bluuebunny/crossref_metadata_2025_split huggingface dataset:
2056-P: Psychiatric Profile and Quality of Life in Subjects with Excess Weight Treated with Transcranial Direct Current Stimulation Combined with Hypocaloric Diet
Authors: NATIVIDADE GABRIELLA RICHTER , ARAUJO CARINA DE , FITZ RAQUEL C. , OSÓRIO AMANDA F. , MERELLO PAULA NUNES , SCHESTATSKY PEDRO , GERCHMAN FERNANDO 
Published: June 2019

Transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex (DLPFC) may reduce appetite and caloric intake. However, it is used as an adjunct treatment for depression by stimulation of the left DLPFC. As a result, its safety in mental health and its impact on quality of life of subjects with excess weight needs to be addressed.
Objective: To assess the effect of repeated tDCS of the right DLPFC on mood, daytime sleepiness, anxiety and quality of life in subjects with excessive weight on a hypocaloric diet.
Methods: We randomly assigned 28 participants to receive 20 sessions of active or sham tDCS for 20 consecutive weekdays. Anode and cathode electrodes were respectively placed on the right and left DLPFC. The Beck Depression Inventory (BDI), a daytime sleepiness questionnaire (DSQ), State-Trait Anxiety Inventory-State (STAI-S) and the 36-Item Short Form Health Survey (SF-36) were administered before (t0) and after (t20) the intervention period.
Results: There were no statistically significant changes in BDI, DSQ, STAI-S and SF-36 subscales between the groups throughout the study (Figure 1A and 1B).
Conclusion: The absence of significant changes in the scales suggests that tDCS is not associated with impairment in mental health and quality of life in this population. ClinicalTrial.gov: NCT02683902.

Disclosure
G.R. Natividade: None. C. de Araujo: None. R.C. Fitz: None. A.F. Osório: None. P.N. Merello: None. P. Schestatsky: None. F. Gerchman: Speaker's Bureau; Self; Novo Nordisk Inc. Other Relationship; Self; Sanofi-Aventis.

Funding
Hospital de Clínicas de Porto Alegre (FIPE15-0119)
2060-P: Serum Wnt Inhibitor DKK1 Is Associated with Adiposity and Insulin Resistance in Nondiabetic North Americans
Authors: ALI HIRA , OCZYPOK ELIZABETH , MILJKOVIC IVA , CVEJKUS RYAN , ZMUDA JOSEPH M. , DELANY JAMES , KERSHAW ERIN E. 
Published: June 2019

Background: The Wnt pathway is known to influence body composition during early human development by regulating bone formation, myogenesis and adipogenesis. We have recently shown that DKK1 is related to measures of adiposity in nondiabetic African ancestry males. Whether these relationships are true across sexes and/or in other human populations remains unknown. In this study we evaluated the relationship of DKK1 with adiposity in a sample of male and female, mixed race, nondiabetic North American individuals.
Methods: Fasting serum DKK1 levels were measured using ELISAs in 201 nondiabetic subjects (age range 30.7-60 years, BMI range 19.9-64.0 kg/m2) recruited from the general population via television advertisement and mass mailing. The subjects were predominantly female (85%) and Caucasian (63%). Anthropometrics were obtained and markers of inflammation and glucose metabolism were measured from fasting serum samples. Spearman and partial Spearman correlation analysis was used to determine the association of DKK1 with measures of adiposity and insulin resistance.
Results: Circulating DKK1 was positively associated with BMI (r=0.30, p&lt;0.001) and waist circumference (r=0.25, p&lt;0.001), independent of age, race and sex. In addition, DKK1 was positively associated with fasting serum insulin level (r=0.18, p&lt;0.01) and HOMA-IR (r=0.19, p&lt;0.01) in age, sex and race adjusted models. However, these associations were no longer significant after adjustment for BMI.
Conclusion: This is the first study looking at correlation of DKK1 with adiposity in North American nondiabetic individuals. Our findings suggest that the link between DKK1 and insulin resistance maybe mediated indirectly through total and regional adiposity and that DKK1 could be a potential early biomarker for diabetes in high risk individuals. These findings support our findings in African ancestry males and add to the evidence favoring potential role of Wnt modulators in adiposity regulation in humans.

