bluuebunny/crossref_metadata_2025 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<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 >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<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<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<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 <7.0mmol/L and/or 2-hour glucose ≥7.8mmol/L and <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.
Safer Glycemic Control Using Fructose-Based Enteral Formula—A Randomized Crossover Clinical Trial
Authors: KUMBIER MAGALI , TEIXEIRA CASSIANO , HELAL LUCAS , ALMEIDA JUSSARA
Published: June 2018

Background: Glycemic control during nutritional therapy in patients under intensive care has shown a great importance in relation to morbidity and mortality. To avoid glycemic oscillation in patients under enteral nutrition, usually a low-carbohydrate diet is offered, but differing among themselves by carbohydrate type. A question that remains unanswered is whether the presence of fructose interferes with glycemic oscillation or not.

Objective: The aim of this clinical trial was to evaluate the effect of two diabetes-specific diets (fructose-based vs. maltodextrin-based) in the glycemic variability of critically ill patients. We hypothesized that patients under the fructose-based diet would have lower glycemic variability.

Materials and Methods: This is a randomized, active-controlled, double-blinded crossover clinical trial comparing diabetes-specific enteral formula with and without fructose in critically ill patients. Twenty-five patients, who developed hyperglycemia during intensive care unit stay, were included. Patients were randomized to receive each diet for 2 days. Capillary blood sample was taken every 4 hours and glycemic variability was defined as the difference between each time point. A significance level of 0.was defined for all statistical inferences.

Results: Patients which underwent the fructose-based diet reduced their glycemic variability against that under usual care overtime -11.92 mg/dL (95% CI -19.22 to -4.63 mg/dL), p = 0.0013 for between-group differences. We observed also some differences on specific time frames, especially in measures 6, 8 and 12. This effect was seen without any risk of hypoglycemia and complications.

Conclusions: Diabetes-specific enteral formula with fructose was associated with lower glycemic variability in critically ill patients when compared to diabetes-specific enteral formula without fructose.

Disclosure

M. Kumbier: None. C. Teixeira: None. L. Helal: None. J. Almeida: None.
Relationship of Vitamin B12 and Homocysteine Status with Nephropathy and Neuropathy in Metformin-Treated Patients with Type 2 Diabetes
Authors: PATIL SHIVAJIRAO , PAWLAK ROMAN , THOMBARE APARNA , BALTARO RICHARD , HICKS KRISTIE , CUMMINGS DOYLE M.
Published: June 2018

Limited evidence suggests that both vitamin B12 (B12) and homocysteine (Hcy) status are impacted by metformin use and may be associated with diabetes complications. The goal of this research project was to assess the cross-sectional association between B12 and Hcy status and kidney function and neuropathy among patients with type 2 diabetes (T2D) taking metformin. Adult patients in an academic primary care clinic (n = 52; mean age = 53 ± 12.5 years; female 56%; African American 70%) with T2D (mean duration = 9.8 year) and taking metformin (mean duration = 9.2 year) provided informed consent and had blood and urine specimens drawn for: A1c, B12, Hcy, serum creatinine (sCr), urine albumin/creatinine ratio, and eGFR. Neuropathy was assessed using the validated Michigan Neuropathy Screening Instrument. Mean B12 and Hcy levels were 568.7pg/ml and 12.85 µmol/L, respectively. Serum B12 was significantly correlated with Hcy (r = -0.3, p = 0.035) and with A1c (r = 0.36, p = 0.01). Hcy was significantly correlated with both sCr (r = 0.70: p = 0.0001) and eGFR (r = -0.68; p = 0.0001). While B12 was not directly correlated with either diabetes duration or duration of metformin therapy, the correlation of B12 with total metformin exposure (dose x years) approached significance (r = -0.26; p = 0.06). There was no relationship of either B12 or Hcy with neuropathy scores. The bivariate relationship of B12 and Hcy to renal function measures was not different in patients with a diabetes duration of less than 10 years vs. 10 or more years. Consistent with previous studies our findings suggest that B12 status, in addition to correlating with renal function, correlated with glycemic control. Periodic measurement of B12 status should be considered in metformin-treated patients with T2D.

