Dipeptidyl peptidase-4 inhibitor compared with sulfonylurea in combination with metformin: cardiovascular and renal outcomes in a propensity-matched cohort study.

BACKGROUND: To determine the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) on the risk of major cardiocerebrovascular and renal outcomes compared with sulfonylurea (SU) combined with metformin in patients with type 2 diabetes from a population-based cohort. METHODS: From a nationwide cohort in Korea (2008-2013), 23,674 patients with type 2 diabetes treated with DPP4i plus metformin or SU plus metformin were selected and matched by propensity score. Composite cardiocerebrovascular events including incident ischemic heart disease (IHD), ischemic stroke (IS), hospitalization for heart failure (HHF), and cardiocerebrovascular death, as well as renal events including incident end-stage renal disease or initiation of renal-replacement therapy were assessed by Cox proportional-hazards models. RESULTS: During a median follow-up of 19.6 months (interquartile range 7.2-36.4), 762 composite cardiocerebrovascular events and 17 end-stage renal events occurred. There was no significant difference in the risk of IHD (hazard ratio [HR], 1.00; 95% CI 0.81-1.23), IS (HR, 0.95; 95% CI 0.74-1.23), or cardiocerebrovascular death (HR, 0.74; 95% CI 0.46-1.18) in the DPP4i group compared to that in the SU group. Likewise, DPP4i therapy was not associated with the risk of end-stage renal outcomes (HR, 1.23; 95% CI 0.41-3.62). However, the risk of HHF was significantly higher in the DPP4i group than in the SU group (HR, 1.47; 95% CI 1.07-2.04). CONCLUSIONS: This real-world database analysis showed that DPP4i therapy did not increase the overall risk of major cardiovascular and renal outcomes compared to SU therapy. However, the DPP4i-associated risk of HHF remained significant.

L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial.

Hypothyroid patients experience fatigue-related symptoms despite adequate thyroid hormone replacement. Thyroid hormone plays an essential role in carnitine-dependent fatty acid import and oxidation. We investigated the effects of L-carnitine supplementation on fatigue in patients with hypothyroidism. In total, 60 patients (age 50.0 ± 9.2 years, 3 males, 57 females) who still experienced fatigue (fatigue severity scale [FSS] score ≥ 36) were given L-carnitine (n = 30, 990 mg L-carnitine twice daily) or placebo (n = 30) for 12 weeks. After 12 weeks, although neither the FSS score nor the physical fatigue score (PFS) changed significantly, the mental fatigue score (MFS) was significantly decreased by treatment with L-carnitine compared with placebo (from 4.5 ± 1.9 to 3.9 ± 1.5 vs. from 4.2 ± 1.8 to 4.6 ± 1.6, respectively; P < 0.01). In the L-carnitine group, 75.0%, 53.6%, and 50.0% of patients showed improvement in the FSS score, PFS, and MFS, respectively, but only 20.0%, 24.0%, and 24.0%, respectively, did so in the placebo group (all P < 0.05). Both the PFS and MFS were significantly improved in patients younger than 50 years and those with free T3 ≥ 4.0 pg/mL by treatment with L-carnitine compared with placebo. Additionally, the MFS was significantly improved in patients taking thyroid hormone after thyroid cancer surgery. These results suggest that L-carnitine supplementation may be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer (ClinicalTrials.gov: NCT01769157).

Effect of Rubus Occidentalis Extract on Metabolic Parameters in Subjects with Prediabetes: A Proof-of-concept, Randomized, Double-blind, Placebo-controlled Clinical Trial.

Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p < 0.05). Homoeostasis model assessment-B was increased (+17.11 ± 10.69, +5.24 ± 4.10, and +0.86 ± 6.01 in HRE, LRE, and placebo, respectively, p < 0.05). Serum levels of monocyte chemoattractant protein-1 and oxidized low-density lipoprotein were significantly decreased by treatment in a dose-dependent manner (monocyte chemoattractant protein-1: -35.0 ± 21.2, +8.4 ± 18.1, and +24.2 ± 14.5; oxidized low-density lipoprotein: -19.7 ± 8.5, -13.1 ± 7.2, and -2.2 ± 11.0 in the HRE, LRE, and placebo, respectively, p < 0.05). The results support the beneficial effects of RO extract on the control of glycemia and vascular inflammation in prediabetic patients. (ClinicalTrials.gov: NCT01964703). Copyright © 2016 John Wiley & Sons, Ltd.

