bluuebunny/crossref_metadata_2025_split huggingface dataset:
2250-PUB: Lower Blood Glucose Values Lead to Higher Sleep Efficiency in Adolescents with Type 1 Diabetes
Authors: MONZON ALEXANDRA , MCDONOUGH RYAN , CLEMENTS MARK A. , PATTON SUSANA R. 
Published: June 2020

Objective: Sleep disturbances occur frequently in youth with type 1 diabetes (T1D) with only 20% of adolescents meeting recommendations for sleep duration during the week. Few studies have directly evaluated the relationship between objectively measured sleep behaviors and mean blood glucose (BG) as measured by continuous glucose monitors (CGM).
Methods: Twenty adolescents with T1D (Age: M= 14.69, SD= 1.58, Sex= 50% female; Race= 80% Caucasian) participated. Youth’s average HbA1c was 9.0% (SD= 1.70), and all participants used an insulin pump. Youth wore an accelerometer on their non-dominant wrist and a CGM for seven consecutive days. We estimated multilevel models using SAS PROC MIXED and reverse-lagged nighttime sleep variables to specifically examined the impact of BG values on each sleep variable the following night. We examined total sleep time (TST), sleep efficiency (i.e., percentage of time spent asleep while in bed), and onset latency (i.e., minutes between going to bed and falling asleep) independently, as proxies for sleep behavior. We entered a dichotomous weekday/weekend variable in the model as a level 2 moderator. Results: Participants averaged 9.1 hours (SD= 84.9 minutes, range= 2.82-11.15 hours) of TST. Sleep variables did not differ on weekdays versus weekends. Our multilevel models did not reveal a significant association between sleep variables predicting mean BG. We did observe an association between within-person mean BG values significantly predicting sleep efficiency (β= -0.06802). This suggests an adolescent’s sleep efficiency may increase when their BG is lower than typical for themselves.
Conclusions: The results of the study add support to previous laboratory studies that indicate lower BG levels associate with better sleep efficiency in youth with T1D. Clinicians may consider assessing sleep patterns in youth with T1D as an additional treatment target for optimal T1D self-management.

Disclosure
A. Monzon: None. R. McDonough: None. M.A. Clements: Consultant; Self; Glooko, Inc. Other Relationship; Self; Glooko, Inc. S.R. Patton: None.
226-OR: The Mediterranean Diet Increases GLP-1 and Oxyntomodulin Compared with Vegetarian Diet in Type 2 Diabetes Subjects
Authors: MAURO ANTONIO DI , TUCCINARDI DARIO , TORO ROSSELLA DEL , MONTE LAVINIA , GIORGINO RICCARDO , RAMPA LORENZO , ROSSINI GIOVANNI , KYANVASH SHADI , SOARE ANDREEA , ROSATI MILENA M. , KHAZRAI YEGANEH MANON , PICCOLI ALESSANDRA , NAPOLI NICOLA , POZZILLI PAOLO , MANFRINI SILVIA 
Published: June 2020

Aim: To compare a Mediterranean dietetic pattern with a vegetarian pattern in terms of hunger-satiety perception through post-prandial assessment of appetite-related hormones glucagon-like peptide 1 (GLP-1) and Oxyntomodulin (OXM), as well as self-rated Visual Analogue Scale (VAS) quantification, in overweight/obese type-2 diabetes (T2D) subjects.
Methods: Twelve T2D subjects (M:F = 7:5), mean age 63 ± 8.5 years, were enrolled in our randomized, controlled, crossover study. Participants were given a vegetarian meal high in complex carbohydrate and dietary fiber (HFV, 35g fiber/1000 Kcal) as well as a Mediterranean (MED) meal in two different days over a one-week washout period. The two meals were isocaloric. Appetite ratings, glucose/insulin and gastrointestinal hormone concentrations were measured at fasting and every 30’ until 4 hours following meal consumption.
Results: GLP-1 and OXM levels were significantly higher following MED meal consumption compared with HFV meal (240’ AUC, P &lt;.022 and P &lt;.023, respectively). Both MED and HFV meal resulted in a biphasic secretion pattern of GLP-1 and OXM, although MED meal was related to a delayed, significantly higher second GLP-1 peak at 150’ compared with that of HFV meal (P &lt;.05). MED meal was related to lower glucose trend compared with HFV meal (P &lt;.039), whereas we did not observe significant changes in terms of self-reported VAS scores and insulin trend.
Conclusions: In T2D overweight/obese subjects, a MED-like meal is more effective than a vegetarian meal in terms of post-prandial plasma glucose homeostasis and GLP-1 and OXM release. These changes were not confirmed by VAS appetite self-assessment over a 4 hours period.

