bluuebunny/crossref_metadata_2025_split huggingface dataset:
127-OR: Changes in Adipocyte-Derived Exosomal MicroRNAs May Play a Role in the Progression from Obese Normoglycemia to Hyperglycemia/Diabetes
Authors: MAGGE SHEELA N. , FREISHTAT ROBERT J. 
Published: June 2019

We previously showed that visceral adipocyte-derived exosomal microRNA content is pathologically altered in obesity to impair insulin receptor signaling. However, why some obese youth (± insulin resistance) remain normoglycemic, while others progress to hyperglycemia, is not fully understood.
We hypothesize that compared to obese normoglycemic youth (ON), circulating adipocyte-derived exosomes from obese hyperglycemic youth (OH) are enriched for microRNAs targeting carbohydrate metabolism and this association is modified by the amount of visceral fat (VFAT).
We conducted a cross-sectional analysis of 55 obese pubertal adolescents (12-17 years), who underwent OGTT, whole body DXA, and serum adipocyte-derived exosomal microRNA assays. Univariate and regression analyses compared ON and OH groups. MicroRNA profiles were evaluated via ANCOVA and ANOVA.
ON (n=32) and OH (n=23) groups were similar for sex, age, race, pubertal stage, BMI, and fat mass (FM). However, OH had increased VFAT compared to ON (88.1±24.6cm2 vs. 71.4±21.6, p=0.01). Between OH and ON, 33 known mature human microRNAs were differentially expressed (p&lt;0.01) in circulating adipocyte-derived exosomes. Once filtered for microRNAs with experimentally confirmed or highly conserved predicted targets, 14 microRNAs remained, which collectively putatively target 2331 mRNAs. These mRNAs were further filtered for association with VFAT (p&lt;0.05), leaving 1304 mRNAs. These mRNAs were enriched for 179 canonical pathways (p&lt;0.05). Notable carbohydrate metabolism targets include activation of PI3K/AKT (z=+1.4; 19/127 elements) and STAT3 signaling (z=+3.3; 21/132 elements).
Although similar to ON for BMI and FM, OH show changes in adipocyte-derived exosomal microRNAs targeting carbohydrate metabolism that are associated with increased VFAT. Circulating visceral adipocyte-derived exosomal microRNAs may help drive the transition from obese normoglycemia to hyperglycemia.

Disclosure
S.N. Magge: None. R.J. Freishtat: Stock/Shareholder; Self; Adipomics, Inc.

Funding
National Institutes of Health
1274-P: Impact of Type 1 Known Diabetes (T1D) Risk on Health-Care Utilization at Diagnosis
Authors: FROHNERT BRIGITTE I. , MANSEAU KATHERINE , ALONSO GUY T. 
Published: June 2019

Despite increasing incidence of T1D worldwide, most newly-diagnosed individuals have no family history. Many experience delay in diagnosis, resulting in &gt;30% of children with new-onset T1D presenting in diabetic ketoacidosis (DKA). Screening for T1D is currently restricted to the research setting. We sought to describe differences in health care utilization at T1D diagnosis in known at-risk patients identified through research studies compared to matched controls. Cases (n=39) were known islet autoantibody positive children (0-19 y) diagnosed with T1D between 2010-2017 at the Barbara Davis Center. Controls were matched 3:1 by dates of birth and diagnosis from community-diagnosed patients (n=117). The Colorado All Payer’s Claims Database was used to count diagnoses, procedures, and healthcare claims in the year before and following diagnosis. Continuous variables were compared using t-test or Wilcoxon rank sum test, categorical by chi-square. There was no difference between cases and controls for age of onset (9.6 +/- 3.6 vs. 9.6 +/- 3.5 y p=1.0) or gender (54 vs. 46% male, p=1.0); however, cases had higher rate of private insurance (72 vs. 49%, p=.01) and higher percentage of non-Hispanic whites (87 vs. 65%, p=.008). At diagnosis with T1D, cases had lower HbA1c (6.7 [6.1, 8.1]% vs. 12.1 [10.5, 14.1]%, p&lt;.0001) and rate of DKA (5 vs. 57%, p&lt;.0001). In the year prior to diagnosis, there were no differences in the number of claims, procedures, diagnoses, or medications. In contrast, in the year of diagnosis, cases had fewer emergency room claims (0 [0, 2] vs. 2 [0, 4], p&lt;.0001), total claims (20 [9, 30] vs. 33 [19, 48], p&lt;.0001), procedures (31 [16, 43] vs. 52 [28, 77] p&lt;.0001) and unique diagnoses (7 [4, 10] vs. 12 [7, 19] p=.0003), while there was no difference in number of medications (8 [4, 10] vs10 [7, 13] p=.07).
In conclusion, antibody-screened patients had lower healthcare utilization in year of diagnosis. Further study, including cost estimation, may lend insight into benefits of T1D screening programs.

