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1. Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis

Author

In-Jin Cho, Ho-Yeon Chung, Sung-Woon Kim, Jae-Won Lee, Tae-Won Lee, Hye-Soon Kim, Sin-Gon Kim, Han Seok Choi, Sung-Hee Choi, Chan Soo Shin, Ki-Won Oh, Yong-Ki Min, Jung-Min Koh, Yumie Rhee, Dong-Won Byun, Yoon-Sok Chung, Jeong Hyun Park, Dong Jin Chung, Minho Shong, Eun-Gyoung Hong, Chang Beom Lee, Ki Hyun Baek, and Moo-Il Kang

Subjects
Ibandronate, Cholecalciferol, 25-hydroxyvitamin D, Bone markers, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

BackgroundThe present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis.MethodsThis was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period.ResultsAfter 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment.ConclusionThe present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

Published
2015
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3. Safety and Efficacy of Modern Insulin Analogues

Author

Hye Jin Yoo, Keun Yong Park, Kang Seo Park, Kyu Jeung Ahn, Kyung Wan Min, Jeong Hyun Park, Sang Ah Chang, Bong Soo Cha, Dong-Jun Kim, Yong Seong Kim, Tae Keun Oh, Suk Chon, Il Seong Nam-Goong, Mi Jin Kim, Hye-Soon Kim, Young Sik Choi, You Hern Ahn, Sora Lee, and Sei Hyun Baik

Subjects
Diabetes mellitus, type 2, Insulin, Republic of Korea, Safety, Treatment outcome, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

BackgroundA1chieve® was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart.MethodsKorean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints.ResultsOut of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7±15.9 to 72.5±13.5) while the mean body weight was slightly increased (0.6±3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%±2.2%, 2.5±4.7 mmol/L, and 4.0±6.4 mmol/L, respectively.ConclusionThe studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

Published
2013
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4. Relationship between Chemerin Levels and Cardiometabolic Parameters and Degree of Coronary Stenosis in Korean Patients with Coronary Artery Disease

Author

Yu-Jin Hah, Nam-Keong Kim, Mi-Kyung Kim, Hye-Soon Kim, Seung-Ho Hur, Hyuck-Jun Yoon, Yoon-Nyun Kim, and Keun-Gyu Park

Subjects
Chemerin, Coronary artery disease, Metabolic syndrome, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

BackgroundChemerin is a novel adipokine that is associated with inflammation and adipogenesis. However, it remains unclear whether chemerin is involved in patients with cardiovascular disease. We investigated whether the serum chemerin levels of Korean patients with coronary artery disease correlated with specific cardiometabolic parameters.MethodsIn total, 131 patients, all of whom had coronary artery stenosis exceeding 50%, participated in this study. Their serum chemerin levels and cardiometabolic parameters were measured. The serum chemerin levels of two groups of patients were compared; those with one stenotic vessel (n=68) and those with multiple stenotic vessels, including left main coronary artery disease (n=63).ResultsSerum chemerin levels correlated positively with the degree of coronary artery stenosis and fasting glucose, triglyceride, total cholesterol, low density lipoprotein cholesterol, and high sensitive C-reactive protein levels. The group with multiple stenotic vessels, including left main disease, had higher chemerin levels than the group with one stenotic vessel (t=-2.129, P=0.035). Multiple binary logistic regression showed chemerin was not an independent risk factor of multiple vessel disease (odds ratio, 1.018; confidence interval, 0.997 to 1.040; P=0.091).ConclusionSerum chemerin levels have a significant correlation with several cardiometabolic risk factors and the degree of coronary artery stenosis in Korean patients with coronary artery disease. However, multiple binary logistic regression showed chemerin was not an independent risk factor of multiple vessel disease. Additional investigations are necessary to fully elucidate the role of chemerin in cardiovascular disease.

Published
2011
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5. Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis.

Author

Gwon-Soo Jung, Jae-Han Jeon, Yun-A Jung, Yeon-Kyung Choi, Hye-Soon Kim, Jung-Guk Kim, Keun-Gyu Park, Mi-Kyung Kim, and In-Kyu Lee

Subjects
Medicine, Science
Abstract

The blockade of angiotensin II (Ang II) is a major therapeutic strategy for diabetic nephropathy. The main roles of Ang II in renal disease are mediated via the Ang type 1 receptor (AT1R). Upregulation of clusterin/apolipoprotein J has been reported in nephropathy models, suggesting it has a protective role in nephropathogenesis. Here, we studied how clusterin acts against Ang II-induced renal fibrosis. Levels of AT1R and fibrotic markers in clusterin-/- mice and Ang II infused rats transfected with an adenovirus encoding clusterin were evaluated by immunoblot analysis, real time RT-PCR, and immunohistochemical staining. The effect of clusterin on renal fibrosis was evaluated in NRK-52E cells, a cultured renal tubular epithelial cell line, using immunoblot analysis and real time RT-PCR. Nuclear localization of NF-κB was evaluated using immunofluorecence and co-immunoprecipitation. Renal fibrosis and expression of AT1R was higher in the kidneys of clusterin-/- mice than in those of wild-type mice. Furthermore, loss of clusterin accelerated Ang II-stimulated renal fibrosis and AT1R expression. Overexpression of clusterin in proximal tubular epithelial cells decreased the levels of Ang II-stimulated fibrotic markers and AT1R. Moreover, intrarenal delivery of clusterin attenuated Ang II-mediated expression of fibrotic markers and AT1R in rats. Fluorescence microscopy and co-immunoprecipitation in conjunction with western blot revealed that clusterin inhibited Ang II-stimulated nuclear localization of p-NF-κB via a direct physical interaction and subsequently decreased the AT1R level in proximal tubular epithelial cells. These data suggest that clusterin attenuates Ang II-induced renal fibrosis by inhibition of NF-κB activation and subsequent downregulation of AT1R. This study raises the possibility that clusterin could be used as a therapeutic target for Ang II-induced renal diseases.

Published
2014
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6. The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study

Author

Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, and Kyu Chang Won

Subjects
cardiovascular diseases, diabetes mellitus, type 2, drug therapy, combination, ezetimibe, rosuvastatin calcium, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM). Methods This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk

Published
2023
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7. High Sodium Intake, as Assessed by Urinary Sodium Excretion, Is Associated with Nonalcoholic Fatty Liver Disease or Sarcopenia

Author

Eugene Han, Mi Kyung Kim, Seung-Soon Im, Hye Soon Kim, Taeg Kyu Kwon, and Byoung Kuk Jang

Subjects
non-alcoholic fatty liver disease, sarcopenia, urinary sodium excretion, metabolic syndrome, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background/Aims: We explored whether high sodium intake, assessed by urinary excretion, determines the risk of sarcopenia and nonalcoholic fatty liver disease (NAFLD). Methods: We analyzed 10,036 adult participants with normal kidney function from the Korea National Health and Nutrition Examination Survey (2008–2011). NAFLD was identified using the fatty liver index, and the muscle mass was evaluated using dual X-ray absorptiometry. The dietary sodium intake was estimated using Tanaka’s equation. Results: The mean 24-hour urinary sodium excretion was 144.2±36.1 mmol/day (corresponding to 3.3 g/day Na) in the total population. The 24-hour urinary sodium excretion showed moderate accuracy in predicting NAFLD (area under the receiver operating characteristic, 0.702; 95% confidence interval [CI], 0.692 to 0.712). A cutoff value of 99.96 mmol/day (corresponding to 2.30 g/day Na) for urinary sodium excretion in predicting NAFLD showed 76.1% sensitivity and 56.1% specificity. The results of multiple adjusted models indicated that the participants with the highest urinary sodium excretion had a significantly higher risk of NAFLD (odds ratio, 1.46; 95% CI, 1.27 to 1.66; p

Published
2023
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8. Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis

Author

Seung Min Chung, Ji-In Lee, Eugene Han, Hyun-Ae Seo, Eonju Jeon, Hye Soon Kim, and Ji Sung Yoon

Subjects
diabetes mellitus, costs and cost analysis, cardiovascular diseases, mortality, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death. Methods This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]–4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed. Results A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321). Conclusion Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.

