bluuebunny/crossref_metadata_2025_split huggingface dataset:
1384-P: Serum Fibroblast Growth Factor 1 Levels and Its Association with ß-Cell Function and Insulin Sensitivity in Adults with Glucose Intolerance
Authors: KIM JI YOON , CHOI JIMI , KIM SIN GON , KIM NAM HOON 
Published: May 2022

Objectives: Beneficial role of Fibroblast growth factor 1 (FGF1) in the regulation of glucose metabolism and adipose tissue remodeling was suggested in rodents. We investigated an association between serum FGF1 levels and metabolic parameters in adults with glucose intolerance.
Research Designs and Methods: Serum FGF1 levels were examined using enzyme-linked immunosorbent assay in 92 individuals with glucose intolerance. Associations between serum FGF1 levels and metabolic parameters including body mass index (BMI) , waist circumference (WC) , glycated hemoglobin (HbA1c) and 75g oral glucose tolerance test-derived parameters including insulinogenic index (IGI) , Matsuda insulin sensitivity index (ISI) , and disposition index (DI) were examined.
Results: Mean age was 49.8 years, and mean BMI was 30.7 kg/m2 of 92 participants. Among them, 87% had type 2 diabetes. There was no significant association between serum FGF1 level and BMI or WC by using censored regression analysis. On the other hand, serum FGF1 level was higher in patients with higher HbA1c (β=0.369, p=0.014) . This association was significant after adjusting for age, sex, and BMI (p=0.005) . Notably, serum FGF1 level was negatively associated with IGI and DI (β=−0.462, p=0.017; β=−0.469, p=0.014, respectively) , but not with ISI. Mean FGF1 concentrations were significantly lower with higher quartiles of IGI and DI (p for trend=0.035 and 0.015 for IGI and DI, respectively) .
Conclusion: Serum concentration of FGF1 was significantly higher in individuals with higher blood glucose and lower insulin secretion, which suggests a possible role of FGF1 in the glucose metabolism, especially in the regulation of β cell function in humans.

Disclosure
J.Kim: None. J.Choi: None. S.Kim: None. N.Kim: None.
1387-P: Impacts of Androgen-Deprivation Therapy on Glucose Metabolism
Authors: GRITSKEVICH ELENA Y. , GRITSKEVICH ALEXANDER , DEMIDOVA TATYANA 
Published: May 2022

Study Objective: to assess the impacts of androgen deprivation therapy (ADT) in prostate cancer (PCa) management on glucose metabolism Study Design: follow-up study
Materials and Methods: A total of 99 consecutive patients with PCa who received ADT followed-up at Pletnev and 62th Moscow Hospitals. The mean age was 69±8,64 y.o. Fasting plasma glucose (FPG) , HbA1c, body mass index (BMI) , waist circumference (WC) , were measured at baseline, after 3, 6 and 12 months ADT with gonadotropin releasing hormone agonists (GnRH agonists) . Ambulatory glycemic profiles (AGP) were obtained in patients with elevated glycemia who received ADT with GnRH agonists for at least 6 months by Flash glucose monitoring systems. Glucose variability indices (AUC, CONGA, JINDEX) were calculated.
Study Results: During ADT there were an increase in FPG and HbA1c over 12 months of ADT regardless of baseline age, BMI, WC, with a maximum increase during the first 3 months of treatment, and progressively after 6 months and 12 months. FPG (mmol/l) initially, 3, 6 and 12 months, were respectively 5,18±0,91; 5,67±0,93; 5,77±0,96; 5,90±1,12 (for all differences p ≤ 0.001) . HbA1c (%) 5,36+0,66; 5,66±0,83; 5,77±0,82; 5,89±0,83 (for all differences p ≤ 0.001) . The proportion of individuals with prediabetes were increased, according to ADA criteria (5,6-6.9 mmol/l) after 3 months 36%, after 6 months 41%, and after 12 months 66%. The impact on glucose metabolism ware in also AGP changes, manifested by an increase in the total daily glycemic load (mean AUC 172,49 (p≤0.001) , glycemic variability (mean CONGA 6,817 (p≤0.001) , and an increased in postprandial glycemia (JINDEX 22,945 (p≤0.001) . Conclusion: ADT with GnRH agonists did worsen metabolic parameters: early, progressive, clinically significant impair of glucose metabolism regardless of baseline age, BMI, WC. AGP deteriorations were increased of glucose variability, total glycemic load gained and peak glycemic values rose.

