bluuebunny/crossref_metadata_2025 huggingface dataset:
218-OR: Does the Reparixin (CXCR1/2 Inhibitor) Improve Islet Cell Engraftment and Clinical Outcomes after Pancreatic Islet Allotransplantation in Patients with Type 1 Diabetes Mellitus? A Randomized, Double-Blind, Prospective Study
Authors: BACHUL PIOTR J. , GOLEBIEWSKA JUSTYNA E. , PARA MONICA , ANTIC FILIP , BASTO LINDSAY , PEREA LAURENCIA , GOLAB KAROLINA , WANG LING-JIA , TIBUDAN MARTIN L. , THOMAS CELESTE C. , WITKOWSK PIOTR
Published: June 2019

We present results of the clinical study testing Reparixin- CXCR1/2 inhibitor for improved engraftment of islet allografts. Twelve patients were randomized blindly (2:1) to receive Reparixin (N=8) or placebo N=4) in addition to the same immunosuppression.

Results: Patient and donor characteristics as well as islet quality and quality did not differ significantly between the groups. Four (50%) patients from Reparixin vs. none (0%) from placebo group achieved persistent insulin independence after only one islet infusion for over 2 years (2.2, >4.5,>5,>5 years) (p=0.2). Islet engraftment index (IEI) measured on day 75 based on the ratio of area under the curve for serum c-peptide (AUC c-peptide) and glucose (AUC glucose) in 120 min mixed meal test standardized for islet mass in IEQ of the first transplant was higher in each of 5 individuals without early complications in Reparixin group: 5.92, 6.02, 7.04, 9.44, 11.99, than in the placebo group (0, 4.56, 5.02) (p=0.035). Islet function after engraftment measured by BETA-2 on day 75 was higher but did not reached statistical difference (p=0.07); BETA-2 was 15.5, 21, 22, 23, 23 in Reparixin vs. 0, 10, 19 in placebo group. Diabetic retinopathy improved in 2 and remained stable in all patients who achieved insulin independence and got worse in one patient who has never become insulin free. Diabetic neuropathy based on EMG and neurological exam improved in 2 patients and remained stable in remaining 8.

Conclusion: Half of the patients from Reparixin group achieved long- term (>2 years) insulin independence after only one islet infusion, while none from placebo group had such outcome. Islet engraftment index was significantly higher in Reparixin group than in placebo, while assessed in patients without complications. Diabetic retinopathy and neuropathy remained stable or improved after successful IT.

Disclosure

P.J. Bachul: None. J.E. Golebiewska: None. M. Para: None. F. Antic: None. L. Basto: None. L. Perea: None. K. Golab: None. L. Wang: None. M.L. Tibudan: None. C.C. Thomas: None. P. Witkowsk: None.

Funding

Dompé Pharmaceuticals
2182-P: Protective Effects of Lin28a-RNA Binding Protein Against Glucotoxicity in Pancreatic Beta Cell
Authors: LEE KYEONG-MIN , HWANG YEOJIN , CHOI JUN-HYEOK
Published: June 2019

In pancreatic beta cell, excessive and prolonged increase of glucose causes beta cell dysfunction which is characterized by impaired insulin synthesis and secretion, termed the glucotoxicity. Although it is known that both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, other molecular mechanisms that protect from glucotoxicity are poorly defined. We investigated the effect of Lin28a overexpression on glucotoxicity-induced beta cell dysfunction. In this study, we found that high glucose leads to a decrease in Lin28a mRNA and protein expression, followed by a decrease in insulin gene expression and secretion in the rat insulinoma cell line, INS-1. In addition, PDX-1and BETA2 mRNA and protein expression were downregulated by high glucose in INS-1. Similarly, mRNA expression of Lin28a and insulin was decreased in pancreas of high fat diet induced diabetic mouse. Adenovirus mediated Lin28a overexpression in INS-1 reversed the glucotoxicity-induced downregulation of insulin, PDX-1 and BETA2 expression, and improved glucose stimulated insulin secretion (GSIS). In mouse islet, mRNA expressions of insulin, PDX-1 and ki67 and GSIS were decreased by glucotoxicity. Lin 28a overexpression in mouse islet partially restored their expression and GSIS. These results suggest that Lin28a protects pancreatic beta cells from glucotoxicity through regulation of insulin transcription factors.

Disclosure

K. Lee: None. Y. Hwang: None. J. Choi: None.

Funding

Daegu Gyeongbuk Institute of Science and Technology (18-LC-01, 2018010133)
2196-P: HB-EGF Signaling Is Required for Glucose-Induced Pancreatic ß-Cell Proliferation in Rats
Authors: MAACHI HASNA , SCOTT DONALD , GHISLAIN JULIEN , POITOUT VINCENT
Published: June 2019

Background: Glucose is a major β-cell mitogen. Despite recent progress, the underlying mechanisms remain unclear. In a rat model of nutrient excess we previously showed that nutrient-induced β-cell proliferation is blocked when either EGF receptor (EGFR) or mTOR signaling is inhibited. Parallel transcriptomic analyses identified the EGFR ligand, HB-EGF as a potential mediator of nutrient-induced β-cell proliferation.

Objective: To determine the role of HB-EGF in glucose-induced β-cell proliferation.

Methods: HB-EGF mRNA levels were assessed by real-time PCR in isolated rat islets following a 24-h exposure to 2.8 or 16.7 mM glucose. The Carbohydrate-Responsive Element-Binding Protein (ChREBP) transcription factor was down-regulated by siRNA in dispersed rat islets. For β-cell proliferation studies islets were exposed to 16.7 mM glucose or HB-EGF (100 ng/ml) in the presence of 2.8 mM glucose for 72 h. Islets were co-cultured with the EGFR inhibitor AG1478 (300 nM) or the HB-EGF inhibitor CRM197 (10 ug/ml). shRNA was used to knockdown HB-EGF in isolated islets and either cultured ex vivo or transplanted under the kidney capsule of glucose-infused rats. β-cell proliferation was assessed by immunohistochemistry for Ki67 and insulin.