Disclosure
H. Ali: None. E. Oczypok: None. I. Miljkovic: None. R. Cvejkus: None. J.M. Zmuda: None. J. DeLany: None. E.E. Kershaw: Research Support; Self; Regeneron Pharmaceuticals.

Funding
National Institutes of Health (T32DK007252); Endocrine Fellows Foundation
2081-P: Obesity and Bariatric Surgery Trends in Type 1 Diabetes
Authors: UWAIFO GABRIEL I. 
Published: June 2019

The prevalence of obesity and its complications and comorbidities continue to increase. It is well established that obesity is a major etiologic factor in the onset of type 2 diabetes (T2DM) and that bariatric surgery (BS) is an effective management strategy for both weight and glycemic control in obese T2DM patients. The relationship between obesity and type 1 diabetes (T1DM) is less clear though recent reports suggest a recent surge in the prevalence of obesity among T1DM patients. To explore the prevalence of obesity in T1DM and the impact of bariatric surgery in these patients a 1 year (2018) retrospective chart review of T1DM patients was done and the identified patients were compared to T2DM patients seen over the same time period in the Ochsner clinical network. Of 93,367 subjects with T2DM seen over the 1 year period, 62, 034 (66.4%) are obese and of these 18,670 (30%) are morbidly obese. The T1DM patients over the same period are 7,143 of which 3,728 (52%) are obese and 969 (26%) are morbidly obese. Over this period while 1,818 Obese T2DM patients (2.9% of the cohort) had BS only 6 obese T1DM patients (0.16%) of the cohort had BS. This group consists of mostly Caucasian (5/6) women (5/6) with 3 having gastric bypass and 4 having sleeve gastrectomy. While the prevalence of cardiometabolic comorbidities (hypertension, dyslipidemia, ESRD, CAD, and CVD) were essentially similar in both cohorts of obese diabetics, the effects of bariatric surgery on weight, HBA1c, blood pressure and lipids were more variable in the T1DM patient than the T2DM patients. Obesity is presently nearly as prevalent in T1DM as T2DM. Morbid obesity is just as prevalent in both diabetes cohorts. While BS remains underutilized as a management strategy in obese T2DM it remains a rarity in obese T1DM and the little data available suggests that its impact on cardiometabolic surrogates may be more variable in this unique cohort. More study is needed of the potential utility and impact of BS in weight management of obese T1DM.

Disclosure
G.I. Uwaifo: None.
2089-P: Regional Renal Hemodynamics and Fatty Acid Uptake: Effects of Obesity and Weight Loss
Authors: REBELOS ELENI , DADSON PRINCE , OIKONEN VESA , IIDA HIDEHIRO , HANNUKAINEN JARNA C. , IOZZO PATRICIA , FERRANNINI ELE , NUUTILA PIRJO 
Published: June 2019

Objective: Changes of obesity on renal perfusion and metabolism are poorly understood. Our aims were to evaluate whether obesity increases renal regional hemodynamics and metabolism in vivo, and to determine the effects of weight loss.
Methods: 23 morbidly obese and 15 age- and sex-matched nonobese controls were recruited. Renal perfusion and fatty acid uptake (FAU) were measured using PET-CT scanning and [15O]- H2O and [18F]fluoro-6-thia-heptadecanoic acid ([18F]THA), respectively. Kidney volumes and radiodensity were measured by CT and cardiac output by MRI. Intraglomerular pressure (Pglo) was estimated by Gomez formula. Obese subjects were re-studied six months after bariatric surgery.
Results: As compared to controls, obese subjects had larger renal volume (340[118] vs. 256[63] ml, median[interquartile range]) and lower renal radiodensity (15.3[13.1] vs. 31.5[9.8] units, p≤0.05 for both), suggesting accumulation of water and/or lipid. Both cardiac output and glomerular filtration rate (eGFR) were increased by ∼25% in the obese. While there were no differences in total renal perfusion between the two groups, Pglo was higher in the obese (61±5 mmHg vs. 55±3 of controls, p&lt;0.001). In both groups, regional blood flow was 50% higher in the cortex than medulla; in either region, FAU was higher in the obese (6.3±1.8 vs. 4.1±1.5 µmol.min-1.100g-1, and 7.5±2.2 vs. 4.6±2.1, both p≤0.05), mostly as a consequence of higher plasma FFA levels. Post-surgery (weight loss = 26±8 kg), renal volume, GFR, and Pglo all decreased and renal radiodensity increased to levels similar to controls. On the contrary, cortical and medullary FAU was not normalized.
Conclusions: In obesity, renal hemodynamics are indicative of an incomplete protection against hyperperfusion and renal fatty acid uptake is increased, driven by higher substrate availability. Surgically-induced major weight loss reverses the hemodynamic but not the metabolic changes.

