bluuebunny/crossref_metadata_2025_split huggingface dataset:
1441-P: Low Morning Cortisol in Early Life Associated with Increased Risk of Islet Autoimmunity
Authors: VEHIK KENDRA , LYNCH KRISTIAN F. , PARIKH HEMANG M. , LERNMARK ÅKE , REWERS MARIAN , MCINDOE RICHARD , TOPPARI JORMA , ZIEGLER ANETTE-GABRIELE , AKOLKAR BEENA , HAGOPIAN WILLIAM , BRUSKO TODD M. , KRISCHER JEFFREY , ROTH ROSWITH L. , JOHNSON SUZANNE B. , STUDY GROUP TEDDY 
Published: June 2024

Introduction & Objective: Stress is implicated as a factor in immune reactivity and autoimmune disorders. Adverse experiences and chronic stress may be associated with low morning cortisol levels. Here, we tested if morning saliva cortisol is associated with the development of islet autoimmunity (IA).
Methods: Saliva was collected 30 minutes upon awakening and assayed for cortisol in 1049 children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study at 42 months. Using Cox proportional hazards models, we examined morning log2 cortisol at 42 months in relation to risk of IA between 4 and 15 years of age (any IA: n=89; GADA-first: n=53; IAA-first, n=23) in addition to TEDDY published factors associated with IA.
Results: Morning saliva cortisol (median log2=3.34) at 42 months is inversely associated with the risk of IA from 4 years of age (HR (95%CI) per log2 increase (0.65 (0.51-0.83), p=0.0005) adjusting for HLA-DR-DQ, diabetes family history, sex, weight-z score at age 12 months, and country. Both high (HR=0.19) and low (HR=1.95) morning cortisol levels are significantly associated with risk of IA, independently, as compared to 79% of children with log2 cortisol levels between 2-3.99 (Figure).
Conclusion: These findings suggest that morning saliva cortisol at 42 months of age is inversely associated with risk of IA in genetically at-risk children followed until 15 years of age.

Disclosure
K. Vehik: None. K.F. Lynch: None. H.M. Parikh: None. Å. Lernmark: Advisory Panel; DiaMyd Medical AB, Stockholm, Sweden. M. Rewers: Advisory Panel; Sanofi. Other Relationship; Sanofi. Consultant; Janssen Pharmaceuticals, Inc. Research Support; Juvenile Diabetes Research Foundation (JDRF). Consultant; Provention Bio, Inc. Research Support; Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases. R. McIndoe: None. J. Toppari: None. A. Ziegler: None. B. Akolkar: None. W. Hagopian: Research Support; Janssen Pharmaceuticals, Inc., Provention Bio, Inc. Consultant; Sanofi-Aventis U.S., Randox R & D. T.M. Brusko: None. J. Krischer: None. R.L. Roth: None. S.B. Johnson: None.

Funding
NIH NIDDK (U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, U01 DK128847, and Contract No. HHSN267200700014C)
1442-P: Type 1 Diabetes (T1D) Clusters in the SEARCH for Diabetes in Youth Study
Authors: HARRALL KYLIE K. , BIRD SARAH M. , KIM CATHERINE , REDONDO MARIA J. , DABELEA DANA 
Published: June 2024

Objective: Youth with T1D are heterogeneous for β-cell insufficiency, insulin sensitivity, autoantibody profile, risk alleles, and inflammatory markers. It is unknown whether subtypes of T1D exist. Such clusters might aid in the identification of youth at increased risk for poor outcomes.
Methods: SEARCH is a population-based observational cohort of youth (&lt; 20 years) with diabetes conducted from 2002 - 2012. Youth with T1D (n=1107) were clustered by inflammatory status and insulin secretion and sensitivity using hierarchical clustering (hclust, R 4.3.1) with C-reactive protein (CRP), C-peptide, and body mass index Z-score (&lt; 1 year since diagnosis). Demographics were compared across clusters.
Results: We found 6 clusters (Table). Youth in clusters 1 and 5 were more likely to be White and younger at diagnosis, with lower C-peptide, BMI Z-score, waist circumference, CRP, and IL-6. Youth in cluster 2 had high prevalence of positive GAD65 antibodies, CRP, and IL-6. Youth in cluster 3 had high prevalence of IA2 antibodies. Youth in cluster 6 were more likely to be Black or Hispanic and older at diagnosis, with higher C-peptide, BMI Z-score, waist circumference, triglycerides, and leptin.
Conclusion: We observed distinct clusters among youth with T1D of short duration. Future studies should examine whether T1D clusters are associated with diabetes outcomes and how T1D clusters compare to conventional risk scores for diabetes complications.