Disclosure
A. Di Mauro: None. D. Tuccinardi: None. R. Del Toro: None. L. Monte: None. R. Giorgino: None. L. Rampa: None. G. Rossini: None. S. Kyanvash: None. A. Soare: None. M.M. Rosati: None. Y. Khazrai: None. A. Piccoli: None. N. Napoli: None. P. Pozzilli: Advisory Panel; Self; Abbott, AstraZeneca, Eli Lilly and Company. Research Support; Self; Medtronic, Sanofi. S. Manfrini: None.
2294-PUB: Investigating Medial Amygdala Circuits in Glucose Homeostasis
Authors: DEVARAKONDA KAVYA , CONNER KAETLYN , GARIBAY DARLINE , STANLEY SARAH 
Published: June 2020

One out of every 10 Americans has diabetes, increasing their risk of death by 50% and more than doubling their health care costs. Delineating how the brain regulates metabolism, including feeding behavior and glucose homeostasis, may shed light on how those processes are altered in disease. The medial amygdalar nucleus (MeA) regulates the intersection of stress, social behavior, and metabolism. Fos expression in the MeA of mice is altered by changes in energy availability - fasting/re-feeding and hyper-/hypoglycemia - suggesting this nucleus may regulate feeding behavior and blood glucose levels in response to internal cues. The primary downstream targets of the MeA are the principle nucleus of the bed nucleus of the stria terminalis (prBNST) and ventromedial hypothalamus (VMH), regions previously shown to regulate metabolism. Cfos immunohistochemistry and retrograde labeling show that MeA neurons that project to the VMH (MeA--&gt;VMH) are preferentially activated by a 36h fast, compared to ad libitum feeding and a 1h refeed. Selectively activating MeA--&gt;VMH neurons using chemogenetics induces hyperglycemia independent of changes to circulating insulin and changes in feeding. Ongoing fos, axonal tracing, and behavioral studies aim to delineate the contributions of different MeA cell types to glucose homeostasis in the context of other competing behaviors including social interaction and stress.

Disclosure
K. Devarakonda: None. K. Conner: None. D. Garibay: None. S. Stanley: None.

Funding
American Diabetes Association/Pathway to Stop Diabetes (1-17-ACE-31 to S.S.); American Heart Association (18PRE33960254)
23-LB: Overexpression of microRNA-16 Derepresses the Mitochondrial Function to Exacerbate Cardiomyopathy in Streptozotocin-Induced Diabetic Mice
Authors: ZHOU JING , ZHU YINGHONG , FAN JING 
Published: June 2020

Introduction: Diabetic cardiomyopathy is initially characterized by myocardial fibrosis, dysfunctional remodeling, and associated diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, were recognized to play significant roles in diabetes. But, it remains unknown whether mitochondrial function is modulated by miRNAs during diabetic cardiomyopathy.
Aim: This study investigates the potential role of microRNA-16 (miR-16) in modulating mitochondrial function during diabetic cardiomyopathy.
Methods and Results: To assess the function of miR-16 in vivo, miR-16 was expressed using a adeno-associated virus serotype 9 (AAV9) viral vector in male 1-week-old mice C57BL/6J mice. At 6-week-old, these mice received three consecutive daily i.p. injections of STZ (55 mg/kg body weight) combined with 18 weeks of high-fat diet to induce T2DM. We demonstrated that miR-16 expression was slight increased in diabetic mice. Overexpression of miR-16 exacerbated diabetic cardiomyopathy which reflected by increasing myocardial fibrosis and displaying a diastolic dysfunction in STZ-induced mice. Impaired mitochondrial function was observed in electron microscopy of myocardium in mice with overexpression of miR-16. In vitro, high glucose (HG) treated cultured cardiomyocytes with overexpression miR-16 showed a worse mitochondrial damage, and inhibition of miR-16 induced a protective effects role in HG-treated cardiomyocytes. Molecular mechanisms linked to the underlying pathophysiological changes include abnormalities in AMP-activated protein kinase, p38 MAPK and PGC1α.
Conclusions: In conclusion, our results show that miR-16 plays an important role in the development of diabetic cardiomyopathy in T2DM mice, which can be targeted for therapeutic intervention.

