bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single and Combined Effects of Peripheral Artery Disease and of Type 2 Diabetes Mellitus on the Risk of Cardiovascular Events in Women
Authors: SAELY CHRISTOPH H. , SCHINDEWOLF MARC , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN DANIELA , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , BAUMGARTNER IRIS 
Published: June 2018

Both peripheral artery disease (PAD) and type 2 diabetes (T2DM) are associated with a high risk of cardiovascular events. However, the single and combined effects of PAD and of T2DM in women have not been investigated yet and are addressed in the present study. We prospectively recorded cardiovascular events in a series of 436 women of whom 94 had PAD and 342 did not have PAD. At baseline, the prevalence of diabetes was higher in women with PAD than in those who did have PAD (41.5 vs. 21.6%, p&lt;0.001). Over a mean follow-up period of 7.2 years we recorded 1cardiovascular events. When compared to the event rate in women with neither PAD nor T2DM (14.9%) the event rate was not significantly increased in those with T2DM but without PAD (16.2%; p=0.972) but was significantly higher in nondiabetic women with PAD (47.3%; p&lt;0.001) and further increased in those with both PAD and T2DM (76.9%; p&lt;0.001). Nondiabetic women with PAD were at a significantly higher cardiovascular risk than women with T2DM who did not have PAD (p=0.001). When compared to women with neither PAD nor T2DM, adjusted hazard ratios were 0.93 [0.48-1.80]; p=0.831, 3.80 [2.02-7.13]; p&lt;0.001, and 7.41 [3.87-14.19]; p&lt;0.001 for women with T2DM only, for those with PAD only and for those with the combination of PAD plus T2DM, respectively. We conclude that T2DM strongly increases the risk of future cardiovascular events in women with PAD. However, type 2 diabetic women who do not have PAD are at a significantly lower cardiovascular event risk than nondiabetic women with PAD. PAD in women is a stronger risk factor than T2DM.

Disclosure
C.H. Saely: None. M. Schindewolf: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin: None. B. Larcher: None. A. Mader: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. I. Baumgartner: None.
NREP Bridges TGF-ß Signaling and Lipid Metabolism in the Epigenetic Reprogramming of NAFLD in the Offspring of Insulin-Resistant Parents
Authors: JESUS DARIO F. DE , ORIME KAZUKI , WANG CHIH-HAO , HU JIANG , DIRICE ERCUMENT , SILVA AMÉLIA M. , TSENG YU-HUA , PIHLAJAMAKI JUSSI , KULKARNI ROHIT 
Published: June 2018

Nonalcoholic fatty liver disease (NAFLD) prevalence is increasing worldwide and few studies have associated maternal diabetes and birth weights with increased risk for NAFLD. We used an unique non-dietary model, manifesting hyperglycemia and hyperinsulinemia-two hallmarks of gestational and type 2 diabetes. We aimed to determine the genetic and epigenetic effects of paternal vs. maternal genetic insulin resistance on the developmental programming in the offspring of the liver-specific insulin receptor knockout (LIRKO) mice. Male control F1 offspring from father LIRKO (FL), mother LIRKO (ML) or control mothers and fathers (C) were weaned on a chow or high-fat-diet (HFD) and followed for 3 months. FL and ML showed impaired growth and body weight composition. FL and ML developed hepatic steatosis compared to C when challenged with HFD and exhibited increased hepatic expression of lipogenesis-associated genes. Hepatic transcriptomic and genome-wide DNA methylation analyses of FL and ML on chow diet presented enriched-pathways associated with TGF-β signaling and lipid synthesis. FL and ML hepatic NREP mRNA levels were decreased 50% (p&lt;0.05) on HFD compared to C. In-vivo and in-vitro modeling of hepatic steatosis in HepG2 and human primary hepatocytes decreased NREP mRNA and protein levels. Knock-down experiments performed in HepG2 cells revealed that NREP acts by regulating triglyceride and cholesterol synthesis transcriptional network via regulation of ATP-citrate lyase (ACL) in a phospho-AKT dependent manner. Finally, reduced NREP mRNA levels in patients with hepatic steatosis by 40% (p&lt;0.05) and recent preclinical trials implicating ACL in NAFLD highlight the translation relevance of our findings. These data suggest that prenatal insulin resistance epigenetically regulates a novel gene, NREP, that has detrimental effects on metabolic adaptation and transcriptional regulation of hepatic metabolism in the development of NAFLD.

