bluuebunny/crossref_metadata_2025 huggingface dataset:
231-OR: Reduced NKX2-2 Expression Enhances Insulin Secretion by Primary Human ß-Cells
Authors: PETTWAY YASMINYE D. , WALKER JOHN , DAI CHUNHUA , ARAMANDLA RADHIKA , HOPKIRK ALEXANDER L. , REIHSMANN CONRAD , DAVIS COREY , JENKINS REGINA , SUSSEL LORI , PARKER STEPHEN , POWERS ALVIN C. , BRISSOVA MARCELA
Published: June 2023

Pancreatic islet endocrine cell phenotype and function are tightly regulated by transcription factor (TF) regulatory networks. In a mouse model of pancreas organogenesis, the key islet-enriched TF NKX2.2 governs both β and α cell specification. Further, loss of NKX2.2 in adult mouse β cells results in glucose intolerance, reduced insulin content, and polyhormonal β cells, demonstrating its importance in the maintenance of β cell phenotype. To understand the undefined role of NKX2.2 in adult human islets, we utilized adenoviral delivery of CRISPR and shRNA constructs in our primary human pseudoislet system to knockout (gNKX2-2) or knockdown (shNKX2-2) NKX2-2 in islet cells, respectively (n=4-6 donors without diabetes). Immunofluorescence analyses of gNKX2-2 pseudoislets demonstrated loss of NKX2.2 signal across β (81 ± 2.0%; p<0.001), α (58 ± 5.5%; p=0.001), and δ cells (83 ± 2.2%; p<0.001) compared to scrambled controls (gSCR). Surprisingly, functional assessment by dynamic perifusion revealed increased insulin secretion in gNKX2-2 versus gSCR pseudoislets measured as area under the curve in response to 16.7 mM glucose (6.64 ± 1.53 vs. 3.55 ± 1.53 ng/100 islet equivalents (IEQs); p=0.007) and cAMP-evoked potentiation with 16.7 mM glucose + 100 μM isobutylmethylxanthine (IBMX) (5.43 ± 0.50 vs. 3.15 ± 0.59 ng/100 IEQs p=0.003) without changes in total insulin content (gNKX2-2 vs. gSCR: 3.64 ± 0.75 vs. 4.78 ± 0.87 ng/IEQ, p=0.45). Furthermore, these findings were recapitulated in shNKX2-2 versus shSCR human pseudoislets (16.7 mM glucose: 10.17 ± 2.46 vs. 6.50 ± 2.51 ng/100 IEQs, p=0.02; 16.7 mM glucose + IBMX: 8.43 ± 1.31 vs. 4.21 ± 1.33 ng/100 IEQs, p=0.0002; insulin content: 6.18 ± 1.05 vs. 7.53 ± 1.26 ng/IEQ, p=0.36), where we observed a reduction in NKX2.2hi β (65 ± 10%; p=0.008), α (52 ± 5.5%; p=0.003), and δ cells (83 ± 4.6%; p=0.003). Collectively, our data indicate a critical role of NKX2-2 in the maintenance of primary adult human β cell function and suggest differential roles in islet function across species.

Disclosure

Y.D.Pettway: None. S.Parker: Research Support; Pfizer Inc. A.C.Powers: None. M.Brissova: None. J.Walker: None. C.Dai: None. R.Aramandla: None. A.L.Hopkirk: None. C.Reihsmann: None. C.Davis: None. R.Jenkins: None. L.Sussel: None.
234-OR: Succinate Potentiates Insulin Secretion through SUCNR1
Authors: SABADELL-BASALLOTE JOAN , ASTIARRAGA BRENNO D. , EJARQUE MIRIAM , REPOLLÉS-DE-DALMAU MARIA , SUREDA FRANCESC X. , DE JESUS DARIO F. , NÚÑEZ ROA CATALINA , MARI ANDREA , KULKARNI ROHIT , VENDRELL JOAN J. , FERNANDEZ-VELEDO SONIA
Published: June 2023

Here, we examined the role of succinate, a metabolite that acts by engaging the succinate receptor 1 (SUCNR1), in regulating insulin secretion by β-cells. We found that glucose increases SUCNR1 expression in β-cells and that activating SUCNR1 with either extracellular succinate or a synthetic agonist boosts glucose-stimulated insulin secretion through the Gq and PKC signaling pathways. Also, we identified that SUCNR1 is essential for preserving insulin secretion in a diet-induced insulin-resistance model. Mice with β-cell-specific SUCNR1 deficiency had impaired glucose tolerance and reduced insulin secretion when fed a high-fat diet, without changes in β-cell mass or insulin sensitivity. To investigate the physiological significance of succinate as a secretagogue in humans, we studied the potential connection between circulating succinate levels and β-cell function in response to oral and intravenous glucose challenges in a cohort of patients with impaired glucose tolerance (IGT). These patients were characterized by presenting hyperinsulinemia during both oral and intravenous glucose tests, compared to normal glucose tolerance (NGT) individuals. Moreover, succinate levels were elevated in IGT patients in response to these challenges compared to NGT patients, whereas circulating GLP-1 levels during the tests were not different between groups. Remarkably, we found that circulating succinate levels are positively correlated with insulin secretion potentiation during intravenous glucose administration, indicating that this system is activated by high glucose levels and partially regulated by the β-cell in an autocrine fashion. These findings suggest that succinate may act as a hormone, potentiating insulin secretion in humans through SUCNR1- a compensatory mechanism particularly relevant in the hyperinsulinemia elicited by insulin resistance. Our work sheds new light on the role of the succinate-SUCNR1 axis as a potential therapeutic target for improving insulin secretion in metabolic disorders.

Disclosure

J.Sabadell-basallote: None. J.J.Vendrell: None. S.Fernandez-veledo: None. B.D.Astiarraga: None. M.Ejarque: None. M.Repollés-de-dalmau: None. F.X.Sureda: None. D.F.De jesus: None. C.Núñez roa: None. A.Mari: Consultant; Eli Lilly and Company. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago.

