bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Myeloperoxidase and MPO Reverses Microvascular Insulin Resistance in High-Fat Diet (HFD)-Fed Rats
Authors: BARRETT EUGENE , AYLOR KEVIN W. , CHAI WEIDONG , GAN LI-MING
Published: June 2018

Chronic, low-level inflammation underlies much of the vascular and metabolic insulin resistance associated with HFD. Release of MPO by leukocytes may be an early contributor to the inflammatory process and endothelial dysfunction that accompanies HFD feeding. Plasma MPO concentrations are increased in both human obesity and diabetes and HFD-fed rats. However, the impact of MPO on microangiopathy and its relation to insulin resistance is unclear. We tested whether AZD5904 (a potent, irreversible inhibitor of MPO, AstraZeneca) improves endothelial function and vascular insulin responses in insulin resistant, adult male SD rats fed a HFD (60% calories from fat) for 2 weeks. HFD fed rats received vehicle (n=8) or AZD5904 (75 µmol/kg/day, n=10) via an Alzet Mini pump for 2 weeks. A 3rd group of rats (n=8, vehicle alone) were fed a chow diet for 2 weeks. After 2 weeks of HFD or control diet, rats were fasted overnight and received a 2-hour euglycemic insulin clamp (3 mU/kg/minutes). Hindleg muscle microvascular perfusion was assessed using contrast-enhanced ultrasound and insulin-stimulated steady-state whole body glucose disposal was determined. Insulin infusion increased muscle microvascular perfusion by 2-3 fold in chow fed rats (p<0.05). HFD feeding abolished insulin-induced microvascular recruitment in muscle, and decreased insulin-mediated glucose disposal by ∼45% (p<0.01). Simultaneous treatment with AZD5904 fully restored insulin-mediated muscle microvascular perfusion (p<0.05) in HFD rats, but did not improve insulin-stimulated glucose disposal in HFD-fed rats. We conclude that inhibition of MPO with AZD5904specifically reverses muscle microvascular insulin resistance in HFD rats. This implicates MPO as a significant contributor to HFD-induced endothelial inflammation and suggests a role for MPO inhibition to improve microvascular complications in patients with vascular insulin resistance.

Disclosure

E. Barrett: None. K.W. Aylor: None. W. Chai: None. L. Gan: Employee; Self; AstraZeneca.
MicroRNA Drivers of the Effects of High-Fat Diet and Bariatric Surgery on the Intestine
Authors: SETHUPATHY PRAVEEN
Published: June 2018

High-fat diet (HFD) leads to obesity and insulin resistance, which are key risk factors for type 2 diabetes (T2D). Many studies have investigated the effects of HFD on several metabolic tissues, but the intestine is highly underexplored. The small intestine is the primary site of the positive metabolic effects of the most successful pharmacologic treatments (metformin) and surgical interventions (bariatric surgery) for T2D. The innermost cell layer of the small intestine is the epithelium, which is the most rapidly renewing tissue in the body and is comprised of several cell types that mediate nutrient absorption and energy homeostasis. The high renewal rate for these cells is driven by a small but highly proliferative population of intestinal stem cells (ISCs). In this study, we showed that an obesogenic HFD significantly increases proliferation of ISCs, and alters allocation of ISCs to different lineages in mice. To define the molecular mechanisms that underpin these effects, we performed whole transcriptome analyses (both small RNA-seq to profile microRNAs (miRNAs) and RNA-seq for long, non-coding RNAs and mRNAs) in Lgr5+ ISCs. We demonstrated that HFD shifts the miRNA profile of ISCs toward that of enterocytes, the cells involved in nutrient absorption. Further bioinformatics analysis revealed that this shift is driven primarily by changes in two miRNAs, miR-194 and miR-375. Specifically, HFD suppresses miR-375 by over five-fold (P < 0.05). Notably, follow-up studies showed that vertical sleeve gastrectomy, which reverses the effects of HFD, significantly rescues the levels of miR-375 in Lgr5+ ISCs. We hypothesized that suppression of miR-375 promotes ISC proliferation and allocation to enterocytes. To test this hypothesis, we generated miR-375-/- mice and showed that loss of miR-375 in vivo leads to a marked increase in ISC proliferation and villus height, mimicking the effects of HFD. Currently we are investigating whether miR-375 is essential for the effects of bariatric surgery.

Disclosure

P. Sethupathy: None.
The Relationship between Sodium Intake and Albuminuria in U.S. Adults with Chronic Kidney Disease With and Without Diabetes
Authors: OZIEH MUKOSO N. , GARACCI EMMA , WALKER REBEKAH J. , EGEDE LEONARD E.
Published: June 2018

Introduction: Low sodium diet has been shown to have blood pressure lowering effects and as such promising effect on slowing CKD progression. The aim of this study is to examine if the relationship between sodium intake and albuminuria differs by diabetes status in patients with CKD.

Methods: We used National Health and Nutrition Examination Survey for adults ≥ age 20 between 2007-2014. Primary outcome variable was Albumin-to-creatinine ratio (ACR). CKD stage was based on estimated glomerular filtration rate and Albumin-to-creatinine ratio. Sodium (Na) intake was calculated as the sum of total dietary and supplement intake. Diabetes and prediabetes were self-reported. Statistical analysis was performed using survey commands to provide nationally representative estimates. A generalized linear regression model was run adjusting for relevant covariates using log transformed ACR, with estimates exponentiated to provide mean ratios (MR).

