Hwa Young Ahn

Android Fat Depot Is More Closely Associated with Metabolic Syndrome than Abdominal Visceral Fat in Elderly People

Background Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. Methods and Findings As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm2 and 126.9±55.2 cm2 in men (P = 0.045) and 120.0±46.7 cm2 and 211.8±65.9 cm2 in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. Conclusions Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution.

Changes in the Clinicopathological Characteristics and Outcomes of Thyroid Cancer in Korea over the Past Four Decades

BACKGROUND Thyroid cancer has increased globally, with a prominent increase in small, papillary thyroid cancers (PTC). The Korean population has a high iodine intake, high prevalence of BRAF V600E mutations, and family histories of thyroid cancer. We examined the clinicopathological characteristics and outcomes of thyroid cancers in Korean patients over four decades. METHODS The medical records of 4500 thyroid cancer patients, between 1962 and 2009 at a single center, including 3147 PTC patients, were reviewed. RESULTS The mean age of the patients was 46.8±13.2 years; women accounted for 82.9% of the patients, and the median follow-up duration was 4.8 years (mean 7.0±5.8 years, range 1-43 years). The number of patients visiting the clinic increased from 411 during 1962-1990 to 2900 during 2000-2009. Age at diagnosis increased from 39.6±12.9 to 48.6±12.4 years. The male to female ratio increased from 1:6 to 1:4.5. The proportion of small (<1 cm) tumors increased from 6.1% to 43.1%, and the proportion of cancers with lymph node (LN) involvement or extrathyroidal extension (ETE) decreased from 76.4% to 44.4% and from 65.5% to 54.8% respectively. Although there were decreases in the proportion of LN involvement and ETE, these decreasing rates were not proportional to the expected rates based on the decreased proportion of large tumors. The overall recurrence and mortality rates were 13.3% and 1.4%. The five-year recurrence rate significantly decreased (from 11% to 5.9%), and the five-year mortality also improved (from 1.5% to 0.2%). CONCLUSIONS The incidence of thyroid cancer has rapidly increased, with a decrease in tumors of large size, LN involvement, and ETE, although the decreasing rates of LN involvement and ETE were not as prominent as decreasing rates of large size tumors. The mortality and recurrence rates have also decreased. Future long-term follow-up of patients diagnosed in the most recent decade is needed to confirm the prognostic characteristics of Korean PTC patients.

Vitamin D Inadequacy Is Associated with Significant Coronary Artery Stenosis in a Community-Based Elderly Cohort: The Korean Longitudinal Study on Health and Aging

CONTEXT Recent studies suggest an association between vitamin D activity and cardiometabolic risk. OBJECTIVE We investigated vitamin D status and its association with subclinical atherosclerosis in a population-based cohort study, the Korean Longitudinal Study on Health and Aging (KLoSHA). PARTICIPANTS Participants were 439 men and 561 women aged 65 yr or older who were recruited by random stratified sampling for KLoSHA. METHODS Anthropometric and biochemical parameters, the concentration of 25-hydroxyvitamin D (25-OHD), and intact PTH were measured. MAIN OUTCOME MEASURES We evaluated the coronary artery calcium score and stenosis using multidetector-row cardiac computed tomography, the intima-media thickness using carotid sonography, pulse wave velocity, and the ankle-brachial index. RESULTS Among the participants, 49.8, 44.2, and 6.0% had 25-OHD deficiency (<15 ng/ml), insufficiency (15-29.9 ng/ml), and adequacy (≥30 ng/ml), respectively. The frequency of coronary artery stenosis (>50%) differed between 25-OHD categories: 18.5, 12.9, and 1.9% in the 25-OHD-deficient, -insufficient, and -adequate groups, respectively (P < 0.05). After adjusting for cardiometabolic risks and intact PTH concentration, multivariate regression analysis showed that participants with a low 25-OHD concentration had a higher risk of significant coronary artery stenosis; the odds ratios were 2.08 for 25-OHD concentration of 15-29.9 ng/ml vs. at least 30 ng/ml and 3.12 for 25-OHD concentration below 15 ng/ml vs. at least 30 ng/ml (both P < 0.05). CONCLUSIONS The association between 25-OHD inadequacy and subclinical atherosclerosis underscores the clinical implications of vitamin D status. An intervention strategy to increase vitamin D level through vitamin D-fortified diet and adequate sun exposure may mitigate the consequences of vitamin D deficiency.

