Gender- and age-group-specific associations between physical performance and bone mineral density, falls, and osteoporotic fractures in Koreans: the Chungju Metabolic Disease Cohort study.

Several factors increase the risk of fragility fracture, including low bone mineral density, falls, and poor physical performance. The associations among these factors have been investigated; however, most of the subjects of previous studies were either elderly men or elderly women, and the associations were controversial. The aim of this study was to evaluate the associations between physical performance and bone mineral density, and the history of falls and fractures, stratified by gender and age group. We analyzed 5368 subjects who were aged 50 years or older, including 1288 younger men (younger than 70 years), 1615 younger women (younger than 70 years), 1087 older men (70 years or older), and 1378 older women (70 years or older). We used the one-leg standing time (OLST) for assessing static balance and the timed up-and-go test (TUGT) for assessing dynamic balance. The subjects in the worst performance quartile for the OLST were more likely to have osteoporosis than those in the best performance quartile. Additionally, women who had experienced a fracture during the past 2 years were 1.68 times more likely to be in the worst performance quartile for the OLST than women without a previous fracture. Although the TUGT time was not associated with either the incidence of osteoporosis or the fracture history, the odds ratios for falling were 1.51 and 1.28 as the TUGT time increased by one standard deviation in younger men and younger women, respectively. The findings of the present study show that the OLST was associated with the incidence of osteoporosis and previous fracture and that the TUGT time was associated with the incidence of falling.

Retinal nerve fiber layer loss is associated with urinary albumin excretion in patients with type 2 diabetes.

OBJECTIVES: To identify the factors associated with retinal nerve fiber layer (RNFL) loss in patients with type 2 diabetes. DESIGN: Cross-sectional study. PARTICIPANTS: Ninety-six nonglaucomatous patients with type 2 diabetes without renal impairment (estimated glomerular filtration rate, ≥60 ml/minute per 1.73 m(2)). METHODS: Eyes were divided into 2 groups based on the presence or absence of RNFL defects detected by red-free retinal fundus photography. All participants underwent an eye fundus examination, and the urinary albumin-to-creatinine ratio (ACR) was determined. A cardiovascular autonomic function test was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to the Valsalva maneuver, and standing. Multiple logistic regression analyses were performed to determine potential risk factors related to the presence of RNFL defects in these patients. MAIN OUTCOMES AND MEASURES: The association between RNFL defects and diabetic complications. RESULTS: Among the patients, 43 (44.8%) had localized RNFL defects (group 1), whereas the others (55.2%) did not (group 2). The RNFL defects occurred more frequently on the superior side (75.6% and 71.0% in right and left eyes, respectively) compared with the inferior side (13.8% and 0.0% in right and left eyes, respectively). Patients with RNFL defects (group 1) had significantly higher rates of diabetic retinopathy (60.5%) compared with those without RNFL defects (group 2; 32.1%; P = 0.007). The urinary ACR was significantly higher in patients with RNFL defects than in those without defects (45.3±72.1 µg/mg vs. 15.4±17.3 µg/mg creatinine, respectively; P = 0.015), whereas autonomic function test grading was similar between the groups. The urinary ACR was the only factor related to visual field defect location in both univariate (P = 0.021) and multivariate (P = 0.036) logistic regression analyses after adjusting for age; gender; presence of diabetic retinopathy; diabetes duration; smoking; statin use; and antiplatelet, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker treatment. CONCLUSIONS: Urinary albumin excretion was associated with nerve fiber layer loss in patients with type 2 diabetes. Careful examination of the optic nerve head may be necessary, particularly in patients with type 2 diabetes exhibiting albuminuria.

Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes.

We evaluated the prevalence of vitamin B12 deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B12 and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12 ≤ 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B12 level was 662.5 ± 246.7 pg/mL. Vitamin B12 deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of ≤ 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and ≥ 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and ≥ 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B12 deficiency, especially at higher dosages (> 1,000 mg) and longer durations (≥ 4 yr) of treatment.

Interobserver agreement and intraobserver reproducibility in thyroid ultrasound elastography.

