bluuebunny/crossref_metadata_2025_split huggingface dataset:
1383-P: Relationship between Body Fat Mass and Insulin Resistance in Nonobese Patients with Idiopathic Hypogonadotropic Hypogonadism and Normal Glucose Tolerance
Authors: XU HUAN , CHEN XUEYAN , YANG XUBIN , XU WEN 
Published: May 2022

Objective: The purpose of this study was to investigate the relations between body fat mass and insulin resistance in non-obese patients with idiopathic hypogonadotropic hypogonadism (IHH) and normal glucose tolerance.
Methods: A total of 42 patients with IHH and BMI lower than 28 kg/m2 from January 2013 to October 2017 were recruited. Patients were required to have a normal glucose tolerance test for inclusion in the study. Ten Healthy subjects having a routine physical examination and a normal glucose tolerance test were also recruited as control group. Laboratory studies included fasting insulin, testosterone, and lipids. Waist circumference (WC) , weight, and body fat mass were measured, and waist-to-hip ratio (WHR) , body mass index (BMI) , HOMA-IR, and LogHOMA-B were calculated. Data were compared between groups, and linear regression was used to determine relations.
Results: Blood pressure, fasting glucose, BMI, WHR, and lipids were similar between the groups. Fasting insulin levels (15.61 ± 7.66 mIU/L vs. 7.60 ± 3.84 mIU/L) , logHOMA-B (2.39 ± 0.29 vs. 2.03 ± 0.21) , HOMA-IR (3.38 ± 1.71 vs. 1.64 ± 0.91) , and body fat mass (30.49 ± 9.46% vs. 21.± 4.31%) were significantly greater in the IHH group compared with those in control group (all, P &lt; 0.05) . Multivariable linear regression showed that in IHH patients body fat mass was an independent predictor of fasting insulin level (β = 0.71, 95% confidence interval [CI]: 0.54, 0.88, P &lt; 0.01) , LogHOMA-B (β = 0.02, 95% CI: 0.001, 0.032, P &lt; 0.05) , and HOMA-IR (β = 0.14, 95% CI: 0.09, 0.18, P &lt; 0.05) .
Conclusion: Body fat mass is an independent predictor of insulin resistance in IHH patients with normal glucose tolerance.

Disclosure
H.Xu: None. X.Chen: None. X.Yang: None. W.Xu: None.

Funding
This study was supported by Natural Science Foundation of Guangdong Province [2018A030313915]; Medical Scientific Research Foundation of Guangdong Province of China [A2018286].
14-LB: Clinical Utility of KidneyIntelX on Patients with Early-Stage Diabetic Kidney Disease—A Real-World Evidence Study
Authors: TOKITA JOJI , DONOVAN MICHAEL J. , FIELDS ROBERT 
Published: May 2022

Introduction: KidneyIntelX is a multiplex immunoassay of 3 plasma biomarkers with 7 clinical variables combined using machine-learning to generate a risk score for progressive decline in kidney function over 5 years in individuals with early-stage diabetic kidney disease (DKD) .
Methods: A Population Health defined Mount Sinai approved care pathway for DKD patients informed by the KidneyIntelX test was introduced into the Mount Sinai Health System in New York, NY as part of a Real World Evidence (RWE) study (NCT04802395) . Decision impact of medication management (anti-hypertensives, SGLT2 inhibitors/GLP1 agonists) and specialist referral was tracked. An interim analysis was performed for 1) Assessing comparability between RWE and a published clinical validation cohort based on KidneyIntelX risk score distribution; 2) Determining if necessary EHR clinical fields were captured; 3) Identifying early evidence of KidneyIntelX impact on provider decision-making.
Results: Between Mar-Nov 2021, 1,112 patients had KidneyIntelX test results, with post-test follow up to 36 weeks. The risk breakdown of RWE population was similar to the clinical validation cohort [High 14% vs. 17%, intermediate 40% vs. 37% and low risk 46% vs. 46%]. EHR record review for care changes confirmed ability to meet study objectives. Compared to patients scored low risk, there were changes in anti-hypertensives (OR 3.0; 95% CI 1.6-5.6) , initiation of SGLT2i/GLP-1a (OR 6.4; 95% CI 2.9-14) and increased referrals to nephrologists, endocrinologists, or dieticians (OR 2.8;95% CI 1.7-4.7) in patients scored as high-risk (Figure) .
Conclusions: KidneyIntelX was successfully deployed in a health care system in a comparable population to the validation cohort with high data capture fidelity. Application of guideline-based
therapies and specialist referral increased in the proportion to reported risk level by 3-6 and &gt;2-fold, respectively.

