Metabolic Diseases Etiology Research Center Research Articles

Association of Insulin Resistance with Lower Bone Volume and Strength Index of the Proximal Femur in Nondiabetic Postmenopausal Women

BackgroundType 2 diabetes mellitus is associated with an increased risk of osteoporotic fracture despite relatively preserved bone mineral density (BMD). Although this paradox might be attributed to the influence of insulin resistance (IR) on bone structure and material properties, the association of IR with femur bone geometry and strength indices remains unclear.MethodsUsing data from the Cardiovascular and Metabolic Disease Etiology Research Center cohort study, we conducted a cross-sectional analysis among nondiabetic postmenopausal women. IR was estimated using the homeostasis model assessment of IR (HOMA-IR). Compartment-specific volumetric BMD (vBMD) and bone volume of proximal femur were measured using quantitative computed tomography. The compressive strength index (CSI), section modulus (Z), and buckling ratio of the femoral neck were calculated as bone strength indices.ResultsAmong 1,008 subjects (mean age, 57.3 years; body mass index [BMI], 23.6 kg/m2), BMI, waist circumference, and vBMD of the femoral neck and total hip increased in a linear trend from the lowest (<1.37) to highest (≥2.27) HOMA-IR quartile (P<0.05 for all). The HOMA-IR showed an independent negative association with total bone volume (standardized β=−0.12), cortical volume (β=−0.05), CSI (β=−0.013), and Z (β=−0.017; P<0.05 for all) of the femoral neck after adjustment for age, weight, height, physical activity, and vitamin D and high-sensitivity C-reactive protein levels. However, the association between HOMA-IR and vBMD was attenuated in the adjusted model (femoral neck, β=0.94; P=0.548).ConclusionsElevated HOMA-IR was associated with lower cortical bone volume and bone strength indices in nondiabetic postmenopausal women, independent of age and body size.

Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) cohort: study protocol and results of the first 3 years of enrollment.

Although the etiologies of cardiovascular disease (CVD) are widely understood, the goal of finding a globally effective solution for preventing CVD is unrealistic. Therefore, we aimed to conduct a community-based prospective study on the prevention and management of CVD in Korean adults. This study was designed to recruit 8,000 healthy adults over the course of 5 years. The baseline assessment includes a wide range of established CVD risk factors, including demographic characteristics, medical history, health behaviors, psychological conditions, body size and composition, blood pressure, the augmentation index, carotid ultrasonography, an electrocardiogram, and biochemical indicators, as well as some novel factors, such as social network characteristics, exposure to environmental pollutants, inflammatory markers, hemostatic markers, and immunosenescence markers. Annual telephone interviews and follow-up health examinations at 5-year intervals after the baseline assessment are planned to collect information on changes in health status and its determinants. Additionally, indirect follow-up using secondary data sources will be conducted to obtain information on health services utilization and death. So far, more than 6,000 adults have been enrolled during the first three and a half years, and almost all participants have been tracked by annual telephone follow-up surveys. The data have been uploaded to iCReaT, the clinical research information management system of the Korea National Institute of Health.

Exposure to bisphenol A is directly associated with inflammation in healthy Korean adults.

It was recently discovered that bisphenol A (BPA) and phthalates are cardiovascular disruptors. Inflammation is central to the initiation and progression of cardiovascular disease (CVD). This study evaluated whether BPA and different phthalate metabolites are associated with the inflammation marker high-sensitivity C-reactive protein (hs-CRP) in healthy Korean adults. This research is part of an ongoing, population-based study of Korean adults (30-64years of age) conducted at the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC). The study enrolled 200 healthy volunteers (96 men, 104 women). Plasma hs-CRP was measured as an inflammation marker. BPA and five phthalate metabolites in urine were analyzed by using liquid chromatography/tandem mass spectrometry. BPA and monobenzyl phthalate (MBzP) differed significantly between the low-hs-CRP (<2mg/L) and high-hs-CRP (≥2mg/L) groups. BPA and MBzP were related to hs-CRP in an inverted L-shaped manner. High BPA levels (≥75th percentile) had significant odd ratios (ORs) for high hs-CRP even after adjusting for confounding factors related to obesity and insulin resistance, such as visceral fat volume, body mass index (BMI), adiponectin, high-density lipoprotein (HDL) cholesterol, hemoglobin A1c (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR) (OR=2.85; 95% CI, 1.16-6.97). However, there was no significant association for MBzP ≥75th percentile. BPA was significantly related to high hs-CRP, even after adjusting for factors related to obesity and insulin resistance. Therefore, BPA could have a direct relationship with systemic inflammation regardless of obesity or insulin resistance.