Results: Glucose increased HB-EGF mRNA levels and this was prevented by ChREBP knockdown. HB-EGF potently stimulated β-cell proliferation. Inhibition of the EGFR or HB-EGF completely blocked not only the proliferative response to HB-EGF but also the response to 16.7 mM glucose. Knockdown of HB-EGF blocked the β-cell proliferative response to glucose in isolated rat islets as well as in transplanted islets.

Conclusion: HB-EGF is a potent β-cell mitogen in rat islets. Glucose increases HB-EGF gene expression via ChREBP. The proliferative response to glucose requires an intact HB-EGF - EGFR pathway. Our findings identify a novel player in the complex mechanisms controlling β-cell proliferation in response to glucose.

Disclosure

H. Maachi: None. D. Scott: None. J. Ghislain: None. V. Poitout: None.

Funding

National Institutes of Health; Fonds de recherche du Québec-Santé
2200-PUB: Interest among T1D and T2D Patients Taking Insulin in Adding a New Drug Therapy to Prevent Nocturnal Hypoglycemia
Authors: LIGGINS RICHARD , PICHE CLAUDE , RIDDELL MICHAEL , WOOD RICHARD , PANG CHRISTIANNE , LAFONTAINE MARTIN , MIDMER MICHAEL
Published: June 2019

Hypoglycemia (HG) and fear of HG are well-known problems for people using insulin, impacting quality of life, glycemic control, and health care cost. We evaluated patient perceptions of the unmet need of HG prevention in insulin users, exploring various patient aims in managing HG (Figure 1) via a survey of 637 T1D and T2D patients. Respondents rated the importance of each aim, and their current satisfaction in meeting them with current therapy. Compared to T2D, T1D patients (and also CGM users compared to non-users) had lower satisfaction with status quo for all aims except in managing meals. T1D and T2D placed greatest importance on avoiding waking due to nocturnal hypoglycemia (NH). Avoiding waking at night and reducing anxiety due to NH were identified as areas of high unmet need (low satisfaction, high importance) in both T1D and T2D (particularly those on MDI) while managing exercise and meals were prominent needs in T1D.

Although CGM technologies are becoming the standard of care for insulin users, and are a proven tool for warning of HG, CGM users have mixed feelings about HG alerts, especially in NH. Respondents were asked about their interest (4 point “intent to use” scale) in adding a drug to their existing regimen (insulin ± CGM) that would prevent NH. There was strong interest in adjunctive use of a therapy to prevent NH from all groups, and CGM users showed the greatest interest in an adjunctive therapy.

Disclosure

R. Liggins: None. C. Piche: Board Member; Self; Zucara Therapeutics Inc. Employee; Self; Locemia Solutions. Stock/Shareholder; Self; Beta Bionics, Bigfoot Biomedical, Biolinq, Capillary Biomedical, Inc., Diasome Pharmaceuticals, Inc. M. Riddell: Advisory Panel; Self; Xeris Pharmaceuticals, Inc. Consultant; Self; Lilly Diabetes. Research Support; Self; Dexcom, Inc., Insulet Corporation, Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Medtronic MiniMed, Inc., OmniPod. Stock/Shareholder; Self; Zucara Therapeutics Inc. R. Wood: Other Relationship; Self; Multiple companies in the diabetes field (>10 companies). C. Pang: Consultant; Self; dQ&A Market Research, Inc. M. Lafontaine: Consultant; Self; Diasome Pharmaceuticals, Inc., Metronom Health Europe, Montmed, Tolerion, Inc., Zucara Therapeutics Inc. Stock/Shareholder; Self; Locemia Solutions. Other Relationship; Self; 360 Marketing Strategic Services. M. Midmer: Employee; Self; Zucara Therapeutics Inc.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
2204-PUB: Risk Factors for Hypoglycemia in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: ECHOUFFO TCHEUGUI JUSTIN B. , DAYA NATALIE R. , PANKOW JAMES S. , WINDHAM B. GWEN , SELVIN ELIZABETH
Published: June 2019

Background: Older adults with type 2 diabetes are at increased risk of hypoglycemia. However, risk factors for hypoglycemia among older adults with diabetes in the general population are largely uncharacterized.

Methods: We included 845 participants with diabetes who attended the recent ARIC visit 6 (2016-2017). An episode of hypoglycemia was defined as the occurrence of one or more self-reported episode of severe low blood sugar reactions in the previous year (i.e., passing out, needing help to treat the reaction). We also examined alternative definitions using both broader (feeling of unacceptably low blood glucose) and stricter (two or more episodes of severely low blood glucose) self-reported criteria. We used logistic regression to evaluate risk factors for hypoglycemia.

Results: The mean age of participants was 79 years (SD: 4.3), 37% were black and 58% were female. There were 53 episodes of hypoglycemia reported. In the fully adjusted analyses, insulin therapy, lipid lowering medication, and dementia were significantly associated with hypoglycemia. Blacks were less likely to experience hypoglycemia. Results were similar with alternative definitions of hypoglycemia definitions.

Conclusions: The identified factors may aid personalization of diabetes management that reduces hypoglycemia risk among older adults, particularly those with dementia, in whom de-escalating therapy may be needed.

