Yun Kyung Jeon

Cystatin C as an Early Biomarker of Nephropathy in Patients with Type 2 Diabetes

This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.

Urinary Cystatin C and Tubular Proteinuria Predict Progression of Diabetic Nephropathy

OBJECTIVE The aim of this study was to evaluate the association of urinary cystatin C, a tubular damage marker, with the progression of type 2 diabetic nephropathy. RESERCH DESIGN AND METHODS The baseline values of serum and urinary cystatin C were measured as primary parameters and those of urinary nonalbumin protein (NAP) were measured as secondary parameters. In this prospective observational study, a total of 237 type 2 diabetic patients were followed up for 29 months (13–44 months). RESULTS Both the urinary cystatin C-to-creatinine ratio (CCR) and NAP-to-creatinine ratio (NAPCR) were significantly different according to the degree of albuminuria. Both markers had strongly positive correlations at baseline. After adjusting for several clinical factors, both urinary CCR and NAPCR had significant associations with the decline of the estimated glomerular filtration rate (eGFR) (r = 0.160, P = 0.021; r = 0.412, P < 0.001, respectively). Urinary CCR had positive correlations with the decline of eGFR in the subpopulation of patients with eGFR ≥60 mL/min/1.73 m2. In patients with eGFR ≥60 mL/min/1.73 m2 and normoalbuminuria, only urinary NAPCR showed a significant association with the decline of eGFR; urinary CCR did not. In multivariate regression analysis, the number of patients who progressed to chronic kidney disease stage 3 or greater was higher in those in the upper tertiles of both the urinary levels of cystatin C and NAP than in those in the lower tertiles. CONCLUSIONS The results of this study suggest that urinary cystatin C and NAP may be predictors of the progression of type 2 diabetic nephropathy.

Coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma: the influence of lymph node metastasis.

The aim of this study was to evaluate the influence of coexistent Hashimotos thyroiditis with papillary thyroid carcinoma on lymph node metastasis.

Clinical implication of plasma and urine YKL-40, as a proinflammatory biomarker, on early stage of nephropathy in type 2 diabetic patients

OBJECTIVE Chronic inflammation has emerged as being a key pathophysiology in the early stages of diabetic nephropathy. YKL-40 has been established as an inflammatory marker in chronic inflammation. The aim of this study was to evaluate the association of plasma and urine YKL-40 with albuminuria in the early stage of type 2 diabetic nephropathy. DESIGN AND METHODS A total of 75 type 2 diabetic patients and 22 nondiabetic controls with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m(2) were enrolled. Plasma and urine concentrations of YKL-40 were analyzed by ELISA kit. RESULTS The plasma levels of YKL-40 were significantly higher in the normoalbuminuric group with diabetes than in the control group, and increased with increasing severity of albuminuria among diabetes. However, urine YKL-40 was only increased in macroalbuminuric state. Plasma YKL-40 was positively correlated with urine YKL-40 (r=0.291, P=0.011). Urinary albumin significantly correlated with both plasma and urine YKL-40 in a univariate analysis. After adjusting for several confounding factors, plasma YKL-40 was significantly correlated with albuminuria (r=0.359; P=0.001), whereas urine YKL-40 did not show significant correlation with albuminuria (r=0.128, P=0.241). CONCLUSIONS Although urine YKL-40 has a limited role, plasma YKL-40, as an proinflammatory marker, was an independent factor associated with albuminuria in early stage of nephropathy in type 2 diabetes and might have an useful role as a noninvasive marker for the early diabetic nephropathy detection.

High-normal serum uric acid predicts the development of chronic kidney disease in patients with type 2 diabetes mellitus and preserved kidney function

AIMS We evaluated whether high-normal serum uric acid (SUA) levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus and preserved kidney function at baseline. METHODS This was a retrospective observational longitudinal study of patients presenting at the Department of Endocrinology and Metabolism, Pusan National University Hospital. A total of 512 patients with type 2 diabetes mellitus and preserved kidney function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2)) and normouricemia were included. The main outcome was development of CKD of stage 3 or greater. The patients were divided into four groups according to quartiles of SUA levels. RESULTS During the follow-up period, 62 (12.1%) patients had progressed to CKD 3 or greater. The group with the highest-normal range of SUA (Q4) showed a higher cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q4 vs. Q3; P = 0.037, Q4 vs. Q2; P<0.001, Q4 vs. Q1; P<0.001). In a univariate analysis, Q4 was significantly associated with the development of CKD 3 or greater (log-rank statistic, 31.93; P<0.001). In a multivariate analysis, Q4 (hazard ratio, 2.97; 95% confidence interval, 1.15-7.71; P = 0.025) showed a significant association with CKD 3 or greater. CONCLUSIONS High-normal SUA may predict the occurrence of CKD stage 3 or greater in patients with type 2 diabetes mellitus and preserved kidney function.

Preoperative ultrasonographic tumor characteristics as a predictive factor of tumor stage in papillary thyroid carcinoma

The purpose of this study was to evaluate the usefulness of tumor characteristics on ultrasonography for predicting the pathologic stage of papillary thyroid carcinoma.

Insulin resistance as a risk factor for gallbladder stone formation in Korean postmenopausal women.

