bluuebunny/crossref_metadata_2025 huggingface dataset:
1498-P: Preemptive Insulin Supplementation for Islet Graft Protection, Optimal Blood Glucose Control, and Fetal Development during the Pregnancy in Insulin-Independent Patient after Islet Transplantation
Authors: GONDEK SARAH , OGLEDZINSKI MATEUSZ , LIN WILLIAM , MILEJCZYK KAMILA , JUENGEL BRADEN , POTTER LISA , BACHUL PIOTR J. , BASTO LINDSAY , PEREA LAURENCIA , WANG LINGJIA , TIBUDAN MARTIN , BARTH ROLF , FUNG JOHN , WITKOWSKI PIOTR
Published: June 2023

Pregnancy increases metabolic demand for insulin, which may lead to the exhaustion of intraportally transplanted islets and postgestational hyperglycemia. Here we report a successful long-term preservation of islet graft function after two subsequent pregnancies while applying preemptive insulin supplementation. 29-year-old female with T1DM achieved long-term insulin independence with HbA1c <5.8% after a single intraportal islet transplant. Before conception, mycophenolate was replaced with azathioprine and tacrolimus target trough level was decreased to 4-6ng/ml. The patient became pregnant twice, 5 years and 7.5 years after her islet transplantation. During the first and second pregnancy patient preemptively supplemented with insulin up to 35-70u/day and up to 35 units daily, respectively to target fasting blood glucose below 90mg/ml. Postpartum the patient was successfully weaned off insulin maintaining optimal blood glucose control with HbA1c below 5.7%. Islet graft function before and after the pregnancy remained optimal as reflected by BETA-2 above 17 and comparable c-peptide secretion and peak blood glucose levels below 130mg/ml during the 8.5-year follow-up in Mixed Meal Tolerance Test. Both newborns were premature and delivered at 34 weeks with emergent c-sections due to preeclampsia. Unfortunately, the first newborn died due to necrotizing enterocolitis. The second child has been developing appropriately up-to-date three months after her birth. Our report confirms that insulin supplementation during pregnancy in insulin-independent patients after islet transplantation was safe and effective in maintaining optimal blood glucose control and islet graft function in the long term. It also underscores the high-risk nature of pregnancy in islet transplant recipients and the need for close clinical monitoring.

Disclosure

S.Gondek: None. L.Wang: None. M.Tibudan: None. R.Barth: None. J.Fung: None. P.Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novartis. M.Ogledzinski: None. W.Lin: None. K.Milejczyk: None. B.Juengel: None. L.Potter: None. P.J.Bachul: None. L.Basto: None. L.Perea: None.
15-LB: Serum Tsukushi Is Associated with Urinary Albumin Excretion in Type 2 Diabetes
Authors: LI YAN Y.
Published: June 2023

Background: Tsukushi (TSK) is a newly identified hepatokine that is associated with lipid and glucose metabolism. Although hyperglycemia, hyperlipemia and metabolic disorder are associated with diabetic nephropathy (DN) development, there is currently no investigation about whether TSK is associated with urinary albumin-creatinine ratio (UACR) and renal function.

Methods: Serum TSK level was quantified by ELISA in 167 normoalbuminuria, 80 microalbuminuria, 31 macroalbuminuria patients with T2DM as compared with 53 healthy subjects. Multiple linear regression and logistic regression analysis were used to analyze the relationship of TSK or other characteristics with UACR and eGFR.

Results: The TSK level in the all T2DM group was prominently higher than that in the control group. Further, TSK level in macroalbuminuria group was significantly higher than normoalbuminuria and microalbuminuria. Multiple linear regression showed that high TSK quartile, systolic pressure, serum creatinine, HOMA-IR, low 2-h post-OGTT glucose and female were the significantly independent factors for UACR. Logistic regression demonstrated that the OR of TSK for eGFR ≤ 90 was 1.636 (95%CI 1.091-2.452, P=0.017).

Conclusion: The circulating TSK increased in T2D patients with albuminuria and associated with UACR and eGFR, implied that TSK may involve in the pathogenesis of DN, which deserved future studies.

Disclosure

Y. Y. Li: None.

Funding

Talents Training Program of Shanghai Pudong Hospital (YQ202101); Social Development Project of Jiangsu Province (BE2018692); Natural Science Foundation of Jiangsu Province (BK20191222)
1508-P: ZnPP-Laden Nanoparticles Improve Glucose Homeostasis and Chronic Inflammation during Obesity
Authors: YANG WANBAO , ARORA MEENAKSHI , HAN HYEWON , JIANG WEN , MI KIM DA , AI WEIQI , PAN QUAN , RAVI KUMAR M.N.V. , BRASHEAR WESLEY , SUN YUXIANG , GUO SHAODONG
Published: June 2023

Type 2 diabetes mellitus (T2DM) characterized by insulin resistance has become a serious health threat. Chronic inflammation is believed to play a pivotal role in the development of T2DM. Previous study has shown that HO-1 plays an anti-inflammatory role, suggesting HO-1 inhibition could be an effective strategy to treat T2DM. However, application of HO-1 inhibitors is restricted due to their low solubility. In this study, we detected the role of HO-1 inhibitor, ZnPP, in regulating glucose homeostasis and inflammation during obesity. We encapsulated ZnPP with nanoparticles to increase its water solubility and delivered ZnPP-laden nanoparticles (Nano-ZnPP) to the obese mice. We found that inhibition of HO-1 by Nano-ZnPP significantly decreases adiposity, increases insulin resistance, and improves glucose tolerance in diet-induced obesity mice. Moreover, Nano-ZnPP treatment attenuated both local and systematical inflammatory levels during obesity. Mechanistically, Nano-ZnPP significantly attenuated glucagon, TNF, and fatty acid synthesis signaling pathway in liver. In white adipose tissue, oxidative phosphorylation signaling pathway was enhanced and inflammation signaling pathway was diminished by Nano-ZnPP. Our results showed that Nano-ZnPP has a better effect on improving glucose homeostasis and attenuating chronic inflammation, as compared to DMSO-dissolved ZnPP. These results indicate that ZnPP-laden nanoparticles could be a potential therapeutic agent to treat T2DM.

Disclosure

W.Yang: None. Y.Sun: None. S.Guo: None. M.Arora: None. H.Han: None. W.Jiang: None. D.Kim: None. W.Ai: None. Q.Pan: None. M.Kumar: None. W.Brashear: None.

