bluuebunny/crossref_metadata_2025_split huggingface dataset:
189-LB: Household Food Insecurity and Associations with Glycemic Control and Acute Diabetes-Related Complications in Youth and Young Adults with Type 1 Diabetes: The SEARCH for Diabetes in Youth Study
Authors: MALIK FAISAL , LIESE ANGELA D. , ELLYSON ALICE M. , REID LAUREN A. , SAUDER KATHERINE A. , FRONGILLO EDWARD A. , PIHOKER CATHERINE , DABELEA DANA , LAWRENCE JEAN M. , JENSEN ELIZABETH T. , SAYDAH SHARON , MARCOVINA SANTICA M. , BOWLBY DEBORAH , MENDOZA JASON A. 
Published: June 2020

Objectives: To examine, among youth and young adults (YYAs) with type 1 diabetes (T1D), the independent association of household food insecurity (HFI) with: 1) glycemic control and 2) episodes of diabetic ketoacidosis (DKA) and severe hypoglycemia.
Methods: This cross-sectional study included SEARCH for Diabetes in Youth participants with T1D examined between 2016-2019. HFI was assessed using the U.S. Household Food Security Survey Module. HbA1c was measured from blood drawn at a research visit; episodes of DKA and severe hypoglycemia were collected by survey. Linear and logistic regression models adjusted for age, sex, race, income, health insurance, diabetes duration, and SEARCH site.
Results: Of 1834 participants (mean age 20.8±5.0 years, 69.9% non-Hispanic white, diabetes duration 11.1±3.2 years), HbA1c was collected for 1029 individuals (mean HbA1c 9.2%±2.0%). The prevalence of HFI was 16.4%. In this sample, 18.7% and 9.9% reported an episode of DKA or severe hypoglycemia in the past 12 months, respectively. Compared to participants who were food secure, HFI was associated with a 0.43% [CI: 0.02%-0.68%] higher HbA1c. In two separate adjusted models, those with HFI had 1.86 [CI: 1.03, 2.34] times the odds of an episode of DKA and 1.64 [CI: 1.03, 2.34] times the odds of an episode of severe hypoglycemia as those without HFI.
Conclusions: HFI is independently associated with poor glycemic control and increased odds of diabetes-related complications in YYAs with T1D. Interventions to reduce HFI and studies to longitudinally examine its impact on glycemic control and complications are warranted.

Disclosure
F. Malik: None. A.D. Liese: None. A.M. Ellyson: None. L.A. Reid: None. K.A. Sauder: None. E.A. Frongillo: None. C. Pihoker: None. D. Dabelea: None. J.M. Lawrence: None. E.T. Jensen: None. S. Saydah: None. S.M. Marcovina: None. D. Bowlby: None. J.A. Mendoza: None.

Funding
Centers for Disease Control and Prevention (00097, DP-05-069, DP-10-001); National Institute of Diabetes and Digestive and Kidney Diseases (1UC4DK108173)
189-OR: Prepregnancy Plant-Based Diet and the Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study of 15,999 Women
Authors: CHEN ZHANGLING , QIAN FRANK , LIU GANG , LI MENGYING , VOORTMAN TRUDY , LEY SYLVIA H. , CHAVARRO JORGE E. , BHUPATHIRAJU SHILPA , SUN QI , HU FRANK , ZHANG CUILIN 
Published: June 2020