Funding

Spanish Ministry of Science and Innovation (SAF2015-65019-R, RTI2018-093919-B-100); Instituto de Salud Carlos III (FI18/00151, CP10/00438, CPII16/00008); Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CB07708/0012); Catalan Association of Diabetes (PV21039S)
249-LB: CRISPR/Cas9-Mediated Deletion of FGF Receptor 1 in AgRP Neurons Results in Obesity and Impaired Glucose Metabolism
Authors: SHOOKSTER DANIEL , HUANG HU
Published: June 2023

Obesity remains a growing epidemic as current treatment approaches have limited success. We have recently identified hypothalamic α-Klotho as a novel metabolic regulator; however, the downstream pathways remain unclear. Using a Cre-dependent CRISPR/Cas9 system alongside transgenic mice to investigate the role of FGFR1 in defined neuron populations of adult mice, we show that deletion of FGFR1 in AgRP neurons results in increased weight gain and adiposity, worsened glucose tolerance, and increased liver lipid accumulation. Mechanistically, deletion of FGFR1 negates pERK signaling and the ability of α-Klotho to reduce fasting-induced AgRP neuron activity in mice. While in hypothalamic cells, knockdown of FGFR1 prevents FOXO1 phosphorylation by α-Klotho, providing evidence of an α-Klotho-FGFR1-PI3K-FOXO1 signaling axis in AgRP neurons. Taken together, our data demonstrate the metabolic role of FGFR1 in AgRP neurons and identify it as a critical regulator of energy and glucose homeostasis.

Disclosure

D. Shookster: None. H. Huang: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (DK121215 to H.H.)
25-LB: Oral APX3330 Reduces the DRSS Worsening after 24-weeks of Daily Treatment—Efficacy and Safety Results of the ZETA-1 Phase 2 Trial in Diabetic Retinopathy
Authors: GONZALEZ VICTOR H. , BRIGELL MITCHELL G. , SU DANIEL , PATEL RONIL , WITHERS BARBARA , KELLEY MARK , HADDAD LOUIS , SOOCH MINA , PEPOSE JAY S. , KAISER PETER K. , BOYER DAVID S.
Published: June 2023

APX3330 is an oral, novel, small-molecule inhibitor of Ref-1, in diabetic retinopathy (DR) patients. ZETA-1 was a multi-center, placebo-controlled, double-masked Phase 2 trial. Subjects were randomized 1:1 to receive APX3330 (total 600 mg/day) or placebo BID for 24 weeks. Eligible subjects had non-proliferative DR (NPDR) or mild proliferative DR, corresponding to DR severity scale (DRSS) scores of 47, 53, or 61 as confirmed by the Duke reading center. The primary efficacy endpoint was the % of subjects with ≥ 2-step DRSS improvement in the study eye at week 24 compared to baseline. Several key pre-specified endpoints were evaluated.

Results: ZETA-1 trial enrolled 103 DR subjects with 90% having NPDR with a baseline DRSS of 47 or 53. The primary endpoint was not met with 8% of study eyes showing ≥ 2-step DRSS improvement in each treatment group. Consistent with its mechanism of action of bringing VEGF and inflammation to physiologic levels, APX3330 demonstrated a statistically significant reduction in binocular ≥ 3-step worsening after 24 weeks, with 16% of placebo subjects worsening compared to 0% of APX3330 subjects (p=0.04). 19% of placebo subjects lost ≥5 BCVA letters compared to 5% of APX3330 subjects (p=0.07). AEs that occurred in ≥5% of subjects were pruritis, rash, and worsening of DR or DME in the placebo group. No subjects withdrew due to rash or pruritis.

Disclosure

V. H. Gonzalez: Consultant; Alimera, Bausch + Lomb, Research Support; Adverum Biotechnologies, AbbVie Inc., Apellis, Genentech, Inc., IQVIA Inc., Iveric Bio, Regeneron. P. K. Kaiser: Consultant; Ocuphire, AbbVie Inc., Bausch + Lomb, Bayer Inc., Regeneron, Ocular Therapeutix, Novartis, REGENXBIO Inc. D. S. Boyer: Advisory Panel; 3Boehringer Ingelheim Canada Ltd. /Ltée, AbbVie Inc., Adverum Biotechnologies, Alexion Pharmaceuticals, Inc., Alkahest, Allergan, Amgen Inc., Apellis, Bausch + Lomb, Chengdu Pharmaceuticals, F. Hoffmann-La Roche Limited, Genentech, Inc., Iveric Bio, Gyroscope, Janssen Pharmaceuticals, Inc., Kodiak Pharmaceuticals, NGM Biopharmaceuticals, Oxurion, Novartis, ocuphire, Roche Pharmaceuticals, REGENXBIO Inc., Other Relationship; 4D Pharma PLC. M. G. Brigell: Consultant; Ocuphire Pharma, ONL Therapeutics. D. Su: None. R. Patel: Employee; Ocuphire Pharma. B. Withers: Employee; Ocuphire. M. Kelley: None. L. Haddad: None. M. Sooch: Board Member; Ocuphire Pharma, Employee; Ocuphire Pharma, Stock/Shareholder; Ocuphire Pharma. J. S. Pepose: Consultant; Acufocus, Bausch + Lomb, Brim Biotechnology, Johnson & Johnson Medical Devices Companies, Kala Pharmaceuticals, Mimetogen, Ocuphire Pharma, OKYO Pharma, Stuart Therapeutics, Thea Pharma.
254-LB: In Vivo Mapping of Postprandial Hepatic Glucose Metabolism Using Stable Isotope-Assisted Metabolic Imaging in Roux-en-Y Gastric Bypass Adults and Nonoperated Controls
Authors: LANGE NAOMI F. , POLI SIMONE , HERZIG DAVID , SCHIAVON MICHELE , DALLA MAN CHIARA , KREIS ROLAND , BALLY LIA
Published: June 2023

We aimed to assess the impact of Roux-en-Y gastric bypass (RYGB) on hepatic glucose (glc) kinetics using stable isotope-assisted magnetic resonance spectroscopy (MRS). Ten post-RYGB adults (2M, age=39.2±3.1 y, BMI=28±1 kg/m2; mean±SE) and ten non-operated adults (HC; 5M, age=36.4±3.2 y, BMI=26±1 kg/m2) underwent metabolic imaging in a 7T (Terra, Siemens) scanner with a triple-tuned surface coil over the liver. Scanning was performed before (T0) and up to 150 min (T150) after oral intake of 60g of deuterated [6,6′-2H2]-Glc using interleaved sequences of 2H2-MRS imaging (hepatic 2H2-glc signal) and 13C-MRS (glycogen). Blood samples were collected for profiling of plasma glc, glc enrichment, insulin and glucagon. General Additive Mixed Models were used for comparative analyses. We observed distinct postprandial profiles of hepatic glc signal (Fig 1). RYGB subjects showed earlier and higher glc peaks, which were mirrored by hepatic glc signal in both groups. Insulin peak levels were higher and glc nadir lower in RYGB. Postprandial endogenous glc was higher in RYGB, which was paralleled by a fall in hepatic glc. In HC, hepatic glc remained elevated until the end of the experiment. Non-invasive stable isotope-assisted MRS imaging has the potential to unravel changes in postprandial hepatic metabolism induced by RYGB and other treatments.