Published
2022
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9. Improvement in Age at Mortality and Changes in Causes of Death in the Population with Diabetes: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018

Author

Eugene Han, Sun Ok Song, Hye Soon Kim, Kang Ju Son, Sun Ha Jee, Bong-Soo Cha, and Byung-Wan Lee

Subjects
mortality, diabetes mellitus, cardiovascular diseases, neoplasms, epidemiology, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background Diabetes is a leading cause of death that is responsible for 1.6 million annual deaths worldwide. However, the life expectancy and age at death of people with diabetes have been a matter of debate. Methods The National Health Insurance Service claims database, merged with death records from the National Statistical Information Service in Korea from 2006 to 2018, was analyzed. Results In total, 1,432,567 deaths were collected. The overall age at death increased by 0.44 and 0.26 year/year in the diabetes and control populations, respectively. The disparity in the mean age at death between the diabetes and control populations narrowed from 5.2 years in 2006 to 3.0 years in 2018 (P

Published
2022
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10. Cardiovascular Risk Is Elevated in Lean Subjects with Nonalcoholic Fatty Liver Disease

Author

Yuna Kim, Eugene Han, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Mi Kyung Kim, Hye Soon Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Yong-ho Lee, and Seung Up Kim

Subjects
nonalcoholic fatty liver disease, lean, liver fibrosis, fatty liver, cardiovascular risk, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear. Methods: Data from the 2008 to 2011 Korea National Health and Nutrition Examination Surveys database were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥-0.640. ASCVD risk was evaluated using the American College of Cardiology/ American Heart Association guidelines. Results: The frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p

Published
2022
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11. Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease

Author

Eugene Han, Mi Kyung Kim, Byoung Kuk Jang, and Hye Soon Kim

Subjects
albuminuria, diabetes mellitus, type 2, non-alcoholic fatty liver disease, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background This study aimed to investigate the association between hepatic steatosis burden and albuminuria in Korean patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods We recruited 100 patients with both T2DM and NAFLD, but without chronic kidney disease. Albuminuria was defined as a spot urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. Transient elastography was performed, and the steatosis burden was quantified by controlled attenuation parameter (CAP) with significant steatosis defined as CAP >302 dB/m. Results The prevalence of significant steatosis and albuminuria was 56.0% and 21.0%, respectively. Subjects with significant steatosis were significantly younger and had a significantly shorter duration of T2DM, greater waist circumference, and higher body mass index, total cholesterol, triglyceride, and low density lipoprotein cholesterol levels, than subjects without severe NAFLD (all P

Published
2021
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12. Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

Author

Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Kim, Hye Soon Kim, Il Seong Nam-Goong, Eun Sook Kim, Jin Ook Chung, Dong-Hyeok Cho, Chang Won Lee, Young Il Kim, Dong Jin Chung, Kyu Chang Won, In Joo Kim, Tae Sun Park, Duk Kyu Kim, and Hosang Shon

Subjects
diabetes mellitus, type 2, drug therapy, combination, hypoglycemic agents, injections, insulin, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P

Published
2021
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13. Cushing syndrome in pregnancy, diagnosed after delivery

Author

Han Byul Kim, Mi Kyung Kim, El Kim, Keun Soo Ahn, Hye Soon Kim, and Nam Kyung Kim

Subjects
complication, cushing syndrome, hypercortisolism, pregnancy, Medicine (General), R5-920
Abstract

Cushing syndrome (CS) is rare in pregnancy, and few cases have been reported to date. Women with untreated CS rarely become pregnant because of the ovulatory dysfunction induced by hypercortisolism. It is difficult to diagnose CS in pregnancy because of its very low incidence, the overlap between the clinical signs of hypercortisolism and the physiological changes that occur during pregnancy and the changes in hypothalamus-pituitary-adrenal axis activity that occur during pregnancy and limit the value of standard diagnostic testing. However, CS in pregnancy is associated with poor maternal and fetal outcomes; therefore, its early diagnosis and treatment are important. Here, we report two patients with CS that was not diagnosed during pregnancy, in whom maternal and fetal morbidity developed because of hypercortisolism.

Published
2021
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14. Can a semi-quantitative method replace the current quantitative method for the annual screening of microalbuminuria in patients with diabetes? Diagnostic accuracy and cost-saving analysis considering the potential health burden.

Author

Yaerim Kim, Seokwoo Park, Myung-Hee Kim, Sang Hoon Song, Won Mok Lee, Hye Soon Kim, Kyubok Jin, Seungyeup Han, Yong Chul Kim, Seung Seok Han, Hajeong Lee, Jung Pyo Lee, Kwon Wook Joo, Chun Soo Lim, Yon Su Kim, and Dong Ki Kim

Subjects
Medicine, Science
Abstract

OBJECTIVES:Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We aimed to determine whether a semi-quantitative urinary albumin-creatinine ratio test could be used as a screening tool for microalbuminuria in diabetic patients. METHODS:We assessed the diagnostic accuracy of the semi-quantitative method. The costs of false results in the semi-quantitative method were calculated based on the annual probability of disease progression analyzed through a systematic literature review and meta-analysis. The pooled long-term cost-saving effect of the semi-quantitative method compared with the quantitative test was assessed using a Markov model simulating a long-term clinical setting. Diagnostic accuracy and the cost-saving effect were also validated in an independent external cohort. RESULTS:Compared with the quantitative test, the semi-quantitative method had sensitivities of 93.5% and 81.3% and specificities of 61.4% and 63.1% in the overall sample of diabetic patients (n = 1,881) and in diabetic patients with eGFR ≥60 ml/min/1.73 m2 and a negative dipstick test (n = 1,110), respectively. After adjusting for direct and indirect medical costs, including the risk of disease progression, which was adjusted by the meta-analyzed hazard ratio for clinical outcomes, it was determined that using the semi-quantitative method could save 439.4 USD per person for 10 years. Even after adjusting the result to the external validation cohort, 339.6 USD could be saved for one diabetic patient for 10 years. CONCLUSIONS:The semi-quantitative method could be an appropriate screening tool for albuminuria in diabetic patients. Moreover, it can minimize the testing time and inconvenience and significantly reduce national health costs.

Published
2020
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16. Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease

Author

Hye Soon Kim, Byoung Kuk Jang, Mi-Kyung Kim, and Eugene Han

Subjects
medicine.medical_specialty, Complications, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Gastroenterology, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Nonalcoholic fatty liver disease, medicine, Albuminuria, business.industry, Diabetes mellitus, type 2, Odds ratio, RC648-665, medicine.disease, Original Article, medicine.symptom, Steatosis, Transient elastography, business, Body mass index, Non-alcoholic fatty liver disease, Kidney disease
Abstract

Background: This study aimed to investigate the association between hepatic steatosis burden and albuminuria in Korean patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).Methods: We recruited 100 patients with both T2DM and NAFLD, but without chronic kidney disease. Albuminuria was defined as a spot urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. Transient elastography was performed, and the steatosis burden was quantified by controlled attenuation parameter (CAP) with significant steatosis defined as CAP >302 dB/m.Results: The prevalence of significant steatosis and albuminuria was 56.0% and 21.0%, respectively. Subjects with significant steatosis were significantly younger and had a significantly shorter duration of T2DM, greater waist circumference, and higher body mass index, total cholesterol, triglyceride, and low density lipoprotein cholesterol levels, than subjects without severe NAFLD (all P

Published
2021

17. Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

Author

Dong Jin Chung, Young Sang Lyu, Tae Sun Park, In Joo Kim, Jun Sung Moon, Young Il Kim, Heung Yong Jin, Eonju Jeon, Ju Hyung Lee, Eun Sook Kim, Seung Min Chung, Sang Soo Kim, Sung Woo Kim, Jung Eun Jang, Tae Nyun Kim, Jin Ook Chung, Nan Hee Cho, Sunghwan Suh, Kyu Chang Won, Chang Won Lee, Duk Kyu Kim, Hye Soon Kim, Jeong Mi Kim, Hosang Shon, Min Hee Jang, Sang Yong Kim, Il Seong Nam-Goong, Dong Hyeok Cho, Kyung Ae Lee, Jin Hwa Kim, and Mi-Kyung Kim

Subjects
Blood Glucose, Drug, medicine.medical_specialty, Combination therapy, Drug/Regimen, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, medicine.medical_treatment, Drug therapy, combination, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Diseases of the endocrine glands. Clinical endocrinology, Injections, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, medicine, Insulin, Humans, Hypoglycemic Agents, Retrospective Studies, media_common, Glycated Hemoglobin, business.industry, Type 2 Diabetes Mellitus, Retrospective cohort study, RC648-665, medicine.disease, Regimen, Diabetes Mellitus, Type 2, Oral hypoglycemic agents, Original Article, business
Abstract

Background Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P

Published
2021

18. Muscle fat contents rather than muscle mass determines nonalcoholic steatohepatitis and liver fibrosis in patients with severe obesity

