bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Perspectives on the Burden of Type 2 Diabetes Mellitus Treatment
Authors: YU-ISENBERG KRISTINA , GRAY GEOF D. , FOLEY CATHERINE , STOKES JONATHAN T. , SHIELDS ALAN , DICKIE GAVIN , LAMOUREUX ROGER , JACKSON CLARK V. , PADILLA BRAD , POLONSKY WILLIAM 
Published: June 2018

Introduction: The burdens associated with type 2 diabetes mellitus (T2DM) treatments, particularly injectable treatments, are liabilities to adherence and desired health outcomes. Patient-focused research was conducted to identify critical aspects of treatment burden related to adequate disease control and adherence to treatment.
Methods: A targeted review of the literature, advice meetings with therapeutic experts, and open-ended qualitative concept elicitation interviews with T2DM patients were conducted. Results from this research were thematically analyzed to identify concepts pertinent to T2DM treatment burden, then harmonized and organized into broader categorical domains.
Results: The literature review (N=26 publications), meetings with global experts (N=13), and patient interviews (N=20; mean age=60.5±9.5 years, 45% female) yielded a total of 45 unique concepts associated with T2DM treatment burden, with the most frequently reported by experts being aversion to needles (n=9), polypharmacy (n=8), and cost of medication (n=8); and by patients, treatment regimen (i.e., process of administering treatment; n=16), storage (i.e., refrigeration of medication; n=16), and planning/preparation of treatment administration (n=15). These 45 concepts were organized into eight broader domains: issues with mode of treatment administration/regimen, side effects and efficacy of treatment, impact on activities of daily living, and emotional, financial, social, and work impacts.
Conclusions: Evidence elicited from this research highlights aspects of T2DM treatment burden and substantiates the significant obligation of disease management for patients. The treatment burdens identified here can inform new (1) treatment technologies and regimens to lessen this burden and, ultimately, encourage adherence, glycemic control, and improvement in other health outcomes for patients with T2DM and (2) outcome assessment strategies to evaluate the burden of existing and novel T2DM treatments.

Disclosure
K. Yu-Isenberg: Employee; Self; Intarcia Therapeutics, Inc. G.D. Gray: Employee; Self; Servier Global Medical Affairs. C. Foley: Consultant; Self; Intarcia Therapeutics, Inc., Servier. J.T. Stokes: None. A. Shields: Consultant; Self; Intarcia Therapeutics, Inc. G. Dickie: Consultant; Self; Intarcia Therapeutics, Inc. R. Lamoureux: Research Support; Self; Intarcia Therapeutics, Inc.. C.V. Jackson: None. B. Padilla: None. W. Polonsky: Consultant; Self; Abbott, AstraZeneca, Dexcom, Inc., Sanofi, Novo Nordisk Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Servier, Ascensia Diabetes Care, Merck & Co., Inc., MannKind Corporation, Glooko, Inc., Roche Diabetes Care Health and Digital Solutions.
Making Sense of Rapid-Acting Insulin Patient Directions in the EMR
Authors: MACMASTER HEIDEMARIE W. , FONG ISABEL , RUSHAKOFF ROBERT J. 
Published: June 2018

Discharge prescription (Rx) instructions for rapid-acting insulin (RAI) are often missing information. Various barriers prevent complete RAI directions in the EMR, including a 140 character limit for e-prescribing which encourages use of abbreviations. Replacing "unit" with "U" has contributed to multiple dose mis-interpretations and unwanted glycemic excursions. Further, for insurance reimbursement, pharmacies must be able to estimate 30 day supplies for prescriptions, which is challenging when integrating a correctional scale into the directions. These barriers often lead prescribers to develop multiple workflows. The e-Rx may be ordered in terms of maxium daily dose (Take up to 60 units daily SQ as directed) while the patient may be provided separate medication instructions. At UCSF, every patient is provided a customized "after visit summary" (AVS) which includes a discharge Patient Medication List (PML), while the PCP is sent the PML and discharge summary electronically, and the PML also serves as a vehicle for prescribing to the pharmacy. A universal patient-centric standard for RAI instructions in the EMR medication list that can be both e-prescribed and used as the patient's instructions is not currently in place. Some medical centers recommend avoiding discharging patients with RAI correctional scales. A 2-month retrospective review of the PML, AVS and discharge provider summary for all adult inpatients discharged from UCSF to home revealed that 82% of patients were prescribed RAI with a correctional scale. (n=107) Of those, within the patient's PML or AVS medication instructions, 86% had range orders with incomplete scale directions, 22% had missing routes of administration, 12% contained unapproved abbreviations and 46% of nutritional RAI orders had missing units. Future efforts include identifying systematic approaches to ensure patients,their health care providers and their pharmacies are provided complete and accurate RAI instructions at discharge.