Disclosure
B.I. Frohnert: None. K. Manseau: None. G.T. Alonso: None.

Funding
JDRF (5-ECR-2017-388-A-N)
1278-P: Innovative Quality Improvement Medical Education Program for General Practitioners in Japan
Authors: MITRI JOANNA , GABBAY ROBERT A. , EL SAYED NUHA ALI , HSU WILLIAM C. , HEINE ROBERT J. 
Published: June 2019

Only around 30% of patients with diabetes meet targets for A1c (A), blood pressure (B) or lipid (C) and 14% meet targets for ABC and non-smoking. Following a survey among general practitioners (GPs) on educational needs, an education program was designed to improve the performance of the GP and the quality of diabetes care in Japan. GPs and nurses learned at a live workshop how to create a plan-do-study-act cycle and established an improvement plan to implement. In a 2nd workshop, held 3 months later, GPs examined whether the improvement plan was carried out and established strategies for further improvement. A, B, C and smoking status were provided by each participant on up to 25 patients pre and post intervention. Goals were: A1c &lt;7%, BP &lt;130/80 mmHg, LDL-C&lt; 120mg/dl (based on Japan Diabetes Society). The proportions of patients in each of the groups at goal pre and post program were compared using chi-square.
Results: 2 cohorts of GPs provided data on 648 patients. The intervention was associated with an increased proportion of patients at goal in the data provided at the post-intervention workshop (Table 1) and an increased odds ratio to achieve goals (Table 2). This innovative program focused on collaboration and quality improvement strategies, has the potential to enhance the quality of diabetes care in Japan. These preliminary data could serve as a platform for the design of broader programs to implement in the GP community.

Disclosure
J. Mitri: Research Support; Spouse/Partner; AbbVie Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; Kowa Pharmaceutical Europe Co. Ltd., National Dairy Council. Research Support; Spouse/Partner; Takeda Pharmaceutical Company Limited. Other Relationship; Self; National Dairy Council. R.A. Gabbay: Advisory Panel; Self; HealthReveal, Hygieia, Lark, Onduo LLC. Consultant; Self; Sanofi. N. El Sayed: None. W.C. Hsu: Consultant; Self; Onduo LLC. R.J. Heine: Employee; Self; Eli Lilly and Company.
128-LB: Insulin Glargine 300 U/mL (Gla-300) vs. First-Generation Basal Insulins (BI) in Insulin-Naïve Type 2 Diabetes (T2D) Patients (Pts) With and Without Cardiovascular Disease (CVD): Outcomes of the Randomized Pragmatic Real-Life Clinical Trial ACHIEVE Control
Authors: FRIAS JUAN P. , EVENOU PIERRE , DALTON DAVID , DUNGAN KATHLEEN M. 
Published: June 2019

ACHIEVE Control demonstrated superiority of Gla-300 vs. standard of care (SOC) BIs (glargine 100 U/mL and detemir), with a significantly greater proportion of insulin-naive T2D pts treated with Gla-300 achieving the composite primary endpoint of individualized HEDIS A1C targets at 6 months without severe and/or symptomatic documented hypoglycemia (blood glucose [BG] ≤70 mg/dL). Here we report outcomes in pts with and without CVD at baseline (BL). Characteristics at BL were generally well balanced between treatments, with a potential difference in GLP-1 receptor agonist use in CVD pts. In pts without CVD, outcomes consistently favored Gla-300 (Table). In CVD pts, composite endpoint attainment at 12 months was similar with Gla-300 and SOC-BI, while avoidance of hypoglycemia, especially serious hypoglycemia (BG &lt;54 mg/dL), showed a trend favoring Gla-300 (Table); changes in A1C from BL to 12 months with Gla-300 and SOC-BI were similar (LS mean difference [95% CI] 0.12% [-0.12 to 0.35]; p=0.34). The results of this analysis are promising and warrant further exploration of the possibility that the more stable action profile of Gla-300 translates to T2D patients with CVD experiencing serious hypoglycemia less often with Gla-300 than first-generation BIs.