Results: About 3535 adults, representing 28,787,552 U.S. adults were included in the study. The mean Na intake for the cohort was 3,082mg (median 2,783mg) and 26% of the cohort had sodium intake <2,000mg. In the unadjusted analysis, an increase of 1,000mg Na was significantly associated with higher ACR (MR=1.04, 95% CI 1.00-1.08). In addition, non-Hispanic blacks (NHB) (MR=1.82, 95% CI 1.52-2.19) and Hispanics (MR=2.31, 95% CI 1.96-2.72) had higher ACR compared to non-Hispanic whites (NHW). After adjusting for relevant covariates including CKD stage, participants with diabetes were more likely to have ACR (MR=1.52, 95% CI 1.28-1.80) while the relationship between Na intake and ACR lost significance (p=0.05).

Conclusions: For every 1000mg increase in sodium intake participants were 4% more likely to have albuminuria. NHB were 82% and Hispanics were 131% more likely to have albuminuria compared to NHW. Future prospective studies should focus on examining the relationship between sodium intake and albuminuria among minorities.

Disclosure

M.N. Ozieh: None. E. Garacci: None. R.J. Walker: None. L.E. Egede: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Advisory Panel; Self; Novo Nordisk Inc..
Safety and Efficacy of Pregabalin Treatment and Quality of Life in Patients Treated with Pregabalin in Painful Diabetic Peripheral Neuropathy
Authors: RADHAKRISHNAN CHANDNI , UT ANJUSHA , K SREEJITH , MANIKATH NEERAJ , CR RINU R.
Published: June 2018

The treatment modalities for painful diabetic peripheral neuropathy (PDPN) include antidepressants, anticonvulsants, capsaicin, membrane stabilizers and analgesics. Recent guidelines recommend pregabalin as a first line treatment for PDPN. But controversy exists about its efficacy and safety.

The main objective of the study is to determine the safety, efficacy of pregabalin treatment for PDPN. An interventional cohort study was carried out in a tertiary care teaching hospital. Subjects who satisfy the inclusion criteria were included in the study after obtaining written informed consent. A total of 52 subjects were enrolled in the study. PDPN was confirmed by means of (1) Diabetic neuropathy symptom (DNS) score of more than one point, (2) Diabetic neuropathy examination score (DNE) of more than three points, (3) Neuropathic disability score (NDS) of more than 6 points and (4) Pain of more than 50% assessed by Visual Analog Scale (VAS). The subjects received pregabalin 75mg once daily for one week followed by 75 mg twice daily for further 3 weeks based on patient’s tolerability. Pain intensity was measured by using Short-Form McGill pain questionnaire. Safety of therapy was assessed from the incidence of adverse events including physical as well as laboratory evaluations. All study subjects’s enrolled received pregabalin. Study showed that pregabalin treatment significantly reduced pain in diabetic peripheral neuropathy with mean pain score 11.52 ± 9.30 (P value 0.00). The most common adverse effects of pregabalin were dizziness, peripheral edema, and somnolence.

The study concluded that pregabalin significantly reduces pain and improve quality of life in PDPN.There was a dose-related increase in efficacy of pregabalin treatment. Moreover, there was a dose-related increase in incidence of most adverse events which are generally mild to moderate.

Disclosure

C. Radhakrishnan: None. A. Ut: None. S. K: None. N. Manikath: None. R.R. Cr: None.
Retrospective Analysis of Correlation between Peripheral Artery Disease and Diabetic Retinopathy in Type 2 Diabetes Patients
Authors: CHANDARANA HARDIK , SABOO BANSHI D. , PATEL AMISH , HASNANI DHRUVI , SHAH SMITA , GOKLANI RUTUL , PANCHAL DHARMENDRA , SAIYED MAHIRA , CHUDASAMA DIPAK B.
Published: June 2018

There are no enough evidences which show the correlation of peripheral arterial disease (PAD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). We have tried to explore the relationship between PAD and DR in this study.

Method: Patients with T2DM since more than 5 years with HbA1c > 7% and patients with DR or with no DR were included in this cross-sectional study. As a part of our clinical protocol at the first visit all type 2 DM patients are assessed through ABI, VPT, CAN and retinoscope for their complications. A history of addiction including smoking and tobacco were recorded. Stages of DR were graded by digital retinal photographs using Zeiss VISUCAM. PAD assessment was done by using Ankle Brachial Index (ABI), Toe Brachial Index (TBI) and ultrasound doppler.

Result: It was found that out of 573 patients attended OPD in month of November 2017 at Dia Care - Diabetes Care and Hormone Clinic were taken into this study. Out of these 573 patients, the HbA1c of 475 patients was uncontrolled (>8%) with duration of diabetes of 7.5 ± 1.2 years.Out of this, 138 patients were having DR [34 Proliferative Diabetic Retinopathy (PDR) and 104 Non-Proliferative Diabetic Retinopathy (NPDR)].It was seen that patients with DR had a significantly higher proportion of Peripheral Arterial Disease (ABI < 1 and > 1.3) compare to patients who did not have DR (53 out of 138 vs. 59 out of 337). The patients with DR also had lower TBI and abnormal duplex ultrasound than patients who did not have DR. This showed the correlation between DR and PAD that in patients with DR the incidence of PAD was more common. We also observed the relation between duration of diabetes and uncontrolled glycemic status with that of PAD and DR. We are still evaluating these patients further to establish a positive relation between these variables.

Conclusion: We should focus on screening PAD in patients with DR in clinical practice.

Disclosure

H. Chandarana: None. B.D. Saboo: None. A. Patel: None. D. Hasnani: None. S. Shah: None. R. Goklani: None. D. Panchal: None. M. Saiyed: None. D.B. Chudasama: None.
The Charcot Foot and Mortality from 2000 to 2016
Authors: ENGBERG SUSANNE , KIRKETERP-MØLLER KLAUS , RASMUSSEN ANNE
Published: June 2018

Introduction: The Charcot foot is a relatively rare but serious foot complication in patients with diabetes and neuropathy. The aim was to study the mortality and compare baseline characteristics at diagnosis between Charcot patients who died or survived during follow-up.

