bluuebunny/crossref_metadata_2025_split huggingface dataset:
1456-P: 2022 State of Type 1 Diabetes in the U.S.—Real World T1D Exchange Multicenter Data from over 60,000 People
Authors: EBEKOZIEN OSAGIE , NOOR NUDRAT , DIMEGLIO LINDA , YAU MABEL , RAPAPORT ROBERT , WEISSBERG-BENCHELL JILL , HANNON TAMARA S. , MCNAMARA KIMBERLY , MILLER KELLEE , MAAHS DAVID M. ,   T1D EXCHANGE QUALITY IMPROVEMENT COLLABORATIVE (T1DX-QI)
Published: June 2023

Background: In response to sub-optimal type 1 diabetes (T1D) care data in the US, intensive quality improvement (QI) programs were implemented in the T1D Exchange QI collaborative (T1DX-QI) to improve outcomes for individuals with T1D. The aim of this analyses is to characterize the T1DX-QI patient population consisting of over 60,000 individuals with T1D
Method: This cross-sectional analysis included 2022 electronic medical record (EMR) data of 60,915 individuals with T1D from 26 diabetes centers. Population attributes analyzed included demographics, duration of diabetes, glycemic outcomes and diabetes technology use.
Result: In this population described in table 1, more adults ≥ 26 years of age were at A1c target goal (&lt;7%) (34%), compared to children and adolescents (22%). Diabetes technology use was higher in the 6-13y age group (CGM: 64%, insulin pump: 53%) relative to adults 26-50y (CGM: 46%, insulin pump: 48%); whereas Hybrid Closed Loop System (HCLS) use was higher in adults 26-65y (13%) relative to children and younger adults 6-26y (6%). Self-reported Diabetes Ketoacidosis events were also higher in the younger age groups.
Conclusion: This study reports characteristics of persons with T1D from a multi-center database and demonstrates that efforts are still needed to improve optimal management of diabetes.
Table 1: T1DX-QI EMR T1D Data Distribution 2022 (N=60915)

Disclosure
O.Ebekozien: Advisory Panel; Medtronic, Research Support; Eli Lilly and Company, Dexcom, Inc. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. .T1d exchange quality improvement collaborative (t1: n/a. N.Noor: None. L.Dimeglio: Advisory Panel; Merck & Co., Inc., Consultant; Abata Therapeutics, Vertex Pharmaceuticals Incorporated. M.Yau: None. R.Rapaport: None. J.Weissberg-benchell: Advisory Panel; Beta Bionics, Inc., Research Support; Beta Bionics, Inc. T.S.Hannon: Advisory Panel; Eli Lilly and Company. K.Mcnamara: None. K.Miller: Consultant; Dexcom, Inc.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust
1465-P: Identification of GCK Gene Variants and Clinical Characterization in Japanese Pediatric MODY2 Cases
Authors: KATASHIMA RUMI , YOSHIDA SUMIKO , WATANABE YUKA , MORITANI MAKI , YOKOTA ICHIRO 
Published: June 2023

Maturity-onset diabetes of the young (MODY) is traditionally characterized by early onset and a heterogeneous autosomal dominant form of inheritance. MODY2 may be common in the Japanese, but the difference in clinical characteristics compared to Europeans and Americans remains unclear. Here, we examined the characteristics in Japanese pediatric patients diagnosed with MODY2. We retrospectively reviewed the diagnostic data of Japanese MODY2 patients diagnosed at our hospital between 2009 and 2022. Genetic screening for MODY2 was performed by direct sequencing followed by multiplex ligation amplification assays. We identified 20 missense mutations in 25 patients and 2 nonsense mutations in 2 patients. We detected 5 deletions in 6 patients. The mean age at diagnosis was 10 years (range 2-14 years), the mean BMI percentile was 46.2%, with none being obese. Mean HbA1c was 6.54%. A glucose tolerance test was performed on 29 patients, 15 of whom were diabetic (7 were diabetic at fasting, 5 were diabetic at 120 min, 3 were diabetic at both) and 14 of borderline diabetes (IFG + IGT: 11, IFG: 2, and IGT: 1). The average glucose tolerance test values were 121.6 mg/dL at 0 min and 182.2 mg/dL at 120 min. No correlation was found between age at onset and plasma glucose value at 0 and 120 min. Reportedly, MODY2 causes a slight increase in post-load blood glucose levels, however the difference between 120 min and 0 min was 56.0 mg/dL (−32 to 140). A negative correlation was observed between 0 min and 120 min blood glucose levels. HOMAIR average was 1.85, 27% of which patients were 2.5 or higher; HOMA-β average was 37.0%, 39% of which showed &lt;30%; and insulinogenic index averaged 0.63, 25% of which showed &lt;0.4, indicating decreased initial insulin secretion. In this study, it is suggested that in Japanese MODY2 cases, glucose sensor dysfunction due to GCK gene mutation causes decreased initial insulin secretion.