Author

Eugene Han, Mi Kyung Kim, Hye Won Lee, Seungwan Ryu, Hye Soon Kim, Byoung Kuk Jang, and Youngsung Suh

Subjects
Liver Cirrhosis, Nutrition and Dietetics, Endocrinology, Non-alcoholic Fatty Liver Disease, Endocrinology, Diabetes and Metabolism, Muscles, Medicine (miscellaneous), Humans, Obesity, Morbid
Abstract

This study aimed to investigate the association of muscle fat contents, nonalcoholic steatohepatitis (NASH), and liver fibrosis in patients with severe obesity.Patients with severe obesity who underwent bariatric surgery were evaluated for NASH and liver fibrosis. Skeletal muscle was assessed by dual energy x-ray absorptiometry, and muscle fat contents (skeletal muscle fat index [SMFI]) were evaluated by computed tomography-based psoas muscle mass and density.A total of 104 patients with severe obesity were enrolled (57 with nonalcoholic fatty liver disease activity score5 and 47 with NASH with nonalcoholic fatty liver disease activity score ≥5). SMFI was higher in patients with NASH than those without NASH (mean [SD], 39.0 [14.5] vs. 46.5 [14.2] for without NASH vs. with NASH; p = 0.009). SMFI was also correlated with hepatic steatosis grade, ballooning severity, and fibrosis stage. Multiple logistic regression analysis showed that SMFI was associated with higher risk of NASH and liver fibrosis (odds ratio = 2.37, 95% CI: 1.13-4.98, p = 0.022 for NASH; odds ratio = 2.93, 95% CI: 1.32-6.48, p = 0.008 for significant liver fibrosis).Muscle fat infiltration rather than muscle mass reflects the severities of hepatic steatosis and fibrosis in patients with severe obesity.

Published
2022

20. Non-alcoholic fatty liver disease and sarcopenia is associated with the risk of albuminuria independent of insulin resistance, and obesity

Author

Eugene Han, Mi Kyung Kim, Seung-Soon Im, Byoung Kuk Jang, and Hye Soon Kim

Subjects
Sarcopenia, Endocrinology, Non-alcoholic Fatty Liver Disease, Risk Factors, Endocrinology, Diabetes and Metabolism, Hypertension, Internal Medicine, Albuminuria, Humans, Obesity, Insulin Resistance
Abstract

Although non-alcoholic fatty liver disease (NAFLD) is associated with metabolic disorders, its influence on albuminuria has not been determined. The aim of this study was to identify the relationship between NAFLD and albuminuria in the general Korean population.Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) of 2008-2011 were analyzed (n = 1795). Albuminuria was defined as an albumin-to-creatinine ratio of ≥30 mg/g in random spot urine samples. NAFLD was defined as a fatty liver index (FLI) ≥60 or NAFLD liver fat score (LFS) -0.64.A total of 289 (16.1 %) subjects were classified as having albuminuria. Subjects with NAFLD exhibited a higher rate of albuminuria than subjects without NAFLD (crude odds ratios [ORs] = 2.60-2.95, all P 0.001). Regardless of hypertension, insulin resistance, or obesity, the risk for albuminuria was higher in the NAFLD group than in the group without NAFLD (measured by either FLI or LFS; all P 0.001). When subjects with NAFLD had sarcopenia, the risk of albuminuria further increased (OR = 4.33-4.64, all P 0.001). Multiple logistic regression analyses also demonstrated that NAFLD was independently associated with albuminuria (OR = 2.58, 95 % confidence interval [CI] = 1.66-4.02, P 0.001 for FLI, OR = 1.87, 95 % CI = 1.28-2.75, P = 0.001 for LFS).NAFLD was associated with an increased risk of albuminuria in the general Korean population. This association was independent of hypertension, insulin resistance, chronic kidney disease, diabetes and obesity, and stronger in subjects with sarcopenia.

Published
2022

21. High Sodium Intake, as Assessed by Urinary Sodium Excretion, Is Associated with Nonalcoholic Fatty Liver Disease or Sarcopenia

Author

Eugene Han, Mi Kyung Kim, Seung-Soon Im, Hye Soon Kim, Taeg Kyu Kwon, and Byoung Kuk Jang

Subjects
Hepatology, Gastroenterology
Abstract

We explored whether high sodium intake, assessed by urinary excretion, determines the risk of sarcopenia and nonalcoholic fatty liver disease (NAFLD).We analyzed 10,036 adult participants with normal kidney function from the Korea National Health and Nutrition Examination Survey (2008-2011). NAFLD was identified using the fatty liver index, and the muscle mass was evaluated using dual X-ray absorptiometry. The dietary sodium intake was estimated using Tanaka's equation.The mean 24-hour urinary sodium excretion was 144.2±36.1 mmol/day (corresponding to 3.3 g/day Na) in the total population. The 24-hour urinary sodium excretion showed moderate accuracy in predicting NAFLD (area under the receiver operating characteristic, 0.702; 95% confidence interval [CI], 0.692 to 0.712). A cutoff value of 99.96 mmol/day (corresponding to 2.30 g/day Na) for urinary sodium excretion in predicting NAFLD showed 76.1% sensitivity and 56.1% specificity. The results of multiple adjusted models indicated that the participants with the highest urinary sodium excretion had a significantly higher risk of NAFLD (odds ratio, 1.46; 95% CI, 1.27 to 1.66; p0.001) and sarcopenia (odds ratio, 1.49; 95% CI, 1.28 to 1.73; p0.001) than those with the lowest urinary sodium excretion. The association between a higher 24-hour urinary sodium excretion and NAFLD was independent of sarcopenia.Participants with a high sodium intake, as assessed by sodium excretion, had a substantial risk of NAFLD and sarcopenia.

Published
2022

23. Effect of Switching from Linagliptin to Teneligliptin Dipeptidyl Peptidase-4 Inhibitors in Older Patients with Type 2 Diabetes Mellitus

Author

Hye Soon Kim, Bong Soo Cha, Eugene Han, Min Young Lee, Eun Seok Kang, Yong Ho Lee, and Byung Wan Lee

Subjects
Pharmacology, medicine.medical_specialty, business.industry, Urology, 030209 endocrinology & metabolism, Dipeptidyl peptidase-4 inhibitor, Type 2 diabetes, 030204 cardiovascular system & hematology, medicine.disease, Linagliptin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Postprandial, chemistry, Internal Medicine, medicine, Glycated hemoglobin, Teneligliptin, business, Dipeptidyl peptidase-4, medicine.drug, Glycemic
Abstract

Introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely prescribed for type 2 diabetes (T2D) and their glycemic control effects are well studied. However, information regarding the effects of switching DPP-4 inhibitors is limited, especially in older patients. Research Design and Methods We investigated whether switching from linagliptin to teneligliptin decreases blood glucose in older (≥65 years) T2D patients. In total, 164 patients with T2D who switched from linagliptin to teneligliptin for >12 weeks were included and the primary outcome was glycemic changes. Results Switching from linagliptin to teneligliptin ameliorated fasting blood glucose (148.1 ± 47.1 to 139.6 ± 43.4 mg/dL), glycated hemoglobin (HbA1c; 7.9 ± 1.3 to 7.5 ± 1.2%), and postprandial blood glucose (224.8 ± 77.4 to 205.8 ± 70.8 mg/dL) levels (all P 8.0%) and chronic kidney disease (estimated glomerular filtration rate

Published
2020

25. Cushing syndrome in pregnancy, diagnosed after delivery

Author

Nam Kyung Kim, Mi-Kyung Kim, Hye Soon Kim, Keun Soo Ahn, El Kim, and Han Byul Kim

Subjects
lcsh:R5-920, medicine.medical_specialty, Pregnancy, Fetus, Obstetrics, business.industry, Incidence (epidemiology), Hypercortisolism, Diagnostic test, Case Report, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, Cushing syndrome, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, lcsh:Medicine (General), Complication, business
Abstract

Cushing syndrome (CS) is rare in pregnancy, and few cases have been reported to date. Women with untreated CS rarely become pregnant because of the ovulatory dysfunction induced by hy percortisolism. It is difficult to diagnose CS in pregnancy because of its very low incidence, the overlap between the clinical signs of hypercortisolism and the physiological changes that occur during pregnancy and the changes in hypothalamus-pituitary-adrenal axis activity that occur during pregnancy and limit the value of standard diagnostic testing. However, CS in pregnancy is associated with poor maternal and fetal outcomes; therefore, its early diagnosis and treatment are important. Here, we report two patients with CS that was not diagnosed during pregnancy, in whom maternal and fetal morbidity developed because of hypercortisolism.