Funding

National Institutes of Health (R01DK095118, R01DK120968, R01DK118334, R01AG064869)
1512-P: The Novel Roles of Intracellular Calcium and Phosphoinositides in Insulin Signaling and Metabolic Disease
Authors: LEE JIN-WOOK , JUNG YUNJAE , IM SEUNG-SOON , HO LEE DAE , LEE HWA-YONG , SUN HONG IN , KIM OK-HEE , OH BYUNG-CHUL
Published: June 2023

Insulin resistance is closely associated with elevated intracellular Ca2+ concentration under ectopic lipid accumulation and hyperglycemia-induced intracellular stress conditions. We recently identified that obesity impairs intracellular Ca2+ homeostasis, which prevents membrane localization of PH domain-containing proteins such as AKT, PLCδ, and IRS through the formation of Ca2+-phosphoinositides (PIPs), resulting in dysregulation of glucose homeostasis and insulin resistance. It is unclear, however, whether insulin sensitivity can be improved by targeting intracellular Ca2+ overload. Therefore, we screened nine angiotensin-II-receptor blockers (ARBs), a class of antihypertensive agents, for beneficial effects on palmitic acid (PA)-induced insulin resistance in human HepG2 cells. Two of the ARBs attenuated PA-induced intracellular Ca2+ overload by inhibiting dysregulated store-operated channel (SOC)-mediated Ca2+ entry into cells, which ameliorated insulin resistance by promoting insulin-stimulated membrane localization of AKT and by increasing the phosphorylation of AKT and its downstream substrates in PA-treated HepG2 cells. Furthermore, certain ARBs ameliorated obesity-induced insulin resistance, hepatic steatosis, and tissue inflammation in mice fed a high-fat diet. Meanwhile, certain ARBs normalized intracellular Ca2+ homeostasis by regulating obesity-associated SOC-mediated Ca2+ entry, which rescued impaired insulin signaling in liver and muscle tissues by promoting postprandial membrane localization of AKT and IRS2. These findings underscore the contribution of dysregulated intracellular Ca2+ homeostasis to the pathophysiology of insulin resistance and suggest a therapeutic strategy to use specific ARBs to ameliorate insulin resistance.

Disclosure

J.Lee: None. Y.Jung: None. S.Im: None. D.Lee: None. H.Lee: None. I.Hong: None. O.Kim: None. B.Oh: None.

Funding

Korean Ministry of Health & Welfare (HI14C1135 to B-C.O.); Basic Science Research Program (2021R1I1A1A01051429 to O-H.K.); Mid-Career Researcher Program (2019R1A2C2008130, 2022R1A2C2092700 to B-C.O.); National Research Foundation of Korea (2021R1A5A203033)
1531-P: Preoptic Anterior Hypothalamus Estrogen Signaling Controls Energy and Temperature Homeostasis
Authors: LUO PEI , YANG XIAOHUA , FENG BING , YE HUI , ANTONY NIMISHA , CARRILLO-SÁENZ LESLIE , TORRES IRIZARRY VALERIA C. , LAYDEN BRIAN T. , HE YANLIN , XU PINGWEN
Published: June 2023

An ovarian hormone, estrogen, has been shown to act on the preoptic anterior hypothalamus (POA) to modulate temperature and energy homeostasis. However, the underlying neural mechanism is still largely less known. Interestingly, we found that POA neurons express high levels of estrogen receptor α (ERα) and β (ERβ), and a subpopulation of POA neurons co-express ERα and ERβ (ERα/βPOA). We showed that ERα agonist stimulates ERα/βPOA neurons, whereas ERβ agonist inhibits ERα/βPOA neurons. Estrogen17β-estradiol (E2) showed mixed actions in the ERα/βPOA neurons, presumably caused by the counterbalance between ERα and ERβ. This dynamic counterbalance may lead to distinct effects of E2 in regulating temperature and energy balance depending on temperature or nutritional status. Consistently, chemogenetic activation of ERαPOA decreased food intake, brown adipose tissue (BAT) thermogenesis, and body temperature, mimicking warm-induced adaptation. Conversely, inhibition of ERβPOA neurons increases food intake, BAT thermogenesis, and body temperature, mimicking cold-induced adaptation. In conclusion, these results support a model that ERα/βPOA neurons service as an integrating center for the estrogenic regulation of temperature and energy homeostasis.

Disclosure

P.Luo: None. P.Xu: None. X.Yang: None. B.Feng: None. H.Ye: None. N.Antony: None. L.Carrillo-sáenz: None. V.C.Torres irizarry: None. B.T.Layden: Consultant; Bayer Inc. Y.He: None.

Funding

National Institutes of Health (R01DK123098, P30DK020595 to P.X.), (P20GM135002, R01DK129548 to Y.H.), (T32AA026577 to V.C.T.I.); American Heart Association (915789 to V.C.T.I.), (20POST35120600 to Y.H.); U.S. Department of Defense (W81XWH-20-1-0075 to P.X
1548-P: GLP-1 and GIP Reduce Insulin Clearance in Individuals with Pancreatic-Insufficient Cystic Fibrosis (PI-CF)
Authors: FLATT ANNELIESE , DOLIBA ANDRIANA , PELECKIS AMY J. , RUBENSTEIN RONALD C. , KELLY ANDREA , RICKELS MICHAEL R.
Published: June 2023

PI-CF is characterized by impaired insulin secretion with disruption of the enteroinsular axis and alterations in incretin secretion and action. We have reported augmented glucose-dependent insulin secretion to glucose-potentiated arginine (GPA) testing with GLP-1 infusion but not GIP, with these effects independent of glucose tolerance in PI-CF.

We aimed to assess the effect of incretin infusion on insulin clearance during GPA testing and explore its relationship to second-phase insulin response in individuals with PI-CF in a retrospective analysis. Thirty-two individuals with PI-CF and abnormal glucose tolerance underwent GPA testing of islet function following intravenous infusion of incretin or placebo in a randomized cross-over study design. Sixteen individuals were randomized to incretin infusion with GLP-1 and sixteen with GIP. Insulin clearance was assessed by the molar ratio of acute C-peptide to insulin response over the 5-minutes following glucose-potentiation of arginine-induced insulin and C-peptide secretion (target glucose ~230 mg/dL).

Insulin clearance was related to second-phase insulin secretion by hyperbolic function (y=P1/(P2 + x) with a reduction in insulin clearance for increasing second-phase insulin secretion (R2=0.20; p<0.001). A reduction in insulin clearance was observed with both GLP-1 vs. placebo (mean±SD 2.7±2.1 vs. 15.5±5.7; p<0.001) and GIP vs. placebo (2.4±0.8 vs. 18.0±10.8; p<0.001).

GLP-1 and GIP appear to reduce insulin clearance in individuals with PI-CF presumably through effects at the liver. Reduced insulin clearance is most apparent following GIP infusion where there is no augmentation of second-phase insulin secretion, supporting that the effect of GIP occurs independently of an increase in pre-hepatic insulin secretion. Further work should explore underlying mechanisms of incretin-induced reduction in insulin clearance in PI-CF that could support therapeutic approaches to improve glucose homeostasis.

Disclosure

A.Flatt: None. A.Doliba: None. A.J.Peleckis: None. R.C.Rubenstein: None. A.Kelly: None. M.R.Rickels: Consultant; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Research Support; Dompé.

Funding

National Institutes of Health (R01DK97830, UL1TR001878, P30DK19525, T32DK007314); Cystic Fibrosis Foundation (to M.R.R.)
1554-P: Carnosic Acid Protects against Short-Term Lipid-Infusion–Induced Glucose Intolerance in Mice
Authors: TSAKIRIDIS NICOLE , VLAVCHESKI FILIP , TSIANI EVANGELIA , GIACCA ADRIA
Published: June 2023

Background: Obesity and type 2 diabetes (T2D) are associated with elevated plasma free fatty acids (FFA). In vivo exposure to FFAs, such as palmitate, by lipid infusion results in insulin resistance as observed in obesity and T2D. In recent years, compounds found in herbs and plants have attracted attention for prevention and treatment of insulin resistance and T2D. In recent studies by our group, carnosic acid (CA), found in rosemary, increased glucose uptake and attenuated the FFA (palmitate)-induced insulin resistance in muscle cells and adipocytes. In addition, CA caused a robust activation of AMP-activated protein kinase (AMPK). Our present study aimed to examine the effects of CA in short-term FFA-induced glucose intolerance in mice.

Material and Methods: C57Bl/6J mice were cannulated in their jugular veins and infused for 48h with ethylpalmitate (EtP, nontoxic method of elevating circulating palmitate because of hydrolysis to palmitate and ethanol by plasma esterases), mimicking elevated FFA levels seen in obesity. In addition, a group of mice were infused with EtP plus 50 mg/kg CA for 48h. Ethanol vehicle with or without CA were two additional control groups. At the end of the infusions, the mice were subjected to a 2 hr hyperglycemic clamp (20 mM glucose) and the glucose infusion rate was measured to assess glucose tolerance.

Results: Preliminary data revealed that mice infused with EtP and CA had a higher glucose infusion rate (GIR; mg/kg*min) (66.5±10, mean±SEM) than mice infused with EtP alone (22.7±10). The EtP and CA was comparable to the GIR of ethanol vehicle infused mice (73±9).

Future Directions: Further analysis of collected plasma and tissue will be used to assess insulin resistance and beta cell function in vivo and to elucidate the mechanisms of CA alleviation of FFA-induced insulin resistance.

Conclusions: Our data indicate that CA has the potential to counteract FFA-induced glucose intolerance in mice.

Disclosure

N.Tsakiridis: None. F.Vlavcheski: None. E.Tsiani: None. A.Giacca: None.
1558-P: The Mitochondrial Calcium Uniporter Regulates Hepatic Mitochondrial Oxidation and Intracellular Redox In Vivo
Authors: LAMOIA TRACI E. , HUBBARD BRANDON T. , GUERRA MATEUS , GOODMAN RUSSELL , NATHANSON MICHAEL H. , SHULMAN GERALD I.
Published: June 2023

The mitochondrial calcium uniporter (MCU) facilitates mitochondrial calcium influx, and several enzymes that catalyze key steps of the TCA cycle require calcium for their activation. As such, it is generally accepted that rates of mitochondrial oxidation correlate with mitochondrial calcium activity. Decreased rates of hepatic mitochondrial oxidation are associated with metabolic dysfunction and ectopic lipid accumulation as seen with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. Despite this, a role for MCU and mitochondrial calcium in regulating hepatic mitochondrial oxidation is still unclear. To address this question, we generated a liver-specific MCU knockout (MCU KO) mouse model which displayed reduced mitochondrial calcium ([Ca2+]mt; p<0.05) and increased cytosolic calcium ([Ca2+]cyt; p<0.01). Despite decreased [Ca2+]mt, we found that deletion of hepatic MCU increased rates of isocitrate dehydrogenase flux (VIDH; p<0.01), α-ketoglutarate dehydrogenase flux (VOGDH; p<0.01), and succinate dehydrogenase flux (VSDH; p<0.05) in vivo, using a novel [13C5]glutamine tracer infusion technique (Q-Flux). Further, we show that rates of [14C16]palmitate oxidation (p<0.01) and intrahepatic lipolysis (p<0.05) were significantly increased in liver slices collected from MCU KO mice compared to WT mice, and were associated with reductions in hepatic triacylglycerol content in vivo (p<0.01). Hepatocellular redox state was also altered with MCU KO, as indicated by a decreased cytosolic redox ratio ([lactate]:[pyruvate]; p<0.05) and increased mitochondrial redox ratio ([β-hydroxybutyrate]:[acetoacetate]; p<0.01).

Conclusion: Here we show that increases in [Ca2+]cyt potently increase hepatic mitochondrial fat oxidation and alters hepatic redox balance to reduce hepatic lipid content independently of [Ca2+]mt in vivo and targeting [Ca2+]cyt may represent a novel therapeutic target to treat NAFLD.

Disclosure

T.E.Lamoia: None. B.T.Hubbard: None. M.Guerra: None. R.Goodman: None. M.H.Nathanson: None. G.I.Shulman: Consultant; Novo Nordisk, DiCerna Pharmaceuticals, Inc., Bayer Consumer Care AG, Kriya Therapeutics, Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Other Relationship; AstraZeneca, Merck & Co., Inc., Janssen Research & Development, LLC, iMetabolic Biopharma Corporation, Maze Therapeutics, 89bio, Inc., Equator Therapeutics, Inc., Generian Pharmaceuticals, Fortress Biotech, Inc., OrsoBio, Aro Biotherapeutics Company, Stock/Shareholder; Levels Health, Inc.