Disclosure
D.F. De Jesus: None. K. Orime: None. C. Wang: None. J. Hu: None. E. Dirice: None. A.M. Silva: None. Y. Tseng: Other Relationship; Self; Chugai Pharmaceutical Co., Ltd.. Research Support; Self; MedImmune. J. Pihlajamaki: None. R. Kulkarni: None.
Bone and Vascular Health in Postmenopausal Women with Type 1 Diabetes
Authors: SHAH VIRAL N. , JOSHEE PRAKRITI , SIPPL RACHEL M. , SNELL-BERGEON JANET K. 
Published: June 2018

The risk for cardiovascular (CV) disease and osteoporotic fractures is higher in postmenopausal women with type 1 diabetes (T1D). However, it is unclear whether these processes have common risk factors. We examined the associations between bone mineral density (BMD), trabecular bone score (TBS), and CV risk measures in 47 postmenopausal women with T1D (62 years, diabetes duration; 41 years and A1c 7.8%) and 51 postmenopausal women without diabetes (64 years and A1c 5.5%).
Age, menopausal duration, BMI, serum creatinine, calcium, 25-OH-D, parathyroid hormone (PTH) and bone turnover markers (BTMs) were similar between two groups. T1D postmenopausal women had lower left femoral neck and distal forearm BMD, and subendocardial viability index (SVI) and higher augmented pressure (AP) and carotid intima media thickness (cIMT) compared to controls (Table).
HbA1c was negatively correlated with distal forearm BMD, TBS and SVI and positively correlated with AP. Total cholesterol and LDL-C were associated with arterial stiffness but not with BMD. PTH and BTMs were associated with lower BMD but not with CV risk measures. Urinary microalbumin was inversely correlated with distal forearm BMD and TBS, and positively correlated with AP and cIMT.
T1D is associated with lower femoral neck and distal forearm BMD and higher arterial stiffness and cIMT. Urine microalbumin was the only factor linked to both low BMD and high CV risk.VariablesPostmenopausal women with T1D (n=47)Postmenopausal women without diabetes (n=51)P-valueLeft femoral neck BMD (g/cm2)0.6±0.10.7±0.10.01Left distal forearm BMD (g/cm2)0.61±0.090.66±0.080.008Lumbar spine BMD(g/cm2)0.9±0.10.9±0.10.9Subendocardial viability index (%)119.0±18.1149.1±23.9&lt;0.001Augmented pressure (mmHG)16.4±6.013.3±5.10.006Carotid intima media thickness (mm)0.7±0.10.6±0.090.01

Disclosure
V.N. Shah: None. P. Joshee: None. R.M. Sippl: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation.
A Comparative Study of the Associations between Modified Low-Density Lipoproteins and Vascular Function in African-American Diabetic Patients
Authors: ADEDAYO AJIBOLA M. , ELUWOLE AYOBAMI , TEDLA FASIKA , KREMER ARYE , MASTROGIOVANNI NICOLE , ROSENBERG CARL , DREIZEN PAUL , LAROSA JOHN , SALCICCIOLI LOUIS , BOUTJDIR MOHAMED , BANERJI MARY ANN , BROWN CLINTON , SALIFU MORO , LAZAR JASON , BAKILLAH AHMED 
Published: June 2018