RAS mutations in indeterminate thyroid nodules are predictive of the follicular variant of papillary thyroid carcinoma.

OBJECTIVE: RAS mutations are the most common mutations in thyroid nodules with indeterminate cytology by fine-needle aspiration cytology (FNAC), and are mutually exclusive with BRAF mutations. However, the diagnostic utility of RAS mutation analysis is uncertain. We evaluated the diagnostic utility of RAS mutation analysis in indeterminate thyroid nodules. DESIGN, PATIENTS, AND MEASUREMENTS: A total of 155 thyroid nodules (90 benign and 65 indeterminate) negative for BRAF(V) (600E) mutations on FNAC were analysed for mutations in RAS codon 61 using pyrosequencing methods. We evaluated diagnostic accuracy of RAS mutation for predicting thyroid malignancy based on the surgical pathologic diagnosis. RESULTS: Among the 65 BRAF(V) (600E) -negative indeterminate thyroid nodules identified by FNAC, 25 (38·5%) exhibited point mutations in RAS 61 consisting of 18 NRAS 61 (72%), and 7 HRAS 61 (28%) mutations. In contrast, only five of 90 (5·6%) nodules with benign cytology had RAS mutations. Only two of 25 (8·0%) RAS 61(+) indeterminate nodules exhibited malignant ultrasonographic features. Of the 15 patients with RAS 61(+) -indeterminate nodules who underwent thyroid surgery, 14 (93·3%) were diagnosed as malignant, including 13 follicular variant of papillary thyroid carcinomas (FVPTC), and one follicular thyroid carcinoma (FTC). The average tumour size was 1·79 ± 0·62 cm. Multifocality was seen in 28·6% of cases, with 7·1% exhibiting extrathyroidal extension; no lymph node or distant metastases were evident. Based on the surgical pathologic diagnosis results, preoperative RAS 61 mutation analysis on FNAC exhibited 93·3% sensitivity, 75·0% specificity, 93·3% positive predictive value, 75·0% negative predictive value and 89·5% diagnostic accuracy for predicting malignancies. CONCLUSION: Our results suggest that RAS mutation analysis holds great promise as a preoperative diagnostic tool for predicting FVPTC in cytologically and sonographically indeterminate nodules negative for BRAF mutations.

In vivo deletion of CAR resulted in high bone mass phenotypes in male mice.

Constitutive androstane receptor (CAR) was originally identified as xenobiotic sensor that regulates the expression of cytochrome P450 genes. However, recent studies suggest that this nuclear receptor is also involved in the regulation of energy metabolism including glucose and lipid homeostasis. This study investigated the role of CAR in the regulation of bone mass in vivo using CAR(-/-) mice. Endogenous mRNA expression of CAR was observed in both primary osteoblasts and osteoclast precursors. CAR(-/-) mice have exhibited significant increase in whole body bone mineral density (BMD) by 9.5% (P < 0.01) and 5.5% (P < 0.05) at 10 and 15 weeks of age, respectively, compared with WT mice in males. Microcomputed tomography analysis of proximal tibia demonstrated a significant increase in trabecular bone volume (62.7%), trabecular number (54.1%) in male CAR(-/-) mice compared with WT mice. However, primary culture of calvarial cells exhibited no significant changes in osteogenic differentiation potential between CAR(-/-) and WT. In addition, the number of tartrate-resistant acid-phosphatase positive osteoclasts in the femur and serum level of CTx was not different between CAR(-/-) and WT mice. The higher BMD and microstructural parameters were not observed in female mice. Interestingly, serum level of testosterone in male CAR(-/-) mice was 2.5-fold higher compared with WT mice and the mRNA expressions of Cyp2b9 and 2b10 in the liver, which regulate testosterone metabolism, were significantly down-regulated in male CAR(-/-) mice. Furthermore, the difference in BMD between CAR(-/-) and WT mice disappeared at 8 weeks after performing orchiectomy. CAR(-/-) mice also exhibited significant increase in serum 1,25(OH)2 D3 levels but Cyp 27B1 which converts 25(OH)D3 to 1,25(OH)2 D3 was significantly down-regulated compared to WT mice. These results suggest that in vivo deletion of CAR resulted in higher bone mass, which appears to be a result from reduced metabolism of testosterone due to down-regulation of Cyp2b.