Published
2020

26. Association Between the Diabetes Drug Cost and Cardiovascular Events for Type 2 Diabetes in Korea: A National Health Insurance Service Database Analysis

Author

Seung Min Chung, Ji-In Lee, Eugene Han, Hyun-Ae Seo, Eonju Jeon, Hye Soon Kim, and JiSung Yoon

Abstract

Background: We aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death. Methods: This retrospective observational study used the 2009–2018 National Health Insurance data in Korea. Among patients with type 2 diabetes, those who were taking antidiabetic drugs and did not have CV events before 2009 were included. Data on the annual cost of each diabetes drug were collected. The 10-year incidence of CV events (cardiac death, non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death were analyzed according to the diabetes drug cost quartiles (Q1 [the lowest] – Q4 [the highest]).Results: A total of 441,914 participants were enrolled (median age, 60 years; male, 57%). CV events and death occurred in 28.1% and 8.36% of patients, respectively. The overall diabetes drug cost was USD 271/year per person (range: 1–18,921). The 10-year incidence of CV events and death was lowest in Q3 and high in Q4 and Q1. After adjusting for CV risk factors, the risk of CV events increased in the sequential order of cost quartiles (hazard ratio (HR)=1 [ref], 1.102 [95% confidence interval (CI): 1.084–1.120], 1.137 [95% CI: 1.118–1.156], and 1.323 [95% CI: 1.3011.346]). The risk of CV death showed U-shaped pattern which was lowest in the Q3 (HR=0.943, 95% CI 0.903-0.984) and highest in the Q4 (HR= 1.234, 95% CI 1.182-1.287).Conclusion: The expenditure for diabetes drug affects 10-year CV events and death. Affording an appropriate diabetes cost at a similar CV risk is an independent protective factor for CV death.Trial registration: retrospectively registered

Published
2021

27. Real-World Analysis of Rapid-Acting Insulin Analog Use and Its Blood Glucose Lowering Effect in Patients with Type 2 Diabetes Mellitus: Results from PASSION Disease Registry in Korea

Author

Hye Soon Kim, Jae Myung Yu, Hak Chul Jang, Eui Kwang Choi, Jeong Hyun Park, Ho Sang Shon, Choon Hee Chung, Keun-Gyu Park, Jae Hyoung Cho, Won Kim, Kyoung Hwa Lee, Jee Hyun Lee, and Soon Jib Yoo

Subjects
Pharmacology, Internal Medicine, Targets and Therapy [Diabetes, Metabolic Syndrome and Obesity]
Abstract

Hye Soon Kim,1 Jae Myung Yu,2 Hak Chul Jang,3 Eui Kwang Choi,4 Jeong Hyun Park,5 Ho Sang Shon,6 Choon Hee Chung,7 Keun-Gyu Park,8 Jae Hyoung Cho,9 Won Kim,10 Kyoung Hwa Lee,10 Jee Hyun Lee,10 Soon Jib Yoo11 1Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea; 2Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 4Department of Internal Medicine, Naedang Dr. Choi’s Clinic, Seoul, Republic of Korea; 5Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; 6Department of Internal Medicine, Catholic University of Daegu, School of Medicine, Daegu, Republic of Korea; 7Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea; 8Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea; 9Department of Endocrinology and Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 10Medical Department Sanofi-Aventis Korea, Seoul, Republic of Korea; 11Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of KoreaCorrespondence: Soon Jib Yoo, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, 14647, Republic of Korea, Tel +82-32-340-7011, Fax +82-32-340-2039, Email sjyoomt@gmail.comPurpose: Although rapid-acting insulins (RAIs) are used frequently in Korean clinical settings, evidence on their use is limited. This study explores the pattern and clinical effectiveness of the use of RAIs in Korean patients with type 2 diabetes mellitus (T2DM).Patients and Methods: This non-interventional, observational study enrolled patients (aged > 18 years) with T2DM who were prescribed RAIs. The pattern of use and effectiveness of RAI analogs were evaluated over 6 months.Results: A total of 299/451 patients were analyzed. Approximately 90% (n/N=270/299) of the patients received insulin glulisine, which significantly reduced their levels of glycated hemoglobin (HbA1c: n=270, mean± standard deviation [SD]; − 1.16± 6.02%, p=0.0017), fasting plasma glucose (n=40; mean±SD: − 54.9± 90.89 mg/dl, p=0.0005), and post prandial blood glucose (n=35, mean±SD: − 89.46± 105.68 mg/dl, p< 0.0001) at 6 months, with a corresponding increase in body weight (BW) (n=197, mean±SD:1.45± 3.64 kg, p< 0.0001). At 6 months, more patients receiving an intensive regimen (basal insulin+≥ 2 RAI injections/day) had HbA1c < 7% than those receiving a non-intensive regimen (basal insulin+1 RAI injection/day) (20.69% vs 7.46%; p=0.0333); the corresponding reduction in HbA1c was also higher in patients receiving the intensive regimen (p< 0.0001). About one-fourth patients (n/N=22/95) were switched to the intensive regimen (from 1 to ≥ 2 RAI injections/day), and only 4.41% (n/N=9/204) of the patients were switched to 1 RAI injection/day. The patients receiving the intensive regimen showed higher levels of HbA1c reductions (mean±SD: − 1.27± 1.96%) compared with the maintenance group-1 RAI injection/day (mean±SD: − 0.72± 1.66%) (p=0.0459), without a significant increase in BW and body mass index.Conclusion: The insulin glulisine intensification regimen showed glycemic target achievement and can be considered a therapeutic tool in the management of T2DM patients.Keywords: glycated hemoglobin, insulin glulisine, intensification, RAI analogs

Published
2021

28. Obesity Degree and Glycemic Status: Factors That Should Be Considered in Heart Failure

Author

Hye Soon Kim

Subjects
medicine.medical_specialty, lcsh:RC648-665, business.industry, Endocrinology, Diabetes and Metabolism, MEDLINE, medicine.disease, Obesity, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Degree (temperature), Editorial, Heart failure, Internal medicine, Diabetes mellitus, Medicine, business, Glycemic
Published
2020

29. Contemporaneity of the Uncontemporary in Korean Immigration Regime and a Proposal of an Immigration-Sensitive Approach

Author

Hye-Soon Kim

Subjects
media_common.quotation_subject, Immigration, Sociology, Genealogy, media_common
Abstract

이 논문은 이민현상의 행위자인 이민자, 내국인, 여론 및 정책입안자가 반영하는 시대적 준거가 다르다는, 비동시성의 동시성에 주목한다. 선발이민국의 경험을 통해 이민시대는 ‘전통이민’, ‘세계화 이민’, 2010년대 들어 구체화된 ‘포스트세계화이민’으로 구분하고, 각 시대 별 이민정책과 동향을 개괄하면서 국가, 국제이주자, 대중(내국인)이 각 시대의 주요 행위자로 부상했음을 보인다. 국내 이민현상의 경우, 여론 및 정책주도층은 전통이민의 논리로 세계화시대 국제이주자를 수용하여 전통이민적인 이민자구성을 야기한 반면, 포스트세계화이민의 징후를 보이는 내국인의 이민정서를 전통이민 시대적이라 평가하는 것으로 분석했다. 여론 및 정책주도층의 시대착오적이고 자가당착적 지향은 이민현상과 관련 한국사회의 특성에 대한 피상적 이해 때문이라 보고 하나의 대안으로 이민관점의 적용을 제안한다.

Published
2019

30. Cardiovascular Risk is Elevated in Lean Subjects With Non Alcoholic Fatty Liver Disease

Author

Yuna Kim, Eugene Han, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Mi Kyung Kim, Hye Soon Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Yong-ho Lee, and Seung Up Kim

Subjects
nutritional and metabolic diseases, digestive system, digestive system diseases
Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) and obesity are independently associated with increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear.MethodsData from the 2008–2011 Korean National Health and Nutrition Examination Surveys database were analysed (n = 4,786). NAFLD was defined as a comprehensive NAFLD score of ≥40 or a liver fat score of ≥–0.640. ASCVD risk was evaluated using the American College of Cardiology/American Heart Association guidelines. A high probability of ASCVD was defined as an ASCVD risk of >10%.ResultsThe frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n = 2,987), 26.6% (n = 1,274), and 11.0% (n = 525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6 ± 14.0 and 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2 ± 11.4 and 39.8%; 7.9 ± 10.9 and 25.5%, all P < 0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio = 2.60 vs. 1.93; P = 0.023).ConclusionsDespite a more favourable metabolic profile, subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high ASCVD risk than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.