Objective: To identify novel modifiable factors that may help prevent gestational diabetes mellitus (GDM) by examining associations of plant-based diet indices with GDM risk.
Methods: We included 15,999 women (22,524 singleton pregnancies) in the Nurses’ Health Study II (1991-2001), who reported at least one singleton pregnancy between 1991 and 2001. Pre-pregnancy plant-based diets (i.e., overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI)) were assessed every 4 years using a food frequency questionnaire. Incident first time GDM was ascertained from a self-reported physician diagnosis of GDM, which was previously validated to have high concordance with medical records. We used log-binomial models with generalized estimating equations to estimate relative risks (RR) and 95% confidence intervals (CI) for quartiles of PDI, hPDI, and uPDI and GDM with adjustment for demographic, lifestyle, and other factors.
Results: We documented 891 GDM cases over the 10 years of follow-up. Both PDI and hPDI were significantly and inversely associated with GDM (PDI: adjusted RR for extreme quartiles (highest vs. lowest) 0.75, (95% CI: 0.62, 0.92), p trend = 0.01; hPDI: RR for extreme quartiles 0.76, (0.61, 0.94), p trend = 0.01). Further adjustment for pre-pregnancy BMI attenuated the associations (RR for extreme quartiles for PDI: 0.87 (0.71, 1.06); for hPDI: 0.81 (0.65, 1.00)). We estimated that pre-pregnancy BMI mediated 61.3% (95% CI: 21.7%, 90.1%) of the association between PDI and GDM, and 44.4% (18.1%, 74.3%) of the association between hPDI and GDM. uPDI was not significantly associated with GDM.
Conclusions: Our study suggests that pre-pregnancy adherence to overall and healthful plant-based diets may be associated with a lower risk of GDM. These associations were substantially mediated through pre-pregnancy BMI.

Disclosure
Z. Chen: None. F. Qian: None. G. Liu: None. M. Li: None. T. Voortman: None. S.H. Ley: None. J.E. Chavarro: None. S. Bhupathiraju: None. Q. Sun: None. F. Hu: None. C. Zhang: None.
1892-P: Meal- and Glucose-Induced Suppression of Ghrelin Release Is Mediated Primarily by Ghrelin Cell-Expressed Insulin Receptors
Authors: SHANKAR KRIPA , TAKEMI SHOTA , GUPTA DEEPALI , MANI BHARATH K. , OSBORNE-LAWRENCE SHERRI , METZGER NATHAN , BERGLUND ERIC , ZIGMAN JEFFREY M. 
Published: June 2020

Objective: The hormone ghrelin both regulates and is regulated by food intake and blood glucose. Yet, the mechanisms restricting ghrelin release after meals or upon glucose delivery have remained elusive. Here, we tested whether meal and glucose-associated rises in plasma insulin act via ghrelin cell-expressed insulin receptors to suppress ghrelin release.
Methods: We generated ghrelin cell-selective insulin receptor-knock out (GIRKO) mice by crossing ghrelin-Cre mice with floxed-insulin receptor mice. We examined ghrelin release using hyperinsulinemic-hypoglycemic clamps, glucose tolerance tests (GTTs), a fast-refeed protocol, and gastric mucosal cell primary cultures.
Results: During clamps, plasma ghrelin fell in WT control groups (by 85%) but not in GIRKO mice, leading to a 29% lower glucose infusion rate in GIRKO mice. During GTTs, plasma ghrelin was suppressed in controls (by 42%) but not in GIRKO mice. During the refeed phase of a fast-refeed protocol, plasma ghrelin fell in controls (by 49%) but not in GIRKO mice. Also, insulin suppressed ghrelin release in isolated ghrelin cells of controls (by 19%) but not of GIRKO mice.
Conclusions: These data suggest that insulin, acting via ghrelin cell-expressed insulin receptors, is a key mediator of ghrelin release in response to meals, glucose administration, and insulin infusion. Further, suppressed ghrelin release resulting from direct insulin action on ghrelin cells restricts ghrelin’s capacity to protect against hypoglycemia during over-insulinization.

Disclosure
K. Shankar: None. S. Takemi: None. D. Gupta: None. B.K. Mani: None. S. Osborne-Lawrence: None. N. Metzger: None. E. Berglund: None. J.M. Zigman: Stock/Shareholder; Self; Medtronic.