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. DeSIGN, PATIENTS, AND MEASUREMENTS: In this 52-week treatment study, 150 patients (mean age, 54·9 ± 12·5 years) with type 2 diabetes and HbA1c of 7·0-10% were treated with sitagliptin 100 mg once and metformin 500 mg twice daily. To assess the predictive parameters for therapeutic efficacy, a multivariate regression analysis was performed with baseline fasting glucose, insulin, C-peptide, and glucagon levels, homoeostasis model assessment-insulin resistance (HOMA-IR) and ß-cell function (HOMA-B), insulinogenic index (IGI, defined as 30-0 min insulin/30-0 min glucose), and area under the curve for glucose, insulin, and C-peptide obtained after 75-g oral glucose tolerance test. RESULTS: After 52 weeks, mean HbA1c levels and fasting and postload 2-h glucose were significantly decreased from 8·7 ± 1·4% to 7·2 ± 1·3%, 9·2 ± 3·0 to 7·2 ± 1·8 mm, and 17·5 ± 5·1 to 10·9 ± 3·6 mm, respectively (P < 0·01). HOMA-B and IGI increased significantly from 50·3 ± 33·5 to 75·1 ± 32·8 and from 11·3 ± 1·3 to 35·0 ± 6·3 at 52 weeks, respectively (P < 0·01). Multivariate regression analysis indicated that the reduction in HbA1c was significantly associated with high baseline HbA1c, low IGI, and short duration of diabetes after adjusting for age, sex, body mass index, blood pressure, triglycerides, creatinine, high-sensitivity CRP, glucagon, C-peptide, HOMA-B, and HOMA-IR. No severe adverse events were observed. CONCLUSION: These results suggest that drug-naïve type 2 diabetic patients with low ß-cell function would benefit the most from early initial combination therapy of sitagliptin and metformin.

Transplantation of mesenchymal stem cells overexpressing RANK-Fc or CXCR4 prevents bone loss in ovariectomized mice.

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and increased risk of fracture. We studied the effects of transplantation of mesenchymal stem cells (MSCs) overexpressing receptor activator of nuclear factor-kappaB (RANK)-Fc and CXC chemokine receptor-4 (CXCR4) using retrovirus on ovariectomy (OVX)-induced bone loss in mice. Ten-week-old adult female C57BL/6 mice were divided into six groups as follows: Sham-operated mice treated with phosphate-buffered saline (PBS) (Sham-op + PBS); OVX mice intravenously transplanted with syngeneic MSCs overexpressing RANK-Fc-DsRED and CXCR4-GFP (RANK-Fc + CXCR4); RANK-Fc-DsRED and GFP (RANK-Fc + GFP); CXCR4-GFP and DsRED (CXCR4 + RED); DsRED and GFP (RED + GFP); or treated with PBS only (OVX + PBS). Measurement of BMD showed that introduction of RANK-Fc resulted in significant protection against OVX-induced bone loss compared to treatment with PBS (-0.1% versus -6.2%, P < 0.05) at 8 weeks after cell infusion. CXCR4 + RED group also significantly prevented bone loss compared to OVX + PBS group (2.7% versus -6.2%, P < 0.05). Notably, the effect of RANK-Fc + CXCR4 was greater than that of RANK-Fc + GFP (4.4% versus -0.1%, P < 0.05) while it was not significantly different from that in CXCR4 + RFP group (4.4% versus 2.7%, P = 0.055) at 8 weeks. Transplantation of MSCs with control virus (RED + GFP group) also resulted in amelioration of bone loss compared to OVX + PBS group (-1.7% versus -6.2%, P < 0.05). Fluorescence-activated cell sorting (FACS) and real-time quantitative PCR (qPCR) analysis for GFP from bone tissue revealed enhanced cell trafficking to bone by co-overexpression of CXCR4. In conclusion, we have demonstrated that intravenous transplantation of syngeneic MSCs overexpressing CXCR4 could promote increased in vivo cell trafficking to bone in OVX mice, which could in itself protect against bone loss but also enhance the therapeutic effects of RANK-Fc.