Disclosure

J.B. Echouffo Tcheugui: None. N.R. Daya: None. J.S. Pankow: None. B. Windham: None. E. Selvin: None.
221-LB: Omega-3 plus Plant Sterols Regulate Glucose and Lipid Metabolism in Impaired Glucose Regulation Individuals: A Parallel, Double-Blind Controlled and Randomized Clinical Trial
Authors: RUIRONG PAN
Published: June 2019

The balance of lipid metabolism has been recognized as one of the significant causes of impaired glucose metabolism in T2DM, which is steadily increasing worldwide. IGR plays a vital role in the prevention and treatment of T2DM. This study focused on roles of plant sterols (PS), omega-3 fatty acids or their combination on IGR individuals, moreover, further clarifying whether there is synergistic effect of combination PS with omega-3 fatty acids on the prevention and treatment of IGR through a randomized, double-blind, placebo-controlled, 2×2 factorial design trial. 200 participants consented were randomized to receive PS and omega-3 fatty acids (n=50), PS alone (n=50), omega-3 fatty acids alone (n=50) and placebo soy bean powder plus placebo capsules (n=50) for 12 weeks. To investigate the characteristics of body composition (weight, height, waistline, BMI, body fat rate, visceral fat rating), blood pressure, glucose metabolism (FPG, FINS, HOMA-IR, HbA1c), lipid metabolism (TG, TC, HDL-C, LDL-C) and inflammatory factors (Hs-CRP, IL-6) in IGR individuals. Compared with placebo group, the combined intervention significantly decreased TG, HDL-C, FBG, HOMA-IR and HbA1c. Omega-3 fatty acids alone led to significant reductions in waistline, TG, FBG, HOMA-IR and Hs-CRP. PS alone just decreased TG and Hs-CRP. No intervention produced significant changes in body weight, BMI, blood pressure, FINS, body fat rate, visceral fat rating, TC, LDL-C and IL-6.

In conclusion, we have demonstrated for the first time that PS, omega-3 fatty acids or their combination significantly improved inflammation, insulin resistance, as well as glucose and lipid metabolism in IGR individuals. And combinative interaction has better effects than single dietary supplement.

Disclosure

P. Ruirong: None.

Funding

Affiliated Hospital of Jiangsu University
221-OR: Pancreas Transplantation from Pediatric Donors: An Opportunity to Increase Donor Pool
Authors: CONTE CATERINA , SOCCI CARLO , SECCHI ANTONIO , MAFFI PAOLA
Published: June 2019

Background: Pancreas transplants (PTx) from pediatric donors (PDs, age <18 years) might expose to greater technical difficulties and provide less insulin independence in the long-term due to smaller beta cells mass. Most available data on pancreas transplants from PDs relate to simultaneous pancreas-kidney transplants, whereas little is known on pancreas transplant alone (PTA) from PDs.

Methods: We retrospectively analyzed perioperative surgical complications and graft survival in T1D recipients of PTA or pancreas after kidney (PAK) transplant from PDs or adult donors (ADs) between Jan 2010 and May 2018. Data were collected through electronic medical record review.

Results: A total of 43 PTx recipients (35 PTA) had data available for analyses. Age at PTx was 40.0±8.3 years, T1D duration 25±10 years, 46.5% female, BMI 23±3 k/m2. Nearly half (49%) pancreas grafts were from PDs. Median donor age was 18 [IQR: 16] years (min. 2, max 45 years). Donor characteristics (age, BMI, body surface area [BSA]) significantly differed between groups (all p<0.05), but recipient characteristics (age at PTx, T1D duration, BMI) were similar. Median length of stay was similar in the AD and PD groups (17.5 [8.5] vs. 14 [7.0] days, p=NS). Rates of any perioperative surgical complications (55% vs. 33%), re-laparotomy (41% vs. 19%) and explanation (36% vs. 10%) were numerically lower and early graft thrombosis was significantly lower (55% vs. 10%, p<0.01) in the PD group. Median graft survival was numerically greater in the AD vs. the PD group (8.5 vs. 5.7 years, p=0.34). However, rejection rate was significantly higher in the PD group (4.5% vs. 52%, p<0.01). We found no correlation between donor characteristics (age, BMI, BSA and donor/recipient BSA ratio) and graft survival.

Conclusions: PTx from PDs tended to be associated with less surgical complications vs. PTx from ADs. Graft survival was similar. Expanding selection criteria to include PDs would increase the availability of pancreas grafts and possibly improve clinical outcomes.

Disclosure

C. Conte: None. C. Socci: None. A. Secchi: None. P. Maffi: None.
2211-PUB: Hand Grip Strength Predicts Mortality Independently from Type 2 Diabetes and the Presence of Coronary Artery Disease
Authors: LARCHER BARBARA , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN-PURIN DANIELA , MADER ARTHUR , SAID ABDURAHMAN , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2019

Hand grip strength (HGS) is widely used as a simple, inexpensive and non-invasive diagnostic parameter for frailty and sarcopenia. Low HGS in community-dwelling populations has been reported to predict a higher mortality risk. Whether this association is independent from the presence of type 2 diabetes (T2DM) and pre-existing coronary artery disease (CAD) is not known and is addressed in the present study. We prospectively recorded deaths over a mean follow-up time of 9.2±3.1 years in a cohort of 845 subjects in whom the baseline CAD state was determined angiographically. At baseline, HGS was higher in male than in female participants (41.5±10.3 vs. 24.0±5.06 kg; p<0.001); it did not differ significantly between patients with T2DM and nondiabetic subjects. Prospectively, low HGS predicted overall mortality both in men and women, with standardized adjusted HRs of 0.90 [0.83-0.99]; p=0.035 and HR 0.65 [0,50-0,82]; p<0.001 after multivariate adjustment including T2DM and the presence of CAD at baseline. We conclude that low hand grip strength predicts mortality independently from T2DM and the presence of CAD.

Disclosure

B. Larcher: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin-Purin: None. A. Mader: None. A. Said: None. H. Drexel: None. C.H. Saely: None.
2214-PUB: Cytokine Profile in Patients with Type 2 Diabetes Mellitus and Evolution of ST-Elevation Acute Myocardial Infarction of Buryat Ethnic Group
Authors: BARDYMOVA TATIANA , PROTASOV KONSTANTIN , BELOCHVOSTIKOVA TATIANA , TSYRETOROVA SESEG , MISTIAKOV MAKSIM , DONIROVA OYUNA , BEREZINA MARINA
Published: June 2019

Inflammatory processes during type 2 diabetes mellitus (T2D) and evolution of ST-elevation acute myocardial infarction (STEMI) are different in various ethnic groups. Buryats are the main northern group of Mongolians, they are a core population of Siberia.

