bluuebunny/crossref_metadata_2025_split huggingface dataset:
2101-P: Roles of Glycolysis Distinct from Mitochondrial Metabolism for Signal Generation in Insulin-Secreting Cells
Authors: ISHIHARA HISAMITSU , NISHIOKA HIDENORI , YAMANA MIDORI , NAGASAWA AKIKO , KOSUDA MINAMI , KOIKE MASAO , KOHNO GENTA , SAITO HITOKI 
Published: June 2020

Glucose produces, through glycolysis, pyruvate, a substrate for mitochondrial metabolism. Mitochondrial metabolism generates signals for insulin exocytosis, which include ATP and other as yet unidentified molecules. Although important roles of mitochondrial metabolism of glucose for insulin secretion is established, roles of glycolysis are not completely understood. Does glycolysis merely produce pyruvate for mitochondrial metabolism or generate its own signal? To study this question, we have created mitochondrial pyruvate carrier 2 (Mpc2) knockout MIN6 cells by the Crispr technology. We first generated MIN6 cells expressing MPC2-Flag under the control of Tet3G transcriptional activator, to assure mitochondrial metabolism of glucose in a condition of Mpc2 alleles being knocked out. Then, stop codons followed by the zeocin or puromycin-resistant gene units were introduced in the second exons of the gene. We have confirmed a complete loss of endogenous MPC2 expression by Western blot analyses and these cells were maintained in the presence of doxycycline, expressing MPC2-Flag. Upon withdrawal of doxycycline, glycolytic flux estimated by 5-[3H]glucose utilization was unaltered at 5 mM glucose but reduced by 37.2% ± 1.2% (Mean ± SE, n = 3, p &lt; 0.05) at 12.5 mM and 55.3% ± 9.6% (p &lt; 0.05) at 20 mM. In MPC2-deficient MIN6 cells, glucose-stimulated insulin secretion was completely abolished at 12.5 and 20 mM glucose, while glutamine (5 mM) plus leucine (5 mM) induced insulin secretion was comparable to that by doxycycline-treated MPC2-Flag expressing cells. Interestingly, when MPC2-deficient MIN6 cells were activated with glutamine plus leucine, 5-20 mM glucose was able to cause further dose-dependent increases in insulin secretion with 1.9 ± 0.3-fold (n = 4, p &lt; 0.05) augmentation at 20 mM. These data suggested that glycolysis generates signals for insulin secretion distinct from those produced by the mitochondria in glucose-stimulated insulin secreting cells.

Disclosure
H. Ishihara: Advisory Panel; Self; Astellas Pharma Inc. Research Support; Self; Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi. H. Nishioka: None. M. Yamana: None. A. Nagasawa: None. M. Kosuda: None. M. Koike: None. G. Kohno: None. H. Saito: None.
2105-P: Beta Cell PCSK1 Deficiency Increases Diabetes Susceptibility in Male Mice
Authors: TAYLOR AUSTIN , CHEN YI-CHUN , VERCHERE BRUCE 
Published: June 2020