Disclosure
E.Y.Gritskevich: None. A.Gritskevich: None. T.Demidova: None.
1397-P: A Cocoa Butter–Based Ketogenic Diet Fails to Improve Glucose Homeostasis and Promote Weight Loss in Obese Mice
Authors: GREENWELL AMANDA A. , SAED CHRISTINA T. , DAKHILI SEYED AMIRHOSSEIN TABATABAEI , HO KIM , GOPAL KESHAV , CHAN JORDAN S.F. , KACZMAR OKSANA , DYER SCOTT A. , EATON FARAH , LOPASCHUK GARY , BATRAN RAMI A. , USSHER JOHN R. 
Published: May 2022

Background: High-fat and very low-carbohydrate based ketogenic diets have gained considerable popularity as a non-pharmacological strategy for treating obesity due to their potential to enhance weight loss and improve glucose homeostasis. However, the effectiveness of a ketogenic diet towards metabolic health is equivocal.
Methods: Male and female mice were fed a 60% cocoa butter fat-based high-fat diet for 16-weeks to induce obesity, following which mice were transitioned to either an 85% cocoa butter fat-based ketogenic diet (KD) , a 10% cocoa butter fat-based low-fat diet (LFD) , or maintained on a high-fat diet for an additional 8-weeks. All experimental diets were matched for sucrose and protein content, and contained an identical micronutrient profile, with complex carbohydrates being the primary carbohydrate source in the LFD.
Results: The transition to a KD was ineffective at inducing significant body fat loss, improving glucose homeostasis, or enhancing insulin sensitivity in obese male and female mice. Alternatively, obese male and female mice transitioned to a LFD exhibited a marked decrease in body weight, which was primarily attributed to a loss of adiposity, and an improved glucose tolerance during an intraperitoneal glucose tolerance test. Despite the improvements in glucose tolerance, insulin sensitivity remained impaired in obese male mice transitioned to a LFD, whereas it was improved in obese female mice. These salutary actions attributed to a transition to a LFD resulting in beneficial body composition changes and improved glucose tolerance, may in part be due to the trend to mild reductions and increases in food intake and energy expenditure, respectively.
Conclusions: Our findings suggest that careful consideration should be taken when consuming a KD as a non-pharmacological strategy for treating obesity, whereas consumption of a diet low in saturated fat and rich in complex carbohydrates imparts numerous beneficial actions.

Disclosure
A.A.Greenwell: None. G.Lopaschuk: None. R.A.Batran: None. J.R.Ussher: None. C.T.Saed: None. S.Tabatabaei dakhili: None. K.Ho: None. K.Gopal: None. J.S.F.Chan: None. O.Kaczmar: None. S.A.Dyer: None. F.Eaton: None.
1401-P: Long-Term Metabolic Effects of Noncaloric Sweeteners
Authors: RATHAUS MORAN , AZEM LOZIANA , LIVNE RINAT , RON SOPHIE , RON IDIT , TIROSH AMIR 
Published: May 2022