Disclosure

N. F. Lange: None. S. Poli: None. D. Herzig: None. M. Schiavon: None. C. Dalla man: Research Support; Sanofi-Aventis Deutschland GmbH, Becton, Dickinson and Company. R. Kreis: None. L. Bally: Research Support; Dexcom, Inc., Ypsomed AG.

Funding

Swiss National Science Foundation (PCEGP3_186978)
255-LB: Liver Pyruvate Carboxylase Deletion in Mice Prevents Fibrosis from a NASH Diet
Authors: IÑIGO-VOLLMER MELISSA MAE R. , KUCEJOVA BLANKA , MIZERSKA MONIKA N. , KHAN SHAHANSHAH , SZWEDA PAMELA A. , ZAKI HASAN , SZWEDA LUKE I. , FU XIAORONG , BURGESS SHAWN C.
Published: June 2023

Obesity and T2D are closely associated with Nonalcoholic Fatty Liver Disease, which can advance to Nonalcoholic Steatohepatitis (NASH) with fibrosis. We previously found that liver pyruvate carboxylase (PC) is required for hepatic gluconeogenesis and the concentration of metabolites essential to mediating redox state and antioxidant function. Liver PC knockout (LPCKO) mice are protected from HFD-induced hyperinsulinemia and glucose intolerance despite retaining excess liver fat and exhibiting reduced antioxidant capacity. Here, we report that despite impaired antioxidant markers and increased inflammatory markers on a HFD, PC loss protected the liver from fibrosis and other indices of liver damage induced by a long-term NASH diet. LPCKO and control mice were fed a high fat, high cholesterol Western Diet (WD) for 13-14 months. After 10 mos. of WD, markers of insulin resistance were assessed by lactate/pyruvate, glucose, and insulin tolerance tests. After sacrifice, liver damage was assessed by serum markers and histology. Oxidative stress and inflammation were evaluated by gene expression, MDA concentration, GSH/GSSG and NADPH/NADP+ redox states, and H2O2 emission potential in isolated mitochondria. LPCKO-WD mice were more sensitive to an insulin tolerance test and exhibited lower fasting blood glucose and better glycemic control during a lactate/pyruvate or glucose tolerance test than controls. Liver malate/pyruvate indicated substantially lower NADPH/NADP+ in LPCKO-WD mice, but there were no differences in MDA levels, GSH/GSSG, and H2O2 emission potential. Despite similar hepatic steatosis, inflammation, and ballooning between LPCKO-WD and controls, fibrosis and serum markers of liver injury were markedly lower in LPCKO-WD mice. The data suggest that liver PC deletion improves glycemia and insulin resistance during chronic Western Diet exposure by reducing hepatic gluconeogenesis and prevents fibrosis independent of steatosis, inflammation, ballooning, and oxidative stress.

Disclosure

M. R. Iñigo-Vollmer: None. B. Kucejova: None. M. N. Mizerska: None. S. Khan: None. P. A. Szweda: None. H. Zaki: None. L. I. Szweda: None. X. Fu: None. S. C. Burgess: None.
274-OR: Do-It-Yourself Automated Insulin Delivery (AID) Systems Are Noninferior to Commercial AID Systems in Glucose Management among Adults with Type 1 Diabetes
Authors: WU ZEKAI , LEBBAR MAHA , BONHOURE ANNE , RAFFRAY MARIE , DEVAUX MARIE , GROU CAROLINE , MESSIER VIRGINIE , BOUDREAU VALERIE , BRAZEAU ANNE-SOPHIE , RABASA-LHORET RÉMI
Published: June 2023

AIM: We aim to compare commercial automated insulin delivery (C-AID) systems with open-source do-it-yourself (DIY)-AID systems for glucose management among adults with type 1 diabetes (T1D) in real-life conditions.

METHODS: A prospective observational, non-inferiority, parallel-cohort study involving 77 adults with T1D, having used an AID for ≥3 months and living in Canada (25 DIY-AID and 52 C-AID users): 59.7% females, mean age 44.0 ± 14.7 years old with mean diabetes duration of 26.9 ± 14.5 years and HbA1c of 6.7 ± 0.7%. A total of 30 days’ data from an additional blinded CGM (Dexcom G6) was used to assess effectiveness [Primary outcome: 24h time in range% (TIR%) for 30 days].

RESULTS: DIY-AIDs were non-inferior to C-AIDs regarding the TIR% [78.3±11.0% vs. 71.2±10.9%, mean difference 7.2% [95% CI 1.9% to 12.5%], P<0.001 for non-inferiority (non-inferiority margin 5%)], even after adjusting for various confounding factors (age, sex, auto-mode%, duration of AID use, annual household income, and educational level). The percentage of time in hypoglycemia (<70 mg/dL) was higher with DIY-AID (3.9±3.1%) than with C-AID (1.8±1.3%) but still below recommended threshold (Table). Differences between both systems are more pronounced during daytime.

CONCLUSION: DIY-AIDs are non-inferior to C-AIDs for TIR% among adults with T1D in real-world settings.

Disclosure

Z.Wu: Other Relationship; Eli Lilly and Company. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. M.Lebbar: None. A.Bonhoure: Consultant; Dexcom, Inc. M.Raffray: None. M.Devaux: None. C.Grou: None. V.Messier: None. V.Boudreau: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé.

