bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of NT-proBNP as a Biomarker in Evaluating Residual Cardiovascular Risk in 200 Type 2 DM Patients Optimized for Conventional CV Risk Markers over Two Years
Authors: GUPTA VISHAL , TELI VAISHALI 
Published: June 2018

Methodology: Two hundred T2DM patients who were on standard glucose lowering agents and who may be on lipid and blood pressure lowering agents were optimised for conventional CV risk markers and followed for a period of 2 years. We evaluated CV risk using markers like BMI, HbA1c, Systolic blood pressure (SBP), diastolic BP (DBP), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), non-HDL cholesterol, cholesterol remnant, highly sensitive CRP (hsCRP), serum creatinine, eGFR and urine microalbumin/creatinine ratio (UACR). At the end of 2 years, N-terminal pro-b type natriuretic peptide (NTpro-BNP) was measured to assess its role as a residual CV risk marker. T2DM patients with recent history (&lt;1 years) of revascularization or any major surgery were excluded. Data was analysed using SPSS version 20 and represented as Mean + 2SD with 95% confidence interval, paired t test was used and p value of 0.was considered significant.
Results: Baseline characteristics were: 101(50.5%) males and 99 (49.5%) females, mean age was 61.63 ± 9.84 years, mean age since diagnosis 11.89 ± 7.3y and mean BMI 30.53 ± 5.7 kg/m2. There was an overall significant reduction from baseline to 2 years in HbA1c (7.61 ± 1.7 to 6.8 ± 1.05; p-&lt;0.001), TC (142.55 ± 42.79 to 134.88 ± 40.56, p-0.01), LDL (79.79 ± 35.98 to 70.37 ± 30.69, p-&lt;0.001), TG (133.31 ± 74.27 to 121.68 ± 74.11, p-0.018), Serum creatinine (0.97 ± 0.29 to 0.93 ± 0.26, p-&lt;0.001), UACR (91.43 ± 34.4 to 56.49 ± 16.74), hsCRP (7.02 ± 2.77 to 4.1 ± 1.85, p-0.001). There was no significant change observed with respect to BMI, SBP, DBP, HDL and eGFR from baseline to 2 years. The mean NTpro-BNP at the end of 2 years was 166.33 ± 23.6.
Conclusion: In the present study, inspite of reduction in various CV risk markers over a period of 2 years, mean NTpro-BNP level remained high. Hence, this may suggest the role of NT pro BNP to be of additional value as a CV risk assessment tool in T2DM patients.

Disclosure
V. Gupta: None. V. Teli: None.
Validation of FINDRISC with Latin American Abdominal Perimeter Cutting Points for Risk of Dysglycemia in Workers of a Peruvian National Hospital
Authors: YOVERA MARLON , DAMAS LUCY , TICSE RAY W. 
Published: June 2018

Introduction: Diabetes screening questionnaires such as FINDRISC need to be evaluated in the target population taking into account their own characteristics.
Material and Methods: A cross-sectional study of diagnostic tests was carried out. We found Original FINDRISC (OF) and Modified FINDRISC (MF) scores with Latin American abdominal obesity cut-offs (male ≥ 94 cm and female ≥ 90 cm) to determine dysglicemia including impaired fasting glucose (IFT), glucose intolerance (GIT), and diabetes mellitus (DM), according to Oral Glucose Tolerance Test in workers of the María Auxiliadora Hospital. The Area under the ROC Curve (AUROC) of the MF and OF was found. The sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of each MF and OF point were calculated. A PLR&gt; 2 was rated as useful and one greater than 10 as excellent, and an NLR &lt;0.5 was considered useful and &lt;0.1 as excellent.
Results: Of 549 subjects, 77.5% were female, 70% were&gt; 45 years old, 75% had a BMI&gt; 25 and 65.4% abdominal obesity with Latin American criteria. About 15% had some history of hyperglycemia or hypertension and 70% did not exercise or did not eat vegetables daily. Half of them had a family member with diabetes. There was dysglicemia in 17.8%, of which 11.4% had IFT; 3.8% GIT and 2.6% DM. The MF presented greater accuracy than OF (AUROC: 0.71 vs. 0.69, p = 0.007). There were no differences in the curves between women or men.The score 11 obtained a sensitivity and specificity of 78.6% and 53.0% respectively and the score 14 a sensitivity and specificity of 56.1% and 76.7 respectively. A PLR, a value of 14 is rated useful and an excellent 21. On the other hand, one NLR qualifies a score of 11 as useful and 2 as excellent.
Conclusion: MF had greater diagnostic accuracy than OF for dysglycemia. Scores of 14 and 21, confer high and very high risk; on the contrary, scores of 11 and 2, low and very low risk.

