Ji Hye Huh

A Prospective Study of Fatty Liver Index and Incident Hypertension: The KoGES-ARIRANG Study

Background Although non-alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, its influence on hypertension development is poorly understood. We investigated whether fatty liver disease, as assessed by the fatty liver index, could predict the development of hypertension independently of systemic insulin resistance, inflammatory status and adipokine levels. Methods Prospective cohort study of 1,521 adults (484 men and 1037 women) aged 40 to 70 years without baseline hypertension examined. An equation was used to calculate fatty liver index and classify patients as follows: fatty liver index <30, no non-alcoholic fatty liver disease; fatty liver index ≥60, non-alcoholic fatty liver disease; and 30≤ fatty liver index <60, intermediate fatty liver index. Results During an average of 2.6 years of follow-up, 153 subjects (10.06%) developed hypertension. Fatty liver index was positively associated with baseline blood pressure, homeostasis model assessment of insulin resistance, urinary albumin/creatinine excretion, and high sensitivity C-reactive protein. After adjustment for confounding factors, including markers of insulin resistance, systemic inflammation and adiponectin levels, the odds ratio [95% confidence interval] for the incident hypertension increased in a graded manner with fatty liver index (<30 vs. 30–59 vs. ≥60 = 1 vs. 1.83 [1.16~2.88] vs. 2.09 [1.08~4.055], respectively). Conclusions Non-alcoholic fatty liver disease assessed by fatty liver index was an independent risk factor for hypertension. Our findings suggest that fatty liver index, a simple surrogate indicator of fatty liver disease, might be useful for identifying subjects at high risk for incident hypertension in clinical practice.

Gender-specific association between urinary sodium excretion and body composition: Analysis of the 2008-2010 Korean National Health and Nutrition Examination Surveys

OBJECTIVE Few studies have reported the relationship between sarcopenia and the estimated amount of sodium excreted in 24 h, as measured by the spot urine test (E24UNA), in a community-dwelling cohort. We investigated the gender specific association between E24UNA values and body composition indices. MATERIALS AND METHODS Data from a total of 7162 participants (3545 men and 3617 postmenopausal women) aged 45 years or older were obtained from multiple Korea National Health and Nutrition Examination Surveys (2008-2010) and analyzed. The total amount of sodium excreted in the urine in a 24-h period was estimated with spot urine specimens. Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight (ASM/Wt) that was less than 1 standard deviation below the sex-specific mean for young adults. RESULTS E24UNA values were positively correlated with body mass index, waist circumference, total fat mass, and blood pressure; in contrast, E24UNA values were negatively correlated with ASM/Wt in both sexes. Compared with those in the lowest E24UNA tertile, participants in the highest E24UNA tertile were at higher risk for sarcopenia (men: odds ratio (OR)=1.3 [95% confidence interval (CI)=1.07-1.59]; women: OR=1.41 [95% CI=1.16-1.73]). Further classification of subjects with sarcopenia into sarcopenic obese and sarcopenic nonobese groups revealed that the highest E24UNA values were found in the sarcopenic obese group; this difference was statistically significant. The next highest levels were found in the sarcopenic nonobese group, followed by the nonsarcopenic group. This trend was observed in both sexes. CONCLUSION High E24UNA values were independently associated with both sarcopenia and obesity in Korean individuals older than 45 years. These results suggest that high salt intake may have a deleterious effect on body composition.