Background: LDL plays a key role in development and progression of atherosclerosis. Elevated LDL amplifies the atherosclerotic process but the significance of modified LDL in pathogenesis of vascular complications is unclear. We aimed to assess plasma modified LDL levels and their relationship with vascular function in African American diabetic patients.
Methods: 125 patients with type-2 diabetes were enrolled. Levels of glycated LDL (g-LDL), carbamylated LDL (c-LDL), nitrated LDL (n-LDL) and oxidized LDL (ox-LDL) were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI), which assesses changes in digital temperature before and after release of arterial cuff occlusion. Carotid-femoral pulse wave velocity (PWV) assessed arterial stiffness using applanation tonometry. B-mode ultrasound image analysis assessed Carotid intima-media thickness (CIMT). Patient population was divided into well-controlled: HbA1c ≤7.0%, N=54; poorly-controlled: HbA1c &gt;7.0%, N=71.
Results: Age 60±8 years; 64% Female, 80% Hypertension, 90% Dyslipidemia and 15% CKD. HbA1c level 8.1±2.2%, diabetes duration 10.29±3.79 years. Mean plasma g-LDL, c-LDL, n-LDL and ox-LDL were 1.56±0.64 mg/dL, 0.85±0.11 mg/dL, 2.33±0.39 ng/mL, and 61.93±9.25 ng/mL. Ox-LDL was positively correlated with CIMT in well-controlled patients (r= 0.45, p=0.001), but not in poorly-controlled (r= 0.12, p=0.30). Multi-regression analysis revealed ox-LDL was independently associated with CIMT, but neither with PWV nor VRI after adjustment for variables such as age, gender, weight, smoking, total cholesterol, HDLc, triglycerides, and LDLc (β= 0.003, p= 0.012; r2= 0.38).
Conclusion: Ox-LDL offered better predictive value for CIMT in well-controlled patients than other forms of modified LDL. These data favor ox-LDL as potential marker to identify diabetic patients at risk of developing atherosclerotic vascular complications.

Disclosure
A.M. Adedayo: None. A. Eluwole: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. J. Lazar: None. A. Bakillah: None.
Protective Role of L-Cysteine Against High Glucose Induces G6PD-Deficiency and Endothelial Dysfunction
Authors: PARSANATHAN RAJESH , JAIN SUSHIL K. 
Published: June 2018

African Americans have high incidences of diabetes and cardiovascular disease, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD supplies NADPH, which recycles GSSG to GSH. Clinical studies demonstrate that lower blood GSH/G6PD correlate with excess oxidative stress with vascular inflammation markers which contribute to the development of complications in diabetic patients. However, the contribution of high glucose (HG) on G6PD deficiency to endothelial activation/dysfunction and monocyte recruitment, a forerunner of atherosclerosis, remains unknown. G6PD-normal and G6PD-deficient HUVEC and monocytic cells were silenced with control or G6PD siRNA (100nM) for 24 h, followed by exposure with normal glucose (5.5mM) or HG (25mM) or glutathione precursor L-Cysteine (LC; 300µM) in basal medium for 6 h. HG reduced the G6PD mRNA and its activity along with GSH in both G6PD-normal and G6PD-deficient endothelial and monocytic cells. Conversely, mRNA levels of iNOS, NOX4, and its activity were significantly upregulated but eNOS and nitrate levels were remarkably decreased under HG treated G6PD-deficient cells compared to G6PD-normal cells. The expression of cell adhesion molecules (CAMs) ICAM-1 and VCAM-1 mRNA levels significantly increased in HG-treated G6PD-deficient cells compared to G6PD-normal cells. Elevated MCP-1 was found in G6PD-deficient cells under HG conditions. Enhanced adherence of monocytes to HUVEC was observed in HG-treated G6PD-deficient cells (15.13%; p&lt;0.005) compared to control cells (10%; ns). LC supplementation significantly increased the G6PD activity, GSH, and decreased CAMs reduced adherence to control level. These findings demonstrate that high glucose induces and fuels a GSH/G6PD-deficient phenotype to impair endothelial function; LC supplementation improves vascular reactivity by restoring GSH/G6PD levels.

