bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood Pressure Variability and Nocturnal Dipping in Diabetic Patients With and Without Chronic Kidney Disease
Authors: LIBIANTO RENATA , BAQAR SARA , VU THUY D. , MACISAAC RICHARD , EKINCI ELIF I. 
Published: June 2018

Background: Both increased blood pressure variability (BPV) and lack of nocturnal blood pressure dipping (NBPD) are independently associated with excess mortality in patients with diabetes mellitus. We hypothesised that patients with diabetes and CKD have higher BPV and are more likely to demonstrate a lack of nocturnal blood pressure dipping, than their counterparts without CKD.
Methods: Clinical and biochemical data were collected from 124 patients attending diabetes clinics at Austin Health, Melbourne Australia. Stage 3 to 5 CKD (from here on referred to as “CKD”) was defined by a CKD-EPI eGFR of &lt;60ml/min/1.73m2. Patients underwent 24h ambulatory blood pressure monitoring within one year either side of the eGFR measurement. BPV was calculated using standard deviation (SD) and coefficient of variation (SD/mean*100). Night-to-day systolic BP ratio of&gt;90% suggested abnormal NBPD (“non dippers”).
Results: Thirty-four patients (27%) had CKD. The mean±SD 24h systolic blood pressure was higher in patients with CKD than those without (135±16mmHg vs. 129±13mmHg respectively, p=0.03), and there was a negative correlation between eGFR and 24h systolic BP (r = -0.21, p=0.02). No association was found between eGFR and BPV. A negative correlation was found between eGFR and night-to-day systolic BP ratio, whereby lower eGFR was associated with higher night-to-day systolic BP ratio (i.e., with lack of NBPD). This relationship remained significant after adjusting for age and sex.
Conclusion: Amongst patients with diabetes, reduced eGFR was associated with higher blood pressure and abnormal NBPD, but not with BPV. Further study is needed to characterise blood pressure fluctuations in diabetic patients with CKD, who constitute a high risk group.

Disclosure
R. Libianto: None. S. Baqar: None. T.D. Vu: None. R. MacIsaac: None. E.I. Ekinci: None.
Prevalence and Associated Factors to Peripheral Arterial Disease in Patients with Diabetes Type 2
Authors: MARMOL FERNANDO A. , BUENO LUIS E. , VASQUEZ DIEGO A. 
Published: June 2018

Type 2 diabetes mellitus (T2DM) is the principal risk factor for developing Peripheral Arterial Disease (PAD), which is the most frequent non cardiac arteriopaty according to the American Heart Association (AHA). The Ankle-Brachial Index (ABI) is the main diagnostic test for PAD with a 90%-95% sensibility and 96%-100% specificity.
Objective: Establish the prevalence and associated factors for PAD in patients with T2DM according to their ABI, in primary care.
Material and Methods: Descriptive and cross-sectional study, in “Sur Valdivia” medical center between August 2015-March 2016, with T2DM patients older than 50 years to whom the ABI test was performed according to the AHA guidelines. A multiple logistic regression analysis was made between independent variables and the presence of an ABI≤0,90.
Results: ABI test was performed on 196 people, 14 were excluded because they weren’t evaluable for having an ABI&gt; 1.40. The final sample was conformed of 182 patients, with an average age of 64.1 years old, consisting of 95 (52.20%) women and 87 (47.8%) men; from which 27 (14.84%) obtained an ABI≤0.90. The multivariate analysis showed a significant relationship with age ≥70 years (p = 0.0001, OR 1.14), having more than 10 years with T2DM (p = 0.036, OR 2.91), and the presence of intermittent claudication (p = 0.025; OR 2.67). An unilateral negative correlation was determined between age and ABI results (rs = -0.279, p = 0.001); In addition, an adjusted model of binary regression was performed in those with less than 10 years with T2DM and intermittent claudication, showing a statistically significant relationship with the presence of an ABI ≤0.90 (p = 0.01, OR 11.46).
Conclusions: The prevalence of an ABI ≤0.90 was higher than the world prevalence. The ABI test should be a common practice in primary care, especially on patients with several years with diabetes, advanced age and/or intermittent claudication.