We have examined the associations between cytokines and high sensitivity C-reactive protein (hs-CRP) in 14 patients (36% males) with T2D and STEMI of Buryat ethnic group (60 years, diabetes duration 7.9 years, A1c 8.0%); in 21 Caucasian patients (48% males) with T2D and STEMI (60 years, diabetes duration 8.0 years, A1c 7.9%); in 13 patients (77% males, 59 years) with STEMI without T2D of Buryat ethnic group and 18 Caucasian patients (72% males, 61 years) with STEMI without T2D.Buryat patients with T2D and STEMI had higher hs-CRP and lower interleukin-8 (IL-8) and interleukin-10 (IL-10) compared to Buryat patients with STEMI without T2D. Caucasian patients with T2D and STEMI had higher hs-CRP and lower tumor necrosis factor alpha (TNF-α) compared to Caucasian patients with STEMI without T2D. Buryat patients with T2D and STEMI had lower interleukin-6 (IL-6), IL-8, IL-10 and hs-CRP compared to Caucasian patients with T2D and STEMI. We have determined decreased secretion of cytokines and hs-CRP in patients with T2D and STEMI of Buryat ethnic group compared to Caucasian patients.

Disclosure

T. Bardymova: None. K. Protasov: None. T. Belochvostikova: None. S. Tsyretorova: None. M. Mistiakov: None. O. Donirova: None. M. Berezina: None.
222-LB: Islet Dysfunction and Progression of NAFLD in Diabetic Patients: Islet-Liver Cross Talk from Metal Study
Authors: WANG NINGJIAN , WANG YUYING , ZHANG WEN , CHEN YI , CHEN XIAOMAN , WANG CHIYU , LU YINGLI
Published: June 2019

Objectives: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in type 2 diabetes, thus crosstalk between islet cells (mainly α and β cells) and liver is suspected. We aim to investigate whether islet dysfunction (evaluated by C-peptide and glucagon) associates with NAFLD progression in Chinese type 2 diabetic adults.

Methods: 4,937 diabetic participants were enrolled from Shanghai, China in 2018. Liver steatosis was detected by ultrasound. Subjects with NAFLD were categorized into simple NAFLD and probable nonalcoholic steatohepatitis (NASH) by the presence of metabolic syndrome. NAFLD fibrosis score was used to identify patients with higher likelihood of bridging fibrosis (stage 3) or cirrhosis (stage 4). Regression analyses were used.

Results: With longer history of type 2 diabetes, individuals were prone to have lower C-peptide, relatively stable glucagon, lower prevalence of probable NASH and higher prevalence of significant fibrosis. C-peptide was positively associated with simple NAFLD and probable NASH, with the ORs of 4.55 (95% CI 3.16, 6.55) and 5.28 (95% CI 3.94, 7.09), comparing quartile 4 with quartile 1 (both P for trend <0.001). Unlike C-peptide, glucagon quartiles were negatively associated with probable NASH (P for trend <0.05). Moreover, 1SD increment of ln(C-peptide/glucagon) was significantly associated with progression ranging from non-NAFLD, simple NAFLD to probable NASH (OR 1.26, 95% CI 1.21, 1.32). Furthermore, 1SD increment of ln(C-peptide), but not glucagon and C-peptide/glucagon ratio, was significantly and negatively associated with fibrotic progression (OR 0.88, 95% CI 0.79, 0.98).

Conclusion: Significant associations were observed among C-peptide, glucagon, C-pepide/glucagon ratio and inflammatory and fibrotic progression of NAFLD. Further understanding the crosstalk among α and β islet cells and liver tissue may help to personalize treatment strategies of NAFLD patients with type 2 diabetes.

Disclosure

N. Wang: None. Y. Wang: None. W. Zhang: None. Y. Chen: None. X. Chen: None. C. Wang: None. Y. Lu: None.

Funding

National Natural Science Foundation of China; Science and Technology Commission of Shanghai Municipality; Commission of Health and Family Planning of Pudong District; Shanghai Municipal Commission of Health and Family Planning
2226-PUB: A Survey of Primary Care Physicians (PCPs): Knowledge of Cardiovascular Outcomes Trials and Treatment Implications
Authors: DAILEY GEORGE E. , PAK JONATHAN , SHUBROOK JAY H.
Published: June 2019

Background: Cardiovascular outcomes trial (CVOT) results have led to changes in diabetes position statements and indications for some glucose-lowering agents. This study aimed to understand PCPs’ knowledge of CVOTs and beliefs about T2D medications for CV disease (CVD).

Methods: WebMD, LLC fielded a 23-item online survey from Sept 18-20, 2018 to 47,534 Medscape members who were randomly selected across U.S. internal medicine and family PCPs (quota=500).

Results: Overall, 503 of 702 PCPs were eligible and completed the survey. Overall, 39% of respondents were slightly/not at all familiar with the 2018 ADA treatment recommendations for those with T2D and atherosclerotic CVD (ASCVD). Many respondents did not know which CVOT showed superiority for major adverse CV events (26%) or CV mortality (31%). PCPs were most familiar with TECOS and LEADER and least familiar with EXAMINE. Also, 24-58% did not know which CVOTs showed an increased risk of AEs (e.g., amputation, genital infection, pancreatitis, retinopathy, etc.). The main challenges PCPs experienced using T2D agents with CV benefits included insurance coverage (75%), cost (73%), and formulary changes (61%). Using T2D medications with CV benefits was ranked the least important treatment priority by 33% (P<.05; Figure).

Conclusions: PCPs have knowledge gaps and treatment barriers using T2D medications for patients with T2D and ASCVD.

Disclosure

G.E. Dailey: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Sanofi US. J. Pak: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J.H. Shubrook: Advisory Panel; Self; Intarcia Therapeutics, Inc. Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc.