Accumulating evidence link sugar-containing foods and beverages to adverse health outcomes. Non-Caloric Sweeteners (NCSs) are an alternative sugar source that lead to reduction in calories, and may mitigate body weight gain and hyperglycemia, especially in patients with diabetes. Yet, contradicting studies suggest that NCSs may mediate metabolic derangements. Here, we aim to assess long-term metabolic effects of chronic consumption of NCSs. To this aim, mice consuming either regular diet or high fat diet (HFD) were supplemented with NCSs in their drinking water at concentrations consumed by humans. Under HFD, mice consuming reb M or sucralose had significant lower body weight compared to fructose. In comparison to fructose consumption, a significantly lower blood glucose levels were observed in mice under chow diet drinking either sucralose or reb M. Under HFD, a significant decrease in blood glucose levels was found only in mice consuming ace-k. On HFD, all NCSs other than saccharin, resulted in significantly improved insulin sensitivity compared to fructose. A significant decrease in fasting glucose was found only in sucralose and reb M groups under these conditions. A trend towards higher levels of plasma insulin was observed in mice under HFD drinking either fructose or saccharin. None of the interventions caused a decrease in fluid consumption as compared to water, nor were significant differences in daily food intake, daily caloric intake or energy expenditure. RER displayed a normal nocturnal pattern in all groups and no significant change in voluntary physical activity was observed. As compared to fructose, NCS consumption decreased markers of NAFLD in obesity.
In summary, our results suggest that chronic consumption of NCS do not result in any observed metabolic alternations, and may attenuate some of the metabolic derangements associated with fructose and high fat-based diet.

Disclosure
M.Rathaus: None. L.Azem: None. R.Livne: None. S.Ron: None. I.Ron: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company.
1403-P: DA-1726, a Balanced GLP1R/GCGR Dual Agonist, Effectively Controls Both Body Weight and Blood Glucose
Authors: KIM TAE-HYOUNG , JUNG IL-HUN , KIM KYUMIN , LEE BORAM , KIM MI-KYUNG , CHAE YUNA 
Published: May 2022

DA-1726 is a novel balanced long-acting oxyntomodulin (OXM) analogue, which is under preclinical development for the treatment of obesity. In this study, the pharmacological effects of DA-1726 were evaluated. DA-1726 exhibited a balanced dual action on GLP-1 receptor (GLP1R) and glucagon receptor (GCGR) in CHO-K1 cells transiently overexpressing each human receptor. In high-fat diet-induced obese mice, 3-week treatment of DA-1726 showed more body weight loss (BWL) and increasing energy expenditure than a pair-fed group. This means that the BWL effect of DA-1726 is due to decreased food intake and increased energy metabolism through GLP1R and GCGR action. In comparison with a GLP1R agonist, DA-1726 showed superior BWL, despite eating more food compared to semaglutide (SEMA) after 4-week treatment in obese mice. At the end of the study, DA-1726 significantly increased the expression of thermogenic genes (Ucp-1 and Ppargc1a) in white adipose tissue (WAT) , and increased WAT browning was histologically confirmed. In addition, DA-1726 inhibited adipocyte differentiation in vitro. Taken together, it suggests that the GCGR action of DA-1726 contributes to reduced adiposity by enhancing fat burning and inhibiting adipogenesis. OXM analogue biased to GCGR fails to control blood glucose despite GLP1R agonism. As a balanced analogue, DA-1726 effectively reduced postprandial glucose excursion in acute oral glucose tolerance test in normal mice. Notably, DA-1726 showed similar glycemic control and excellent BWL to SEMA in hyperglycemic and obese FATZO mice after 4-week treatment. Simultaneously, DA-1726 enhanced insulin sensitivity by significantly reducing fasting plasma insulin and glucose levels. Meanwhile, DA-1726 showed no hypoglycemia risk in overnight fasted normal mice unlike SEMA after a single injection, regardless of dose escalation. Our findings suggest that DA-1726 is a balanced GLP1R/GCGR dual agonist that effectively reduces body weight and blood glucose levels.

Disclosure
T.Kim: None. I.Jung: None. K.Kim: None. B.Lee: None. M.Kim: None. Y.Chae: None.
1407-P: Deletion of the Abi3 Immune Gene Locus in Mice Results in Obesity and Systemic Metabolic Disruption
Authors: SMITH DANIEL C. , KARAHAN HANDE , WIJERATNE H.R. SAGARA , AL AMIN MD MAMUN , MCCORD BRIANNE , MOON YOUNGHYE , KIM JUNGSU 
Published: May 2022