Materials and Methods: A retrospective cohort study including all patients with a Charcot diagnosis at our centre from 2000 to 2016. Poisson regression analyses were done.

Results: A total of 164 patients had the diagnosis Charcot (DM146) and 52 (31.1%) died during follow-up. They lived for 1973 days (range: 219-4895) i.e., 5.4 years. Patients were followed for 1122 years in total, median 6.0 years/patient (Q1-Q3=3.2-10.0). The mortality rate was 4.6/100 person-years-at-risk. Patients who died were significantly older (61±10 vs. 54±11 years), had less often type 1 diabetes (40 (27-55) vs. 60% (50-70)), were less often non-smokers (35 (22-49) vs. 52% (42-61)), had a lower hemoglobin (7.9±1.2 vs. 8.3±0.9), a higher creatinine (114 [88-161] vs. 85 [69-109]) and were more often treated with antitrombotic agents (71 (57-83) vs. 53% (43-62)) compared to survivors. Rate ratios for death were insignificantly different among smokers and non-smokers, among patients with type 1 and 2 diabetes, among patients with a diabetes duration below or above 10 years and among patients with HbA1c above or below 60 mmol/mol-both in univariate analyses and after adjustment for age and gender.

Conclusion: The mortality rate among patients with Charcot feet was 4.6%/person-years-at-risk and was not affected by diabetes type, smoking, diabetes duration or HbA1c-level.

Disclosure

S. Engberg: None. K. Kirketerp-Møller: None. A. Rasmussen: None.
Effects of Essential Oils on Biofilm-Forming Microorganisms from Patients with Diabetic Foot
Authors: NIKOLAYEVA ANTONINA B. , AKHMETOVA SAULE B. , GAZALIYEVA MERUERT A. , SIROTA VALENTINA B. , ZHUMALIYEVA VERA A. , ZHAKENOVA SAULE R.
Published: June 2018

Our study was focused on the possibility of using essential oils (EOs) in the prevention of biofilm development by microorganisms isolated from patients with diabetic foot. Dominant microorganisms with a strong production of biofilms and effects of EOs on them are presented on the Table. Growth of biofilms was carried out in polystyrene microplates at 37°C for 24 hours. The EOs were extracted from following plants: Matricaria chamomilla (Asteraceae) (MCEO), Eucalyptus (Myrtaceae) (EEO), Tanacetum fruticulosum (Asteraceae) (TFEO), Thymus marschallianus (Labiatae) (TMEO) and Artemisia sieversiana (Asteraceae) (ASEO). Serial dilutions of EOs were prepared with dimethyl sulfoxide (1:1 v/v) and then in Mueller-Hinton broth with 0.5% Tween 20. The EOs were diluted to the following dilutions: 12.5%, 6.25%, 3.13%, 1.56%, 0.78%, 0.39%, 0,195%, 0,097%, 0,048%, and 0,024%. The EOs were deposited in wells of microplates with bacterial suspensions at 37°C for 24 hours and then we determined minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of EOs by OD (optical density) reading at a wave length of 600 nm. According to our study, strong effects of MCEO on gram-positive and gram-negative microbes were shown. The moderate effects were detected for other investigated EOs. Our results encourage research related to the application of essential oils to fight diabetic complications.Activity of essential oils against biofilm-forming microorganisms from patients with diabetic footEssential oilsMCEOEEOTFEOTMEOASEOMicroorganismsMIC,%: MBC,%MIC,%: MBC,%MIC,%: MBC,%MIC,%: MBC,%MIC,%: MBC,%Staphylococcus aureus0.195:0.396.25:6.250.78:3.131.56:3.133.13:6.25Staphylococcus haemolyticus0.097:0.1956.25:12.50.78:1.560.39:0.783.13:3.13Escherichia coli0.024:0.0480.78:3.130.39:0.390.78:3.130.39:0.78Enterococcus cloaceae0.024:0.0973.13:3.130.195:0.1950.39:0.780.39:0.39Enterococcus faecalis0.048:0.0970.78:3.130.195:0.780.39:0.390.78:1.56Klebsiella spp.0.097:0.1953.13:3.130.097:0.390.195:0.780.78:0.78

Disclosure

A.B. Nikolayeva: None. S.B. Akhmetova: None. M.A. Gazaliyeva: None. V.B. Sirota: None. V.A. Zhumaliyeva: None. S.R. Zhakenova: None.
Orthosis DCFzO in Charcot Neuroarthropathy Management
Authors: IMMANUEL JULIUS N.
Published: June 2018

Study was aimed to evaluate the effectiveness of Innovative Orthosis: Diabetic Charcot Foot Customized Orthosis [DCFzO] in terms of Comfort, Distortion Containment and Rehabilitation Care in patients with Charcot Neuroarthropathy(CN). DCFzO is a unique pattern Custom Designed and Fabricated Poly Ethylene Orthosis: for patients with CN/Diabetic Charcot Foot. CN develops among Diabetic patients with peripheral neuropathy, leading to pathological fracture/dislocation at Ankle and foot. “CN” potentially compromises normal Gait-Pattern [Ambulation] at Early-stage, Causes disability at Later-stage and can potentially end up in Amputation if neglected.

Data: Involved group (3:1) Charcots Stage- 2 and Stage- 3. Patients* [CN Ankle/foot depended on Orthosis (Rehabilitation Aid)for independent Standing and Walking].

Method: Alignment comparison with and with-out DCFzO(W and WOD) : CN ankle/foot Stability during weight bearing stance. Ability to Ambulate (W and WOD) : Balance and Confidence. Data comparison of Girth record: Follow-up schedule. Visual reports comparison [Photograph records]. Patients* personal Feed-back: Orthosis effect in terms of comfort as AID device and suggestions.