Disclosure
H.W. Macmaster: None. I. Fong: None. R.J. Rushakoff: None.
Physically Active Diabetics Report Lower Rates of Impaired Cognitive Function—Findings from the 2012 National Health Interview Survey
Authors: FU ZHUO , KOMELSKI MATTHEW , KUMAR AAKSHAY 
Published: June 2018

Background: Diabetics are known to be at increased risk for impaired cognitive function (ICF). Some studies have suggested this risk may be reduced through physical activity. We examined associations among age, obesity, leisure time physical activity (LPA), and ICF in a large sample of U.S. diabetics.
Methods: A secondary data analysis was conducted using data from the 2012 National Health Interview Survey (NHIS), which collects self-reported data on a variety of health-related constructs (n=32866). A logistic regression was used to investigate the associations between diabetes, obesity, LPA and ICF across three age groups: young adults (YA):18 to 38 year; middle-aged adults (MA):39-59 year; and older adults (OA): 60+ year.
Results: All MAs (OR: 2.18 CI95%: 1.78-2.66) and OAs (OR: 3.62 CI95%: 3.02-4.35) in the total sample were more likely to report experiencing ICF than YAs. Obese YAs and MAs, but not OA, reported a slightly higher rate of ICF compared with non-obese peers within their age groups. Diabetes was strongly associated with ICF among YAs (OR: 3.25 CI95%:2.10- 5.01), MAs (OR: 3.57 CI95%:2.77- 4.61), and OAs (OR: 1.67 CI95%:1.41- 1.99). However, among diabetics, individuals who met weekly PA goals (guidelines from Office of Disease Prevention and Health Promotion) reported significantly lower rates of ICF, in all age groups: Among diabetic YAs 1.71% (CI95%: 0.16 -3.26%) of goal achievers reported ICF compared to 9.79% (CI95%: 5.84-13.73%) in inactive diabetic peers*. Among MAs it was 5.32% (CI95%: 3.11-7.53%) compared to 14.58% (CI95%: 11.64-17.52%)*; and among OAs it was 5.57% (CI95%: 3.78-7.37%) compared to 12.04% (CI95%: 10.33-13.75%)*. *: p&lt;p=0.001.
Conclusion: These findings support the hypothesis that both aging and diabetes increase risk of ICF. Obese YAs and MAs had slightly higher rates of ICF. Among diabetic individuals in all age groups, meeting PA guidelines was associated with significantly lower rates of ICF.

Disclosure
Z. Fu: None. M. Komelski: None. A. Kumar: None.
Predicting Future Glucose Fluctuations Using Machine Learning and Wearable Sensor Data
Authors: HAYERI AMIR 
Published: June 2018

Predicting blood glucose values (BG) using machine learning (ML) algorithms and data fusion techniques. There has been a recent explosion of interest in BG prediction due to its application in the development of insulin regulating algorithms for the Artificial Pancreas Project. During this study, we measured the predictive accuracy of a software system designed to predict glucose behaviour using step-count and heart-rate data in addition to BG-insulin dynamics. The software was tested in a blinded pilot study at BC Children's Hospital for 9 type 1 diabetic children. Using continuous glucose monitors (CGM) and fitness wearables (Fitbit), the software aggregated 60-days of continuous data from each participant. The data from the first 30-days of the study was used to train the algorithem. The trained algorithm was then used to make predictions every 5mins for the next 30days. On average, the software was able to predict user's future glucose values with 93% accuracy rate for 60-mins ahead of time. Although encouraging, the algorithm required further testing. We have since released the app under the commercial name "DiaBits" for more testing and further data collection.