Disclosure
J.P. Frias: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Sanofi. Consultant; Self; Echosens, Genentech, Inc., Johnson & Johnson Diabetes Institute, Novo Nordisk Inc., Zafgen, Inc. Research Support; Self; AbbVie Inc., Akcea Therapeutics, Allergan, Amgen Inc., AstraZeneca, Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Cirius Therapeutics, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Enanta Pharmaceuticals, Inc., GENFIT, Intarcia Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Oramed Pharmaceuticals, Pfizer Inc., Sanofi, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc. Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. P. Evenou: Employee; Self; Sanofi US. D. Dalton: Employee; Self; Sanofi US. K.M. Dungan: Advisory Panel; Self; Eli Lilly and Company, Elsevier, Sanofi-Aventis. Research Support; Self; Eli Lilly and Company, GlaxoSmithKline plc., Novo Nordisk Inc., Sanofi-Aventis, Viacyte. Other Relationship; Self; DKBmed, UpToDate.

Funding
Sanofi US
128-OR: Clustering of Metabolomics, Clinical Biomarkers, and Ectopic Liver Fat in Children/Adolescents: An Integrated Network Analysis
Authors: CIOFFI CATHERINE E. , VENKAT NARAYAN K.M. , UPPAL KARAN , PIERPONT BRIDGET , CAPRIO SONIA , SANTORO NICOLA , VOS MIRIAM B. 
Published: June 2019

Hepatic fat accumulation is often associated with cardiometabolic disease (CMD) risk factors in children, but the mechanism is unclear. We measured untargeted metabolomics in plasma from 219 obese children/adolescents with (37%) and without (63%) fatty liver assessed by magnetic resonance imaging. An integrative network analysis, which involved several steps including pairwise association analyses and a multilevel community detection algorithm, was performed using xMWAS to explore clustering patterns of metabolomics, clinical biomarkers, and abdominal and hepatic fat. This identified 3 communities consisting of significantly correlated variables (|r| &gt; 0.4, p &lt; 0.05) as depicted in Figure 1. Notably, the community featuring hepatic fat clustered with several CMD risk factors, including insulin resistance and dyslipidemia. Pathway analyses of the metabolites in this cluster using mummichog showed enrichment in carnitine shuttle and glycerophospholipid metabolism (p&lt;0.05), including several acyl-carnitine species and linoleic acid. Other metabolites in the cluster were the aromatic and branched chain amino acids tyrosine and isoleucine, respectively. These results suggest that hepatic fat is more closely correlated with CMD risk factors compared to other abdominal fat depots and may offer insights into biological mechanisms that underlie this finding.

Disclosure
C.E. Cioffi: None. K. Narayan: None. K. Uppal: None. B. Pierpont: None. S. Caprio: None. N. Santoro: None. M.B. Vos: Advisory Panel; Self; Intercept Pharmaceuticals, Inc. Board Member; Self; TARGET PharmaSolutions. Consultant; Self; Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Shire. Research Support; Self; Gemphire Therapeutics Inc., Immuron, TARGET PharmaSolutions.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK111038, T32DK007734, P30DK111024); Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD028016, R21HD089056)
1283-P: PTS Diagnostics A1CNow+: A Valuable Tool in a Value-Based World
Authors: SZABLOWSKI CARRIE J. , DAVIS KADDY , ANDERSON JAMES H. 
Published: June 2019

Background: Value-based medicine is a new healthcare model to shift physician focus from the quantity of services and revenue generated to quality and value of healthcare provided. The basis for this model is the idea of the right care for the right patient in the right environment at the right time, also known as Patient Centered Medical Home (PCMH). Point-of-care A1C testing can maximize patient and provider engagement by obtaining the results in real-time which allows for effective communication, healthy discussions, and improved healthcare. This study evaluated the accuracy of A1CNow+ as a tool to assist with PCMH for diabetes management.
Method: Blood was collected from PTS employees. A1C values ranged from 4.4 - 12.4% A1C for a total of 90 data points. Capillary blood was tested on the PTS Diagnostics A1CNow+ system while venous blood was tested at PTS Diagnostics on the Tosoh G8 and Roche Cobas® Integra® 400 Plus as clinical laboratory (CL) comparators. For reference, venous blood was tested at LabCorp on the Roche Cobas c513. Deming regression analysis was used to evaluate accuracy and paired differences to measure bias. Clinical risk was assessed using A1C clinical cut points of &lt; 5.7, 5.7 - 6.4, and ≥ 6.5% A1C. Fisher’s exact test was used to assess differences amongst methods.
Results: Average paired percent bias was -0.83% for the A1CNow+ and +0.17% for the CL analyzers. Slopes were 0.92 and 0.93 (p=0.35) and intercepts were 0.42 and 0.44 (p=0.098) for the A1CNow+ and CL, respectively. Clinical risk agreement was 89% for A1CNow+ and 97% for CL analyzers (p=0.08).
Conclusion: The A1CNow+ was shown to be as accurate as the clinical lab in measuring A1C. Risk analysis showed no statistical difference between the CL and A1CNow+ in classifying A1C clinical cut points. The A1CNow+ is a valuable tool to help meet the goals of the Quadruple Aim which seeks to improve the health of the population, improve the patient experience of care, improve the provider experience of giving care, and reduce the cost of healthcare in a value-based world.