Clinical factors predicting the successful discontinuation of hormone replacement therapy in patients diagnosed with primary hypothyroidism.

BACKGROUND: Although reversible in some patients, primary hypothyroidism is considered a permanent condition requiring lifelong hormone therapy. This study aimed to investigate the factors predicting the successful discontinuation of levothyroxine (L-T4) therapy in patients with primary hypothyroidism. METHODS: A retrospective study was performed in primary hypothyroidism patients who met inclusion criteria: patients who maintained stable L-T4 therapy for more than 1 year, following gradual dose reduction of L-T4 based on the clinical decision (L-T4 tapering); patients receiving either no L-T4 or a fixed minimum dose for more than 1 year after L-T4 tapering. Reduction in L-T4 dosage by 12.5-50 µg within 3 months was considered as L-T4 tapering. Serum free T4, TSH, and clinical symptoms were evaluated before, during and after tapering. Logistic regression and decision tree analyses were performed to predict the successful discontinuation of L-T4. RESULTS: Among 382 patients, 22.5% and 58.4% showed successful discontinuation (T4-Discontinued) and dose reduction (T4-Reduced) of L-T4 therapy, while other did not obtained any reduction of L-T4 dose (T4-Unchanged). The median number of tapering visit was 1.0 (range, 1.0-4.0). In T4-Discontinued group, the TSH level and the positive rate of anti-thyroperoxidase at the time of L-T4 initiation were lower, the duration of L-T4 therapy was shorter, and the maintenance dose of L-T4 at the time of tapering was lower than those in the T4-Unchanged group. In ultrasonography, normal parenchyma was preserved in the T4-Discontinued group while others showed higher rates of heterogeneous or hypoechoic parenchymal changes. Among those different characteristics, the longer duration of L-T4 therapy and the higher maintenance dose of L-T4 at the time of tapering significantly predicted the failure of discontinuation of L-T4 in multivariate analysis. A decision tree showed that patients with a duration of L-T4 therapy >4.6 years had lower success rate of discontinuation. CONCLUSION: Shorter duration of L-T4 therapy and lower L-T4 dose at the time of tapering are the predictable factors for successful L-T4 tapering in stably maintained primary hypothyroidism patients.

Actual causes of death in thyroid cancer patients in Korea: A Nationwide Case Control Cohort Study.

OBJECTIVE: Thyroid cancer (TC) incidence has increased robustly in Korea. However, the actual cause of death, overall mortality risk, and cause-specific mortality risk in TC patients have not been clearly elucidated. DESIGN: Retrospective cohort study. METHODS: We analyzed 4082 TC patients from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS, 2002-2013) with a median of 48-month follow-up. We compared these patients with 12 246 controls matched for age, sex, and histories of major cardiovascular disease (CVD) to investigate the cause of death and risks of overall and cause-specific mortality. RESULTS: Overall, 61 deaths (1.5%) occurred in the TC group. The most common cause of death was TC-specific mortality (32.8%), followed by other malignancy-related mortality (31.1%) and CVD mortality (13.1%). The overall mortality risk was comparable between the TC and control groups (unadjusted hazard ratio (HR): 1.17; 95% confidence interval (CI): 0.87-1.58); the adjusted HR remained at 1.25 (95% CI: 0.90-1.74) after multivariate adjustment for body mass index (BMI), socioeconomic status (SES), smoking, alcohol consumption, and histories of hypertension, diabetes mellitus, and dyslipidemia. In addition, there was not enough evidence against the surmise that the CVD mortality risk was similar between the TC and control groups, with an HR of 0.50 (95% CI: 0.22-1.16) after adjustment for CVD risk factors. CONCLUSIONS: Excellent overall survival was observed in TC patients. The most common cause of death was TC-specific mortality, suggesting the importance of thyroid cancer treatment. The overall and cause-specific mortality risks, particularly CVD mortality risk, did not differ between TC patients and the general population.