MPS 04-03 MORNING HYPERTENSION WITH NOCTURNAL HYPERTENSION WAS RELATED WITH HIGHER CENTRAL BLOOD PRESSURE AND INCREASED ARTERIAL STIFFNESS

Objective: Recent study reported that morning hypertension was associated with worse cardiovascular outcomes in hypertensive patients. There are not enough studies about the inter-relationship between morning hypertension/nocturnal hypertension and central hemodynamics until now. Design and Method: Ambulatory blood pressure monitoring and central BP were measured in 1062 consecutive subjects enrolled in Cardiovascular and Metabolic Disease Etiology Research Center - HIgh Risk Cohort (CMERC-HI, NCT02003781). Morning hypertension was defined as mean systolic BP (SBP) within 2 hours after awake > 135mmHg and nocturnal hypertension as mean night SBP > 120mmHg or diastolic BP (DBP ≥ 70mmHg. We divided morning hypertension into 3 subtypes. 1) morning normotension 2) morning hypertension without nocturnal hypertension and 3) morning hypertension with nocturnal hypertension. Results: Morning hypertension was found in 494 (46.5%) patients and morning hypertension with nocturnal hypertension was in 403 (37.9%) patients. Central SBP/DBP (129/79 ± 21/11 vs. 116/75 ± 17/9mmHg, both p < 0.001), augmentation index (AIx, 30.6 ± 11.4 vs. 27.4 ± 13.3, p < 0.001) and carotid to femoral pulse wave velocity (cfPWV, 986 ± 245 vs. 887 ± 198 cm/s, p < 0.001) were higher in morning hypertension than in morning normotension. There were significant difference in central SBP (120/75 ± 16/8 vs. 116/75 ± 17/9mmHg, p = 0.027 for SBP, p = 0.746 for DBP) and cfPWV (932 ± 220 vs. 887 ± 198 cm/s, p = 0.049) not 24-hour SBP/DBP (p = 0.150/p = 0.219) between morning normotension and morning hypertension without nocturnal hypertension group. The morning hypertensive patients with nocturnal hypertension had higher central SBP/DBP (131/79 ± 21/11 vs. 120/75 ± 16/8mmHg, both p < 0.001) and cfPWV (998 ± 248 vs. 932 ± 220 cm/s, p = 0.020) compared to those without nocturnal hypertension. Conclusions: We reported that morning hypertension, especially with nocturnal hypertension was related to higher central BP and increased arterial stiffness. Further studies for assessing whether morning hypertension with or without nocturnal hypertension relates to clinical outcomes should be warranted.

MPS 08-04 The association between ST interval and blood pressure in a general population of Korea

Objective: To evaluate the association of PR interval, QRS duration, and ST interval with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a general population of Korea. Design and Method: We conducted a cross-sectional analysis from the data of Cardiovascular and Metabolic diseases Etiology Research Center, an ongoing cohort of general population. Total 587 men and 1065 women were separately analyzed. PR interval, QRS duration and QT interval was obtained from electrocardiogram; ST interval was calculated by subtracting QRS duration from QT interval. Resting blood pressure was measured using an automatic sphygmomanometer. Linear regression analysis was used to obtain the estimates of each SBP and DBP with each PR interval, QRS duration, and ST interval, adjusting for age, body mass index, heart rate, triglyceride, high density lipoprotein cholesterol, smoking behavior, insulin, and diagnosis of hypertension or diabetes. Results: One beat per minute increase of resting heart rate was significantly associated with high DBP in both sexes, and low SBP in women. In men, the estimates (p value) for SBP (mmHg) with 10 millisecond increase of each PR interval, QRS duration, and ST interval was −0.013 (0.86), 0.467 (0.10), and 0.303 (0.01), respectively. The corresponding estimates (p value) was −0.045 (0.41), −0.255 (0.20), and −0.356 (<.001) for DBP (mmHg). In women, the estimates (p value) was 0.020 (0.61), 0.073 (0.37), and 0.053 (0.01) for SBP, and −0.017 (0.53), −0.053 (0.34), and −0.041 (0.004) for DBP. Conclusions: Beyond the three components of a heart rhythm, ST interval was significantly associated with high SBP and low DBP. This finding suggests that period of ventricle depolarization is associated with blood pressure.