OBJECTIVE: The objective of this study was to evaluate interobserver agreement and intraobserver reproducibility in thyroid ultrasound elastography. SUBJECTS AND METHODS: Fifty-six patients (56 nodules) were enrolled for this prospective study between December 2010 and March 2011. All patients were scheduled for thyroid surgery because their nodules had been found by fine-needle aspiration biopsies to be malignant, suspicious for malignancy, or follicular/Hürthle cell neoplasm. On each patient, three endocrinologists performed ultrasound elastography examinations using a commercial ultrasound machine. No external compression with the transducer was applied because pulsation from the carotid artery was used. Each endocrinologist repeated an elastography examination on the same thyroid nodule. An elasticity contrast index, which quantifies the local strain contrast within a nodule, was interactively determined after a nodule's boundary was delineated by the endocrinologist. A large elasticity contrast index value indicates an increased probability of the nodule being malignant. Pearson correlation coefficient was used to evaluate the interobserver and intraobserver agreement in the measured elasticity contrast index values, and p values < 0.05 were considered statistically significant. RESULTS: Significant interobserver and intraobserver agreement was found in thyroid ultrasound elastography. Pearson correlation coefficients between two observers were 0.79 (observers 1 and 2, p < 0.01), 0.77 (observers 1 and 3, p < 0.01), and 0.73 (observers 2 and 3, p < 0.01). Pearson correlation coefficients for intraobserver agreement were 0.87 (p < 0.01), 0.73 (p < 0.01), and 0.84 (p < 0.01) for observers 1, 2 and 3, respectively. CONCLUSION: Good interobserver and intraobserver agreement exists in thyroid ultrasound elastography. Compared with external compression elastography, we found that thyroid elastography with intrinsic compression can produce reliable results.

Thyroid nodule parameters influencing performance of ultrasound elastography using intrinsic compression.

The influence of nodule parameters on the diagnostic accuracy of ultrasound (US) elastography in differentiating thyroid nodules was evaluated. One hundred seventy-six nodules (83 benign, 93 malignant) from 156 patients were included. Conventional B-mode and elastography examinations were performed. External compression with a transducer was not applied, as the pulsation from the carotid artery was used. Three nodule parameters (size, depth and distance to the carotid artery) were measured. The elasticity contrast index, in which increases with the stiffness of the nodules, was correlated with distance to the carotid artery (correlation coefficient = 0.283 in all nodules and 0.415 in malignant nodules, p < 0.01 in both groups). The diagnostic accuracy of elastography was significantly associated with a nodule's distance to the carotid artery (p < 0.05). No significant correlation was found between the diagnostic accuracy of elastography and the other parameters. Elastography results for nodules close to the carotid artery should be interpreted with caution.

Elastography can effectively decrease the number of fine-needle aspiration biopsies in patients with calcified thyroid nodules.

When calcification, frequently found in both benign and malignant nodules, is present in thyroid nodules, non-invasive differentiation with ultrasound becomes challenging. The goal of this study was to evaluate the utility of elastography in differentiating calcified thyroid nodules. Consecutive patients (165 patients with 196 nodules) referred for fine-needle aspiration who had undergone both ultrasound elastography and B-mode examinations were analyzed retrospectively. Calcification was present in 45 benign and 20 malignant nodules. On 65 calcified nodules, elastography had 95% sensitivity, 51.1% specificity, 46.3% positive predictive value and 95.8% negative predictive value in detecting malignancy. Twenty-three of 45 benign calcified nodules were correctly diagnosed with elastography compared with 4 of 45 by B-mode ultrasound. Although it is difficult to differentiate benign and malignant calcified thyroid nodules solely with B-mode ultrasound, elastography has the potential to reduce the number of fine-needle aspiration biopsies performed on calcified nodules.

Severe hypokalemia and thyrotoxic paralysis from painless thyroiditis complicated by life-threatening polymorphic ventricular tachycardia and rhabdomyolysis.

A 61-year-old man presented with lower extremity paralysis and severe hypokalemia. His thyroid function test showed thyrotoxicosis. Despite attempts to correct his hypokalemia, he developed pulseless polymorphic ventricular tachycardia two hours later. He was successfully resuscitated after defibrillation. We performed continuous venovenous hemodiafiltration for 10 days due to acute kidney injury and rhabdomyolysis. We observed life-threatening polymorphic ventricular tachycardia requiring urgent defibrillation, as well as rhabdomyolysis requiring dialysis during the transient thyrotoxic phase of painless thyroiditis. Pay attention to the possibility of the development of life-threatening ventricular tachycardia associated with hypokalemia in the setting of thyroiditis and thyrotoxic paralysis.

Presence of macroalbuminuria predicts severe hypoglycemia in patients with type 2 diabetes: a 10-year follow-up study.