Disclosure
M. Yovera: None. L. Damas: None. R.W. Ticse: None.
Effect of Obesity and Exercise on Amino Acid Metabolites in American-Indian Adolescents at Risk for Diabetes
Authors: SHORT KEVIN R. , CHADWICK JENNIFER , TULLIER MARY A. , WOLBERT LISA D. , COLEMAN CHARLOTTE L. , COPELAND KENNETH C. 
Published: June 2018

Circulating amino acids (AA) and their metabolites are biomarkers for insulin resistance and future diabetes in adults, but there are few, and conflicting findings in studies of adolescents. We performed amino acid metabolomic profiling in American Indian adolescents to determine whether specific analytes would vary with body composition and insulin sensitivity, and/or be altered in response to exercise training. Boys and girls, 11-18 years who were normal weight (NW, n=36) or obese (Ob, n=58) completed tests of fitness, body composition, and a fasting blood draw. Forty-two of the Ob group were retested after completing 16 weeks of aerobic exercise training. A panel of 42 plasma amino acids and metabolites were measured by UPLC/MS/MS. The Ob group had several risk factors for future diabetes, including higher body fat, lower aerobic fitness, and lower insulin sensitivity (iHOMA2). The Ob group had 16 analytes that were higher and 8 lower than the NW group. Among those that were higher in the Ob group were branched chain AAs (Val, Leu, Ile, +13-17%) and aromatic AAs (His, Phe, Tyr, +15-34%); those AAs were also correlated with body fat (r=0.32 to 0.53) and insulin sensitivity (r=-0.32 to -0.60). The Lys metabolite, α-aminoadipic acid, a predictor of diabetes in adults, was 46% higher in the Ob group and correlated with insulin sensitivity (r=-0.43). β-aminoisobutyric acid, a myokine related to insulin resistance in adults, was 29% lower in the Ob vs. the NW group and correlated with insulin sensitivity (r=0.32). Exercise training resulted in a 10% increase in aerobic fitness, but body composition and insulin sensitivity were unchanged. Only two AAs were changed (His, Cys) after training. These novel findings in adolescents demonstrate that several plasma AAs are altered by obesity and serve as biomarkers of insulin action, but are not altered with this exercise intervention.

Disclosure
K.R. Short: None. J. Chadwick: None. M.A. Tullier: None. L.D. Wolbert: None. C.L. Coleman: None. K.C. Copeland: Other Relationship; Self; Novo Nordisk Inc..
Concordance of Glucose-Based and of HbA1c-Based Diagnoses of Diabetes in Patients with Peripheral Artery Disease—A Comparison between Two Age Groups
Authors: SAELY CHRISTOPH H. , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN DANIELA , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ 
Published: June 2018

Concordance between glucose-based and HbA1c-based diagnoses of diabetes differ between populations. Here, we aimed at investigating their concordance in younger and in older patients with peripheral artery disease (PAD). We measured fasting glucose as well as HbA1c and performed 75g oral glucose tolerance tests in 188 consecutive patients, 113 older and 75 younger than 65 years, who had sonographically proven PAD but not previously diagnosed diabetes. Based on glucose values, diabetes was diagnosed with fasting plasma glucose (FPG) ≥126 mg/dl or post-challenge glucose ≥200 mg/dl 2 hours after the oral glucose load; based on HbA1c values diabetes was diagnosed with HbA1c ≥6.5%. Among PAD patients &lt;65 years, 5 had diabetes based on glucose criteria, of whom 3 also had diabetes according to the HbA1c criterion, and 70 did not have diabetes according to glucose criteria, of whom 67 also did not have diabetes using HbA1c criteria; among those ≥65 years, 19 had diabetes based on glucose criteria, of whom 10 also had diabetes according to the HbA1c criterion and 94 did not have diabetes based on glucose criteria, of whom 93 also did not have diabetes according to HbA1c criteria. Concordance of glucose and HbA1c criteria was similar in younger and older PAD patients (93.3% and 91.2%; p=0.589). Applying glucose criteria as a standard, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the HbA1c criterion for PAD patients &lt;65 years were 60.0%, 95.7%, 50.0%, and 97.1%, and for those ≥65 years 52.6%, 98.9%, 90.9%, and 91.2%. We conclude that the concordance of glucose and HbA1c criteria among patients with PAD is high and is similar in older and younger subjects. However, for both age groups the sensitivity of the HbA1c criterion is poor in this patient population.