PS 08-43] THE PATTERNS OF AMBULATORY BLOOD PRESSURE IS QUITE DIFFERENT IN PATIENTS WITH END-STAGE RENAL DISEASE ACCORDING TO DIALYSIS MODALITY

Objective: Since accurate assessment of blood pressure (BP) is essential to control BP adequately, ambulatory blood pressure monitoring (ABPM) is widely used for estimation of BP status and has prognostic significance in patients with hypertension including end-stage renal disease (ESRD). Although the ABPM patterns might be distinguished due to the inherent characteristics of dialysis modality, there has been lacking evidences until now. Therefore, the aim of this study was to elucidate difference of ABPM parameters and pattern according to dialysis modality. Design and Method: Patients were prospectively enrolled by Cardiovascular and Metabolic Disease Etiology Research center (CMERC) of Yonsei University College of Medicine between November 2013 and August 2015. We analyzed the differences of baseline characteristics, office BPs, ABPM parameters and ABPM patterns (dipper, non-dipper and reverse dipper) in ESRD patients according to dialysis modality. Results: Among a total of 174 patients, 109 (62.6%) were hemodialysis (HD) patients and 65 (37.4%) were peritoneal dialysis (PD) patients. 155 (89.1%) patients had hypertension, 96 (89.2%) in HD and 59 (90.8%) in PD. All measured diastolic BP (DBP) and 24 hours mean arterial pressure (MAP) were significantly higher in PD (office DBP, 24 h mean DBP, daytime DBP and night DBP; respectively p = 0.011, 0.006, 0.010 and 24 hours MAP; p = 0.047) compared to those in HD. The prevalence of non-dipper was higher in PD than HD (dipper vs non-dipper; 33.0% vs 39.4% in HD and 26.2% vs 47.7% in PD). Total number of antihypertensive medications was higher in PD than HD. Conclusions: ABPM patterns, DBP and 24 hours MAP in dialysis patients were significant different according to dialysis modality. Despite the effort for controlling BP by using more antihypertensive medications, BP control based on office BP is not satisfactory and adverse ABPM pattern is more prevalent in PD patients than HD.

PS 05-87 INCREASED CORONARY ARTERY CALCIUM SCORE IS ASSOCIATED WITH LOCALIZED RETINAL NERVE FIBER LAYER DEFECTS ON OPTICAL COHERENCE TOMOGRAPHY

Objective: Retinal damages have been suggested a surrogate marker of end-organ damage and prognostic marker in hypertensive patients. Recent study reported that localized retinal nerve fiber layer defect (RNFLD) assessed by noninvasive optical coherence tomography (OCT) was related to the degree of hypertension severity and cerebrovascular disease. Design and Method: RNFLD and coronary artery calcium score (CACS) were assessed by retinal OCT and coronary calcium scan in 765 consecutive subjects enrolled in Cardiovascular and Metabolic Disease Etiology Research Center - HIgh Risk Cohort (CMERC-HI, NCT02003781). We excluded patients with glaucoma, which is known to be related to RNFLD independently of cardiovascular (CV) risk factors. The 2013 AHA/ACC guideline defined high risk coronary artery calcium score (CACS) group as 300 ≥ Agatston Units (AU). Results: RNFLD was found in 170 (22.2%) patients. The patients with RNFLD were higher in frequency in men and had lower estimated glomerular filtration rate (eGFR) compare to those without RNFLD. The RNFLD patients had higher CACS (306 ± 613 vs. 192 ± 500AU, p = 0.028) compared to those without RNFLD. There were higher prevalence of high risk CACS group (23.5% vs. 15.1%, p = 0.015) and lower prevalence of zero CACS group (29.4% vs. 42.0%, p = 0.003) in RNFLD patients. Multivariate logistic regression analysis revealed that RNFLD was independently associated with high CACS after controlling for other CV risk factors including smoking, eGFR (odd ratio; 1.650, 95% confidence interval; 1.014–2.684, p = 0.044). Conclusions: We reported that RNFLD on OCT was related to higher CACS for the first time. Further studies which validate RNFLD as a cardiovascular surrogate and end organ damage marker should be warranted.