Disclosure

S. Patil: None. R. Pawlak: None. A. Thombare: None. R. Baltaro: None. K. Hicks: None. D.M. Cummings: None.
Decrease in High Readings and Severe Hyperglycemic Events for People with T2D over the Full Year of 2017 in Users Monitoring with a Digital Diabetes Management System
Authors: HERSHCOVITZ YIFAT , DAR SHARON , FENIGER EITAN
Published: June 2018

One of the goals of a digital diabetes management system is to improve patient’s self-management and control of their condition. High blood glucose level is defined as 180-400 mg/dL while severe hyperglycemia (above 400 mg/dL) is considered a medical emergency. Digital engagement can play a pivotal role in the care of patients with diabetes and other chronical conditions, assisting patients to enhance their compliance. The DarioTM Blood Glucose Monitoring System (BGMS) connects physically to a smart mobile device and automatically logs blood glucose measurements into designated App. Data is transmitted to the Dario cloud.

Method: A retrospective data evaluation study was performed on the DarioTM cloud database. A population of active type 2 diabetic (T2D) users that continuously measured their blood glucose using DarioTM BGMS during the full year of 2017 was evaluated. The study assessed the ratio of high (180-400 mg/dL) and hyperglycemic (>400mg/dL) blood glucose readings during full year of 2017 as recorded in the database. The average of high and hyperglycemic glucose readings were calculated in periods of 30-60, 60-90, 90-120, 120-150, 150-180, 180-210, 210-240, 240-270, 270-300, 300-330, 330-360 days and compared to first 30 days as a starting point of analysis.

Results: For 225 T2D active users the ratio of high events (180-400 mg/dL) was reduced gradually in 19.6% (from 23.4% to 18.8% of the entire measurements) from baseline compared to the 12th month of the year. Moreover, the ratio of severe hyperglycemia events (>400 mg/dL) was decreased in 57.8% (from 0.90% to 0.38% of the entire measurements) at the same period.

Conclusion: By means of glucose meter and App patients have the potential to promote behavioral modification and enhance adherence to diabetes management, demonstrating better glycemic control.

Disclosure

Y. Hershcovitz: Employee; Self; DarioHealth. S. Dar: Employee; Self; DarioHealth. E. Feniger: Employee; Self; DarioHealth.
Effect of Fiber Intake on Glycemia, Insulin Secretion, and Inflammation in Patients with Type 2 Diabetes
Authors: TANG CHI , GHANIM HUSAM , GREEN KELLY , MAKDISSI ANTOINE , BATRA MANAV , CHAUDHURI AJAY , DANDONA PARESH
Published: June 2018

Hypothesis. In view of the reduction in post prandial glucose concentrations and an increase in insulin concentrations and the inhibition of post prandial endotoxemia and increases in TLR-4 and TLR-2 expression following the intake of fiber with a high fat high calorie meal (HFHC) in normal subjects, we hypothesized that a similar effect would be observed following the intake with such a meal in patients with type 2 diabetes.

Methods. Ten patients with type diabetes were included in the study and were administered the HFHC meal alone on one day and with dietary fiber (28gram of mainly insoluble fiber) a week later. Fasting premeal and post meal samples were obtained sequentially at hourly intervals for 5 hours. Blood samples were processed for preparation of peripheral blood mononuclear cells (MNC), plasma and serum.