Disclosure
E. Rebelos: None. P. Dadson: None. V. Oikonen: None. H. Iida: None. J.C. Hannukainen: None. P. Iozzo: None. E. Ferrannini: None. P. Nuutila: Research Support; Self; AstraZeneca.

Funding
Academy of Finland; University of Turku; Turku University Hospital
21-OR: Final Results of a Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of the MetAP2 Inhibitor ZGN-1061 in Patients with Type 2 Diabetes
Authors: KIM TERRI , ZHUANG DONGLIANG , HAUGEN TONYA L. , KIM DENNIS D. , TAYLOR KRISTIN 
Published: June 2019

ZGN-1061 is a second-generation methionine aminopeptidase 2 (MetAP2) inhibitor in development for treatment of T2D. This clinical trial evaluated ZGN-1061 (0.05, 0.3, 0.9, or 1.8 mg) vs. placebo (PBO) administered SC every 3 days for 12 weeks on change from baseline in A1C in individuals with T2D at multiple sites in Australia/New Zealand. Stable noninsulin diabetes therapy was permitted. Baseline (ITT population N=175): 52% female, 77% white, (mean±SD) age 54±8 y, A1C 8.6±1.1%, BMI 37±7 kg/m2, T2D duration 8±6 y. Interim analysis results (0.05, 0.3, 0.9 mg ZGN-1061) were presented previously. Here, we report additional results with 0.9 and 1.8 mg ZGN-1061. The LS mean±SE A1C change for PBO was 0.2±0.1% (N=42) vs. -0.4±0.1% (N=44) and -0.9±0.2% (N=23) for 0.9 and 1.8 mg ZGN-1061, respectively. The LS mean±SE difference vs. PBO was -0.6±0.2% and 1.1±0.2% for 0.9 mg (p=0.0003) and 1.8 mg (p&lt;0.0001). The LS mean±SE weight change for PBO was -0.6±0.3 kg vs. -1.4±0.3 kg (p=ns) and -2.8±0.5 kg (p&lt;0.001) for 0.9 and 1.8 mg ZGN-1061. Dose-dependent fasting and postprandial glucose reductions were observed for ZGN-1061 (p&lt;0.05 vs. PBO); β-cell function and insulin sensitivity were improved with 1.8 mg ZGN-1061 (p&lt;0.05 vs. PBO). ZGN-1061 also improved triglycerides, hsCRP, adiponectin, and leptin (p&lt;0.05 vs. PBO). Across all ZGN-1061 treatment groups, adverse events (AEs) were primarily mild/moderate without any notable trends. The completion rate was 93% (163/175). Three subjects in ZGN-1061 groups withdrew due to AEs (sensory disturbance, 0.05 mg; upper abdominal pain, 0.9 mg; injection site urticaria, 1.8 mg). There were no reports of venous thrombosis or changes in thrombosis markers indicative of a thrombosis event. ZGN-1061 (1.8 mg) demonstrated statistically significant and clinically meaningful efficacy; the largest reductions in A1C and weight were observed at 12 weeks with no evidence of a waning effect and no notable safety signals.