Funding
National Institutes of Health (R01DK119341-01A1, R01DK103884 to J.M.Z.), (R01DK109408 to E.B.), (R01DK119341 to J.M.Z., E.B.); David and Teresa Disiere Foundation (to J.M.Z.); Diana and Richard C. Strauss Professorship in Biomedical Research; Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine; Kent and Jodi Foster Distinguished Chair in Endocrinology (to J.M.Z.); Uehara Memorial Foundation (to S.T.)
1926-P: Potent Weight Loss Mechanism of a Novel Long-Acting Glucagon Analog, HM15136, in Animal Models of Obesity
Authors: LEE JONG SUK , LEE SEON MYEONG , KIM JUNG KUK , LEE JONGSOO , LEE SANG DON , BAE SUNGMIN , KIM DAEJIN , CHOI IN YOUNG 
Published: June 2020

Several studies have demonstrated that glucagon plays an essential role in the regulation of body weight via both increase of energy expenditure and suppression of appetite, suggesting its potential application for obesity management. Consistent with this, we previously observed that chronic treatment of the novel long-acting glucagon analog, HM15136, led to efficient body weight loss (BWL) in diet-induced obesity (DIO) mice. To further investigate the therapeutic benefits of HM15136 in obesity, the present study compared the BWL effect with available GLP-1 agonists and investigated the underlying mechanism for efficient BWL by HM15136. In DIO mice, chronic treatment of HM15136 showed greater BWL (-38.5% vs. vehicle) than GLP-1 agonists such as liraglutide, dulaglutide, and semaglutide (-16.8, -2.5, and -11.0% vs. vehicle). Of note, unlike liraglutide, more BWL was observed even under pair-feeding conditions, indicating the appetite regulation-independent BWL by HM15136. As to the responsible mechanism, HM15136 increased the expression of PGC-1α and UCP-1 in white adipose tissue (WAT), leading to enhanced energy expenditure. Together with the reduced respiratory exchange ratio, these results suggest that HM15136 induce WAT browning through which fat utilization and energy expenditure increases. To explore an additional mechanism for BWL by HM15136, oral lipid tolerance test (oLTT) was performed. Interestingly, blood TG level during oLTT was significantly decreased by HM15136 treatment, which coincided with decreased blood bile acid and ApoB48. These results suggest that the inhibition of lipid absorption is involved, at least in part, in efficient BWL by HM15136. Therefore, HM15136 could be a potential option for the management of obesity via favorable regulation of energy expenditure and lipid absorption in addition to appetite inhibition. Efficacy study in obese patients is ongoing to assess the clinical relevance of these findings.

Disclosure
J. Lee: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. J. Kim: Employee; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Spouse/Partner; Hanmi Pharmaceutical. S. Bae: Employee; Self; Hanmi Pharmaceutical. D. Kim: Board Member; Self; Hanmi Pharmaceutical. I. Choi: Board Member; Self; Hanmi Pharmaceutical.
1932-P: A Novel Antiobesity Peptide Secreted from Brown Adipocytes
Authors: ZHANG ZHUO , ZHANG XIAOXIAO , ZHONG HONG , CHI XIA , CUI XIANWEI , JI CHENBO 
Published: June 2020

Obesity, the most common metabolic disorder worldwide, is characterized by excess adipose tissue accumulation and causes to serious complications. Many studies have suggested that brown adipocytes contribute to weight loss with increased energy expenditure. Since white adipocytes could be convertible to a “brown-like” state, and induction of browning of white fat also become a promising strategy in the treatment of obesity. Notably, brown fat is not only a heat-producing but also a secretory organ communicating with other metabolic organs. In this study, we focused on peptides secreted by brown adipose tissue to discover new treatment against obesity and metabolic disorder. We successfully obtained a novel polypeptide from the secretory components of brown adipocytes named as BATSP1 (Brown Adipose Tissue Secreted Peptide), which played crucial role in stimulating browning of white adipocytes. The function and mechanism of BATSP1 were comprehensively evaluated in animal models, and we found that administration of BATSP1 stimulated browning of white adipose tissue and elevated mitochondria number dramatically consisting with the activation of energy metabolism. Moreover, to evaluate the feasibility of BATSP1 as a treatment for obesity, we treated DIO mice with BATSP1 and caused significant weight loss as well as decreased glucose and triglyceride content via browning. Taken together, we described an anti-obesity peptide secreted from brown adipocytes, and the underlying mechanism require further study to develop its clinic application.