Disclosure
A. Hayeri: Other Relationship; Self; Dexcom, Inc., Fitbit, Inc.. Research Support; Self; BC Children's Hospital - Vancouver Canada. Other Relationship; Self; University Of British Columbia.
High-Intensity Interval Training and Hypoglycemia Minimization in Adults with Type 1 Diabetes (HIIT HYPO T1D Study)
Authors: LEE ANGELA S. , WAY KIMBERLEY L. , JOHNSON NATHAN A. , TWIGG STEPHEN M. 
Published: June 2018

This study examined if reductions in evening basal insulin can minimize overnight hypoglycemia following afternoon high-intensity interval training (HIIT) exercise in adults with type 1 diabetes.
In a randomized, two-arm crossover trial participants each undertook on separate days: moderate-intensity continuous exercise with 20% overnight basal insulin reduction (CONT20), and a series of 3 HIIT isocaloric sessions, with 10% (HIIT10), 20% (HIIT20) and 30% (HIIT30) overnight basal insulin reduction. Post-exercise glucose response was measured by Freestyle Libre Pro Flash Glucose Monitoring, and compared with a non-exercise day (NON). Participants were given standardised instructions throughout to reduce dinner insulin bolus by 25% post-exercise, have a bedtime snack, and to ensure pre-bed glucose &gt;7.0mM.
Twelve adults participated (9F/3M, 9 MDI/3 CSII, mean age 40.4 ± 9.9y, duration 16.5 ± 9.8y, HbA1c 8.0 ± 0.8%, and BMI 26.9 ± 5.2kg/m2). Whilst overnight glucose profiles were not significantly different across all regimens (Table), the smallest change in glucose from 2300 to 0600 was seen after HIIT30, compared with other exercise regimens. Glucose profiles were not significantly different 24h post each regimen (p=0.28).
Thus, while data suggests HIIT30 may be a preferred approach, there were no differences in hypoglycemia rates in exercise regimens applied in this study.

Disclosure
A.S. Lee: None. K.L. Way: None. N.A. Johnson: None. S.M. Twigg: Advisory Panel; Self; Abbott. Consultant; Self; Abbott. Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Speaker's Bureau; Self; AstraZeneca, Merck Sharp & Dohme Corp.. Other Relationship; Self; Abbott.
Moderate- and High-Intensity Exercise Training Improve “Free-Living” Glycemic Control Independently of Weight Loss
Authors: SCHLEH MICHAEL W. , RYAN BENJAMIN J. , GILLEN JENNA B. , LUDZKI ALISON , HOROWITZ JEFFREY F. 
Published: June 2018

The independent effects of exercise training (without weight loss) on glycemic control are controversial, and the influence of exercise intensity is not well understood. The aim of this study was to determine the effect of 12 weeks (4 sessions/week) of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) without weight loss, on “free-living” 24h glycemic control using continuous glucose monitoring (CGM). Eighteen obese adults (33±3 kg·m-2) performed HIIT, involving 10 x 1 min intervals at ∼90% HRmax interspersed with 1 min recovery (n=8), or MICT, involving 45 min at ∼70% HRmax (n=10). CGM was performed under standardized dietary control for 48h before and after training. After training, subjects exercised the day before, but not on Day 1 of CGM measurement. On Day 2 of post-training CGM data collection, participants performed their regular exercise session (HIIT or MICT) before breakfast. This approach allowed us to assess the effects of exercise training on glycemic control on a day with and without exercise. On Day 1 post-training, 24h glucose area under the curve (AUC) was modestly lower than pre-training in both groups (HIIT: 130±11 vs. 126±7 mM·h-1 · 24h; MICT: 138±7 vs. 133±7 mM·h-1 · 24h, p=0.02). There were no differences between HIIT and MICT (p=0.22). The improved 24h glycemic control after training was primarily due to modestly lower postprandial responses to breakfast (p=0.03) and dinner (p=0.002), with no differences between HIIT and MICT. On Day 2 post-training, which included a session of exercise, glycemic control remained better than pre-training in both groups (p=0.006), but interestingly was not improved further by the acute exercise session (p=0.82 for Day 1 vs. Day 2 post-training).
In conclusion, exercise training improved 24h “free-living” glycemic responses in the absence of weight loss, and in general, the intensity of exercise training did not impact this improvement in glycemic control.