Conclusion: Orthosis “DCFzO” exhibited efficacy in aiding CN Foot: in terms of Comfort, Protection, Assistance in ambulation and Restore maximum possible ankle foot anatomical structure’ at Stage 2 and 3 treated at ALD- PMR hospital.

Disclosure

J.N. Immanuel: None.
Impacting Postprandial Glucose (PPG) Control with Faster-Acting Insulins—Effect of Online Education on Physician Knowledge and Confidence
Authors: SENDAYDIEGO ANNE M. , TRIER JOACHIM , MONTANYA EDUARD
Published: June 2018

Purpose: To determine if online medical education for diabetologists/endocrinologists (diabs/endos) and primary care physicians (PCPs) can improve knowledge regarding the consequences of elevated PPG, the need for better PPG control and more physiologic mealtime insulin replacement, PK/PD profiles, and latest clinical data of investigational faster-acting insulin analogs.

Methods: The educational activity consisted of a 30-min online video panel discussion amongst four experts with synchronized slides. Educational effect was assessed with a repeated pairs pre- and post-assessment study using a 3-item, multiple-choice, knowledge and competence questionnaire plus a confidence assessment in which participants act as their own controls. A χi-squared test assessed statistical significance at the P <.level. The activity launched December 21, 2016; data collected until February 1, 2017.

Results: Participation in the activity significantly improved knowledge of diabs/endos (average from 47% to 69%; n=73) and PCPs (from 55% to 72%; n=112) with respect to latest clinical data and potential benefits of new and emerging faster-acting insulins. On pre-assessment, clinicians showed high levels of knowledge (87%/82%) about the consequences of elevated PPG which was primarily reinforced on post-assessment. After participation, 51% of diabs/endos and 67% of PCPs demonstrated greater confidence in their understanding of the clinical profile of emerging faster-acting insulins for PPG management.

Conclusions: Participation in online education resulted in improvement or reinforcement of knowledge and confidence regarding the importance of good PPG control and the clinical profile of investigational faster-acting insulins. Further education is warranted on complications that correlate with elevated PPG, physiologic action of mealtime insulin replacement and latest clinical data of new and emerging faster-acting insulins.

Disclosure

A.M. Sendaydiego: None. J. Trier: None. E. Montanya: Employee; Spouse/Partner; Almirall, S.A.. Advisory Panel; Self; AstraZeneca. Consultant; Self; Intarcia Therapeutics, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Menarini Group. Consultant; Self; MSD K.K.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, AstraZeneca, Medscape. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Servier. Consultant; Self; Novartis Pharmaceuticals Corporation.
Assessing Efficacy of Diabetes School by Diabetes Knowledge Scale in Turkey
Authors: TASKIRAN BENGUR , CANSU GUVEN B. , MUTLUAY RUYA
Published: June 2018

Aim: The prevalence of DM increased dramatically from 7.2% to 13.7% in Turkey. Ministry of Health has been supporting diabetes school, a model of structured group education, since 2014. The efficacy of this programme has not been evaluated beyond hemoglobin A1c control. In this study, we aimed to evaluate knowledge of diabetes before and immediately after the school.

Methods: We recruited patients with a diagnosis of DM who were registered to diabetes school in September 2017. The programme was executed by a multidiciplinary team as 90 minutes sessions a week for 4 consecutive weeks. The participants who attended at least 3 sessions were given certificates. Due to low sociocultural profile true/false version of Michigan Diabetes Knowledge Scale (MDKS), which was translated into Turkish, was used. The scale includes 20 items regarding nutrition, comorbidities, blood glucose control, exercise, medication, and complications. The patients chose true/false or “don’t know” for each statement in the questionaire.

Results: Ninety four patients registered to the school. However only 54 attended the programme and 41 agreed to take the survey. Among them 25 patients completed ≥3 sessions and 23 participated in the survey before and after the programme. The most common correctly identified answers were related to the items regarding the importance of regular check-up in detecting and preventing complications (before: 69%, after: 100%). The number of patients correctly identifying more than half of the statements was 15 (38%) before and 17 (73%) after the programme. Among 23 patients who completed both the programme and the surveys, 19 (82%) showed significant improvement in correct answers.

Conclusions: Participation and adherence to diabetes school programme was low. Despite low number of patients studied, knowledge of diabetes improved after the programme. MDKS can be used along with school programmes to select the subgroup of patients that need more simplified, interactive, and repetitive sessions.

Disclosure

B. Taskiran: None. G.B. Cansu: None. R. Mutluay: None.
Implementation of Person-Centered Methods in Group-Based Diabetes Education
Authors: STENOV VIBEKE , WIND GITTE , VALLIS MICHAEL , REVENTLOW SUSANNE , HEMPLER NANA F.
Published: June 2018

Healthcare professionals’ (HCPs) skills in person-centeredness are pivotal for delivering successful diabetes self-management education and support (DSMES). Many HCPs favor person-centered methods as a concept but implementation in practice remains challenging. The main focus is on information about diabetes, complications, medications, diet and exercise. This study explored how HCPs implement new methods to facilitate person-centered DSMES in groups.

The study was guided by action research and divided into three phases (investigation, action, and pilot) using a variety of qualitative methods. In step one, observations were conducted across five educational settings including 49 persons with T2DM and 13 HCPs to explore HCPs’ person-centered skills. In step two, 14 HCPs collaborated in two workshops to develop new methods e.g., exercises and dialog tools to prompt discussions about psychosocial aspects of diabetes and to fit educational needs to both the individual and the group. In step three, we pilot-tested the methods using observations in three settings and interviewed 5 HCPs and 27 participants with T2DM. A final workshop was conducted to evaluate the methods. Systematic text condensation and hermeneutic analysis were used to analyze data.

Implementation of the methods was characterized by three categories. Some HCPs chose not to implement the methods because they conflicted with their usual practice relying on the biomedical model. Other HCPs agreed with the concept but was unable to structure the process, leaving participants uncertain about the aim. Finally, some HCPs succeeded with implementation promoting participants’ needs, reflections and discussions in groups.