Published
2020

31. Effect of Switching from Linagliptin to Teneligliptin Dipeptidyl Peptidase-4 Inhibitors in Older Patients with Type 2 Diabetes Mellitus

Author

Eugene, Han, Minyoung, Lee, Yong-Ho, Lee, Hye Soon, Kim, Byung-Wan, Lee, Bong-Soo, Cha, and Eun Seok, Kang

Subjects
linagliptin, endocrine system diseases, type 2 diabetes mellitus, dipeptidyl peptidase 4 inhibitor, teneligliptin, older patients, chronic kidney disease, Original Research
Abstract

Introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely prescribed for type 2 diabetes (T2D) and their glycemic control effects are well studied. However, information regarding the effects of switching DPP-4 inhibitors is limited, especially in older patients. Research Design and Methods We investigated whether switching from linagliptin to teneligliptin decreases blood glucose in older (≥65 years) T2D patients. In total, 164 patients with T2D who switched from linagliptin to teneligliptin for >12 weeks were included and the primary outcome was glycemic changes. Results Switching from linagliptin to teneligliptin ameliorated fasting blood glucose (148.1 ± 47.1 to 139.6 ± 43.4 mg/dL), glycated hemoglobin (HbA1c; 7.9 ± 1.3 to 7.5 ± 1.2%), and postprandial blood glucose (224.8 ± 77.4 to 205.8 ± 70.8 mg/dL) levels (all P < 0.05). Low-density lipoprotein cholesterol concentration was reduced while liver and kidney functions were maintained. Subgroup analysis showed that glucose control improved more in patients with uncontrolled hyperglycemia (HbA1c > 8.0%) and chronic kidney disease (estimated glomerular filtration rate

Published
2020

33. Can a semi-quantitative method replace the current quantitative method for the annual screening of microalbuminuria in patients with diabetes? Diagnostic accuracy and cost-saving analysis considering the potential health burden

Author

Kwon Wook Joo, Seokwoo Park, Seungyeup Han, Jung Pyo Lee, Hye Soon Kim, Seung Seok Han, Myung Hee Kim, Dong Ki Kim, Yong Chul Kim, Sang Hoon Song, Yon Su Kim, Yaerim Kim, Chun Soo Lim, Hajeong Lee, Won Mok Lee, and Kyubok Jin

Subjects
Physiology, Economics, 030232 urology & nephrology, Social Sciences, Urine, Cardiovascular Medicine, Biochemistry, Cohort Studies, 0302 clinical medicine, Endocrinology, Mathematical and Statistical Techniques, Chronic Kidney Disease, Medicine and Health Sciences, Mass Screening, Diabetic Nephropathies, 030212 general & internal medicine, health care economics and organizations, Multidisciplinary, Hazard ratio, Statistics, Metaanalysis, Body Fluids, Nephrology, Cardiovascular Diseases, Meta-analysis, Creatinine, Cohort, Physical Sciences, Medicine, medicine.symptom, Anatomy, Cohort study, Research Article, medicine.medical_specialty, Endocrine Disorders, Science, Urinalysis, Research and Analysis Methods, 03 medical and health sciences, Health Economics, Cost Savings, Diabetes mellitus, Albumins, Republic of Korea, medicine, Diabetes Mellitus, Albuminuria, Humans, Statistical Methods, business.industry, Biology and Life Sciences, Proteins, Reproducibility of Results, medicine.disease, Annual Screening, Health Care, Metabolic Disorders, Emergency medicine, Microalbuminuria, business, Biomarkers, Mathematics
Abstract

Objectives Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We aimed to determine whether a semi-quantitative urinary albumin-creatinine ratio test could be used as a screening tool for microalbuminuria in diabetic patients. Methods We assessed the diagnostic accuracy of the semi-quantitative method. The costs of false results in the semi-quantitative method were calculated based on the annual probability of disease progression analyzed through a systematic literature review and meta-analysis. The pooled long-term cost-saving effect of the semi-quantitative method compared with the quantitative test was assessed using a Markov model simulating a long-term clinical setting. Diagnostic accuracy and the cost-saving effect were also validated in an independent external cohort. Results Compared with the quantitative test, the semi-quantitative method had sensitivities of 93.5% and 81.3% and specificities of 61.4% and 63.1% in the overall sample of diabetic patients (n = 1,881) and in diabetic patients with eGFR ≥60 ml/min/1.73 m2 and a negative dipstick test (n = 1,110), respectively. After adjusting for direct and indirect medical costs, including the risk of disease progression, which was adjusted by the meta-analyzed hazard ratio for clinical outcomes, it was determined that using the semi-quantitative method could save 439.4 USD per person for 10 years. Even after adjusting the result to the external validation cohort, 339.6 USD could be saved for one diabetic patient for 10 years. Conclusions The semi-quantitative method could be an appropriate screening tool for albuminuria in diabetic patients. Moreover, it can minimize the testing time and inconvenience and significantly reduce national health costs.

Published
2020

34. Manifestations of Sasang Typology according to Common Chronic Diseases in Koreans

Author

So Jin Shin, Seung Wan Hong, Il Do Ha, Hye Soon Kim, Jae Seok Hwang, Sung Won Jung, Young Kyu Kwon, Dae Hyun Kim, Mi-Kyung Kim, Young Sung Suh, Kyung Sik Park, and Chi Heum Cho

Subjects
medicine.medical_specialty, Article Subject, business.industry, Outcome measures, lcsh:Other systems of medicine, Medical classification, lcsh:RZ201-999, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Complementary and alternative medicine, Sasang constitution, Internal medicine, Diabetes mellitus, medicine, Major depressive disorder, In patient, Adenomyosis, 030212 general & internal medicine, business, Body mass index, 030217 neurology & neurosurgery
Abstract

Sasang typology is a traditional Korean medical classification scheme that combines medical management with general medicine and can be applied to chronic diseases. We aimed to analyze differences in Sasang Personality Questionnaire (SPQ) and Sasang Digestive Function Inventory (SDFI) results in patients with diabetes mellitus (DM), hypertension, functional dyspepsia, major depressive disorder (MDD), and adenomyosis. In this cross-sectional study, data were collected at a medical college hospital in South Korea. A total of 248 patients were included: 52 with DM, 47 with hypertension, 36 with functional dyspepsia, 26 with MDD, and 87 with adenomyosis. The subjects took both the SPQ and the SDFI. The outcome measures in this study were body mass index (BMI), SPQ score, and SDFI score. The DM and hypertension groups, which were expected to demonstrate many Taeeum-type traits, exhibited high BMI, high SPQ-Behavior and SDFI-Appetite scores, and low SPQ-Emotionality and SDFI-Digestion scores. The functional dyspepsia group showed low BMI and high scores for SPQ-Behavior, SPQ-Emotionality, SDFI-Digestion, and SDFI-Appetite. The MDD group demonstrated high SPQ-Emotionality and SDFI-Digestion scores, low BMI, and low SPQ-Behavior and SDFI-Appetite scores. The adenomyosis group demonstrated high scores for SPQ-Behavior, SDFI-Digestion, and SDFI-Appetite, low BMI, and low SPQ-Emotionality scores. Different characteristics distinguishing Sasang traits according to chronic diseases were ascertained, especially for Taeeum and Soeum types.

