Nordisk A/S. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi. L.Olsen: None.
39-OR: Improved Psychosocial and Quality of Life Measures in Children and Youth with Type 1 Diabetes Initiating Control-IQ Technology
Authors: ZUIJDWIJK CAROLINE S. , COURTNEY JENNILEA , MITSAKAKIS NICHOLAS , HAYAWI LAMIA , LAWRENCE SARAH E.
Published: May 2022

Objective: To determine perceptions of the impact of Control-IQ™ technology (CIQ) on psychosocial functioning and quality of life (QoL) in children/ youth with T1D and their parents, using patient and parent reported outcome measures (PROMs) .

Research Design and Methods: Single-center prospective real-world study of 6-18 year olds with T1D using the t:slim X2™ insulin pump, who were initiating CIQ. Youth (≥ 8years) and parents completed validated PROMs at baseline and end of study (16 weeks) . INSPIRE (INsulin delivery Systems: Perceptions, Ideas, Reflections and Expectations) end of study scores were the primary outcome with a score > 60 considered to indicate a perceived benefit of CIQ on psychosocial functioning and QoL. Glycemic control measures were recorded at baseline and every 4 weeks.

Results: In total, 65 children/youth with T1D participated; 50.8% female, median (IQR) age 13.9 (11.1, 15.7) years and T1D duration 6.2 (3.1, 8.4) years. INSPIRE end of study mean (SD) scores were 73.0 (11.6) for youth (n=49) and 70.7 (12.2) for parents (n=45) , both significantly > 60 (p < 0.001) . Diabetes Impact and Devices Satisfaction - Device Satisfaction subscale score increased by a mean (95% CI) of 0.43 (0.11, 0.74) in youth (p = 0.01) and 0.58 (0.31, 0.85) in parents (p<0.001) . WHO-5 well-being index median (IQR) score increased from 60 (48, 76) to 72 (60, 80) (p=0.25) in youth, and from 68 (55, 76) to 76 (68, 80) (p=0.002) in parents. Hypoglycemia Fear Survey mean (SD) score improved from 1.7 (0.6) to 1.4 (0.5) (p=0.01) in youth and from 2.0 (0.7) to 1.7 (0.6) (p<0.001) in parents. Time in range improved from 50.8% (baseline) to 62.2% (4 weeks) , with mean difference (95% CI) 9.62 (7.01, 12.23) , p<0.001; this was sustained to 16 weeks.

Conclusions: Initiation of CIQ in a real-world setting significantly improved measures of psychosocial functioning and QoL in children/youth with T1D and their parents. The change tended to be greater for parents than youth.

Disclosure

C.S.Zuijdwijk: Other Relationship; Medtronic, Research Support; Tandem Diabetes Care, Inc. J.Courtney: None. N.Mitsakakis: None. L.Hayawi: None. S.E.Lawrence: Advisory Panel; Pfizer Inc., Research Support; Tandem Diabetes Care, Inc.

Funding

Tandem Diabetes Care
390-P: Adipose Insulin Resistance Relates to Perturbed Renal Hemodynamics in Obese Youth with and without Type 2 Diabetes
Authors: PLATNICK CARSON , PRASAD POTTUMARTHI V. , LI LU-PING , PYLE LAURA , NELSON ROBERT G. , VAN RAALTE DANIËL , NADEAU KRISTEN J. , BJORNSTAD PETTER
Published: May 2022

Our objective was to compare renal hemodynamic function between obese youth with and without type 2 diabetes (T2D) and relate these measures to adipose insulin resistance (IR) .

We assessed insulin sensitivity and kidney function in obese youth with (n=31, 15.8 ± 1.8 years, BMI 35.6 ± 6.6 kg/m2) , and without (n=20, 15.3 ± 2.1 years, BMI 38.2 ± 7.4 kg/m2) T2D. A hyperglycemic clamp was performed with 20% dextrose to maintain mild hyperglycemia for 240 minutes. Free fatty acids (FFA) were measured at baseline and every minutes during the steady state. FFA suppression (baseline FFA subtracted from steady state FFA) was used to estimate adipose IR. Iohexol and p-aminohippurate clearances were used to measure GFR and renal plasma flow, respectively. Renal hemodynamic parameters were calculated using Gomez equations.