Results. Post meal glucose concentrations were not altered significantly but the peak increase in post meal insulin concentrations was greater after fiber (34±6 vs. 26±4µU/ml, p<0.01) as well as the area under curve (AUC5h) (3234±733 vs. 2214±464µU*5h*ml-1, p<0.01). Fiber intake also induced an early peak of GLP-1 within 15 minutes (29±15% over baseline, NS) which was missing without fiber. Reactive oxygen species (ROS) generation and NFκB binding by MNC was significantly suppressed after fiber by 32±11% and 38±13%, respectively (p<0.01), as was the magnitude of endotoxemia AUC5h by 23±8% (p<0.05). In addition, the increase in the expression of TLR-4 and TLR-2 was also suppressed by 42±15% and 36±14%, respectively (p<0.05)

Conclusions. The intake of fiber resulted in an early peak of GLP-1 and a greater increase in insulin concentrations but the increase in glucose was not altered. Fiber intake also suppressed ROS generation and NFκB binding while reducing the magnitude of endotoxemia and the receptor to endotoxin. Thus, the intake of fiber increases insulinogenesis and reduces oxidative and inflammatory stress in patients with type 2 diabetes.

Disclosure

C. Tang: None. H. Ghanim: None. K. Green: None. A. Makdissi: Speaker's Bureau; Self; Eli Lilly and Company. M. Batra: Speaker's Bureau; Self; Eli Lilly and Company. A. Chaudhuri: Speaker's Bureau; Self; AstraZeneca, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca.
The Effect of Two Isocaloric and Energy-Matched Plant-Based and Processed-Meat Meals on Glucose Metabolism, Gastrointestinal Hormones, and Satiety in Subjects with T2D, Obese Subjects, and Healthy Controls—A Randomized Crossover Study
Authors: KLEMENTOVA MARTA , BELINOVA LENKA , HALUZIK MARTIN , PAVLOVICOVA RENATA , HILL MARTIN , PELIKANOVA TEREZIE , KAHLEOVA HANA
Published: June 2018

Objective: Gastrointestinal hormones play a key role in glucose metabolism and energy homeostasis.

Methods: A randomized cross-over study was used to test the effects of two energy- (600 kcal) and macronutrient-matched plant-based and processed-meat meals (41% carbohydrates, 19% protein, and 40% lipids) on glucose metabolism, plasma concentrations of gastrointestinal hormones, and satiety in subjects with T2D (n=20), obese subjects (n=20) and healthy controls (n=20). Plasma concentrations of glucose, immunoreactive insulin, C-peptide, GLP-1, GIP, amylin and PYY, along with satiety, were determined at 0, 30, 60, 120 and 180 min. Repeated-measures ANOVA was used for statistical analysis.

Results: An increase in stimulated secretion of immunoreactive insulin was observed in T2D and obese subjects (p=0.005, and p=0.045, respectively) after the plant-based meal. We observed an increase in stimulated secretion of C-peptide in all groups after the plant-based meal (p<0.001 for T2D, p=0.014 for obese subjects, and p=0.001 for healthy controls). An increase in postprandial concentrations of amylin was observed in T2D and healthy controls after the plant-based meal (p<0.001 for both groups). An increase in stimulated secretion of GLP-1 was observed in T2D obese subjects and healthy controls (p<0.001, and p=0.01, respectively) after the plant-based meal. A decrease in peak concentrations of GIP (at 60 min.), and an increase in peak concentrations of PYY, were observed in all groups after the plant-based meal. The participants in all groups reported greater satiety after the plant-based meal (p=0.004 for T2D, p<0.001 for obese subjects, and p<0.001 for healthy controls).

Conclusions: Our study suggests that plant-based meals may be effective in increasing stimulated secretion of GLP-1, insulin, amylin and PYY, as well as in promoting satiety.