Disclosure
R. Parsanathan: None. S.K. Jain: None.
Vasoprotective Effects of Vildagliptin in Mice Is Masked by Metformin—Overlapping Mechanisms Implied
Authors: KUSHIMA HIDEKI , MORI YUSAKU , KOSHIBU MASAKAZU , HIROMURA MUNENORI , KOHASHI KYOKO , TERASAKI MICHISHIGE , HIRANO TSUTOMU 
Published: June 2018

Preclinical and small clinical studies have demonstrated the direct cardiovascular protective effects of dipeptidyl peptidase 4 inhibitors (DPP-4Is). However, cardiovascular benefits have not been proven in large clinical trials that utilized multiple antidiabetic agents. We hypothesized that the cardiovascular protective effects of the first-line antidiabetic agent metformin (Met) affects those of DPP-4Is, so we evaluated the vasoprotective effects of vildagliptin (Vil) in combination with Met in mice.
Methods: We randomly assigned C57BL6 and diabetic db/db mice (8 weeks old) to treatment with vehicle, Vil (3 mg/kg/d), Met (400 mg/kg/d), or the combination of Vil and Met. The mice were subjected to femoral artery wire injury to induce arterial remodeling. Four weeks after the injury, the femoral arteries were collected. Human umbilical vein endothelial cells (HUVECs) were used in the in vitro experiments.
Results: In wild type mice, the biological parameters were similar among the groups. Both Vil and Met treatment reduced neointimal area and vascular cell proliferation to a similar extent (40% reduction) compared to that of the vehicle, and combining the two drugs did not further reduce those values. Similarly, both Vil and Met treatment reduced neointimal area in db/db mice (50% reduction) without affecting biological parameters, but no additive effect was found. In wild type mice, cotreatment with the nitric oxide (NO) synthase inhibitor completely abolished the vascular effects of both Vil and Met, suggesting that Vil and Met had common mechanisms that are dependent on endothelial NO. In HUVECs, Vil did not directly affect NO production. In contrast, glucagon like peptide (GLP)-1 did stimulate NO production. Met also stimulated NO production. However, the combination of GLP-1 and Met did not increase NO production.
Conclusions: Metformin masks the vasoprotective effects of vildagliptin, possibly because of overlapping mechanisms that are dependent on endothelial NO.

Disclosure
H. Kushima: None. Y. Mori: None. M. Koshibu: None. M. Hiromura: None. K. Kohashi: None. M. Terasaki: None. T. Hirano: Speaker's Bureau; Self; Novo Nordisk Inc., AstraZeneca.
Inhibition of NF-κB Pathway with IKK-16 or Linagliptin Attenuates the Cardiac Dysfunction Associated with Polymicrobial Sepsis in Mice with Preexisting Type 2 Diabetes Mellitus (T2DM)
Authors: ZOUBI SURA AL , CHEN JIANMIN , MARTIN LUKAS , MURPHY CATHERINE , PURVIS GARETH S. , CHIAZZA FAUSTO , COLLOTTA DEBORA , COLLINO MASSIMO , THIEMERMANN CHRISTOPH 
Published: June 2018

Introduction: Patients with diabetes are more susceptible to infections and sepsis. Activation of nuclear factor-κB (NF-κB) plays a substantial role in the pathophysiology of sepsis and diabetes. Here we investigate i) the effect of preexisting type 2 diabetes mellitus on cardiac dysfunction associated with sepsis and ii) whether inhibition of NF-κB using IKK-16 or linagliptin attenuates cardiac dysfunction in mice with sepsis and diabetes.
Methods: Ten-week old male C57BL/6 mice received high fat (HFD) or chow diet for 12 weeks, and were then subjected to caecal ligation and puncture (CLP) or sham surgery for 24 hours. At 1 hour after CLP, mice received IKK-16, linagliptin, or vehicle.
Results: Administration of HFD resulted in a significant impairment in glucose tolerance and a small, but significant, reduction in ejection fraction. Immunoblot analysis of hearts tissue showed that HFD caused significant NF-κB pathway activation and expression of inducible nitric oxide synthase (iNOS). Mice on HFD subjected to CLP showed further (i) decline in EF, (ii) increase in NF-κB pathway activation, (iii) increase in iNOS expression, (iv) an increase in serum ALT, and (v) a significant renal dysfunction. Treatment of HFD-CLP mice with IKK-16 or linagliptin resulted in significant reduction of the CLP-induced i) cardiac dysfunction, ii) NF-κB pathway activation, and iii) iNOS expression when compared to mice treated with vehicle.
Conclusion: Our results show that HFD results in inflammation and cardiac dysfunction. Moreover, a preexisting diabetic phenotype worsened the cardiac dysfunction associated with CLP-sepsis. Most notably, inhibition of NF-κB reduced the cardiac dysfunction caused by sepsis in animals with preexisting T2DM.