FFA suppression was attenuated in youth with T2D compared to obese controls (55.6% vs. 92.1%, p<0.0001) . Impaired FFA suppression was associated with higher intraglomerular pressure (r= -0.49, p=0.005) , higher efferent arteriolar resistance, (r= -0.53, p=0.002) and higher renal vascular resistance (r= -0.59, p=0.0005) .

Youth with T2D had impaired FFA suppression compared to obese controls, indicating adipose IR. Impaired FFA suppression was associated with perturbed renal hemodynamics, indicating a potential role for adipose IR in the development of early diabetic kidney disease.

Disclosure

C.Platnick: None. P.V.Prasad: None. L.Li: None. L.Pyle: None. R.G.Nelson: None. D.Van raalte: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi. K.J.Nadeau: None. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company.
400-P: More Pronounced Effect of Empagliflozin-Losartan Combination Therapy on Measured GFR and Blood Pressure vs. Either of the Drugs: A Crossover RCT in People with Type 2 Diabetes
Authors: VAN RAALTE DANIËL , HEERSPINK HIDDO L. , SCHOLTES ROSALIE
Published: May 2022

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and renin-angiotensin system inhibitors (RASi) improve kidney outcomes in people with type 2 diabetes (T2D) . Both drugs favorably affect kidney hemodynamic function which is characterized an acute GFR drop (reflecting reduced glomerular pressure) which, in part, underlies their protective effects. However, the interaction of these drugs on systemic and kidney hemodynamics is unstudied.

Methods: During this 4-arm, cross-over, placebo-controlled, double-blind intervention trial, twenty-four T2D patients on metformin and/or sulfonylurea therapy, (age 66±6 years, HbA1c 7.4±0.9%, measured GFR 108±20 mL/min, hypertension treated by beta blockers) were randomized to one-week treatment with empagliflozin (EMPA) 10mg QD, losartan (LOS) 50mg QD, empagliflozin+losartan (EMPA+LOS) and placebo. Fasting GFR was measured by steady-state plasma iohexol clearances. Blood pressure and heart rate (HR) were recorded. Statistical comparisons were done by Friedman test and Wilcoxon rank test correcting for multipele comparisons.

Results: Versus placebo, EMPA and LOS monotherapy reduced GFR by 7.0 mL/min (p=0.003) and 7.3 mL/min (p=0.01) respectively, while EMPA+LOS reduced by GFR by 10.7 mL/min (p<0.001) . Versus placebo, all treatment lowered blood pressure: EMPA -8.7 mmHg (p=0.04) , LOS -12.4 mmHg (p=<0.001) and EMPA+LOS -15.1 mmHg (p<0.001) . HR was unchanged. No safety concerns were observed.

Conclusion: In people with T2D and preserved kidney function, empagliflozin-losartan therapy induces more pronounced effects on measured GFR and blood pressure versus either of the drugs. These data support their combined use to improve kidney outcomes.

Disclosure

D.Van raalte: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi. H.L.Heerspink: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., Goldfinch Bio, Inc., Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Mundipharma, Traveere Pharmaceuticals, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. R.Scholtes: None.
413-P: The Role of Retinol-Binding Protein 4 in the Regulation of Adipocyte Renin-Angiotensin System via Toll-Like Receptor 4
Authors: ZHANG KANGZHEN , YANG QIN
Published: May 2022

Objective: To explore the relationship between serum adipokine retinol binding protein 4 (RBP4) levels and essential hypertension as well as the role of RBP4 in activating adipocyte renin-angiotensin system (RAS) .