PS 05-47 THE FLUID OVERLOAD ASSESSED BY BIOIMPEDANCE ANALYSIS IS SIGNIFICANTLY ASSOCIATED WITH NOT ONLY ARTERIAL STIFFNESS BUT ALSO VASCULAR CALCIFICATION IN PATIENTS WITH HYPERTENSION

Objective: The overhydration (OH) is independently associated with vascular dysfunction and established risk factors for cardiovascular morbidity and mortality in chronic kidney disease patients. However, the effect of OH on the cardiovascular risks in hypertensive patients with relatively preserved renal function was not fully investigated. The aim of this study is to elucidate the relationship between OH and the cardiovascular surrogates in hypertensive patients. Design and Method: Hypertensive (n = 295) and pre-hypertensive with the family history of cardiovascular events (n = 96) patients from the Cardiovascular and Metabolic Disease Etiology Research Center–High Risk Cohort (CMERC-HI, NCT02003781) are eligible in present study. Fluid status was measured by bioimpedance analysis and OH was defined by using the ratio of extracellular water to total body water (ECW/TBW, OH group: ECW/TBW ≥ 0.39). Results: OH more frequently observed in hypertensive patients than pre-hypertensive patients as a control group (202 [32.8%] vs. 9 [9.4%], P < 0.001). The mean age of the study subjects with hypertension was 60.0 ± 11.8, and 159 (59.3%) patients were male. Coronary calcium score (CCS, 79 [4–551] vs. 18 [0–114], P < 0.001), carotid intima-media thickness (CIMT, 0.79 ± 0.18 vs. 0.75 ± 0.15 mm, P = 0.038), and pulse-wave velocity (PWV, 1628 ± 341 vs. 1483 ± 269 cm/sec, P < 0.001) were significantly higher in OH group compared to the non-OH group. The ECW/TBW was positively correlated to 24-hr daytime and nighttime pulse pressure (day: r = 0.123, P = 0.034; night: r = 0.205, P < 0.001), PWV (r = 0.290, P < 0.001), and CCS (r = 0.198, P = 0.001). Meanwhile, 24-hr diastolic blood pressure (all day [r = −0.137, P = 0.018], daytime [r = −0.114, P = 0.050], and nighttime [r = −0.139, P = 0.017]), hemoglobin (r = −0.431, P < 0.001), and serum albumin (r = −0.184, P = 0.002) showed a negative correlation with ECW/TBW. Conclusions: Hypertensive patients were much prevalent OH than pre-hypertensive patients. Even though in hypertensive patients with normal renal function, OH is significantly associated with the surrogates of cardiovascular risks. Present study suggests that the strict control of OH could be more helpful to reduce the cardiovascular risks in these individuals.

Association between blood glucose level derived using the oral glucose tolerance test and glycated hemoglobin level.

Background/Aims:Glycated hemoglobin (HbA1c) is widely used as a marker of glycemic control. Translation of the HbA1c level to an average blood glucose level is useful because the latter figure is easily understood by patients. We studied the association between blood glucose levels revealed by the oral glucose tolerance test (OGTT) and HbA1c levels in a Korean population.Methods:A total of 1,000 subjects aged 30 to 64 years from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort were included. Fasting glucose levels, post-load glucose levels at 30, 60, and 120 minutes into the OGTT, and HbA1c levels were measured.Results:Linear regression of HbA1c with mean blood glucose levels derived using the OGTT revealed a significant correlation between these measures (predicted mean glucose [mg/dL] = 49.4 × HbA1c [%] − 149.6; R2 = 0.54, p < 0.001). Our linear regression equation was quite different from that of the Alc-Derived Average Glucose (ADAG) study and Diabetes Control and Complications Trial (DCCT) cohort.Conclusions:Discrepancies between our results and those of the ADAG study and DCCT cohort may be attributable to differences in the test methods used and the extent of insulin secretion. More studies are needed to evaluate the association between HbA1c and self monitoring blood glucose levels.

Visceral Fat Mass Has Stronger Associations with Diabetes and Prediabetes than Other Anthropometric Obesity Indicators among Korean Adults.

PurposeThis study determined which obesity measurement correlates the best with diabetes and prediabetes.Materials and MethodsThis cross-sectional study enrolled 1603 subjects (611 men, 992 women; age 30–64 years) at the Cardiovascular and Metabolic Diseases Etiology Research Center. Body mass index, waist circumference, waist-height ratio, waist-hip ratio, waist-thigh ratio, and visceral fat were used as measures of obesity. Visceral fat was acquired using dual-energy X-ray absorptiometry (DXA). The prevalences of diabetes and prediabetes were defined using the criteria in the American Diabetes Association 2015 guidelines.ResultsAfter adjusting for age and other potential confounding factors, participants with a visceral fat mass in the upper 10th percentile had a higher odds ratio (OR) for diabetes and prediabetes than the upper 10th percentile of other adiposity indices [men, OR=15.9, 95% confidence interval (CI)=6.4–39.2; women, OR=6.9, 95% CI=3.5–13.7]. Visceral fat mass also had the highest area under the curve with diabetes and prediabetes in both men (0.69, 95% CI=0.64–0.73) and women (0.70, 95% CI=0.67–0.74) compared to other anthropometric measurements of obesity.ConclusionVisceral fat mass measured using DXA is an indicator of diabetes or prediabetes, due to its ability to differentiate between abdominal visceral and subcutaneous fat.

