bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Novel MicroRNA and Cell-Free DNA Biomarkers of Beta-Cell Death and Diabetes Progression
Authors: JOGLEKAR MUGDHA , FARR RYAN , WONG WILSON , ROTHER KRISTINA , JENKINS ALICIA , YAJNIK CHITTARANJAN S. , MA RONALD C. , CRAIG MARIA E. , JONES TIM , HARDIKAR ANAND ,   PREDICT T1D STUDY GROUP
Published: June 2018

Type 1 diabetes (T1D) is characterized by the loss of insulin-producing beta-cells. We currently lack diagnostic tools to measure T1D progression. Using systematic approaches involving unprejudiced discovery analyses in human tissues and clinical samples, we identify microRNAs that are: i) associated with insulin expression during embryonic development (N&gt;60); ii) predictive of and necessary for insulin transcription (N=698); and iii) dysregulated in individuals with (vs. without) T1D (N=200). Insulin cfDNA (assessed by ddPCR) and microRNA (assessed by TaqMan qPCR) biomarkers were measured in around; i) N=400 Australian T1D individuals; ii) N=30 longitudinal samples from children at risk of T1D; iii) N=100 clinical trial samples from individuals receiving IFN-a or Exenatide vs. placebo; iv) N=400 Hong Kong Chinese individuals with T1D; v) N=700 Danish individuals at diagnosis of T1D and vi) N=400 Asian Indian T1D subjects. Among N=600 Australian samples, we identified miRNAs (N=5) that were significantly increased in the circulation of T1D individuals (vs. controls), decreased (at least 2 Fold Change/FC, P&lt;0.05, N=7miRNAs) in T1DCx+ vs. T1DCx- (no T1D complications) or significantly increased (2 FC, P&lt;0.05, N=5) in T1D individuals with detectable C-peptide vs. non-detectable C-peptide. Our studies highlight the potential of circulating microRNAs and cfDNA in quantifying beta cell death before clinical diagnosis of T1D. These data demonstrate that microRNA/cfDNA signatures not only facilitate the potential prediction of diabetes progression, but can also help in stratifying individuals at risk of T1D as well as assess treatment efficacies in trials aiming to retard beta-cell death. We also present our preliminary analysis of cross-ethnic variation in these cfDNA/miRNA biomarkers and present ongoing/future studies to develop a diagnostic test for T1D prediction.

Disclosure
M. Joglekar: None. R. Farr: None. W. Wong: None. K. Rother: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. C.S. Yajnik: None. R.C. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd.. M.E. Craig: None. T. Jones: None. A. Hardikar: None.
Nonglycaemic Effects of Sitagliptin—Systematic Review and Meta-analysis of Six Published Randomised Controlled Clinical Trials
Authors: KHURANA GIRISH , GUPTA VIPUL , MAKKAR BRIJ M. , SHARMA JUGAL K. , KHURANA HARDIK , WADHWA NAVNEET 
Published: June 2018

We explorde the evidence for contemporary role of sitagliptin and evaluate for the non-glycemic effects of sitagliptin, through analysing the quantity and quality of the published evidences through the highest level of evidences ie: Randomised Controlled Clinical Trials (RCCTs). We searched Cochrane Library, pubmed- MEDLINE, IndMED databases to conduct a systematic review of published Randomised Controlled Clinical Trials (RCCTs) evaluating the contemporary role of sitaglitin for the non-glycemic effects. Only the trials with the comparator arms were included, studies evaluating glycemic effects of sitaglitin were excluded by appropriate Boolean operators. Only the RCCTs with healthy subjects and nondiabetics were included. Graph pad prism 7.0 version software and t-test was utilised for statistical analysis. 295 clinical trials published in last 10 years (20to 2017) were screened which yielded eight RCCTs, of which six met inclusion criteria, were compared for study design, patient characteristics, geography, impact factor of journals, intervention, duration and outcomes by using the appropriate statistical methods. Cumulatively, 269 patients (mean 45 patients, SD ± 64, SEM ± 26, minimum 6 patients, maximum 174 patients, 95% CI -23 to 112, p=0.147) have been evaluated across 6 RCCTs. Duration of RCCTs varies from 1 day to 1 year (n=2). Based on the impact factor of journals (mean 3.5, min 1.5, max 5.5, SD ± 1.4, SEM ± 0.59, 95% CI 2 to 5.1; p=0.0019), we formulated an indexed weightage score (mean 100, min 43.34, max 156.4, SD ± 40.9, SEM ± 16.7, 95% CI 57.to 142.9). Sitagliptin has systemic and adipose anti-inflammatory effects in cART-treated HIV+ adults with impaired glucose tolerance, improvement in the left and right ventricular ejection fraction changes from baseline to 6 months of follow-up is evident. Sitagliptin is useful in varied clinical conditions with non-glycemic effects which needs validation across global multicentric trials.