Proinsulin (PI) is processed to mature insulin by prohormone convertases 1/3 (Pcsk1) and 2 (Pcsk2). In individuals with T1D and T2D, there is an increase in the circulating PI:insulin ratio. We hypothesized that beta-cell Pcsk1 deletion would result in beta-cell dysfunction and hyperglycemia.
Male and female Pcsk1flox/flox Ins1cre/+ (Pcsk1beta-KO) and Pcsk1+/+ Ins1cre/+ (Pcsk1beta-WT) mice were fed either a chow or a high fat diet (HFD; 45% fat) and monitored until 30 weeks of age. Despite an approximately 150-fold increase in fasting plasma PI (p &lt; 0.001) and only immature insulin granules detectable by electron microscopy, chow-fed Pcsk1beta-KO male mice had normal glucose tolerance early in life and only developed glucose intolerance by 26 weeks of age (AUC: 934±294 vs. 597±223; p = 0.008). Histological analysis showed that male Pcsk1beta-KO mice displayed a trend toward increased beta-cell area (1.3±0.6 vs. 0.8±0.4%; p = 0.08). The unexpectedly mild hyperglycemia in Pcsk1beta-KO mice is likely due to incomplete disruption of proinsulin processing, as mass spectrometry and western blot analysis of Pcsk1beta-KO islets confirmed markedly elevated proinsulin, but detectable mature insulin. In HFD-fed cohorts, 3/10 Pcsk1beta-KO male mice developed sustained fasting hyperglycemia (&gt;16 mM) after 19 weeks of diet. Chow and HFD-fed female Pcsk1beta-KO mice displayed no differences in glycemia or body weight from Pcsk1beta-WT controls. Deletion of both Pcsk1 and Pcsk2 in beta cells (Pcsk1flox/flox Pcsk2flox/flox Ins1cre/+) resulted in undetectable mature insulin in islets (western blot), and impaired glucose tolerance at 10 weeks of age in both chow-fed male and female mice.
Our results suggest that beta-cell Pcsk1 deficiency is not sufficient to drive diabetes development, but increases diabetes susceptibility in conditions of increased insulin secretory demand. Our data in mice support the idea that beta-cell prohormone processing errors likely contribute to pathogenesis of diabetes but not obesity.

Disclosure
A. Taylor: None. Y. Chen: None. B. Verchere: Advisory Panel; Self; Integrated Nanotherapeutics Inc., Sirona Biochem. Stock/Shareholder; Self; Integrated Nanotherapeutics Inc.

Funding
Canadian Institutes of Health Research (PJT153156)
211-LB: Branched-Chain Amino Acid Levels Negatively Associate with Postprandial ß-Cell Function in Type 1 Diabetes
Authors: KARUSHEVA YANISLAVA , STRASSBURGER KLAUS , MARKGRAF DANIEL F. , ZAHARIA OANA P. , BODIS KALMAN , TURA ANDREA , PACINI GIOVANNI , BURKART VOLKER , SZENDROEDI JULIA , RODEN MICHAEL 
Published: June 2020

Understanding the role of insulin resistance (IR) in type 1 diabetes (T1D) may help to improve its treatment. Postprandial insulin secretion stimulates amino acid (AA) uptake and protein synthesis. Consequently, impaired insulin-mediated AA clearance could raise postprandial branched-chain AA (BCAA: valine (VAL), leucine (LEU), isoleucine (ILE)) levels and in turn contribute to BCAA-induced IR. We hypothesized that BCAA levels associate negatively with postprandial ß-cell function already in recent-onset T1D. In a cross-sectional study, volunteers of the German Diabetes-Study with T1D (n=10, diabetes duration &lt;1 year) and excellent glycemic control (HbA1C 6.6±0.9%/48±9 mmol/mol), and age-, sex- and BMI- matched glucose tolerant humans (control, CON, n=10, HbA1C 5.1±0.3%/32±3 mmol/mol) underwent a mixed-meal tolerance test (MMT) to assess ß-cell function through disposition index (DI, the product of insulin sensitivity (IS) and acute insulin response to glucose) and postprandial IS (PREDIM index, predicted M-value). Adipose tissue (AT) IR index was calculated as fasting plasma levels of FFA (mmol*l-1) x insulin (pmol*l-1). Postprandial total BCAA, VAL and LEU levels were 25% higher in patients with T1D compared with CON (AUC 11167±5136 vs. 8410±3298, 14363±959 vs. 11754±3890, 11980±4317 vs. 8476±4257 µmol*l-1*3 h-1, p&lt;0.05, respectively). PREDIM was lower in T1D (3.3±1.1 vs. CON 7.0±1.4 ml*min-1*m-2, p&lt;0.01), while fasting and postprandial AT IR were not different. Persons with T1D showed an inverse relationship between BCAA concentrations and C-peptide levels (total BCAA: r=-0.76, p&lt;0.01; VAL: r=-0.80, p&lt;0.01; LEU: r=-0.71, p&lt;0.05; ILE: r=-0.67, p&lt;0.05) and DI (total BCAA: r=-0.71, p&lt;0.05; VAL: r=-0.78, p&lt;0.01; LEU: r=-0.75, p&lt;0.01; ILE: r=-0.69, p&lt;0.05).
In conclusion, persons with even well-controlled recent-onset T1D exhibit elevated postprandial BCAA concentrations, likely due to impaired ß-cell function, which contribute to postprandial IR.