Disclosure
C.H. Saely: 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.
Using MetS Severity to Track Risk for T2D during Intervention with Lifestyle and Metformin
Authors: DEBOER MARK D. , FILIPP STEPHANIE L. , GURKA MATTHEW J. 
Published: June 2018

While a metabolic syndrome severity Z-score (MetS-Z) predicts incident type 2 diabetes (T2D) in observational cohorts, it is unclear whether MetS-Z can track response to medical intervention and whether changes in MetS-Z during treatment reflect altered risk for T2D. We evaluated data from the Diabetes Prevention Program, which randomized individuals with glucose intolerance (age 51±11 years) to receive: placebo (n=882), metformin 850 mg bid (n=867), or an intensive lifestyle modification program (n=827). We assessed levels of MetS-Z and the individual MetS components during 3 years of intervention (Figure), revealing 1-year decreases in MetS-Z among those treated with lifestyle (effect size -0.6), metformin (-0.3) and placebo (-0.1), driven by improvements in the individual MetS components. We assessed how change in MetS-Z affected T2D risk, finding that each 1-point increase in a participant’s effect size of MetS Z between 0 and 1 year (difference per participant/baseline SD) increased odds of incident T2D by year 3 by 70% (adjusting for intervention group; Figure). This positive association was found in individual models and in a joint model that included changes in MetS-Z and in each MetS component—suggesting independent associations of changes in MetS-Z with future T2D risk. These data support MetS-Z as an important outcome to follow for response to medical treatment in research studies and clinical care.

Disclosure
M.D. DeBoer: None. S.L. Filipp: None. M.J. Gurka: None.
Cardiometabolic Risk Disparities Associated with Health Insurance Status in a Latino Community in California
Authors: AXELROD CEARA , CHAVEZ ELOISA , BEVIER WENDY C. , CREASON JAMIE , CASTORINO KRISTIN , KERR DAVID 
Published: June 2018

In the U.S., rates of type 2 diabetes (T2D) are higher in Latinos than in non-Latino whites. In 2015, we began a free community outreach program (Mobile Health Screenings, MHS) for the local Latino community to assess diabetes prevalence, cardiovascular risk and their relationships to insurance status. From July 2015 to November 2017, we measured HBA1c (A1c Now+®, PTS Diagnostics, Indianapolis, IN), body mass index (BMI), and blood pressure (BP) in 593 people at 24 MHS events. Health insurance status and current medications for diabetes and hypertension (HTN) were also recorded. More than half of those screened (55%) had HBA1c values between 5.7-6.4% or ≥6.5%. Of the 589 participants who provided insurance information, 262 (44%) reported either having no insurance (n=212, 36%) or not knowing if they had insurance (n=50, 8%). Individuals with private insurance (n=101) had significantly lower HBA1c levels than those with either government insurance (MediCal, Medicare, etc., (n=113), [5.7±0.7% vs. 6.0±1.0%, p=0.017] and no insurance (n=201), [5.7±0.7% vs. 6.0±1.2%, p=0.002]. The highest rates of prediabetes and diabetes (45% and 17%) were in the uninsured group and the lowest rates (30% and 12%) were in the privately insured group. Those without insurance also took fewer medications for HTN vs. those with insurance (11.3% vs. 20.0%, p=0.005). BMI was also significantly lower for insured participants [28.8±5.4 kg/m2 (n=344) vs. uninsured participants 30.0±5.5 kg/m2 (n=206, p=0.016].
In conclusion, there is an excess burden of cardio-metabolic disease on uninsured adult Latinos in Santa Barbara.

Disclosure
C. Axelrod: None. E. Chavez: None. W.C. Bevier: None. J. Creason: None. K. Castorino: None. D. Kerr: Advisory Panel; Self; Glooko, Inc.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Sanofi-Aventis. Stock/Shareholder; Self; Cellnovo. Advisory Panel; Self; Novo Nordisk Inc..
Performance of Clinical/Proteomic Biomarker Panels to Predict Coronary Artery Disease Presence or Cardiovascular Prognosis in Patients With and Without Diabetes Mellitus
Authors: SHRESTHA SHREYA , MCCARTHY CIAN P. , IBRAHIM NASRIEN E. , KIMMENADE ROLAND VAN , GAGGIN HANNA , MUKAI RENATA , MAGARET CRAIG A. , BARNES GRADY , RHYNE RHONDA F. , JANUZZI JAMES 
Published: June 2018

Background: Patients with diabetes mellitus (DM) are at increased risk for prevalent coronary artery disease (CAD) and incident major adverse cardiac events (MACE) such as cardiovascular death, myocardial infarction, and stroke. Prediction of risk in those with DM may be challenging. Using unbiased proteomics we recently described biomarker panels to predict prevalent CAD (HART-CAD) and incident MACE (HART-CVE; both Prevencio, Kirkland, WA) in unselected patients undergoing diagnostic coronary angiography. In this study, we sought to compare accuracy of these panels in patients with and without DM.
Methods: The HART-CAD panel includes 2 clinical variables (male sex and prior PCI) and 4 biomarkers: adiponectin, apolipoprotein CI, kidney injury molecule 1 (KIM 1), and midkine. The HART-CVE panel includes 4 biomarkers (amino-terminal pro-B type natriuretic peptide, KIM 1, osteopontin, and tissue inhibitor of matrix metalloproteinase-1). These panels were derived in 167 DM and 482 non-DM patients; performance of each was validated in a second cohort of patients (N=278) with and without DM.
Results: In patients with DM, the HART-CAD panel had excellent performance for prediction of coronary stenosis ≥ 70%, with area under the curve (AUC) of 0.81 (p&lt;0.001), sensitivity 85%, specificity 69%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 58% for detection of CAD, results comparable to those without DM. HART-CVE was highly predictive of incident 1 year MACE in those with DM: AUC of 0.80 (p=0.002), sensitivity 78%, specificity 69%, PPV 47%, and NPV of 90%, again, comparable to those without DM. In Kaplan-Meier analyses, an elevated HART-CVE score predicted shorter time to first MACE (p&lt;0.001).
Conclusion: Previously described multivariate proteomic biomarker panels effectively predict prevalent CAD and risk for incident MACE in at-risk patients with DM.

Disclosure
S. Shrestha: None. C.P. McCarthy: None. N.E. Ibrahim: None. R. van Kimmenade: None. H. Gaggin: Research Support; Self; Roche Diagnostics Corporation, Portola. Consultant; Self; Roche Diagnostics Corporation, Amgen Inc., Ortho clinical. Other Relationship; Self; EchoSense, Radiometer. R. Mukai: None. C.A. Magaret: Consultant; Self; Prevencio. G. Barnes: Employee; Self; Prevencio. R.F. Rhyne: None. J. Januzzi: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Board Member; Self; Jana Care Inc.. Research Support; Self; Prevencio.
A Novel Ceruloplasmin Mutation Causing Aceruloplasminemia with Diabetes in China
Authors: XIAO YUANYUAN 
Published: June 2018

Background: Hereditary aceruloplasminemia is a rare adult-onset autosomal recessive disease characterized by a ceruloplasmin(CP) gene mutation and defective or absent ceruloplasmin function. The absence of ceruloplasmin leads to pathological iron overload in the liver, pancreas, retina, and central nervous system. It is clinically characterized by diabetes mellitus, anaemia, retinal degeneration and neurological abnormalities.
Material and Methods: A 34-year-old Chinese woman who had had diabetes mellitus characterized by fast plasma glucose increasing for more than 3 years. She had tried all kinds of hypoglycemic medicines,the postprandial blood glucose could be well controlled, but still had a fast hyperglycemia. Here, we reported the identification, clinical characterization, and analysis of a novel mutation in the ceruloplasmin gene of this patient and her family members.
Results: Laboratory findings revealed a complete undetectable serum Cp. Increased serum ferritin levels, elevated iron saturation, as well as results of iron quantification in the liver and CT scan also suggested iron overload in the liver. Imaging examination showed a pronounced hyperintensity in the bilateral putamina, caudate, thalamus and dentate nuclei suggesting the presence of iron overload. By sequencing the ceruloplasmin gene, A novel homozygous ceruloplasmin gene mutation, c.146+1G&gt;T, was identified as the cause of aceruloplasminemia in this patient. Another healthy family members were heterozygous as well.
Conclusion: So far, less than 60 families cases of aceruloplasminemia have been reported world-wide and mainly missense and nonsense mutations in the ceruloplasmin gene were detected. There was only one case about aceruloplasminemia has been reported in China before. We report herein a case of aceruloplasminemia accompanied by diabetes with a novel mucutation of CP gene, which suggests that increased awareness should be paid to this disorder as diabetes is an important typical symptoms of it.