Disclosure
G. Khurana: None. V. Gupta: None. B.M. Makkar: None. J.K. Sharma: None. H. Khurana: None. N. Wadhwa: None.
Continued Follow-Up by a Hospital Diabetes Care Team Improves HbA1c at 1 Year after Elective Orthopedic Surgery
Authors: GARG RAJESH , BHANDARI SHREYA , REIN RAQUEL , MCDONNELL MARIE E. 
Published: June 2018

Hospitalization is considered an opportunity to improve long-term glycemic control in patients with poor glycemic control at the time of admission. Previous studies have shown an improvement in HbA1c at 3 months, followed by deterioration at 1 year after discharge. In a randomized controlled trial of patients with high HbA1c (≥8%) undergoing an elective surgery, we found that continued care (CC) by a hospital diabetes care team as compared to the usual care (UC) had no significant effect on HbA1c at 1 year after discharge. Here, we present a secondary analysis of these data to evaluate the effect of type of surgery on our outcomes. We hypothesized that patients undergoing an orthopedic surgery may have a higher reduction in HbA1c in response to our intervention. Out of 151 patients, 35 patients had undergone an orthopedic surgery, 18 in the CC group and 17 in the UC group. Baseline characteristics and clinical outcomes are shown in Table 1. Patients undergoing an orthopedic surgery had a significant reduction in HbA1c in the CC group while those in the UC group had no change at one year. In contrast, patients undergoing a non-orthopedic elective surgery had similar reduction in HbA1c in the CC and UC groups. These data suggest that the effect of intervention to improve long-term glycemic control after discharge from the hospital is affected by the hospital diagnosis.Table 1. Patient characteristics and clinical outcomes.Orthopedic SurgeryNon-orthopedic SurgeryVariableCC groupN=18UC groupN=17P valueCC groupN=59UC groupN=57P valueAge, years67±764±110.3764±1062±100.28Female Gender6 (33)4 (23)0.5129 (49)21 (37)0.18White Race18 (100)15 (88)0.1355 (93)55 (96)0.40Duration of diabetes, years12.4±10.612.8±6.70.9111.2±8.212.2±9.80.55BMI, kg/m234.7±8.638.0±13.00.3935.2±8.533.5±8.10.31Serum Creatinine, mg/dL0.86±0.150.88±0.240.851.1±0.61.1±0.50.90eGFR, mL/min58.5±3.459.3±5.40.8855.0±11.055.5±9.70.82Baseline HbA1c8.5±0.48.9±0.70.039.0±1.19.2±1.20.25HbA1c at 1-year after discharge7.8±1.08.9±1.30.018.3±1.48.4±1.50.76Change in HbA1c at 1-year from baseline0.7±0.90.0±1.20.050.7±1.50.9±1.60.56Data are presented as mean with SD for continuous variables and N with % for categorical variables.