Disclosure

M. Klementova: None. L. Belinova: None. M. Haluzik: None. R. Pavlovicova: None. M. Hill: None. T. Pelikanova: None. H. Kahleova: None.
Motivational Interviewing to Improve Insulin Acceptance in Insulin-Naïve Korean Patients with Type 2 Diabetes
Authors: SONG YOUNGSHIN , CHO JEONGHWA , LEE HYUNJIN , PARK KEUMOK , LEE YOONHEE , KIM BOHYUN , SEO KAWOUN , LIM ANCHO , JUN YOUNGHEE , NAM SOOHYUN
Published: June 2018

Despite the well documented effectiveness of insulin on glycemic control, many patients with type 2 diabetes are reluctant to receive insulin therapy, called Psychological Insulin Resistance (PIR). Motivational Interviewing (MI) is a client-centered counseling method that may improve PIR and insulin acceptance behavior. The purpose of the study was to examine the effect of MI on insulin acceptance in insulin naïve patients with type 2 diabetes. Participants were recruited from outpatient clinics in two academic affiliated hospitals in South Korea. A matched subjects design was used to allocate the intervention (n=55) and control (n=55) groups based on age, gender, and the stage of intention to receive insulin therapy. The stages of intention to receive insulin therapy were pre-contemplation, contemplation, and action stages. Sociodemographic and clinical factors (years of diabetes diagnosis, medications, HbA1c, comorbidity) were collected by chart reviews. Six MI sessions (2 face-to-face [60 min/session] + 4 telephone sessions [20 min/session]) were provided to the intervention group by 6 trained nurses for 3 months. The effect of MI was measured by attitudes toward diabetes, PIR, and intention to receive insulin therapy at baseline and at 3 months using validated measures. Data were analyzed with paired t-test, t-test, and χ²-test. There was no significant difference in clinical factors, attitudes toward diabetes, PIR, and intention to receive insulin therapy between intervention and control groups at baseline. After the 6 MI sessions, the intervention group improved the intention to receive insulin therapy (χ²=10.44, p=.01) and attitudes toward diabetes (t=2.60, p<.01), and <significantly decreased PIR (t=-2.71, p<.01). MI combined with face-to-face and telephone sessions may be an effective strategy to improve attitudes toward diabetes, PIR, and intention to receive insulin therapy in insulin naïve Korean patients with type 2 diabetes.

Disclosure

Y. Song: None. J. Cho: None. H. Lee: None. K. Park: None. Y. Lee: None. B. Kim: None. K. Seo: None. A. Lim: None. Y. Jun: None. S. Nam: None.
Stigmatization of Adults with Type 1 Diabetes in Asia
Authors: LAM AMANDA Y.R. , GARDNER DAPHNE , RAMA CHANDRAN SURESH , TEO EDMUND P. , ZHU LING , KOH GERALD , GOH SU-YEN
Published: June 2018

Background: Type 1 diabetes (T1D) is uncommon in Asia. Limited awareness can lead to stigmatization of those with T1D.

Aims: We aimed to evaluate diabetes stigma in adults with T1D in Singapore.

Methods: This was a cross-sectional sampling of adults with T1D in a tertiary public hospital, using the Type 1 Diabetes Stigma Assessment Scale (DSAS-1). Higher scores indicate greater levels of stigma.

Results: 125 Singaporeans (mean age 31.2 ± 11.2 y), T1D duration 13.8 ± 7.3 y, M/F: 51/74, 107 on insulin injections, 18 on insulin pumps were sampled. Item response patterns (Figure) suggest a greater burden of stigma in the blame and judgment and identity concerns subscales. DSAS-1 scores did not differ by gender, treatment regimen, age, education level or employment. Identity concerns subscale scores were lower in those with T1D for >10y (n=73) than those with shorter T1D duration (18.9 ± 5.6 v 21.7 ± 7.3, p=0.045). Total DSAS-1 and subscale scores were similar to those of an Australian (Oz) cohort (n=900) (Sg-v-Oz: Total score 53.1 ± 12.9 vs. 53.0 ± 15.6, Treated differently 13.6 ± 4.0 v 13.6 ± 5.4, Blame and Judgment 19.9 ± 5.2 v 19.9 ± 6.0, and Identity Concerns: 19.6 ± 6.4 v 19.5 ± 7.2, all p>0.05).