Disclosure
R.Katashima: None. S.Yoshida: None. Y.Watanabe: None. M.Moritani: None. I.Yokota: None.
1544-P: Circadian Timing of SGLT2 Inhibitor Administration Modulates Therapeutic Effects on Pancreatic Islet Function, Composition, and Gene Expression
Authors: DHANASEKARAN MAHESWARAN , RAKSHIT KUNTOL , HER TRACY K. , MATVEYENKO ALEKSEY 
Published: June 2023

Timing of drug administration based on endogenous circadian cycles (i.e., chronotherapy) has been shown to enhance treatment efficacy and improve outcomes in type 2 diabetes (T2DM). Sodium-Glucose Co-transporter 2 inhibitors (SGLT2i) are potent glucose lowering agents which improve cardiovascular health and exert systemic benefits on metabolic organs (e.g., pancreatic islets). Systemic benefits of SGLT2i are attributed to their ability to mimic a fasting state thus raising a question whether chronotherapeutic exposure to SGLT2i timed to the fasting vs. feeding circadian cycle will produce divergent benefits in T2DM. To address this, we generated a diet-induced T2DM mouse model by exposing male C57BL/6 mice to 14 weeks of high fat/high sucrose (HFHS) diet. Following induction of diabetes, mice were assigned into 3 groups for 4 weeks: 1) DAPAFAST: mice with daily Dapagliflozin (DAPA) oral gavage (1 mg/kg) given at the onset of the fasting (FAST) circadian cycle; 2) DAPAFED: daily DAPA oral gavage at the onset of the feeding (FED) cycle; 3) DAPAVEH: daily vehicle (VEH) gavage. DAPAFAST and DAPAFED groups demonstrated comparable lowering of basal and OGTT glucose versus DAPAVEH (~30%, p&lt;0.05). In contrast, whereas improved glucose tolerance in DAPAFAST was associated with enhanced insulin secretion (p&lt;0.05 vs. DAPAVEH), no changes in β-cell function was noted in DAPAFED mice. Consistently, RNAseq analysis of DAPAFAST isolated islets revealed attenuated expression of genes enriched for key pathways regulating β-cell failure such as p53, FOXO, and TGFβ signaling (all p&lt;0.05). We also noted divergent effects on islet morphology with DAPAFAST group uniquely characterized by increased α-cell mass compared to DAPAFED and DAPAVEH (~70% increase, p&lt;0.05). These data demonstrate divergent metabolic and islet effects of SGLT2i therapy highlighting the importance of chronotherapeutic approaches for optimal treatment of T2DM.

Disclosure
M.Dhanasekaran: None. K.Rakshit: None. T.K.Her: None. A.Matveyenko: None.
1553-P: Postprandial C-Peptide–to–Glucose Ratio Is Valuable in Assessing Beta-Cell Function in Japanese Patients with Type 2 Diabetes
Authors: MATSUHASHI YUKI , ABE TAKAHIRO , FUJITA TOMOYUKI , MIZUSHIRI SATORU , CHIKAZAWA SHINJI , DAIMON MAKOTO 
Published: June 2023