Disclosure
Z. Zhang: None. X. Zhang: None. H. Zhong: None. X. Chi: None. X. Cui: None. C. Ji: None.

Funding
National Natural Science Foundation of China (81770866, 81770837, 81900783)
1936-P: The Role of Adipose Tissue in Intestinal Functions
Authors: LONG KEKAO 
Published: June 2020

Introduction: Adipokines regulate whole-body energy homeostasis, insulin sensitivity and immunity by mediating the crosstalk between adipose tissues and multiple tissues, including liver, skeletal muscle, brain, pancreas and intestines. Recent studies revealed that intestines also exhibit insulin resistance and dysregulated immune homeostasis in obese condition. On the other hand, several adipokines including adiponectin and adipocyte fatty acid binding protein have been shown to regulate intestinal function. Here, we aim to investigate the relationship between the adipose tissue and gut homeostasis using lipodystrophy animal models.
Methods: We employed our recently developed lipodystrophic mouse model, in which adipocyte MDM2 is genetically deleted (so-called Adipo-MDM2-KO mice). In fat transplantation experiment, subcutaneous fat form their wild type (WT) littermates was transplanted to the Adipo-MDM2-KO mice for 8 weeks. To assess gut permeability, Adipo-MDM2-KO mice and their wild type (WT) littermates were orally gavaged with DX-4000-FITC for 1 hour. Circulating LPS level were measured using the endotoxin assays, which reflects gut permeability and endotoxemia. For assessment of gut morphology, ileum isolated from Adipo-MDM2-KO mice and their WT littermates were subjected to Haemotoxylin and Eosin (H and E) staining.
Results and Conclusion: Adipo-MDM2-KO mice exhibited impaired gut barrier function and altered gut microbiota composition when compared with the WT littermates. A higher level of DX-4000-FITC in the serum of Adipo-MDM2-KO mice were detected. In addition, circulating level of LPS was significantly increased in Adipo-MDM2-KO mice. H and E staining showed a change in gut morphology and an increased number of inflammatory cells in the ileum of Adipo-MDM2-KO mice. These results demonstrated that fat loss leads to intestinal dysfunction, therefore, the adipose tissue is required for gut homeostasis.

Disclosure
K. Long: None.

Funding
National Natural Science Foundation of China (91857119)
195-LB: Metabolomic Characterization of Laron and Guevara-Rosenbloom Syndromes Using UHPLC-HRMS
Authors: RUBIO VANESSA , CHAMBERLAIN CASEY A. , WASSERFALL CLIVE , GUEVARA-AGUIRRE JAIME , GUEVARA ALEXANDRA , ROSENBLOOM ARLAN L. , ATKINSON MARK A. , YOST RICHARD A. , GARRETT TIMOTHY J. 
Published: June 2020