Methods: From December 2016 to March 2019, 96 essential hypertension patients without any anti-hypertensive drugs and 64 age- and gender-matched healthy subjects were recruited. Serum RBP4 was determined by enzyme linked immunosorbent assay (ELISA) . Mouse primary white adipocytes were exacted and treated with adenovirus carrying the expression sequence of RBP4 with or without Toll-like receptor 4 (TLR4) inhibitor TAK242. The level of Angiotensin II (Ang II) in the cell supernatant was measured by ELISA. Western Blot and qRT-PCR were used to detect the expression of adipocyte differentiation-related genes and key genes of RAS system.

Results: RBP4 was significantly higher in patients with essential hypertension [median (interquartile range) : 30.14 (23.76-40.65) ng/mL] than in healthy controls [25. (20.05-31.04) ng/mL] (P<0.01) . Multivariate logistic regression analysis showed that RBP4 was an independent risk factor for hypertension (OR=1.12, P=0.002) . In adipocytes, overexpression of RBP4 increased the expression of angiotensin converting enzyme, angiotensinogen, renin/angiotensin-forming enzyme 1 and Angiotensin II Receptor 1, as well as the secretion of Ang II (P<0.05) . Treatment of TLR4 inhibitor TAK242 alleviated RBP4 overexpression-induced activation of RAS system in adipocytes (P<0.05) .

Conclusions: Elevated serum RBP4 is associated with increased risk of essential hypertension. The mechanism might be related to the active effects of RBP4 on RAS system via TLR4 in adipocytes. [Keywords] retinol binding protein 4; essential hypertension; RAS system; adipocytes; Toll-like receptor 4

Disclosure

K.Zhang: None. Q.Yang: None.

Funding

National Institutes of Health (R01DK100385 and R01DK121146)
414-P: Effects of Obesity and Type 2 Diabetes on Cardiac Structure and Arterial Stiffness
Authors: ENGE DANIEL , SCHÄFER MICHAL , FUJIWARA TAKASHI , CLARK ETHAN , ENGLUND ERIN , SCALZO REBECCA L. , RAFFERTY DEIRDRE , SCHAUER IRENE E. , ABUSHAMAT LAYLA , WHIPPLE MARY O. , HUNTER KENDALL S. , NADEAU KRISTEN J. , REGENSTEINER JUDITH G. , BARKER ALEX J. , REUSCH JANE
Published: May 2022

T2D is a global epidemic leading to excess cardiovascular (CV) mortality including heart failure (HF) . Strategies are emerging to prevent HF progression, so early detection is needed. We have identified preclinical cardiac dysfunction associated with central arterial stiffness and decreased cardiorespiratory fitness. We hypothesized that cardiac magnetic resonance (CMR) would identify changes in diabetes.

Methods: Age and BMI-similar premenopausal women and men with (n=24) and without (n=30) uncomplicated T2D were studied. CMR for cardiac function, regionally resolved pulse wave velocity (PWV) via 2D phase-contrast MRI assessed proximal arterial stiffness, and carotid to femoral applanation tonometry PWV (C-F PWV) using SphygmoCor assessed global arterial stiffness. The vascular territories covered by SphygmoCor does not include the ascending aorta.

Results: CMR showed significant changes consistent with cardiac dysfunction in T2D (Table 1) . PWV was significantly greater with T2D in the ascending and proximal descending aorta (p<0.05) . Subclinical diastolic cardiac dysfunction (EDVi) correlated with proximal PWV in T2D (p=0.046, r2=0.24) . C-F PWV did not differ between groups.

Conclusions: CMR detects early arterial stiffening in people with uncomplicated T2D and mild cardiac dysfunction. These findings support the use of CMR for detecting central arterial stiffness and incipient CV complications.

Disclosure

D.Enge: None. M.O.Whipple: None. K.S.Hunter: None. K.J.Nadeau: None. J.G.Regensteiner: None. A.J.Barker: None. J.Reusch: Advisory Panel; Medtronic. M.Schäfer: None. T.Fujiwara: None. E.Clark: None. E.Englund: None. R.L.Scalzo: None. D.Rafferty: None. I.E.Schauer: None. L.Abushamat: None.