Prevalence of osteoporosis among North Korean women refugees living in South Korea: a comparative cross-sectional study.

OBJECTIVE: To investigate the prevalence of osteoporosis among North Korean women refugees when compared with South Korean women, who have identical genetic backgrounds but experience different environments. DESIGN: Comparative cross-sectional study. SETTING: North Korean Refugee Health in South Korea (NORNS) study in South Korea. PARTICIPANTS: We evaluated 122 North Korean women who participated in NORNS study and 366 age-matched/menopausal status-matched South Korean women from the Korea University Medical Center (KUMC) health examination cohort. The median age of the NORNS participants was 46 years (IQR, 40-60 years) with 52 women (42.6%) being postmenopausal. RESULTS: Among the postmenopausal women, NORNS participants had a higher body mass index and number of pregnancies and lower physical activity than the KUMC participants. The overall prevalence of osteoporosis was 48% (25/52) and 17% (27/156) in NORNS and KUMC participants, respectively. The bone mineral density (BMD) values at the lumbar spine, femur neck and total hip were significantly lower in postmenopausal NORNS women than in the postmenopausal KUMC women. Old age, low body weight and late age of menarche were associated with low BMD among the postmenopausal North Korean refugees. In premenopausal participants, the NORNS women had lower body weight and physical activity than the KUMC women at baseline. All the NORNS women had normal Z-scores, although the BMD at the lumbar spine was significantly lower in NORNS women than in the KUMC women (0.952 vs 1.002 g/cm2, p<0.001). CONCLUSIONS: Osteoporosis is a prevalent health problem in postmenopausal North Korean women refugees living in South Korea. It is conceivable to prepare vigilant countermeasures for bone health deterioration in this growing population, especially for postmenopausal women. Further research is warranted to determine the cause of the differences between participants of the same ethnic group.

Lower bone mineral density is associated with higher coronary calcification and coronary plaque burdens by multidetector row coronary computed tomography in pre- and postmenopausal women.

OBJECTIVES: There is growing evidence for the association between bone mineral density (BMD) and vascular calcification, which is related to cardiovascular disease. Coronary multidetector row computed tomography (MDCT) is a noninvasive tool developed to evaluate coronary status precisely. We used MDCT to evaluate this association. DESIGN AND PATIENTS: Eight hundred and fifteen subjects received routine checkups. After excluding subjects with factors affecting bone metabolism and cardiovascular disease, 467 subjects were analysed. MEASUREMENTS: Coronary calcification was measured with MDCT and BMD was measured with dual X-ray absorptiometry (DXA). RESULTS: The BMD of the femur and the lumbar spine (L-spine) were negatively associated with the coronary calcium score (CCS) after adjusting for age in women but not in men. This inverse correlation was stronger in women with a longer time since menopause (r = -0.35 at femur, postmenopausal women vs. r = -0.10 at femur, premenopausal women, P < 0.05), and it was stronger at the femur than in the L-spine (r = -0.35 at femur vs. r = -0.16 at L-spine, P < 0.01). The relationship was also stronger in postmenopausal women with osteoporosis and osteopaenia than in women with normal BMD. The lower BMD was associated with higher coronary plaque burdens and multidiseased coronary vessels in both men and women (P < 0.01). CONCLUSIONS: Increased CCS and subclinical atherosclerosis of plaque burdens as revealed by MDCT was associated with a low BMD in all women, independent of cardiovascular risk factors and age.