Disclosure
F.A. Marmol: None. L.E. Bueno: None. D.A. Vasquez: None.
Serum Ferritin Independently Associated with Carotid Intima-Media Thickness in Male Patients with T2DM from Tibetan Plateau
Authors: CHENGHUI ZHANG , SUYUAN WANG , YUNHONG WU 
Published: June 2018

Background: Although the association with serum ferritin (SF) and carotid intima-media thickness (IMT) has been demonstrated by various studies, SF levels in those studies were mostly in the normal reference range. High SF levels were usually found in the patients who suffered from hematological system diseases and hereditary hemochromatosis. Our data (unpublished) had shown SF levels in Tibetan population had increased, and this study focused on the male Tibetan patients with T2DM to explore the association between SF and IMT.
Methods: This cross-sectional study involved 718 male Tibetan patients with T2DM. BMI, SBP and duration were collected. SF, HbA1c and blood lipid profiles were measured in clinical laboratory in our hospital. IMT was performed by carotid artery ultrasonography examination. Patients were categorized into four groups based on the level of SF. Multivariate regression was used to examine the association of SF and IMT.
Results: Patients in the fourth quintile were more likely to present higher baseline of BMI, TC, HbA1c and IMT. After adjustment for age, duration and BMI, comparing with the first quintile, the β, 95% CI and p-value of the second, third as well as fourth quintile of serum ferritin were 0.029 (-0.001, 0.059) (p = 0.056), 0.046 (0.017, 0.076) (p = 0.002) and 0.053 (0.023, 0.083) (p &lt;0.001), respectively. After further adjustment for HbA1c, TC and SBP, the β, 95% CI and p-value of the second, third as well as fourth quintile of SF were 0.025 (-0.005, 0.055) (p = 0.102), 0.040 (0.010, 0.071) (p = 0.008) and 0.045 (0.015, 0.076) (p = 0.004), respectively.
Conclusion: SF was independently associated with IMT in male patients with T2DM from Tibetan plateau, the cutoff of serum ferritin in this study would help us to find an appropriate value to intervene the hyperferritinemia.

Disclosure
Z. Chenghui: None. W. Suyuan: None. W. Yunhong: None.
Few Pediatric Diabetes Patients Access Outpatient Psychotherapy following Screening and Referral
Authors: TSIKIS JOANNA , VALENZUELA JESSICA M. , VASSILOPOULOS ARETI , WILCOCKS CHELSEA , REITBLAT LITAL , BLANCO ERNESTO J. , NICHOLLS SHELLEY , WOLF RISA 
Published: June 2018

Introduction: Adolescents and young adults (AYAs) with diabetes are at risk for suboptimal psychological functioning. This study aims to describe the prevalence of elevated depression scores, outpatient psychotherapy referrals, and individuals receiving follow-up care in a clinic with an integrated psychologist. Further, we examine whether having an integrated psychologist leads to better access to mental health services for AYA.
Methods: Participants were seen in a multidisciplinary diabetes clinic from September 2016 to 2017. Assessment included a semi-structured interview and depression screener (PHQ). Families with concerns related to diabetes management were offered on-site outpatient psychotherapy, others given community referrals. Follow-up with referrals was assessed at next diabetes visit.
Results: Participants included 100 ethnically diverse AYAs, 11-21 years (M=16.06±2.42; 56% female), diagnosed with type 1 (79%), type 2 (19%), or MODY (2%), with a range of glycemic control (HbA1c 5.5 to &gt;14%). PHQ scores were: no/minimal (58%), mild (26%), moderate (11%), moderately severe (3%), and severe (2%). 59% of patients were referred for outpatient psychotherapy. Referral reasons included depression, anxiety, behavioral difficulties, family conflict, and diabetes management challenges. At follow-up, only 9% were receiving services. Barriers included transportation, organization (e.g., losing referral), and stigma.
Conclusions: Pediatric psychologists within integrated diabetes teams offer effective mental health screening and referrals. Almost half (42%) of AYA in our cohort had ≥5 depressive symptoms, and while 59% were referred for outpatient therapy, only 9% received these services. Despite patient access to a pediatric psychologist in clinic, a large discrepancy between referral and follow-up rates remains. This disparity highlights the importance of identifying and reducing barriers to follow-up care for AYAs with diabetes.