Disclosure
J. Zhou: None. Y. Zhu: None. J. Fan: None.
2300-PUB: Activation of GLP-1 Signaling Attenuates FFAs-Induced Muscle Dysfunction and Senescence
Authors: LI HSIN-HUA , LIN CHIH-LI , HUANG CHIEN-NING , KORNELIUS EDY , YANG YI SUN , PENG CHIUNG-HUEI , LI CHING RU , LIU SHIANG-TING 
Published: June 2020

Obesity and insulin resistance are frequently associated with type 2 diabetes (T2D). Evidence is now revealed that plasma free fatty acid (FFA) levels are often elevated in most T2D patients, and this can cause peripheral insulin resistance directly. As a result, these FFAs inhibit insulin-stimulated glucose uptake, thus contributing to the onset of insufficient energy within cells. Among various T2D-related complications, the continuously loss of muscle is one of the most important adverse effects. Blocked insulin signaling in skeletal muscle is manifested by decreased insulin sensitivity and impaired muscle cell function including glucose transport, glucose phosphorylation, reduced glucose oxidation and glycogen synthesis that might ultimately lead to muscle loss. Interestingly, recent studies have found that GLP-1 agonists appear to slow muscle wasting during T2D. Since GLP-1 receptors are abundantly expressed on the membrane of muscle cells, indicating that they may play some important roles in muscle physiology. However, the detailed mechanism is still not well understood. In this study, we investigated the effect of GLP-1 agonist against FFA-induced muscle wasting. We used mouse C2C12 myotubes to evaluate effects of GLP-1 agonists FFA-induced muscle loss and dysfunction. Our data indicated that FFA induces insulin resistance, oxidative stress muscle loss and cell senescence in muscle cells. Moreover, FFA also decreased glucose uptake and reduced myotube mass and function. Conversely, GLP-1 agonists could protect against FFAs-induced myotube dysfunctions, including insulin resistance, oxidative stress, cell loss and senescence, that eventually reversed myotube mass and function through AMPK/SIRT1 pathway. We expect our results can extend the contributing role of GLP-1 signaling in FFA-induced insulin resistance of muscle cells, and the modulation of GLP-1 signaling may be a workable strategy for muscle wasting prevention.

Disclosure
H. Li: None. C. Lin: None. C. Huang: None. E. Kornelius: None. Y. Yang: None. C. Peng: None. C. Li: None. S. Liu: None.

Funding
Ministry of Science and Technology of Taiwan (108-2320-B-040-029-MY2)
2308-PUB: A Protective Role of H2S from Obesity-Associated Metabolic Stress in GLP-1 Regulation
Authors: MEZOUARI ANIA , GAGNON JEFFREY , NANGIA RADHIKA 
Published: June 2020

Background: Obesity is a risk factor in the development of a variety of diseases including cardiovascular disease and type 2 diabetes. Circulating fatty acids (including palmitate) and protein glycation are both increased in obesity and diabetes and are known to cause metabolic stress. This includes the impairment of the glucoregulatory hormone glucagon-like peptide-1 (GLP-1) secreted from intestinal L-cells. Recently, the gastrointestinal microbiome has been implicated in the regulation of GLP-1. We believe that the bacterial metabolite hydrogen sulfide (H2S) can play a protective role in L-cell metabolic stress.
Methods: Our study was conducted on both human NCI H716 and mouse GLUTag GLP-1 secreting L-cells. L-cell stress was assessed using the total reactive oxygen species (ROS) dye DCF-DA. ROS levels were examined during incubation with palmitate (PA), glycated albumin (GA), and the bacterial gas donor GYY4137(H2S). Next, GLP-1 secretion was measured after treating cells with PA and GA, along with H2S using a GLP-1 ELISA.
Results: We have demonstrated that elements of the obese physiological environment: PA and GA, cause an increase of reactive oxygen species (ROS) in L-cells. Specifically, 500μm PA and 200μg/mL GA caused a 75% and 50% increase in ROS generation, respectively. Furthermore, these treatments led to a 25% reduction of GLP-1 secretion in human L-cells. Finally, the microbial gas H₂S reduced basal and PA-induced ROS by nearly half.
Conclusion: The microbial gas H2S reduces metabolic stress in GLP-1 cells. This study will lay the foundation for future work exploring how bacterial products such as prebiotics and probiotics may be used as a treatment for complications associated with obesity and diabetes.

Disclosure
A. Mezouari: None. J. Gagnon: None. R. Nangia: None.