Funding

Boehringer Ingelheim; Eli Lilly and Company
2229-PUB: Comparison of Cardiovascular (NTProBNP) and Renal Biomarkers in 280 T2DM Patients with Microalbuminuria vs. Normoalbuminuria
Authors: GUPTA VISHAL , TELI VAISHALI
Published: June 2019

Methodology: 280 T2DM patients aged 18-75 years irrespective of their A1c, on standard glucose lowering, lipid lowering and BP lowering therapy were divided into 2 groups, group 1N (105 patients normoalbuminuria UACR <30) and group 2M (175 patients microalbuminuria eUACR >30). Both groups were followed-up for 2 years and assessed every 3-6 months for for renal (creatinine, eGFR, UACR) and CV (BP, BMI, Lipid profile, hs-CRP, NTProBNP) parameters. Patients with history of major surgery, coronary intervention, IHD or hospitalization in last 1 year, eGFR <45, potassium >5.3 were excluded. Data was analyzed using PSPP version 1.0.1 and represented as Mean (SD) and paired t-test was used, P-value of 0.01 was considered to be significant.

Results: Baseline treatment characteristics were well matched. For BP, use of ARB was 82.9% (1N) and 96.1% (2M) group, CCB was 35.2% (1N) and 61.2% in (2M) group. At Baseline SBP (2M 139.17±22.35 vs. 1N 131.91 ±14.66, p<0.001), Cr (2M 1.02 ±0.29 vs. 1N 0.91 ±0.23, p<0.001), UACR (2M 429.69 ±1214.86 vs. 1N 11.08 ±5.87), Non-HDL (2M 101.29 ±44.5 vs. 1N 85.83 ±30.87, p-0.001 were higher in 2M group. In both group there was a significant reduction in A1c, TC, LDL, TG, non-HDL, hsCRP. In addition, mean chol remnant 12.56 (95% CI 8.60-16.51 p <0.001) and UACR 215.97 (95% CI 88.70-343.23, p-0.001) reduced significantly in 2M group. At the end of 2 years mean SBP (2M 135.9 ±17.34 vs. 1N 128.58 ±15, p<0.001), potassium (2M 4.63 ±0.5 vs. 1N 4.46 ±0.44, p-0.007), UACR (2M 218.82 ±622.48) vs. 1N 11.80 ±7.54) was higher in 2M group. The NTproBNP was elevated in both groups (1N 136.57 ±202.14 vs. 2M 176.40 ±252.38, p-0.17).

Conclusion: Patients with eUACR had a significantly elevated SBP, non-HDL cholesterol, and creatinine, compared to nUACR at baseline. Despite CV risk factor optimization systolic-BP remained significantly higher in eUACR group. NTProBNP remained high in both groups although it trended to be slightly elevated in eUACR group although it was statistically NS.

Disclosure

V. Gupta: None. V. Teli: None.
2235-PUB: Detection and Validation of Hidden Driven Networks in Diabetic Microangiopathy
Authors: CHEN YANMING , LI HAICHENG , GUAN DAOGANG
Published: June 2019

Aim: To find the molecular interact network specific for different diabetic microangiopathy complications that will direct us to research the mechanism involved in the pathological process of those complications. At present, the plentiful multiomics data of microvascular complications allow us to construct multidimentional regulator network for different microvascular complications from a integrated system perspective. In this study, we introduced hierarchical Bayesian Mode, drivenRN, to decode multi-regulation that form inner regulatory networks in different microvascular complications by combining multi-regulator and transcriptional kinetics into one single model framework, drivenRN can naturally integrate gene expression data and regulator-binding signals in order to identify the hidden driven networks and to detect the key function gene signature. Our study finds out the specific driven networks related to diabetic nephropathy, diabetic retinopathy and diabetic feet respectively. These complication specific driven networks not only offer a new kind biomarker for susceptible patients’ identification but also help us to research the pathological process of microvascular complications systematically. Then offer potential therapy targets and forewarning mechanisms for clinical practice.

Figure 1. The Specific Driven Networks for Different Microvascular Complications of Diabetes Mellitus.

Disclosure

Y. Chen: None. H. Li: None. D. Guan: None.

Funding

National Key Research and Development Program of China (2017YFA0105803); National Natural Science Foundation of China (81770826); Sun Yat-sen University (2015015); Science and Technology Plan Projects of Guangdong Province (2016A050502010); Key Special Projects of Medical and Health Collaborative Innovation of Guangzhou City (201604020016); Special Scientific Research Project of Guangzhou City (2060404)
2240-PUB: Healing Effect of Intracavernosal Platelet-Rich Plasma Transplantation in the Presence of Clopidogrel (Plavix) on the Progression of Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats
Authors: GUR SERAP , YILMAZ-ORAL DIDEM
Published: June 2019

Erectile dysfunction (ED) is one of the most neglected complications of diabetes. Platelet-rich plasma (PRP) is an autologous concentrate prepared from the collected blood and contains a high concentration of platelet growth factors which induce angiogenesis and provide the nerve regeneration. Clopidogrel is a platelet inhibitor or thienopyridine class inhibitor of P2Y12 ADP platelet receptors. In this study, we aimed to determine the effect of intracavernous injection of PRP and clopidogrel on ED in streptozotocin (STZ)-induced diabetic rats. A total of thirty Sprague-Dawley rats was divided into two groups: control and STZ-induced diabetic (45mg/kg, 8wk). In vivo erectile responses were measured after intracavernosal injection of PRP or clopidogrel and their combination in anesthetized rats. The relaxant effect of Clopidogrel in corpus cavernosum (CC) was obtained from in vitro study. The protein expression of endothelial and neuronal markers (eNOS, nNOS), HIF-1α and VEGF in the penile tissue was determined by Western blotting. Diabetic rats displayed significantly reduced in vivo erectile responses and basal intracavernosal pressure after were partially restored by intracavernosal administration of PRP and clopidogrel. Interestingly, combined intracavernosal administration completely improved decreased in vivo erectile responses. Clopidogrel caused marked relaxation in diabetic and control rat CC. In the diabetic group, increased HIF-1α protein levels and decreased eNOS, nNOS and VEGF protein levels were prevented by the combined treatment. These results may contribute to new insights in the management of ED linked to diabetes and encourage the development of novel therapeutic strategies in regenerative medicine. Further studies should need to focus on expanding combinations of PRP and an antiplatelet agent useful for clinical outcomes in diabetic men with ED.