Disclosure
J. Tsikis: None. J.M. Valenzuela: None. A. Vassilopoulos: None. C. Wilcocks: None. L. Reitblat: None. E.J. Blanco: None. S. Nicholls: None. R. Wolf: None.
Alogliptin and Pioglitazone, Alone or in Combination, Prevent Palmitate-Induced Apoptosis and Autophagy in Human Cardiac Progenitor Cells
Authors: INCALZA MARIA ANGELA , D'ORIA ROSSELLA , CACCIOPPOLI CRISTINA , LEONARDINI ANNA , SCHIPANI ROSSELLA , CIGNARELLI ANGELO , NATALICCHIO ANNALISA , PERRINI SEBASTIO , MARGARI VITO , PAPARELLA DOMENICO , LAVIOLA LUIGI , GIORGINO FRANCESCO 
Published: June 2018

Physiological tissue turnover in the heart requires proper activation and viability of multipotent cardiac progenitor cells (CPCs). A defective CPC compartment, in terms of CPC number and maturation capacity, contributes to diabetes- and hyperglycemia-related heart failure in humans. GLP-1-based therapies, including the DPP-4 inhibitors, improve cardiac function in vivo and ameliorate myocardial and endothelial dysfunction in vitro. Pioglitazone has also demonstrated pleiotropic anti-oxidant and anti-atherogenic effects. The aim of this study was to evaluate the effects of alogliptin and pioglitazone, alone or in combination, on the viability of human CPCs exposed to 0.25 mM palmitate for 16 h. Human CPCs were obtained from patients undergoing cardiac surgery for coronary artery bypass grafting and/or valve surgery. Exposure of human CPCs to both alogliptin (10 µM) and pioglitazone (10 µM) for 16 h resulted in Akt, but not Erk, activation. Exposure to palmitate was associated with increased human CPC apoptosis and autophagy evaluated by ELISA assay and LC3-II immunoblotting, respectively (p&lt;0.05). Pretreatment with alogliptin, alone or in combination with pioglitazone for 1 h before exposure to palmitate, reduced palmitate-induced apoptosis and autophagy (p&lt;0.05).
In conclusion, palmitate induces apoptosis and autophagy in human CPCs, and alogliptin and pioglitazone, as well as their combination, prevent the effects of palmitate, likely through enhancement of pro-survival pathways. Hence, DPP-4 inhibitors and thiazolidinediones, alone or in combination, may limit the lipotoxic damage of the human heart by preserving the viability of myocardial progenitor cells.

Disclosure
M. Incalza: None. R. D'Oria: None. C. Caccioppoli: None. A. Leonardini: None. R. Schipani: None. A. Cignarelli: Advisory Panel; Self; Aegerion Pharmaceuticals. Consultant; Self; Roche Diagnostics Corporation, Eli Lilly and Company. A. Natalicchio: None. S. Perrini: None. V. Margari: None. D. Paparella: None. L. Laviola: Advisory Panel; Self; AstraZeneca, Animas Corporation. Speaker's Bureau; Self; A. Menarini Diagnostics. Advisory Panel; Self; Boehringer Ingelheim GmbH, Eli Lilly and Company. Speaker's Bureau; Self; Medtronic, Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novo Nordisk Inc., Roche Diabetes Care Health and Digital Solutions, Sanofi-Aventis, Takeda Development Centre Europe Ltd. F. Giorgino: Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim GmbH. Research Support; Self; Eli Lilly and Company, Johnson & Johnson Services, Inc.. Consultant; Self; MedImmune, Merck Sharp & Dohme Corp., Roche Diabetes Care Health and Digital Solutions, Sanofi. Research Support; Self; Takeda Development Centre Europe Ltd..
Metformin Ameliorates Renal Fibrosis in Mice with Unilateral Ureteral Obstruction and Inhibits TGF-ß1-Induced Upregulation of Cadherin-6 in Renal Proximal Tubule Epithelial Cells
Authors: LIANG DIEFEI , LIU SHANYING , SONG ZIJIAO , LIANG WEIWEN , CHANG RUIMING , LI YAN 
Published: June 2018

Background: Metformin has been reported of nephroprotective effects by suppressing TGF-β1-induced renal tubulointerstitial fibrosis. The mechanisms have not been fully clarified. Cadherin-6(CDH6) is a TGF-β1 target gene related to epithelial-to-mesenchymal transition(EMT). This study aimed to examine the effects of metformin on TGF-β1-induced expression of CDH6 and renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and HK-2 human renal proximal tubule epithelial cells.
Methods: Six-week-old male Kunming mice(n=18) were randomly divided into three groups: 1. Sham: sham-operated mice; 2. UUO: mice underwent UUO; 3. MET+UUO: UUO mice received metformin by gavage for 21 days after UUO. Kidneys were harvested for histopathologic examination and urine was collected for creatinine evaluation. HK-2 cells were stimulated with either TGF-β1 and/or metformin. RT-qPCR and Western Blot were used to evaluate mRNA and protein level respectively.
Results: Masson’s Trichrome staining showed significant tubulointerstitial accumulation of extracellular matrix in obstructed kidneys, which could be reduced by metformin. Meanwhile, urinary creatinine was increased with metformin treatment. Upregulation of CDH6, COL1A1, PAI-1 mRNA level was observed in obstructed kidneys, which was reduced in MET+UUO group. Immunohistochemistry showed increased expression of CDH6, α-SMA in obstructed kidneys, which was alleviated in metformin treated group. In HK-2 cells, TGF-β1 upregulated mRNA level of CDH6, vimentin, PAI-1 and protein level of CDH6. Pretreatment with metformin attenuated TGF-β1-induced upregulation of CDH6, vimentin, PAI-1 mRNA level.
Conclusion: Metformin prevents renal fibrosis partly through inhibition of TGF-β1-induced increase of CDH6 expression and EMT in renal proximal tubule epithelial cells.

Disclosure
D. Liang: None. S. Liu: None. Z. Song: None. W. Liang: None. R. Chang: None. Y. Li: None.
Number of Intact Teeth and Nutritional Status Are Correlated in Hemodialysis (HD) Patients with Type 2 Diabetes
Authors: FUNAKOSHI SATOSHI , OHATA YUKO , FUJIMORI KATSUTOSHI , ETOH RICA , SAWASE KENJI , HASHIGUCHI JYUNICHIRO , MORI YUTAKA , UTSUNOMIYA KAZUNORI , HARADA TAKASHI , HAYASHIDA MASATOSHI , KAWANO MAI 
Published: June 2018

Objective: To investigate oral health status in patients receiving maintenance hemodialysis (HD) and to examine the characteristics of diabetic patients receiving HD.
Methods: A questionnaire survey was conducted in a total of 249 outpatients receiving HD using the Japanese Academy of Clinical Periodontology’s Self-administered Questionnaire on Periodontal Disease to compare oral/nutritional health status between diabetic and nondiabetic patients.
Results: Of the patients surveyed, diabetic and nondiabetic patients totaled 83 and 166 (mean age, 64.3 ± 21.7 years and 73.9 ± 33.3 years), respectively. While there was no significant difference in the prevalence of periodontal disease between the diabetic and nondiabetic patients (26.5% and 34.9%), the diabetic patients had a significantly fewer number of intact teeth than the nondiabetic patients (14.9 ± 11.5 vs. 21.7 ± 12.9) as well as a lower geriatric nutritional risk index than the nondiabetic patients (85.7 ± 20.9 vs. 93.9 ± 27.4).
Conclusions: While there was no difference in the prevalence of periodontal disease between the diabetic and nondiabetic patients among those receiving HD, the diabetic patients were associated with a fewer number of intact teeth as well as poorer nutritional status. Further study is required to investigate whether these may represent causes or consequences of diabetes and/or nutritional status.

Disclosure
S. Funakoshi: None. Y. Ohata: None. K. Fujimori: None. R. Etoh: None. K. Sawase: None. J. Hashiguchi: None. Y. Mori: None. K. Utsunomiya: None. T. Harada: None. M. Hayashida: None. M. Kawano: None.
Quality of Life in Type 2 Diabetic Patients With and Without Proliferative Retinopathy and Macular Edema
Authors: RADHAKRISHNAN CHANDNI , CK SHAHANAS , K. SREEJITH , S. BINDU 
Published: June 2018

Diabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness in adults. In India diabetes is an epidemic, so the prevalence of diabetic retinopathy is also increasing. The main objective of the study is to compare both health related and vision targeted quality of life of type 2 diabetic patients with and without proliferative diabetic retinopathy or diabetic macular edema. A prospective, observational study was conducted in a tertiary care referral hospital at Kerala, India, over a period of 7 months. Patients age between 33-76 years, suffering from type 2 diabetes mellitus either with or without proliferative diabetic retinopathy or diabetic macular edema were interviewed using EQ 5D 5L questionnaire and national eye institute visual function questionnaire to assess their quality of life. Out of 189 type 2 diabetic patients included in the study, 94 were with Proliferative diabetic retinopathy or diabetic macular edema and remaining 95 were without PDR or DME. Presence of PDR or DME does not affect health related quality of life (p&gt;0.05). Severity of retinopathy significantly reduces health related QoL (p=0.004). Presence of PDR or DME reduces vision related QoL significantly (p=0.000). Vision related QoL is also affected by severity of retinopathy (p=0.000). There was statistically significant correlation between duration of diabetes and severity of retinopathy (p=0.018). Both HRQoL and vision related QoL were positively correlated (p=0.001).