Disclosure
Y. Karusheva: None. K. Strassburger: None. D.F. Markgraf: None. O.P. Zaharia: None. K. Bodis: None. A. Tura: None. G. Pacini: None. V. Burkart: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S.
2112-P: Sarco/Endoplasmic Reticulum ATPase (SERCA2) Deficiency in the Nonobese Diabetic (NOD) Mouse Accelerates Type 1 Diabetes Development
Authors: BONE ROBERT N. , REISSAUS CHRISTOPHER A. , KONO TATSUYOSHI , EVANS-MOLINA CARMELLA 
Published: June 2020

Recent evidence has implicated pathways intrinsic to the β cell, such as endoplasmic reticulum (ER) stress, as potential triggers of T1D. ER stress is increased by the loss of ER Ca2+, leading to decreased β cell function and increased β cell apoptosis. Maintenance of intraluminal ER Ca2+ stores is primarily regulated by the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2) pump, and we have shown that β cell SERCA2 expression is reduced in islets from mouse models of T1D prior to, and after, disease onset. Thus, we hypothesized that SERCA2-mediated ER Ca2+ dyshomeostasis could be a major contributor to T1D development. To test this, we generated a mouse model haploinsufficient for SERCA2 on the NOD background (NOD-S2+/-). Compared to wild type littermates (NOD-WT), NOD-S2+/- mice had a higher incidence of diabetes (p&lt;0.0001) and incidence was accelerated (14.5 wks vs. 19 wks, p&lt;0.0001). Prior to diabetes onset, NOD-S2+/- islets also had increased MHC-I expression, which has been reported to follow increased ER stress and lead to increased β cell immunogenicity. To test whether SERCA2 activation may have beneficial therapeutic effects, we treated NOD-WT and NOD-S2+/- mice with CDN1163, an allosteric activator of SERCA2, from 6-8 wks of age and observed a two week delay in NOD-S2+/- average onset (p&lt;0.05). To characterize patterns of islet immune infiltration in response to SERCA2 loss, we are utilizing the CODEX multiplexed tissue imaging platform. Our pilot study used a ten antibody panel to label and image spleen, pancreatic lymph nodes, and islets from NOD-WT. Using Indiana University-developed software, Volumetric Tissue Exploration Analysis, our preliminary analysis yields a high fidelity of nuclear segmentation and low (∼10%) false positive identification of markers. Taken together, our data suggest that loss of SERCA2 exacerbates T1D development and indicates SERCA2 may be a novel T1D therapeutic target.

Disclosure
R.N. Bone: None. C.A. Reissaus: None. T. Kono: None. C. Evans-Molina: Consultant; Self; Bristol-Myers Squibb.
212-LB: Gestational Exposure to Low-Dose Benzene Predisposes to Diabetes in Adulthood
Authors: KOSHKO LISA , DEBARBA LUCAS K. , DIDYUK OLESYA , FAKHOURY PATRICK I. , SADAGURSKI MARIANNA , KLUEH ULRIKE 
Published: June 2020

Benzene is a well-known human carcinogen that is one of the major components of air pollution. Sources of benzene in ambient air include cigarette smoke, e-cigarettes, vaping, and evaporation of benzene-containing petrol processes. Epidemiological studies demonstrated the association with type 2 diabetes (T2D) and the development of insulin resistance (IR). Because maternal environmental stressors can greatly affect offspring health, we hypothesized that exposure to low concentrations of benzene during critical windows of development may contribute to the escalating prevalence of metabolic imbalance and diabetes in offspring. Specifically, we tested the hypothesis that prenatal exposure to benzene at concentrations relevant to cigarette smoking or vaping, would prime hypothalamic gliosis, resulting in exacerbated metabolic outcomes following exposure to a high-fat diet in adulthood. Pregnant C57BL/6JB dams were exposed to benzene at 50ppm or filtered air throughout gestation, and offspring metabolic phenotype was evaluated before and after high-fat-diet (HFD) feeding for 6 months. The male offspring of benzene-exposed dams exhibited exaggerated hyperglycemia on a chow diet compared to the male offspring of control dams, whereas female offspring did not differ according to prenatal treatment. No changes in body weight, body composition, or early postnatal hypothalamic glial activation were observed between groups. Regardless, adult male offspring of benzene-exposed dams exhibited severe impairment in the parameters of energy homeostasis (Vo2, VCO2, and heat production), suggesting the effect of metabolic reprogramming in whole-body metabolic regulation in adult offspring.
In summary, prenatal benzene exposure at low dose programs offspring for increased susceptibility to diet induced metabolic changes in adulthood in a sexually dimorphic manner.