Disclosure
C.J. Szablowski: Employee; Self; PTS Diagnostics. K. Davis: None. J.H. Anderson: Board Member; Self; Generex Biotechnology Corp., VoCare. Consultant; Self; Know Labs. Employee; Self; PTS Diagnostics. Other Relationship; Self; Lilly Diabetes.
1289-P: The Impact of Medication Interventions in a Clinical Pharmacy Specialist Medication Management Clinic on A1C Reduction and Glycemic Goals
Authors: DESKO LAUREN 
Published: June 2019

Background: To identify the effects of medication interventions made in diabetic patients in a clinical pharmacy specialist (CPS) medication management clinic on A1C reduction and achievement of glycemic goals in a Department of Veterans Affairs (VA) clinic setting.
Methods: A total of 61 new patients referred to the CPS medication management clinic between October 1, 2017, and March 31, 2018, were evaluated. The number of medication interventions at the initial CPS visit, and all visits in the first 6 months of clinic enrollment, were assessed. The patient’s baseline A1C was assessed prior to enrollment in clinic, followed by re-assessment 3 and 6 months later. The number of patient visits during the 6-month period was individualized.
Results: A total of 53 patients were included. The average baseline A1C was 9.19% (range of 5.2% to 14%). The average A1C at 3 months was 7.96%, and the average A1C at 6 months was 7.29%. The average change in A1C was -1.3% in 3 months and -2.27% in 6 months. The CPS made a median of 2 medication interventions at the initial visit (range of 0 to 7), including a median of 2 diabetes medication interventions (range of 0 to 5). The CPS made a total of 259 medication interventions during the 6-month period, with a median of 5 medication interventions per patient (range of 1 to 11). The CPS had 243 total patient visits during the 6-month period, with a median of 4 visits per patient (range of 1 to 12). Seventeen patients (32%) had achieved A1C goal at 3 months, and twenty-five patients (47%) had achieved A1C goal at 6 months. Forty-two patients (79%) had achieved appropriate statin use at 3 months.
Conclusions: This project demonstrates how the CPS medication management clinic achieved substantial A1C reduction within the first 6 months of patient referral, as well as positive impacts on glycemic goals. The CPS in the VA is uniquely poised to positively impact patient outcomes, and this practice model has potential for future adaptation to other settings.

Disclosure
L. Desko: None.
1291-P: Type 1 Diabetes Patients Can Achieve Stable Glycemic Control with Routine Clinical Visits: Results of a Novel Integrated Outpatient Diabetes Management System
Authors: XIE YUTING , LI XIA , LIU FANG , ZHOU ZHIGUANG 
Published: June 2019

Objective: To describe a novel integrated outpatient diabetes management system set up in China. To evaluate its effectiveness in type 1 diabetes (T1D) control.
Methods: A multiple disciplinary clinic, assembling a diabetologist, a diabetes education nurse, a dietitian, an ophthalmologist team, a psychiatrist, and a physiotherapist was set up to evaluate patient’s characteristics. The integrated outpatient care was carried out at baseline and every 3-6 months based on patient’s condition with an individualized principle tailored to meet each patient’s needs. Cross sectional data from type 1 diabetes patients attending the clinic through 2015 to 2018 were compared. Outcome measures included HbA1c levels, percentage of patients within HbA1c targets, quality of life score, and diabetes self-management score.
Results: A total of 749 T1D patients (380 children and 369 adults) attended the clinic within three years. Mean HbA1c level at baseline was 9.21±2.66%, with 93 (30.2%) children and 87 (26.4%) adults achieving HbA1c targets. 285 (44.7%) patients had an HbA1c level over 9%. Mean HbA1c declined by 1.44% - 1.85% within routine follow-up visits and remained stable at 7.36%-7.77% for up to three years (p&lt;0.01). Percentage of children achieving HbA1c targets (&lt;7.5%) increased to 67.3%. Percentage of adults achieving HbA1c targets (&lt;7.0%) increased to 63.6%. Mean scores for self-management skills and quality of life increased significantly (p&lt;0.05).
Conclusions: This new outpatient management system can significantly improve the overall diabetes control of T1D patients with sustainable influences. It is a dramatic improvement on T1D management over conventional clinics in China, and provides insights into a more rounded diabetes management model routinely involving six specialists.