Onset of type 2 diabetes (T2D) is based on the insulin secretion (loss of β-cell function) and resistance. Residual β-cell function is a key factor in achieving optimal glycemic control in T2D patients. Glucagon stimulates insulin, therefore glucagon stimulation test (GST) is a reliable marker for β-cell function. Fasting C-peptide (CPR) to glucose ratio (CPR[ng/ml] to glucose[mg/dl] x100; F-CPR-index) is used as a marker of insulin secretion. We evaluated the efficacy of postprandial CPR to glucose ratio (P-CPR-index) for evaluating β-cell function in T2D. Japanese T2D patients with inadequate glycemic control (HbA1c&gt;7.0) were enrolled in the study (n=500, insulin therapy=283). HbA1c, fasting CPR and glucose, postprandial (120 min after breakfast) CPR and glucose were measured, and F-CPR-index and P-CPR-index were calculated. GST was performed as follows: 1mg of glucagon was injected intravenously, CPR was determined before and 6 min after injection, GSTΔCPR (CPR[6 min] - CPR[0 min]) was calculated. Factors correlated with GSTΔCPR were analyzed using simple and multiple stepwise regression analysis. P value&lt;0.05 was defined as statistically different. F-CPR-index, P-CPR-index and GSTΔCPR were 1.60±0.95, 2.67±1.92 and 1.93±1.21, respectively. Simple regression analysis showed that GSTΔCPR was significantly correlated with age, height, body weight (BW), BMI, waist circumference, duration of diabetes, retinopathy, insulin therapy, urinary CPR, F-CPR-index and P-CPR-index. Multiple stepwise regression analysis revealed that independent factors contributing to GSTΔCPR were BW (β=0.336), duration of diabetes (β= −0.107), presence of retinopathy (β= −0.121), use of DPP-4i (β= −0.099), metformin (β= −0.109), SGLT2i (β= −0.108, p=0.002) and P-CPR-index (β=0.432)(R2=0.453). Our date demonstrated that P-CPR-index was valuable and simple method in assessing residual β-cell function with/without insulin therapy in daily clinical practice.

Disclosure
Y.Matsuhashi: None. T.Abe: None. T.Fujita: None. S.Mizushiri: None. S.Chikazawa: None. M.Daimon: None.
1573-P: Association of Thyroid Hormone Levels with NAFLD in Recent-Onset Diabetes
Authors: SAATMANN NINA , SCHÖN MARTIN , ZAHARIA OANA P. , HUTTASCH MAXIMILIAN , STRASSBURGER KLAUS , TRENKAMP SANDRA , KUPRIYANOVA YULIYA , SCHRAUWEN-HINDERLING VERA , KAHL SABINE , BURKART VOLKER , WAGNER ROBERT , RODEN MICHAEL 
Published: June 2023

Nonalcoholic fatty liver disease (NAFLD) is a growing health concern associated with obesity and type 2 diabetes (T2D). Thyroid hormones are important regulators of lipid homeostasis. Indeed, people with hypothyroidism are at greater risk for NAFLD and it has been suggested that humans with T2D are more likely to develop hypothyroidism. However, little is known about the relationship of thyroid function with NAFLD in type 1 diabetes (T1D) and T2D.
We hypothesized that (i) low free thyroxin (fT4) and high thyroid-stimulating hormone (TSH) levels are associated with increased hepatocellular lipid content (HCL) and (ii) that fT4 and TSH can identify persons at high-risk for hepatic steatosis in people with recent-onset diabetes. We examined people with T1D (n=358) or T2D (n=596) and 175 healthy participants of the German Diabetes Study (GDS). First, validation of the fatty liver index (FLI) against quantification of HCL by 1H-magnetic resonance spectroscopy revealed a close correlation (ß=0.715, p&lt;0.001; n=446). Second, FLI negatively correlated with fT4 in males (ß=−0.139, p&lt;0.01), but not in females with T2D (ß=−0.086, p=0.26). Likewise, TSH associated positively with FLI in males (ß=0.116, p&lt;0.05), but not in females with T2D (ß=−0.057, p=0.45). TSH and FLI were differently associated between males and females before (p&lt;0.05), but not after (p=0.82) adjustment for BMI. Finally, fT4 had a low diagnostic precision for steatosis (by FLI) as derived from the respective area under the receiver operating curve (0.57, 95% CI [0.53;0.62]; p&lt;0.001) in T2D and was not significant in other groups. TSH had no diagnostic precision for steatosis in any groups.
In conclusion, FLI can be used as a surrogate measure of HCL in recent-onset diabetes. The correlation of FLI with lower thyroid function in male T2D suggests a sex-specific interaction between thyroid and liver lipid metabolism, which is mainly driven by body mass. Both, fT4 and TSH offer no relevant efficacy to detect steatosis at least in recent-onset diabetes.

