Yun Hyi Ku

A 3-year prospective radiographic evaluation of marginal bone level around different implant systems

The aim of this study was to evaluate the change of marginal bone level radiographically around three different implant systems after 3 years in function. Fifty-four patients were included and randomly assigned to three treatment groups of rough-surface implants (TiUnite, n = 37), hybrid of smooth and rough-surface implants (Restore, n = 38) and rough surface with microthread implants (Hexplant, n = 45). Clinical and radiographic examinations were conducted at the time of implant loading (baseline), 1 and 3 years after loading. A three-level mixed-effect analysis of covariance (ancova) was used to test the significance of the mean marginal bone change of the three implant groups. A total 120 of 135 implants completed the study. None of the implants failed to integrate. Significant differences were noted in the marginal bone loss recorded for the three groups (P < 0.0001). At 3 years, the rough surface with microthread implants had a mean crestal bone loss of 0.59 +/- 0.30 mm; the rough-surface implants, 0.95 +/- 0.27 mm; and the hybrid surface implants, 1.05 +/- 0.34 mm. Within the limitations of this study, rough-surface implants with microthread at the coronal part might have a long-term positive effect in maintaining the marginal bone level against functional loading in comparison with implants without these two features.

Differential proteome profiling using iTRAQ in microalbuminuric and normoalbuminuric type 2 diabetic patients.

Diabetic nephropathy (DN) is a long-term complication of diabetes mellitus that leads to end-stage renal disease. Microalbuminuria is used for the early detection of diabetic renal damage, but such levels do not reflect the state of incipient DN precisely in type 2 diabetic patients because microalbuminuria develops in other diseases, necessitating more accurate biomarkers that detect incipient DN. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify urinary proteins that were differentially excreted in normoalbuminuric and microalbuminuric patients with type 2 diabetes where 710 and 196 proteins were identified and quantified, respectively. Some candidates were confirmed by 2-DE analysis, or validated by Western blot and multiple reaction monitoring (MRM). Specifically, some differentially expressed proteins were verified by MRM in urine from normoalbuminuric and microalbuminuric patients with type 2 diabetes, wherein alpha-1-antitrypsin, alpha-1-acid glycoprotein 1, and prostate stem cell antigen had excellent AUC values (0.849, 0.873, and 0.825, resp.). Moreover, we performed a multiplex assay using these biomarker candidates, resulting in a merged AUC value of 0.921. Although the differentially expressed proteins in this iTRAQ study require further validation in larger and categorized sample groups, they constitute baseline data on preliminary biomarker candidates that can be used to discover novel biomarkers for incipient DN.

Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones.

Background Sulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic β-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator-activated receptor γ (PPARγ), one of the nuclear receptors. In this study, we investigated the effects of sulfonylurea on PPARγ transcriptional activity and on the glucose uptake via PPARγ. Methods Transcription reporter assays using Cos7 cells were performed to determine if specific sulfonylureas stimulate PPARγ transactivation. Glimepiride, gliquidone, and glipizide (1 to 500 µM) were used as treatment, and rosiglitazone at 1 and 10 µM was used as a control. The effects of sulfonylurea and rosiglitazone treatments on the transcriptional activity of endogenous PPARγ were observed. In addition, 3T3-L1 adipocytes were treated with rosiglitazone (10 µM), glimepiride (100 µM) or both to verify the effect of glimepiride on rosiglitazone-induced glucose uptake. Results Sulfonylureas, including glimepiride, gliquidone and glipizide, increased PPARγ transcriptional activity, gliquidone being the most potent PPARγ agonist. However, no additive effects were observed in the presence of rosiglitazone. When rosiglitazone was co-treated with glimepiride, PPARγ transcriptional activity and glucose uptake were reduced compared to those after treatment with rosiglitazone alone. This competitive effect of glimepiride was observed only at high concentrations that are not achieved with clinical doses. Conclusion Sulfonylureas like glimepiride, gliquidone and glipizide increased the transcriptional activity of PPARγ. Also, glimepiride was able to reduce the effect of rosiglitazone on PPARγ agonistic activity and glucose uptake. However, the competitive effect does not seem to occur at clinically feasible concentrations.