Disclosure
M.W. Schleh: None. B.J. Ryan: None. J.B. Gillen: None. A. Ludzki: None. J.F. Horowitz: None.
Exercise Training Alters Sorbin and SH3 Domain Containing 3 DNA Methylation in Human Skeletal Muscle
Authors: DAY SAMANTHA E. , GARCIA LUIS , COLETTA RICHARD L. , DEFILIPPIS ELEANNA , MANDARINO LAWRENCE , COLETTA DAWN K. 
Published: June 2018

The physiological changes observed in skeletal muscle following exercise training may be due to epigenetic modifications. Previously, we have shown increased methylation of cytosines (5.0 to 24.4%) in sorbin and SH3 domain containing 3 (SORBS3) in obesity. In another study, we showed decreased methylation (-5.6 to -24.2%) of SORBS3 following weight loss induced by bariatric surgery. The aim of this study was to determine whether an exercise training regimen alters DNA methylation of SORBS3. Skeletal muscle biopsies were obtained basally from five insulin-resistant obese (BMI: 32.3±0.8 kg/m2) participants (41.8±3.3 years) before and after 8-weeks of supervised exercise training. After training, BMI and total body weight were unchanged. Training increased peak aerobic capacity (VO2peak) from 20.2±1.9 to 24.3±2.7 mL/kg/min. We performed next generation methylation reduced representation bisulfite sequencing on DNA isolated from the vastus lateralis muscle biopsies. MethylSig analysis revealed 4 cytosines that were decreased in methylation following the exercise training (chr8.22423199: -19.3%, chr8.22423207: -14.6%; chr8.22423252: -27.5% and chr8.22423257: -12.3%, all Benjamini Hochberg q&lt;0.05). All 4 differentially methylated sites fell within the 5’ untranslated region of SORBS3 variant 2. Our results demonstrate that exercise training for 8-weeks in obese participants alters the methylation of SORBS3. To date, we have provided evidence that SORBS3 is epigenetically regulated in skeletal muscle under a number of metabolic conditions including obesity, in response to weight loss by surgical intervention and in response to an 8-week exercise training regimen.

Disclosure
S.E. Day: None. L. Garcia: None. R.L. Coletta: None. E. DeFilippis: None. L. Mandarino: None. D.K. Coletta: None.
Branched-Chain Amino Acid (BCAA) Metabolism, Insulin Sensitivity (IS), and Liver Fat Response to Exercise Training in Sedentary Prediabetic and Normoglycemic Men
Authors: LEE SINDRE , GULSETH HANNE L. , REFSUM HELGA , LANGLEITE TORGRIM M. , HOLEN TORGEIR , JENSEN JØRGEN , DREVON CHRISTIAN A. , BIRKELAND KARE I. 
Published: June 2018

