bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Inactivity and Sleep Inefficiency Accentuate the Genetic Risk of Obesity
Authors: WOOD ANDREW R. , JONES SAMUEL E. , RICHMOND REBECCA , AHMAD SHAFQAT , YAGHOOTKAR HANIEH , BEAUMONT ROBERT , RUTH KATHERINE S. , TUKE MARCUS , MURRAY ANNA , FREATHY RACHEL M. , SMITH GEORGE DAVEY , LEE I-MIN , TIMPSON NIC , CHASMAN DANIEL , KUTALIK ZOLTAN , WEEDON MICHAEL N. , TYRRELL JESSICA , FRAYLING TIMOTHY M. 
Published: June 2018

Gene-lifestyle interactions of relevance to type 2 diabetes have been difficult to identify but may help stratify groups of people at especially high risk. In large genetic studies, measures of diabetes risk factors such as diet and activity are usually limited to self-reported data. We used genetic and accelerometer data from 97,8individuals to test for genetic interactions with physical activity and sleep lifestyles. We tested the hypothesis that lower levels of physical activity and abnormal sleep patterns accentuate genetic susceptibility to obesity. We used 82,322 individuals from the UK Biobank, 10,885 from the Women’s Genome Health Study (WGHS) and 4,599 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We derived measures for physical activity and sleep, including total physical activity, time spent undertaking sedentary, light, moderate and vigorous activity, and sleep duration and sleep efficiency. We used BMI as the outcome and tested for interactions between a BMI genetic risk score (GRS) and the accelerometer derived measures of activity and sleep. We also performed several negative control experiments to test for residual confounding. We found evidence of gene-activity interactions. For example, in the UK Biobank, when analysing non-sedentary physical activity, the 10% of individuals carrying the most BMI-raising alleles were 5.9kg heavier if they were inactive compared to active (for height 1.73m). In contrast, the 10% of individuals carrying the fewest BMI-raising alleles were 4.1kg heavier if they were inactive compared to active (Pinteraction=4×10-4). This observation was consistent in the WGHS and ALSPAC data although not all tests reached P&lt;0.05. The results were robust to negative control tests, including the testing of interactions using random variables simulating the BMI-activity correlations. Our results are consistent with previous studies suggesting that low levels of physical activity accentuate the genetic risk of obesity.

Disclosure
A.R. Wood: None. S.E. Jones: None. R. Richmond: None. S. Ahmad: None. H. Yaghootkar: None. R. Beaumont: None. K.S. Ruth: None. M. Tuke: None. A. Murray: None. R.M. Freathy: None. G. Davey Smith: None. I. Lee: None. N. Timpson: None. D. Chasman: None. Z. Kutalik: None. M.N. Weedon: None. J. Tyrrell: None. T.M. Frayling: None.
The Effect of Efpeglenatide on Lipid Profiles and Overall Metabolism in Patients with Type 2 Diabetes and Obese Patients without Diabetes
Authors: PRATLEY RICHARD E. , KANG JAHOON , CHOI IN YOUNG , TRAUTMANN MICHAEL E. , HOMPESCH MARCUS , YOON KUN-HO , SORLI CHRISTOPHER H. 
Published: June 2018

Once-weekly (QW), subcutaneous efpeglenatide (efpeg) is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) in development for T2D. Efpeg reduced blood glucose and body weight (BW) in Phase 2 trials in patients with T2D (EXCEED 203) and patients with obesity without diabetes (BALANCE 205; Table). To assess whether these effects were associated with benefits on lipids, the effects of efpeg QW on total cholesterol [TC], high [HDL-C], low [LDL-C], and very low density lipoprotein cholesterol [VLDL-C] and triglycerides [TG] were assessed in patients from these Phase 2 trials (VLDL-C measured in BALANCE 2only). In the 12-week EXCEED 203 study in patients with T2D, efpeg QW led to significant (p&lt;0.05) reductions vs. placebo in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and BW (3-mg and 4-mg doses), and significant reductions in LDL-C and TG (4 mg only; Table). In the 20-week BALANCE 2study in nondiabetic patients with obesity, efpeg QW led to significant reductions vs. placebo in BW, HbA1c, FPG, TC, VLDL-C, TG (4-mg and 6-mg doses) and LDL-C and HDL-C (6 mg only). The safety profile of efpeg in both trials was consistent with GLP-1 RAs. These findings suggest that BW loss and glycemic effects with efpeg are accompanied by significant benefits on lipid profiles, providing an overall improvement in the abnormal metabolic state associated with T2D.

