bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Prognostic Value of Coronary Computed Tomography Angiography in Asymptomatic Elderly Population Including Diabetic Patients
Authors: MOON SUN JOON , LEE DONG-HWA , TOH AE JUNG , KIM KYOUNG MIN , CHOI SUNGHEE , JANG HAK CHUL , LIM SOO 
Published: June 2018

Objectives: There is still controversy about the long-term prognostic value of coronary computed tomography angiography (CCTA) for coronary heart disease (CHD) in asymptomatic individuals including diabetic patients. Also, long term CCTA’s role among elderly population has not been established. We investigated the long-term prognostic value of CCTA in asymptomatic elderly patients with or without diabetes.
Methods: A community based-cohort study of 470 asymptomatic elderly individuals (mean age 75.1 ± 7.3 years) who underwent CCTA was conducted. Among them, there were 156 [33.2%] diabetic patients and 55 [11.7%] patients with HbA1c of more than 7% (HbA1c &gt;7%). Major adverse cardiac events (MACE) defined as composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization and coronary revascularization were measured. CCTA findings were categorized by various means including the presence of proximal LAD or left main disease (pLAD/LM). Coronary calcium score (CACS) and Framingham risk score (FRS) were adjusted for analysis.
Results: There were 57 individuals (12.1%) with pLAD/LM finding for overall population and 8 (14.5%) for diabetic patients with HbA1c &gt;7%. During median follow-up of 8.1 years (interquartile range: 7.7-8.2), MACE occurred in 28 (6%) subjects among overall population and 6 (10.9%) among diabetic patients with HbA1c &gt;7%. Compared to individuals with negative pLAD/LM finding, positive group was significantly associated with MACE for overall population (HR 2.817 [95% CI 1.044-7.601], p = 0.041). Among diabetic patients with HbA1c &gt;7%, there is more significant association between pLAD/LM finding and MACE (HR 6.525 [95% CI 1.147-37.121], p = 0.034).
Conclusion: Among asymptomatic elderly population, CCTA showed considerable prognostic value additive on CACS and FRS over 8 years. And this result was more significant in elderly diabetic patients with poor glycemic control.

Disclosure
S. Moon: None. D. Lee: None. T. Oh: None. K. Kim: None. S. Choi: None. H. Jang: None. S. Lim: None.
Elevated Fibroblast Growth Factor-21 Protect Endothelial Function in Type 2 Diabetes Patients
Authors: HU YANJIN , XU YUAN , WANG GUANG 
Published: June 2018

Background: Fibroblast growth factor 21 (FGF-21) is a metabolic regulator with multiple effects on improving glucose metabolism and energy utilization. Recent researches pointed that FGF-21 protect endothelial function against high glucose induced cell damage. Our research tried to detect the relationship of FGF-21 and endothelial dysfunction in newly diagnosed type 2 diabetes (T2D) patients.
Methods: Fifty newly diagnosed T2D patients and fifty healthy controls were recruited in the research. Clinical and biological data, FGF-21 were measured. Endothelial function was tested by reactive hyperaemia index (RHI) approved by American Food and Drug Administration.
Results: T2DM patients had higher FGF-21 levels (155.57±85.3 vs. 117.39±68.9ug/l,P&lt;0.05) and more serious endothelial dysfunction (1.73±0.51 vs. 2.05±0.52,P&lt;0.05) than controls. RHI was negatively related with low density lipoprotein cholesterol (LDL-C) (r=-0.322, P&lt;0.05) and positively with FGF-21 (r=0.543, P&lt;0.01). In the multivariate linear analysis, FGF-21 (β=0.551,P&lt;0.01) and LDL-C (β=-0.188,P&lt;0.01) were independently predictors of RHI. FGF-21 was the protective factor of endothelial function in the T2D patients.
Conclusions: T2D patients had endothelial dysfunction even in the early period. Elevated FGF-21 might protect endothelial dysfunction.