Funding
Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-05905)
235-OR: Incidence of Significant Changes in Pulmonary Function during a 2-Year Study with Inhaled Technosphere Insulin
Authors: JONES MARISA C. , TRAN TIFFANY S. , KRUEGER JOHN A. , MOREY PATRICK M. , HOOGWERF BYRON J. , KENDALL DAVID M. 
Published: June 2020

The impact of inhaled Technosphere Insulin (TI) on measures of pulmonary function remain an important component of clinical use. TI is an ultra rapid-acting prandial insulin delivered via deep pulmonary inhalation allowing for prompt absorption in the alveoli. Prior studies have demonstrated that, on average, changes in pulmonary function testing (PFT) are limited to small changes (∼1%) in forced expiratory volume in 1 second (FEV1). This comprehensive post-hoc analysis examined the incidence of significant decline in FEV1 over two years in subjects with type 1 and type 2 diabetes treated with TI. Subjects were included if they had at least five FEV1 measurements (including baseline and month 24). FEV1 must have been ≥70% of predicted at baseline. At each time point, subjects were classified as having a significant change in FEV1 if there was a ≥15% decline from baseline. Of the 377 subjects, 331 (87.8%) had no measure with ≥15% decline in FEV1 at any time point. Of subjects who had at least one measure with a decline of ≥15%, the majority (n=38) experienced this decline on a transient basis (defined as occurring at two or fewer time points). Eight individuals (2.1%) demonstrated a persistent decline in FEV1 (occurring at three or more time points). Four subjects in the comparator arm (0.7%, n=586) had persistent decline.
In conclusion, persistent significant decline in FEV1 during the use of TI was uncommon.

Disclosure
M.C. Jones: Employee; Self; MannKind Corporation. T.S. Tran: Employee; Self; MannKind Corporation. J.A. Krueger: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; Eli Lilly and Company, MannKind Corporation. P.M. Morey: Employee; Self; MannKind Corporation. B.J. Hoogwerf: Consultant; Self; MannKind Corporation. Employee; Spouse/Partner; MannKind Corporation. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. D.M. Kendall: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; Eli Lilly and Company.
24-OR: Electronic Decision Support for Insulin Therapy Is Safe and Efficient in Inpatients with Type 2 Diabetes
Authors: HOCHFELLNER DANIEL A. , ZIKO HARIS , SAGMEISTER MAXIMILIAN H. , ELSAYED HESHAM , CIGLER MONIKA , POETTLER TINA , ABERER FELIX , SENDLHOFER GERALD , BECK PETER , MADER JULIA K. 
Published: June 2020

Attainment of good glycemic control in hospitalized patients with type 2 diabetes (T2D) is often hampered by fear of hypoglycemia and insufficient knowledge in insulin therapy. An electronic algorithm-based decision support system (GlucoTab®, decide Clinical Software GmbH, Graz, Austria) for inpatient management was developed and has proven efficacy in clinical trials. After implementing GlucoTab® in routine care, a retrospective analysis of T2D patients requiring subcutaneous insulin therapy on an Endocrinology ward was performed. Data from days when patients received algorithm-steered basal-bolus insulin therapy (BBI) was compared with days when insulin therapy was performed according to local standard care (SC) provided by an endocrinologist. As the treating physician was free to start/stop decision support during inpatient stay, patients switched between BBI and SC. During the first six months following GlucoTab® implementation, a total of 71 T2D patients required subcutaneous insulin therapy and subsequently were included in this analysis. Incomplete treatment days (e.g., admission and discharge days; days, where both therapy schemes applied) were excluded, resulting in 261 BBI and 274 SC days. Baseline characteristics were as follows: 39 % women, 99 % Caucasian, age 73.5 ± 12.5 years, diabetes duration 15.4 ± 10.6 years, HbA1c 70.4 ± 24.2 mmol/mol, BMI 29.0 ± 5.5 kg/m² and creatinine 1.6 ± 1.2 mg/dL. Mean daily glucose was lower for BBI vs. SC: 156.9 ± 35.7 mg/dL vs. 172.1 ± 47.3 mg/dL. Total daily insulin dose was higher for BBI vs. SC: 42.2 ± 25.2 U vs. 33.7 ± 20.9 U. Blood glucose (BG) in target (70-180 mg/dL) was higher for BBI vs. SC: 70 % vs. 61.2 %. BG &lt;70 mg/dL was 1.6 % vs. 1.9 % and BG &lt;54 mg/dL was 0.2 % vs. 0.6 % (BBI vs. SC, respectively). Continuous use of BBI resulted in a BG decline from 182 (day 1) to 147 mg/dL (day 10) while it remained elevated in SC (188 to 177 mg/dL). BBI showed beneficial glycemic control compared to SC in routine use during inpatient diabetes management.