Funding

Canadian Institutes of Health Research (148464)
339-OR: Timing of the Pre-exercise Temporary Target with Advanced Hybrid Closed-Loop (AHCL) and Hypoglycemia Risk
Authors: MORRISON DALE , KURTZ NATALIE , COHEN OHAD , VIGERSKY ROBERT A. , O'NEAL DAVID N.
Published: June 2023

Aim: People with type 1 diabetes using hybrid closed loop (HCL) are advised to set a temporary elevated glucose target (TT) 1-2h pre-exercise. We aim to assess hypoglycemia risk with AHCL with TT set < 1h pre-exercise.

Method: To date 7 adults with type 1 diabetes using MiniMedTM 780g AHCL have completed 16 exercise bouts, including 40 min moderate intensity (MIE) at 50% VO2max in the morning (mMIE40) and evening (eMIE40); 90 min MIE at 50% VO2max in the evening (eMIE90]; and 40 min high intensity with 5×4min intervals at 90% VO2max in the evening (eHIE40). A TT (150mg/dL) was set: i) 1h prior [t60]; ii) 20min prior [t20]; iii) onset [t0]; iv) no TT [tNil]. For eMIE90 up to 45g supplemental CHO was given during exercise as per guidelines for exercise >60 min. CGM metrics were compared from exercise commencement to 2h post.

Results: For all TT conditions mean glucose with mMIE40 was higher than eMIE40 (7.9 [6.8, 9.3]mg/dL vs 6.5 [5.5, 7.2]mg/dL; p<0.05) with less time spent below 70mg/dL (0.0 [0.0, 0.0]% vs 6.3 [0.0, 13.3]%; p<0.001). Timing of initiating TT pre-exercise had minimal effect on glycemia with 40 min exercise while reducing hypoglycemia with 90min evening exercise (Table 1).

Conclusion: Supplemental CHO may be required for evening MIE of <60 min duration, while a TT set prior to long duration MIE in the evening reduces the risk of hypoglycemia. Morning MIE results in less time spent in hypoglycemia than evening MIE.

Disclosure

D.Morrison: None. N.Kurtz: Employee; Medtronic. O.Cohen: Employee; Medtronic. R.A.Vigersky: Employee; Medtronic. D.N.O'neal: None.
353-OR: Cdkn2a Regulates Beige Fat Maintenance through BECN1-Mediated Autophagy
Authors: JIANG YUWEI
Published: June 2023

Summary: A potential therapeutic target to curb the obesity and diabetes epidemic is thermogenic beige adipocytes. However, beige adipocytes quickly transition into white adipocytes upon removing stimuli. Here, we define the critical role of Cdkn2a as a molecular pedal for the beige-to-white transition. Beige adipocytes lacking Cdkn2a exhibit prolonged lifespan, and mice are more resistant to diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance. Mechanistic studies demonstrate that Cdkn2a promotes the expression and activity of BECN1 by directly binding to its mRNA and its negative regulator BCL2L1, activating autophagy and accelerating the beige-to-white transition. Notably, reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced by Cdkn2a-ablation. Furthermore, hyperactive BECN1 alone significantly accelerates the beige-to-white transition. Collectively, these findings show that Cdkn2a-mediated autophagy serves as a brake system for beige adipocyte maintenance and is a highly promising target for anti-obesity and antidiabetes therapy.

Keywords: Beige adipocyte, UCP1, Cdkn2a, BECN1, Autophagy, Obesity

Disclosure

Y. Jiang: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K01DK11177, R03DK127149, R01DK132398); Diabetes Research and Training Center (P30DK020595)
370-OR: Optimized Weight Loss with Bimagrumab—Reduced Fat Mass with Increased Muscle Mass by Appetite-Independent Mechanisms
Authors: ATTIE KENNETH M. , HEYMSFIELD STEVEN B. , MINDEHOLM LINDA , SPRUILL SUSAN , PRUZANSKI MARK , KLICKSTEIN LLOYD
Published: June 2023

Background: Obesity is managed with lifestyle changes or incretin Tx to produce wt loss that is challenging to maintain long-term, perhaps because lean mass loss accounts for 20-40% of total wt loss. Semaglutide Tx results in rapid wt loss with 35% lower caloric intake, no further wt loss after 1 yr and rapid wt regain post-Tx. Bimagrumab (bima), a mAb to ActRIIA/ActRIIB, blocks activin pathways, leading to increased lean mass/decreased fat mass in numerous clinical studies (N=1561). Effects of bima IV or SC on fat and muscle were evaluated by DXA and MRI.

Results: In a Ph2 study of bima 10 mg/kg IV q4wks vs placebo (respectively) in persons with overweight/obesity and T2DM (N=75), LS mean change at Wk 48 in body wt was −5.9 vs −0.8 kg (p<0.001; −7.5% vs −1.1%), with minimal change in daily caloric intake. DXA: LS mean change at Wk48 in total body (TB) fat mass was −7.5 vs −0.2 kg (p<0.001; −22.2% vs −0.3%), TB lean mass +1.7 vs −0.4 kg (p<0.001; +3.6% vs -0.9%), and appendicular lean mass +0.5 vs −0.3 kg (p=0.009; +2.5% vs −1.1%); fat mass loss was maintained 12 wks post-last dose. MRI: LS mean change at Wk24 in visceral adipose tissue was −1.5 vs +0.2 L (p<0.001; −36.1% vs +3.6%), absolute hepatic fat fraction (FF, %) −4.6 vs +0.2 (p=0.006; -23.6% vs +14.3%), and paravertebral muscle (PVM) mass +363.3 vs −331.0 mm2 (p=0.003; +6.4% vs -4.6%); a trend for decreased PVM fat fraction and intermuscular adipose tissue was observed (p=NS). Bima improved HbA1c (%) by -0.76 vs +0.04. AEs included diarrhea, muscle spasms. In a Ph1 study comparing bima 525 mg SC (N=12) and 700 mg IV (N=8), q4wks X3, fat mass loss and lean mass (total body and appendicular) increase were similar, with fat mass loss maintained 12 wks post-last dose; SC arm had fewer AEs than IV arm.

Conclusions: Bimagrumab Tx results in decreased fat deposition in tissues and increased muscle mass despite minimal change in caloric intake, which could lead to durable, high quality wt loss. A study of bima in obesity without T2DM is ongoing (NCT05616013).