Implementing methods to deliver person-centeredness is complex and requires systematic training of HCPs. The training should be structured stepwise incorporating techniques directed towards existing skills including ample time to train and reiterate skills.

Disclosure

V. Stenov: None. G. Wind: None. M. Vallis: Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk Inc.. Speaker''s Bureau; Self; AbbVie Inc.. Advisory Panel; Self; Valeant Pharmaceuticals International, Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. S. Reventlow: None. N.F. Hempler: None.
The Development and Testing of MyT1DHope—A Website for Parents of Children with Type 1 Diabetes
Authors: HOLTZ BREE , MURRAY KATHARINE , HERSHEY DENISE , NUTTALL AMY K. , COTTEN SHELIA , PARK TAIWOO , DUNNEBACK JULIE K. , WOOD MICHAEL A.
Published: June 2018

Background: Caring for a child with type 1 diabetes (T1D) may be stressful for the entire family. Management is complex and requires parents to take on this complex responsibility. As a result, parents are at risk of being diagnosed with depression and anxiety, and may experience feelings of isolation. Diabetes education and support group involvement can lead to successful adjustment to life with a child with T1D. Websites have the ability to provide this type of support, and many T1D websites exist. However, a well-organized, parent-focused tool with social support capabilities is needed.

Objective: The objective of this study was to develop and conduct a randomized controlled pilot test of a website, MyT1DHope, for parents of children with T1D.

Methods: Once the website was developed, participants were recruited through a Michigan family network, to begin the 8-week testing. Participants (N=102) were randomly assigned to receive access to our website (n=51) or receive a PDF packet (n=51) on T1D. All participants were assessed pre- and post-intervention on validated measures of parents’ diabetes knowledge, health literacy, social support, self-efficacy, quality of life as well as usability and acceptability of the website.

Results: Our concept for the website was well received by participants in the formative research phases. Specifically, parents stated a need for a “one-stop-shop” for all information a parent with a child with T1D may need and to organize that information by stages of the child’s development. Our preliminary results suggest that parents in both groups started the study with high diabetes knowledge, social support, self-efficacy, and quality of life. Data analysis of the 8-week pilot test is ongoing.

Conclusion: Many websites exist with the purpose of providing information to those impacted by T1D. This paper reports results of testing a website, MyT1DHope, for parents with children with T1D. MyT1DHope has the potential to improve the lives of parents caring for a child with T1D.

Disclosure

B. Holtz: None. K. Murray: None. D. Hershey: None. A.K. Nuttall: None. S. Cotten: None. T. Park: None. J.K. Dunneback: None. M.A. Wood: Research Support; Self; Medtronic MiniMed, Inc..
Magnetic Resonance Diffusion Tensor Imaging of the Human Calf in Subjects With and Without Type 2 Diabetes during Rest and Isometric Plantarflexion Exercise
Authors: EDALATI MASOUD , SORENSEN CHRISTOPHER J. , HASTINGS MARY , ZAYED MOHAMED A. , MUELLER MICHAEL J. , ZHENG JIE
Published: June 2018

Aim: This project aims to study differences in diffusion properties of the human calf muscle in subjects with and without type 2 diabetes mellitus (DM) using diffusional properties of water molecule.

Methods: Twenty-one subjects were examined in a 3T MRI scanner after obtaining consents. Two groups were tested: 8 participants without DM (WDM) and 13 participants with DM. We used a custom-made MRI compatible ergometer that allows a constant exercise load. Finally, we calculated diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), and eigenvalues (λ1, λ2, λ3) for further analysis.

Results: Statistical analysis revealed no significant differences (P>0.05) in diffusion indices of muscles between WDM and DM at the rest position. However, all the muscles in DM showed (Figure) an overall statistically significant increase (P<0.05) in MD, λ2, and λ3 in response to exercise, in comparison with the WDM (MD= 15.02%; λ2= 16.50%; λ3= 14.22% for the MG).

Conclusion: There were considerable changes in diffusion indices between WDM and DM groups during the calf exercise. This study demonstrated that structural muscle damage due to the diabetes can be readily distinguished from nondiabetes using DTI.

Disclosure

M. Edalati: None. C.J. Sorensen: None. M. Hastings: None. M.A. Zayed: None. M.J. Mueller: None. J. Zheng: None.
Predictor of Mortality after Hospital Discharge in the Elderly with Type 2 Diabetes Mellitus—Follow-Up of Two Years
Authors: BERETTA MILENI V. , FELDMAN JULIANE V. , RODRIGUES TICIANA
Published: June 2018

Muscle-related loss of the aging process can worsen the individual’s functionality as well as reduce gait and strength of the handgrip. The Gait speed test reflects the health and functional status of the elderly as well as being a predictor of survival. In older adults with diabetes there seems to be a strong correlation between gait and worse outcomes.

Objective: To determine the relationship between gait speed test and all-cause mortality after discharge in the elderly with type 2 diabetes melito (T2DM).

Methodology: A prospective study that included hospitalized patients at the Hospital de Clínicas of Porto Alegre (HCPA, South of Brazil) from July 2015 to December 2016, with T2DM, aged over 60 years and up to 48 hours of hospitalization in one unit. Follow-up was done by telephone and by consulting the medical records. In order to evaluate the walk, a 6-meter walking test, such as Time Up and Go (TUG), was performed, muscle strength was measured using an dynamometer and muscle mass was measured in the largest region of the circumference of the calf (CC). The patients were considered with reduced gait when they completed the test in the value below 0.8 m/s. This project was approved by the HCPA Ethics Committee under Number150068.