Disclosure
C. Radhakrishnan: None. S. Ck: None. S. K.: None. B. S.: None.
Regulation of Immune Cell Proliferation by microRNAs
Authors: JOGLEKAR MUGDHA , MAYNARD CODY-LEE , HARDIKAR ANAND 
Published: June 2018

Transplantation of cadaveric islets is currently the only clinically recognized cell therapy for treatment of type 1 diabetes. Long-term success of this therapy is severely limited by multiple factors, including the immune-mediated destruction of transplanted islets. Development of molecular immunosuppressive strategies could offer much efficient graft survival thereby improving graft function and quality of life. Here we demonstrate that one of the novel mechanisms of immune regulation involves inter-cellular transfer of microRNAs via exosomes.
We have established and extensively characterized human islet-derived progenitor cells (hIPCs), which are generated following epithelial-to-mesenchymal transition (EMT) and proliferation (expansion) of human cadaveric islet cells. Initial characterization of hIPCs indicates that they exhibit most of the characteristics of mesenchymal stem cells, including expression of CD73, CD90 and CD105. We observed that hIPCs can significantly inhibit (&gt;90%) in vitro proliferation of different immune cell subsets (CD4+ T, CD8+ T, CD19+ B) of (PHA)-stimulated PBMCs in a co-culture system. RNA-sequencing and validation studies pointed to a potential role of microRNAs in inhibition of T cell proliferation. Recently, microRNAs have been demonstrated to shuttle between cells and are reported to be involved in inter-cellular gene regulation. When microRNAs were analysed in hIPCs alone and in hIPCs co-cultured with PBMCs, we found a small subset of significantly altered microRNAs. These microRNAs showed increase in abundance in PBMCs from co-culture setting and were higher in co-culture supernatant. When exosomal inhibitors were used to prevent the transfer of microRNAs from hIPCs in a co-culture setting, we found that T-cell proliferation was rescued back to normal.
We believe that this study could help in discovering novel immunoregulatory molecules that may have a potential role for improving graft survival in islet transplantation for type 1 diabetes.

Disclosure
M. Joglekar: None. C. Maynard: None. A. Hardikar: None.
Insulin Initiation and Intensification Strategies—Effect of Case-Based Online Education on Physician Competence and Confidence
Authors: GRIFFITH GILLIAN A. , PRATO STEFANO DEL , TRIER JOACHIM 
Published: June 2018

Purpose: To determine if case-based online medical education for primary care physicians (PCPs) and diabetologists/endocrinologists (diabs/endos) can improve competence and confidence regarding the appropriate initiation of insulin therapy and intensification with novel basal insulins/GLP-1 receptor agonist (GLP-1 RA) fixed-ratio combinations (FRCs) in complex patients with T2DM.
Methods: This educational activity featured an interactive case study that challenged learners to develop and apply the skills needed for providing optimal treatment of T2DM. Educational effect was assessed with a repeated pairs pre- and post-assessment study with a 3-item, multiple-choice, competence, one-item confidence questionnaire in which participants act as their own controls. A χi-squared test assessed statistical significance at the P &lt;.level. The activity launched April 25, 2017; data were collected until June 1, 2017.
Results: Participation in the activity significantly improved competence of PCPs (average from 52% to 75%; n=869) and diabs/endos (from 55% to 71%; n=209) regarding the role of basal insulin analogs in improving glycemic control, the expected effects of a basal insulin/GLP-1 RA FRC on a patient’s weight and risk of hypoglycaemia, and the appropriate recommended starting dose of such a novel insulin FRC in a given case scenario (p&lt;.05). Confidence levels in selecting appropriate treatment regimens for patients sub-optimally controlled on basal insulin also improved (41% in PCPs, 28% in diabs/endos).
Conclusions: Participation in online interactive case-based education resulted in improvement of competence and confidence regarding the initiation and intensification of insulin therapy in a complex patient with T2DM. Further education is warranted on the utility of novel insulin formulations and intensification strategies, available novel FRCs, and their appropriate use in patients with poorly controlled T2DM.

Disclosure
G.A. Griffith: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Servier, Sanofi, Takeda Pharmaceuticals U.S.A., Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Takeda Pharmaceuticals U.S.A., Inc.. Advisory Panel; Self; Janssen Biotech, Inc., Abbott. J. Trier: None.