Inter-Arm Difference in Brachial Blood Pressure in the General Population of Koreans.

Background and ObjectivesWe investigated the inter-arm difference in blood pressure of the general Korean population to identify associated factors.Subjects and MethodsA total of 806 participants aged 30 to 64 years without history of major cardiovascular disease were analyzed in this cross-sectional study. They participated in the Cardiovascular and Metabolic Disease Etiology Research Center cohort study that began in 2013. Brachial blood pressure was measured simultaneously for both arms using an automated oscillometric device equipped with two cuffs in seated position. After five minutes of rest, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured three times. The average of the three measurements was used for analysis. Multivariate logistic regression models were used to identify factors associated with inter-arm differences in blood pressure.ResultsThe mean inter-arm difference was 3.3 mmHg for SBP and 2.0 mmHg for DBP. Large inter-arm differences (≥10 mmHg) in SBP and in DBP were found in 3.7% and 0.9% of subjects, respectively. A large inter-arm difference in SBP was associated with mean SBP (p=0.002) and C-reactive protein (p=0.014) while a large inter-arm different in DBP was only associated with body mass index (p=0.015). Sex, age, and anti-hypertensive medication use were not associated with differences in inter-arm blood pressure.ConclusionLarge inter-arm difference in blood pressure is only present in a small portion of healthy Korean adults. Our findings suggest that high SBP, chronic inflammation, and obesity may be associated with larger difference in inter-arm blood pressure.

Abstract 15581: Nocturnal Blood Pressure is Associated With Localized Retinal Nerve Fiber Layer Defects on Optical Coherence Tomography

Introduction: Retinal damages have been suggested a surrogate marker of end-organ damage and prognostic marker in hypertensive patients. Recent study reported that localized retinal nerve fiber layer defects (RNFLDs) assessed by noninvasive optical coherence tomography (OCT) was related to the degree of hypertension severity and cerebrovascular disease. Purpose: We hypothesize that RNFLDs are related to the parameters of 24 hour ambulatory blood pressure monitoring (ABPM). Methods: RNFLDs were assessed by retinal OCT in 562 consecutive subjects enrolled in Cardiovascular and Metabolic Disease Etiology Research Center - HIgh Risk Cohort (CMERC-HI, NCT02003781). We excluded the patients with glaucoma, which known to be related to RNFLD independently of cardiovascular risk factors. Results: RNFLD was found in 129 (23.0%) patients. In patients with RNFLD, there were higher proportion of men, higher prevalence of hypertension, higher glucose levels and lower HDL-cholesterol levels. The RNFLD patients had higher 24 hour mean systolic and diastolic blood pressure (SBP/DBP, 133±16/80±9 vs. 129±13/78±8, p=0.022/p=0.015, respectively) and nocturnal mean SBP/DBP (124±19/74±9 vs. 120±15/72±9, p=0.013/p=0.010, respectively) compared to those without RNFLD. Multivariate stepwise linear regression analysis revealed that RNFLD was independently associated with nocturnal mean SBP after controlling for age, gender, diabetes mellitus, smoking, body mass index, brachial systolic blood pressure, heart rate, estimated glomerular filtration rate, heart to femoral pulse wave velocity (β=0.093, p=0.036, R2=0.263). Conclusion: We reported that RNFLD on OCT was related to nocturnal blood pressure in 24 hour ABPM for the first time. Further studies which validate RNFLD as a cardiovascular surrogate and risk marker should be warranted.

Epidemiologic Characteristics of Dyslipidemia in Korea

Epidemiologic Characteristics of Dyslipidemia in Korea Kyoung Hwa Ha, Hyuk-Sang Kwon, Dae Jung Kim Department of Endocrinology and Metabolism, Ajou University School of Medicine, Cardiovascular and Metabolic Disease Etiology Research Center, Ajou University School of Medicine, Suwon, Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea