Won Jin Kim

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.

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.

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.

Association between Serum Fibroblast Growth Factor 21 and Coronary Artery Disease in Patients with Type 2 Diabetes

The aim of this study was to evaluate the association of plasma fibroblast growth factor (FGF)-21 with angiographically significant coronary artery disease (CAD) in patients with type 2 diabetes mellitus. Serum FGF-21 was measured in 120 patients undergoing coronary angiography. Patients were divided into 4 groups based on the presence/absence of type 2 diabetes mellitus and of significant CAD. The atherosclerotic burden was obtained by two angiographic scores: Gensini score (GS) and Extent score (ES). FGF-21 levels were higher in type 2 diabetes mellitus than in non-diabetic patients (P = 0.014). FGF-21 levels were significantly correlated with GS (r = 0.358, P < 0.001) and ES (r = 0.324, P < 0.001) in univariate analysis with all patients. After adjusting for several confounding factors, both GS and ES were associated with FGF-21 in all patients (r = 0.271, P = 0.014; r = 0.217, P = 0.041, respectively). However, FGF-21 lost significant correlation with both GS and ES with type 2 diabetes mellitus in the final model. The patients with type 2 diabetes mellitus and CAD feature had elevated FGF-21 levels. Despite of a limited role in diabetic patients, FGF-21 levels are independently associated with angiographic severity and extent of CAD. Graphical Abstract

Nonalbuminuric proteinuria as a biomarker for tubular damage in early development of nephropathy with type 2 diabetic patients

The aim of this study was to evaluate the association between urinary nonalbumin protein (NAP) and urinary tubular markers in early diabetic nephropathy.

Association of the Preoperative Neutrophil-to-ymphocyte Count Ratio and Platelet-to-Lymphocyte Count Ratio with Clinicopathological Characteristics in Patients with Papillary Thyroid Cancer

Background Several inflammatory biomarkers, especially a high preoperative neutrophil-to-lymphocyte count ratio (NLR) and platelet-to-lymphocyte count ratio (PLR), are known to be indicator of poor prognosis in several cancers. However, very few studies have evaluated the significance of the NLR and PLR in papillary thyroid cancer (PTC). We evaluated the association of the preoperative NLR and PLR with clinicopathological characteristics in patients with PTC. Methods This study included 1,066 female patients who underwent total thyroidectomy for PTC. Patients were stratified into 4 quartiles by preoperative NLR and PLR. And the combination of preoperative NLR and PLR was calculated on the basis of data obtained value of tertile as follows: patients with both an elevated PLR and an elevated NLR were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. Results The preoperative NLR and PLR were significantly lower in patients aged ≥45 years and in patients with Hashimotos thyroiditis. The PLR was significantly higher in patients with tumor size >1 cm (P=0.021).When the patients were categorized into the aforementioned four groups, the group with the higher preoperative PLR was found to have a significantly increased incidence of lateral lymph node metastasis (LNM) (P=0.018). However, there are no significant association between the combination of preoperative NLR and PLR and prognostic factors in PTC patients. Conclusion These results suggest that a preoperative high PLR were significant associated with lateral LNM in female patients with PTC.

High prevalence of papillary thyroid cancer in Korean women with insulin resistance.

The purpose of this study was to determine if hyperinsulinemia and/or insulin resistance are/is associated with the prevalence of papillary thyroid cancer (PTC) in Korean women.

Concurrence of Primary Hyperparathyroidism and Metastatic Breast Carcinoma Affected a Parathyroid Gland

OBJECTIVE Involvement of the parathyroid glands by metastatic tumor is rare. Breast is 1 of the primary sites in metastatic cancers. We introduce a rare case of metastatic breast carcinoma affecting a parathyroid gland, which was clinically combined with parathyroid gland hyperplasia. CASE REPORT A 65-year-old woman was referred due to hypercalcemia and constipation. The patient had a history of left breast carcinoma. She was admitted to the hospital because of the recent discovery of hypercalcemia and elevation of PTH. A Tc99m-sestamibi scan showed retained uptake in the right thyroid and in the lower pole of the left thyroid gland. Aspiration biopsy results revealed that the nodule in the posterior portion of the right thyroid was metastatic breast cancer and the nodule in the left thyroid gland was the hyperplastic parathyroid gland. CONCLUSION This case illustrates that hyperparathyroidism caused by parathyroid hyperplasia was concurrent with metastatic breast cancer to a parathyroid gland without disseminated systemic metastasis. Although this case is very uncommon and it is not clear whether there is a relationship between breast cancer and primary hyperparathyroidism, that possibility should always be considered as the cause of hypercalcemia in patients with breast cancer.

Low serum bilirubin level predicts the development of chronic kidney disease in patients with type 2 diabetes mellitus

Background/Aims We evaluated whether serum bilirubin levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). Methods This was a retrospective observational longitudinal study of patients presenting at the Pusan National University Hospital. A total of 349 patients with T2DM and preserved kidney function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) were enrolled. The main outcome was the development of CKD stage 3 or greater. The patients were divided into four groups according to the quartiles of the total serum bilirubin levels at baseline. Results The group with the lowest range of total serum bilirubin level (Q1) showed the highest cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q1 vs. Q4; hazard ratio [HR], 6.75; 95% confidence interval [CI], 1.54 to 29.47; p = 0.011). In multivariate analysis, the risk of developing CKD stage 3 or greater was higher in the second lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q2 vs. Q4; HR, 9.36; 95% CI, 1.33 to 65.73; p = 0.024). In the normoalbuminuria subgroup (n = 236), multivariate analysis showed that the risk of developing CKD stage 3 or greater was higher in the lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q1 vs. Q4; HR, 7.36; 95% CI, 1.24 to 35.82; p = 0.019). Conclusions Serum bilirubin might be an early clinical marker for predicting the progression of CKD in patients with T2DM and preserved renal function.

Incidentally Detected Inoperable Malignant Pheochromocytoma with Hepatic Metastasis Treated by Transcatheter Arterial Chemoembolization

Malignant pheochromocytoma (PCC) is a rare condition. Although the liver is the second most frequent site of metastasis in malignant PCC, no definite treatments have been established. Herein, we report a case of liver metastasis of PCC that was successfully treated by transcatheter arterial chemoembolization (TACE). A 69-year-old man was admitted to the Department of Gastroenterology for evaluation of an incidental hepatic mass in August 2013. He had undergone right adrenalectomy in May 2005 and PCC had been confirmed on the basis of histopathological findings. Liver biopsy was performed, and metastatic PCC was diagnosed. The lesion appeared inoperable because of invasion of the portal vein and metastases in the lymph nodes along the hepatoduodenal ligament. Thus, TACE was performed instead. After TACE, symptoms including dizziness and cold sweating improved, and the patients serum catecholamine levels decreased. On the basis of this case, we believe that TACE may be a useful treatment for liver metastasis in malignant PCC.