Funding

National Institutes of Health (F31DK126362, T32GM007324)
1585-P: MAFLD in Obesity with Deteriorating Glucose Control
Authors: FORST THOMAS , BOTZ ISABEL , BERSE MATTHIAS , BAUMANN SYBILLE K. , SCHULTZ ARMIN
Published: June 2023

The incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rising in parallel with increasing bodyweight and loss of glucose control, implicating a high risk of hepatic and extra-hepatic complications. This longitudinal observational study analysed several indicators for MAFLD in 240 overweight subjects (body mass index (BMI) > 28 kg/m²) at 2 visits within in average 16 months. Subjects were categorised according to their insulin sensitivity (HOMAIR) and diabetic status. Liver fat and liver stiffness were measured with sonographic elastography (FibroScan®), and by calculation of Fatty Liver Index (FLI), and NAFLD Fibrosis Score (NFS). Parameters indicative for liver steatosis, i.e., the controlled attenuation parameter (CAP) and the FLI, were significantly higher in the T2DM group compared to the normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) groups (p<0.05). FLI values and the HOMAIR significantly correlated with sonographic liver fat content (CAP) (r=0.53, p<0.0001; r=0.34, p<0.001, respectively). An inverse correlation was observed between serum adiponectin levels and CAP (r=-0.20; p<0.019) and adiponectin levels and FLI (r=-0.37; p<0.0001). Over 16 months, fasting insulin levels and HOMAIR score increased mainly driven by the group of obese subjects with T2DM. No significant change in liver fat or stiffness was observed that period.

In subjects with a BMI ≥ 28kg/m², the prevalence of MAFLD increases in line with increasing insulin resistance and loss of glucose control. Despite some further deterioration in insulin sensitivity, liver fat content appeared relatively unchanged over 16 months.

Disclosure

T.Forst: Consultant; Pfizer Inc., Speaker's Bureau; Amarin Corporation, AstraZeneca, Boehringer Ingelheim Inc., Cipla Inc., Daiichi Sankyo, Eli Lilly and Company, MSD Life Science Foundation, Novo Nordisk, Sanofi. I.Botz: None. M.Berse: None. S.K.Baumann: None. A.Schultz: None.
1593-P: Insulin-Degrading Enzyme (IDE) Regulates Glucagon Signalling and Mitochondrial Respiration in Hepatocytes
Authors: GONZÁLEZ-CASIMIRO CARLOS M. , CÁMARA-TORRES PATRICIA , MERINO BEATRIZ , SANTO-DOMINGO JAIME , DE LA FUENTE MIGUEL A. , ALONSO ANDRÉS , COZAR-CASTELLANO IRENE , PERDOMO GERMAN
Published: June 2023

IDE is a ubiquitous metalloprotease with cytosolic and mitochondrial subcellular localization that degrades insulin and glucagon. People with T2D and diet-induced obese mice show lower hepatic IDE levels. We revealed a key role of IDE on the insulin-mediated repression of hepatic gluconeogenesis, but its function on glucagon-dependent activation of gluconeogenesis and mitochondrial respiration in hepatocytes remains completely unknown. Here, we aim to elucidate the role of IDE on glucagon signalling and its impact on gluconeogenesis and energy metabolism in hepatocytes. Liver homogenized and primary hepatocytes obtained from L-IDE-KO mice (deletion of IDE in liver) showed decreased expression of glucagon receptor (~60%), CREB protein (~40%), and lower phosphorylation of CREB (~50%) upon glucagon stimulation compared to controls. Similar results were found in AML12-shRNA-Ide cells, in which IDE protein levels were reduced by ~50%. Additionally, glucagon stimulation resulted in lower (~30%) cAMP levels and diminished phosphorylation of PKA substrates in AML12-shRNA-Ide. Surprisingly, these alterations in glucagon signalling paralleled with ~20-fold increases in the expression of the gluconeogenic genes G6p6 and Pck1. Of note, basal and uncoupler-stimulated respiration increased ~4-fold in AML12-shRNA-Ide in parallel with a ~2-fold increment of mitochondrial and glycolytic ATP production. Finally, similar mitochondrial phenotype was found in human hepatocytes lacking IDE (HepG2-IDE-KO cells), which exhibited higher FoxO1 levels and fragmented mitochondria. The effects on mitochondrial respiration were independent of IDE's proteolytic activity.

In summary, reduced IDE expression in hepatocytes has a deleterious effect on glucagon signalling leading to up-regulated gluconeogenesis and mitochondrial respiration. We conclude that IDE is a mechanistic link to couple hepatic gluconeogenesis with mitochondrial energy production.

Disclosure

C.M. González-Casimiro: None. P. Cámara-Torres: None. B. Merino: None. J. Santo-Domingo: None. M.A. de la Fuente: None. A. Alonso: None. I. Cozar-Castellano: None. G. Perdomo: None.

Funding

Ministerio de Ciencia e Innovación-Spain (PID2019-110496RB-C22)
160-OR: Youth with T1D and Elevated A1C —Pandemic Experiences and Psychosocial Factors
Authors: WAGNER DAVID V. , RAYMOND JENNIFER , WONG JENISE C. , NARANJO DIANA , REED ALISON , TORRES KRISTEN A. , MELNICK SYDNEY , MITCHELL SUSANNE , YGLECIAS LOREN , FLORES GARCIA JAQUELIN , TORRES SANCHEZ ALEJANDRA , BONILLA OSPINA ANDREA , CLEMENTS MARK A. , HARRIS MICHAEL A.
Published: June 2023

Background: Individuals with T1D and elevated A1c may be differentially impacted by the COVID-19 pandemic. We examined the pandemic experiences and psychosocial factors of youth with T1D and their families.

Methods: Youth 12-17 years of age with T1D for ≥1 yr and A1c ≥ 10% were enrolled at 5 sites. Caregivers and youth reported pandemic experiences, family functioning, parenting practices, social support, diabetes distress, and family-medical team relationship. Pandemic experiences were compared to benchmark data, and significant associations were examined.