Disclosure
S. Al Zoubi: None. J. Chen: None. L. Martin: None. C. Murphy: None. G.S. Purvis: None. F. Chiazza: Other Relationship; Self; Boehringer Ingelheim GmbH. D. Collotta: None. M. Collino: None. C. Thiemermann: None.
The Effect of Resveratrol on Reducing Neointimal Growth after Femoral Artery Injury in AMPKα2 Knockout Mice Given High-Fat Diet
Authors: ZHOU LIWEI , GUO JUNE , ZHANG HANGJUN , HEXIMER SCOTT , GIACCA ADRIA 
Published: June 2018

The rates of restenosis after percutaneous transluminal angioplasty are higher in diabetic than nondiabetic patients. Insulin is protective against restenosis, but these effects are diminished in the case of insulin resistance, which develops with high fat diet (HFD). Therefore, it makes sense to use an insulin-sensitizing compound which also has vasculoprotective effects such as resveratrol. Resveratrol is a phenolic compound found in plant tissues such as the skin of grapes, and has been hypothesized to account for the lower rates of cardiovascular disease among countries with high wine consumption. We have shown that resveratrol decreases neointimal formation in both mouse and rat models of arterial injury, and also that these effects are exerted through eNOS (endothelial nitric oxide synthase). We hypothesized that resveratrol acts though Sirt1, a NAD+-dependent deacetylase, to activate eNOS and decrease neointimal formation, but did not see any difference between neointimal growth of control and Sirt1-/- mice given HFD. AMPK (AMP-activated protein kinase) is an energy sensor which also protects against neointimal hyperplasia in the vasculature via directly activating eNOS and inhibiting the migration of vascular smooth muscle cells. Knocking out the α2 subunit of AMPK in particular has been shown to increase neointimal growth in mouse carotid artery in response to injury. We investigated the effect of resveratrol on neointimal growth after femoral arterial injury of wild type and AMPKα2 knock-out mice given HFD. Resveratrol was given at 0.0375% in the diet two days after wire injury. After 28 days, arteries were harvested and histomorphometric analysis was performed on the cross-sections. We found that neointimal growth was significantly higher in AMPKα2 knock-out mice given resveratrol compared to wild type mice given resveratrol (p&lt;0.05). These results suggest that the vasculoprotective effects of resveratrol are mediated through AMPK.

Disclosure
L. Zhou: None. J. Guo: None. H. Zhang: None. S. Heximer: None. A. Giacca: None.
Tofogliflozin Suppresses the Progression of Atherosclerosis and Reduces Inflammation in Macrophages of STZ-Diabetic ApoE KO Mice due to Improvement of Glucose Tolerance
Authors: IWAMOTO MASAHIKO , KUBOTA NAOTO , KUBOTA TETSUYA , SAKURAI YOSHITAKA , WADA NOBUHIRO , TAKAMOTO ISEKI , SHIODA SEIJI , KADOWAKI TAKASHI 
Published: June 2018

Background: Selective sodium-glucose cotransporter 2 inhibitor (SGLT2i) has become widely used for treatment of diabetes. Recently, EMPA-REG OUTCOME and CANVAS Program showed that SGLT2i reduce cardiovascular events in patients with type 2 diabetes, but the mechanism still remains uncertain. We investigated the mechanisms of vascular protection of Tofogliflozin (Tofo), one of the SGLT2i.
Method: 1) Streptozotocin (STZ)-diabetic apolipoprotein-E-deficient (ApoE KO) mice were separated into two groups, one group were fed normal chow and the other were fed normal chow containing 0.005% Tofo for ad libitum. After 6weeks, all mice were administered thioglycolate intraperitoneally, and 4 days later, peritoneal macrophages were collected to investigate the expressions of inflammatory cytokines of peritoneal macrophages by real-time PCR. Histological analyses were carried out by Sudan IV, Oil Red O, and MOMA-2 staining. 2) The same experiment targeted were carried out towards nondiabetic ApoE KO mice.
Results: 1) Tofo increased food and water intake and decreased blood glucose, but there were no significant changes in body weight, serum levels of free fatty acid, triglyceride and total cholesterol between two groups. The legions of atherosclerosis and macrophages accumulations were significantly suppressed in Tofo group. Moreover, the expression levels of TNF-α, IL-β were significantly suppressed in macrophages from Tofo group. 2) Nondiabetic ApoE KO mice showed similar increase in food and water intake, but failed to exhibit differences in blood glucose, Sudan IV staining, and expressions of inflammatory cytokines in macrophages, as observed in diabetic ApoE KO mice.
Conclusion: Tofogliflozin suppresses the progression of atherosclerosis and reduces inflammation in macrophages of STZ- diabetic ApoE KO mice. These beneficial effects may be exerted due to improvement of glucose tolerance.