Disclosure
N. Saatmann: None. M. Schön: None. O.P. Zaharia: None. M. Huttasch: None. K. Strassburger: None. S. Trenkamp: None. Y. Kupriyanova: None. V. Schrauwen-Hinderling: None. S. Kahl: None. V. Burkart: None. R. Wagner: Speaker's Bureau; Novo Nordisk, Sanofi. Advisory Panel; Daiichi Sankyo. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis. Consultant; TARGET PharmaSolutions, Inc. Research Support; Sanofi.
1590-P: Post-Oral Glucose Load Hyperinsulinemia in Individuals with Metabolic Syndrome and Metabolic-Associated Fatty Liver Disease—First Steps toward the Development of Type 2 Diabetes?
Authors: TRÉPANIER GABRIELLE , GIGNAC THEO , PRADEAU MARION , MORISSETTE ARIANNE , AGRINIER ANNE-LAURE , GAGNON CLAUDIA , VOHL MARIE-CLAUDE , MARETTE ANDRE , CARREAU ANNE-MARIE 
Published: June 2023

Introduction: Metabolic associated fatty liver disease (MAFLD) increases the risk of incident type 2 diabetes (T2D), but mechanisms involved have not been clearly elucidated.
Objective: To assess post-oral glucose tolerance test (OGTT) glucose metabolism, insulin resistance, secretion and clearance in individuals with metabolic alterations, with or without increased liver fat.
Methods: Individuals with a BMI &gt;25 kg/m2 and at least 1 criteria for metabolic syndrome were included in this analysis. Liver fat was quantified using MRI and participants were assigned to 2 groups according to &gt; 5% liver fat (MAFLD group) or ≤ 5%. A 3h frequently-sampled OGTT was performed and oral minimal model was used to measure insulin sensitivity, secretion and disposition index.
Results: Fifty participants were included in this analysis and 50% had a liver fat &gt; 5%. Post-OGTT glucose concentrations and iAUC glucose were not different between groups (p -≥ 0.50), whereas post-OGTT insulin concentrations and iAUC were significantly higher in the MAFLD group (p &lt; 0.03) and significantly associated with liver fat. The components of insulin secretion (dynamic, static and total) were not different between groups (p -≥ 0.27). Insulin sensitivity and dynamic disposition indices were lower in the MAFLD group and significantly associated with liver fat. but in a multivariable regression model including sex and BMI, liver fat was not statistically associated with these indices. Insulin clearance indices were significantly lower in the MAFLD group, and liver fat statistically explained most of the variance in the multivariate model (p&lt; 0.02).
Conclusion: Among individuals with metabolic alterations, the presence of MAFLD is associated with impaired insulin clearance and post-oral glucose load hyperinsulinemia. Insulin sensitivity and dynamic beta-cell function are also altered, features of the early pathophysiology of T2D.

Disclosure
G.Trépanier: None. T.Gignac: None. M.Pradeau: None. A.Morissette: None. A.Agrinier: None. C.Gagnon: Advisory Panel; Novo Nordisk, Other Relationship; Ascendis Pharma A/S, Research Support; Novo Nordisk. M.Vohl: None. A.Marette: Advisory Panel; Valbiotis, Amancia, Plexus, Acasti. A.Carreau: Advisory Panel; Novartis, Consultant; Valbiotis, Speaker's Bureau; Novo Nordisk Canada Inc.
1596-P: Homozygous Mutations in MFN2 Aggravated Fat Deposition in Mouse Hepatocytes
Authors: YU YUE , LUO YINGYING , ZHOU XIANGHAI , JI LINONG 
Published: June 2023