Published
2018

35. Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active-controlled, randomized, double-blind study with open-label extension (the EVERGREEN study)

Author

Moon-Kyu Lee, Mi-Kyung Kim, Eun Sook Kim, Gyuri Kim, Soo Lim, Kyu Jeung Ahn, Hye Soon Kim, Ie Byung Park, Sin Gon Kim, Min Kyong Moon, Chang Beom Lee, Tae Ho Kim, Seok Won Park, Hyuk-Sang Kwon, Kang Seo Park, Su Kyoung Kwon, Choon Hee Chung, Dong Jin Chung, and Cheol-Young Park

Subjects
Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Linagliptin, Type 2 diabetes, continuous glucose monitoringdipeptidyl peptidase‐4 inhibitorevogliptinglycaemic variabilitylinagliptintype 2 diabetes, Piperazines, Double blind study, Endocrinology, Double-Blind Method, Internal medicine, Evogliptin, Internal Medicine, medicine, Humans, Hypoglycemic Agents, In patient, Adverse effect, Glycated Hemoglobin, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Incidence (epidemiology), Blood Glucose Self-Monitoring, Original Articles, medicine.disease, Treatment Outcome, Diabetes Mellitus, Type 2, Original Article, Drug Therapy, Combination, Open label, business, medicine.drug
Abstract

Aim To investigate the efficacy and safety of evogliptin compared with linagliptin in patients with type 2 diabetes. Materials and Methods In this 12‐week, multicentre, randomized, double‐blind, active‐controlled, and 12‐week open‐label extension study, a total of 207 patients with type 2 diabetes who had HbA1c levels of 7.0%‐10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycaemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92). Results After 12 weeks of treatment, the mean change in HbA1c in the evogliptin group and in the linagliptin group was −0.85% and −0.75%, respectively. The between‐group difference was −0.10% (95% CI: −0.32 to 0.11), showing non‐inferiority based on a non‐inferiority margin of 0.4%. The change in MAGE was −24.6 mg/dL in the evogliptin group and −16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by −0.94%, with HbA1c values of

Published
2019

36. Patient Understanding of Hypoglycemia in Tertiary Referral Centers

Author

Mi Hae Seo, Hyun Ae Seo, Nam Kyung Kim, Eon Ju Jeon, Eugene Han, Hye Soon Kim, Jun Hwa Hong, Ji Eun Lee, Mi-Kyung Kim, Jun Sung Moon, and Nan Hee Cho

Subjects
Pediatrics, medicine.medical_specialty, Referral, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, media_common.quotation_subject, 030209 endocrinology & metabolism, Hypoglycemia, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Education, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Personal history, Medicine, Insulin, 030212 general & internal medicine, Clinical Care/Education, media_common, lcsh:RC648-665, business.industry, Diabetes, nutritional and metabolic diseases, medicine.disease, INSULIN USE, Emergency medicine, Original Article, Worry, business, Complication
Abstract

BACKGROUND Hypoglycemia is an important complication in the treatment of patients with diabetes. We surveyed the insight by patients with diabetes into hypoglycemia, their hypoglycemia avoidance behavior, and their level of worry regarding hypoglycemia. METHODS A survey of patients with diabetes, who had visited seven tertiary referral centers in Daegu or Gyeongsangbuk-do, Korea, between June 2014 and June 2015, was conducted. The survey contained questions about personal history, symptoms, educational experience, self-management, and attitudes about hypoglycemia. RESULTS Of 758 participants, 471 (62.1%) had experienced hypoglycemia, and 250 (32.9%) had experienced hypoglycemia at least once in the month immediately preceding the study. Two hundred and forty-two (31.8%) of the participants had received hypoglycemia education at least once, but only 148 (19.4%) knew the exact definition of hypoglycemia. Hypoglycemic symptoms identified by the participants were dizziness (55.0%), sweating (53.8%), and tremor (40.8%). They mostly chose candy (62.1%), chocolate (37.7%), or juice (36.8%) as food for recovering hypoglycemia. Participants who had experienced hypoglycemia had longer duration of diabetes and a higher proportion of insulin usage. The mean scores for hypoglycemia avoidance behavior and worry about hypoglycemia were 21.2±10.71 and 23.38±13.19, respectively. These scores tended to be higher for participants with higher than 8% of glycosylated hemoglobin, insulin use, and experience of emergency room visits. CONCLUSION Many patients had experienced hypoglycemia and worried about it. We recommend identifying patients that are anxious about hypoglycemia and educating them about what to do when they develop hypoglycemic symptoms, especially those who have a high risk of hypoglycemia.

Published
2018

37. Strategic Risk Management of Hazardous Goods Supply Chains

Author

Su-Han Woo, Hye-Soon Kim, and Sally Martin

Subjects
Hazardous waste, Supply chain, 0502 economics and business, 05 social sciences, Business, 010501 environmental sciences, 01 natural sciences, 050203 business & management, Industrial organization, Strategic risk, 0105 earth and related environmental sciences
Published
2017

39. Association between Serum Dipeptidyl Peptidase-4 Concentration and Obesity-related Factors in Health Screen Examinees

Author

Ji Yeon Lee, Byoung Kuk Jang, Mi-Kyung Kim, Hye Soon Kim, and Min Kyung Song

Subjects
0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Obese group, Dipeptidyl peptidase-4, Obesity, Related factors, Creatinine, lcsh:RC648-665, business.industry, Significant difference, Biomarker, medicine.disease, 030104 developmental biology, Endocrinology, chemistry, Lean body mass, Biomarker (medicine), Original Article, business
Abstract

Background : Dipeptidyl peptidase-4 (DPP-4) is an aminopeptidase that inhibits the enzymatic degradation of glucagon-like peptide-1, glucose-dependent insulinotropic polypeptides, neuropeptides, and various chemokines. Recent studies reported that serum DPP-4 concentration is correlated with clinical parameters of obesity. However, research on these correlations has never been conducted in Korea. Therefore, we investigated the relationship between serum DPP-4 concentration and various clinical parameters of obesity in the Korean population. Methods : Patients who visited the Health Promotion Center at Keimyung University Dongsan Medical Center for a regular medical examination between January 2013 and March 2013 and consented to participate in this study were included. We measured and analyzed parameters of obesity. In addition, serum DPP-4 concentration was determined using an enzyme-linked immunosorbent assay kit. Results : Serum DPP-4 concentration was positively correlated with lean body mass, total cholesterol level, and creatinine level. Serum DPP-4 concentration was higher in the obese group than in the normal body mass index (BMI) group. No significant difference in serum DPP-4 concentration was found between the metabolically healthy group and metabolically unhealthy group. Conclusion : Serum DPP-4 concentration was higher in the obesity group than in the normal BMI group, which was associated with obesity-related factors.

Published
2017

40. Clinical Characteristics of Patients with Adrenal Insufficiency in a General Hospital

Author

Nam Kyung Kim, Nan Hee Cho, Jong Won Lee, Hye Soon Kim, Mi-Kyung Kim, and Ye Yeon Lee

Subjects
medicine.medical_specialty, Pediatrics, Weakness, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Anorexia, Adrenocorticotropic hormone, Hypopituitarism, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, medicine, Adrenal insufficiency, 030212 general & internal medicine, Intensive care medicine, Hydrocortisone, lcsh:RC648-665, business.industry, Adrenal crisis, medicine.disease, Population characteristics, Original Article, medicine.symptom, business, medicine.drug, Hormone
Abstract

Background Adrenal insufficiency (AI) is a life-threatening disorder caused by the deficiency of adrenal steroid hormones. This retrospective cross-sectional study investigated the characteristics of patients with AI in Korea. Methods All consecutive patients with suspected AI who received care at a tertiary referral center in Korea in 2014 and underwent adrenocorticotropic hormone stimulation or insulin-tolerance testing were identified through a review of medical charts. Patients diagnosed with AI were enrolled. Their demographic, clinical, and treatment details were extracted. Results Of 771 patients with suspected AI, 183 (23.7%) received a definitive diagnosis. The most common reason for testing was the presence of suspicious AI-related symptoms (30.0%), followed by a history of steroid medications (23.5%). Their mean age was 66.7 years, and females predominated (67.8%). The most common symptoms were general weakness, anorexia, arthralgia, and fever. Approximately half (53.6%) had a history of steroid use. Hydrocortisone was the most common treatment (71.6%), with most patients taking a 30 mg dose (44.2%). The most common dose frequency was twice a day (78.6%). Fourteen patients were treated for adrenal crisis (n=10, 5.5%) or an intercurrent illness (n=4, 2.2%). Conclusion AI may have been caused by steroid medication use in many of the patients included in this study. The detection of AI can be improved by careful history-taking and being alert to the possibility that a patient has used steroids.