The Long-Term Outcomes of the Second Generation of Familial Nonmedullary Thyroid Carcinoma Are More Aggressive than Sporadic Cases

BACKGROUND Familial nonmedullary thyroid carcinoma (FNMTC) is frequently detected, but the prevalence or the aggressiveness of FNMTC is still unclear. We aimed to investigate the prevalence, clinical characteristics, and prognosis of FNMTC. METHODS This study included 3056 nonmedullary thyroid carcinoma (NMTC) patients who were pathologically confirmed to exhibit differentiated thyroid carcinoma from January 1962 through March 2010. The duration of follow-up was 6.2±6.2 years. RESULTS The prevalence of FNMTC was 9.6%; 37.9% of the FNMTC patients exhibited a parent-offspring relationship, and 62.1% exhibited a sibling relationship. FNMTC was smaller in tumor size (1.2±0.9 vs. 1.4±1.1 cm) and more multifocal (33.6% vs. 27.0%) than sporadic cases. FNMTC presented higher recurrence rates (29.5% vs. 19.8%) and shorter recurrence-free survival than sporadic NMTC (p=0.046). When we compared sporadic NMTC with parent-offspring or sibling FNMTC separately, parent-offspring FNMTC was more multifocal (39.3% vs. 27.0%), while sibling FNMTC was more prevalent in female patients (89.6% vs. 82.5%) and presented smaller tumors (1.2±0.8 vs. 1.4±1.1 cm) than sporadic NMTC. The recurrence rate was higher than that of sporadic NMTC in parent-offspring FNMTC (35.6% vs. 19.8%) but not in sibling FNMTC. Among the 123 parent-offspring FNMTC cases, the second generation exhibited an earlier age at the diagnosis (38±11 vs. 57±11 years), more extrathyroidal invasion (57.8% vs. 29.4%), a higher recurrence rate (50.0% vs. 19.0%), and shorter recurrence-free survival (p=0.015) than the first generation. CONCLUSION FNMTC was found to have a very high prevalence in our population. Parent-offspring FNMTC demonstrated higher recurrence than sporadic NMTC; specifically, the second generation of parent-offspring FNMTC cases exhibited more aggressive clinical characteristics than the first generation.

Factors predicting therapeutic efficacy of combination treatment with sitagliptin and metformin in type 2 diabetic patients: the COSMETIC study

Objective  We assessed the predictive parameters for therapeutic efficacy of initial combination therapy with sitagliptin and metformin in drug‐naïve type 2 diabetic patients.

Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance

Bisphenol A (BPA) is a widely used endocrine disruptor. Recent epidemiologic results have suggested an association between exposure to BPA and cardiovascular disease, type 2 diabetes, and obesity. We investigated the in vivo effects of long-term oral exposure to BPA on insulin resistance and glucose intolerance. In the present study, 4- to 6-week-old male mice on a high-fat diet (HFD) were treated with 50 μg/kg body weight per day of BPA orally for 12 weeks. Long-term oral exposure to BPA along with an HFD for 12 weeks induced glucose intolerance in growing male mice. Intraperitoneal glucose tolerance tests showed that the mice that received an HFD and BPA exhibited a significantly larger area under the curve than did those that received an HFD only (119.9±16.8 vs. 97.9±18.2 mM/min, P=0.027). Body weight, percentage of white adipose tissue, and percentage of body fat did not differ between the two groups of mice. However, treatment with BPA reduced Akt phosphorylation at position Thr308 and GSK3β phosphorylation at position Ser9 in skeletal muscle. BPA tended to decrease serum adiponectin levels and to increase serum interleukin 6 and tumor necrosis factor α, although these findings were not statistically significant. Treatment with BPA did not induce any detrimental changes in the islet area or morphology or the insulin content of β cells. In conclusion, long-term oral exposure to BPA induced glucose intolerance and insulin resistance in growing mice. Decreased Akt phosphorylation in skeletal muscle by way of altered serum adipocytokine levels might be one mechanism by which BPA induces glucose intolerance.

Effect of seasonal changes on the transition between subclinical hypothyroid and euthyroid status.

CONTEXT The widespread use of thyroid tests in asymptomatic individuals identifies many patients with transient subclinical hypothyroidism. OBJECTIVE Our objective was to determine the effect of seasonal change on serum TSH levels and the transition between subclinical hypothyroid and euthyroid status. DESIGN, SETTING, AND SUBJECTS This was a retrospective longitudinal study of 1751 subclinical hypothyroid and 28 096 euthyroid subjects aged over 18 years who underwent serial thyroid function tests at a health screening center between October 2003 and May 2011. MAIN OUTCOME MEASURES Age-adjusted geometric mean values of the TSH level by month were calculated using linear mixed models. Adjusted odds ratios of test season and multiple baseline clinical factors were determined using generalized estimating equations. RESULTS During a median 36 months of follow-up, 57.9% of subclinical hypothyroid subjects reverted to euthyroidism, and 4.3% of euthyroid subjects developed subclinical hypothyroidism. The monthly distribution of follow-up TSH levels indicated a biphasic pattern, ie, an increase during the winter-spring season and a decrease during the summer-fall season, with a maximal TSH difference of 0.69 mIU/L in subclinical hypothyroid and 0.30 mIU/L in euthyroid subjects. Normalization of subclinical hypothyroidism was increased 1.4-fold in follow-up tests during the summer-fall follow-up, whereas subclinical hypothyroidism increased 1.4-fold in euthyroid subjects during the winter-spring follow-up. CONCLUSIONS The season in which thyroid testing was performed was independently related to the transition between subclinical hypothyroid and euthyroid status. Seasonal variations in TSH concentration should be considered before deciding on treatment of subclinical hypothyroidism, particularly in the areas with a wide annual temperature range.