Disclosure
R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc. J. Kang: Employee; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. M.E. Trautmann: Consultant; Self; ProSciento. Stock/Shareholder; Self; Eli Lilly and Company. Consultant; Self; Hanmi Pharmaceutical, CeQur Corporation, Intarcia Therapeutics, Inc., Servier. M. Hompesch: Other Relationship; Self; Hanmi Pharmaceutical. K. Yoon: None. C.H. Sorli: Employee; Self; Sanofi.
Euglycemic Diabetic Ketoacidosis—Newer Class of Medication Can Lead to Rare Presentation of an Old Foe
Authors: BREAUX BRITTANI M. , DIPP SUSANA L. 
Published: June 2018

Background: Diabetic ketoacidosis (DKA) is a complication of diabetes mellitus (DM) that has high morbidity and mortality. Most are aware of diagnostic criterion including uncontrolled hyperglycemia, metabolic acidosis, and ketonemia. However, with the development of newer pharmacologic therapies, specifically the sodium-glucose co-transporter (SGLT2) inhibitor, we should be aware of a rarer presentation of DKA that may have normal serum glucose levels. We present a case euglycemic DKA.
Clinical Case: We present a 31 year old male with a past medical history of hypertension and type 2 DM, initially treated with glucophage. While this lowered his HgA1C, he self-discontinued therapy due to gastrointestinal side effects. He later developed symptoms of “acid reflux” and vomiting. He was admitted to an outside facility for hyperglycemia and acute kidney injury. DKA was ruled out, and his home regimen was adjusted to glucophage, canagliflozin, and sitagliptin. After starting the medications, he self-discontinued glucophage due to reoccurrence of symptoms, but continued canagliflozin and sitagliptin. Four days later, he presented to our clinic with additional symptoms of blurry vision and light-headedness. Canagliflozin was discontinued and stat labs were drawn. They were significant for acidosis (pH 7.16), elevated anion gap, elevated beta hydroxybutyrate, and a glucose level of 131 mg/dL (normal range: 70-120 mg/dL). Despite the relatively normal serum glucose, these findings were consistent with DKA. If one had focused on the serum glucose and not the entire biochemical picture, the diagnosis would have been overlooked.
Conclusion: Diagnosing and appropriate management of DKA, regardless of serum glucose, is critical for diabetic patients. With increasing use of newer anti-hyperglycemic medications, one must have a basic knowledge of the SGLT2’s direct/indirect effects that lead to increased counter regulatory hormones, as this mechanism can lead to euglycemic DKA.

Disclosure
B.M. Breaux: None. S.L. Dipp: None.
Evaluation of Diabetes-Related Outcomes Up to Two Years after Discharge from Ambulatory Clinical Pharmacist Clinics in a Large Public Safety Net Health System
Authors: CHOW DIEM , BOATRIGHT STEVEN M. , HULSTEIN JEFF , MOSS ELIZABETH , MATHEW ANNIE C. , ALVAREZ KRISTIN S. 
Published: June 2018

There are 10 clinical ambulatory pharmacy specialist (CAPS) providing direct patient care under physician-approved drug therapy management protocols within the health system. Patients were referred to CAPS by their primary care physician (PCP) and subsequently discharged from CAPS services when individualized diabetes goals were met. Patients continued follow-up with their PCP for continuity of care. The primary outcomes are the A1Cs at 1 year (± 90 days) and 2 years (± 90 days) post-discharge from CAPS. Secondary outcomes include 1 and 2 year results in the number of emergency department (ED) visits, hospitalizations, and other clinical visits completed.
Results: At baseline, patients discharged from CAPS had an A1C of 6.7% (n=195). At 1 and 2 year post-discharge, the A1Cs were 7.5% (n=118) and 8% (n=100), respectively. In the first year following discharge, 1 patient had an ED visit and 2 patients required hospitalization for diabetes-related events. In the second year post discharge, 3 patients were seen in the ED and 4 diabetes related hospitalizations occurred. Patients continued to see their PCP 2.7 and 2.3 times a year in the first and second year post-discharge, respectively. A small number of patients were referred to nutrition (n=16), diabetes classes (n=2), and diabetes clinic (n=5) in the 2 year time frame. Patients were also referred back to CAPS for continued diabetes management (n=5 in year 1, n=13 in year 2) and these A1Cs were removed from analysis. While not all patients discharged from CAPS had subsequent A1Cs for analysis, the main reason identified was a lack of A1C results in the specified time frame.
Conclusions: Patients were able to fairly control their diabetes up to 2 years after discharge from clinical pharmacy services.