Disclosure
T. Kim: Employee; Spouse/Partner; Celgene Corporation. Employee; Self; Zafgen, Inc. D. Zhuang: Employee; Self; Zafgen, Inc. T.L. Haugen: Employee; Self; Zafgen, Inc. D.D. Kim: Employee; Self; Zafgen, Inc. K. Taylor: Employee; Self; Zafgen, Inc.
211-LB: Developing "Gold Standard" Diagnoses for Type 1 and Type 2 Diabetes in Adults from Electronic Health Record Data
Authors: SUE KIRKMAN M. , NOONEY JENNIFER G. , BENOIT STEPHEN R. , BERGAMO KATHERINE A. , BULLARD KAI M. , CAMPIONE JOANNE R. , MARDON RUSS , PFAFF EMILY , ROLKA DEBORAH B. , SAYDAH SHARON 
Published: June 2019

Type 1 (T1D) and type 2 (T2D) diabetes are distinct diseases, but most federal surveys used to monitor diabetes prevalence have not included questions on diabetes type. To design and validate survey questions that will distinguish between T1D and T2D in adults, we developed a survey sample in whom we first determined a "gold standard" for diabetes type from review of electronic health record (EHR) data. From &gt;50,000 adult patients in the UNC Health Care System with diabetes, we assembled a sample of 2479 patients using a "strawman" definition based on diabetes-related diagnostic codes, laboratory results, and drugs. We stratified the sample using age, sex, race/ethnicity and crude diabetes type, oversampling T1D. For visits between 10/2014 and 9/2017, we collected clinical and demographic data including body mass index, diagnosis codes, medications, family history, and laboratory tests. We also abstracted chart notes, using trained personnel, to find additional information including diabetes duration and historical treatments. We created two models to determine diabetes type. The first was a decision tree, in which higher nodes sorted straightforward cases; lower nodes included more specific factors for those not categorized in higher nodes. The second was a weighted model, in which factors drawn from clinical or epidemiologic literature weighed weakly, moderately, or strongly in favor of or against each type of diabetes. The two models were 89% congruent for T1D and 96% congruent for T2D. An endocrinologist reviewed and determined type for the 10% of patients for which results of the two models were not congruent or for which neither was able to determine type. Overall, 70% of our sample has T2D, 27% has T1D, and 3% has indeterminate or other diabetes. We will use this sample to validate survey questions to determine type of diabetes. Such "gold standard" determinations may support validation of new and improved methods for measuring diabetes type among the adult population.

Disclosure
M. Kirkman: Research Support; Self; Bayer AG, Novo Nordisk A/S, Theracos, Inc. J.G. Nooney: None. S.R. Benoit: None. K.A. Bergamo: None. K.M. Bullard: None. J.R. Campione: None. R. Mardon: None. E. Pfaff: None. D.B. Rolka: None. S. Saydah: None.

Funding
Centers for Disease Control and Prevention
2156-P: Development of the Immune System in the Normal Rat Pancreas
Authors: GOLDEN THEA , WORTHEN G. SCOTT , SIMMONS REBECCA A. 
Published: June 2019

The role of resident immune cells in organogenesis has not been extensively studied in pancreas. We hypothesized that during the critical stage of ß-cell remodeling during the newborn period, immune cell populations would also change. Using flow cytometry and immunohistochemistry, we identified immune cell populations in the endocrine (islets) and exocrine portion of the pancreas at postnatal day 1, 7 and 14. When corrected for the expected increase in pancreatic weight, immune cell populations increase in the exocrine pancreas in males and females from P1 to P7 but not further at P14. Interestingly, in islets the number of immune cells further increases in males from P7 to P14. Macrophages, T cells, B cells, granulocytes and NK cells are present in islets and exocrine pancreas. Macrophages are the dominant population in islets (M: 47%, F: 47%) and exocrine (M:30%, F: 34%) pancreas. In islets, M2 macrophages are favored at P1. M1 macrophages dramatically decrease with age. In exocrine pancreas, M1 macrophages are initially favored, but with age the M2 population increases. T cells are also present in islets (M:6%, F:6%) and exocrine (M:8%, F: 6%) pancreas. Cd3+ Cd4- Cd8- is the dominant T cell population at P1 but decreases with age replaced by Cd3+ Cd4+ Cd8- cells. In islets from male, but not females, the number of T cells, specifically Cd4+ T cells, increases with age. B cells (Cd45Ra+) are present in islets (M:20%, F:19%) and exocrine (M:20%, F:25%) pancreas and numbers do not change with age. Neutrophils (HIS48hi Cd68) are also present in islets (M:6%, F:6%) and exocrine (M:13%, F: 10%) pancreas. NK cells are a minor cell population present at about 1% of total immune cells in male and female pancreas at P1. Interestingly, NK cells increase with age in females in islets and exocrine pancreas. These data demonstrate significant sex specific changes in the pancreas during the critical period of postnatal pancreas development suggesting a role for immune cells in normal postnatal development and function in the endocrine and exocrine pancreas.