Disclosure
Y. Xie: None. X. Li: None. F. Liu: None. Z. Zhou: None.

Funding
National Key Research and Development Program of China (2016YFC1305000, 2016YFC1305002, 2017YFC1309604)
1293-P: Health Center Services and Glycemic Control in Latinos with Diabetes
Authors: KATZ JOSHUA , WAN WEN , STAAB ERIN M. , LAITEERAPONG NEDA , BAIG ARSHIYA A. 
Published: June 2019

Background: Health centers (HCs) provide care to many racial and ethnic minority patients with diabetes. However, limited research has described the types of services HCs offer and their association with glycemic control.
Objective: To examine the relationship between HC services and glycemic control among Latino patients with diabetes.
Methods: We conducted a cross-sectional observational survey of providers in Midwestern HCs about the services offered at their sites. The provider-level report of HC services was summarized as medians of means per HC. HC-level data on glycemic control was obtained from the Uniform Data System. A linear mixed model was used to assess associations between the presence of HC services and the percent of Latino, non-Hispanic white, and overall patients with A1c &lt;9% served at the HC.
Results: Survey responses were received from 620 providers practicing at 97 HCs in 10 Midwestern states. There were positive associations between percent of Latino patients with A1c &lt;9% and access to community outreach workers/promotoras (p=0.01), and percent of overall patients with A1c &lt;9% and access to a dietician (p=0.002). There were negative associations between the percent of Latino patients with A1c &lt;9% and access to Spanish-speaking front desk staff (p=0.02) and provider education on diabetes (p=0.02). Serving a higher percentage of patients with diabetes who were Latino was negatively associated with the percent of Latino patients with A1c &lt;9% (p=0.0003).
Conclusions: Access to promotoras and dieticians were associated with higher percentage of Latino patients with A1c &lt;9%, suggesting the importance of a multidisciplinary approach to control of diabetes. Spanish-speaking front desk staff and provider education were associated with lower percentage of Latino patients with A1c &lt;9%, likely related to high levels of HC efforts to address care needs. Future studies need to assess how access to specific services impact A1c control among Latinos with diabetes who receive care at community HCs.

Disclosure
J. Katz: None. W. Wan: None. E.M. Staab: None. N. Laiteerapong: None. A.A. Baig: None.

Funding
National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
1296-P: Self-Reported Symptoms and Frequency of Hypoglycemia in Primary Care Patients with Type 2 Diabetes Mellitus: A Cross-Sectional, Multicenter Study
Authors: XU YINGQI , LEE JOYCE Y. 
Published: June 2019

Objective: Hypoglycemia remains an unpredictable side effect of insulin use or oral hypoglycemic agents therapy in patients with diabetes. However, Limited data exist on the prevalence of hypoglycemia in patients attending primary care diabetes clinics. This study aimed to determine the frequency and symptoms of self-reported hypoglycemia in patients with type 2 diabetes (T2DM).
Methods: This was a cross-sectional, multicenter study conducted in three outpatient clinics in Singapore. Patients aged ≥ 21 years old with T2DM and polypharmacy were included. Patients who were unable to communicate independently were excluded. The 5-item self-reported questionnaire about hypoglycemia awareness, symptoms, frequency and measures were administered to all eligible patients.
Results: Among the 254 patients who were eligible for the study, 45.7% experienced at least one hypoglycemic episode in the past seven days. Lightheadness (24.0%) was the most common symptoms reported, followed by weakness (15.8%) and intense hunger (14.2%). Among the patients who reported hypoglycemic symptoms, 52.6% took sweets and 35.1% achieved timely relief. Of the patients who reported hypoglycemia, 11.4% suffered severe hypoglycemia, requiring the assistance of another person to take corrective actions. Overall, approximately 48.0% reported fear of low blood sugar but only 31.9% performed self-monitoring of blood sugar (SMBG) with an average monitoring frequency of 3.31 ± 3.73 times within the last seven days. The severity and frequency of self-reported hypoglydemic symptoms were not associated with HbA1c, age, body-mass index, duration of T2DM and insulin use.
Conclusion: The frequency and severity of self-reported hypoglycemia among patients with T2DM appeared to be high and unrelated to patient demographics or disease control. The use of SMBG should be emphasized among patients with T2DM regardless of type of antidiabetic agents used.

Disclosure
Y. Xu: None. J.Y. Lee: None.