Disclosure
M. Iwamoto: None. N. Kubota: None. T. Kubota: None. Y. Sakurai: None. N. Wada: None. I. Takamoto: None. S. Shioda: None. T. Kadowaki: Consultant; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sanofi, Kyowa Hakko Kirin Co., Ltd., Novo Nordisk A/S, Astellas Pharma, Daiichi Sankyo Company, Limited, Takeda, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Astellas Pharma, AstraZeneca, Merck Sharp & Dohme Corp., Ono Pharmaceutical Co., Ltd., Takeda, Eli Lilly and Company, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk A/S.
Role of Hyaluronic Acid on Apolipoprotein A1 and HDL-Mediated Cholesterol Efflux in Macrophages
Authors: MATSUKI KOTA , OGURA MASATSUNE , HARADA-SHIBA MARIKO 
Published: June 2018

Diabetic macroangiopathy are characterized by increased arterial stiffness and hyaluronic acid (HA) deposition in the large elastic arteries. It is noteworthy that systemic inhibition of HA synthesis by 4-methylumbelliferone interferes with the protective function of the endothelial glycocalyx, thereby facilitating leukocyte adhesion, inflammation, and progression of atherosclerosis. Apolipoprotein A1 (ApoA1) and High-density lipoprotein (HDL) mediates cholesterol efflux, which is the initial and rate-limiting step of reverse cholesterol transport preventing from atherosclerosis. The aim of the present study was to investigate the role of HA on ApoA1 and HDL-mediated cholesterol efflux in macrophages. Murine J774.1 macrophages and human THP-1 macrophages were labeled with 3H-cholesterol and incubated with ApoA1 (10 μg/ml) for 24 hours or HDL (50 μg/ml) for 4 hours. The percentage cholesterol efflux was calculated by dividing the media-derived radioactivity by the sum of the radioactivity in the media and the cells. The effect of HA on the cholesterol efflux was studied, adding that into the medium before the analysis of the cholesterol efflux. Under the existence of medium molecular weight HA (75-350 kDa), the HDL-mediated cholesterol efflux had significantly increased by 10.9% (n=4, p&lt;0.01) in J774.1 macrophages. We also researched the relationship between HA and ATP-binding cassette transporter G1 (ABCG1), because expression of ABCG1 enhances cholesterol efflux to HDL. Predictably, HA significantly increased ABCG1 mRNA expression in macrophage (n=4, p&lt;0.01), determined by Real-time Quantitative RT-PCR. These data suggest that HA increases HDL-mediated cholesterol efflux via ABCG1 in macrophages and the difference of molecular weight on HA may influence ApoA1 and HDL-mediated cholesterol efflux. The relationship between HA and cholesterol efflux might be one of the important mechanisms to prevent progression of atherosclerosis and diabetic macroangiopathy.

Disclosure
K. Matsuki: None. M. Ogura: None. M. Harada-Shiba: Advisory Panel; Self; Aegerion Pharmaceuticals. Speaker's Bureau; Self; Amgen Inc., Astellas Pharma US, Inc., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Daiichi Sankyo Company, Limited, MSD K.K.. Research Support; Self; Sanofi, Aegerion Pharmaceuticals, Kowa Pharmaceuticals America, Inc..