Disclosure
Y. Hu: None. Y. Xu: None. G. Wang: None.
Prevalent Prediabetes at Admission due to Acute Myocardial Infarction Does Not Affect One-Year Mortality Rates of Patients Who Were Discharged Alive
Authors: PARK IE BYUNG , LEE DAE HO , YU SEUNG HEE , LEE KIYOUNG 
Published: June 2018

Background: Although prediabetes increases AMI risk, long-term clinical implication for prevalent prediabetes in AMI patients is not clear. The present study aimed to evaluate whether prediabetes at admission increases long-term cardiovascular (CV) and total mortalities in AMI patients who were discharged alive.
Methods: We obtained AMI patient data from The Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry. Total and CV mortalities at 12 months after AMI were assessed.
Results: A total of 13104 patients with AMI from the registry database were analyzed. 552 patients (4.2%) were destined to in-hospital mortality or hopeless discharge. We classified the remaining patients into control, prediabetes, and diabetes groups according to one of fallowing parameters: prevalent diabetes by past history, diabetes medication during hospitalization, or in the remaining cases with no diabetes history or medication data by hemoglobin A1c level at admission. Patients without any data about above-mentioned parameters were excluded in this study (n= 3583), and a total of 8969 AMI patients were available for analysis (control group, n=2379; prediabetes group, n=2321; and diabetes, n=4269). After adjustment for multiple factors, hazard ratios (HRs) (95% CI) for total mortality in prediabetic group vs. control group and diabetic group vs. control group were 1.536 (0.879-2.685, p=0.132) and 1.94 (1.184-3.190), p&lt;0.01), respectively. However, CV mortality were not different between the three groups.
Conclusions: Our results show that that prediabetic state at AMI admission do not increase CV mortality and all-cause mortalities at 1-year after survival discharge, whereas diabetes increase 1-year all-cause mortality.

Disclosure
I. Park: None. D. Lee: None. S. Yu: None. K. Lee: None.
Glycemic Variation and Cardiovascular Risk during the VADT
Authors: ZHOU JIN , SCHWENKE DAWN , REAVEN PETER 
Published: June 2018

There is uncertainty about the importance of visit-to-visit glycemic variability in cardiovascular disease (CVD) complications in type 2 diabetes (T2D) patients. Using the Veteran Affairs Diabetes Trial (VADT), we investigated this relationship, and assessed whether it is influenced by intensive or standard glucose control. During the VADT, fasting glucose and HbA1c were measured every 3 months for up to 84 months in 1791 individuals. Visit-to-visit variability measures included coefficient of variation (CV) and average real variability (ARV). By Cox proportional hazard models, variability measures of fasting glucose showed significant association with CVD even after adjusting for other risk factors, including mean fasting glucose. This relationship was evident in the intensive treatment group but not in the standard group (Figure 1). Additional adjustment for severe hypoglycemic episodes, did not alter the effect of glucose variability on CVD. Interestingly, HbA1c variability was not associated with CVD after adjusting for multiple baseline risk factors. Our analysis indicates that in the VADT, variability of fasting glucose plays a role in the development of CVD complications beyond the influence of the mean glucose measures. The adverse consequences of glucose variability on CVD appear greatest in those receiving intensive glucose control.
Figure 1 Hazard ratio (HR) estimates for quintiles of Log(CV)-glucose and ARV-glucose for the primary composite CVD outcome adjusted for ethnicity, baseline HbA1c, baseline HDL and LDL cholesterol, baseline total cholesterol and triglycerides, history of hypertension, diabetes duration, prior CVD event, and the cumulative mean of glucose. Vertical bars are the 95% confidence interval (95% CI) associated with HR estimates. “***” indicates estimated HR in the related variability quintile is significantly higher than the HR of lowest variability quintile (quintile 1). Figure 1. Hazard ratio (HR) estimates for quintiles of Log(CV)-glucose and ARV-glucose for the primary composite CVD outcome adjusted for ethnicity, baseline HbA1c, baseline HDL and LDL cholesterol, baseline total cholesterol and triglycerides, history of hypertension, diabetes duration, prior CVD event, and the cumulative mean of glucose. Vertical bars are the 95% confidence interval (95% CI) associated with HR estimates. “***” indicates estimated HR in the related variability quintile is significantly higher than the HR of lowest variability quintile (quintile 1).

Disclosure
J. Zhou: None. D. Schwenke: None. P. Reaven: Research Support; Self; AstraZeneca, Amgen Inc., Bristol-Myers Squibb Company.
Relationship between Fasting Insulin Concentration as a Risk Factor for Cardiovascular Disease and High-Density Lipoprotein Cholesterol Levels in Patients with Chronic Hepatitis C
Authors: DRAGUT RAMONA MARIA , RUSU EMILIA , CURSARU RALUCA , RUSU FLORIN , CURSARU ADRIAN , POPESCU HORATIU , RADULIAN GABRIELA 
Published: June 2018