Disclosure

K.M.Attie: Employee; Versanis Bio. S.B.Heymsfield: None. L.Mindeholm: Consultant; Versanis Bio, Novartis AG, Stock/Shareholder; Novartis AG, Alcon Research, LLC, Novo Nordisk A/S. S.Spruill: None. M.Pruzanski: None. L.Klickstein: None.
386-P: Inpatient Hypoglycemic Rate Reduction through the Implementation of Prescriber Targeted Decision Support Tools
Authors: GOLDSTEIN REBECCA , ODOM JESSICA M.
Published: June 2023

Introduction: Hypoglycemia has been shown to increase mortality and length of hospital stay in patients with and without diabetes. The purpose of this study is to determine if the implementation of prescriber targeted decision support tools reduces the incidence of inpatient hypoglycemic events.

Methods: This pre-post intervention study included adult patients who experienced an inpatient hypoglycemic event within 24 hours of insulin administration from October 2018 to December 2019. Pregnant women and patients receiving insulin infusions were excluded. Best Practice Alerts (BPAs) and banners were implemented in January 2019 to alert providers of patients at risk for hypoglycemia. Triggers for the BPAs and banners include use of sulfonylureas with reduced renal function, high weight-based basal doses, a previous episode of hypoglycemia during the admission, or concomitant use of fluoroquinolones and scheduled insulin. The primary outcome was to measure the incidence of hypoglycemia per 1000 patient days in pre- vs. post-intervention groups.

Results: In total, 1186 hypoglycemic events in the pre-intervention group were compared to 5260 events in the post-intervention group. The implementation of EMR alerts significantly decreased hypoglycemia (glucose ≤ 70 mg/dL) from 22.91 events/1000 patient days to 18.27 events/1000 patient days (p<0.001). Severe hypoglycemia (glucose < 54 mg/dL) was not significantly reduced (1.65 events/1000 patient days vs. 1.79 events/1000 patient days (p=0.453)). The use of high weight-based basal insulin doses was reduced in the post-intervention patients with normal renal function, 23.0% vs. 16.7% (p<0.001), and patients with impaired renal function, 7.1% vs. 4.9% (p=0.017).

Conclusion: The implementation of prescriber targeted decision support tools was successful in reducing the overall incidence of inpatient hypoglycemia.

Disclosure

R.Goldstein: None. J.M.Odom: None.
40-OR: Insulin Stabilized Arterial Plaque by Regulating Vascular Smooth Muscle Cell Metabolism and Differentiation
Authors: LI QIAN , FU JIALIN , PARK KYOUNGMIN , WU I-HSIEN , KING GEORGE L.
Published: June 2023

The main pathology of cardiovascular diseases (CVD) in insulin resistance and diabetes is an acceleration of atherosclerosis and increased risk for the development of unstable plaques. Insulin’s effect on vascular smooth muscle cell (VSMC) has been attributed to be pro-atherogenic due to its actions to increase migration and proliferation. We reported that insulin receptors (IR) are responsible for increasing arterial intimal hyperplasia after wire injury. Surprisingly, mice with VSMC specific deletion of IR (Myh11IRKO/ApoE-/-), atherosclerosis was increased with plaques exhibited unstable pathologies of less VSMC and ECM, but more macrophages and necrosis than ApoE-/- mice. To characterize these unexpected findings in the arterial plaques of Myh11IRKO/ApoE-/- mice, we performed single cell RNA sequencing study of VSMC comparing 4 groups of mice including ApoE-/- and MyH11IRKO/ApoE-/- on normal chow or high fat diet (HFD). Bioinformatics analysis demonstrated that VSMC can be separated into 21 distinctive clusters with those expression enriched for contractile and mitochondrial genes separated from clusters which expressed heat shock protein (HSP) or inflammatory genes. Aorta of HFD insulin resistant WT ApoE-/- mice exhibited significantly increases of multiple clusters of inflammatory VSMCs and, surprisingly, also those clusters enriched for mitochondrial metabolism. However, in Myh11IRKO/ApoE-/- mice on HFD, aortic VMSC clusters with contractile and mitochondrial genes were significantly reduced, but distinct VMSC clusters with expressions of HSP or inflammatory genes were greatly increased. These novel findings, along with metabolic studies in cultured VSMC, indicated that insulin’s actions on VSMC metabolism to reduce the transition of VSMCs subsets from mitochondria enriched VSMCs to stressed and inflammatory VSMCs, which is critical to increase plaque stability and decrease CVD risks in people with insulin resistance and diabetes.

Disclosure

Q.Li: None. J.Fu: None. K.Park: None. I.Wu: None. G.L.King: Research Support; Janssen Research & Development, LLC.
410-P: Two-Year (2y) eGFR Slope in People with Type 2 Diabetes (T2D) Receiving a Very Low Carbohydrate Diet (VLCD) Intervention
Authors: ATHINARAYANAN SHAMINIE J. , ROBERTS CAROLINE G.P. , ADAMS REBECCA N. , VOLK BRITTANIE M. , PHINNEY STEPHEN D. , VOLEK JEFF , MCKENZIE AMY L.
Published: June 2023

A VLCD including nutritional ketosis is an effective T2D intervention, but its use is cautioned in renal disease. We compared eGFR slope among people with T2D with varying renal function who received a VLCD intervention via continuous remote telemedicine care (CCI, n=262) or Usual Care without carbohydrate restriction (UC, n=87) over two years. Four ketosis trajectory classes (KTs) were identified within CCI using latent class trajectory modeling. We compared eGFR slopes for CCI KTs using a linear mixed effect model with UC as the reference. The eGFR slope was positive in all CCI KTs and negative in UC (Table 1). eGFR slope improved in CCI (p=0.045), in sustained nutritional ketosis (SNK) group (p=0.01), and in those with baseline eGFR <90 (p<0.001) compared with UC. KT with higher blood ketones (SNK and MDNK) had greater eGFR rise. These results show that eGFR slopes rose in people with T2D on CCI and declined in UC. Rise of eGFR slope appears to have a dose-dependent relationship with endogenous ketone concentration and duration of maintenance of ketosis, including those with stage 2 chronic kidney disease, suggesting nutritional ketosis VLCD may provide benefit rather than risk in early renal disease.