Impaired Cortisol and Growth Hormone Counterregulatory Responses among Severe Hypoglycemic Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Elevated levels of cortisol and growth hormone are critical counterregulatory responses to severe hypoglycemia. However, the proportion and clinical characteristics of patients with type 2 diabetes mellitus (DM) who fail to show appropriate cortisol and/or growth hormone secretion in response to severe hypoglycemia have not been investigated. METHODS: We measured plasma cortisol and growth hormone levels in type 2 DM patients with severe hypoglycemia who visited the emergency department between 2006 and 2015. RESULTS: Of 112 hypoglycemic patients, 23 (20.5%) had an impaired cortisol response (<18 µg/dL) and 82 patients (73.2%) had an impaired growth hormone response (<5 ng/mL). Nineteen patients (17.0%) had impaired responses to both cortisol and growth hormone. The patients with impaired responses of cortisol, growth hormone, and both hormones were significantly older and more likely to be female, and had higher admission rates, lower growth hormone levels, and lower adrenocorticotropic hormone levels than the patients with a normal hormonal response. Multivariate logistic regression analysis indicated that an impaired growth hormone response was significantly associated with advanced age, shorter DM duration, a higher admission rate, and a higher body mass index (BMI). An impaired cortisol response was significantly associated with growth hormone levels. Patients with an impaired growth hormone response had higher admission rates than patients with a normal response. CONCLUSION: A considerable number of type 2 DM patients had impaired cortisol and/or growth hormone responses to severe hypoglycemia. Advanced age, shorter DM duration, and higher BMI were independently associated with an abnormal growth hormone response.

Two cases of ectopic adrenocorticotropic hormone syndrome with olfactory neuroblastoma and literature review.

Olfactory neuroblastomas are rare, slow-growing malignant tumors, usually diagnosed at advanced stages. Ectopic adrenocorticotropic hormone (ACTH) syndrome caused by an olfactory neuroblastoma is extremely rare. We reported two Korean women who suffered from ectopic ACTH syndrome (EAS) caused by olfactory neuroblastomas. The first patient was a 66-year-old woman who had been diagnosed as olfactory neuroblastoma and refused the management two years before and the second patient was a 37-year-old woman on chemotherapy for olfactory neuroblastoma. In the first case, she presented the Cushingoid appearance with systemic edema and her tumor was removed surgically. ACTH secretion by the tissue was confirmed by immunohistochemistry. By contrast, the second patient presented as severe pneumonia caused by cytomegalovirus and was treated with anti-viral agent followed by chemotherapy and radiotherapy, and her residual mass remained. However, after treatment, both patients' plasma ACTH and cortisol levels returned to normal without any adrenolytic therapy. Considering the causative tumors of EAS can be rarely cured and EAS increases the susceptibility to infections, it is prudent to suppress any hypercortisolemia initially, apart from treating the causal malignancy.

Effects of thyroid hormone withdrawal on metabolic and cardiovascular parameters during radioactive iodine therapy in differentiated thyroid cancer.

Objective To investigate the cardiometabolic effects of a severe hypothyroid state induced by withdrawal of thyroid hormone replacement before radioactive iodine therapy. Methods Patients with thyroid cancer who were scheduled to receive radioactive iodine ablation were enrolled. Cardiometabolic parameters were measured using blood samples taken immediately before levothyroxine withdrawal, 4 weeks following withdrawal (on radiotherapy day), and 4 weeks following reinstitution of levothyroxine. Results Out of 48 patients (age 49.4 ± 10.5 years; 77.1% [37/48] female), the severe hypothyroid state induced by levothyroxine withdrawal significantly aggravated the majority of lipid parameters, particularly in patients with a greater number of metabolic syndrome components. Fasting plasma glucose levels and homeostatic model assessment values for insulin resistance and ß-cell function significantly decreased following levothyroxine withdrawal. Serum high-sensitivity C-reactive protein, fibrinogen and cystatin C levels significantly decreased, and homocysteine levels increased during the severe hypothyroid state. All of these changes were reversed by levothyroxine reinstitution. Conclusions Severe hypothyroid state induced pronounced changes in cardiometabolic parameters. Further studies should identify the long-term effects of changes in these parameters on cardiovascular morbidity and mortality in relation to thyroid disease.

Predicting Extrathyroidal Extension in Patients With Papillary Thyroid Microcarcinoma According to a BRAF Mutation.