Disclosure
L. Koshko: None. L.K. Debarba: None. O. Didyuk: None. P.I. Fakhoury: None. M. Sadagurski: None. U. Klueh: Research Support; Self; Abbott. Other Relationship; Self; Cell and Molecular Tissue Engineering, LLC.
2121-P: Proinflammatory Cytokines Alter Beta-Cell Exosome Cargo and Function to Enhance Activation of the CXCL10-CXCR3 Axis in Diabetes
Authors: JAVEED NAUREEN , HER TRACY K. , BROWN MATTHEW , VANDERBOOM PATRICK M. , EGAN AOIFE M. , VELLA ADRIAN , LANZA IAN R. , PATEL TUSHAR , MATVEYENKO ALEKSEY 
Published: June 2020

Coordinated activity among islet cells is necessary for glucose homeostasis. Chronic exposure to diabetogenic factors such as pro-inflammatory cytokines, perturbs islet cell crosstalk and β-cell function in diabetes. Secretory nanovesicles - exosomes (EXO) derived from cytokine exposed β-cells modulate physiological and pathological responses to β-cell stress. However, the mechanisms governing this process remain unknown. We tested the hypothesis that β-cell failure in diabetes is mediated in part through β-cell autocrine release of pro-inflammatory EXO to promote inflammation and inhibit β-cell function. Assessment of EXO concentrations from Min6 β-cells exposed to diabetogenic cytokines (IL-1β, TNF-α, and IFNγ, cytoEXO) revealed a 2-fold increase in EXO secretion (p&lt;.05, vs. control (ctl) EXO). While acute inhibition of EXO formation with the compound GW4869 (neutral sphingomyelinase inhibitor) showed significant restoration in β-cell function (GSIS) in cytokine-exposed mouse and human islets (∼7 and 2 fold vs. cytokines alone, p&lt;.05). Moreover, functional assessment of mouse islets exposed to cytoEXO (48h) resulted in suppression of GSIS (∼55%, vs. untreated, p&lt;.05). Identification of cytoEXO content through proteomic analysis revealed a significant upregulation of the chemokine, CXCL10 (∼40 fold vs. ctlEXO) and RNA-Seq analysis of cytoEXO treated mouse islets depicted a marked upregulation of transcripts associated with CXCL10-CXCR3 signaling (p&lt;.001) and subsequent downstream pathways (e.g., NFκB; p=.016 and JAK/STAT; p=.021). Furthermore, inhibition of cytoEXO (GW4869) with cytokines markedly decreased CXCL10 (∼30%) and CXCR3 (∼65%) expression in Min6 cells. These data suggests that cytokines enhance CXCL10 expression in β-cell EXO to enhance inflammation-induced diabetes through EXO-autocrine release of CXCL10 consequently activating CXCR3 signaling and downstream pathways to impair β-cell function.