Disclosure

S.J.Athinarayanan: Employee; Virta Health Corp. C.G.P.Roberts: Employee; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.D.Phinney: Board Member; Virta Health Corp., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. J.Volek: Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp.
428-P: Diabetic Retinopathy Predicts Hemodialysis Induction in Subjects with Type 2 Diabetes with Normo- and Microalbuminuria and Normal Renal Function
Authors: MORIYA TATSUMI , SUZUKI AKIHIKO , HAYASHI AKINORI , MATSUBARA MADOKA , MIYATSUKA TAKESHI
Published: June 2023

It is important to elucidate which factors are associated with the progression of diabetic nephropathy (DN) toward end-stage renal disease, i.e., hemodialysis (HD) as early stage of DN as possible. We hypothesized that different grades of diabetic retinopathy (DR) affect the progression toward HD in persons with type 2 diabetes with normoalbuminuria (NA) or microalbuminuria (MA), and normal renal function.278 NA and 170 MA persons with type 2 diabetes with normal renal function (GFR≥60 ml/min/1.73m2) whose GFRs had been measured by iohexol injection in 1995-2013 and followed for over 5 years were analyzed (n=448). At the baseline, HbA1c levels was divided into HbA1c≥7.0 (n=327) and <7.0 (n=121) groups. 86 subjects had simple DR (SDR), and 65 had proliferative DR (PDR). 217 had hypertension. The subjects were followed up for 16 ± 6 years. During the study period, 7 subjects in NA and 11 subjects in MA started to receive HD. A Kaplan-Meier analysis revealed that DR (Wilcoxon 5.82, p=0.016), PDR (Wilcoxon 8.53, p=0.014) and MA (Wilcoxon 5.87, p=0.015) were associated with a significantly higher risk of HD induction than no DR, SDR, and NA, respectively while HbA1c and hypertension were not associated with the risk of HD induction in whole diabetic subjects. In the multivariate analysis, DR (p=0.042), but not MA, was significantly associated with the HD induction in all the subjects. As each group analysis, a Kaplan-Meier analysis demonstrated that PDR was associated with HD induction in NA. However, SDR and PDR were not associated with HD in MA. HbA1c or hypertension did not affect HD induction in each group. In conclusions, MA itself is a risk factor of HD induction, and DR is a more predominant predictor for HD induction at the early stage of DN. PDR is a risk factor for HD induction even in NA subjects with normal renal function.

Disclosure

T.Moriya: None. A.Suzuki: None. A.Hayashi: Research Support; Abbott Japan Co., Ltd., Roche Diabetes Care, Speaker's Bureau; Abbott Japan Co., Ltd., Medtronic, Terumo Corporation. M.Matsubara: None. T.Miyatsuka: Speaker's Bureau; Eli Lilly Japan K.K., Novo Nordisk, Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Sanwa Kagaku Kenkyusho, Daiichi Sankyo.
46-LB: Effect of Nonnutritive Sweetener (Sucralose) on Gut Microbiome in Asian Indian adults with Type 2 Diabetes—A Randomized Clinical Trial
Authors: MOHAN VISWANATHAN , ABIRAMI KUZHANTHAIVELU , RAJAGOPAL GAYATHRI , SOUNDARARAJAN PADMAVATHI , UNNIKRISHNAN RANJIT , MOHAN ANJANA RANJIT , VASUDEVAN SUDHA , KAMALA KRISHNASWAMY
Published: June 2023

Background: Non-Nutritive Sweeteners (NNS) can help reduce calorie intake when substituted for added sugar. Some studies have reported detrimental effect of NNS on gut microbiome when given at high doses in animal models. Clinical studies have been done mostly in small sample sizes. This study aims to evaluate the effect of using sucralose in coffee, tea and fruit juices on gut microbiome in Asian Indian adults with type 2 diabetes (T2D).

Method: A parallel arm, randomized trial was carried out for 12 weeks in adults with T2D aged 30-50 yrs and glycated haemoglobin between 7-11 %. Participants were randomized into Intervention group (sucralose added in beverages) and Control group (No sucralose). Both groups received standard of care for diabetes. Faecal samples were collected from participants, V3-V4 libraries were generated and sequenced using illumina Miseq NGS. Alpha and beta diversity were derived for both groups to assess within and between groups changes. Ratio of fermicutes to bacteroidetes was also computed.

Results: Interim data of 38 participants who completed the study (Control group, n=14 and Intervention group, n=24) was analysed for changes in operational taxonomical units (OTU) of gut microbiome. Major phyla detected across all samples were Fermicutes, Actinobacteria, Bacteroidetes, Proteobacteria and Verrucomicrobiota. Alpha and beta diversity analysis showed no significant changes between intervention and control groups. Fermicutes to bacteroidetes ratio did not show any significant difference between groups. At end of 12 weeks significant reduction in body weight (p<0.004) and body fat % (p<0.04) was observed in the intervention group.

Conclusion: Use of sucralose in beverages produced no significant change in gut microbiome in Asian Indian adults with T2D but helped in reduction of body weight and body fat.

Clinical trial registry: CTRI/2021/04/032686

Disclosure

V. Mohan: None. K. Abirami: None. G. Rajagopal: None. P. Soundararajan: None. R. Unnikrishnan: None. R. Anjana: None. S. Vasudevan: None. K. Kamala: None.