Conclusion: This is novel data documenting significant levels of diabetes stigma among adults in Singapore, particularly relating to blame and judgment and identity concerns. Despite the low prevalence of T1D in Asia, levels of stigma appeared similar to that of an Australian T1D cohort.

Disclosure

A.Y.R. Lam: None. D. Gardner: None. S. Rama Chandran: None. E.P. Teo: None. L. Zhu: None. G. Koh: None. S. Goh: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim GmbH, Amgen Inc., Novo Nordisk A/S, Sanofi-Aventis, Servier.
Imeglimin Protects INS-1 Cells and Human Islets against High Glucose– and High Fructose–Induced Cell Death by Inhibiting the Mitochondrial PTP Opening
Authors: LABLANCHE SANDRINE , TUBBS EMILY , COTTET-ROUSSELLE CÉCILE , LAMARCHE FREDERIC , MOISAN ANAÏCK , PERSOONS VIRGINIE , BENHAMOU PIERRE Y. , HALLAKOU-BOZEC SOPHIE , FONTAINE ERIC
Published: June 2018

Imeglimin (IME) is a novel glucose-lowering agent improving insulin secretion in response to glucose and insulin sensitivity by targeting mitochondrial bioenergetics. IME is currently in phase 3 in Japan. The toxicity of high glucose or fructose concentrations in INS-1 cells was linked to the opening of the permeability transition pore (PTP), a mitochondrial channel involved in cell death. IME has been shown to prevent PTP opening in human endothelial cells under oxidative stress. This study investigated whether IME could also prevent PTP opening and cell death induced by high glucose or fructose concentrations in INS-1 cells and human pancreatic islets. PTP status in intact cells was assessed by confocal microscopy by measuring mitochondrial membrane potential (TMRM) and NAD(P)H (autofluorescence). Cell viability was measured by flow cytometry. In INS-1 cells and human islets, 30 mM Glucose or 2.5 mM Fructose for 24h led to PTP opening (increase in the NAD(P)H/TMRM ratio), this phenomenon being prevented by 100µM IME. Compared to normal glucose concentration (100%), cell viability significantly decreased (p<0.05) in cells exposed to 30 mM Glucose (76±5% and 47±18% in INS-1 cells and human islets, respectively) and to 2.5 mM Fructose for 72h (78±3% and 35±11% in INS-1 cells and human islets, respectively) but remained unchanged when these cells were preincubated with 100µM IME (in 30mM glucose: 94±3% and 98±3% / in 2.5mM fructose: 96±4% and 79±6% in INS-1 cells and human islets, respectively). We conclude that (i) IME is able to prevent high glucose and fructose-triggered cell death through an inhibition of PTP opening and (ii) a PTP-targeted strategy can prevent beta cell death. In addition to its beneficial effect on beta cell function, IME may have the potential to preserve beta cell mass in a dysmetabolic environment via its inhibitory effect on PTP opening.

Disclosure

S. Lablanche: Other Relationship; Self; Poxel SA. E. Tubbs: None. C. Cottet-Rousselle: None. F. Lamarche: None. A. Moisan: None. V. Persoons: None. P.Y. Benhamou: Consultant; Self; Abbott, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Eli Lilly and Company, Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Diabeloop S.A.. S. Hallakou-Bozec: None. E. Fontaine: Other Relationship; Self; Poxel SA.
Blog Use Is Associated with Lower Hemoglobin A1c in Adults with Type 1 Diabetes
Authors: OSER SEAN M. , OSER TAMARA , MCGINLEY ERIN L. , BERG ARTHUR , STUCKEY HEATHER L.
Published: June 2018

Recent technological advances in T1D self-management include not only devices like glucose meters, insulin pumps, and continuous glucose monitors (CGM), but also social media and the ability to find peer support more easily and quickly than ever. However, it is largely unknown how some social media, including blogs, are used in self-management and what effects they might have. This study compared A1c in adults with T1D who read T1D-themed blogs and adults with T1D who do not read such blogs.