Disclosure
J. Tokita: None. M. J. Donovan: Employee; Renalytix. R. Fields: None.
140-OR: Machine Learning for Metabolite Estimation to Examine Contributors to Glucose Homeostasis and Adiposity: The GUARDIAN Consortium
Authors: ALLRED NICHOLETTE , AINSWORTH HANNAH C. , GUO XIUQING , MACKAY ADRIENNE W. , NYASIMI FESTUS , MELIA OWEN , LIANG YANYU , BOWDEN DONALD W. , TAYLOR KENT , RAFFEL LESLIE J. , BUCHANAN THOMAS A. , WATANABE RICHARD M. , ROTTER JEROME I. , WAGENKNECHT LYNNE E. , LANGEFELD CARL D. , IM HAE K. 
Published: May 2022

Diabetes is characterized by metabolic dysregulation. Metabolomics captures interactions of cellular processes and environmental exposures to promote disease and can improve mechanistic understanding to identify clinically relevant targets. However, use is limited by cost and sample availability. To facilitate investigation, machine learning approaches were used in the Insulin Resistance Atherosclerosis Family Study (n=943 Mexican Americans) with empiric metabolites (Metabolon HD4) and GWAS data to generate genetically regulated metabolite estimation models for broad application. 950 metabolites were heritable. Ridge and LASSO regression had cross validated correlation &gt;0.1 for 448 metabolites. In an independent set, LASSO (enforcing sparsity) outperformed Ridge (full polygenic architecture) regression. Estimation was extended to the GUARDIAN Consortium (n∼4377) to assess the association of genetically predicted metabolites with glucose homeostasis and adiposity. Multiple associations (FDR P&lt;0.05) were observed. For glucose homeostasis, mannose, which predicts diabetes development, was inversely associated with glucose effectiveness (P=7.1E-3) . For adiposity, urate was positively associated with BMI and waist circumference, capturing lifestyle contributions. In addition, three uncharacterized metabolites were associated with measures of adiposity (P=0.014-3.1E-6) suggesting this approach could contribute to metabolite characterization.
In conclusion, we have developed algorithms for estimating 448 metabolites using genetic data that had good performance in an independent dataset. Estimation models were used to assess association with glucose homeostasis and adiposity highlighting known and novel associations and demonstrating utility. Future work will expand genetic coverage to include rare variants and phenotypic associations to further characterize metabolic dysregulation.

Disclosure
N.Allred: None. L.J.Raffel: None. T.A.Buchanan: None. R.M.Watanabe: None. J.I.Rotter: None. L.E.Wagenknecht: None. C.D.Langefeld: None. H.K.Im: None. H.C.Ainsworth: None. X.Guo: None. A.W.Mackay: None. F.Nyasimi: None. O.Melia: None. Y.Liang: None. D.W.Bowden: None. K.Taylor: None.