OBJECTIVE: We investigated the factors that might influence the development of severe hypoglycemia in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: From January 2000 to December 2002, patients with type 2 diabetes aged 25-75 years without chronic kidney disease (estimated glomerular filtration rate ≥60 mL/min/1.73 m(2)) were consecutively recruited (n = 1,217) and followed-up in January 2011 and May 2012. Severe hypoglycemia (SH) was defined as an event requiring the assistance of another person to actively administer glucose, hospitalization, or medical care in an emergency department. We used Cox proportional hazard regression analysis to test the association between SH episodes and potential explanatory variables. RESULTS: After a median 10.4 years of follow-up, 111 (12.6%) patients experienced 140 episodes of SH, and the incidence was 1.55 per 100 patient-years. Mean age and duration of diabetes were 55.3 ± 9.8 and 9.8 ± 6.5 years, respectively. The incidence of SH events was higher in older patients (P < 0.001), in those with a longer duration of diabetes (P < 0.001), in those who used insulin (P < 0.001) and sulfonylurea (P = 0.003), and in those who had macroalbuminuria (P < 0.001) at baseline. Cox hazard regression analysis revealed that SH was associated with longer duration of diabetes and the presence of macroalbuminuria (normoalbuminuria versus macroalbuminuria: hazard ratio, 2.52; 95% CI 1.31-4.84; P = 0.006). CONCLUSIONS: The development of SH was independently associated with duration of diabetes and presence of macroalbuminuria, even with normal renal function in patients with type 2 diabetes.

Non-FDG-avid primary papillary thyroid carcinoma may not differ from FDG-avid papillary thyroid carcinoma.

BACKGROUND: FDG (2-[(18)F]Fluoro-2-D-deoxyglucose-positron emission tomography (PET)/computed tomography (CT), which can detect a change in glucose metabolism in cancer cells, has been introduced as a diagnostic and prognostic tool in papillary thyroid carcinoma (PTC). However, differences in the clinicopathological and biological characteristics between primary PTCs with FDG uptake and those without FDG uptake are not well established. METHODS: A total of 188 patients with PTC who had preoperative PET/CT scans were enrolled to compare the differences of clinicopathological parameters between FDG-avid (F-PTC; n = 150) and non-FDG-avid tumors (FN-PTC; n = 38). Immunohistochemical staining for glucose transporter (GLUT)-1 and hypoxia-inducible factor-1 alpha (HIF-1α) was performed. RESULTS: FN-PTCs were smaller; had a lower incidence of lymphatic invasion, vascular invasion, multifocality, and central lymph node metastasis; and had a lower maximum standardized uptake value than F-PTCs. After exclusion of high-risk patients for recurrence, FN-PTCs remained smaller (p < 0.001) and had less lymphatic invasion (p = 0.061). Among tumors larger than the spatial resolution of the PET/CT scan, macrocalcification was more frequent in FN-PTC than in F-PTC (p = 0.043). While FN-PTC and F-PTC showed no difference in GLUT-1 expression (50% vs. 75%, p = 0.363), FN-PTC showed lower HIF-1α immunoreactivity than F-PTC (25.0% vs. 75.0%, p = 0.032). CONCLUSION: Tumor size and macrocalcification are clinicopathological differences between FN-PTC and F-PTC. Biologically, HIF-1α may be responsible for increased FDG uptake in PTC.

A Case with Multiple Punched-out Lesions in the Skull and Generalized Fractures Associated with Steroid-induced Osteoporosis.

Steroid-induced osteoporosis is the most common cause of secondary osteoporosis and accounts for one-fifth of all osteoporosis cases. The fracture incidence under steroid may be as high as 50%. However, many patients do not undergo appropriate risk assessment and treatment before and after steroid exposure. We described a 56-year-old male patient with multiple punched-out lesions in skull unusually as well as vertebral, fibular, rib and humeral fractures during steroid use without proper management.

Effects of a 6-Month Exenatide Therapy on HbA1c and Weight in Korean Patients with Type 2 Diabetes: A Retrospective Cohort Study.

BACKGROUND: While many studies have shown the good efficacy and safety of exenatide in patients with diabetes, limited information is available about exenatide in clinical practice in Korean populations. Therefore, this retrospective cohort study was designed to analyze the effects of exenatide on blood glucose level and body weight in Korean patients with type 2 diabetes mellitus. METHODS: We reviewed the records of the patients with diabetes who visited Seoul St. Mary's Hospital and for whom exenatide was prescribed from June 2009 to October 2011. After excluding subjects based on their race/ethnicity, medical history, whether or not they changed more than 2 kinds of oral hypoglycemic agents with exenatide treatment, loss to follow-up, or whether they stopped exenatide therapy within 6 months, a total of 52 subjects were included in the final analysis. RESULTS: The mean glycated hemoglobin (HbA1c) level and weight remarkably decreased from 8.5±1.7% to 6.7±1.0% (P<0.001) and from 82.3±15.8 kg to 78.6±16.3 kg (P<0.001), respectively. The multiple regression analysis indicated that the reduction in HbA1c level was significantly associated with a shorter duration of diabetes, a higher baseline HbA1c level, and greater weight reduction, whereas weight loss had no significant correlation with other factors. No severe adverse events were observed. CONCLUSION: These results suggest that a 6-month exenatide injection therapy significantly improved patients' HbA1c levels and body weights without causing serious adverse effects in Korean patients with type 2 diabetes.