Disclosure
R. Garg: None. S. Bhandari: None. R. Rein: None. M.E. McDonnell: None.
Emergency Department Access in Diabetic Patients
Authors: PIFFER SILVANO 
Published: June 2018

Introduction: Access of diabetic patients to Emergency Departments (ED) is an indicator of the filtering capabilities of territorial services.
Aims: To analyze the access to ED of the Trento province (540.000 inhabitants-north-east Italy) by diabetic patients in the period 2012-2016.
Methods: Accesses of diabetics patients (ICDIXCM 250-251), were analyzed from the Database of ED considering year, gender, age class, month and week day, citizenship, way of arrival, triage score, area (urban/rural) of the residents cases, the proportion of hypoglycemia accesses, hospitalization.
Results: A total of 2839 diabetic patients accessed to the ED in the study period (567/year), 70% were type 2. The time trend is slightly decreasing. Males are 54%; the age group 0-14:6%, 15-29 5%, 30+years 89%. Males median age is 61 y, Females median age 66 y. Foreigners represent 10% of the cases. Most subjects arrived by ambulance/helicopter (44%); 2,7% were in red code. There were no differences in relation to the month or day of the week; 52.7% are hospitalized. The ED access rate is 7.7/10.000/year for urban and 10/10.000/year for rural area residents (p&lt;0,01). Hypoglycemia occur in 28% of total access of diabetics without any change over time; 60% were in type 1. There were no differences in relation to gender and age-class, compared to general cases and no change in relation to the month or day of the week or geographical area for resident cases as well. Patients with hypoglycemia at access are more serious considering that 76% accessed by ambulance or helicopter and 4.2% were in red code (p&lt;0,001). The proportion of hospitalized cases is 30,2%, lower than the general case series.
Conclusions: The access of diabetic patients to the ED of the province of Trento does not change over time. The proportion of patients with hypoglycemia is considerable, with a higher prevalence in case of type 1 diabetes. It does not change over time and requires substantial costs for the transfer to health structures.

Disclosure
S. Piffer: None.
Evaluating T1DM Patient Experience Using the Patient Assessment of Chronic Illness Care Survey
Authors: MORRISEY ROBIN , KACZMAR ELIZABETH , TSIMIKAS ALEXIA , ARNOLD FRANCES M. , CLARK TAYLOR , MCCALLUM JAMES , FORTMANN ADDIE L. 
Published: June 2018

Aligning diabetes care with components of the Chronic Care Model (CCM) facilitates productive interactions between a proactive care team and an informed, activated patient, allows the care plan to be individualized, and can improve care and outcomes. The Patient Assessment of Chronic Illness Care (PACIC) survey assesses patient experience with CCM-based healthcare delivery components. In the Division of Diabetes and Endocrinology at Scripps Health, a large integrated health system in San Diego, CA, patients with T1DM have access to an interdisciplinary team of clinicians who provide care, education, and ongoing support. Guided by the CCM, an interactive care delivery system involving the endocrinologist, PCP, diabetes educator, RD, behavioral specialist and the patient was implemented to facilitate proactive and productive care but some interactions remained isolated. Between June and August 2017, the PACIC survey was administered by research assistants to N=47 adults with T1DM who have received care in the Division for at least 6 months. Overall, patients reported high satisfaction with care (M=4.77 out of 5; SD=0.56). Results also indicated high ratings for specific CCM elements, including Patient Activation, Delivery System Design/Decision Support, and Self-Management Support (M=4.29-4.55). Lower ratings were observed for Follow-Up/Coordination (M=3.81; SD=1.01), suggesting a need for enhanced post-visit contact with patients, referrals to community programs, dietitians, and counselors, and discussion of specialist appointments. In line with the Institute for Healthcare Improvement’s Triple Aim focused on improving the health of populations through optimization of health system performance, an RN with specialized experience in T1DM was added to the team as the Diabetes Care Manager to assist with follow-up and care coordination. The PACIC will be re-administered after 6 months to determine the impact on patient perceptions of follow-up/coordination between visits.