Disclosure

S. Gur: None. D. Yilmaz-Oral: None.
225-OR: Key Role for Glucose-Alanine Cycling in the Regulation of Hepatic Mitochondrial Oxidation during Starvation in Humans
Authors: PETERSEN KITT , DUFOUR SYLVIE , CLINE GARY , SHULMAN GERALD I.
Published: June 2019

We examined whether starvation alters rates of hepatic mitochondrial oxidation in humans by applying a novel 13C Positional Isotopomer NMR Tracer Analysis (PINTA) method to assess rates of hepatic mitochondrial oxidation in healthy volunteers (n=15) following an overnight (12h) and a 60h fast. A 3h intravenous infusion of [3-13C] lactate (4.3 μmol/Kg-min), [1,2,3,4,5,6,6-2H7] glucose (0.22 μmol/Kg-min), and [13C4]-β-hydroxybutyrate (BOHB) (0.01 mg/Kg-min) was administered and blood was collected for GC-MS, LC-MS/MS and 13C MRS PINTA analyses. Following the 60h fast rates of endogenous glucose production decreased by 27% (p=0.0002) and rates of hepatic mitochondrial oxidation decreased by 52% (p=0.0014) whereas rates of hepatic pyruvate carboxylase flux remained unchanged. To ascertain whether decreased rates of alanine turnover during starvation play a role in promoting decreased rates of hepatic mitochondrial oxidation we infused [3-13C] alanine in a subgroup (n=5) of subjects and found that 60h of fasting promoted a 28% reduction in alanine turnover (p=0.044 vs. 12h fast). In order to determine whether this reduction in alanine turnover was responsible for the reduced rates of hepatic mitochondrial oxidation we infused unlabeled alanine to a subgroup (n=9) of the 15 subjects in a repeat 60h fasting study to increase rates of alanine turnover to rates measured after 12h of fasting and found that this perturbation increased rates of hepatic mitochondrial oxidation by 63% (p=0.009 vs. 60h fast) to rates similar to the 12h fasting state (60h+ala: 232±21 vs. 12h: 295±44 μmol/min, p=0.303).

Conclusion: These studies demonstrate that 60h of starvation in humans induces marked reductions in rates of hepatic mitochondrial oxidation, which in turn can be attributed to reduced rates of glucose-alanine cycling.

Disclosure

K. Petersen: Advisory Panel; Spouse/Partner; Aegerion Pharmaceuticals, AstraZeneca, AstraZeneca, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk A/S. Consultant; Spouse/Partner; Gilead Sciences, Inc. Consultant; Self; Merck & Co., Inc. Consultant; Spouse/Partner; Nimbus Discoverey. Consultant; Self; Novo Nordisk A/S. S. Dufour: None. G. Cline: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, Merck & Co., Inc. Advisory Panel; Spouse/Partner; Merck & Co., Inc. Board Member; Self; Novo Nordisk A/S. Consultant; Self; Aegerion Pharmaceuticals, IMetabolic BioPharma Corporation, Longitude Capital, Nimbus Discovery, Inc., Staten Biotechnology B.V.

Funding

National Institutes of Health
2262-PUB: Hypercortisolism as the Cause of Diabetes Mellitus Type 2
Authors: ISAZA ADRIAN
Published: June 2019

According to the first global report of the World Health Organization, the number of adults with diabetes has increased to 422 million while causing 1.6 million deaths per year. This rise is largely due to type 2 diabetes mellitus. This study involved a literature search (PUBMED) which identified randomized controlled trials and systematic/literature reviews for interventions with an antidiabetic effect and risk factors that caused diabetes mellitus. Then studies were searched on the effect on cortisol for the interventions and risk factors. 71 natural interventions and 12 pharmaceuticals were found to decrease cortisol and exert an antidiabetic effect. On the other hand, 2 pharmaceuticals, 6 categories of pharmaceuticals and 20 risk factors increased cortisol and caused diabetes mellitus type 2. These results suggest that the hypothesis of diabetes mellitus type 2 being caused by chronic cortisol overproduction is plausible.

Disclosure

A. Isaza: None.
2263-PUB: Implementation of a Diabetes Self-Management Education (DSME) Program as Part of Discharge Counseling at a County Hospital
Authors: MULALA LISELI I.
Published: June 2019

Implementation of a Diabetes Self-Management Education (DSME) Program as part of Discharge Counseling at a County Hospital.

The CDC reports 30.3 million people in the United States have diabetes. Adults with diabetes that received Diabetes Self Management Education (DSME) have been shown to have improved outcomes and reduced healthcare expenditures. Those that did not receive DSME are four times more likely to develop complications. The 2016 American Diabetes Association (ADA) Standards of Care in Diabetes recommends that every person receive DSME at diagnosis and as needed thereafter, such as during hospital discharge.

Diabetes education is most commonly provided by a Certified Diabetes Educator (CDE), most of whom are nurses or dietitians but about 8% of CDEs are pharmacists. At Zuckerberg San Francisco General Hospital and Trauma Center, there has not been a certified diabetes nurse educator (RN CDE) for the past 4 years. Pharmacists have the clinical training and counseling skills to be effective diabetes educators whether or not they are CDEs. Since August 2017, a pharmacist CDE along with the clinical pharmacy staff have been providing diabetes education along with discharge medication counseling to patients with diabetes prior to hospital discharge.