Studies suggest a role for BCAA in decreased IS and type 2 diabetes. Exercise improves IS, but the relationship with BCAA metabolism is unclear. We studied the effects of a 12 w exercise intervention on IS, liver fat and BCAA metabolism in prediabetic (n=13) and normoglycemic men (n=13). We estimated IS by hyperinsulinemic-euglycemic clamp, transcriptomics by mRNA-seq of skeletal muscle and adipose tissue biopsies, liver fat by MRI/MRS, and plasma (p)BCAA by HPLC, before and after the intervention. At baseline, liver fat and p-BCAA were higher, whereas IS and BCAA skeletal muscle and adipose tissue catabolism were lower in prediabetic vs. control men. Sum of pBCAA were elevated by 14% in prediabetic men and correlated negatively with IS (Figure A, p&lt;0.05). Liver fat and adipose tissue BCAA catabolism correlated significantly to pBCAA levels. The exercise intervention increased IS by 29%, lowered liver fat by 25% and increased BCAA catabolism, whereas no significant change were observed in mean p-BCAA levels and changes did not correlate to changes in IS (Figure B).
In conclusion, exercise intervention did not alter the mean pBCAA, despite significantly improved IS. We suggest that elevated pBCAA levels may not play a direct role causing insulin resistance, but rather is a consequence of accompanying alterations in liver, skeletal muscle and adipose tissue.

Disclosure
S. Lee: None. H.L. Gulseth: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S, Sanofi, Merck & Co., Inc., AstraZeneca. H. Refsum: None. T.M. Langleite: None. T. Holen: None. J. Jensen: None. C.A. Drevon: None. K.I. Birkeland: Research Support; Self; AstraZeneca, Novo Nordisk A/S, Eli Lilly and Company, Sanofi, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp..
Two Weeks of Interval vs. Continuous Exercise Training on Endothelial Function in Adults with Prediabetes
Authors: MALIN STEVEN K. , GILBERTSON NICOLE M. , EICHNER NATALIE , HEISTON EMILY M. , BARRETT EUGENE , WELTMAN ARTHUR , MILLER STEPHANIE L. 
Published: June 2018

Hyperglycemia promotes vascular complications through, in part, an inflammatory-mediated impairment in endothelial function. However, the effects of interval (INT) vs. continuous (CONT) training on endothelial function prior to clinically meaningful weight loss is unknown in adults with prediabetes. Twenty-six subjects with prediabetes (60±1y; 33±1kg/m2; 2h-PG OGTT: 145±7mg/dl) were randomized to 60min of CONT (n=12; 70% of HRpeak) or work-matched INT exercise training (n=14; alternating 3-min at 90 and 50% HRpeak) for 2 weeks. Aerobic fitness (VO2peak) and body composition (bioelectrical impedance) were assessed before and after training. Flow-mediated dilation (FMD) was measured after an overnight fast during a 2-h 75g OGTT (0, 60 and 120min) to assess endothelial function. Post-prandial FMD stimulation was averaged and defined as the percent change from fasting. Glucose tolerance was calculated by total area under the curve. Fasting plasma VCAM and ICAM were also assessed as indicators of vascular inflammation. Both interventions improved VO2peak and reduced body fat (P&lt;0.004). Although VCAM (P=0.009) and glucose tolerance (P=0.08) were reduced following both treatments, there was no effect on ICAM or fasting and post-prandial FMD. However, impaired fasting FMD prior to training was correlated with enhanced fasting FMD (r=-0.81, P=0.001) as well as FMD stimulation (r=0.46, P=0.03) post-training. Further, adults with the greatest improvement in fasting FMD after training had the smallest change in post-prandial FMD (r=-0.59, P=0.004). Lowering of VCAM after training was linked to this smaller change in post-prandial FMD (r=0.41, P=0.06) and enhanced fasting FMD (r=-0.38, P=0.05). Taken together, endothelial function is not improved after short-term training, regardless of intensity. However, prediabetic adults with impaired endothelial function at baseline exhibit exercise-induced improvement in FMD, which is linked to vascular inflammation.