The objective of this study was to evaluate the association between fasting insulin concentration—as a cardiovascular risk factor—and the high density lipoprotein level (HDL-c) in patients with chronic hepatitis C.
Material and Methods: In this cross-sectional study, were included 171 patients from Bucharest, to which were followed anthropometric indexes. Biochemical parameters followed were glucose fasting insulin, glycosylated hemoglobin, lipid profile, liver profile, blood counts. The 10-year coronary heart disease (CHD) was calculated for each patient using the UKPDS risk engine.
Results: The mean age of patients was evaluated 53.14 ± 8.3 years, females representing 53.8% (n=92) of total. Using the UKPDS score 24% (n=41) and 20.5% (n=44) presented moderate and high risk of cardiovascular disease. Levels of fasting insulinemia was significantly high in patients with increase (12.2 uUI/ml) and moderate risk (16.4 uUI/ml) of cardiovascular disease (p&lt;0.001). Level of HDL-cholesterol was significantly lower in patients with increase cardiovascular risk (34.41 mg/dl) vs. patients with reduce (43.03 mg/dl) or moderate cardiovascular risk (39.59 mg/dl) (p&lt;0.001). UKPDS score was positively correlated with age (r=0.62, p=0.001), Forns index (r=0.55, p=0.001), BMI (r=0.39, p=0.001), smoking status (r=0.52, p=0.001), HbA1c (r=0.41, p=0.001), triglycerides (r=0.43, p=0.001), LDL-c (r=0.43, p=0.001), AST (r=0.33, p=0.001), ALT (r=0.26, p=0.001) and GGT (r=0.31, p=0.001) and negative with HDL-c (r=-0.44, p=0.001) and albumin (r=-0.29, p=0.001).
Conclusions: A higher fasting insulin concentration or hyperinsulinemia was significantly associated with an increased cardiovascular risk. This study suggests that early fasting insulin ascertainment in the patients with HCV may help clinicians identify those who are potentially at high risk of CVD.

Disclosure
R. Dragut: None. E. Rusu: None. R. Cursaru: None. F. Rusu: None. A. Cursaru: None. H. Popescu: None. G. Radulian: None.
Severe Hypoglycemia and Clinical Cardiovascular Events in Cohorts with No vs. Early Microvascular Complications
Authors: FAHRMANN ELKE R. , ADKINS LAURA J. , DRISCOLL HENRY 
Published: June 2018

Based on basic research it might be intuitive that the relationship between hypoglycemia requiring assistance (SH) and clinical cardiovascular events (CVE) differs in cohorts with no vs. early microvascular complications (PRIM vs. SEC) in type 1 diabetes (T1DM). We analyze Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) data to examine whether PRIM vs. SEC differences exist in effect of cumulative SH on CVE. At DCCT baseline, 726 PRIM and 715 SEC (with minimal to moderate nonproliferative retinopathy and &lt; 200 mg / 24 h of albuminuria) volunteers were enrolled. Otherwise, subjects (ages 13-39) were in overall good health. Mean follow-up was 27 years. Cox proportional hazard models assessed the effects of time-dependent updated mean SH rate per 100 years on CVE risk. Two outcomes were analyzed: MAJOR (fatal or nonfatal myocardial infarction (MI) or stroke) and ANYCVE (MAJOR, subclinical MI, angina, revascularization, or congestive heart failure). All models were adjusted for clinical covariates. Due to skewness, SH rate was log transformed: ln(SH rate+1). Interaction between mean updated SH rate and ANYCVE (or MAJOR) was significant with p&lt;0.001 (p&lt;0.01). In further analyses by cohort, SH emerged as an independent CVE factor in SEC with hazard ratios of 1.19 (CI95% 1.08-1.31), p&lt;0.001, for ANYCVE and 1.32 (CI95% 1.14-1.53), p&lt;0.001, for MAJOR. No associations were found for PRIM. To get additional insight, DCCT-SH and updated mean EDIC-SH effects on CVE were analyzed during EDIC period (1994-2013). In SEC, DCCT-SH emerged as a significant ANYCVE and MAJOR factor; EDIC-SH was associated with MAJOR but did not reach significance with ANYCVE (p∼0.09). To our best knowledge, this is the first T1DM analysis demonstrating an association of cumulative SH with clinical CVE for SEC patients. In addition to HbA1c, SH in T1DM should be considered as a non-traditional chronic CVE risk factor in SEC and managed accordingly.