Results: Participants (n=157) had mean age of 14.6 ± 1.6 years and mean A1c 11.0 ± 1.9%. Some pandemic experiences (e.g., change of schooling, loss of job) of youth with elevated A1c were similar to reports of other samples of youth with T1D, but youth with elevated A1c endorsed higher frequency of more severe COVID illness (43.9%), less strict social distancing (57.8%) and lower positive diabetes experiences (7.3%). Youth, caregiver, family, and family-medical team relationships were significantly associated with pandemic-related distress and T1D experiences during the pandemic (see Table).

Conclusion: Youth with elevated A1c reported more frequent negative pandemic experiences compared to other samples, with related youth, family, caregiver, and family-medical team factors identified as potential targets for screening and intervention.

Disclosure

D.V. Wagner: None. 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. S. Mitchell: None. L. Yglecias: None. J. Flores Garcia: None. A. Torres Sanchez: None. A. Bonilla Ospina: None. M.A. Clements: Consultant; Glooko, Inc. Research Support; Dexcom, Inc., Abbott Diabetes. M.A. Harris: None.

Funding

JDRF
1601-P: Childhood Plasma Amino Acid Profiles Predict the 10-Year Risk of Nonalcoholic Fatty Liver Disease—The BCAMS Study
Authors: LI MING , GAO SHAN ,   BCAMS GROUP
Published: June 2023

Background and Aims: Amino acid profiles have been proved a promising tool to identify novel biomarkers and insight of the mechanisms of metabolic diseases; however, date on youth was still limited, particularly nonalcoholic fatty liver disease (NAFLD). We aimed to prospectively investigate if there exist any association between childhood plasma amino acid profiles and adulthood NAFLD, and explore the early predictor and the underlying mechanism for the development of hepatic steatosis.

Methods: A total of 307 subjects aged 12.1±3.0 years at baseline were enrolled in this study at 10-year follow-up, recruited from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study cohort, including 99 NAFLD patients and 208 normal controls. Thirty-two amino acids (AAs) in fasting plasma at baseline were evaluated by liquid chromatograph-mass spectrometry. NAFLD was diagnosed by abdominal ultrasonography at follow-up.

Results: Among the 32 qualified AAs, 14 AAs showed significant differences (p<0.05) between NAFLD and normal controls, including four AAs survived Bonferroni correction (p<0.0016). Adjustment for age, gender and lifestyle factors, there were 10 AAs remain significant, including alanine, asparagine, glutamine, glycine, isoleucine, tyrosine, serine and threonine etc. Further adjustment for BMI, lower levels of asparagine (OR: 0.62, 95% CI: 0.44-0.87), glutamine (OR: 0.73, 95% CI: 0.53-0.99) and serine (OR: 0.71, 95% CI: 0.51-0.98) remain significant predictors of NAFLD at the 10-year follow-up.

Conclusion: Plasma amino acid profiles in childhood can predict risk of NAFLD in young adults. Plasma asparagine, glutamine and serine are likely to be early predictors of NAFLD independently of adiposity.

Disclosure

M.Li: None. S.Gao: None. Bcams group: n/a.

Funding

National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014); National Natural Science Foundation of China (81970732, 82270924); Capital's Funds for Health Improvement and Research (2020-2Z-40117); CAMS Innovation Fund for Medical Sciences (C
1603-P: Differential Effects of Cocoa Butter, Sunflower, Soybean, and Fish Oil Based Sucrose-Free HFDs on Hepatic Steatosis, Lipogenesis, Inflammation, and Insulin Resistance in Mice
Authors: AHMAD RASHEED , JACOB TEXY K. , KOCHUMON SHIHAB P. , THOMAS REEBY S. , SHENOUDA STEVE , AKHTER NADEEM , WILSON AJIT , BAHMAN FATEMAH , HASAN AMAL , ALRASHED FATEMA , AREFANIAN HOSSEIN , AL MADHOUN ASHRAF , ALMULLA FAHD , SINDHU SARDAR T.A.K.
Published: June 2023

Nonalcoholic fatty liver disease (NAFLD) is a risk factor of type-2 diabetes and cardiovascular disease. Obesity induced by various high-fat diets from different sources results in different types of meta-inflammatory derangements, including NAFLD. Fats are a central part of healthy diets, however, the impact of various dietary fats, lacking in sucrose, on liver fat accumulation and expression of lipogenic and inflammatory markers remains unclear. To study this, C57BL/6J mice were fed sucrose-free HFDs comprising fat from diverse sources, including cocoa butter (c-HFD), sunflower oil (s-HFD), soybean oil (so-HFD), and fish oil (f-HFD). Mice fed c-HFD or so-HFD developed more severe liver steatosis, compared with those fed s-HFD or f-HFD. Liver histopathology displayed high levels of lobular inflammation in mice fed c-HFD, so-HFD, and s-HFD. Kupffer cell counts were higher in mice fed c-HFD and s-HFD. Hepatic fibrosis was seen in mice fed s-HFD or so-HFD. Of note, there was no hepatic fibrosis in mice fed f-HFD. None of the diet had a significant impact on total body weight. However, liver weight was slightly increased in mice fed c-HFD or s-HFD. Mice fed c-HFD, s-HFD, and so-HFD displayed insulin resistance. Expression of the key genes of glycolysis (Pklr), de novo lipogenesis (Acaca, Fasn, Scd1), fatty acid oxidation (Cpt1a, Ppar-α), inflammation (Tnf-α) was upregulated in mice fed c-HFD or s-HFD. No significant difference was seen regarding genes of fatty acid uptake (Cd36, Fabp2), and chemokine-associated inflammation (Ccl2). Interestingly, hepatic IL-1β and IL-6 were elevated only in mice fed c-HFD. Taken together, these findings indicate that mice fed the sucrose-free HFDs comprising lipids from various dietary sources may have differential effects on hepatic steatosis at levels of de novo lipogenesis, hepatic inflammation, and whole-body insulin resistance.

Disclosure

R. Ahmad: None. T.K. Jacob: None. S.P. Kochumon: None. R.S. Thomas: None. S. Shenouda: None. N. Akhter: None. A. Wilson: None. F. Bahman: None. A. Hasan: None. F. Alrashed: None. H. Arefanian: None. A. Al Madhoun: None. F. Almulla: None. S.T.K. Sindhu: None.