Disclosure
K.K. Harrall: None. S.M. Bird: None. C. Kim: None. M.J. Redondo: None. D. Dabelea: None.

Funding
National Institutes of Health (U18DP006517); National Institutes of Health (R21HD108508)
145-OR: Assessing the Current State of Diabetes Care in Long-Term Facilities Using Continuous Glucose Monitoring
Authors: SLYNE CHRISTINE , ROBERTS KIRSTEN , CONERY COLIN D. , BRABANT HALEY , KRAKOFF NOA , TOSCHI ELENA , MUNSHI MEDHA 
Published: June 2024

Introduction: Recommendations for diabetes care in long term care facilities (LTCF) focuses on avoidance of hypoglycemia and symptomatic hyperglycemia. Using continuous glucose monitoring (CGM), we evaluated the current state of glycemia in LTCF residents with multiple comorbidities.
Methods: We conducted a cross-sectional study using CGM in 8 LTC facilities in the United States. A masked Dexcom G6 pro CGM was placed for 10 days on residents with diagnosis of diabetes mellitus (DM) who were on any oral or injectable hypoglycemic medications. Clincial and demographic information were collected from medical records.
Results: We evaluated 65 residents (mean age 65 years, 50% female). Fourteen percent of the cohort was on sulfonylurea medications and 68% were on insulin. CGM data showed 26% of the cohort with &gt;1% time spent in hypoglycemia (time &lt;70 mg/dL). A larger burden of hyperglycemia was seen with 54% of the cohort spending &gt;10% time &gt;250mg/dL, 37% spending &gt;25% time &gt;250 mg/dL, and 14% spending &gt;90% time &gt;250 mg/dL. Only 44% of the cohort had &gt;50% Time-in-Range (70-180 mg/dL). The latest A1C was &lt;7% in 45% of the cohort, 7-8% in 27%, 8.1-9% in 12%, and &gt;9% in 16%. Fingerstick reading frequency was 2 or fewer times/day in 74% of the cohort, 3 times/day in 13%, and 4 or more times/day in 13%. On average, this cohort had 13 comorbidities, with 85% having functional disabilities. There was 14% with dementia and 42% with obesity (BMI&gt;30). All 100% of the participants had polypharmacy(≥5 medications/day).
Conclusions: In this multi-morbid cohort of residents with diabetes living in LTCF, we identified a high burden of both hypoglycemia and severe hyperglycemia, despite fair control of A1C. More consistent use of CGM could help identify glycemic excursions to improve therapeutic decision-making.

Disclosure
C. Slyne: None. K. Roberts: None. C.D. Conery: None. H. Brabant: None. N. Krakoff: None. E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sanofi. M. Munshi: Consultant; Sanofi.

Funding
Supported by an investigator initiated grant from Dexcom
1450-P: Associations between Marginalization and Insulin Pump Use among Adults with Type 1 Diabetes in Ontario
Authors: SOLIMAN YOUSTINA , EVERETT KARL , SHULMAN RAYZEL , AUSTIN PETER , LIPSCOMBE LORRAINE , BOOTH GILLIAN L. , WEISMAN ALANNA 
Published: June 2024

Introduction & Objective: We evaluated associations between marginalization and pump use in the context of a public funding program, and temporal trends in marginalization among new insulin pump program applicants.
Methods: We conducted population-based studies of adults with type 1 diabetes using administrative data. Unadjusted and adjusted logistic regression was used to assess associations between marginalization [determined by postal code using the Ontario Marginalization Index (ON-MARG)] and insulin pump use on March 31, 2021. Unadjusted ordinal logistic regression was used to evaluate association between insulin pump application year (2007-2022) and odds of being in a higher marginalization quintile.
Results: 16,471 (60%) of 27,453 adults used insulin pumps. Higher ON-MARG quintile was associated with lower odds of insulin pump use [adjusted OR 0.44 (0.39-0.48) for lowest vs. highest quintile]. The most marginalized individuals were the smallest proportion of applicants to the insulin pump program between 2007 and 2022 (Figure 1). While narrowing of marginalization distribution occurred from 2007-2010, widening occurred from 2020-2022.
Conclusion: Disparities in pump use persistent even in the context of public funding, and the COVID-19 pandemic may have disproportionately prevented more marginalized individuals initiating pump therapy. Residual barriers to pump use must be addressed.
Figure: Distribution of material resources quintile for all new applicants to ADP by fiscal year for all ages (n=21,002)