Disclosure
T. Golden: None. G. Worthen: None. R.A. Simmons: None.

Funding
National Institutes of Health
2187-P: Gsα Deficiency in Pancreatic a Cells Leads to Enlarged Islets
Authors: TAIRA AKIKO , SUN HUI , LE CHRISTINA , GAVRILOVA OKSANA , CHEN MIN , WEINSTEIN LEE 
Published: June 2019

Pancreatic β-cell dysfunction leads to diabetes with reduced β-cell mass and impaired glucose-stimulated insulin secretion. The G protein α subunit Gsα couples receptors to generate cAMP, which mediates the insulinotropic effects of incretin hormones, such as GLP-1. We previously reported that β-cell-specific Gsα deficiency causes insulin-deficient diabetes due to reduced islet size and β-cell mass, and that mice with whole pancreatic Gsα deficiency develop insulin deficient diabetes and reduced β-cell mass, but also showed increased proliferation of α-cells, indicating that Gsα plays divergent roles in pancreatic α-and β-cell growth. In the present study, we generated mice with α-cell-specific Gsα deficiency (αGsKO) by mating Gsα-floxed mice with glucagon-cre mice and studied the metabolic consequences. Deletion of Gsα in α-cells did not affect growth, blood glucose, or serum insulin or glucagon levels. However, αGsKO mice displayed enlarged islet size of normal architecture with significant increases in both α- and β-cell numbers, accompanied with increased β-cell proliferation and reduced apoptosis. This increased β-cell proliferation could be detected as early as at 3 days after birth. Consistent with this, αGsKO mice showed increased insulin response to acute glucose loading (3mg/g i.p.), although they had unaltered glucose tolerance when given a lower dose of glucose (2 mg/g i.p.). The results of RT-PCR on pancreatic islets isolated from aged mice (9-10 months old) showed that expression of Maf B and Pax6, transcription factors required for β-cell development, tended to be increased; whereas cell cycle factors, such as Cyclin D1, D2, and CDK4, tended to be decreased. Taken together, our results show that Gsα/cAMP signaling pathway in pancreatic α-cells is critical for both α- and β-cell growth as well as for maintenance of β-cell mass.

Disclosure
A. Taira: None. H. Sun: None. C. Le: None. O. Gavrilova: None. M. Chen: None. L. Weinstein: None.

Funding
National Institutes of Health
2218-PUB: Increased Platelet Reactivity Is Associated with Inflammation and Arterial Stiffness in Subjects with Prediabetes
Authors: PINO ANTONINO DI , URBANO FRANCESCA , SCICALI ROBERTO , PIRO SALVATORE , RABUAZZO AGATA MARIA , PURRELLO FRANCESCO 
Published: June 2019