Disclosure
Y. Xiao: None.
Caloric Restriction Increases the Resistance of Aged Heart to Myocardial Ischemia/Reperfusion Injury
Authors: GUO ZHIJIA , ROUSSELLE THOMAS , LI JI 
Published: June 2018

Ischemic tolerance of heart decreases with age. Caloric restriction (CR) is the most reliable intervention to extend lifespan and prevent age-related disorders. We have revealed that both AMPK and SIRT1 signaling pathways are involved in the impairments occurred in aged hearts. We hypothesize that cardiac AMPK-SIRT1 signaling cascade mediates the increased tolerance of aged heart to ischemic insults by caloric restriction. Aged (18-20 months) mice were divided into 2 groups: al libitum (AL) food intake group and caloric restriction (diet 70% of standard food intake for 6 weeks) (CR) group. Each group was divided into sham operations and ischemia/reperfusion (I/R) semi-groups. I/R groups were subjected to ligation of left anterior descending coronary artery for 30 min of ischemia and 24 hours of reperfusion. The body fat composition was significantly decreased in CR group vs. AL group, moreover, the maximum of oxygen consumption was significantly improved in CR group vs. AL group. Importantly, there is a significantly smaller myocardial infarction size induced by ischemia (30 min) and reperfusion (24 hours) in CR group than that in AL group. The immunoblotting results demonstrated that the impaired ischemic AMPK activation in AL group was augmented in CR group, and the AMPK downstream acetyl CoA carboxylase (ACC) phosphorylation and PGC-1alpha phosphorylation were also augmented in CR vs. AL group in response to ischemic insults. Intriguingly, the expression levels of a longevity protein, SIRT1, were upregulated in the heart of CR group vs. the corresponding AL group. Furthermore, the inducible cardiomyocyte SIRT1 deficiency mice (icSIRT1 KO) did not show any recused impaired ischemic AMPK activation in the CR group vs. icSIRT1 KO AL group. Thus, caloric restriction is a non-pharmacological approach to increase the tolerance of aged heart to ischemic insults. The AMPK-SIRT1 signaling cascade plays a critical role in the cardiac CR benefits in the elderly.

Disclosure
Z. Guo: None. T. Rousselle: None. J. Li: None.
Circulating Netrin-1 as a Novel Biomarker for Impaired Fasting Glucose and Newly Diagnosed Type 2 Diabetes Mellitus
Authors: JUNG HYE-IN , BAE JAEHYUN , HAN EUGENE , KIM GYURI , LEE JI-YEON , KIM SO RA , LEE BYUNG-WAN , KANG EUN SEOK , AHN CHUL WOO , CHA BONG-SOO , LEE YONG-HO 
Published: June 2018

Aims/Hypothesis: Netrin-1 has been introduced as a neuronal guidance cue, acting as a chemoattractant and chemorepulsive force during axonal migration. In recent studies, netrin-1 was shown to play various roles including tissue regeneration and modulation of inflammatory action. Inflammation is one of the major contributing factors in the development of insulin resistance and type 2 diabetes (T2DM). However, little is known about the possible relationship between serum netrin-1 and the risk of T2DM. Therefore, we investigated the association between levels of netrin-1 and glycometabolic parameters.
Methods: Serum samples were collected from a total of 218 individuals (41 normal controls, 85 subjects with impaired fasting glucose (IFG) and 92 subjects with newly diagnosed T2DM). Clinical and biochemical parameters were assessed after receiving consent. Netrin-1 levels were determined by commercial enzyme-linked immunosorbent assay. Spearman correlation analyses and multivariable-adjusted linear regression analyses were conducted to examine the relationship between serum netrin-1 levels and glycometabolic parameters.
Results: Serum netrin-1 level in subjects with IFG or T2DM was significantly higher than in normal control subjects (mean netrin-1 level; normal, IFG and T2DM; 275.9, 436.6 and 441.0 pg/mL, respectively; p for trend &lt;0.001). Serum netrin-1 levels had a significant positive correlation with fasting glucose, HbA1c, HOMA-IR, AST and ALT. Meanwhile, statistically inverse correlation was found between netrin-1 and HDL cholesterol and eGFR levels. In addition, Serum netrin-1 was independently associated with the presence of IFG or T2DM after adjusting covariates and potential confounders. In terms of the AUC, serum netrin-1 levels presented an AUC of 0.784 for the prediction of IFG or T2DM.
Conclusions/Interpretation: Our results suggest that netrin-1 may be a new biomarker for early detection for IFG or T2DM (Clinical trial no. NCT02650830).

Disclosure
H. Jung: None. J. Bae: None. E. Han: None. G. Kim: None. J. Lee: None. S. Kim: None. B. Lee: None. E. Kang: None. C. Ahn: None. B. Cha: None. Y. Lee: None.