Obesity is a global epidemic that affects 13% of adults world-wide, and over 40% of adults in the United States. Further, obesity contributes substantially to global morbidity and mortality and acts as a major risk factor for type II diabetes, among many other diseases. Therefore, efforts to understand the pathobiology of obesity and generate novel methods of prevention are paramount.
Recent findings suggest the importance of immune cells in the progression and onset of obesity, prominently including microglia, the immune cells of the central nervous system (CNS) , and peripheral macrophages. To this end, our project proposes to explore the role of these immune cells in the etiology and progression of obesity.
Our laboratory found that deletion of the Abi3 gene locus, which is a gene primarily involved in the regulation of actin dynamics within immune cells, resulted in the induction of obesity in mice. Specifically, mice lacking Abi3 had increased body weight and body fat percentage compared to wild-type mice. Additionally, mice without Abi3 showed impaired glucose tolerance and insulin sensitivity, but no changes in acute energy expenditure or food intake. Further, through RNA-seq analysis, we observed that deletion of the Abi3 gene locus substantially altered the expression of immune genes in both the CNS and peripheral tissue.
Through this study, we aimed to metabolically characterize mice with and without the Abi3 gene locus in order to discover the mechanisms by which this deletion alters central and peripheral immune cells to facilitate the onset of obesity. This and future studies will enable us to understand how perturbations to microglia and peripheral immune cells alter metabolic regulation to mediate susceptibility to metabolic disease.

Disclosure
D.C.Smith: None. H.Karahan: None. H.Wijeratne: None. M.Al amin: None. B.Mccord: None. Y.Moon: None. J.Kim: None.

Funding
Indiana University Diabetes and Obesity Research Training Program, DK064466
141-LB: Targeting Workflow Inefficienes to Improve Continuous Glucose Monitor (CGM) Prescription Rates in Type 1 Diabetes (T1D)
Authors: MAHALI LAKSHMI PRIYANKA , XU SHIMING , AGARWAL SHIVANI , MATHIAS PRIYANKA M. 
Published: May 2022

Background: Racial/ethnic disparities exist in CGM prescription rates for people with T1D, and are associated with disparities in glycemic outcomes. We identified healthcare system inefficiencies that may be contributing to inequity and targeted interventions to improve prescription workflow.
Methods: At our large urban diabetes center, we used quality improvement (QI) methodology to implement and test changes in our CGM prescription workflow and examined effect on CGM prescription rates. Since October 2021, we collaborated with a specialty pharmacy to simplify CGM e-prescription for providers to improve device access for patients. We conducted PDSA cycles to add new office workflows for insurance prior authorization, standardize documentation, train support staff, and created change packages for spread across our diabetes practice sites. We examined effects by extracting monthly aggregate CGM prescription data from the electronic medical record and compared CGM prescription rates before and after initiation of the workflow.
Results: We included 717 people with T1D [mean age 38 years; 42.3% Hispanic (n=303) , 29% non-Hispanic Black (n=208) , 14.5% non-Hispanic White (n=104) , 14.3% other (n=102) ; 69% publicly insured]. In the five months since the introduction of the workflow, CGM prescriptions increased by 9.0% (49.4% to 58.4%) . CGM prescription rates in Hispanic and non-Hispanic Black patients were equivalent to White.
Conclusion: Simple, trackable, and iterative changes to CGM prescription workflows are feasible and can effectively increase CGM prescription rates in a short period of time. Further changes to clinic processes using QI methodology may result in meaningful improvements in outcomes.

Disclosure
L. Mahali: None. S. Xu: None. S. Agarwal: Advisory Panel; Medtronic, Consultant; Beta Bionics, Inc. P. M. Mathias: None.
142-OR: Global Extended Polygenic Score Predicts Incident Type 2 Diabetes in Women with History of Gestational Diabetes
Authors: CHOI JAEWON , LEE HYUNSUK , HAN MINSEOK , CHOI DAEHO , JANG HAK CHUL , PARK KYONG SOO , KWAK SOO HEON 
Published: May 2022