Currently, national rates of newly diagnosed patients that report receiving DSME in their first year ranges from 4-7%. The Center for Disease Control (CDC) reports that 57.4% of people with diabetes report ever attending a DSME class and that 59.8% report ever attending a DSME class within California. At ZSFG, the pharmacist CDE and clinical pharmacy staff provide DSME to patients with newly diagnosed diabetes, diabetic ketoacidosis and diabetic exacerbations. From May 2017 to September 2018 quarterly DSME rates increased from 0.6% in quarter 2 of 2017 to 97.8% in quarter 3 of 2018. Thus, showing that pharmacists can be a valuable resource to improve inpatient diabetes education rates in an institutional setting.

Disclosure

L.I. Mulala: None.
2268-PUB: Level of Physical Activity and Perceived Barriers to Exercise in Adults with Type 2 Diabetes in Argentina
Authors: MARTIN CAROLINA GOMEZ , POMARES MARIA L. , MURATORE CAROLINA M. , APOLONI SUSANA , AVILA PABLO J. , RODRIGUEZ MARTIN ,   ACTIGRAD STUDY GROUP
Published: June 2019

Physical activity (PA) is a mainstay in the management of type 2 diabetes (T2D) treatment. Data about level of PA and perceived barriers to exercise in adults with T2D is lacking in Argentina.

Objectives: Primary: To assess the percentage of adults with T2D who perform PA according to intensity level. Secondary: 1. To describe the barriers to exercise. 2. To describe the association between level of PA and metabolic control and other variables in the study population. 3. To evaluate sedentary time.

Methods: Multicenter, observational, cross-sectional study of data collection through 2 questionnaires: International PA Questionnaire (IPAQ) short form and the “Barriers to being Active Quiz” developed by Center for Disease Control (CDC). Clinical and biochemical data were also collected. We included adults with T2D age 18 to 65 years, in 17 Argentine diabetes centers, from May 2nd to July 15th, 2018.

Statistical Methods: Chi2, t student, Pearson and Spearman correlations, multiple logistic regression and multiple linear regression.

Results: 270 men (age 54.9 ± 9.8 years) and 225 women (age 55.3 + 9.6 years) were included. Diabetes duration: 8.2 ± 6.3 years. BMI men: 32.0 ± 10.6 Kg/m2 and women: 32.5 ± 7.2 Kg/m2. Two last HbA1c: 7.6 ± 1.7% and 7.5 ± 1.6%. 32.5% treated with insulin. 12.7% had cardiovascular disease; 13.7% nephropathy; 20.8% neuropathy; 6.1% diabetic foot and 14.1% retinopathy. The level of PA by IPAQ was low in 52.3% and moderate in 30.5%. The most frequent barriers were: "lack of will" (59.6%), "lack of energy" (37.2%) and "lack of time" (31.5%). Multivariate analysis: low level of PA was associated with age (OR: 1.05 per year of age, p <0.001); A1c (OR: 1.16 per 1% p <0.05); BMI (OR: 1.06 per kg/m2, p <0.001) and sex (OR: 1.69 for women, p <0.01). Sedentary time: median of 5 hours/day, with a 75th percentile of 6 hours/day. It was associated with HbA1c in the multivariate analysis (p = 0.02).

Conclusions: 52.3% showed a low level of PA and the main barriers are related to low personal motivation.

Disclosure

C. Gomez Martin: None. M.L. Pomares: None. C.M. Muratore: None. S. Apoloni: None. P.J. Avila: None. M. Rodriguez: None.
2271-PUB: Correlation of Glycaemic Control with pH and Buffering Capacity of Saliva in Patients with Fibrocalculous Pancreatic Diabetes
Authors: RADHAKRISHNAN CHANDNI , VADAKKEKUTTICAL ROSAMMA JOSEPH , KOZHITHODI SHAHNAS BEEGAM
Published: June 2019

Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes secondary to chronic calcific pancreatitis. Microvascular and macrovascular complications of diabetes are reported in FCPD. Periodontitis is considered as the sixth complication of diabetes. Studies regarding the salivary pH, buffering capacity and periodontal health status of FCPD subjects are scarce in the literature. This Study comprised of 30 FCPD, 30 T2DM and 33 healthy controls. Study subjects were assessed for salivary pH and buffering capacity, modified gingival index, plaque index, OHI-s index, DMFT index, probing pocket depth and clinical attachment level and systemic parameters FPPG, PPPG, HbA1c, complete blood count, liver and renal function tests, FLP, ESR and CRP. The mean (±SD) salivary pH was 6.57 ± 0.63 in FCPD and 7.21±0.44 in T2DM groups (p<0.05) and buffering capacity was 4.5± 0.6 in FCPD and 5.38± 0.96 in T2DM groups(p<0.05). There was a significant negative correlation between HbA1c and salivary buffering capacity (Pearson correlation coefficient r=-0.46, p=0.012) and a weak negative correlation between HbA1c and salivary pH(r=-0.105, p=0.589) in FCPD group. The prevalence of periodontitis was 90% in FCPD and 100%T2DM groups respectively. The proportion of severe periodontitis was 56.7% in T2DM, 40% FCPD and 12.1% in control groups respectively. This study shows that the saliva is more acidic and buffering capacity is low in FCPD group compared to T2DM and control groups. As the glycaemic control worsens, salivary pH and buffering capacity decreased in FCPD subjects. The pathophysiologic mechanism responsible for the pancreatic gland destruction may also contribute to the changes in salivary pH and buffering capacity in FCPD subjects.

Disclosure

C. Radhakrishnan: None. R.J. Vadakkekuttical: None. S. Kozhithodi: None.
2278-PUB: Motivation and Attitudinal Assessment in Patients with T1D Using Multiple Daily Injections or Insulin Pump Therapy
Authors: ALFORD JORDIN , KOOBATIAN MAXWELL , DAIGLE BEN , MATHEWS KIERON , DIAS LOUIS
Published: June 2019

Objective: To assess the attitudinal impact of patients living with T1D in the United States.