Disclosure
R. Morrisey: None. E. Kaczmar: None. A. Tsimikas: None. F.M. Arnold: None. T. Clark: None. J. McCallum: None. A.L. Fortmann: None.
CB4211 Is a Potential Treatment for Metabolic Diseases with a Novel Mechanism of Action—Sensitization of the Insulin Receptor
Authors: GRINDSTAFF KENT , MAGNAN REMI , SHANG ROBIN , STENGER EMILY , HOLLAND JENNA S. , PEREZ-TILVE DIEGO , CUNDY KENNETH C. 
Published: June 2018

Metabolic dysfunction and insulin resistance are common underlying factors in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and many age-related diseases, including obesity and type 2 diabetes. CB4211 is a novel peptide analog of MOTS-c, a mitochondrially encoded peptide with a potential role in metabolic homeostasis. CB4211 reduces free fatty acid release from cultured adipocytes, improves NAFLD activity score (NAS) in STAM® mice, and selectively decreases fat mass in DIO mice. We investigated the mechanism of action (MOA) of CB4211 in regulating fatty acid metabolism, glucose homeostasis, and insulin sensitivity. CB4211 potentiated insulin mediated inhibition of lipolysis in isoproterenol stimulated adipocyte cultures without changing maximal response, while CB4211 alone had no effect. Inhibitors of IR auto-phosphorylation (GSK183705A) or downstream PI3K/Akt signaling pathway components (wortmannin, Akti-1/2) abolished the antilipolytic effects of insulin alone and in combination with CB4211. Further supporting sensitization of insulin signaling, CB4211 enhanced insulin mediated phosphorylation of IR, IRS-1, and Akt, without affecting IGF mediated phosphorylation of IGF-1R. Consistent with activity through IR, CB4211 potentiated insulin induced reduction in glucose production in H4-IIE cells. The acute in vivo effect of CB4211 on insulin tolerance was determined in fasted DIO mice. Administration of CB4211 with insulin enhanced insulin sensitivity, prolonging the reduction in blood glucose levels compared to insulin alone.
In conclusion, CB4211 potentiates insulin effects on fatty acid metabolism and glucose homeostasis by acting at the level of IR. The observed MOA of CB4211 therefore supports its potential utility for treatment of NASH, obesity, type 2 diabetes, and other metabolic disorders.

Disclosure
K. Grindstaff: Employee; Self; CohBar, Inc.. R. Magnan: None. R. Shang: Employee; Self; CohBar Inc. E. Stenger: Employee; Self; CohBar, Inc.. J.S. Holland: None. D. Perez-Tilve: Research Support; Self; Novo Nordisk A/S, Cohbar. K.C. Cundy: Employee; Self; CohBar, Inc.. Stock/Shareholder; Self; CohBar, Inc..
Pancreas Volume Declines over the First Year after Diagnosis with Type 1 Diabetes (T1D)
Authors: VIROSTKO JACK , HILMES MELISSA A. , WILLIAMS JONATHAN M. , WRIGHT JORDAN , DU LIPING , KANG HAKMOOK , RUSSELL WILLIAM E. , MOORE DANIEL J. , POWERS ALVIN C. 
Published: June 2018