Disclosure
D.A. Hochfellner: None. H. Ziko: None. M.H. Sagmeister: None. H. Elsayed: None. M. Cigler: None. T. Poettler: None. F. Aberer: None. G. Sendlhofer: None. P. Beck: Employee; Self; decide Clinical Software. Stock/Shareholder; Self; decide Clinical Software. J.K. Mader: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Medtronic, Prediktor Medical, Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis.
248-LB: Spexin Promotes Insulin Secretion and ß-Cell Proliferation
Authors: LIU RUI 
Published: June 2020

Spexin was firstly discovered as a neuropeptide and was also detected in peripheral tissues including liver, fat and pancreatic islets. Recently, studies documents that diabetes patients had lower circulation level of Spexin. It is unclear whether Spexin exerts glucose homeostasis regulating effects. Here, we provide evidence that Spexin stimulates β cell proliferation and insulin secretion in mice and human islets. Acute administration of Spexin prior glucose challenge promoted insulin secretion and improved glucose tolerance in a dose dependent manner (35-200 μg/kg BW). Meanwhile, Spexin treatment had no effect on insulin tolerance. The addition of Spexin to mouse islets increased β cell proliferation demonstrated by 2-fold increase of BrdU(+) β-cells. Spexin promoted cell growth of INS-1 cells in a dose dependent manner with maximum effect at dose of 25 ng/ml. In a high-fat diet (HFD)-induced β cell proliferation and β cell mass expansion model, the percentage of Ki67(+) β-cells increased by 2-fold compared to chow diet (CD)-fed mice. Spexin provoked further 80% increase. Consistently, HFD feeding increased β-cell mass by 2-fold and Spexin made further 58% increase. To identify the mechanism of Spexin-stimulated β cell proliferation, we tested whether the expression of well-established β cell cycle regulators was controlled by Spexin. Spexin treatment of INS-1 cells for 24 h significantly increased mRNA levels of cyclin D1 and Cyclin E1 compared with controls. Spexin stimulated the phosphorylation of CREB (p-CREB) with a peak at 10 min. The addition of H89, a potent PKA inhibitor blocked the effect of Spexin on activation of p-CREB and stimulation of the expression of Ki67, Cyclin D1 and Cyclin E1. Furthermore, Spexin stimulated the p-CREB, promoted insulin secretion and increased β cell proliferation in human islets. Thus, Spexin is an important factor for islet β cell proliferation, and our study provides previously unrecognized evidence of a factor governing endocrine pancreas growth and function.

Disclosure
R. Liu: None.

Funding
National Natural Science Foundation of China (81200622, 81570518, 81630020)
248-OR: Visualizing Heterogeneous Islet Autoantibody Trajectories of Children Who Develop T1D from Multisite Birth Cohort Studies
Authors: KWON BUM CHUL , ACHENBACH PETER , ANAND VIBHA , DUNNE JESSICA L. , HAGOPIAN WILLIAM , LUNDGREN MARKUS , VEIJOLA RIITTA , FROHNERT BRIGITTE I. ,   THE T1DI STUDY GROUP
Published: June 2020

We investigated evolution of islet autoantibodies (IAs) prior to onset of T1D from 5 large-scale birth cohort studies. Our analysis revealed three distinct IA trajectories leading up to diagnosis of T1D. Of 24673 children from five prospective studies (DAISY, DiPiS, DIPP, DEW-IT, and BABYDIAB), 688 who were diagnosed with T1D and had 3 or more visits were included in this analysis. Hidden Markov Models were developed to label visit-level observation of each subject based on three IAs: GADA, IAA, and IA-2A. Interactive visualizations were then applied to explore model outcomes, identify IA evolution trajectories, and examine their clinical characteristics. Three trajectories were identified (Figure 1) with a majority of children having multiple IA (Tr1: n=265) or IAA first (Tr2: n=282) at seroconversion; the minority seroconverted with GADA first (Tr3: n=131). The Tr3 group had seroconversion and T1D onset at an older age in months (58, 132) than Tr1 (42, 96) and Tr2 (31, 88), P &lt; .01. Distribution of HLA DR/DQ differed between groups: higher DRX/X and lower DR3/4 in Tr3 (18%, 24%) than Tr1 (11%, 26%) and Tr2 (10%, 31%). The three IA trajectories show distinctive antibody patterns, ages of seroconversion and T1D onset and HLA DR/DQ group distributions among them. Furthermore, heterogeneity is also shown within each trajectory in terms of progression time and needs further investigation.

Disclosure
B. Kwon: None. P. Achenbach: None. V. Anand: None. J.L. Dunne: None. W. Hagopian: Consultant; Self; Novo Nordisk Inc. M. Lundgren: None. R. Veijola: None. B.I. Frohnert: None.

Funding
JDRF (1-IND-2019-717-I-X, 1-SRA-2019-722-I-X, 1-SRA-2019-723-I-X, 1-SRA-2019-719-I-X, 1-SRA-2019-721-I-X, 1-SRA-2019-720-I-X)