Methods: Between Sep 10th-Oct 21st, 2018, a representative sample of United States patients (n=600, 56% male, mean age 40.6 years, managing their T1D with multiple daily injections (MDI) or insulin pump therapy completed a 102-question online survey (5- or 7-point Likert scale) designed by Inspired Insight (Boston, Massachusetts, U.S.) in partnership with Medtronic. Respondent sample was identified and screened with standard methods. Analyses were conducted using Pearson’s correlation and quadratic equation modeling.

Results: Of the respondents, 47% agreed that T1D is a burden, 65% agreed that they wished they could escape their disease, 60% felt they were in control of their diabetes, and 57% agreed that their diabetes did not define them. Additionally, 60% of the respondents felt they were very knowledgeable about their disease, 71% were very motivated to manage their disease, and 72% were very interested in learning more about managing their disease. The longer that respondents had been living with diabetes, the less likely they felt in control of managing diabetes (Pearsons’ r=-0.108, p=0.008). While at the same time, motivation to manage their disease tended to increase (p=0.073, non-linear regression) and the overall level of knowledge tended to increase (r=0.071, p=0.067).

Conclusions: Not surprisingly, T1D is being perceived as a burdensome disease that many patients wish to escape from. Although patients who have been living with T1D longer feel that they lose control of diabetes management, they tend to become motivated to increase their knowledge toward better management of their diabetes.

Disclosure

J. Alford: Employee; Self; Medtronic. M. Koobatian: Employee; Self; Medtronic. B. Daigle: Research Support; Self; Medtronic MiniMed, Inc. K. Mathews: Other Relationship; Self; Medtronic. L. Dias: Employee; Self; Medtronic.
2279-PUB: Assessing the Impact of T1D in Patients on MDI or Insulin Pump Therapy
Authors: ALFORD JORDIN , KOOBATIAN MAXWELL , DAIGLE BEN , MATHEWS KIERON , DIAS LOUIS
Published: June 2019

Objective: To assess patient attitudes, reactions, and motivations resulting from living with T1D.

Methods: Between Sep 10th-Oct 21st, 2018, a representative sample of United States patients (n=600, 56% male, mean age 40.6 years, managing their T1D with multiple daily injections (MDI) or insulin pump therapy completed a 102-question online survey (5- or 7-point Likert scale) designed by Inspired Insight (Boston, Massachusetts, U.S.) in partnership with Medtronic. Respondent sample was identified and screened with standard methods. Analyses were conducted using Pearson’s correlation and quadratic equation modeling.

Results: The survey showed that 58% of the respondents reported their disease as severe. Since the time of diagnosis, 44% of the individuals reported that living with diabetes has had a positive impact on their life, while 41% reported that it has had a negative impact on their life. Those respondents who felt that living with the disease negatively impacted their life, reported that the negative aspects were related to self-confidence (59%), achieving emotional wellbeing (58%), and the ability to be happy/optimistic (57%). Interestingly, those respondents who felt that living with the disease has positively impacted their life, reported that the positive aspects were related to having self-confidence (81%), being physically fit/active (80%), and achieving emotional wellbeing (80%).

Conclusions: Though the majority of patients who were assessed recognized the severity of their disease, they were polarized when it came to reporting how living with diabetes has impacted their life. Some found that their self-confidence and emotional wellbeing were positively impacted, while a proportionate number felt the opposite.

Disclosure

J. Alford: Employee; Self; Medtronic. M. Koobatian: Employee; Self; Medtronic. B. Daigle: Research Support; Self; Medtronic MiniMed, Inc. K. Mathews: Other Relationship; Self; Medtronic. L. Dias: Employee; Self; Medtronic.
2283-PUB: Association between Higher Health-Related Quality of Life Physical Component Score Measured by SF-8 and Lower All-Cause Mortality Risk among Japanese Patients with Type 2 Diabetes: A Prospective Cohort Study
Authors: HAYASHINO YASUAKI , OKAMURA SHINTARO , ISHII HITOSHI
Published: June 2019

Health-related quality of life (HRQoL) was reportedly associated with mortality; however, these studies used questionnaires with relatively large number of items ranging from 20 to 30. We thus evaluated the prospective association between HRQoL measured by Short-Form (SF)-8, a short version of SF-36, in Japanese individuals with type 2 diabetes. Longitudinal data of 3,269 individuals with diabetes were obtained from a large Japanese diabetes registry. To assess the independent correlation between the 10-point increment of SF-8 physical component summary score (PCS) or mental component summary score (MCS) and all-cause mortality, the Cox proportional hazards model was used with adjustment for age, sex, body mass index, HbA1c, types of diabetes therapy, urinary albumin-creatinine ratio, history of diabetic retinopathy, symptomatic diabetic neuropathy, and past medical history (acute myocardial infarction, chronic stable angina, peripheral artery disease, leg ulceration, ischemic stroke, and hemorrhagic stroke). The mean age, body mass index, and HbA1c level were 64.9 years (SD 11.2), 24.6 kg/m2 (SD 3.9), and 7.5% (SD 1.2) [or 58.6 mmol/mol (SD 12.7)], respectively. We recorded 248 deaths during the median follow-up of 6.1 years (incidence ratio = 14.0/1,000 person-years). We observed significant association of PSC score and all-cause mortality, and multivariable-adjusted hazard ratio (HR) was 0.775 [95% confidence interval (CI), 0.668-0.899; p = 0.001] per 10-point increment of PCS score. We did not observe significant association between MCS score and all-cause mortality [HR = 0.864 (95% CI, 727-1.027; p = 0.097)].

In conclusion, higher PCS of SF-8, not MCS, was associated with lower risk of all-cause mortality in Japanese individuals with type 2 diabetes. SF-8 could be useful for predicting mortality in individuals with diabetes.

Disclosure

Y. Hayashino: Speaker's Bureau; Self; Astellas Pharma Inc., Kowa Pharmaceuticals, Kyowa Hakko Kirin Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd. S. Okamura: None. H. Ishii: None.

Funding

Manpei Suzuki Diabetes Foundation; Japan Society for the Promotion of Science (25460641)