Funding

Kuwait Foundation for the Advancement of Sciences (RAAM-2016-007)
1616-P: Effects of Hazelnuts Consumption Combined with Physical Activity on Lipid Metabolism and Correlations with Marrow Adiposity Homeostasis
Authors: FERRULLI ANNA , MASSARINI STEFANO , MACRÌ CONCETTA , SENESI PAMELA , TERRUZZI ILEANA , ROSSO GINEVRA , CHARRON MELANIE , MENTA ROBERTO , LUZI LIVIO
Published: June 2023

Consumption of hazelnuts has been associated with reduced cardiovascular risk and improved metabolic outcomes. Furthermore, the Bone Marrow Fat (BMF) might contribute to skeletal as well as systemic metabolism, modulating insulin sensitivity and, consequently, cardiovascular risk. Previously, we demonstrated a beneficial effect of hazelnuts and cocoa integration on vascular reactivity and metabolic profile in healthy individuals. Aim of this randomized controlled interventional study with 3 parallel groups was to investigate the effects of a daily supplementation with 30 g of hazelnuts, with or without aerobic physical activity (PA), throughout 8 weeks, on insulin sensitivity and resistance, lipid profile, and on BMF content (evaluated by proton magnetic resonance spectroscopy) in healthy individuals. Twenty-five adults (age 18-50 yrs; BMI 18-28 Kg/m2) were randomized in 3 groups: 9 subjects (5F/4M, age 25.6±8.8 yrs, BMI 23.3±2.5) received 30 g of hazelnuts associated with diet (Group 1); 9 subjects (6F/3M, age 26.3±6.3 yrs, BMI 22.0±2.1) received 30 g of hazelnuts associated with diet and aerobic PA (Group 2); 7 subjects (4 F/3 M, age 29.7±6.4 yrs, BMI 23.3±4.2) received only diet (Group 3). After the 8 weeks-intervention, an improvement in LDL-Cholesterol was found in Groups 1 and 2 [-9.3±11.5% (Group 1) vs -5.0±13.6% (Group 2) vs +21.9±35.7% (Group 3); p=0.02]. BMF content variation negatively correlated with LDL-Cholesterol change in Group 1 (r=-0.802, p=0.054); variations in BMF content and in HDL-Cholesterol positively correlated in Group 2 (r=+0.8687, p=0.011). This study confirms the beneficial effects of hazelnuts, in association with PA in improving lipid profile. The correlations between HDL- and LDL-cholesterol and BFM changes suggest an impact of bone homeostasis on whole-body lipid metabolism, through a rapid utilization of lipids, drawing them out of the circulation and decreasing their deposition in the organ tissues.

Disclosure

A.Ferrulli: None. S.Massarini: None. C.Macrì: None. P.Senesi: None. I.Terruzzi: None. G.Rosso: Employee; Soremartec Italia Srl, Ferrero Group. M.Charron: Employee; Soremartec Italia Srl, Ferrero Group. R.Menta: Employee; Soremartec Italia Srl, Ferrero Group. L.Luzi: Advisory Panel; Eli Lilly and Company, Medtronic, Research Support; Gelesis, Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Novo Nordisk, Novartis.

Funding

IRCCS MultiMedica (Ricerca Corrente)
162-LB: ¡Más Fresco! More Fresh—Impact of a Fruit and Vegetable Prescription Program in a Pediatric Type 2 Diabetes Clinic
Authors: CHAN KAREN , HILLER-VENEGAS SARAH P. , KIM JANE J. , KLEIN KAREN O. , RHEE KYUNG
Published: June 2023

Fruit and vegetable prescription (FVRx) programs have shown to improve fruit and vegetable intake and glycemic control in adults with diabetes; however, pediatric data is lacking. The aim of this study was to assess if a FVRx program improved fresh fruit and vegetable intake and health outcomes of children with type 2 diabetes mellitus (T2D). Families with a child with T2D and enrolled in Medi-Cal were recruited from our pediatric diabetes clinic. Families were randomized to either receive vouchers immediately (intervention group) or after a 6-month waiting period (delayed-control group). Monthly vouchers were given for 1 year to purchase fresh fruits and vegetables. Families completed surveys including the Dietary Screening Questionnaire and U.S. Household Food Security Survey every 6 months. Physiologic data and standardized laboratory tests were also collected. Of the 57 families with baseline surveys, the majority identified as Latino/Hispanic (84%) and the mean age of children was 14.3 years. Of the 49 parents who completed the baseline U.S. Household Food Security Survey, 46.9% reported low household food security and 16.3% reported very low food security. There were 29 families who completed our baseline and 6-month surveys. For the intervention group (n=14), there was an increase in parent-reported fruit and vegetable intake from baseline to 6-months for parents (2.4 vs 3.6 cups per day, p=0.0034) and children (2.6 vs 4.4 cups per day, p=0.0264). Children self-reported increased fresh vegetable intake between baseline and 6-months (0.17 vs 0.53 cups per day, p=0.014). There was no statistically significant difference in these measures for the delayed-control group (n=15). There was no significant change in BMI Z-score or hemoglobin A1c for the two groups after 6 months. A FVRx program is a viable intervention to improve fruit and vegetable intake for families with a child with T2D. Further research is needed to assess its impact on BMI and glycemic control.

Disclosure

K. Chan: None. S. P. Hiller-venegas: None. J. J. Kim: None. K. O. Klein: Consultant; AbbVie Inc., Tolmar Pharm, Azurity. K. Rhee: None.

Funding

U.S. Department of Agriculture-National Institute of Food and Agriculture (2021-06512)
1620-P: Royal Jelly Improved Dysbiosis and Glucose Intolerance in db/db Mice
Authors: OKAMURA TAKURO , HAMAGUCHI MASAHIDE , OKAMOTO HIDETO , OKUMURA NOBUAKI , FUKUI MICHIAKI
Published: June 2023

In this study, we have investigated the mechanisms of improvement of glucose intolerance via changes in gut microbiota using db/db mice. Eight-week-old db/m and db/db mice were divided into 5 groups and housed for eight weeks (n=6 for each group): db/m group without RJ (db/m), db/db mice without RJ (db/db), db/db mice with 0.2% RJ (db/db + 0.2% RJ), db/db mice with 1% RJ (db/db + 1% P), db/db mice with 5% RJ (db/db + 5% RJ) (Figure A). Body weight of db/db mice was higher than that of db/db mice fed with RJ (Figure B). Moreover, glucose tolerance evaluated by iPGTT and ITT were improved by RJ (Figure C-F). Next, the expression of inflammation-related genes (Tnfa, Ifng) and nutrient transporter genes (Cd36, Sglt1, and Pept1) in small intestine were increased in db/db mice more than in db/m mice, nevertheless significantly decreased by RJ (Figure G-K). In the gut microbiota analyses by 16S rRNA sequencing, it was found that seven taxa, including Firmicutes, were overexpressed in db/db mice, while seven taxa including short-chain fatty acid-producing bacteria such as the family Ruminococcaceae, the genus Butyricioccus, and the genus Acetiviblio were overexpressed in db/db +5%RJ mice in the LEfSe algorithm (Figure L).