Disclosure
D. Chow: None. S.M. Boatright: None. J. Hulstein: None. E. Moss: None. A.C. Mathew: None. K.S. Alvarez: None.
Developing a Health Economic Model for Asians with Type 2 Diabetes Based on the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial
Authors: TANAKA SHIRO , LANGER JAKOB , MORTON TIM , WILKINSON LARS , TANAKA SACHIKO , KAWASAKI RYO , MORIYA TATSUMI , HORIKAWA CHIKA , AIDA REI , ARAKI ATSUSHI , SONE HIROHITO 
Published: June 2018

Cost-effectiveness analyses (CEAs) are becoming increasingly important in Japan following the introduction of the pilot-based health technology assessment (HTA) from April 2016. Although health economic (HE) models for type 2 diabetes (T2D) have been developed, most models are not generalizable to patients in Asia whose risk factor profiles are different from Caucasians, since they are based on risk equations derived from the United Kingdom Prospective Diabetes Study (UKPDS). The objective was to develop a HE model for T2D using risk equations validated in Japanese patients (JJ Risk Engine) designed to meet the criteria in the guidelines of the Ministry of Health, Labour and Welfare in Japan. The model cohort is defined by patient characteristics and four risk factors (HbA1c, BMI, blood pressure and cholesterol), and treatment effects on macro and micro vascular complications and mortality are applied as risk factor modification over specified duration. In addition to outcomes included in the JJ Risk Engine, end-stage renal disease, amputation, hypoglycemia, utilities and costs were incorporated in the model using data available in the literature. The HE model estimates risks of macro and microvascular complications, cost of complications and treatments, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses can be conducted for assessment of uncertainty. Simulation settings related to e.g., time horizon, treatment duration, and discount rates can be varied. This HE model offers an opportunity for decision-makers to assess the long-term cost-effectiveness of interventions in Asian patients with T2D.

Disclosure
S. Tanaka: None. J. Langer: Employee; Self; Novo Nordisk Pharma Ltd.. Stock/Shareholder; Self; Novo Nordisk A/S. T. Morton: Consultant; Self; Novo Nordisk Inc. L. Wilkinson: Employee; Self; Novo Nordisk A/S. S. Tanaka: None. R. Kawasaki: None. T. Moriya: None. C. Horikawa: None. R. Aida: None. A. Araki: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..
Opportunities to Encourage Mail Order Pharmacy Use in Diabetes—A Qualitative Study
Authors: SCHMITTDIEL JULIE , MARSHALL CASSONDRA , WILEY DEANNE , CHAU CHRISTOPHER V. , TRINACTY CONNIE M. , WHARAM JAMES F. , KENRIK DURU O. , KARTER ANDREW J. , ESTACIO KAREN , BROWN SUSAN 
Published: June 2018

Medication non-adherence is a major contributor to poor outcomes in diabetes. Previous research has shown an association between mail order pharmacy (MOP) and better medication adherence, but little is known about the barriers and facilitators to MOP use in diabetes patients. This qualitative study examined factors related to use of MOP vs. traditional pharmacies to obtain prescription medications. We conducted four 90-minute focus groups in 2016 among 28 diabetes patients in the Hawaii and Northern California regions of Kaiser Permanente, a large integrated health care delivery system. We queried participants on their preferred pharmacy use and perceptions of barriers and facilitators of MOP use. One researcher independently coded each focus group transcript, with two transcripts double-coded by an additional researcher to promote reliability. We employed thematic analysis guided by the Capability, Opportunity, Motivation, and Behavior (COM-B) framework using NVivo 11 software. The average age of participants was 64.1; 57% were female; 21% were Asian; 21% were black/African-American; 7% were Hispanic/Latino, and 14% were Native Hawaiian/Pacific Islander. Analysis uncovered 26 themes related to the decision to use MOP for dispensing medications. Most themes (18 out of 26) fell into the COM-B category of ’Opportunity.’ Barriers to MOP use included unpredictability of medication delivery date, concerns about mail security, and difficulty of coordinating refill orders for multiple prescriptions. In contrast, facilitators included greater access and convenience (e.g., no need to wait in line or arrange transportation) compared to traditional pharmacies. Receiving a MOP incentive of free one-month supply of prescriptions was a motivational facilitator to using MOP for delivering medications. These findings can be used to design interventions and quality improvement initiatives to increase MOP usage and improve medication adherence in diabetes patients across health care systems.