Disclosure
Y. Soliman: None. K. Everett: None. R. Shulman: Advisory Panel; Dexcom Canada. Speaker's Bureau; Dexcom Canada. P. Austin: None. L. Lipscombe: Other Relationship; Novo Nordisk Canada Inc. G.L. Booth: None. A. Weisman: None.

Funding
Banting Research Foundation & Canadian Statistical Sciences Institute (CANSSI) Ontario Discovery Award
1461-P: DNA Methylation (DNAm) and 28-Year Risk of Diabetic Peripheral Neuropathy (DPN) in Type 1 Diabetes (T1D)—The Epidemiology of Diabetes Complications (EDC) Study
Authors: ZHOU JIAYI , MYCHALECKYJ JOSYF , ONENGUT-GUMUSCU SUNA , ORCHARD TREVOR J. , COSTACOU TINA , MILLER RACHEL G. 
Published: June 2024

DPN is a common T1D complication that can greatly affect quality of life. DPN likely results from a combination of genetic risk and glycemic exposure. DNAm may help identify potential therapeutic targets; however, epigenome-wide association studies (EWAS) of DPN are lacking. We performed a prospective EWAS of 28-yr DPN risk and assessed associations adjusting for established risk factors in the EDC study of childhood-onset (&lt;17 yrs) T1D (baseline mean age 27, T1D duration 19 yrs). DPN was defined as ≥2 of: DPN symptoms, decreased tendon reflexes, abnormal sensory exam. After quality control, baseline whole blood DNAm (EPIC array) at 683,597 CpGs was analyzed in Cox models for time to DPN in 282 persons free of DPN at baseline. Models were adjusted for T1D duration, sex, smoking pack years, estimated blood cell composition and technical variables. False discovery rate (FDR)&lt;0.05 was considered significant. Genetic variants (meQTLs) associated with significant CpGs were identified. Over 28 yrs, 154 (54.6%) developed DPN. Three CpGs significantly associated with DPN: cg06163904 (CHMP6, log β per 5% DNAm=-0.98±0.19, p=1.05E-07, FDR=0.04), cg10835127 (CACNA1B, log β=-0.79±0.15, p=1.12E-07, FDR=0.04), and cg18945945 (PKNOX1, log β=-0.99±0.19, p=1.93E-07, FDR=0.04). Both cg10835127 and cg18945945 were associated with albumin excretion rate (β=-0.51±0.17, p&lt;0.01; β=0.50±0.23, p=0.03) but their associations with DPN were unaltered after adjustment. There were 75 meQTLs for cg18945945 in the PKNOX1 region, 59 of which were previously reported cg18945945 meQTLs in the Chronic Renal Insufficiency Cohort. This prospective EWAS in T1D identified loci where DNAm associated with DPN after adjusting for known risk factors, highlighting mechanisms for further study including cell repair/death (CHMP6), presynaptic depolarization and calcium channel activity (CACNA1B), and chemokine transcription regulation (PKNOX1).

Disclosure
J. Zhou: None. J. Mychaleckyj: None. S. Onengut-Gumuscu: None. T.J. Orchard: None. T. Costacou: None. R.G. Miller: None.