Laron syndrome (LS) is a rare autosomal recessive growth hormone (GH) insensitivity condition due to GH receptor mutation, and with phenotypic features likened to GH deficiency. The incidence of LS in Ecuador is very high and has gained worldwide attention due to its low incidence of cancer and diabetes mellitus. A more recently described population is affected with “Guevara-Rosenbloom syndrome” (GRS). While both groups exhibit severe short stature (-4 to -12 SDS), GRS subjects have normal GH signaling and responses and, unlike LS, have intrauterine growth retardation and early onset type 2 diabetes (T2DM). Since both groups have diminished insulin secretion, there is a unique opportunity to investigate their metabolome under each specific disease. Levels of certain amino acids in insulin-resistant (IR) states such as T2DM are distinct and special attention has been given to the predicting power of branched chain and aromatic amino acids, carnitines, and free fatty acids for IR and T2DM risk assessment. Our aim was to understand the metabolic differences between LS and GRS, which both have diminished insulin secretion but different GH counter-regulation as well as to compare these groups to normal controls. The metabolome of these 3 cohorts was assessed at the following instances: a) At the fasting state, and b) After an oral challenge of 1.5 mg/kg of glucose per kilogram of body weight, administered immediately after the fasting sample was drawn (samples were taken every 30 minutes for 5 hours [5h]). Preliminary results (by ANOVA) show a strong correlation, in the fasting state, between the control and the LS groups with clear discrimination from the GRS cohort, as determined by a heatmap of the top 100 features. Furthermore, the analysis of the 5h profile after the glucose challenge in the 3 groups revealed significant correlations in the levels of amino-acids that have been related to the genesis of IR and T2DM. This work represents the first deep-metabolome analysis in this unique study group.

Disclosure
V. Rubio: None. C.A. Chamberlain: None. C. Wasserfall: None. J. Guevara-Aguirre: None. A. Guevara: None. A.L. Rosenbloom: None. M.A. Atkinson: None. R.A. Yost: None. T.J. Garrett: None.

Funding
National Institutes of Health (U24DK097209)
195-OR: Safety and Performance of the Tandem T:slim X2 with Control-IQ Automated Insulin Delivery System in Preschoolers, Age 2-6 Years Old
Authors: EKHLASPOUR LAYA , FORLENZA GREGORY P. , SCHOELWER MELISSA , DEBOER MARK D. , HSU LIANA , KINGMAN RYAN S. , BORANIAN EMILY , EMORY EMMA , WADWA R. PAUL , BUCKINGHAM BRUCE A. , BRETON MARC D. 
Published: June 2020

Glycemic control is particularly challenging for young children with T1DM. We studied the Tandem Control-IQ AP system (CIQ) in children ages 2-5.9 years old during 48hr of supervised outpatient hotel/Airbnb use (SH) followed by 3 days of at home use (H). A minimum of 48hr Tandem standard pump therapy at home (B) preceded the SH phase. Meals and snacks were chosen by parents, without restrictions, and boluses were estimated per parents’ routine. While on closed-loop, all participants were remotely monitored by study staff. There were at least 30 minutes of exercise each day of SH phase. Twelve participants with &gt;3 months of T1D, mean age 4.7±1y, A1C 7.3±0.8%, weight 19.3±3.1kg were enrolled at 3 sites. All were using sensor augmented pumps before entry, with or without automation. All participants completed the study with no adverse events. Outcomes are reported below. CIQ improved mean glucose and TIR without an increase in hypoglycemia during the SH phase; at home CIQ improved all hypoglycemia outcomes as well as TIR, with a tendency towards a better mean glucose. All overnight outcomes were further improved. The Tandem Control IQ system was safe and significantly improved glycemic control in these young children in both the supervised hotel/Airbnb and the home setting.

Disclosure
L. Ekhlaspour: None. G.P. Forlenza: Advisory Panel; Self; Medtronic. Consultant; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. M. Schoelwer: Research Support; Self; Tandem Diabetes Care. M.D. DeBoer: Research Support; Self; Tandem Diabetes Care. L. Hsu: Stock/Shareholder; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. R.S. Kingman: None. E. Boranian: Other Relationship; Self; American Diabetes Association. E. Emory: None. R. Wadwa: Advisory Panel; Self; Eli Lilly and Company, Medtronic. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, MannKind Corporation, Medtronic, Novo Nordisk Inc., Tandem Diabetes Care. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. M.D. Breton: Research Support; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi, Tandem Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc., Tandem Diabetes Care.