Regulatory Effect of Common Promoter Polymorphisms on the Expression of the 11β-Hydroxysteroid Dehydrogenase Type 1 Gene

Background/Aims: Glucocorticoids play an important role in the pathogenesis of obesity and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to active cortisol, has become an emerging therapeutic target for type 2 diabetes mellitus and obesity. In this study, we examined the association between HSD11B1 polymorphisms and type 2 diabetes and metabolic phenotypes in Koreans. Methods: We sequenced all exons including exon-intron boundaries and the promoter region of the HSD11B1 gene. Of 8 polymorphisms identified, we selected 4 common single-nucleotide polymorphisms (g.–19835G>A, g.–19609A>G, g.+27447G>C and g.+27810C>T) based on location, linkage disequilibrium and frequency and which were genotyped in 757 subjects with type 2 diabetes and 644 nondiabetic subjects. Results: There was no association between the 4 common polymorphisms of HSD11B1 and type 2 diabetes. g.–19835G>A and g.–19609A>G showed modest associations with fasting plasma glucose and body mass index but the significance of these associations was lost after adjustment for multiple comparison. With regard to promoter polymorphisms in the HSD11B1 gene, a haplotype construct carrying both g.–19835A and g.–19609G showed significantly decreased promoter activity compared to other common haplotype constructs. Conclusion: The variations in HSD11B1 were not associated with susceptibility to type 2 diabetes or metabolic phenotypes in Koreans. However, the common promoter variants of the gene might exert a polymorphic regulatory effect on HSD11B1 expression.

Central lymph node metastasis in papillary thyroid microcarcinoma can be stratified according to the number, the size of metastatic foci, and the presence of desmoplasia.

BACKGROUND Lymph node (LN) metastasis is common in papillary thyroid microcarcinoma (PTMC). The aim of this study was to investigate the impact of LN metastasis and its risk stratification on PTMC recurrence. METHODS We retrospectively reviewed the data of 336 patients with PTMC who underwent surgery from 2005 to 2006 at a single institution. LN metastasis was stratified according to the number of metastatic LNs, the ratio of metastatic to removed LNs, the size of metastatic foci in LNs, and the presence of extranodal extension and desmoplasia. RESULTS Of the 336 patients, 93 (28%) had LN metastasis. During the follow-up of 5.3 years, 16 (4.8%) experienced locoregional recurrence. Among several clinicopathologic factors, LN metastasis was the most important risk factor for recurrence (P = .02). Lateral LN metastasis was correlated with recurrence-free survival (P < .01), whereas central LN metastasis was not (P = .20). When central LN metastasis was stratified, a high number of metastatic LNs (≥3), larger metastatic foci (≥0.2 cm), and the presence of desmoplasia were associated with recurrence-free survival (P < .05). CONCLUSION The prognostic significance of central LN metastasis can differ according to the number of metastatic LNs, the size of metastatic foci, and the presence of desmoplasia. Patients with a high number of metastatic LNs, larger metastatic foci, and presence of desmoplasia in LNs should be treated aggressively and supervised carefully for PTMC recurrence.

A Relationship Between Alzheimer's Disease and Type 2 Diabetes Mellitus Through the Measurement of Serum Amyloid-β Autoantibodies

Increasing evidence suggests that type 2 diabetes mellitus (T2DM) is strongly correlated with Alzheimers disease (AD). To examine the relationship between T2DM and AD, autoantibodies against amyloid-Abeta were measured in the serum of T2DM patients and age-matched controls. Levels of Abeta autoantibody were measured by ELISA in serum samples of T2DM patients (n=92) and age-matched control group (n=106). Abeta autoantibody levels were increased in T2DM compared with age-matched controls by 45.4 +/- 8.1% (p< 0.001). Females had higher Abeta autoantibody levels than males in both T2DM and control group. Abeta autoantibody levels in the T2DM group were positively correlated with the levels of cholesterol (p=0.011), low density lipoprotein cholesterol (p=0.020), and triglycerides (p=0.039). In conclusion, the level of Abeta autoantibody is dramatically elevated in patient serum of T2DM, and, as such, might be used as a possible biomarker for T2DM.

Carotid intimal-medial thickness is not increased in women with previous gestational diabetes mellitus.