Methods: Participants were recruited online through popular T1D-themed blogs and through a mailing to adults with T1D listed in the Penn State diabetes registry. Self-reported A1c, blog use, insulin pump use, CGM use, and sociodemographic factors were assessed. Univariate analysis evaluated for A1c differences between groups across variables including blog use, insulin pump use, and CGM use. Linear regression adjusted for significant covariates.

Results: 282 completed surveys were received (214 blog readers, 68 blog non-readers). A1c was lower for blog readers than blog non-readers (7.vs. 7.48, P=.006), for insulin pump users than multiple daily injections (7.04 vs. 7.65, P=.001), and for CGM users than CGM non-users (6.99 vs. 7.47, P=.001). After adjusting for significant covariates, the association between blog use and A1c remained significant (P=.039).

Conclusions: Reading T1D-themed blogs was found to be associated with glycemic control; self-reported A1c was 0.43% lower among blog readers than among blog non-readers, a clinically significant difference approaching the magnitude seen with CGM use (0.48%) and insulin pump use (0.61%). The A1c differences among pump users and CGM users in this study are similar to those found by others, lending support to the likelihood of a true association between A1c and blog use. To our knowledge, this is the first study to evaluate blog use and A1c and therefore the first to find an association between them. Further research should seek to explain the reasons for this association.

Disclosure

S.M. Oser: None. T. Oser: None. E.L. McGinley: None. A. Berg: None. H.L. Stuckey: Consultant; Spouse/Partner; Calibra Medical, Eli Lilly and Company. Research Support; Spouse/Partner; Novo Nordisk Inc.. Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc..
Diabetes Distress and Glycemic Control in Working People with Type 1 Diabetes—The Role of Intentional Hyperglycemia at Work
Authors: HANSEN ULLA M. , OLESEN KASPER , SKINNER TIMOTHY C. , WILLAING INGRID
Published: June 2018

Aims: We set out to test the hypothesis that intentional hyperglycemia at work (henceforward IHW) mediates the link between diabetes distress and glycemic control in working adults with type 1 diabetes.

Methods: Clinical information on HbA1c, complications, diabetes duration and age was linked with self-report measures of psychosocial health and work life from people with type 1 diabetes of working age attending a specialist diabetes clinic in Denmark. Diabetes distress was assessed with a work-comprehensive measure encompassing the PAID-5 and two additional items assessing distress in reconciling diabetes and work life. IHW was assessed with one item. Glycemic control was assessed with HbA1c. Using structural equation modeling techniques we modelled a theory-based structural path model and tested the mediation hypothesis using bootstrap estimates and goodness-of-fit tests.

Results: The sample consisted of 1,126 working adults with type 1 diabetes. The model suggested that the effect of diabetes distress on glycemic control was fully mediated by IHW. Diabetes distress was associated with more frequent IHW (β = .23, p < .001) which in turn was associated with elevated HbA1c (β = .28, p < .001). The final model was able to account for 20% of the variance of IHW, and 11% of the variance in glycemic control. There was an excellent fit to the data according to established criteria (in parenthesis); X2/DF=3.3 (<5), GFI=.995 (=.95), CFI=.990 (=.95), RMSEA=.047 [.030-.065] (<.050).

Discussion: This study highlights the role of IHW as a mediator for the link between diabetes distress and glycemic control specific to working adults with type 1 diabetes. A sound understanding of the mechanisms linking diabetes distress to suboptimal glycemic control in working people with type 1 diabetes can inform intervention development and ultimately increase the chance of improving diabetes self-care and quality of life of working people with type 1 diabetes.

Disclosure

U.M. Hansen: None. K. Olesen: None. T.C. Skinner: Board Member; Self; Decision Support Analytics. I. Willaing: None.