Background/Aims The objective of this study was to determine whether insulin resistance is associated with gallbladder stone formation in Korean women based on menopausal status. Methods The study included 4,125 consecutive Korean subjects (30-79 years of age). Subjects who had a medical history of diabetes, hypertension, dyslipidemia, other cardiovascular disorders, or hormone replacement therapy were excluded. The women were subdivided into two groups according to their menopausal status. Results Analysis of premenopausal women showed no significant differences in the homeostasis model of assessment-insulin resistance (HOMA-IR) index between the two groups in terms of gallstone disease. The associations between the occurrence of gallbladder stones and age, obesity, abdominal obesity, hyperinsulinemia, and high HOMA-IR index were statistically significant in the analysis with postmenopausal women. In a multiple logistic regression analysis, low high density lipoprotein-cholesterol was an independent predictor of gallbladder stone formation in premenopausal women. However, the multiple logistic regression analysis also showed that age and HOMA-IR were significantly associated with gallbladder stone formation in postmenopausal women. In an additional analysis stratified by obesity, insulin resistance was a significant risk factor for gallbladder stone formation only in the abdominally obese premenopausal group. Conclusions Insulin resistance may be associated with gallbladder stone formation in Korean postmenopausal women with abdominal obesity.

Adiposity in the Relationship between Serum Vitamin D Level and Insulin Resistance in Middle-Aged and Elderly Korean Adults: The Korea National Health and Nutrition Examination Survey 2008

Background The role of adiposity in the relationship between serum vitamin D levels and insulin resistance has not yet been fully studied. This aim of this study is to clarify the role of adiposity in the relationship between serum vitamin D level and insulin resistance among middle-aged and elderly Korean adults. Methods We used data from 2,710 individuals aged ≥50 years based on national data from a representative sample of the fourth Korea National Health and Nutrition Examination Survey IV-2 in 2008. Results After adjustment for potential confounders, body mass index (BMI) was significantly associated with 25(OH) vitamin D (P=0.008). However, waist circumference was not significantly associated with 25(OH) vitamin D. In the stratified analyses, 25(OH) vitamin D was found to be negatively associated with fasting insulin and homeostasis model assessment estimate of insulin resistance (HOMA-IR) in participants with BMIs ≥25 kg/m2 (P=0.003 for both insulin and HOMR-IR) but was not found to be associated in those with BMIs <23 kg/m2. However, we observed a significant inverse in the association of 25(OH) vitamin D with fasting insulin and HOMA-IR in both the normal (P=0.001 and P<0.001 and the abdominally obese group (P=0.010 and P=0.009) in the stratified analyses according to abdominal obesity. Conclusion Our results support that the idea that endogenously-produced vitamin D might be stored in subcutaneous fat deposits. In addition, the association of vitamin D with insulin resistance in middle-aged and elderly Korean adults was stronger when it was stratified by BMI than when abdominal obesity status.

Expression of Glucagon-Like Peptide 1 Receptor during Osteogenic Differentiation of Adipose-Derived Stem Cells

Background Glucagon-like peptide 1 (GLP-1), an incretin hormone well known for its glucose-lowering effect, was recently reported to exert an anabolic effect on bone. Although the exact mechanism is not known, it likely involves the GLP-1 receptor (GLP-1R), which is expressed in some osteoblastic cell lines. Adipose-derived stem cells (ADSCs) have mesenchymal stem cell-specific characteristics, including osteoblastic differentiation potential. We evaluated the expression of GLP-1R during osteogenic differentiation of ADSCs. Methods ADSCs were isolated from subcutaneous adipose tissue obtained from three male donors during plastic surgery and were subjected to osteogenic induction. Mineralization was assessed by Alizarin Red staining on day 21. Expression of alkaline phosphatase (ALP), osteocalcin (OC), and GLP-1R was measured by real-time polymerase chain reaction in triplicate for each patient on days 0, 7, 14, and 21. Target mRNA expression levels were normalized to that of β-actin. Results ADSCs were fibroblast-like in morphology, adhered to plastic, and had multipotent differentiation potential, as assessed using specific antigen markers. The osteogenic markers ALP and OC were notably upregulated at 21 days. Osteogenic differentiation resulted in a time-dependent increase in the expression of GLP-1R (P=0.013). Conclusion We demonstrated upregulation of GLP-1R gene expression during osteogenic differentiation of ADSCs. This finding suggests that GLP-1 may induce osteogenic differentiation in bone tissue.

Detection of plasma BRAF(V600E) mutation is associated with lung metastasis in papillary thyroid carcinomas.

Purpose The BRAFV600E mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid carcinoma (PTC). The purpose of this study was to determine the clinical significance of free circulating mutant BRAFV600E in predicting the advanced disease of PTC. Materials and Methods Seventy seven matched tumor and plasma samples obtained from patients with both benign and PTC were analyzed for BRAFV600E mutation using a peptide nucleic acid (PNA) clamp real-time polymerase chain reaction (PCR). Results The BRAFV600E mutation was absent in tumor DNA samples obtained from patients with benign follicular adenomas or adenomatous goiter. In contrast, 49 of 72 (68.1%) PTC tumors were positive for the BRAFV600E mutation. Among them, 3 (6.1%) patients with PTC were positive for BRAFV600E mutation in plasma and tumor. However, all 3 patients (100%) had lateral lymph node and lung metastasis. Conclusion These findings suggest that the BRAFV600E mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis. Future studies are warranted to determine clinical significance of serum BRAFV600E mutation in large prospective studies.