The Relationship between BMI and Glycated Albumin to Glycated Hemoglobin (GA/A1c) Ratio According to Glucose Tolerance Status

Glycated albumin to glycated hemoglobin (GA/A1c) ratio is known to be inversely related with body mass index (BMI) and insulin secretory capacity. However, the reasons for this association remain unknown. We aimed to investigate whether BMI directly or indirectly influences GA/A1c by exerting effects on insulin secretion or resistance and to confirm whether these associations differ according to glucose tolerance status. We analyzed a total of 807 subjects [242 drug-naïve type 2 diabetes (T2D), 378 prediabetes, and 187 normal glucose tolerance (NGT)]. To assess the direct and indirect effects of BMI on GA/A1c ratio, structural equation modeling (SEM) was performed. GA/A1c ratio was set as a dependent variable, BMI was used as the independent variable, and homeostasis model assessment-pancreatic beta-cell function (HOMA-β), homeostasis model assessment-insulin resistance (HOMA-IR), glucose level were used as mediator variables. The estimates of a direct effect of BMI on GA/A1c to be the strongest in NGT and weakest in T2D (−0.375 in NGT, −0.244 in prediabetes, and −0.189 in T2D). Conversely, the indirect effect of BMI on GA/A1c exerted through HOMA-β and HOMA-IR was not statistically significant in NGT group, but significant in prediabetes and T2D groups (0.089 in prediabetes, −0.003 in T2D). It was found that HOMA-β or HOMA-IR indirectly influences GA/A1c in T2D and prediabetes group through affecting fasting and postprandial glucose level. The relationship between GA/A1c and BMI is due to the direct effect of BMI on GA/A1c in NGT group, while in T2D and prediabetes groups, this association is mostly a result of BMI influencing blood glucose through insulin resistance or secretion.

An association of metabolic syndrome and chronic kidney disease from a 10-year prospective cohort study

OBJECTIVE Although metabolic abnormalities have been considered important risk factors of chronic kidney disease (CKD), the impact of metabolic syndrome (MS) and insulin resistance on renal function deterioration is poorly understood. We investigated the association between MS and incident CKD/rapid decline of estimated glomerular filtration rate (eGFR) in a 10-year population-based longitudinal study. MATERIAL AND METHODS Among 10,030 subjects, 6065 without history of CKD or cardiovascular disease at baseline were analyzed using data generated from the Ansan-Ansung cohort of the Korean Genome Epidemiology Study. Participants were categorized into two groups based on the presence of MS at baseline. Incident CKD was defined as eGFR <60ml/min per 1.73m2, and rapid decline of eGFR was defined as >3ml/min per 1.73m2/yr over 10years. RESULTS During the 10-year follow-up period, CKD developed in 893 subjects (14.7%). Compared to subjects without MS, the odds ratio (OR; 95% confidence interval, CI) of incident CKD in those with MS was 1.38 (1.16-1.64) after controlling for confounding factors. The risk of rapid decline of eGFR was also higher in subjects with MS than those without MS (OR: 1.20, 95% CI: 1.04-1.39). In addition, we found that higher levels of homeostatic model assessment of insulin resistance (HOMA-IR) were associated with incident CKD and rapid decline of eGFR independently of traditional CKD risk factors (OR: 1.24, 95% CI: 1.04-1.47). CONCLUSION Both MS and insulin resistance were independent risk factors of incident CKD and rapid decline of eGFR in healthy Korean population.

High Serum Irisin Level as an Independent Predictor of Diabetes Mellitus: A Longitudinal Population-Based Study.

AbstractIrisin, a novel exercise-induced myokine, has been suggested to regulate energy homeostasis and insulin sensitivity. However, it remains unclear whether circulating irisin plays a role in the development of DM in human. We investigated the possible association between circulating irisin levels and incident DM in a 2.6-year longitudinal study of a population-based cohort comprised of rural Korean subjects.We conducted a longitudinal study within the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) study from November 2005 to January 2008. Cases (n=85) were patients with incident DM during the follow-up period and controls (n = 85) were matched to incident DM cases based on sex and age at baseline. The relative risk of serum irisin/adiponectin level for incident DM was analyzed using conditional logistic regression analysis.Baseline irisin_ENREF_1 levels were significantly higher in subjects who developed DM than in subjects who did not. The serum irisin level was positively associated with glycated hemoglobin (HbA1c) and postprandial glucose. Irisin was negatively associated with adiponectin (R = –0.189, P = 0.014). After adjustment for potential confounders, including body mass index, the odds ratios [95% confidence intervals] for incident DM increased in a graded manner as the serum irisin level increased (Quartile 1 vs Quartile 2 vs Quartile 3 vs Quartile 4 = 1 vs 0.80 [0.28–2.35] vs 3.33 [1.11–10.00] vs 4.10 [1.35–12.44], respectively), whereas the odds ratios for incident DM decreased in a graded manner as the serum adiponectin level increased.High serum irisin was independently associated with the development of DM, indicating that irisin may be a useful predictor of DM in Korean adults.