In summary, it is suggested that RJ might altere the gut microbiota and contributed to the improvement of metabolic disorders by changing the expression of genes related to nutrient absorption in the small intestine.

Disclosure

T. Okamura: Research Support; Yamada Bee Company, Inc. M. Hamaguchi: Research Support; Yamada Bee Company, Inc. H. Okamoto: Employee; Yamada Bee Company, Inc. N. Okumura: Employee; Yamada bee company, Inc. M. Fukui: None.
1627-P: Enhancer Regulator MLL4 Programs Skeletal Muscle Metabolic Efficiency by Limiting AMPK-Mediated Fuel Catabolism
Authors: YANG LIKUN , LIU LIN , DING CHENYUN , FU TINGTING , ZHOU ZHENG , GAN ZHENJI
Published: June 2023

Skeletal muscle adapts to nutrient availability and physiological demands by fine-tuning gene expression patterns and metabolism to maximize metabolic efficiency. The mechanisms that enable and mediate muscle transcriptional and metabolic responses to environmental cues remain unclear, however. We have shown previously that enhancer regulator MLL4 is required for establishing and maintaining slow type I fiber program to ensure running endurance (J Clin Invest. 2020;130(9):4710-4725). Here, we report that MLL4 plays a critical role in directing muscle metabolic transcriptional adaptation that governs metabolic efficiency and systemic metabolism. MLL4 expression is regulated by nutrient availability, and skeletal muscle-specific ablation of MLL4 protects mice against diet-induced obesity and improves systemic glucose homeostasis despite reducing exercise endurance. Combining comprehensive metabolic and genomic analysis of the MLL4-depleted muscles using multidimensional ‘omics’ technologies, we gained insight into the molecular targets and biological functions of the MLL4 protein. Specifically, this seemingly paradoxical phenotype is due to markedly enhanced fuel catabolism in MLL4 deficient muscles, a favorable metabolic reprogramming caused by the activation of muscle AMPK. Isotopic 13C-glucose tracing experiments in myocyte provided further evidence that MLL4 exerts control upon muscle fuel catabolism. Remarkably, pharmacologic targeting the MLL4 pathway activates muscle AMPK, confers resistance to diet-induced obesity and ameliorates obesity-related insulin resistance and liver steatosis. These results identify an enhancer regulator limiting AMPK-mediated muscle fuel catabolism and offer a new potential therapeutic strategy for obesity-related metabolic disorders.

Disclosure

L.Yang: None. L.Liu: None. C.Ding: None. T.Fu: None. Z.Zhou: None. Z.Gan: None.
1636-P: The Effects of MS-275 Derivative in Diabetic Skeletal Muscle Atrophy
Authors: LEE NAMI , KIM YUJIN , CHOI SUJI , KIM YOUNGHA , SON YOUNGHO , CHOI SUNGE , KANG YUP Y. , YOUNG JEON JA , JIN HAN SEUNG , JIN KIM HAE , HO KIM TAE , AN SOYEON , LEE KWANWOO
Published: June 2023

Aim/hypothesis: Histone Deacetylase (HDAC) is considered one of the pathogenic factors that induced muscle atrophy. MS-275, HDAC inhibitor, plays an important role in many physiological processes, and includes muscle contraction, mitochondrial metabolism, and decision of cell fate. Recently it was reported MS275 prevented insulin resistance and obesity. However, the effects of MS-275 derivative in diabetic skeletal muscle atrophy have not been well studied. In this study, we investigated the preventive effects of MS-275 derivative in diabetic muscle atrophy using db/db mice.

Method: To investigate the effects of MS-275 derivative on diabetic muscle atrophy, db/db mice were randomly divided into three groups: control group, db/db group, and db/db plus MS-275 derivative group. The mice were administered MS-275 derivative (7 mg/kg/i.p) for 4 weeks. The H&E stained sections were measured for cross-sectional area analyses using Image J software. To investigate the molecular mechanisms of MS-275 derivative, several factors related with muscle atrophy were tested using RT-PCR.

Results: Administration of MS-275 derivative to db/db mice suppressed muscle weight loss and insulin resistance. As a result of examining muscle mass and fat accumulation in the hindlimb by MRI, we found MS-275 derivative reduced fat accumulation and improved muscle loss. Tibialis anterior (TA) muscle and gastrocnemius (GA) muscle had significantly induced muscle atrophy in db/db mice. However, treatment with MS-275 derivative prevented weight loss of TA and GA muscles and it also recovered reduction of muscle fiber size. Interestingly, MS-275 derivative dramatically reduced atrophy related gene expressions in TA muscle.

Conclusion: In this study, MS-275 derivative ameliorated muscle atrophy through a reduction of atrophy related gene expressions in db/db mice. These results suggest MS-275 derivative may be a basis for the development of therapeutic drugs as applied to atrophy-related muscular or metabolic diseases.

Disclosure

N.Lee: None. H.Kim: None. T.Kim: None. S.An: None. K.Lee: None. Y.Kim: None. S.Choi: None. Y.Kim: None. Y.Son: None. S.Choi: None. Y.Y.Kang: None. J.Jeon: None. S.Han: None.
1649-P: Biased GLP-1 Improves Weight Loss with Additional Benefits on Glucose Homeostasis via Biased GIP in Diabetic Rodent Models
Authors: RODRIGUEZ RUBEN , TRACY TED , MORALES MARIKRIS , HERGARDEN ANNE , LAM DAVINA , KRISHNAN SHYAM , HANSEN STIG K. , CHAKRAVARTHY MANU
Published: June 2023