Published
2017

41. 1140-P: Efficacy and Safety of Evogliptin in Patients with Type 2 Diabetes: A Multicenter, Active-Controlled, Randomized Study with Open Label Extension (EVERGREEN Study)

Author

Choon H. Chung, Hyuk-Sang Kwon, Kang Seo Park, Sin Gon Kim, Eunsook Kim, Tae Ho Kim, Soo Lim, Cheol-Young Park, Hye Soon Kim, Su Kyoung Kwon, Ie Byung Park, Kyu Chang Won, Moon-Kyu Lee, Kyu Jeung Ahn, Mi-Kyung Kim, Chang Beom Lee, Min Kyong Moon, Seok Won Park, Gyuri Kim, and Dong Jin Chung

Subjects
medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Linagliptin, medicine.disease, Gastroenterology, Confidence interval, law.invention, Randomized controlled trial, law, Internal medicine, Evogliptin, Internal Medicine, medicine, Adverse effect, business, Body mass index, Glycemic, medicine.drug
Abstract

Background and Aims: Evogliptin is a new dipeptidyl peptidase-4 (DPP-4) inhibitor. We investigated the efficacy and safety of Evogliptin compared with linagliptin in patients with type 2 diabetes (T2D). Materials and Methods: A total of 207 untreated patients with T2D (mean age, 56.1±10.4 years; body mass index, 26.1±3.4 kg/m2) who had HbA1c 7.0-10.0%, prior to the screening were randomized 1:1 for 5 mg Evogliptin (n=102) or 5 mg linagliptin (n=105) once daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint included the change in mean amplitude of glycemic excursion (MAGE) assessed by 72-hour continuous glucose monitoring. In the extended study for another 12 weeks, open-label treatment with Evogliptin 5 mg qd was conducted in both groups; Evogliptin/Evogliptin group (n=95) and Linagliptin/Evogliptin group (n=92). Results: After 12 weeks of treatment, the mean changes in HbA1c of Evogliptin group and linagliptin group were −0.85% and −0.75%, respectively; the between-group difference was -0.10% (95% confidence interval, −0.32-0.11%), demonstrating non-inferiority, meeting the pre-specified margin of 0.40%. The changes in MAGE were −24.6 mg/dL in the Evogliptin group and −16.7 mg/dL in the linagliptin group, which were significantly lower compared with baseline values in both groups. In the Evogliptin/Evogliptin group at week 24, the mean changes from baseline in HbA1c was −0.94%, achieving HbA1c Conclusion: In this study, once-daily evoglipitin 5 mg treatment significantly decreased HbA1c levels by 0.94% at week 24 and improved glycemic variability without any serious adverse events in Korean patients with T2D (ClinicalTrials.gov Identifier: NCT02974504). Disclosure S. Lim: None. G. Kim: None. H. Kwon: None. I. Park: None. K. Ahn: None. C. Park: None. S. Kwon: None. H. Kim: None. S. Park: None. S. Kim: None. M. Moon: None. E. Kim: None. C.H. Chung: None. K. Won: None. K. Park: None. M. Kim: None. D. Chung: None. C. Lee: None. T. Kim: None. M. Lee: None.

Published
2019

42. Solitary bone and brain metastasis in a patient with papillary thyroid carcinoma mimicking cavernous angioma

Author

Sun Young Kwon, Eugene Han, Mi-Kyung Kim, El Kim, Ye Yeon Lee, Sang Pyo Kim, and Hye Soon Kim

Subjects
Thyroid nodules, Thyroid neoplasm, Pathology, medicine.medical_specialty, endocrine system diseases, Neoplasm metastasis, medicine.medical_treatment, 030209 endocrinology & metabolism, medicine.disease_cause, Metastasis, Thyroid carcinoma, 03 medical and health sciences, 0302 clinical medicine, medicine, Letter to the Editor, Thyroid cancer, business.industry, Thyroid, Thyroidectomy, Brain, medicine.disease, medicine.anatomical_structure, 030220 oncology & carcinogenesis, business, Brain metastasis
Abstract

To the Editor, There has been a recent increase in the global incidence rate of thyroid carcinoma. In Korea, this rate of increase is 23.3% per year and, as a result, thyroid carcinoma has been the most common cancer in Korea since 2009 [1]. Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma and accounts for up to 80% of all newly diagnosed thyroid carcinoma cases. Although metastasis to local or regional lymph nodes can occur, distance metastasis is unusual. In particular, brain metastasis is very rare and is reported in only 1% of patients with thyroid carcinoma [2]. Here, we report a case of bone and brain metastasis in a patient with PTC in which the brain lesion mimicked cavernous angioma, a type of blood vessel malformation. A 76-year-old woman with a history of diabetes mellitus presented with memory disturbances that had begun 3 months prior. The patient was cooperative but could not recall recent memories. A physical examination revealed a 5 cm mass without tenderness in the sternum but no palpable masses were detected in the thyroid gland. The vital signs of the patient were stable and apart from the presence of hyperglycemia (serum glucose level, 510 mg/dL) the laboratory findings were all within normal limits. Brain magnetic resonance imaging (MRI) scans of the patient revealed a lobulated lesion in the right frontal lobe with a mixed signal core surrounded by a low intensity rim; the lesion was not enhanced in the contrast image. These particular MRI features are consistent with those of cavernous angioma with hemorrhage (Fig. 1A and ​and1B1B). Figure 1. Radiological findings. (A) T1-weighted brain magnetic resonance image showing low mixed signal intensity (arrow). (B) T2-weighted image showing an isointense-to-hypointense lesion (arrow). (C) Chest computed tomography scan showing a 52mm mass with necrosis ... A chest computed tomography (CT) scan was performed to assess the mass in the sternum and revealed a huge infiltrating tumor mass with necrosis extending into the manubrium (Fig. 1C). The patient underwent a craniotomy to remove the brain tumor and the manubrium mass was biopsied. A histological analysis of the brain mass under a low-power view revealed a cystic and solid tumor mass that was infiltrating into the brain parenchyma with hemorrhage (Fig. 2A and ​and2B)2B) and a histological analysis under a high-power view revealed predominant branching papillary structures in the tumor that were composed of columnar cells with increased nuclear stratification (Fig. 2C). The sternum mass had identical histological features, i.e., the presence of complex papillary structures and equivalent cytological findings (Fig. 2D). To determine whether the sternum mass was a metastatic lesion from the lung, the mass was subjected to immunohistochemistry (IHC) analyses for cytokeratin 7, thyroid transcription factor-1 (TTF-1), and napsin A. The mass was positive for cytokeratin 7 and TTF-1 but negative for napsin A (Fig. 2E-​-2G).2G). Because metastatic thyroid cancer is characterized by a papillary structure and TTF-1 expression, the sternum mass was assessed for thyroglobulin expression and the IHC analysis revealed a strong expression of thyroglobulin (Fig. 2H). The final pathological diagnosis was metastatic columnar cell-variant PTC, which is a very rare variant [3]. Figure 2. Microscopic findings of the brain and sternum tumor masses. (A) Low-power view of the resected right frontal mass showing a cystic and solid mass with hemorrhage (H&E, ×10). (B) Low-power view of the brain mass revealing the branching ... To evaluate the primary cancer, thyroid ultrasonography was performed. A single hypoechoic nodule (5 × 5 × 10 mm sized) with coarse calcification in the isthmus (Fig. 3A) and two indistinct subtle hyperechoic masses (8 × 8 × 11 mm and 4 × 5 × 5 mm) were detected in the right thyroid. All lymph nodes appeared normal and fine-needle aspiration of the isthmic thyroid nodule confirmed the diagnosis of PTC (Fig. 3B). A real-time polymerase chain reaction analysis revealed the presence of the BRAF mutation (V600E) and a thyroid function test revealed a state of euthyroidism (thyroglobulin antibody [TgAb] concentrations > 1,000 ng/mL). To determine whether there were additional metastatic lesions, a positron emission tomography-CT scan was performed and revealed a low density and mildly hypermetabolic nodule in the right lobe of the thyroid gland (Fig. 3C) as well as a large infiltrating intensely hypermetabolic mass in the manubrium and upper sternum body (Fig. 3D). Figure 3. Findings from the thyroid ultrasonography, fine-needle aspiration, and positron emission tomography-computed tomography (PET-CT) scans. (A) Ultrasonography scan showing the presence of a 5 × 5 × 10 mm hypoechoic nodule with coarse calcification ... Thyroidectomy and radiotherapy were recommended for the brain lesion but the patient refused all treatment. Four months later, follow-up neck CT scans showed that the metastatic mass in the manubrium had undergone a marked increase in volume, the destruction of the sternum was evident, and there was new involvement of lymph nodes including an enlarged metastatic right level III lymph node that exhibited a probable invasion of the right internal jugular vein. A brain CT scan performed at the same time revealed newly developed meningeal metastasis and an intracranial hemorrhage in the right frontoparietal area. Five months after this follow-up visit, the patient expired due to pneumonia and sepsis. In summary, the present 76-year-old female patient was initially diagnosed with cavernous angioma but her final diagnosis was thyroid cancer with brain and bone metastasis. In most cases, thyroid cancer has an excellent prognosis. In fact, the 5-year relative survival rate for patients with thyroid cancer is almost 99.9% and the overall survival rate of patients with PTC is 98% [1]. However, some histological variants of PTC are associated with an unusually poor prognosis including the conventional form, the follicular variant, the tall cell variant, the oncolytic variant, the columnar cell variant, the diffuse sclerosing variant, and the solid form. The present patient was diagnosed with the columnar cell variant, which is characterized by pseudostratified columnar cells and subnuclear vacuolization that resembles early secretory endometrium. Although this PTC variant is very rare and only accounts for 0.15% to 0.2% of all PTCs, it is associated with aggressive behaviors such as a propensity for extrathyroidal extension, distant metastasis, and the death of the tumor. Additionally, these tumor cells are usually positive for TTF-1 and show variable thyroglobulin immunoreactivity but the typical nuclear features are not well-represented and may be mistaken for other kinds of adenocarcinomas [3]. Serum TgAb is a predictive marker of thyroid malignancy in thyroid nodules. The prevalence of TgAb in thyroid malignancy patients is 10% to 30%, which is higher than among the normal population, and a high serum TgAb titer decreases after thyroid malignancy treatment while a sustained high serum TgAb titer could reflect early relapse [4]. The survival rate of PTC patients significantly decreases when metastasis occurs. The average overall survival duration of patients with PTC and brain metastasis is 4.7 months but if the PTC is well-differentiated with brain metastasis then the median survival duration is 12.4 months [1,2]. The common symptoms of patients with thyroid carcinoma and brain metastasis include headache, nausea, motor weakness, gait disturbances, sensory deficits, visual loss, and seizures but some patients with brain metastasis do not exhibit any symptoms and are only diagnosed with brain metastasis upon a postmortem examination. Among all PTC cases, the median interval between a diagnosis of PTC and the identification of brain metastasis is 2.9 years. Patients with brain metastasis from PTC tend to be older, have a large primary tumor size, and exhibit extrathyroidal invasion. Due to the low incidence of brain metastatic PTC, a universal standard treatment protocol has yet to be established. However, the current treatment of choice is typically surgical resection because the removal of a brain metastasis significantly improves survival and is an independent predictor of better outcomes [2]. Radiosurgery should be considered for patients who are unable to undergo surgery and whole brain radiation therapy can also be used to treat multiple metastases. Although brain radiation is not associated with a survival benefit, several cases have been reported indicating a regression of brain metastasis after such therapy [5]. Similarly, there is no evidence of a treatment response to radioactive iodine or doxorubicin-based chemotherapy. Brain metastasis accounts for about 20% of cause-specific deaths in patients with PTC while other causes include pneumonia, sepsis, and local invasion [5]. The present case was an extremely rare example of brain metastasis from columnar cell-variant PTC in which the brain metastatic lesion mimicked a cavernous angioma. These findings suggest that, depending on the PTC variant, even small PTCs should be treated with caution because they can lead to brain metastasis.