1,5-anhydroglucitol as a useful marker for assessing short-term glycemic excursions in type 1 diabetes

Background Type 1 diabetes is associated with more severe glycemic variability and more frequent hypoglycemia than type 2 diabetes. Glycemic variability is associated with poor glycemic control and diabetic complications. In this study, we demonstrate the clinical usefulness of serum 1,5-anhydroglucitol (1,5-AG) for assessing changes in glycemic excursion in type 1 diabetes. Methods Seventeen patients with type 1 diabetes were enrolled in this study. A continuous glucose monitoring system (CGMS) was applied twice at a 2-week interval to evaluate changes in glycemic variability. The changes in serum glycemic assays, including 1,5-AG, glycated albumin and hemoglobin A1c (HbA1c), were also evaluated. Results Most subjects showed severe glycemic excursions, including hypoglycemia and hyperglycemia. The change in 1,5-AG level was significantly correlated with changes in the glycemic excursion indices of the standard deviation (SD), mean amplitude of glucose excursion (MAGE), lability index, mean postmeal maximum glucose, and area under the curve for glucose above 180 mg/dL (r=-0.576, -0.613, -0.600, -0.630, and -0.500, respectively; all P<0.05). Changes in glycated albumin were correlated with changes in SD and MAGE (r=0.495 and 0.517, respectively; all P<0.05). However, changes in HbA1c were not correlated with any changes in the CGMS variables. Conclusion 1,5-AG may be a useful marker for the assessment of short-term changes in glycemic variability. Furthermore, 1,5-AG may have clinical implications for the evaluation and treatment of glycemic excursions in type 1 diabetes.

Obesity is more closely related with hepatic steatosis and fibrosis measured by transient elastography than metabolic health status

OBJECTIVE The pathogenesis of non-alcoholic fatty liver disease (NAFLD) involves multiple concomitant events induced by obesity and metabolic health condition. This study aimed to assess the risk of NAFLD according to metabolic health and obesity status using transient elastography (TE). MATERIALS AND METHODS A total of 2198 asymptomatic adults without chronic liver disease and who underwent a medical health check-up were recruited. Subjects were categorized into four groups according to metabolic health and obesity statuses: metabolically healthy non-obese (MHNO); metabolically unhealthy non-obese (MUNO); metabolically healthy obese (MHO); and metabolically unhealthy obese (MUO). Hepatic steatosis was defined as controlled attenuation parameter (CAP)≥238dB/m, and significant liver fibrosis was defined as liver stiffness measurement (LSM) >7.0kPa, as defined by TE. RESULTS Compared with MHNO group, the odds ratios (ORs) [95% confidence interval (CI)] for hepatic steatosis were 2.94 [2.32-3.71], 4.62 [3.52-6.07], and 12.02 [9.08-15.92] in the MUNO, MHO, and MUO groups, respectively (P<0.001) in crude model. Regarding liver fibrosis, there was no significant difference in the ORs in MUNO group (ORs: 0.95 [95% CI, 0.33-2.78], P value = 0.929), whereas there was a significant increase in the ORs in MHO group compared with MHNO group (ORs: 4.32 [95% CI, 1.73-10.76], P=0.002) in the fully adjusted model. CONCLUSION Our results show that MHO was associated with both liver steatosis and fibrosis assessed by transient elastography. Our results suggest that a healthy metabolic profile does not protect obese adults from hepatic steatosis or fibrosis, indicating that obesity itself might contribute to liver fibrosis.