We investigated markers of platelet reactivity and low-grade inflammation, and their association with early markers of vascular disease in subjects with prediabetes and new onset type 2 diabetes (NODM).
Methods: 121 subjects without history of diabetes were stratified into 3 groups according to glycemic status: controls (n=41), prediabetes (n=42) and NODM (n=39). Platelet reactivity was evaluated as 11-dehydro thromboxane B2 urinary levels (TXB2), mean platelet volume (MPV) and platelet/lymphocytes ratio (PLR); cardiovascular risk was evaluated with arterial stiffness [pulse wave velocity (PWV), Augmentation pressure (AP), Subendocardial viability ratio (SEVR)] and intima media thickness (IMT).
Results: Subjects with prediabetes exhibited: higher TXB2 urinary levels (10.7 ± 4.8 vs. 6.4 ± 1.8 pg/mg creatinine, p&lt;0.05), PLR (143.7 ± 43 vs. 106.1 ± 26.7, p&lt;0.05) and lower MPV (8.7 ± 0.7 vs. 9.5 ± 1.1 fl, p&lt;0.05). Prediabetes showed higher fibrinogen and C creative protein (CRP) serum levels (333.2 ± 63 vs. 310.6 ± 58 mg/dL, p&lt;0.05; 0.34 (0.11-0.47) vs. 0.14 (0.08-0.27) mg/dL, p&lt;0.05, respectively). Subjects with prediabetes exhibited increased PWV, AP and IMT (8.1 ± 0.9 cm/sec vs. 7.5 ± 1.5, p&lt;0.05; 13.2 ± 9.5 mmHg vs. 11.2 ± 4.6, p&lt;0.05 and 710.2 ± 93.4 vs. 659 ± 93.1 μm, p&lt;0.05, respectively) and decreased SEVR (159.4 ± 11 vs. 171.8 ± 32.3, p&lt;0.05) compared with controls. No differences were found between prediabetes and NODM subjects regarding platelet reactivity and cardiovascular risk markers.TXB2 urinary levels were independently associated with hs-CRP, fibrinogen and HbA1c in multiple regression analysis. In simple regression analysis AP, PWV and SEVR showed a significant association with TXB2 urinary levels (r=0.32, p&lt;0.05, r=0.16, p&lt;0.05 and r=0.26 p&lt;0.05 respectively).
Conclusions: Subjects with prediabetes showed increased platelet reactivity and inflammation markers. These alterations were associated with early markers of cardiovascular disease.

Disclosure
A. Di Pino: None. F. Urbano: None. R. Scicali: None. S. Piro: None. A. Rabuazzo: None. F. Purrello: None.

Funding
University of Catania
2228-PUB: Meta-analysis of Recent Data from Several Independent Sources Suggests That Methylgloxal (MGO) Is Trapped by Dietary Flavonoids and Excreted in Urine as MGO-Flavonoid Adducts
Authors: SZWERGOLD BENJAMIN , MILLER CRAIG B. 
Published: June 2019

Methylglyoxal (MGO) is a reactive α-dicarbonyl produced as an unavoidable byproduct of glycolysis. Because it reacts readily with amino acids, nucleic acids and ethanolamine in phospholipids, MGO is deleterious to living systems and contributes significantly to diabetic complications. The primary defense against MGO is the glyoxalase system that oxidizes MGO to D-lactate. However, about 1% of MGO evades this mechanism and remains free to react with susceptible biomolecules. Consequently MGO, whose concentrations increase chronically in diabetics and temporarily in all individuals after meals, leads to increasing production of Advanced Glycation Endproducts (AGE) in diabetes and aging. Several recent papers suggest that residual MGO, can be trapped by scavengers with the resulting adduct safely removed via the urinary system One such report is Metformin, a drug that not only reduces blood glucose but is also beneficial for cardiovascular health and lowers mortality. In 2016 Kinsky et al. showed that Metformin reacts with MGO in diabetics and the adduct is eliminated in urine. This MGO-scavenging activity is also seen with some endogenous amine-containing compounds such as carnosine, taurine and creatine. In addition to metformin and other amine-based scavengers, there is solid evidence that phytochemicals, such as flavonoids in fruit and vegetables, are also MGO scavengers. Most recently Schalkwjik et al. have published data showing that modest ingestion of quercetin, reduces MGO in plasma by 10%. Prior to that, Sang et al. have shown that three other polyphenols: genistein, 6-shagaol and epicatechin, react with MGO in mice and are subsequently excreted as covalent adducts in urine. These studies can be interpreted in many ways, however the simplest interpretation may be that scavenging of MGO and its elimination may account, in part, for the widely reported positive effects of flavonoids on human health.

Disclosure
B. Szwergold: None. C.B. Miller: None.