Funding
American Diabetes Assoication (1-19-JDF-109); NIDDK (R01DK034818); Rossi Memorial Fund (Pittsburgh, PA)
1464-P: Targeted Delivery of shRNA-Lipids to Activated Monocytes and Inhibition of Neovascularization in Proliferative Retinopathy
Authors: IMAM UDDIN MD 
Published: June 2024

Introduction & Objective: Proliferative retinopathy is a vision threatening condition in diabetic patients. We observed, using single cell RNA sequencing data analysis, activation of bone marrow-derived cells in peripheral blood from patients with Type-1 diabetes, and also in animal models of proliferative retinopathy. These activated monocytes and progenitor cells migrate into the retina in response to inflammation and neovascularization. However, contribution of these cells to neovascularization is largely unknown. We describe here the synthesis of a new hybrid nanoparticle for targeted delivery and gene silencing in activated monocytes that are associated with pathological neovascularization.
Methods: Single cell RNA sequencing data analysis were performed to characterize mRNA expression in peripheral blood from patients with Type-1 diabetes, and in oxygen-induced retinopathy (OIR) model. Targeted AS-shRNA-lipids were synthesized by conjugating diacyl-lipids to anti-sense short hairpin RNA with an anti-sense sequence complimentary to endoglin mRNA.
Results: Endoglin mRNA expression was associated with CD14high and IL1B positive activated monocytes in peripheral blood from Type-1 diabetic patients, and in OIR model. In addition, endoglin mRNA expression was inhibited by AS-shRNA-lipid. In addition, significant reduction of neovascularization was achieved in OIR after intraperitoneal injection of AS-shRNA-lipids.
Conclusions: Diabetes may contribute to monocyte activation and inhibition of endoglin mRNA could regulate the activation. We have developed a novel method for targeted delivery and inhibition of mRNA targets in activated monocytes in the living tissues using AS-shRNA-lipids. These studies may provide a framework for a novel strategy to inhibit retinal neovascularization.

Disclosure
M. Uddin: None.

Funding
American Diabetes Association (11-22-IBSPM-12); R01EY029693, R01EY023397
1465-P: The C1858T Polymorphism in PTPN22 Modulates the Human Pancreatic Islet Transcriptome
Authors: SULEIMAN MARA , DE LUCA CARMELA , SEMERARO ROBERTO , BOSI EMANUELE , MAGI ALBERTO , TESI MARTA , DEL GUERRA SILVIA , PAGLIAROSI OLIVIA , CUDINI ANNAMARIA , ROSSI LEONARDO , EIZIRIK DECIO L. , CNOP MIRIAM , MARCHETTI PIERO , MARSELLI LORELLA , FIERABRACCI ALESSANDRA 
Published: June 2024

Introduction & Objective: PTPN22 encodes for a lymphoid-specific intracellular phosphatase involved in T-cell receptor signaling. The C1858T PTPN22 polymorphism induces gain of function of the encoded Lyp phosphatase and associates with T1D. Since PTPN22 is expressed in human pancreatic islets (HI), we assessed whether the C1858T variant affects HI function and molecular features.
Methods: Genomic DNA of 105 nondiabetic (ND) donors was analyzed and HI were isolated from the same subjects. Islet insulin release was assessed in response to 16.7 mM glucose (G), glyburide (Glyb) and arginine (Arg). RNA-sequencing was performed in hand-picked HI. Islet functional and transcriptomic data of 8 carriers of the polymorphism and 11 wild type (WT) matched donors were compared.
Results: Insulin stimulation indexes in response to G, Glyb and Arg did not differ significantly between C1858T and WT islets (respectively 3.17±1.18 vs 2.80±0.94, 3.85±1.41 vs 3.75±1.30, and 3.20±1.14 vs 2.16±1.13). Comparison between the mutated vs WT islet transcriptomes evidenced 21 differentially expressed genes (FDR&lt;0.05, absolute fold-change&gt;1.5): 3 were up-regulated (DCD, MIR205HG, SNORA72) and 18 down-regulated (the top 5 being H2BC17, RRM2, IQGAP3, CYBB and FN1). GSEA retrieved 34 gene sets significant at FDR &lt; 25% threshold. At nominal p value of &lt; 1%, 6 of them were positively enriched in C1858T islets (Myc target_V1 and Myc target_V2, Unfolded protein response, Pancreas beta cells, DNA repair, E2F targets) and 18 were negatively enriched (including IFN-gamma response, IFN-alpha response, TNFA signaling via NFKB, Complement, Inflammatory response).
Conclusion: These results suggest that the C1858T PTPN22 polymorphism affects the islet transcriptome, including cellular stress, inflammation, and innate immunity pathways, without a major impact on insulin secretion. The ultimate mechanism(s) behind the role for the C1858T PTPN22 polymorphism in T1D-mediated beta cell damage remains to be clarified.