Disclosure
E.R. Fahrmann: None. L.J. Adkins: None. H. Driscoll: None.
Coronary Artery Calcium Trajectory Predicts Coronary Artery Disease Events—The CACTI Study
Authors: SNELL-BERGEON JANET K. , KESHAWARZ AMENA , KINNEY GREGORY L. , SCHAUER IRENE E. , SHAH VIRAL N. , PYLE LAURA 
Published: June 2018

Coronary artery calcium (CAC), a marker of subclinical atherosclerosis, predicts coronary artery disease (CAD) events, but the best use of CAC in risk prediction remains unclear. We examined whether group-based trajectory modeling of CAC in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study could independently predict CAD events. Four CAC trajectory groups (Figure 1a) were identified using longitudinal CAC in people free from CAD (Proc TRAJ in SAS Version 9.4), and these groups were used to predict a subsequent CAD event (myocardial infarction or coronary revascularization) using survival analysis. People with type 1 diabetes (T1D) were more likely to be in higher CAC trajectory groups than those without diabetes (non-DM, p&lt;0.0001). Over 17,417 person-years of follow-up, 75 CAD events occurred (56 in T1D and 19 in non-DM individuals). Higher CAC trajectory group predicted CAD events in a dose-response manner (Figure 1b). In cox proportional hazards adjusted for age, sex, T1D, smoking, LDL, HDL, triglycerides and systolic blood pressure, being in a higher CAC group increased CAD risk, with a 33-fold increased risk in Group 4 (95% CI 12-91). A 3.3-fold excess risk (95% CI 1.7-6.4) for CAD remained for people with T1D. CAC trajectory group modeling can identify individuals at very high risk for a CAD event. However, T1D increases CAD risk independently of traditional risk factors and CAC trajectory.

Disclosure
J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation. A. Keshawarz: None. G.L. Kinney: None. I.E. Schauer: None. V.N. Shah: None. L. Pyle: None.
Virtual Diabetes Prevention Program—Effects on Medicare Advantage Health Care Costs and Utilization
Authors: CHIGULURI VINAY , BARTHOLD DOUGLAS , GUMPINA RAJIV , SWEET CYNTHIA CASTRO , PIERATT JASON , CORDIER TRISTAN A. , MATANICH ROGER , RENDA ANDREW , PREWITT TODD G. 
Published: June 2018

This study evaluated the impact of a virtual version of the Diabetes Prevention Program (DPP) on healthcare utilization and costs in a Medicare Advantage population. The program was offered during 2015 to a random sample of 9,497 individuals who had metabolic syndrome or prediabetes. Program enrollees (n=501) received a 12-month virtual DPP including a wireless scale, pedometer, nutrition tracker, educational lessons, health coaching, and peer group support through an online platform. Participants with available administrative claims data during the 12 months before and 24 months following program start (n=495, mean age=69 years; 64% female; 85% white) were propensity-score matched on demographic, behavioral, and clinical factors in a ratio of 1:1 to a comparison group (n=495, selected from 6,490; mean age=69 years; 58% female; 87% white) who did not receive the DPP. In the 24 months following DPP enrollment, participants averaged 0.2 inpatient admissions, 0.3 emergency department visits, and 12.2 physician visits, compared to 0.2, 0.4, and 12.0 for controls. While the utilization values do not show a large change, a difference-in-differences regression analysis of total medical and pharmacy cost for 24 months following program start showed cost savings. The adjusted difference-in-differences effect on average cumulative cost difference was $1,110 per participant, or $46.25/month. Medical and pharmacy costs were consistently lower for participants in the post-program year. Pharmacy savings were statistically significant during the last 6 months, with a 24-month cumulative adjusted savings of $408. These cost estimates do not include the cost of the program. Results suggest that a virtual DPP can change the pattern of utilization and reduce costs in a Medicare population.

Disclosure
V. Chiguluri: None. D. Barthold: None. R. Gumpina: None. C. Castro Sweet: Employee; Self; Omada Health, Inc.. J. Pieratt: None. T.A. Cordier: Employee; Self; Humana Inc.. Stock/Shareholder; Self; Humana Inc.. R. Matanich: None. A. Renda: None. T.G. Prewitt: None.
Wavelet Phase Coherence Analysis between the Respiratory Activity and the Microcirculation—The Effects of Type 1 Diabetes
Authors: PERRELLA ANTONIA , SORELLI MICHELE , FRANCIA PIERGIORGIO , CAPIRCHIO LAURA , ANICHINI ROBERTO , BELLIS ALESSANDRA DE , GULISANO MASSIMO , BOCCHI LEONARDO 
Published: June 2018