OBJECTIVES: The aim of this study was to evaluate the association between preoperative parameters and extrathyroidal extension (ETE) of papillary thyroid microcarcinoma (PTMC) according to the BRAF mutation and to evaluate the preoperative predictability of ETE. METHODS: We analyzed the medical records of 332 patients with PTMC (140 in the BRAF- group and 192 in the BRAF+ group). The presence of ETE was subjected to a correlation analysis with age, sex, tumor size, clinical nodal status, and ultrasonography (US) findings. Among the US findings, the correlation between tumors and the thyroid capsule was categorized into four groups; US group A, intraparechymal; US group B, tumor abutting the capsule <50% of diameter; US group C, tumor abutting >50% of diameter; and US group D, tumor destroyed the capsule. The predictive value of ETE, including sensitivity, specificity, and positive and negative predictive values were evaluated. RESULTS: Tumor size and US group were significantly correlated with gross ETE in the BRAF- and BRAF+ groups. Tumor size of 0.5 cm and US groups B and C in the BRAF- group were cutoff values for gross ETE, with a negative predictive value of 100%, whereas tumor size of 0.7 cm and US groups A and B in the BRAF+ group had negative predictive values of 92.4% and 100%, respectively. CONCLUSION: Excluding of ETE by US was categorized according to tumor size and US findings. A different categorization to exclude ETE is needed according to the BRAF mutation.

Determinants of Long-Term Durable Glycemic Control in New-Onset Type 2 Diabetes Mellitus.

BACKGROUND: Long-term durable glycemic control is a difficult goal in the management of type 2 diabetes mellitus (T2DM). We evaluated the factors associated with durable glycemic control in a real clinical setting. METHODS: We retrospectively reviewed the medical records of 194 new-onset, drug-naïve patients with T2DM who were diagnosed between January 2011 and March 2013, and were followed up for >2 years. Glycemic durability was defined as the maintenance of optimal glycemic control (glycosylated hemoglobin [HbA1c] <7.0%) for 2 years without substitution or adding other glucose-lowering agents. Clinical factors and glycemic markers associated with glycemic durability were compared between two groups: a durability group and a non-durability group. RESULTS: Patients in the durability group had a higher baseline body mass index (26.1 kg/m² vs. 24.9 kg/m²) and lower HbA1c (8.6% vs. 9.7%) than the non-durability group. The initial choice of glucose-lowering agents was similar in both groups, except for insulin and sulfonylureas, which were more frequently prescribed in the non-durability group. In multiple logistic regression analyses, higher levels of education, physical activity, and homeostasis model assessment of ß-cell function (HOMA-ß) were associated with glycemic durability. Notably, lower HbA1c (<7.0%) at baseline and first follow-up were significantly associated with glycemic durability (adjusted odds ratio [OR], 7.48; 95% confidence interval [CI], 2.51 to 22.3) (adjusted OR, 9.27; 95% CI, 1.62 to 53.1, respectively), after adjusting for confounding variables including the types of glucose-lowering agents. CONCLUSION: Early achievement of HbA1c level within the glycemic target was a determinant of long-term glycemic durability in new-onset T2DM, as were higher levels of education, physical activity, and HOMA-ß.

Prevalence of metabolic syndrome and its related factors among North Korean refugees in South Korea: a cross-sectional study.