Disclosure
J. Schmittdiel: None. C. Marshall: None. D. Wiley: None. C.V. Chau: None. C.M. Trinacty: None. J.F. Wharam: None. O. Duru: None. A.J. Karter: None. K. Estacio: None. S. Brown: None.
Hospitalizations during a Month of Emergency in a Department of Diabetology
Authors: AMOR NADIA BEN , MAMI FAIKA BEN 
Published: June 2018

Introduction: Tunisia is not immune to the heavy expenses related to diabetes, especially the cost of hospitalization. The aims of the work were to evaluate the number of hospitalizations in a diabetes unit during an emergency month and to study the indications of these hospitalizations.
Material and methods: Our work is a retrospective, descriptive study, performed in the department C of the National Institute of Nutrition and Food Technologies of Tunis. The patients included in our study had all consulted the dispatching of the Institute during October 2017 and carried the indication to emergency hospitalization.
Results: The number of patients hospitalized was 90. The majority was female(72.2%). The mean duration of hospitalization was 5.3±2.8 days (from 3 to 21 days). The mean age was 39.8±4.7 years (from 16 to 81 years). The indications for hospitalization were as follows: acid-ketotic decompensation in 4.4%(n=4); ketotic decompensation in 14.4%; hyperosmolarity in 4.4%; diabetic foot in 5.6%; unstable diabetes in 7.8%; unbalanced diabetes in 22.2%; discovery of gestational diabetes in 21.1%; pregnancy and unbalanced diabetes mellitus in 16.7% and exploration of hypoglycaemia in a nondiabetic patient in 3.3%. The imbalance or decompensation factors for diabetes were lipodystrophy in 38.9%; drug and/or dietary non-compliance in 46.7%; an infection in 21.1%; insulin resistance in 16.7% and the absence of fast insulin bolus in 7.8%. As for hypoglycaemia in nondiabetics (n=3), two cases were confirmed and these were functional hypoglycaemias. The third case reversed was addressed in neurology and cardiology for exploration of discomforts.
Conclusions: The main indication of emergency hospitalization was decompensated or unbalanced diabetes with lipodystrophies and poor adherence as the main causes. This underscores the importance of the repetition of education sessions for diabetic patients and the psychological care of them.

Disclosure
N. Ben Amor: None. F. Ben Mami: None.
Results from a Population Health Strategy for Diabetes in a Large Health Care System
Authors: SUBRAMANIAN SAVITHA , HIRSCH IRL B. , EVERT ALISON 
Published: June 2018

Population health is defined as the health outcomes of a group of individuals, including the distribution of such outcomes within the group. Awareness of population health management is increasing but the concept is not clearly defined or understood. Nevertheless, the overarching goal is to keep the patient population as healthy as achievable. Since diabetes is a chronic and progressive illness, population health management strategies hold promise and can be measured using health outcomes, disease burden or metabolic status. University of Washington Medicine, a large healthcare system in the greater Seattle area comprised of academic and community-based primary care clinics, recently initiated a diabetes population health (DPH) program. The is a centralized outlier management and surveillance system where a specialized team (endocrinologist and certified diabetes educator) remotely supports care teams (primary care providers, nurses) in diabetes management. In this pilot initiative, focus was on the highest risk patients with type 2 diabetes such as individuals who had chronically elevated A1C &gt;9% over the past 12 months. The DPH team identified these individuals from an internal database, conducted chart reviews to identify potential areas for improvement, reached out to clinical care teams and offered individualized patient management strategies for the identified patients. Care of all identified patients remained with primary care teams. In 6 months there was a 1.4% point reduction in A1C (10.8% to 9.4%, n=34, p&lt;0.01) primarily through the team’s work with care management nurses who in turn conducted outreach to patients to enable engagement, offered diabetes self-management support and improved care coordination. Thus, the number of individuals with diabetes and elevated A1C at any given period in the past 8 months was decreased by 60%. These early results suggest that an active diabetes surveillance program has the potential to improve health outcomes in diabetes.