The microvascular perfusion is modulated by physiological functions, which have been associated with specific frequency ranges. Although cardio-respiratory interactions have been widely analyzed at a macrocirculation level, only few studies have been conducted with the aim to understand the effect of breathing on the peripheral circulation. Diabetic microangiopathy is characterized by structural and functional alterations of the blood microvessels, which reflect in a modification of the physical properties of peripheral microvascular beds, such as vascular stiffness. A wavelet phase coherence (WPC) analysis was performed to elucidate the time-phase relationship between the respiratory activity and vascular-dependent features of the peripheral pulse, reconstructed by means of a novel multi-Gaussian modeling algorithm. The present WPC analysis was conducted on a group of 24 healthy volunteers, mean age 30±15 years, in comparison with 21 type-1 diabetic (T1D) subjects, mean age 26±3 years, in order to detect the effects of T1D on the physiological coupling between breathing and microcirculation. The peripheral cutaneous perfusion was assessed on the pulp of the index finger with the laser Doppler flowmetry (LDF) technique, while the respiratory signal was simultaneously recorded with a wearable chest band. In 17 out of the 24 control subjects involved (i.e., 71%), significant WPC values were identified in the respiratory frequency range (0.145-0.6 Hz), with respect to the area beneath the diastolic portion of the peripheral pulse (median WPC: 77.9%). This outcome indicates that the diastolic phase of the pulse exhibits a marked periodicity linked to the breathing activity. The analysis conducted on the T1D group highlighted a loss of synchronization, with significant WPC levels found in only 33% of the investigated subjects. These results suggest that the proposed method is able to detect the detrimental effects of T1D on the blood microcirculation.

Disclosure
A. Perrella: None. M. Sorelli: None. P. Francia: None. L. Capirchio: None. R. Anichini: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation, Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company, AstraZeneca. Speaker's Bureau; Self; Merck & Co., Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Sanofi, Janssen Pharmaceuticals, Inc.. Research Support; Self; Grünenthal Group. A. de Bellis: Speaker's Bureau; Self; Eli Lilly and Company, AstraZeneca, Novo Nordisk A/S. Research Support; Self; Grünenthal Group. M. Gulisano: None. L. Bocchi: None.
Effects of Early Intensive Insulin Therapy on Endothelial Progenitor Cells in Patients with Newly Diagnosed Type 2 Diabetes
Authors: WANG HONGDONG , BI YAN , LIU FANGCEN 
Published: June 2018

Objective: Reduced level of endothelial progenitor cells (EPCs) is a critical event in the pathogenesis of vasculopathy in type 2 diabetes. This study aimed to investigate circulating EPCs alteration in newly diagnosed type 2 diabetic patients and how they are affected by early intensive insulin therapy.
Methods: Twenty-one newly diagnosed type 2 diabetic patients and 22 control subjects matched by age, gender, and BMI were enrolled. All of the diabetic patients received intensive insulin therapy. EPC numbers were assessed by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor.
Results: Level of EPC was higher in diabetic patients compared to control subjects (0.071±0.08% vs. 0.016±0.017%, P&lt;0.001). Notably, EPC number was significantly decreased after therapy (0.007±0.005%, P&lt;0.001 vs. pre-treatment). Level of vascular endothelial growth factor (VEGF), a major contributor of EPC mobilization, was significantly higher in diabetic patients compared to control subjects (26.34±9.15 vs. 17.91±6.6, P=0.002), and decreased dramatically after insulin therapy (21.01±4.64, P=0.0039). Moreover, compared with control subjects, pro-inflammatory cytokines were significantly higher in diabetic patients (TNF-α: 18.74±1.65 vs. 15.7±2.16, P&lt;0.001; IL-1β: 14.04±5.6 vs. 9.41±1.94, P=0.017; IFN-γ: 16.47±3.37 vs. 11.71±3.39, P=0.013) and decreased markedly after insulin therapy (17.27±1.78, P=0.009; 10.81±1.35, P&lt;0.001; 13.72±3.21, P&lt;0.001).
Conclusions: These results showed that type 2 diabetes is associated with increased circulating EPC level at the onset of diabetes, indicating increased compensatory mobilization. Additionally, early intensive insulin therapy exerts a preserved effect on EPC level partly through improving inflammation status, thereby implying a putative long term beneficial effect on vascular integrity via suspending excessive EPC exhaustion.

Disclosure
H. Wang: None. Y. Bi: None. F. Liu: None.