OBJECTIVES: To determine the prevalence of metabolic syndrome (MetS) and its related factors among North Korean refugees (NKR) in South Korea. DESIGN: Cross-sectional study conducted using a questionnaire and anthropometric and biochemical data on NKR in South Korea. SETTING: Seoul, South Korea. PARTICIPANTS: A sample of NKR who voluntarily underwent medical examinations in Anam Hospital of Korea University, Seoul, South Korea (N=708, consisting of 161 males and 547 females). To compare the prevalence of MetS, 1416 age- and gender-matched individuals from the South Korean population (SKP, at a ratio of 1:2 to NKR) were randomly selected from the fifth Korean National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: The prevalence of MetS and its related factors among NKR in South Korea and comparison with its prevalence among the general SKP. RESULTS: The prevalence of MetS among male and female NKR in South Korea was 19.7% and 17.2%, respectively. Although obesity is more prevalent in South than in North Korea, we found no difference in the prevalence of MetS between the female NKR and SKP groups (17.2% vs 16.6%, respectively; p=0.830). As regards the males, the small sample size of the NKR group yielded insufficient evidence of any difference in MetS prevalence between the NKR and SKP groups (19.7% vs 26.2%, respectively; p=0.134). We found that excess weight gain (≥5%) in South Korea was significantly associated with MetS among NKR. CONCLUSIONS: The prevalence of MetS among NKR did not differ from that in the SKP group despite the lower prevalence of obesity in NKR than in the general SKP. The fact that excess weight gain in South Korea was associated with the risk of MetS suggests that public health policy makers should focus on preventing excess weight gain in NKR during resettlement in South Korea.

Vitamin D status and associated metabolic risk factors among North Korean refugees in South Korea: a cross-sectional study.

OBJECTIVE: Vitamin D deficiency is now recognised as a common health problem associated with various chronic diseases; however, it has not been fully elucidated among the minority groups. Here, we aimed to investigate the prevalence of vitamin D deficiency and its associated metabolic risk factors among North Korean refugees living in South Korea. DESIGN: Cross-sectional analysis from the longitudinal cohort, the North Korean refugee health in South Korea (NORNS) study. PARTICIPANTS: A total of 386 North Korean refugees aged ≥30 years, who measured serum 25-hydroxy vitamin D (25(OH)D) level. RESULTS: The prevalence of vitamin D deficiency (25(OH)D <20 ng/mL) was 87% and no participants had an adequate vitamin D level (25(OH)D ≥30 ng/mL). Underweight participants (body mass index (BMI) <18 kg/m(2)) had significantly lower 25(OH)D levels than individuals with normal BMI (≥18.5 and<23 kg/m(2)). In the multivariate logistic regression analysis, the lowest 25(OH)D level (<10 ng/mL) was significantly associated with metabolic syndrome (OR, 6.37, 95% CI 1.34 to 30.3), high triglyceride (OR, 6.71, 95% CI 1.75 to 25.7), and low high-density lipoprotein (OR, 5.98, 95% CI 1.54 to 23.2) compared with 25(OH)D levels ≥20 ng/mL after adjusting for age, sex, season, length of residence in South Korea, physical activity and BMI. CONCLUSIONS: Vitamin D deficiency is very common among North Korean refugees in South Korea. Despite their lower BMI, vitamin D deficiency was associated with metabolic syndrome in this population.

A Possible Association Between Thyroid Cancer and Breast Cancer.

BACKGROUND: Several lines of evidence suggest that breast cancer (BC) and thyroid cancer (TC) occur together in the same female patients more frequently than would be expected by chance. This study investigated the prevalence and clinicopathological characteristics of second primary BC in TC patients and second primary TC in BC patients. METHODS: A retrospective case-controlled study was performed in 4243 patients with differentiated TC and 6833 patients with BC. Age-matched control groups without second malignancies were selected. RESULTS: Of the 4243 patients with TC, 55 patients developed subsequent BC during a five-year follow-up (range 2-40 years); the standardized incidence ratio (SIR) was 2.45 [confidence interval (CI) 1.83-2.96]. Among the 6833 patients with BC, 81 patients developed subsequent TC during a 6.2-year follow-up (range 2-40 years); the SIR was 2.18 [CI 1.43-2.82]. Subsequent second BC or TC diagnosed within five years of the initial primary malignancy showed more clinical characteristics consistent with early-stage cancer than did control BC or TC patients. Notably, the expression of both the estrogen and progesterone receptors was significantly higher in the tissues of BC patients with coexisting TC compared with those with BC alone. CONCLUSIONS: The overall risk of second primary TC or BC is increased in patients with prior BC or TC, respectively. The early detection of second cancer might have contributed to these findings. However, BC that coexisted with TC had a higher expression of hormone receptors, suggesting an association between the molecular pathogenesis of TC and BC.