Funding
R01DK118062
1408-P: Acute Aerobic Exercise Unveils Serum Metabolomics Markers That Distinguish Overweight and Healthy Weight Individuals
Authors: NELSON ALISA B. , CHOW LISA S. , HUGHEY CURTIS C. , MYERS CHAD , HAN XIANLIN , CRAWFORD PETER A. , PUCHALSKA PATRYCJA 
Published: May 2022

Exercise confers metabolic benefits to both normal weight and overweight populations. Responses of the metabolome to acute aerobic exercise may predict cardiovascular fitness and longer-term outcomes, including the development of diabetes and its complications. We applied an LC-MS based untargeted metabolomics platform to evaluate the effect of acute exercise on the serum metabolome of overweight trained (OWT, n = 11, HOMA-IR 1.6 ± 0.1) and normal weight trained (NWT, n = 14, HOMA-IR, 0.9 ± 0.2, p &lt; 0.01) runners. Trained individuals were studied to limit the effects of a deconditioned acute stress response. While NWT and OWT metabolic profiles shared increased circulating acylcarnitines and free fatty acids (FFAs) with exercise, intermediates of adenine metabolism, inosine and hypoxanthine, were strongly correlated with body fat percentage (R = 0.67) and VO2max (R = 0.70) . Untargeted metabolomics-guided follow-up quantitative lipidomic analysis revealed that, as expected, baseline levels of fatty acid esters of hydroxy fatty acids (FAHFAs) were generally diminished in the OWT group. FAHFAs negatively correlated with visceral fat mass and HOMA-IR. Strikingly, a 4-fold decrease in FAHFAs was provoked by acute aerobic running in NWT, an effect that negatively correlated with circulating IL-6 (R ≤ -0.7) . These effects of exercise were not observed in the OWT group. Machine learning models based on a profile including FAHFAs, FFAs, and adenine intermediates predicted 53% of the variation in cardiovascular fitness. Taken together, these findings in relatively insulin resistant overweight human participants and healthy controls have implications for metabolic crosstalk between adipose tissue and skeletal muscle and support the notion that FAHFAs could modulate the inflammatory response, fuel utilization, and insulin resistance.

Disclosure
A.B.Nelson: None. L.S.Chow: Other Relationship; Dexcom, Inc. C.C.Hughey: None. C.Myers: None. X.Han: None. P.A.Crawford: Advisory Panel; Abbott Diabetes, Johnson & Johnson Global Services. P.Puchalska: None.

Funding
NIH (DK091538, AG069781, DK098203, TR000114, UL1TR002494)
141-OR: Associations between Type 2 Diabetes Partitioned/Process-Specific Polygenic Scores and Metabolic Traits
Authors: WEDEKIND LAUREN E. , HSUEH WEN-CHI , KOBES SAYUKO , BAIER LESLIE , BOGARDUS, III CLIFTON , KNOWLER WILLIAM C. , MAHAJAN ANUBHA , MCCARTHY MARK , HANSON ROBERT L. 
Published: May 2022

Polygenic scores (PS) for type 2 diabetes (T2D) associate strongly with disease status. Since T2D is heterogenous, using “partitioned” PS (pPS) that capture distinct etiological processes may improve clinical utility. A previous study in Europeans identified 6 pPS from genetic clusters (GCs) based on association patterns across traits, among 3T2D-associated variants: adiposity (GC1) , lipids (GC2) , insulin action (GC3) , beta cell function (GC4, GC5) , and mixed features (GC6) . Few data exist on how pPS associate with T2D and subphenotypes in non-European populations.
The current analysis reconstructed these pPS using genotypes for 245 of the 3variants captured in a genome-wide association study in an Indigenous study population from the Southwest US. pPS associations were analyzed with T2D (N=7659) , % body fat (PFAT, non-diabetic only, n=557) , insulin action from hyperinsulinemic-euglycemic “clamp” (logM, non-diabetic only, n=557) , and acute insulin response from an IVGTT (lgAIR, normal glucose tolerance only, n=404) . Results (table) show that T2D pPS strongly associate with the subphenotype corresponding to the putative etiologic mechanism.
These results demonstrate transferability of the phenotypic classifications of the T2D pPS and suggest that genetic influences on adiposity, insulin action, and insulin secretion contribute to development of T2D in this population.

Disclosure
L.E.Wedekind: None. W.Hsueh: None. S.Kobes: None. L.Baier: None. C.Bogardus: None. W.C.Knowler: None. A.Mahajan: Employee; Genentech, Inc. M.Mccarthy: Employee; Genentech, Inc. R.L.Hanson: None.
1414-P: Dapagliflozin Protects Human Cardiac Progenitor Cells from Deleterious Effects of the Secretome from Visceral Adipose Cells of Obese Subjects
Authors: PALMA GIUSEPPE , CACCIOPPOLI CRISTINA , DORIA ROSSELLA , GENCHI VALENTINA ANNAMARIA , SANTARPINO GIUSEPPE , CIGNARELLI ANGELO , NATALICCHIO ANNALISA , LAVIOLA LUIGI , PEZZOLLA ANGELA , GIORGINO FRANCESCO , PERRINI SEBASTIO 
Published: May 2022

Dysfunction of visceral and epicardial adipose tissue may alter heart performance and promote adverse cardiovascular outcomes in obesity and diabetes. We assessed whether the secretome from abdominal visceral (AV) and epicardial (E) adipose stem cells (ASC) and from AV mature adipocytes might affect the viability of human cardiac progenitor cells (hCPC) in human obesity, and the effects of dapagliflozin (DAPA) , a selective SGLT-2 inhibitor. ASC and mature adipocytes were isolated from AV and E adipose tissue biopsies of obese (Ob) and non-obese subjects, respectively. hCPC were isolated from right auricle biopsies of non-Ob, non-diabetic donors. hCPC were pretreated with uM DAPA for 24 h or left untreated, and then exposed to the conditioned media (CM) of AV-ASC, E-ASC, and AV mature adipocytes. The CM of AV-ASC, E-ASC, and AV mature adipocytes induced apoptosis, assessed by ELISA for cytoplasmic oligonucleosomes, in hCPC after 24 h (p&lt;0.05) . Exposure of hCPC to the CM of AV-ASC, E-ASC, and AV mature adipocytes for 24 h also resulted in impaired organization of the hCPC actin filaments, assessed by indirect immunofluorescence (p&lt;0.05) . In addition, the CM of AV-ASC, E-ASC, and AV mature adipocytes induced c-Jun phosphorylation, a measure of JNK activation, after 4 h and 8 h (p&lt;0.05) . Importantly, these effects were not observed when the hCPC were exposed to the CM of AV-ASC, E-ASC, and AV mature adipocytes from non-Ob subjects. Pretreatment of hCPC with DAPA resulted in reduced apoptosis and less impairment of actin filaments following exposure to the CM of AV-ASC, E-ASC, and AV mature adipocytes (p&lt;0.05) , as well as in reduced c-Jun phosphorylation (p&lt;0.05) .
In conclusion, in human obesity, the secretome of both AV and E ASC and mature adipocytes induces stress kinase activation in hCPC and impairs their viability and functionality, and these effects can be counteracted by SGLT-2 inhibitors directly acting on the hCPC.

Disclosure
G.Palma: None. F.Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Lilly Diabetes, Sanofi, Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. S.Perrini: None. C.Caccioppoli: None. R.Doria: None. V.Genchi: None. G.Santarpino: None. A.Cignarelli: None. A.Natalicchio: Consultant; Novo Nordisk, Other Relationship; AstraZeneca, Lilly Diabetes, Sanofi. L.Laviola: Advisory Panel; Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Speaker's Bureau; A. Menarini Diagnostics, Abbott Diabetes, Medtronic, Terumo Corporation. A.Pezzolla: None.
1418-P: Effect of Eight-Hour Time-Restricted Eating vs. Daily Calorie Restriction on Cardiovascular Disease Risk Factors in Adults with Obesity
Authors: LIN SHUHAO , CIENFUEGOS SOFIA , GABEL KELSEY , EZPELETA MARK , VARADY KRISTA , CHAKOS KAITLIN , MCSTAY MARA , MULAS ANDREA 
Published: May 2022

Background: Time restricted eating (TRE) is a form of intermittent fasting that involves confining the period of eating to 8-h and fasting with zero-calorie beverages for 16-h. Short-term studies (2-3 month) suggest that 8-h TRE produces moderate weight loss and improves blood pressure and plasma lipids. What remains unknown is whether these improvements by TRE would become more pronounced over longer periods of time (6-months) , and whether these benefits are comparable to that of daily calorie restriction (CR) .
Objective: Accordingly, this study compared the effects of 8-h TRE versus CR and a no-intervention control group on body weight and cardiovascular disease risk factors in adults with obesity over 6-months.
Design: Adults with obesity (n = 63) were randomized to 1 of 3 interventions for 6-months: 8-h TRE (ad libitum eating between 12:00 to 8:00 pm, fasting between 8:00 to 12:00 pm) ; CR (25% energy restriction daily) ; or control (ad libitum food intake with no meal timing restrictions) .
Results: By month 6, body weight decreased (P = 0.02) by CR (-4.9 ± 1.4%) but not TRE (-3.4 ± 0.7%) , versus controls (-0.7 ± 1.1%) . Diastolic blood pressure was significantly (P = 0.04) reduced by TRE (-4.0 ± 1.4 mm Hg) , but not CR (-0.1 ± 1.7 mm Hg) , versus controls (1.6 ± 1.5 mm Hg) . Changes in systolic blood pressure, fat mass, visceral fat mass, lean mass, LDL cholesterol, HDL cholesterol, triglycerides, and heart rate did not differ between groups at month 6. Adherence to 8-h TRE remained high throughout the trial, i.e. subjects adhered to the 8-h eating window on 6 ± 0.1 days/week.
Conclusions: These preliminary findings suggest CR may produce greater weight loss compared to TRE over 6-months. While TRE did not produce significant weight loss, the diet did lower diastolic blood pressure. This would suggest that this intermittent fasting regimen may produce improvements in cardiovascular parameters in the absence of body weight reductions.

Disclosure
S. Lin: None. S. Cienfuegos: None. K. Gabel: None. K. Varady: None. A. Mulas: None.

Funding
NIH-NIDDK (1R01DK128180 - 01A1)
1422-P: The Potential of Semaglutide Once-Weekly in Patients without Type 2 Diabetes with Weight Regain or Insufficient Weight Loss after Bariatric Surgery
Authors: LAUTENBACH ANNE , WERNECKE MARIE , STOLL FABIAN D. , MEYHÖFER SEBASTIAN M. , MEYHÖFER SVENJA , ABEREL JENS 
Published: May 2022

Background: About 20-25% of patients experience weight regain (WR) or insufficient weight loss (IWL) after bariatric surgery (BS) associated with relapse of obesity-related comorbidities. Therefore, we aimed to assess the effectiveness of Semaglutide once-weekly as synthetic analogue of the hormone GLP-1 in patients without type 2 diabetes (T2D) with WR or IWL after BS.
Methods: Post-bariatric surgery patients without T2D with WR or IWL (n=48) were included in the analysis. The primary endpoint was weight loss 3 and 6 months after initiation of add-on treatment with Semaglutide. Secondary endpoints included change in BMI, HbA1c, lipid profile, hs-CRP, pancreatic lipase and liver enzymes.
Results: Patients initiated Semaglutide approximately 64.4 months [interquartile range (IQR) 27-97 months] after BS. Mean postoperative weight regain after reaching weight nadir following surgery to initiation of Semaglutide was 11.5kg and 12.9%, respectively. Over 3.2 (IQR 3.0-3.5 months) (n=36) and 5.8 months (IQR 5.8-6.4 months) (n=14) taking Semaglutide, mean total weight loss was 6.2% (IQR 3.5-8.6%) and 9.8% (IQR 5.8-13.3%) , respectively. Categorical weight loss data indicate that 64% of patients reached more than 5% weight loss, 17% more than 10% weight loss and 6% more than 15% weight loss at visit 2. With regard to type of surgery, there were no significant differences in drug-induced total weight loss (p=0.8) .
Discussion and Conclusion: Weight loss options for excess weight management in post-bariatric surgery patients are limited. Our results suggest that post-bariatric patients with WR or IWL may benefit from add-on treatment with Semaglutide once-weekly. Our results might be the basis for a prospective randomized-controlled trial to evaluate larger cohorts of patients to determine if Semaglutide once-weekly may close the gap between lifestyle intervention and revision surgery to treat weight recidivism or IWL after BS.

Disclosure
A.Lautenbach: Advisory Panel; Novo Nordisk, Speaker's Bureau; Boehringer Ingelheim International GmbH, Novo Nordisk. M.Wernecke: None. F.D.Stoll: None. S.M.Meyhöfer: None. S.Meyhöfer: None. J.Aberel: Advisory Panel; Novo Nordisk, Speaker's Bureau; Novo Nordisk.
1436-P: Metformin Increases Skeletal Muscle Mitochondrial Function and Acute Phase Insulin Sensitivity in Obstructive Sleep Apnea
Authors: ZUNICA ELIZABETH R.M. , HEINTZ ELIZABETH C. , HEBERT REBEKAH C. , TANKSLEY MAKAYLA C. , MADER EDWARD C. , KIRWAN JOHN P. , AXELROD CHRISTOPHER L. , SINGH PRACHI 
Published: May 2022

Introduction: Obstructive sleep apnea (OSA) is a prevalent sleep disorder with high type 2 diabetes (T2D) risk. OSA therapy includes positive airway pressure (PAP) treatment, which resolves breathing events but modestly improves metabolic health. Metformin is recommended for T2D prevention but is not advocated in patients with OSA. Our pilot study evaluated the effects of metformin on glucose metabolism and mitochondrial function in OSA patients.
Methods: Sixteen adults (50.5±1.6 years, BMI: 36.4±0.8 kg/m2) with OSA (apnea hypopnea index: 53.2±21.1 events/hour) were randomized to receive placebo (n=8) or metformin (n=8) treatment along with PAP for 3 months in a double-blind parallel-group design. Whole body and adipose tissue-specific insulin sensitivity (IS) was determined by oral glucose tolerance test (OGTT) . Skeletal muscle mitochondrial function was determined by high-resolution respirometry using biopsies obtained at baseline and after 3 months of treatment.
Results: Change in whole body IS (Matsuda index) was not different in metformin or placebo treated groups (p=0.46) . However, improved acute phase responses during OGTT - glucose uptake (p=0.02) , insulin release (p=0.03) , and suppressed lipolysis (p=0.03) were observed with metformin treatment relative to control. Increased skeletal muscle mitochondrial function was evident with metformin relative to control. Specifically, metformin increased complex I phosphorylation and complex IV electron transfer capacity.
Conclusion: Metformin treatment improves acute phase IS and insulin suppression of lipolysis in OSA patients. Strikingly, metformin improved skeletal muscle mitochondrial function independent of changes in second phase glucose disposal and BMI, indicating improved tissue metabolic function. These data suggest that in patients with OSA, improvement in tissue level metabolic function may precede changes in whole-body IS and metformin may improve metabolism.

Disclosure
E.R.M.Zunica: None. E.C.Heintz: None. R.C.Hebert: None. M.C.Tanksley: None. E.C.Mader: None. J.P.Kirwan: None. C.L.Axelrod: None. P.Singh: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (DK123456789) ;National Institute of General Medical Sciences (GM123456789)