The pancreas is smaller in individuals with T1D, but it is unclear if these individuals are born with a smaller pancreas or whether their pancreatic volume declines as part of disease progression. To determine the dynamics of pancreas volume in new-onset T1D, we performed longitudinal magnetic resonance imaging (MRI) of the pancreas in individuals with recent-onset T1D (n = 51, mean age 13.7 y, range 8-24 y) within the first 100 days after diagnosis (mean 67 days), six months after diagnosis, and one year post diagnosis. In agreement with and extension of our results presented at 2017 ADA Scientific Sessions, we found that at disease onset, young individuals with T1D had a smaller pancreas (median volume = 29.6 ml) than similarly aged controls (median volume = 49.6 ml, n = 51, p &lt; 0.001). Pancreas volume was lower in T1D individuals when normalized by subject weight (p &lt; 0.001), as well as when adjusted for age, gender and body mass index (p &lt; 0.001). Longitudinal measurements of pancreas volume increased in controls over the year, corresponding with adolescent growth, but pancreas volume declined over the first year after T1D diagnosis (p &lt; 0.001). Pancreas volume measurements normalized by body weight were stable in controls, but declined in subjects with T1D (p &lt; 0.001). We also performed MRI in 14 individuals enrolled in TrialNet with multiple autoantibodies portending the development of T1D, and found that pancreas volume was similar to controls (median volume = 59.1 ml), but significantly greater than the T1D cohort (p &lt; 0.001). To interrogate microstructural changes in the pancreas, we performed diffusion-weighted MRI and found that individuals with recent-onset T1D had a higher apparent diffusion coefficient (p = 0.023), indicating reduced restrictions on water diffusion in the pancreas in T1D. These results indicate the existence of ongoing pancreatic atrophy during the first year after diagnosis with T1D which may be reflected by microstructural changes in the pancreas.

Disclosure
J. Virostko: None. M.A. Hilmes: None. J.M. Williams: None. J. Wright: None. L. Du: None. H. Kang: None. W.E. Russell: None. D.J. Moore: None. A.C. Powers: None.
Comparison of Different Anthropometric Indices for Identifying Insulin Resistance in Two Indigenous Communities Living at Different Altitudes
Authors: HIRSCHLER VALERIA ,   SAN ANTONIO DE LOS COBRES STUDY GROUP
Published: June 2018

Background: Anthropometric measurements might be valuable tools for identifying children at risk of developing type 2 diabetes.
Objective: To compare the abilities of waist circumference (WC), BMI, and WC/height to identify children with insulin resistance in two indigenous communities from similar ethnic backgrounds, but living at different altitudes.
Methods: Cross-sectional study of 142 (66 f) indigenous school children (4-14 y) from San Antonio de los Cobres (SAC), 3,750 m above sea level, and 171 (86 f) from Chicoana (CH), 1,400 m, were assessed for weight, height, WC, glucose, and insulin levels. ROC curves were generated for BMI, WC, and WC/height, with HOMA-IR&gt;III quartile as the dichotomous variable in both SAC and CH.
Results: There was not a significant difference in age between SAC and CH children (8. 9 vs. 9.3 years, respectively). However, SAC had a significantly lower z-BMI (-0.16 vs. 0.68), WC (59.8 vs. 67.3 cm), and WC/height (45.9 vs. 48.7) than CH. The prevalence of overweight and obesity was significantly lower in SAC than in CH (9.2% vs. 41.8%). Significant univariate association (P&lt;0.05) was found between WC with insulin (r = 0.58), and HOMA-IR (r = 0.40); BMI with insulin (r = 0.51), and HOMA-IR (r = 0.37); and WC/height with insulin (r = 0.33), and HOMA-IR (r = 0.24). The areas under the ROC curve in SAC children were as following: WC= 0.81 ± 0.04 (95% CI 0.72-0.90), BMI= 0.80 ± 0.(95% CI 0.70-0.90), and WC/height= 0.71 ± 0.(95% CI 0.59-0.81). The areas under the ROC curve in CH children were as following: WC= 0.75 ± 0.(95% CI 0.66-0.85), BMI= 0.76 ± 0.(95% CI 0.67-0.85), and WC/height= 0.67 ± 0.(95% CI 0.56-0.79).
Conclusion: The prevalence of obesity was significantly lower in SAC than in CH probably due to high altitude-induced chronic hypoxia. However, WC and BMI were acceptable indicators for insulin resistance in both communities living at different altitudes; whereas WC/height was a fair indicator for insulin resistance.