Objective: Studies had found that homozygous mutations at p.R707W in the mitofusin-2 (MFN2) gene cause severe lipids metabolic abnormalities, and the mechanism has not been elucidated. In this study, we aim to explore the effect of the mutant protein on hepatocyte lipids deposition.
Methods: Primary hepatocytes of wild-type (WT), heterozygous and homozygous mutation were isolated from 8 weeks old mice. Hepatocytes were treated with 600μmol/L free fat acid (FFA) of oleic acid/palmitic acid (2︰1) mixture for 12 hours to establish a NAFLD model in vitro. The lipid accumulation of hepatocytes was observed by Oil red O staining and the contents of triglyceride (TG).
Results: Mutant mice carrying a novel p.R707W (CGA to TGG) mutation and silent mutation (p.D708=(GAT to GAC)) were identified (Fig. 1A). The results of Oil Red O staining and TG content measurement before FFA treating showed that more lipid was deposited in the homozygous hepatocyte than in WT cells (Fig. 1B, Fig. 1C) (*P&lt;0.05), revealing that different genotypes of mice already have varied liver lipid contents at 8 weeks. After stimulation with FFA, TG content and lipidosis area in homozygous hepatocytes were significantly higher than those in WT (**P&lt;0.01). And there was no significant difference between heterozygote and WT hepatocytes with or without FFA stimulation.
Conclusion: Homozygous mutation at p.R707W in MFN2 aggravated lipid deposition in mouse.

Disclosure
Y.Yu: None. Y.Luo: None. X.Zhou: None. L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics.

Funding
China International Medical Foundation (2021-N-03)
1602-P: Galectin-3 Inhibition Protects ApoE Knockout Mice against Western Diet–Induced Nonalcoholic Steatohepatitis and Glucose Intolerance
Authors: ARAUJO LAYANNE , SUCUPIRA FELIPE , DIAS CAROLINA C.B. , AMARAL ANDRESSA , PAULO CAMPOREZ JOAO 
Published: June 2023

Nonalcoholic Fatty Liver Disease represents a broad spectrum of histological abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis or hepatocellular carcinoma. NASH is characterized by steatosis, hepatic inflammation, hepatocellular ballooning, and fibrosis. Therefore, the aim of this work was to evaluate the effect of modified citrus pectin (MCP), inhibitor of galectin-3, in ApoE KO mice fed a western diet (WD). ApoE KO mice were divided into 3 groups: standard diet-fed (SD) group, WD-fed group, and WD-fed + MCP-treated group (WD+MCP). WD-fed mice displayed increased hepatic triacylglycerides (TAG-290%), and plasma ALT (115%) and AST (130%) compared with SD group. MCP treatment decreased hepatic TAG (30%) in WD-fed mice, plasma ALT and AST were reverted. WD-fed mice also displayed increased hepatic collagen deposition (18%), and MCP treatment inhibited this increase. These results were similar with hydroxyproline concentration in liver. WD-fed mice showed an impaired glucose tolerance compared with SD-fed mice, while MCP treatment improved glucose tolerance in WD-fed mice. Also, WD-fed mice presented increased fasting insulin (140%) compared with SD-fed mice, and MCP treatment reverted this increase by 100%. Gene expression of F4/80 was increased by 76% in the WD group compared with SD group, however had not significant difference between WD+MCP and SD group. Gene expression of matrix metalloproteinase 2 was increased by 5-fold in WD group compared with SD group, while this increase was inhibited with MCP treatment. Also, it was observed an increase in JNK phosphorylation by 3-fold in WD group, and MCP treatment inhibited this increase. Taken together, we confirm WD-fed ApoE KO mice as a suitable experimental model of NASH, and the inhibition of galectin-3 by the treatment with MCP protects ApoE KO mice against the development of NASH and glucose intolerance.

Disclosure
L. Araujo: None. F. Sucupira: None. C.C.B. Dias: None. A. Amaral: None. J. Camporez: None.