Disclosure
M. Suleiman: None. C. De Luca: None. R. Semeraro: None. E. Bosi: None. A. Magi: None. M. Tesi: None. S. Del Guerra: None. O. Pagliarosi: None. A. Cudini: None. L. Rossi: None. D.L. Eizirik: None. M. Cnop: None. P. Marchetti: Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. L. Marselli: None. A. Fierabracci: None.

Funding
RF-2019-12369889 AND Innovative Medicines Initiative 2 (115797, 945268)
1470-P: Modeling Familial Partial Lipodystropy Type 2 (LMNAp.R482W) Utilizing iPSC-Derived Adipocytes
Authors: BORREGO ALVAREZ ALUET , LIU KATIE , GOBBLE MCKINLEE R.S. , GRUPE MICHAEL , MOHAMMED ALI LINA , BUCHSER WILLIAM J. , BALDRIDGE DUSTIN , STONE STEPHEN I. 
Published: June 2024

Familial partial lipodystrophy type 2 (FPLD2) is a genetic syndrome characterized by loss of adipose tissue in the trunk and limbs and accumulation of supraclavicular fat. The most common genetic cause of FPLD2 is a pathogenic variant in the lamin A gene (LMNA; c.1444C&gt;T; p.R482W). Our goal was to model FPLD2 in an induced pluripotent stem cell (iPSC) line. CRISPR/Cas9 gene editing was used to knock-in the heterozygous LMNA p.R482W variant into AN1.1 control iPSCs. Wild type and mutant iPSCs underwent a 2-stage differentiation process, first to mesenchymal cells then to adipocytes. Functional studies included 2-deoxyglucose (2-DG) uptake and mitochondrial stress testing. Adipocytes also underwent flow cytometry, RNA sequencing, and microscopy. We observed that both wild-type and mutant clones successfully differentiated to adipocytes after 26 days in adipogenic differentiation media. Adipogenic differentiation was diminished in mutant cells. Basal and insulin-stimulated uptake of 2-DG was impaired in mutant cells. Mitochondrial stress testing in mutant cells demonstrated decreased oxygen consumption rate (OCR), which was driven by a significant decrease in maximal respiration and coupling efficiency. RNA sequencing showed that the mutant cells had significant reduction in the expression of key adipogenic genes including ADIPOQ, CD36, ITIH5, CHCR7, LIPE, ITGA7, and OMD. Preliminary results from flow cytometry and high content microscopy both demonstrated decreased lipid droplet accumulation in the mutant cell lines. Our results show that an iPSC-based model system can recapitulate the adipose tissue dysfunction seen in FPLD2. We propose that this system is a useful model for studying pharmaceuticals aimed at restoring the metabolic function of adipose tissue in FPLD2. Additionally, our work suggests that iPSC-derived adipocytes may be used to study novel candidate disease genes in individuals with atypical lipodystrophy.

Disclosure
A. Borrego Alvarez: None. K. Liu: None. M.R.S. Gobble: None. M. Grupe: None. L. Mohammed Ali: None. W.J. Buchser: None. D. Baldridge: None. S.I. Stone: None.

Funding
UL1TR002345 Clinical and Translational Research Funding Program. This project is funded through the Pilot Translational and Clinical Studies function of the WU ICTS.
1475-P: Genetic Evaluation of Human Lipidome Identifies Multiple Loci Associated with Metabolite Phenotypes Involved in Energy Metabolism and Inflammation in Type 2 Diabetes—Results from the Asian Indian Diabetic Heart Study (AIDHS)
Authors: ROUT MADHUSMITA , SANGHERA DHARAMBIR K. , BEHALF OF THE INVESTIGATORS OF THE AIDHS CONSORTIUM ON 
Published: June 2024