Around 30-50% of women with history of gestational diabetes (GDM) develop type 2 diabetes (T2D) within years after parturition. However, the role of polygenetic score on prediction of T2D in these women is still unclear. We aimed to investigate the utility of global extended polygenic scores (gePS) in predicting incident T2D using GDM cohorts from 1) UK Biobank (N=941) , 2) Seoul National University Hospital (SNUH, N=357) , and 3) Korean Genome and Epidemiology Study (KoGES, N=379) . We calculated gePS for T2D using Bayesian regression and continuous shrinkage priors, with summary statistics from representative genome-wide association studies in Europeans and East Asians. We performed time-to-event analysis for incident T2D with gePS and assessed improvement of C-statistic when gePS was added to clinical risk factors. In addition, risk of T2D was estimated for those who were in the top percentile of gePS compared to the remainders. The incidence of T2D was 19.8% in UK Biobank, 28.3% in SNUH, and 23.5% in KoGES cohort with median follow-up duration of 28, 4, and 28 years, respectively. The normalized mean PRS for those who developed T2D was higher in each cohort: 0.25±1.vs. -0.06±0.99 in UK Biobank, 0.22±1.vs. -0.09±0.97 in SNUH, and 0.52±0.96 vs. -0.16±0.96 in KoGES (all P&lt;0.01) . When meta-analyzed, adding gePS to clinical risk factors improved the C statistic from 0.715 (95% confidence interval [CI] 0.658-0.766) to 0.743 (95% CI 0.698-0.784) . The standardized gePS was associated with incident T2D in women with history of GDM when the results of the three cohorts were meta-analyzed: hazard ratio 1.68 (95% CI 1.52-1.86, P&lt;0.001) . Furthermore, those who were in the top percentile had 3.52-fold increased risk of T2D: (95% CI 2.68-4.62, P&lt;0.001) . To sum up, genetic information in women with previous GDM pregnancy could be used to identify those who are at high risk of future development of T2D and provide the opportunity for tailored prevention.

Disclosure
J.Choi: None. H.Lee: None. M.Han: None. D.Choi: None. H.Jang: None. K.Park: None. S.Kwak: None.
1426-P: Increased Insulin Secretion and Glucose Effectiveness Result in Improved Glucose Tolerance in Obese Subjects Two Months after Gastric Bypass and Sleeve
Authors: VISENTIN ROBERTO , BRODERSEN KATRINE , RICHELSEN BJØRN , MOLLER NIELS , MAN CHIARA DALLA , NIELSEN MICHAEL F. 
Published: May 2022

The early effects of bariatric surgery on insulin secretion and action in obese subjects with type 2 diabetes (T2D) remains poorly investigated. Here we assessed the mechanisms resulting in improved glucose intolerance using the oral minimal model approach. An oral glucose tolerance test was performed before and 2 months after bariatric surgery in 16 obese T2D subjects (9 bypass, 7 gastric sleeve) and in 8 healthy control subjects. For each visit, body mass index (BMI) was measured, and the oral glucose and the insulin and C-peptide minimal models were used to estimate insulin sensitivity (SI) , glucose effectiveness (GE) , total β-cell responsiveness (Φtot) , disposition index (DI) and total hepatic insulin extraction (HE) . Bariatric surgery resulted in a significant reduction (similar between bypass and sleeve groups) in BMI by 14% (from 42±5 to 36±4 kg/m2) . Glucose tolerance increased comparably after bypass and sleeve, but remained impaired compared to the control group (Figure 1) : GE, Φtot, DI and HE were equally increased following bariatric surgery, whereas insulin action (SI) remained unaltered in the two groups. These results suggest that improved glucose tolerance in obese T2D subjects 2 months after bariatric surgery is attributable mainly to an increase in insulin secretion and glucose effectiveness rather than an improvement in insulin action.

Disclosure
R. Visentin: Research Support; Becton, Dickinson and Company, MannKind Corporation, Sanofi-Aventis Deutschland GmbH. K. Brodersen: None. N. Moller: None. C. Dalla Man: Research Support; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. M.F. Nielsen: None.