Funding

Zydus Wellness Products Ltd.
472-P: Pro-B-Type Natriuretic Peptide Strongly Predicts Future Cardiovascular Events in Cardiovascular Disease Patients with NAFLD as Well as in Those without NAFLD
Authors: MAECHLER MAXIMILIAN , SPRENGER LUKAS , MADER ARTHUR , LARCHER BARBARA , VONBANK ALEXANDER , PLATTNER THOMAS , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2023

Elevated pro-B type natriuretic peptide (pro-BNP) has been found to be a strong marker of cardiovascular risk in several high-risk populations. However, the power of pro-B type natriuretic peptide (pro-BNP) to predict future cardiovascular events in patients with the combination of established cardiovascular disease and nonalcoholic fatty liver disease (NAFLD) is unclear and is addressed in the present study. We enrolled 794 patients with established cardiovascular disease, 553 with angiographically proven stable CAD and 241 with sonographically proven peripheral artery disease. Prospectively, cardiovascular events were recorded over a mean follow-up period of 8.7±3.3 years. At baseline, pro-BNP was not significantly different in patients with NAFLD (n=394) than in those who did not have NAFLD (796±2208 vs. 798±2520 pg/ml; p=0.234). During follow-up, 376 patients suffered cardiovascular events; the event rate was significantly higher in patients with NAFLD than in subjects without NAFLD (56.6 vs. 43.4%; p<0.001). Pro-BNP predicted cardiovascular events in the total study population, with a standardized adjusted hazard ratio (HR) of1.36 [1.26-1.46]; p<0.001. Further, pro-BNP predicted cardiovascular events in patients with NAFLD (HR 1.45 [1.28-1.65]; p<0.001) as well as in those who did not have NAFLD (HR 1.34 [1.19-1.50]; p<0.001). Interaction terms pro-BNP x NAFLD were non-significant for cardiovascular events (p=0.198), indicating that the power of pro-BNP to predict cardiovascular events did not differ significantly between cardiovascular disease patients with NAFLD and those who did not have NAFLD. We conclude that pro-BNP strongly predicts cardiovascular events in cardiovascular disease patients with NAFLD as well as in those without NAFLD.

Disclosure

M. Maechler: None. L. Sprenger: None. A. Mader: None. B. Larcher: None. A. Vonbank: None. T. Plattner: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
48-OR: Maternal Triglycerides in Diet-Controlled GDM Correlate with Newborn Triglycerides and Infant Fat Mass at Four Months of Life
Authors: ROZANCE PAUL J. , BARBOUR LINDA (LYNN) A. , DUNN EMILY Z. , FARABI SARAH S. , HIRSCH NICOLE , ROLLOFF KRISTY P. , FRIEDMAN JACOB E. , HERNANDEZ TERI L.
Published: June 2023

The early hours of newborn (NB) life are critical for metabolic transition from the prenatal to postnatal period and possibly subsequent metabolic development. Although the relationship between maternal glucose and neonatal hypoglycemia in gestational diabetes (GDM) is strongly supported, little is known about the relationship between maternal and NB triglycerides (TG). We tested the hypothesis that maternal TG in GDM would correlate positively with NB pre-feed TG (NBpfTG) at 24hrs, and that NBpfTG would correlate with infant adiposity (Inf%fat). After GDM diagnosis (~28-30 wks), 16 diet-controlled GDM women (mean±SD; BMI 32±1) were randomized to eucaloric diets differing in carbohydrate and fat percentages (all food provided). Fasting (F) and 1-hr/2-hr postprandial (PP) glucose, insulin, and TG were measured during breakfast test meals at 31 and 36 wks. Newborn “fasting” blood (NBpfTG, NBpfGluc) was collected at 24 hrs. Inf%fat was measured at 24 hrs and 4 mos (PeaPod). All women met conventional glucose targets with diet alone; no neonates had hypoglycemia. At 31 but not 36 wks, maternal FTG and PPTG were correlated with NBpfTG (92±7mg/dL)(r=0.52-0.53, p=0.03 both) and NBpfTG correlated with 24 hr Inf%fat (r=0.50, p=0.06). Maternal fasting insulin, HOMA-IR, glucose and PP glucose at 31 and 36 wks correlated with Inf%fat at 24 hrs (r=0.47-0.68, p<0.05 all). Strikingly, NBpfTG were uniquely and highly correlated with Inf%fat at 4 mos (r=0.81, p<0.0001); NBpfGluc was not. Inf%fat was similar between maternal diet groups (p>0.05). These data show that maternal TG soon after GDM diagnosis correlated with NBpfTG, which in turn correlated with Inf%fat at 24 hrs, but had a sustained, stronger correlation with Inf%fat at 4 mos. This connection between 32 wk maternal TG and NBpfTG, and their association with Inf%fat from 24 hrs to 4 mos support future studies to address whether maternal TG might be therapeutically targeted to normalize fetal growth in well-controlled GDM.

Disclosure

P.J.Rozance: None. L.A.Barbour: None. E.Z.Dunn: None. S.S.Farabi: None. N.Hirsch: None. K.P.Rolloff: None. J.E.Friedman: None. T.L.Hernandez: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK101659); Janssen Research and Development; National Center for Advancing Translational Sciences (UL1TR002535)
522-P: HealSmart—Evaluating Key Factors Affecting Diabetic Wound Healing for Personalized Care
Authors: CAY GOZDE , FINCO GRACI , GARCIA JASON A. , SALAZAR ELIA , VIGANO DAVIDE , MACAGNO MAURIZIO , ARMSTRONG DAVID G. , NAJAFI BIJAN
Published: June 2023

Diabetic foot ulcers (DFUs) are serious complication of diabetes. Offloading devices treat DFUs by distributing force and reducing pressure across the wound. Adhering to appropriate use of offloading devices is a key strategy to promote DFU healing. However, some people who are highly adherent to offloading device use still do not heal. Factors such as wound and diabetes characteristics, motor function, and patient reported outcomes may help distinguish healed and non-healed patients. In our study, we analyzed data from 23 participants. Factors were graded on a scale from 0 to 10 based on thresholds found in the literature (Figure 1). We then calculated the effect size of each factor using Cohen's d between the healed and non-healed groups (Figure 2). Our results showed that cognition had the largest effect size, with a value of d = 1.63.

Disclosure

G.Cay: None. G.Finco: None. J.A.Garcia: None. E.Salazar: None. D.Vigano: Board Member; Sensoria Health Inc. M.Macagno: Board Member; Sensoria Health Inc. D.G.Armstrong: Research Support; Medaxis LLC. B.Najafi: Consultant; BioSensics LLC, Mölnlycke Health US, LLC, Research Support; AVAZZIA, EO2 Concept, LifeNet, Neurometrix, Medline, SmarTek21.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124789)
527-P: mHealth Intervention for Low-Income Chinese Immigrant Families with Type 2 Diabetes—Feasibility, Acceptability, and Potential Efficacy
Authors: SHI YUN , ISLAM NADIA , ANN SEVICK MARY , LI HUILIN , WANG CHAN , BAO HAN , XU XINYI , LIEU RICKI , JIANG YULIN , HU LU
Published: June 2023

Objectives: To test the feasibility, acceptability, and potential efficacy of a mHealth intervention tailored for low-income Chinese immigrant families with type 2 diabetes (T2D).