Disclosure
S.K. Malin: None. N.M. Gilbertson: None. N. Eichner: None. E.M. Heiston: None. E. Barrett: None. A. Weltman: None. S.L. Miller: None.
Two Years Supervised Resistance Training Prevented Diabetes Incidence in People with Prediabetes—A Randomized Control Trial
Authors: YUAN XIAODAN , LOU QINGQING 
Published: June 2018

Objective: To explore the long-term effects of aerobic training (AT), resistance training (RT) and both (AT+RT) on prevention of incidence of type 2 diabetes(T2D) in patients with prediabetes.
Methods: Randomized control trial conducted in two Chinese medical centers between October, 2014 and November, 2016. Of 724 subjects, 122 declined, 430 were excluded, and 172 with prediabetes (fasting glucose ≥5.6mmol/L and &lt;7.0mmol/L and/or 2-hour glucose ≥7.8mmol/L and &lt;11.1mmol/L in the 75g oral glucose tolerance test) were included for randomization. Supervised exercise programs including AT, RT and AT+RT were completed for 60 minutes, three nonconsecutive times per week for 24 months respectively.
Primary outcome was incidence of T2D; secondary outcomes included hemoglobin (HbA1c), fasting plasma glucose (FPG), standard 2-hour oral glucose tolerance (2hPG), and lipid profile.
Results: 137 (80%) subjects, mean age 59 years, 45 men, 92 women, entered final analysis. After 24 months of intervention, the incidences of T2D adjusted by sex and age were significantly decreased by 74% (95% CI 0.38-0.89%), 65%(95% CI 0.21-0.85%) and 72% (95% CI 0.36-0.87%) with AT+RT, RT and AT, as compared with control group ((HRR 0.26(95% CI 0.11−0.62) in AT+RT 0.35(0.15-0.79)RT, and 0.28(95% CI 0.13-0.64)AT)), and the cumulative T2D incidences were significantly lower in AT+RT, RT, and AT group, compared to that of the control group(21%, 26% and 22% vs. 69%). Blood glucose and lipid profile in AT, RT and AT+RT improved more than in the control group, which had prevailed over time.
Conclusions: Resistance training and resistance training plus aerobic training were as effective as isolated aerobic training in preventing progression to T2D. Patients with prediabetes can choose aerobic training, resistance training or both to prevent T2D. This can have substantial impact on engaging patients with lifestyle change to prevent or delay T2D onset.

Disclosure
X. Yuan: None. Q. Lou: None.
BZ043, a Novel Amylin Analog, in a Fixed Combination with Insulin Glargine—Nonclinical Results
Authors: NASCIMENTO CAIO V.F. , LACATIVA PAULO G. , BRIAND FRANÇOIS , LIMA LUIS M.T.R. 
Published: June 2018

Amylinomimetics are important adjunctive drugs for treating type 1 diabetes (T1D). Here we describe the amylin analog BZ043 and its potential to be mixed with insulin glargine (GLAR) in a fixed combination (FC). The effect of BZ043 over fed glycemia, either alone or co-administered with GLAR, was investigated in rats with streptozotocin-induced diabetes (STZ). Fasted STZ rats (3 h) received a single treatment of BZ043 (0.15, 0.6 or 1.2 mg/kg), GLAR (1.5 IU/rat), or BZ043 plus GLAR (separate injections), and then had free access to food (5% glucose rich) and water. BZ043 dose-proportionally prevented meal-induced increase of glycemia and the co-treatment (0.6 or 1.2 mg/kg) with GLAR restored normoglycemia (100 mg/dL) without abrupt variations of glycemia (Figure. 1A), as further shown by comparison of the area under the blood glucose curve (Figure. 1B). Adding BZ043 to a commercial vial of GLAR at 0.1 or 0.5 mg/mL did not result in observable alteration of the average molecular radius of the samples after 24 weeks of incubation at 4 °C, as shown by dynamic light scattering (Figure. 1C). In STZ rats, BZ043 showed a prolonged anti-hyperglycemic effect and, together with GLAR, promoted a long-lasting normoglycemia, with flat variation of glycemia. While further investigation on the physicochemical stability of the combination is ongoing, our data suggest that BZ043 and glargine in a FC might improve the control of T1D in humans.

Disclosure
C.V.F. Nascimento: Employee; Self; Biozeus Biopharmaceutical S.A. P.G. Lacativa: Employee; Self; BIOZEUS Biopharmaceutical. F. Briand: Employee; Self; Physiogenex S.A.S.. Stock/Shareholder; Self; Physiogenex S.A.S. L.M.T. Lima: Research Support; Self; BioZeus.