Funding
Tandem Diabetes Care
1960-P: A Novel Nitric Oxide Releasing Nanomatrix Gel Prevents High-Fat Diet-Induced Obesity and Insulin Resistance
Authors: REN GUANG , SHAW AUBREY L. , HWANG PATRICK , MILLICAN REID C. , JUN HO-WOOK , KIM JEONGA 
Published: June 2020

Endothelial dysfunction is characterized by reduction of the bioavailability of nitric oxide (NO), and is associated with metabolic syndrome including, obesity, insulin resistance, hypertension, coronary heart disease, and aging. Because NO plays important roles in mitochondrial biogenesis, we hypothesize that exogenous application of NO may prevent high fat diet (HFD)-induced obesity and insulin resistance by promotion of adipose tissue browning. In the current study, we developed a novel NO releasing nanomatrix gel with natural peptide amphiphiles (PANO). 8 week old male C57BL/6 mice were randomly divided into 2 groups, and then either vehicle (PA) or PANO was subcutaneously injected into brown adipose tissue area every 2 weeks for 11 weeks while the mice were fed HFD. The mice injected with PANO gained less body weight compared to the mice injected with vehicle. PANO injected mice demonstrated improved glucose tolerance and insulin tolerance. Fasting glucose, insulin and leptin levels were lower in the PANO injected mice compared to the vehicle injected mice. Furthermore, the expression of pro-inflammatory genes in epididymal fat tissue was lower, and the expression of uncoupled protein (UCP1) in brown adipose tissue and inguinal adipose tissue was higher in the PANO-injected mice compared to the vehicle injected mice. Thus, the novel nitric oxide releasing nanomatrix gel ameliorated HFD-induced obesity and insulin resistance by promotion of adipose tissue browning. The results suggest that injection of PANO can be a novel therapeutic for obesity and insulin resistance.

Disclosure
G. Ren: None. A.L. Shaw: None. P. Hwang: None. R.C. Millican: None. H. Jun: None. J. Kim: None.

Funding
National Institutes of Health (1R01HL125391-01)
1963-P: Short- and Long-Term Empagliflozin Treatment Improves Cardiac Function in Rats with Chronic Heart Failure
Authors: SOULIÉ MATTHIEU , STEPHAN YOHAN , NICOL LIONEL , HENRY JEAN-PAUL , RICHARD VINCENT , PIEPER MICHAEL , MULDER PAUL 
Published: June 2020

Introduction: The SGLT2 inhibitor empagliflozin (EMPA) exerts beneficial cardiovascular effects in type-2 diabetes, but whether this occurs in chronic heart failure (CHF) is unknown. Thus we investigated, using a rat model whether EMPA exhibits protective effect in chronic heart failure (CHF).
Methods: Rats with CHF were treated with EMPA (30 mg/kg PO for 7 days starting 83 days after coronary artery ligation or 90 days starting 7 days after coronary artery ligation) to assess effects on left ventricular (LV) function and hemodynamics (echocardiography, LV catheterization).
Results: After 90 days untreated CHF rats presented LV systolic and diastolic dysfunction, illustrated by the decreases in LV end-systolic pressure (LV ESP) and in LV end-systolic pressure volume-relation (LV ESPVR) as well as the increases in LV end-diastolic pressure (LV EDP) and LV end-diastolic pressure volume-relation (LV EDPVR). Seven- and ninety-day EMPA treatment improved systolic and diastolic LV function, illustrated by the increases in LV ESP and in LV ESPVR as well as the reductions in LV EDP and in LV EDPVR.
Conclusion: Short- and long-term EMPA treatment prevents LV dysfunction in rats with CHF. These results suggest that EMPA may exert protective effects in humans with CHF.

Disclosure
M. Soulié: None. Y. Stephan: None. L. Nicol: None. J. Henry: None. V. Richard: None. M. Pieper: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. P. Mulder: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA.

Funding
Boehringer Ingelheim