Methods: We conducted a RCT with baseline, 3-, and 6-month measurements. Participating dyads, Chinese immigrants with T2D and their families/friends from NYC were randomized into the intervention group (n=11) or the wait-list control group (n=12). Dyads in the intervention group received 2 videos weekly for 12 weeks. Video topics cover T2D self-management, behavioral techniques, and family-oriented sessions. Study staff helped participants set goals for T2D management, followed their progress biweekly, and addressed any concerns. Feasibility and acceptability were measured respectively by the retention rate and video watch rate, and a satisfaction survey. Patients’ HbA1c, weight, and self-management behaviors were also assessed.

Results: Most patients (n = 23; mean age 56±9 years; 52% male) and families/friends (mean age 54±11 years; 52% female) had high school education or less (69% and 69%), annual household income > $25,000 (68%), and limited English proficiency (87% and 86%). The retention rates at both follow-ups were 87% with a mean watch rate of 76.7% (7.0%). Patients and families/friends rated satisfaction as 9.4 and 10 out of 10. Despite no between-group differences, the intervention group had significantly lower HbA1c (p=0.014) and improved self-management (p=0.009), and lost 12 lbs on average in 6 months (p=0.079).

Conclusions: A culturally-tailored, family-based mHealth intervention is feasible and acceptable among low-income, limited English-proficient Chinese families with T2D in NYC. Significant changes in HbA1c and self-management in the intervention group indicate this intervention may have potential efficacy. Given the small sample size of this study, a future RCT with adequate power is needed to test efficacy.

Disclosure

Y.Shi: None. L.Hu: None. N.Islam: None. M.Sevick: None. H.Li: None. C.Wang: None. H.Bao: None. X.Xu: None. R.Lieu: None. Y.Jiang: None.

Funding

National Institutes of Health (P30DK111022)
54-LB: The Kids Are Not Alright—Capturing the Need for Effective Intervention for Adolescents with Elevated A1C
Authors: WAGNER DAVID V. , CLEMENTS MARK A. , RAYMOND JENNIFER , WONG JENISE C. , NARANJO DIANA , REED ALISON , TORRES KRISTEN A. , MELNICK SYDNEY , FLORES GARCIA JAQUELIN , BONILLA OSPINA ANDREA , HILLIARD MARISA E. , HARRIS MICHAEL A.
Published: June 2023

Background: Adolescents with T1D and elevated A1c are at high risk of acute and chronic complications. While behavioral health interventions have demonstrated promise in optimizing A1c, real-life clinical practice indicates uncertainty regarding which youth will show improvement, extent of improvement, and factors predicting complications over time.

Methods: This 5-site longitudinal study enrolled caregivers (n=218) of youth aged 12-17 yrs (M=14.6 ±1.6 yrs) with T1D for >1 year and ≥ one A1c >10% in past year. Data included admissions, ED visits, and A1c one year pre- through 6 months post-enrollment. Family members reported on baseline functioning across multiple domains. Inferential tests (e.g., chi square, nonparametric) examined change over time in A1c and utilization as well as predictors of future ED visits.

Results: Acute utilization did not change over time. A1c post enrollment significantly decreased from 11.1% ±1.5% to 10.9% ±2.1% (p=.03), but absolute change was minimal. 40.2% of youth did not have an A1c value available post enrollment. Caregiver reports of higher diabetes distress, higher conflict with healthcare providers, and lower social support were associated with risk of future ED visits (p<.01).

Conclusion: Findings indicate strong need for systematic psychosocial screening and more intensive tailored behavioral intervention efforts for this youth with elevated A1c.

Disclosure

D. V. Wagner: None. A. Bonilla ospina: None. M. E. Hilliard: None. M. A. Harris: None. M. A. Clements: Consultant; Glooko, Inc., Research Support; Dexcom, Inc., Abbott Diabetes. J. Raymond: None. J. C. Wong: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. D. Naranjo: None. A. Reed: None. K. A. Torres: None. S. Melnick: None. J. Flores garcia: None.

Funding

JDRF
553-P: Perspectives on Culture, Health Beliefs, and Diabetes Risk among Asian Indians in Atlanta—A Qualitative Study
Authors: ARORA DIVYA , RAJWANI INAARA , SHAH MEGHA K.
Published: June 2023

Background and Purpose: South Asians are a fast-growing ethnic minority in the Atlanta metro area and are at high risk for developing diabetes. In order to create culturally competent practices and interventions, it is critical to understand the nuances in health beliefs, attitudes towards diabetes, and cultural and religious practices.

Methods: Design: Key informant interviews were conducted with participants as part of a mixed-methods study. After 5 interviews, a codebook was created with themes through inductive analysis, and interview questions were adjusted for clarity. Analyses were done using MAXQDA. Transcripts were reviewed and coded; any discrepancies in coding were discussed and resolved in weekly meetings. Semi-structured 60 minute interviews (n=8) were conducted online or in-person and recorded.

Results: Of 2,460 participants enrolled in the parent study, 71 were selected for interviews based on age (18-79), gender, and religious backgrounds. Stratifying by generational cohort and nativity revealed differences in beliefs about healthy behavior (including physical activity and nutritional preferences) and interactions with various healthcare systems. Participants’ beliefs on mindfulness, meditation, and cultural foods affected their health and lifestyle choices. Most immigrants had different perceptions of western medicine and experiences with the U.S. healthcare system compared to ayurvedic medicine. Common areas of confusion included prescriptions and obtaining medications, insurance status, and distrust in medical practitioners. Conversely, first generation participants reported greater health knowledge and engagement in healthy practices to prevent diabetes.

Discussion: Health beliefs and practices among South Asians vary by nativity, education, age, generational cohort, and sociocultural customs. Future studies should address how nativity and age might affect engagement in lifestyle change for South Asians.

Disclosure

D.Arora: None. I.Rajwani: None. M.K.Shah: None.