Combination of initial stimulation thyroglobulins and staging system by revised ATA guidelines can elaborately discriminate prognosis of patients with differentiated thyroid carcinoma after high-dose remnant ablation.

PURPOSE: The aim of this study was to evaluate prognostic role of thyroglobulin (Tg) levels at the time of ablation (A-Tg) and stimulation Tg levels at 6-12 months after remnant ablation (S-Tg) combined with revised American Thyroid Association (ATA) guidelines risk stratification. PATIENTS AND METHODS: Data of 359 patients (median follow-up duration: 66.3 months) with papillary thyroid carcinoma who had high-dose remnant ablation were analyzed. The cutoff value of A-Tg to predict the persistent/recurrent disease was calculated by receiver operating characteristic curve analysis. In each risk group by ATA guidelines, the association of A-Tg with persistent/recurrent disease was evaluated. The role of A-Tg and ATA risk stratification in each S-Tg group (group with S-Tg <2 ng/mL, 2-10 ng/mL, or >10 ng/mL) was also evaluated. Tg response was determined by the difference between A-Tg and S-Tg with consideration of the dose of radioactive iodine ablation. RESULTS: A-Tg above 5.22 ng/mL was associated with persistent/recurrent disease in all risk groups by ATA guidelines. A-Tg above the cutoff value and ATA risk assessment was related to persistent/recurrent disease in patients with S-Tg 2 to 10 ng/mL (P = 0.003) and S-Tg above 10 ng/mL (P = 0.019). However, no difference in the incidence of persistent/recurrent disease was found according to Tg response. The scoring system made up of A-Tg, S-Tg, and ATA staging showed elaborate discrimination of prognosis. CONCLUSION: Risk stratification using combined scoring with initial stimulated Tg levels, including A-Tg and S-Tg, and staging system by revised ATA guidelines can effectively predict persistent/recurrent disease in patients with papillary thyroid carcinoma.

Role of [(18)F]-fluorodeoxy-D-glucose positron emission tomography and computed tomography in the early detection of persistent/recurrent thyroid carcinoma in intermediate-to-high risk patients following initial radioactive iodine ablation therapy.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) scan has a role in the surveillance of patients with a history of thyroid carcinoma. Its efficacy after remnant ablation as far as detecting persistent or recurrent thyroid carcinoma before other surveillance methods is not known, however. In intermediate-to-high risk thyroid carcinoma patients we studied whether PET/CT scan, performed 6-12 months after the first remnant ablation, could provide more information than ultrasonography (US) and thyrotropin-stimulated serum thyroglobulin (Tg) determination with diagnostic whole-body scan (DxWBS). METHODS: We studied 71 subjects with differentiated thyroid cancer (DTC) who were intermediate-to-high risk for persistent/recurrent disease and who had received PET/CT scan, US, and DxWBS simultaneously with stimulated Tg levels 6-12 months after remnant ablation. To evaluate the diagnostic efficacy of PET/CT scan, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. RESULTS: Ten subjects (14%) had persistent/recurrent disease detected 6-12 months after remnant ablation. Persistence/recurrence was detected in nine (12.7%) of these patients by conventional methods, including US and DxWBS, along with stimulated Tg levels. The remaining case was detected solely by a PET/CT scan, which showed a mediastinal prevascular lesion; this was confirmed by a therapeutic WBS after additional radioiodine therapy. Among the six patients whose PET/CT scan showed positive results, five had persistent/recurrent disease. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET/CT scan for detecting persistent/recurrent thyroid carcinoma were 50%, 98.4%, 83.3%, 92.3%, and 91.5%, respectively. CONCLUSION: In intermediate-to-high risk patients with DTC seen 6-12 months after their first remnant ablation, there is almost no complementary role for adding a PET/CT scan to conventional follow-up methods, an US and a DxWBS simultaneously with stimulated Tg levels.