Disclosure
S. Subramanian: Advisory Panel; Self; Intarcia Therapeutics, Inc., Akcea Therapeutics. I.B. Hirsch: Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care Health and Digital Solutions, ADOCIA. A. Evert: None.
Supporting Diabetes Management—Perspectives on Care Management in a Medicaid Health Home in Alabama
Authors: AGNE APRIL A. , MONDESIR FAVEL , SHELLEY JOHN P. , PISU MARIA , CHERRINGTON ANDREA 
Published: June 2018

Background: Chronic diseases like diabetes require constant and ongoing self-management. The Health Home model provides a unique platform to facilitate diabetes management and connect patients to community resources that support and promote self-management. However, little is known about specific activities, barriers, and needs that exist in Health Homes particularly in Alabama which suffers disparately high rates of diabetes compared to other regions. To address this knowledge gap, the purpose of this study is to understand how a Medicaid Health Home facilitates diabetes management in Alabama.
Methods: Three interviewers conducted semi-structured interviews with six staff at a health home organization. A guide facilitated discussion on patient recruitment, frequency and mode of communication with patients and health care delivery team, and clinical and non-clinical patient-related barriers. Content analysis was performed to identify major themes using an iterative, combined deductive and inductive approach.
Results: Six female participants were aged a mean 49 years; majority employed 4 to 5 years in current role. Professional qualifications included a dietician, social worker, and nurses. Five care management domains were identified: health education, medication management, nutrition therapy, and addressing psychosocial issues. Facilitators of staff roles discussed were a high degree of collaboration within their organization and externally with providers and other professionals. For example, staff described the value of reciprocal relationships in which providers interacted with the health home. Barriers to care management included state Medicaid cost-sharing policies, medication limits, timely access to care, and variation in the availability of community resources.
Conclusions: These findings suggest that opportunities exist to intervene at the policy and healthcare system level to improve adult diabetes management for a vulnerable population.

Disclosure
A.A. Agne: None. F. Mondesir: None. J.P. Shelley: None. M. Pisu: None. A. Cherrington: Advisory Panel; Self; AstraZeneca. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc..
Longitudinal Evaluation of Cardiometabolic and Diabetes Risk Factors in a Rural College-Aged Population
Authors: CYPHERT HOLLY , POWELL ROBERT 
Published: June 2018

Throughout the U.S., obesity and diabetes rates continue to rise, especially in West Virginia. In fact, West Virginia’s obesity and diabetes rates exceed 40 percent of its population. Previous literature has demonstrated that childhood and early adult lifestyles, including poor dietary choices and reduced physical activity, predict future metabolic and cardiac issues. Therefore, we sought to determine the levels of risk factors for diabetes and cardiometabolic disease in college students in rural WV via a 4-year longitudinal study termed HERD2020 (Higher Education Reducing Diabetes). Freshmen were recruited at Marshall University and were stratified by BMI status to assess differences in physiological, molecular, and psychological status (BMI&lt;25 kg/m2 vs. BMI≥25 kg/m2). Fifty three percent of the students were deemed overweight or obese (BMI≥25 kg/m2). Baseline analysis yielded no significant differences between BMI category and fasting glucose (p=.31); cholesterol (p=.473); triglycerides (p=.38); or HDL (p=.56). Strikingly, students with a BMI≥25 kg/m2 recorded fasting insulin levels twice as high as students with a BMI&lt;25 kg/m2, (.42 vs. .96ng/ml, p=.003). This data suggests overweight/obese students are in a state of insulin-resistance, placing them at greater risks for future cardiometabolic diseases. Lastly, we evaluated plasma bile acid levels due to their newfound interest as antidiabetic molecules. Of the four bile acids altered (urodeoxycholic acid (UDCA), hyocholic acid (HCA), glycochenodeoxycholic acid (GCDCA), and taurodeoxycholic acid (TDCA)), two were higher in overweight patients (UDCA and TDCA) while the other two bile acids were lower in overweight patients (HCA and GCDCA). Continual recruitment and analysis of this study will provide more insight into the strength of these associations following lifestyle intervention. Future strategies should consider these factors to encourage successful lifestyle modification in this population.

Disclosure
H. Cyphert: None. R. Powell: None.