Results: 312 patients with T2DM were included, mean age 71.31 ± 6.45 of which 51% were women, 82% were Caucasian. The mean velocity in the TUG was 0.54 m/s (0.46-0.66) and presented a positive correlation with age (r = 0.283, p <0.001), duration of hospitalization (r = 0.081, p = 0.17) and negative correlation with BMI (r = -0.42, p = 0.48). The mortality was 45.3%. In the multivariate analysis after adjustment for age, sex, physical activity, and BMI the lower gait speed test and the CC maintained an association with post-high mortality (OR = 2.064, 95% CI 1.048-4.063 p = 0.036 and OR = 0.872, 95% CI 0.78-0.96 p = 0.010).

Conclusion: patients with DM2 who had reduced speed gait and CP, had a greater risk of death after hospital discharge.

Disclosure

M.V. Beretta: None. J.V. Feldman: None. T. Rodrigues: None.
Characterization of Islet-Infiltrating Lymphocytes in Type 1 Diabetes
Authors: FELTON JAMIE L. , BONAMI RACHEL H. , HULBERT CHRYS , THOMAS JAMES W.
Published: June 2018

Type 1 diabetes (T1D) results in the immune-mediated destruction of insulin-producing beta cells in the pancreas. As such, immune intervention to prevent or delay T1D is an appealing therapeutic approach. Development of an antigen-specific intervention that targets the diabetogenic immune response without compromising systemic immunity is complicated by an expanding list of antigenic targets, including post-translationally modified peptides generated at the site of autoimmune attack in the islet. Thus, development of effective antigen-based therapy requires not only antigen identification, but also understanding of the unique antigen processing environment facilitated by the islet itself. Recently, cellular metabolism has emerged as a potent modulator of immune cell function. However, the metabolic state lymphocytic infiltrate in the islet, termed insulitis, is not known. Given the highly vascularized nature of the islet needed to accommodate the metabolic demand associated with insulin secretion, we sought to characterize the islet’s distinct metabolic environment and its influence on T-B cell interactions at the site of autoimmune attack. Using a transgenic mouse model that develops accelerated diabetes (VH125SD.NOD), we assessed the metabolic signature of islet-infiltrating lymphocytes compared to those in the spleen and pancreatic lymph nodes. We determined that islet-infiltrating lymphocytes are characterized by decreased glucose uptake in CD4 and CD8 T cell subsets. Mitochondrial mass and polarity were decreased in all subsets compared to secondary lymphoid organs, suggesting reduced metabolic fitness. These studies reveal a metabolic distinction between islet-infiltrating and secondary lymphoid organ lymphocytes and suggest that metabolic features that differentiate immune cells at the site of autoimmune attack are a potential target for selective therapeutic interventions in T1D.

Disclosure

J.L. Felton: None. R.H. Bonami: None. C. Hulbert: None. J.W. Thomas: None.
A Collaborative Approach to Health Promotion Targeting People with Mental Illness at Risk of Diabetes—A Process Evaluation
Authors: HEMPLER NANA F. , LEVISEN VINIE H. , PALS REGITZE S. , KROGH NAJA RAMSKOV , LAURSEN RIKKE H.
Published: June 2018

People with mental illness (users) have a notable higher risk of developing type 2 diabetes than the general population. Recent studies show that traditional lifestyle interventions focusing solely on exercise and diet targeting users have small effect. Studies suggest that collaborative approaches as a starting point for health behavior change is more beneficial, but implementation into practice is a challenge. Using the Medical Research Council’s guidance for process evaluation, we explored implementation of a collaborative approach in health promotion activities targeting users at risk of diabetes. The collaborative approach focused on involvement of users in the agenda setting and reflection about readiness to change health behavior and was supported by dialogue tools (e.g., quotes and games), developed in collaboration with users. Educators received three days of training in applying the approach. Collected data included questionnaires for users (n=154) and educators (n=158), interviews with users (n=14) and educators (n=10) and observations of health activities (n=37). Data were analyzed using descriptive statistics and systematic text condensation. The majority of educators tested the approach in their practice and tried at least one tool (96%). Users expressed that the approach supported them in expressing their thoughts regarding their health and directed focus on their needs rather than the agenda of the educator. Most users strongly agreed that educators were open-minded and responsive (93%). However, observations showed that some educators overlooked cues from users regarding motivation for health behavior change. Furthermore, educators pointed to lack of involvement from their managers as a barrier for implementation. Implementation of a collaborative approach was feasible in practice. However, training of educators in active listening and involvement of managers prior to implementation should be prioritized further.

Disclosure

N.F. Hempler: None. V.H. Levisen: None. R.S. Pals: None. N. Ramskov Krogh: None. R.H. Laursen: None.
Effectiveness and Tolerability of Vildagliptin plus Metformin Compared with Other Oral Dual Antidiabetes Agents in Patients with Type 2 Diabetes—A Real-World Study (China PDS)
Authors: HAN YING , CHEN LIXIAN , HU DAQING , JIN HUI , YANG NAILONG , SHI XIAOYUN , LI QUANMIN , LIANG LINLANG , ZANG LI , LIU MINGMING , HE JAMES , MU YIMING
Published: June 2018

Background and Aims: This real-world study aimed to assess the effectiveness and safety of vildagliptin plus metformin (VM) vs. other oral dual antidiabetes agents (OD) in type 2 diabetes mellitus (T2DM) patients in China.

Materials and Methods: This prospective, 1-year, real-world study was conducted in 52 sites in patients inadequately controlled by monotherapy. Eligible patients were assigned either vildagliptin dual therapy or other OD according to local physician’s decision. The primary outcome was the proportion of patients with HbA1c<7%, without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event) at 12th month. Secondary outcomes included subgroup analysis and tolerability.