Disclosure
N. Javeed: None. T.K. Her: None. M. Brown: None. P.M. Vanderboom: None. A.M. Egan: None. A. Vella: Advisory Panel; Self; vTv Therapeutics, Zealand Pharma A/S. Research Support; Self; Novo Nordisk A/S, Xeris Pharmaceuticals, Inc. I.R. Lanza: None. T. Patel: None. A. Matveyenko: None.
2136-PUB: GLP-1 Agonist Exendin-4 Protects Endothelial Cells against Hyperhomocysteinemia by Alleviating ER Stress and Enhancing Protein Folding Machinery
Authors: CHENG CHAK KWONG , LUO JIANG-YUN , LAU CHI WAI , TIAN XIAO YU , HUANG YU 
Published: June 2020

Hyperhomocysteinemia (HHcy) is a risk factor for higher mortality in type 2 diabetic patients. HHcy induces endothelial dysfunction, which precedes overt hyperglycemia in type 2 diabetic patients. In addition, endothelial dysfunction predisposes diabetic patients to cardiovascular disorders, such as atherosclerotic cardiovascular diseases and retinopathy. HHcy induces oxidative stress and endoplasmic reticulum (ER) stress to impair endothelial cells. GLP-1 agonist exendin-4 was shown to attenuate ER stress in endothelial cells although detailed mechanism remains elusive. The current study intends to reveal the beneficial effects of exendin-4 on HHcy-impaired endothelial cells.
HHcy was induced by feeding C57BL/6 mice a high methionine low folate diet for 12 weeks. To assess endothelial function, mouse aortae and mesenteric arteries were mounted on wire myograph to determine acetylcholine-induced endothelium-dependent relaxations (EDRs). OGTT and ITT were conducted to study in vivo glucose metabolism. Dihydroethidium staining and lucigenin-enhanced chemiluminescence were used to measure ROS production. The ER stress markers expression was measured by biochemical assays. The role of ER chaperone was studied by adenoviral overexpression and siRNA-mediated knockdown.
A 4-week subcutaneous injection of exendin-4 significantly improved glucose tolerance, insulin sensitivity and EDRs in arteries of diet-induced HHcy mice. Exendin-4 inhibited ROS production and ER stress markers expression in mouse aortae and human endothelial cells. Such inhibitions were ablated by compound C, an AMPK inhibitor. By AMPK activation, exendin-4 up-regulated endothelial expression of ER oxidoreductase (ERO1α), an ER chaperone. In short, through AMPK-dependent upregulation of ERO1α in endothelial cells, GLP-1 agonist exendin-4 lowers HHcy-induced ER stress and oxidative stress to restore endothelial function.

Disclosure
C. Cheng: None. J. Luo: None. C. Lau: None. X. Tian: None. Y. Huang: None.

Funding
Health and Medical Research Fund (05162906); Early Career Scheme (24122318); Hong Kong Research Grants Council (14112919); Collaborative Research Fund (C4024-16W)
2137-PUB: Exercise and Stevia R. Extracts Attenuate Diabetic Cardiomyopathy in Type 2 Diabetic Rats via Upregulation of Nrf2 and Suppression of Oxidative Stress, Fibrosis, Apoptosis, and Sympathetic Overactivity
Authors: HUSSEIN ABDELAZIZ , EID ELSAYED A. , TAHA MEDHAT , LASHIN LASHIN 
Published: June 2020

Objectives: In the current work, we studied the effects of exercise and stevia extracts on diabetic cardiomyopathy in type 2 diabetic rats and their possible underlying mechanisms.
Methods: Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia extracts: type 2 diabetic rats received methanolic stevia extracts. By the end of experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Also, the expression of nuclear factor erythroid-like factor 2 (nrf2) was measured in myocardial tissues.
Results: We found that T2DM caused significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, nrf2 and TH density with significant decrease in serum insulin and myocardial GSH and CAT. On the other hand, treatment with either exercise or stevia extracts caused in significant improvement in studied parameters.
Conclusions: exercise and methanolic stevia extracts have cardioprotective effects against DCM, which might be due to attenuation of fibrosis, oxidative stress, p53, TH and upregulation of nrf2. Moreover, stevia extracts offered more protective effect than exercise.