Funding
São Paulo Research Foundation (FAPESP)
1629-P: Association between Dyslipidemia and Myosteatosis Evaluated by Abdominal Computed Tomography
Authors: SEUNG KIM HWI , NA JUNG HAN , KYUNG CHO YUN , JE LEE WOO , HEE JUNG CHANG 
Published: June 2023

Introduction: The association between dyslipidemia and myosteatosis measured using muscular quality map in abdominal computed tomography(CT) was analyzed in a large population.
Methods: Abdominal CT of 20,210 subjects were evaluated to measure total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA: good quality muscle) and low attenuation muscle area (LAMA: poor quality muscle). Myosteatosis indices used were SMA/body mass index(BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. Dyslipidemia was defined as high-density lipoprotein cholesterol(HDL-C) less than 40mg/dL in men and 50mg/dL in women, low-density lipoprotein cholesterol(LDL-C) greater than 160mg/dL, or triglycerides(TG) greater than 150mg/dL.
Results: According to multiple logistic regression analyses, the odds ratios (ORs) of dyslipidemia according to HDL and LDL definitions showed a decreasing trend with increasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA (P for trend &lt; 0.001 for all). The adjusted ORs (95% confidence intervals[CIs]) for dyslipidemia in Q2, Q3, and Q4 for NAMA/TAMA compared with Q1 were 0.87 (0.79-0.96), 0.76 (0.69-0.85) and 0.55 (0.49-0.61) according to the HDL definition and 0.93 (0.83-1.05), 0.95 (0.84-1.07), and 0.69 (0.60-0.79) according to the LDL definition. Conversely, the ORs of dyslipidemia according to HDL and LDL showed an increasing trend according to increasing LAMA/BMI quartiles (P for trend &lt; 0.001 for all). Dyslipidemia according to TG did not show a significant association after adjustment.
Conclusion: Dyslipidemia according to HDL-C and LDL-C definitions is associated with myosteatosis, positively with bad quality (unhealthy) muscle and negatively with good quality (healthy) muscle. Muscle quality may be an important risk factor for dyslipidemia and ensuing cardiometabolic diseases.

Disclosure
H.Kim: None. H.Jung: None. Y.Cho: None. W.Lee: None. C.Jung: None.
1635-P: Sex Differences in Skeletal Muscle Mitochondrial Function in Rats Fed a High-Fat/High-Sucrose Diet
Authors: KNAUB LESLIE , HULL SARA , HULETT NICHOLAS A. , KELLER AMY C. , REUSCH JANE E.B. , SCALZO REBECCA L. 
Published: June 2023

Women maintain their metabolic health at greater body mass indexes compared with men, delaying the onset of type 2 diabetes (T2D). Skeletal muscle is responsible for the bulk of glucose uptake and oxidation; these functions are impaired in T2D. Skeletal muscle mitochondria support muscle bioenergetics balancing oxidative phosphorylation of ATP with the production of reactive oxygen species. We hypothesized that skeletal muscle mitochondria in females would be protected from the oxidative metabolic stress of high-fat/high-sucrose (HFHS) diet compared with males. Wistar rats fed a chow or HFHS diet for 14 weeks were sacrificed at 18 weeks. HFHS fed males gained more body weight compared with females (P &lt; 0.0001), yet fat mass was greater with HFHS diet in both sexes when controlled for body mass (P &lt; 0.0001). Glucose was greater in males and HFHS fed rats (P &lt; 0.001). Insulin resistance (HOMA-IR) was greater in males (P = 0.01) but unaffected by diet. HFHS fed males had greater mitochondrial respiration compared with females (P &lt; 0.01 diet by sex interaction). Nutrient stress can induce reactive oxygen species. Hydrogen peroxide (H2O2) production measured with Amplex Red at this respiration steady state was 34% greater in HFHS fed males compared with 11% in females. ADP titration revealed a greater area under the curve for HFHS fed males for both oxygen (P = 0.02) and H2O2 flux (P = 0.07). Protein content of mitochondrial complexes I and III, the sites of electron leak and generation of mitochondrial reactive oxygen species, were greater in males (P &lt; 0.02), and complex V, the site of ATP production, was greater in females (P = 0.01). These data suggest that males respond to an obesogenic challenge with greater mitochondrial respiration and accompanying oxidant production whereas females with similar fat mass accrual are protected from excess oxidant production in this setting. Sex-specific adaptation to nutrient excess may play a role in a higher obesity threshold for women compared to men at risk for T2D.

Disclosure
L.Knaub: None. S.Hull: None. N.A.Hulett: None. A.C.Keller: None. J.E.B.Reusch: Advisory Panel; Medtronic. R.L.Scalzo: None.

Funding
U.S. Department of Veterans Affairs (BX004533-01, BX002046); National Institutes of Health (5T32AG000279-20)