Results: Totally 604 patients received VM and 670 patients received OD. After propensity score-matched, baseline HbA1c and BMI were similar in both groups. After 12-month treatment, 55.4% patients in VM and 36.2% in OD reached primary outcome (P<0.001; OR, 1.88; 95% CI 1.47-2.40). In all subgroups, VM significantly benefited the primary outcome (Figure 1). Numerically, less tolerability events occurred in VM vs. OD (5.8% vs. 14.8%).

Conclusion: China PDS demonstrates that in a real-life setting, vildagliptin plus metformin is effective in glycemic control and is well tolerated.

Disclosure

Y. Han: None. L. Chen: None. D. Hu: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.
Predictors of Preferences for Use of MK-1293 Pens among Patients with Diabetes—Findings from a Multinational Study in the U.S., Canada, and U.K.
Authors: ALEMAYEHU BERHANU , NGUYEN ALLISON M. , DIBONAVENTURA MARCO , SHAH-MANEK BIJAL , KARKI CHITRA , CRUTCHLOW MICHAEL
Published: June 2018

This study examines the predictors of preferences of pen devices used with originator insulin glargine and MK-1293, a recently approved biosimilar insulin glargine (referred to as “Pen X”), among patients with diabetes. Adult patients with type 1/type 2 diabetes were recruited from commercial panels in the U.S., Canada, and the UK for one hour study visits. Respondents rated several attributes of each pen along with overall preferences for each of the two insulin pens. Non-inferiority analyses were conducted to compare ratings of the originator insulin glargine pen with Pen X. Logistic regression modeling was conducted to identify predictors of overall preference. A total of N=177 patients completed the study: mean age of 53.2 years, 56% males, with 73% type 2 diabetes. Overall, 63.2% preferred Pen X, 22.3% preferred originator insulin glargine pen and 14.5% had no preference. Except for employment, demographics were not significantly associated with overall preference, however the ease of pushing the injection button, instruction booklet and overall quality of the pen were predictive of an overall preference of Pen X (Table 1).The current study suggests that >60% of patients preferred Pen X and that overall, functional use and individual pen characteristics were the strongest predictors of preference, after adjusting for other pen characteristics.

Disclosure

B. Alemayehu: Employee; Self; Merck & Co., Inc. A.M. Nguyen: Employee; Self; Merck & Co., Inc. M. DiBonaventura: Employee; Self; Pfizer Inc.. Consultant; Self; Merck & Co., Inc.. B. Shah-Manek: None. C. Karki: None. M. Crutchlow: Employee; Self; Merck & Co., Inc.. Consultant; Spouse/Partner; Novo Nordisk Inc., Zealand Pharma A/S, XOMA Corporation.
Clinical Outcomes of Patients with Type 2 Diabetes Treated with Multiple Daily Injection (MDI) of Insulin—A Retrospective Cohort Analysis
Authors: LUDDEN THOMAS , ERMAKOVA ANASTASIA , XIONG YAN , SIERADZAN RAY , SACKS NAOMI C. , CYR PHILIP L. , PHILLIPS SHAY , TAYLOR STEPHANIE D.
Published: June 2018

Objective: We retrospectively analyzed clinical outcomes in type 2 diabetes mellitus (T2DM) multiple daily injections (MDI) insulin therapy patients compared with non-MDI insulin therapy patients. MDI was defined as patients having at least one basal and one prandial/bolus insulin prescription during a one year period starting October 2015.

Methods: We compared a cohort of patients with an ICD-10 code of E11, 18 years of age and older, not pregnant, with a minimum of one office visit between October 2015 and April 2016. Data such as HbA1c, LDL, Body Mass Index (BMI), cardiovascular and renal disease were pooled from one hospital EMR system in the southeastern United States for MDI (n=11742) and non-MDI (n=56025) patients. T-tests were conducted.

Results: All mean differences were significant (p<0.001). Overall, the average patient population in the MDI group was 2.4 years younger with a slightly larger proportion of female gender in the MDI group. Patients in the MDI group had an average HbA1c of 8.3% (SD=1.9) vs. 7.2% (SD=1.4) in the non-MDI group, but average proportion of patients with glycemic control (HbA1c <7%) was 23.9% vs. 54.8% respectively. The rate of cardiovascular disease in the MDI group was 37.8% vs. 21.8% in the non-MDI group. The rates of renal disease in the MDI group at 30.8% far exceeded the rates in the non-MDI group at 13.5%. Average BMI of 33.9 kg/m2 (SD=8.4) in the MDI group was greater than the non-MDI group at 32.9 kg/m2 (SD=8.6). The percentage of patients with blood pressure less than 140/90 mmHg was 78.3% in the MDI group vs. 81.4% in the non-MDI group, but the average LDL was 87.4 mg/dL (SD=37.4) vs. 88.7 mg/dL (SD=32.2) respectively.

Conclusion: These results suggest MDI insulin therapy patients have poorer glycemic control and greater rates of macro and micro vascular complications compared with non-MDI insulin therapy patients within a large healthcare system.

Disclosure

T. Ludden: None. A. Ermakova: Employee; Self; Becton, Dickinson and Company. Y. Xiong: Employee; Self; Becton, Dickinson and Company. R. Sieradzan: Employee; Self; Becton, Dickinson and Company. N.C. Sacks: Consultant; Self; Becton, Dickinson and Company. P.L. Cyr: Consultant; Self; Becton, Dickinson and Company. S. Phillips: None. S.D. Taylor: Employee; Self; Becton, Dickinson and Company.
Quality of Life in Patients Treated with Insulin Pump Compared with MDI in Croatia
Authors: BILIC-CURCIC INES , VUKOJEVIC VALENTINA , GRADISER MARINA , BERKOVIC MAJA CIGROVSKI
Published: June 2018

Introduction: The aim of this study was to investigate parameters of glycemic control (HbA1c and incidence of hypoglycemia), and quality of life in patients treated with insulin pump compared to those treated with multiple daily injections (MDI).