Maternal age at first delivery is associated with the risk of metabolic syndrome in postmenopausal women: from 2008-2010 Korean National Health and Nutrition Examination Survey.

Background Recent cross-sectional studies demonstrated that earlier maternal age at first childbirth is correlated with a higher risk of diabetes in postmenopausal women. In this study, we evaluated whether the age at first delivery is associated with the risk of metabolic syndrome (MetS) in postmenopausal women. Methods A total of 4,261 postmenopausal women aged 45 years or older were analyzed using data generated from Korea National Health and Nutrition Examination Surveys (2008–2010). Subjects were divided into three groups according to the maternal age at first delivery as follows: ≤ 20 years (n=878), 21-25 years (n=2314), and ≥ 26 years (n=1069). Results Approximately 37% of subjects had MetS. The prevalence of MetS showed a gradual increase as maternal age at first delivery decreased (≥ 26 years = 30.9% vs. 21-25 years = 39.9% vs. ≤ 20 years = 50.8%, respectively, p < 0.001). Central obesity indices such as trunk fat mass and waist circumference were significantly higher in the group aged ≤ 20 years than other groups. After adjustments for confounding factors, the odds ratios (ORs) for predicting the presence of MetS increased gradually as first delivery age decreased (≥ 26 years vs. 21-25 years vs. ≤ 20 years: OR [95% CI] = 1 vs. 1.324 [1.118-1.567] vs. 1.641 [1.322-2.036], respectively). Among components of MetS, younger maternal age at first delivery (≤ 20 years) was significantly associated with increased waist circumference (OR [95% CI] = 1.735 [1.41-2.13]), elevated blood pressure (1.261 [1.02-1.57]), high triglyceride (1.333 [1.072-1.659]), and low HDL-cholesterol (1.335[1.084-1.643]). Conclusions Our findings suggest that younger maternal age at first delivery is independently associated with a higher risk of central obesity and MetS in postmenopausal women.

High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis.

Background Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans. Methods We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008–2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka’s equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD. Results The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26–1.55, in HSI; OR 1.75, CI 1.39–2.20, in FLI, both P < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values. Conclusions High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis.

Fatty liver index as a simple predictor of incident diabetes from the KoGES-ARIRANG study

Abstract The fatty liver index (FLI), calculated from serum triglyceride, body mass index, waist circumference, and gamma-glutamyltransferase, is considered a surrogate marker of nonalcoholic fatty liver disease (NAFLD). We investigated whether FLI predicts the development of diabetes mellitus (DM) and assessed the predictive ability of FLI for new onset of DM in a prospective population-based cohort study. We analyzed a total of 2784 adults (944 men and 1840 women) aged 40 to 70 years without DM at baseline. Participants were classified according to FLI values into 3 groups: FLI < 30, no NAFLD; 30 ⩽ FLI ⩽ 59, intermediate NAFLD; and FLI ≥ 60, participants with NAFLD. The area under the receiver-operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to determine whether FLI improved DM risk prediction. During a mean of 2.6 years follow-up, 88 (3.16%) participants developed DM. The odds ratio analyzed from multivariable-adjusted models (95% confidence interval [CI]) for new onset of DM increased in a continuous manner with increased FLI (<30 vs 30–59 vs ≥60 = 1 vs 1.87 [95% CI 1.05–3.33] vs 2.84 [95% CI 1.4–5.75], respectively). The AUC significantly increased when FLI was added to the conventional DM prediction model (0.835, 95% CI: 0.789–0.881, P = 0.0289 vs traditional DM prediction model). The category-free NRI was 0.417 (95% CI: 0.199–0.635) and the IDI was 0.015 (95% CI: 0.003–0.026) for overall study participants. We found that FLI, a surrogate marker of hepatic steatosis, resulted in significant improvement in DM risk prediction. Our finding suggests that FLI may have clinical and prognostic information for incident DM among the Korean adult population.