Funding
Novo Nordisk Foundation
1442-P: Association of Elevated Serum FABP1 with Hyperuricemia in Patients with Obesity and the Alteration after Sleeve Gastrectomy
Authors: QU SHEN , HUI YOU 
Published: May 2022

Aims: FABP1’s relationship with obesity-related hyperuricemia remains unknown. We aimed to evaluate FABP1-level changes in patients with obesity-related hyperuricemia and changes after laparoscopic sleeve gastrectomy (LSG) .
Materials and Methods: Participants were categorized according to uric acid (UA) level: normal UA group (NUA, men≤420 μmol/L, women≤360 μmol/L) and high UA group (HUA, men&gt;420 μmol/L, women&gt;360 μmol/L) . The cross-sectional analysis included 123 non-obese individuals (NUA, n=90; HUA, n =33) and 76 patients with obesity (NUA, n =31; HUA, n =45) who underwent LSG. FABP1 levels were measured at baseline and 3, 6, and 12 months post-LSG.
Results: In non-obese individuals, FABP1 did not differ statistically between the NUA and HUA groups (15.52±15.62 ng/mL vs. 18.44±11.47 ng/mL, P=0.330) . However, in patients with obesity, FABP1 was positively correlated with UA and higher in the HUA than in the NUA group (32.47±22.35 ng/mL vs. 22.84±14.54 ng/mL, P&lt;0.05) . Multiple linear regression found a positive correlation between FABP1 and UA (R2=0.101, β=0.317, 95% CI=0.020-0.110, P&lt;0.01) , and binomial logistic regression found that FABP1 could predict HUA in patients with obesity (OR=1.031, 95% CI=1.002-1.061, P&lt;0.05) . UA and FABP1 levels, whether in the NUA or HUA group, decreased at 3, 6, and 12 months postoperatively. But FABP1 decreased faster in the HUA than NUA group, and there was a statistical difference at 12 months.
Conclusions: FABP1 increased in obesity-related hyperuricemia in contrast to only obesity. And FABP1 decreased faster in the HUA than in the NUA group among obesity postoperatively. Key words: FABP1, Obesity, Hyperuricemia, Laparoscopic sleeve gastrectomy

Disclosure
S.Qu: n/a. Y.Hui: None.

Funding
NSFC 81700752，2021SYPDRC059
1446-P: Sex-Specific Effects of Nr4a1 in the Pancreatic Beta Cell
Authors: TESSEM JEFFERY S. , HERRING JACOB 
Published: May 2022

A central aspect of type 2 diabetes disease progression is impaired functional β-cell mass. The hyperglycemic and hyperlipidemic environment present in type 2 diabetes corresponds with impaired beta cell function. The orphan nuclear receptor Nr4a1 is critical for fuel utilization in various tissues, however little is known regarding its function in the β-cell. Nr4a1 expression is decreased in the β-cell of rodent models of type 2 diabetes, as well as in primary human islets from type 2 diabetics. Here we demonstrate sex specific effects of β-cell specific Nr4a1 deletion under high fat chow feeding. While female and male βNr4a1-/- mice were no different than wild type controls when fed a standard chow diet, a clear sex dependent difference is observed when fed a high fat diet. High fat fed male βNr4a1-/- have improved fasting and non-fasting blood glucose levels, high fat fed female βNr4a1-/- mice have impaired glucose tolerance as early as two months after beginning high fat feeding. Furthermore, female βNr4a1-/- mice have decreased β-cell mass and improved insulin tolerance. Given the sex specific differences in glucose tolerance, we demonstrated that female mice fed a high fat diet have increased circulating estrogen, and that treatment of INS-1 832/13 cells and primary mouse islets with estradiol resulted in increased expression of Nr4a1 and not the other two Nr4a family members. Our data suggest that Nr4a1 is critical for estrogen mediated maintenance of beta cell function and mass under obesogenic conditions, and that loss of Nr4a1 under conditions of obesity and overnutrition in females results in impaired beta cell compensation and function.

Disclosure
J.S.Tessem: None. J.Herring: None.

Funding
National Institutes of Health (1R15DK124835-01A1)