Methods: Out of 104 diabetes type 1 patients included in the study, 52 were treated with an insulin pump and the other 52 were treated with MDI. All participants filled out questionnaires containing sociodemographic data, data related to their disease, quality of life (WHOQoL-BREF) and depression and anxiety questionnaires.

Results: Average age of patients was 26 years (interquartile range 22 to 35 years) without difference between groups. Patients treated with insulin pumps compared to those treated with MDI were more likely to visit diabetologist, majority of them were regularly counting carbohydrate units, however frequency of ketoacidosis was increased (p <0.01 for all). Patients treated with MDI had higher level of HbA1c and were more likely to experience hypoglycemia. Also, insulin pump group of patients had significantly lower values ​​of HbA1c and decreased number of hypoglycemia after initiating pump therapy (p <0.01 for all). Both groups of patients controlled glycemia on average 3-5 times per day, most common complication was glycemic variability which was also the most common reason for initiating pump therapy while majority considered insulin pump treatment more advantageous compared to MDI. Insulin pump treated patients had better quality of life (p <0.01) including physical health, mental health and environmental parameters. Regarding depression and anxiety there were no differences between groups.

Conclusion: Our results are supporting the fact that the insulin pump therapy is one of the most successful diabetes treatments today which not only improves glycemic control but also significantly affects the quality of life. This fact should encourage authorities to provide greater access to insulin pump treatment for type 1 diabetes patients.

Disclosure

I. Bilic-Curcic: None. V. Vukojevic: None. M. Gradiser: None. M. Cigrovski Berkovic: None.
Maternal Diabetes Induces Congenital Heart Defects by Suppressing Mitochondrial Fusion through the miR-140 Mitofusin 1 Circuit
Authors: CHEN XI , SHEN WEI-BIN , YANG PEIXIN
Published: June 2018

Pregestational maternal diabetes is a significant risk factor for congenital heart defects (CHDs) in the offspring. Increased apoptosis is implicated in CHD formation, yet the underlying mechanism is still unclear. Mitochondrial fusion and fission dynamics play a key role in the regulation of cell viability. Embryonic cardiomyocytes exposed to maternal diabetes display impaired fusion and enhanced fission, suggesting that maternal diabetes represses mitofusion gene expression. Here, we demonstrated that maternal diabetes in vivo and high glucose in vitro significantly increased microRNA-140 (miR140) expression whereas down-regulated its putative target gene Mitofusin 1 (Mfn1) expression in cardiomyocytes. We found that miR140 bound to the 3’ untranslated region of Mfn1 mRNA, leading to Mfn1 mRNA degradation. A miR140 mimic induced mitochondrial fragmentation, Mfn1 reduction and cell apoptosis, whereas a miR-140 inhibitor abrogated high glucose-repressed Mfn1 expression and mitochondrial fusion. Deletion of the miR140 gene in vivo reversed diabetes-suppressed Mfn1 expression, restored mitochondrial fusion, blocked cardiac cell apoptosis leading to a significant reduction of CHDs in diabetic pregnancy. Analysis of the miR-140 gene promoter revealed several putative binding sites of the transcription factor, c-Jun, which is downstream of JNK2. Deletion of the Jnk2 (c-Jun NH2-terminal kinase 2) gene using the JNK2-/- mice mimicked the effect of miR-140 deficiency in suppressing diabetes-induced CHDs. JNK2 deletion abolished the increase of miR-140 and restored Mnf1 expression and mitochondrial fusion. Our findings support the hypothesis that the JNK2-miR140-Mfn1 circuit is critically involved in maternal diabetes-induced mitochondrial fusion impairment and CHD formation.

Disclosure

X. Chen: None. W. Shen: None. P. Yang: None.
The Study on the Clinical Efficacy of Insulin Degludec/Insulin Aspart (IDegAsp)
Authors: KUSAMA MINORU
Published: June 2018

Aim: Insulin degludec and aspart (IDegAsp) is the first soluble insulin preparation to combine two different types of insulin analogs in one pen. However, there are few reports describing the long-term use of IDegAsp in clinical practice.

Method: 140 outpatients received IDegAsp during the period between Feb 2016 and Dec 2017 and were retrospectively analyzed for HbA1c, body weight, and units of insulin used (mean follow-up period, 8.2 months). Also, a questionnaire survey was conducted 3 months after the introduction of IDegAsp, to assess patient satisfaction (Q1, device usability; Q2, glycemic control; Q3, frequency of hypoglycemia; Q4, formulation not requiring suspension procedure). The subjects were 69 men and 71 women with a mean age of 64 years, HbA1c of 8.8 %, and body weight of 59.0 kg. Treatment before IDegAsp introduction included no previous insulin therapy (group A) in 46 patients, once daily injection of long-acting insulin in 28 patients, twice daily injection of premixed insulin in 20 patients, once daily injection of premixed insulin in 13 patients, and intensive insulin therapy in 33 patients.

Results: The changes in HbA1c after the introduction of IDegAsp in the subjects overall were 8.1% (1 month [M]), and 7.3% (6 M), showing significant improvement as compared with the values before introduction. The body weights were 57.5 kg (1 M), and 57.6 kg (6 M), showing no significant changes. The changes in HbA1c, according to prior treatment, were 10.3% (0 M), 8.7% (1 M), and 7.0% (6 M) in group A, with each value showing significant improvement as compared with the baseline. In the patient survey on the use of IDegAsp, the percentages of patients responding "very good" or "good" to Q1, Q2, Q3, and Q4 were 31%, 85%, 91%, and 43%, respectively.

Discussion: The introduction of IDegAsp consistently improved glucose metabolism. Also, the patient questionnaire showed mostly favorable results with use of IDegAsp. We plan to conduct a further study and report the results including a detailed assessment of each group.

Disclosure

M. Kusama: None.