Disclosure
A. Hussein: None. E.A. Eid: None. M. Taha: None. L. Lashin: None.
2141-PUB: Advanced Age, Higher FPG, and Conservative Treatment Increases in Hospital Mortality Risk in Female Patients with Acute Myocardial Infarction: A Retrospective Study
Authors: LUO SHUNKUI , LUO GUOJING , WANG LINGLING , ZHAN YANLI , LI TENGLING , PANG LICHUN , LU HONGYUN 
Published: June 2020

Background: previous researches demonstrated that gender affected the in-hospital prognosis of acute myocardial infarction (AMI). Recent studies showed conflicting results. This study aimed to investigate the influence of gender, age, glycemia, treatment, and some risk factors on the in-hospital mortality after a first AMI.
Method: Consecutive patients admitted with AMI from 2002 to 2018 were included in this study. Analysis were conducted with the SPSS 25.0 software.
Results:1607 cases were enrolled in this study. Female patients had worse outcome, higher rate of cardiac shock, heart failure, Unadjusted in-hospital mortality was higher in women. Beides, female was older than male , had higher rate of diabetes, and preferred to take conservative treatment. Even though different gender had significant different outcome after AMI attack, logistic analysis revealed that gender itself was not the risk factor of AMI mortality. It showed that FPG≥7.0mmol/l,conservative treatment and age≥75 years-old were the risk factor of AMI mortality. Previous studies considered that gender is the important factor that affects the mortality rate of AMI, our study found it was not gender itself made that difference, it related to age, treatment and glycemia.

Disclosure
S. Luo: None. G. Luo: None. L. Wang: None. Y. Zhan: None. T. Li: None. L. Pang: None. H. Lu: None.

Funding
Five & Five Youth Talent Scientist Programme
2144-PUB: Elevated Carotid Intima-Media Thickness Is an Important Predictor of Major Cardiovascular Events and All-Cause Death in Elderly Women with Diabetes
Authors: DABROWSKI MARIUSZ , DEREZINSKI TADEUSZ , URUSKA ALEKSANDRA , ZOZULINSKA-ZIOLKIEWICZ DOROTA 
Published: June 2020

Background and Aims: The presence of diabetes mellitus (DM) is associated with unfavorable long-term outcomes. The aim of this study was to assess the risk factors of clinically significant end points associated with the presence of diabetes in the 6.5-year follow-up of a group of elderly women.
Material and Methods: A group of 364 women aged 65-74 (98 with DM) were included in the study in 2012. After 6.5 years of follow-up we evaluated risk factors (anthropometric, metabolic and clinical, including carotid intima/media thickness - CIMT) associated with the occurrence of composite major cardiovascular (CV) event (MACE) (non-fatal myocardial infarction [MI], non-fatal stroke or CV death), and all-cause death depending on the baseline presence of DM.
Results: During follow-up MACE occurred in 26 women (12 with DM) and 40 females died (15 with DM). Survival data were available for all 364 women, while MACE data for 290. Baseline DM was associated with significantly higher relative risk (RR) of MACE, RR 1.69 (95% CI 1.07-2.68), P=0.043, and CV death, RR 2.53 (1.65-3.89), P=0.004. In a group with DM older age, higher CIMT and history of CV event were associated with both MACE and all-cause death. We established the best cut-off point for CIMT at 1.2 mm. Women with CIMT ≥1,2 mm had significantly higher risk of MACE, RR 5,13 (1.85-14.27), P=0.003, and of all-cause death, RR 6.24 (2.53-15.39), P&lt;0.001, compared to those with lower CIMT. In the multiple logistic regression analysis significant predictors of MACE were both CIMT ≥1,2 mm, RR 5.09 (1.15-22,57), P=0.032 and history of MI or stroke, RR 5.47 (1.10-27.07), P=0.037, while CIMT ≥1,2 mm was the only independent predictor of all-cause death, RR 7,29 (1,99-26,67), P=0.003.
Conclusions: CIMT ≥1.2 mm seem to be an important predictor of MACE and the best predictor of all-cause death in elderly women with diabetes. Thus, CIMT assessment can be useful in identifying persons at very high risk of these outcomes.

Disclosure
M. Dabrowski: Other Relationship; Self; Ascensia Diabetes Care, AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Mundipharma International, Novo Nordisk Inc., Sanofi-Aventis, Servier. T. Derezinski: None. A. Uruska: None. D. Zozulinska-Ziolkiewicz: None.