GLP-1 and GIP when combined can deliver complementary pharmacology. CT-868 (CT) and CT-859 are biased dual GLP-1 and GIP receptor modulators with no β-arrestin coupling on either receptor. Effect of both compounds on weight loss (WL) and glucose (GLUC) homeostasis were assessed in relevant rodent models. At non-GIPR engaging doses in ob/ob mice, 30 nmol/kg CT achieved greater WL vs 200 nmol/kg Liraglutide (LI), an unbiased GLP-1RA (19.8% vs 11.5%, p=0.002), indicating biased GLP-1 improves WL vs unbiased GLP-1. GLUC tolerance test (GTT) in GIPR-/- mice showed similar reduction in AUCGLUC with LI and CT-859 at 20 nmol/kg 4h after dosing (53% vs 62%, p=NS), but only CT-859 maintained significant reduction after 24h and 48h, indicating biased GLP-1 induces a sustained GLUC lowering effect. After 14d of dosing in Akita mice with non-GIPR engaging doses of CT 20 nmol/kg, blood glucose (BG) decreased 30% vs LI 20 nmol/kg (p=0.01) indicating superior effect of biased GLP-1 on glycemic control. At GIPR engaging doses, CT 200 nmol/kg on background of insulin (INS) significantly lowered BG vs LI 200nmol/kg in Akita (↓35%, p=0.009) and DIO-STZ (↓32%, p<0.0001) mice. Akita mice treated for 14d with CT 300 nmol/kg + low INS normalized BG to same extent as vehicle + high INS, but with 68% lower INS levels (p < 0.0001). In GLP-1R-/- mice, CT 300 nmol/kg lowered AUCGLUC 38% vs vehicle (p<0.0001) without concomitant INS excursion, showing that GIP enhances INS independent GLUC disposal or INS sensitivity. In response to pyruvate challenge, CT 100 nmol/kg suppressed AUCGLUC 36% (p<0.05) and 14% (p=0.006) on a background of INS treatment in Akita and GLP-1R-/- mice, respectively, suggesting GIPR activation may contribute to suppression of endogenous GLUC production. Together, these data demonstrate that CT provides improved WL via biased GLP-1 with enhanced GLUC homeostasis via biased GIP relative to unbiased GLP-1 (LI). These findings have translated to T2D patients treated with CT-868.

Disclosure

R.Rodriguez: Employee; Carmot Therapeutics, Inc. T.Tracy: Employee; Carmot Therapeutics, Inc. M.Morales: None. A.Hergarden: Employee; Carmot Therapeutics, Inc. D.Lam: Employee; Carmot Therapeutics, Inc. S.Krishnan: Employee; Carmot Therapeutics, Inc. S.K.Hansen: Board Member; Carmot Therapeutics, Inc. M.Chakravarthy: Employee; Carmot Therapeutics, Inc.
1656-P: Glucagon-Like peptide-1 (GLP-1) Secretion from Intestinal L-Cells Is Mediated by hERG Potassium Channels
Authors: YANG JIN-KUI , LIU CHANG , WANG HAO , YUAN YINGCHAO
Published: June 2023

The hERG protein is a member of voltage-gated potassium (Kv) channels. Previous reports showed that patients with long QT syndrome due to mutations in hERG channel had higher responsive glucagon-like peptide-1 (GLP-1) secretion. However, the role of hERG in GLP-1 secretion remains uncertain. Here we report that hERG is co-expressed in GLP-1-expressing L cells in rodent intestinal epithelium (Fig. 1). In a murine L-cell model, GLUTag cell line, downregulation of hERG significantly prolonged action potential duration, increased intracellular calcium concentration ([Ca2+]i), and promoted GLP-1 secretion (Fig. 2) after stimulation of nutrients. These results reveal a direct role of hERG in GLP-1 secretion in murine L-cells, suggesting intestinal hERG is a potential target for the treatment of diabetes.

Disclosure

J.Yang: None. C.Liu: None. H.Wang: None. Y.Yuan: None.

Funding

National Natural Science Foundation of China (82170809, 81930019)
166-LB: Clinical Improvements and Extracellular Vesicle Size following Lifestyle Intervention in Latino Youth with Nonalcoholic Fatty Liver Disease
Authors: PIRAS IGNAZIO , WU XIUMEI , PIRROTTE PATRICK , OLSON MICAH , KHAN SOOFIA , XANTHAKOS STAVRA , SHAIBI GABRIEL Q. , DISTEFANO JOHANNA
Published: June 2023

Latino youths with obesity are disproportionately impacted by nonalcoholic fatty liver disease (NAFLD). Lifestyle intervention can improve established biomarkers such as serum transaminases and hepatic fat fraction (HFF) in NAFLD patients. Circulating levels of extracellular vesicles (EVs) have been associated with NAFLD and may track with changes in liver fat. Here we assessed changes in EV concentration and size following a comprehensive lifestyle intervention in 18 Latino adolescents (12 males/6 females; average age 13.3 ±1.2y) with obesity and NAFLD, as defined by MRI-measured hepatic fat fraction (HFF) ≥5%. Participants completed a 6-month lifestyle intervention that targeted improvements in eating behaviors (e.g., decreased sugar and saturated fat intake, portion control, and increased fiber intake) and increases in physical activity. EVs were isolated from fasting plasma samples taken at baseline and following intervention using size exclusion chromatography and characterized by nanoparticle tracking analysis. Significant improvements (pre- vs post-intervention) were observed in percent body fat (44.7 ±4.8% vs 42.2 ±5.3%, p<0.0001), alanine transaminase (ALT; 24.8 ±7.4 U/L vs 23.2 ±5.6 U/L p=0.02), and HFF (12.5 ±5.5% vs 9.6 ±4.9%, p=0.008). We observed a significant reduction in mean EV size (128.4 ±16.5 vs 120.2 ±16.4, p=0.03) and a non-significant reduction in EV concentration (1.14E+09 ±4.1E+08 vs 1.09E+09 ±1.8E+08, p=0.61) following the intervention. Change in mean EV size was significantly and positively associated with changes in SAT (cm3), HDL (mg/dl), fat (kg) and BMI (all p < 0.05). These results suggest that improvements in NAFLD-related phenotypes following lifestyle intervention correspond with reductions in EV size in Latino adolescents with obesity and NAFLD.

Disclosure

I. Piras: None. X. Wu: None. P. Pirrotte: None. M. Olson: Advisory Panel; Rhythm Pharmaceuticals, Inc. S. Khan: None. S. Xanthakos: None. G. Q. Shaibi: None. J. Distefano: None.

Funding

National Institutes of Health (R01DK127015)