BACKGROUND Gestational diabetes mellitus (GDM) is known to increase the risk of cardiovascular diseases. Measuring the carotid artery intimal-medial thickness (CIMT) is a non-invasive technique used to evaluate early atherosclerosis and to predict future cardiovascular diseases. We examined the association between CIMT and cardiovascular risk factors in young Korean women with previous GDM. METHODS One hundred one women with previous GDM and 19 women who had normal pregnancies (NP) were recruited between 1999 and 2002. At one year postpartum, CIMT was measured using high-resolution B-mode ultrasonography, and oral glucose tolerance tests were performed. Fasting glucose, glycated hemoglobin A1c (HbA1c), insulin levels and lipid profiles were also measured. CIMTs in the GDM and NP groups were compared, and the associations between CIMT and cardiovascular risk factors were analyzed in the GDM group. RESULTS CIMT results of the GDM group were not significantly different from those of the NP group (GDM, 0.435±0.054 mm; NP, 0.460±0.046 mm; P=0.069). In the GDM group, a higher HbA1c was associated with an increase in CIMT after age adjustment (P=0.011). CIMT results in the group with HbA1c >6.0% were higher than those of the normal HbA1c (HbA1c ≤6.0%) (P=0.010). Nine of the patients who are type 2 diabetes mellitus converters within one year postpartum but showed no significant difference in CIMT results compared to NP group. CONCLUSION Higher HbA1c is associated with an increase in CIMT in women with previous GDM. However, CIMT at one year postpartum was not increased in these women compared to that in NP women.

Medullary Thyroid Carcinoma with Ectopic Adrenocorticotropic Hormone Syndrome

Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

Preoperative Localization and Intraoperative Parathyroid Hormone Assay in Korean Patients with Primary Hyperparathyroidism

Background The intraoperative parathyroid hormone (IOPTH) assay is widely used in patients with primary hyperparathyroidism (PHPT). We investigated the usefulness of the IOPTH assay in Korean patients with PHPT. Methods We retrospectively reviewed the data of 33 patients with PHPT who underwent parathyroidectomy. Neck ultrasonography (US) and 99mTc-sestamibi scintigraphy (MIBI scan) were performed preoperatively and IOPTH assays were conducted. Results The sensitivity of neck US and MIBI scans were 91% and 94%, respectively. A 50% decrease in parathyroid hormone (PTH) levels 10 minutes after excision of the parathyroid gland was obtained in 91% (30/33) of patients and operative success was achieved in 97% (32/33) of patients. The IOPTH assay was 91% true-positive, 3% true-negative, 0% false-positive, and 6% false-negative. The overall accuracy of the IOPTH assay was 94%. In five cases with discordant neck US and MIBI scan results, a sufficient decrease in IOPTH levels helped the surgeon confirm the complete excision of the parathyroid gland with no additional neck exploration. Conclusion The IOPTH assay is an accurate tool for localizing hyperfunctioning parathyroid glands and is helpful for evaluating cases with discordant neck US and MIBI scan results.

Derivation of a new equation for estimating creatinine clearance by using fat-free mass and serum creatinine concentration in Korean patients with type 2 diabetes mellitus

AIMS Equations to predict creatinine clearance (Ccr) or glomerular filtration rate have limitations in applying to a wide range of ethnicities with different fat-free mass (FFM). We aimed to determine the serum creatinine (Scr) concentrations that indicate renal insufficiency and formulate a new equation to estimate Ccr by a function of FFM in Korean type 2 diabetic patients. METHODS Ccr was measured in 283 type 2 diabetic patients by 24-h urine collection. Receiver operating characteristic (ROC) curve was used to determine the Scr concentration corresponding to a Ccr of 60 mL min(-1) x 1.73 m(-2). A new equation to predict Ccr was derived by using Scr and FFM. RESULTS The Scr concentration corresponding to a Ccr of 60 mL min(-1) x 1.73 m(-2) was 1.15 mg/dL in men and 0.95 mg/dL in women. The regression equation estimating the Ccr was expressed as (1.72 x FFM-0.23 x age)/Scr, and it showed a good correlation with the measured Ccr (r=0.718, P<0.001). CONCLUSIONS Scr concentrations indicating renal insufficiency in the Korean patients were considerably lower than those in Caucasians. The equation derived in this study would be more useful in Korean or other Asian type 2 diabetic patients.