Funding

National Institutes of Health (CX001532) University of Colorado Denver (NCT03419195) National Institutes of Health (R01-DK-124344) National Institutes of Health (K25HL119608)
420-P: Cystatin C Predicts Major Cardiovascular Events in Patients with Coronary Artery Disease Both among Patients with Type 2 Diabetes and in Nondiabetic Individuals
Authors: MADER ARTHUR , SAELY CHRISTOPH H. , MAECHLER MAXIMILIAN , LARCHER BARBARA , SPRENGER LUKAS , LEIHERER ANDREAS , MUENDLEIN AXEL , VONBANK ALEXANDER , DREXEL HEINZ
Published: May 2022

Cystatin C is an established biomarker for renal function, and, given the close association of chronic kidney disease and cardiovascular disease might indicate new-onset or deteriorating cardiovascular disease. However, evidence for cystatin C as a predictor of cardiovascular events is limited and controversial. We therefore aimed at investigating the role of Cystatin C as a predictor of future major adverse cardiovascular events (MACE) in a high risk-cohort of patients with coronary artery disease (CAD) . Cystatin C was measured in 1098 patients with angiographically proven CAD. Vascular events were recorded over a mean follow-up of 8.0±5.0 years. At baseline, 239 patients had T2DM and 859 did not have diabetes. During follow-up, 30.0% of our patients suffered MACE. Cystatin C proved to be a strong and independent predictor of vascular events in the total study cohort (standardized adjusted HR 1.20 [1.12-1.28], p<0.001) . When diabetes status was taken into account, cystatin C significantly predicted major cardiovascular events in non T2DM patients (HR=1.16 [1.08-1.26], p<0.001) and in patients with T2DM (HR=1.34 [1.13-1.60], p=0.001) . We conclude that cystatin C predicts major cardiovascular events in patients with coronary artery disease both among patients with type 2 diabetes and in nondiabetes individuals.

Disclosure

A.Mader: None. C.H.Saely: None. M.Maechler: None. B.Larcher: None. L.Sprenger: None. A.Leiherer: None. A.Muendlein: None. A.Vonbank: None. H.Drexel: None.
427-P: Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Are Mutually Independent Predictors of Major Cardiovascular Events in Patients with Established Cardiovascular Disease
Authors: SPRENGER LUKAS , MAECHLER MAXIMILIAN , VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: May 2022

Non-Alcoholic Fatty Liver Disease (NAFLD) is associated with insulin resistance, type 2 diabetes (T2DM) and cardiovascular disease. However, data on NAFLD in patients with established cardiovascular disease (CVD) are scarce.

Here, we therefore aimed at investigating the association of NAFLD with T2DM as well as its impact on the incidence of major cardiovascular events (MACE) in a large series of 1517 patients with established CVD (1199 patients with angiographically proven coronary artery disease and 318 patients with sonographically proven peripheral artery disease) , using the validated fatty liver index for the diagnosis of NAFLD.

At baseline, the prevalence of NAFLD was significantly higher in patients with T2DM than in non-diabetic subjects (61.3% vs. 39.8%; p<0.001) respectively. Prospectively, we recorded 498 MACE over a mean follow-up period of 10.0±4.5 years. The risk of MACE was higher in NAFLD patients than in those who did not have NAFLD (49.5 vs. 43.5%; p=0.020) and in patients with T2DM than in non-diabetic subjects (41.4 vs. 28.1%; p<0.001) . Cox regression models adjusting for conventional cardiovascular risk factors proved NAFLD and T2DM to be mutually independent predictors of MACE, with adjusted hazard ratios of 1.34 [1.06-1.69] p=0.013 and 1.59 [1.32-1.92]; p<0.001, respectively.

We conclude that NAFLD and T2DM are mutually independent predictors of MACE in patients with established CVD.

Disclosure

L.Sprenger: None. M.Maechler: None. A.Vonbank: None. B.Larcher: None. A.Mader: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None. C.H.Saely: None.