Disclosure
V. Hirschler: None.
Are Black Pediatric Patients with Type 1 Diabetes (T1D) Prescribed Higher Doses of Insulin than White Patients?
Authors: CHALEW STUART , GOMEZ RICARDO , HEMPE JAMES M. 
Published: June 2018

Black youth with T1D have been noted to have higher HbA1c’s, less frequent monitoring of capillary glucose and higher reported occurrence of hypoglycemia compared to white patients. We hypothesized that this combination of factors would be associated with higher prescribed doses of insulin in black patients compared to whites. A retrospective analysis was performed on data collected from patients at the Children’s Diabetes Center, New Orleans, LA who participated in a study of racial differences in hemoglobin glycation. Patients self-identified as either black or white and were under the clinical care of several different attending diabetologists. The influence of race on total daily prescribed dose of insulin per kg body weight (TDDI), was evaluated in a general linear model adjusted for HbA1c, insulin delivery method, gender, and chronologic age as well as the interactive effect of race and HbA1c. Hemoglobin Glycation Index (HGI) was also calculated and substituted in the model for HbA1c. The population studied consisted of 33 (19F, 14M) black patients and 52 (22F,30 M)whites. Average age was 14.0±3.6 years and duration of diabetes 5.7±3.9 years. As previously reported from this population blacks had higher HbA1c even after adjustment for age and mean blood glucose level (MBG). Mean TDDI was 0.89±0.33 units/kg/d. TDDI was highly correlated with both HbA1c (r=0.40,p&lt;0.0001)and MBG (r=0.43,p&lt;0.0001) before adjustment. In the linear model TDDI was significantly associated with HbA1c (p=0.0003) but not race, age, gender or insulin delivery mode. There was no interactive effect of race and HbA1c. There was no significant effect of HGI. We found that prescribed TDDI increased with increasing HbA1c in both black and white patients. This preliminary study suggests that prescribing physicians increase insulin dosage in an attempt to bring HbA1c to goal for their patients but do not vary dose based on ethnicity.

Disclosure
S. Chalew: None. R. Gomez: None. J.M. Hempe: None.
Maternal and Neonatal Outcomes in Pregnancy Complicated by Type 1 Diabetes Mellitus
Authors: BI YAN , XU QIANYUE , LU JING , HU JUN , LI JINGJING , GE ZHIJUAN , ZHU DALONG 
Published: June 2018

Aims: To assess the risk of adverse pregnancy outcomes in pre-gestational type 1 diabetes mellitus (T1DM) as compared to gestational diabetes mellitus (GDM) or pregnancy without diabetes and examine the effect of glycemic control in late pregnancy on these outcomes in T1DM.
Methods: This retrospective study comprised of 61 cases of pre-gestational T1DM, 244 cases of GDM, and 244 control pregnancies. Data regarding demographics, obstetric and perinatal outcomes were extracted from the hospital discharge database.
Result: Compared to the pregnancies without diabetes, women with T1DM had higher risks of polyhydramnios [odds ratio(OR) 4.5] and cesarean section (OR 21.2), while the odd ratios for these outcomes in GDM were 2.4 and 1.9, respectively. Preeclampsia, preterm delivery, preterm premature rupture of membranes and postpartum hemorrhage occurred more in women with T1DM than GDM. Severe perinatal outcomes including stillbirth and congenital malformations were reported in T1DM only. Moreover, women with T1DM were more likely to present abnormal fetal growth, either low birthweight (OR 4.0) or large for gestational age (OR 5.0). Severe perinatal outcomes including stillbirth and congenital malformations were reported in T1DM only. Poorly controlled HbA1c in late pregnancy was significantly associated with an increased risk of preterm birth (OR 2.01) in T1DM.
Conclusions: Women with T1DM have considerably increased risks of adverse pregnancy outcomes, which appear more critical than the contemporary outcomes in women with GDM. Thus, a specific routine is required for pregnancy in T1DM to improve the glycemic control and obstetric care.

Disclosure
Y. Bi: None. Q. Xu: None. J. Lu: None. J. Hu: None. J. Li: None. Z. Ge: None. D. Zhu: None.