Dickkopf-1 inhibits thyroid cancer cell survival and migration through regulation of β-catenin/E-cadherin signaling.

Wnt/β-catenin signaling plays a role in tumorigenesis of human papillary thyroid cancer (PTC). Dickkopf-1 (Dkk-1) is an inhibitor of Wnt/β-catenin signaling. We investigated the therapeutic potential of Dkk-1 in human PTC cell lines, SNU-790, B-CPAP, and BHP10-3. Dkk-1 reversed the aberrant expression of β-catenin from nucleus to membrane and inhibited basal levels of TCF/LEF-dependent transcriptional activities. Furthermore, Dkk-1 inhibited cell viability in a dose-dependent manner and adenoviral transduction of constitutively active β-catenin blocked these effects, thus suggesting that the Dkk-1 anti-tumoral effect is mediated by Wnt/β-catenin signaling. Bromodeoxyuridine assay showed minimal effects of Dkk-1 on cell proliferation. Flow cytometric analysis with Annexin V staining showed marked induction of cell apoptosis by Dkk-1 treatment. Dkk-1 also restored the loss of membranous E-cadherin expression with consequent inhibition of cell migration and invasion. In conclusion, Dkk-1 inhibited the survival and migration of human PTC cells by regulating Wnt/β-catenin signaling and E-cadherin expression.

Tumor Size and Age Predict the Risk of Malignancy in Hürthle Cell Neoplasm of the Thyroid and Can Therefore Guide the Extent of Initial Thyroid Surgery

BACKGROUND The majority of patients having a diagnosis of Hürthle cell neoplasm (HCN) on fine-needle aspiration (FNA) of a thyroid nodule have a diagnostic thyroid lobectomy to make the final diagnosis. If the nodule is malignant, they require a completion thyroidectomy. The objective of this study was to devise a simple clinical scheme capable of predicting malignancy in patients with cytologic diagnosis of HCN and, therefore, guide the extent of initial thyroid surgery. METHODS A total of 57 patients who underwent thyroid surgery after an FNA diagnosis of HCN were retrospectively studied. The patients were examined for clinical features, preoperative imaging studies, and pathology reports. The risk of malignancy was calculated using a multiple logistic regression model. RESULTS The overall rate of malignancy in patients with HCN was 46% (26/57). The predictors of malignancy based on multiple logistic regression analysis were tumor size >1.5 cm (odds ratio [95% confidence interval] = 8.0 [1.9-33.4]) and patient age >45 years (odds ratio [95% confidence interval] = 2.3 [0.6-8.6]). In patients with nodules larger than 1.5 cm, the predicted probability of malignancy was greater in patients over 45 years than in younger patients (65% for >45 years vs. 44% for ≤45 years). In patients with a nodule 1.5 cm or less, the probability of malignancy was relatively low and not significantly different between the two age categories (18% for >45 years vs. 10% for ≤45 years). CONCLUSIONS This study suggests that tumor size and age can be integrated into decision making for patients with an FNA diagnosis of HCN to facilitate patient selection for surgical referral and, particularly, to determine in which patients a thyroidectomy rather than a lobectomy should be the initial surgery.

Analysis of Hemodialysis-Associated Hypoglycemia in Patients with Type 2 Diabetes Using a Continuous Glucose Monitoring System

BACKGROUND Adequate glycemic control is important for patients with end-stage renal disease on maintenance hemodialysis (HD). Continuous glucose monitoring (CGM) systems are reported as a useful method for glucose monitoring in patients under maintenance HD. The object of this study was to describe glucose profiles and hypoglycemia associated with HD in diabetes patients using a CGM system. METHODS We recruited nine medically stable patients with type 2 diabetes under maintenance HD. CGMS System Gold (Medtronic MiniMed, Northridge, CA) was applied to the subjects for 144 h. During the period, HD using glucose-containing dialysate was performed every other day. Various glucose profiles were calculated from the CGM readings and compared between the day on and the day off dialysis. RESULTS Mean ± SD for age, duration of diabetes, and hemoglobin A1c were 67 ± 9 years, 24 ± 9 years, and 8.6 ± 1.2%, respectively. Hemoglobin A1c was correlated with mean glucose (ρ = 0.780, P < 0.05) and with area under the curve for glucose above 180 mg/dL (ρ = 0.797, P<0.05). Although there was no difference for mean amplitude of glycemic excursion between the day on and off HD, hypoglycemia occurred predominantly with day on HD. In the subjects who maintained antidiabetes agents with day on HD, glucose levels decreased with initiation of HD, causing significantly lower glucose levels compared to those during the equivalent time of the following day without HD. CONCLUSIONS According to the CGM system, glucose variability was not affected by HD. However, in spite of glucose-containing dialysate, HD seemed to increase the risk of hypoglycemia.