Background: Despite the success of genome-wide association studies (GWAS), the genetic mechanisms that predispose people to type 2 diabetes (T2D) remain poorly understood. Metabolomics has rapidly progressed from a single-gene/single-metabolite association to a genome-wide/metabolome-wide approach. However, limited data are available on non-white populations. Here, we have performed global lipidomic profiling and a targeted genetic association study to understand the genetic influences of T2D-associated variants on circulating lipid metabolites using a T2D cohort of Punjabi Sikhs from India.
Methods: Untargeted lipidomic analysis was performed on blood samples of 3000 individuals (1723 T2D cases and 1277 controls) using liquid chromatography and high-resolution mass spectrophotometry (LC-MS). The association of T2D with 7463 (1743 known and 5720 unknown) metabolites was identified using multivariate mixed regression modeling. We further analyzed the association of 366 and 391 T2D-associated metabolites in serum and plasma, respectively, by conducting a GWAS using up to 14,959,825 million imputed SNPs as part of discovery and replication cohorts.
Results: Our study identified 11 significant associations (p ranging from 6.8×10−10 to 4.8x10-20), including nine robust signals in the genes (TRPV4, RIPOR2, LDHC, MYRF, FADS1, and DNAH11) involved in transient receptor potential (TRP) channel, and calcium signaling pathways with the metabolites connected with energy metabolism, fatty acid transport, inflammation, and glucose metabolism.
Conclusions: In our first metabolome-GWAS in Asian Indians, we have identified novel molecular signatures and pathways associated with T2D. If validated, these results can potentially contribute to developing new therapeutic strategies to improve the prediction and treatment of T2D.

Disclosure
M. Rout: None. D.K. Sanghera: None.

Funding
National Institutes of Health (R01DK082766, R01DK118427); National Institute of Diabetes and Digestive and Kidney Diseases grants from the Presbyterian Health Foundation of Oklahoma
148-OR: Increased Insulin Secretion and Decreased Insulin Sensitivity in South Asian Youth without Diabetes
Authors: STEFANOVSKI DARKO , KELLY ANDREA , HITT TALIA A. , ZEMEL BABETTE S. , MAGGE SHEELA N. 
Published: June 2024

Introduction & Objective: The mechanisms underlying increased T2DM risk at lower BMI in South Asians (SA) compared to other ancestries are not known, but greater visceral fat (VFAT) for given BMI has been implicated. We examined the relationships of VFAT with insulin sensitivity (Si) and insulin secretory rate (ISR) in SA vs White (W) and African American (AA) adolescents and young adults (AYA).
Methods: SA, W, and AA aged 12-21y, BMI ≥ 80%ile for age and sex or BMI ≥ 23 kg/m2, without diabetes, underwent DXA for VFAT area and a 3-hr, 10-sample OGTT with Si by Minimal Model, and ISR by parametric deconvolution of C-peptide kinetics (2-compartment model). ISR incremental AUC was calculated. Ancestry groups were compared using Kruskal Wallis or chi2; Spearman correlations tested associations between VFAT and metabolic indices. Linear regression with adjustment for age, sex and inclusion of a VFAT-by-ancestry interaction term examined ancestry differences in Si and ISR.
Results: AYA (n= 51 SA, 39 W, 25 AA) were of similar age (median (IQR); SA 20.3y (18.9, 21.5); W 19.3y (18.3, 21.1); AA 19.0y (18.0, 20.4)), BMIZ (mean ± SD; SA 1.21 ± 0.53; W 1.14 ± 0.57; AA 1.38 ± 0.60), and BMI (SA 27.9 kg/m2 (25.1, 29.4); W 25.9 (24.6, 29.7); AA 27.3 (25.3, 35.5)), but differed by female sex: SA 52.9%; W 56.4%; AA 88.0% (p=0.009). SA had higher VFAT (97.5 cm2 (82.0,121.0)) than W (87.2 (64.1,108.0) and AA (75.0 (51.2,102), p= 0.029. One cm2 increase in VFAT associated with 41% lower Si (p=0.03) and 82% greater increase in ISR (p&lt;0.001) in SA compared to W. Compared to AA, for 1cm2 VFAT increase, SA had similar Si decrease, but 82% greater ISR increase (p=0.004).
Conclusion: Among AYA of similar BMI, SA had higher VFAT than W and AA. However, for similar increase in VFAT, SA had a greater reduction in Si and higher ISR increase compared to W. SA had a similar reduction in Si compared to AA, but again a greater increase in ISR. Thus, the higher T2DM risk in SA may be due to greater hyperinsulinemic compensation, resulting in beta cell exhaustion.

Disclosure
D. Stefanovski: None. A. Kelly: None. T.A. Hitt: None. B.S. Zemel: None. S.N. Magge: None.

Funding
National Institutes of Health (R01DK115648); National Institutes of Health (UL1TR001878); National Institutes of Health (UL1TR001079)