Published
2016

43. Prognostic Significance of Tissue Leptin Expression in Colorectal Cancer Patients

Author

Sun Young Kwon, Mi-Kyung Kim, Seong Kyu Baek, Hye Soon Kim, and Woon Kyung Jeong

Subjects
Oncology, Leptin, medicine.medical_specialty, Survival rate, business.industry, Colorectal cancer, Gastroenterology, medicine.disease, Group A, Immunohistochemistry, Group B, Colorectal neoplasms, Endocrinology, Internal medicine, Tissue array analysis, Medicine, T-stage, Surgery, Original Article, Stage (cooking), business
Abstract

Purpose Leptin is encoded by the ob gene and is involved in the control of food intake and energy expenditure. Recent studies have implicated leptin expression to be an indicator of tumor features and prognosis. The purpose of this study was to investigate the association of tissue expression of leptin with the clinicopathological characteristics and clinical outcomes in colorectal cancer patients. Methods Patients who had undergone a curative surgical resection for a colorectal adenocarcinoma from 2000 to 2004 were included in the study. Immunohistochemical analyses of leptin expression were performed, and clinicopathological parameters were evaluated. Results Clinical data and tumor tissues of 146 patients were evaluated. The mean age was 68.6 ± 11.3 years, and 61.0% were men. Immunohistochemically, the rates of negative, weak, moderate, and strong leptin expression were 2.7% (4 of 146), 5.5% (8 of 146), 43.2% (63 of 146), and 48.6% (71 of 146), respectively. We compared the negative, weak, and moderate expression group (group A) with the strong expression group (group B). Leptin expression was inversely associated with nodal stage (P = 0.007) between the two groups. Leptin expression was not significantly associated with differentiation (P = 0.37), T stage (P = 0.16), and American Joint Committee on Cancer stage (P = 0.49), and no significant differences in the disease-free and the overall survivals (P = 0.78 and P = 0.61) were observed. Conclusion Results demonstrated an inverse association of nodal stage with high leptin expression. Higher leptin expression level might predict better oncologic outcome. However, further studies are warranted to identify the exact role of leptin expression in colorectal cancer.

Published
2015

44. Exercise training-induced changes in metabolic syndrome parameters, carotid wall thickness, and thyroid function in middle-aged women with subclinical hypothyroidism

Author

Nayoung Ahn, Hye Soon Kim, and Kijin Kim

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Physiology, Clinical Biochemistry, Thyroid Gland, Blood lipids, Body fat percentage, Carotid Intima-Media Thickness, 03 medical and health sciences, 0302 clinical medicine, Hypothyroidism, Physiology (medical), Internal medicine, medicine, Aerobic exercise, Humans, Obesity, Exercise, Subclinical infection, Metabolic Syndrome, business.industry, Thyroid, Resistance Training, Middle Aged, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Blood pressure, Endocrinology, Carotid Arteries, Female, Metabolic syndrome, Thyroid function, business, 030217 neurology & neurosurgery
Abstract

This study analyzed the differences in effects of a 12-week combination of exercise training program with resistance training and aerobic exercises on the risk factors of metabolic syndrome, carotid wall thickness, and thyroid function, between subclinical hypothyroidism patients and obese groups, in middle-aged women. Subjects consisted of either 20 middle-aged women in the subclinical hypothyroidism (SCH) group or 20 obese (body mass indices [BMI], ≥ 25 kg/m2) women without hypothyroidism in the obese (OB) group. The body composition, blood lipid factors, hormones associated with thyroid functions, blood pressure (BP), and carotid intima-media thickness were measured, while physical fitness was ascertained. In the SCH group, waist circumference (WC) and high-density lipoprotein cholesterol values were outside the normal ranges, while WC and systolic BP (SBP) were outside the normal ranges in the OB group. Following the 12-week training program, significantly positive changes occurred in body fat percentage, sit and reach test results, and SBP (p

Published
2018

45. Association between nonalbumin proteinuria and renal tubular damage of N-acetyl-β-d-glucosaminidase and its clinical relevance in patients with type 2 diabetes without albuminuria

Author

Mi-Kyung Kim, Yong Ho Lee, Eugene Han, Byung Wan Lee, and Hye Soon Kim

Subjects
Blood Glucose, Male, medicine.medical_specialty, Time Factors, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Urinary system, Urology, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, urologic and male genital diseases, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Acetylglucosaminidase, Internal Medicine, Medicine, Albuminuria, Humans, Diabetic Nephropathies, Aged, Retrospective Studies, Proteinuria, urogenital system, business.industry, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Nap, Cross-Sectional Studies, Kidney Tubules, Diabetes Mellitus, Type 2, Female, medicine.symptom, Insulin Resistance, Waist Circumference, business, Body mass index, Biomarkers
Abstract

Although albuminuria and urinary N-acetyl-β-d-glucosaminidase (uNAG) are known as progression markers of diabetic kidney disease, there is limited information regarding the association between urinary nonalbumin proteinuria (NAP) and uNAG and the clinical relevance thereof in patients without albuminuria.This cross-sectional study included samples from 244 consecutive patients with type 2 diabetes mellitus (T2D) without albuminuria. Proteinuria and albuminuria were defined according to protein-to-creatinine ratio (uPCR) and albumin-to-creatinine ratio (uACR), respectively. NAP was indirectly calculated by the difference between uPCR and uACR.NAP and uNAG excretion were significantly correlated (r = 0.525, P 0.001). Individuals whose NAP levels were in the highest tertile had a longer duration of diabetes, uncontrolled hyperglycemia, and impaired insulin stimulation (all P 0.05), although more patients in the highest NAP tertile were prescribed insulin and sulfonylurea. Multiple linear regression analyses revealed associations among uNAG, diabetes duration, and waist circumference.T2D patients without albuminuria excrete proteinuria and that presence of the protein in urine is associated with uNAG. NAP was positively correlated with T2D duration and waist circumference, but negatively correlated with body mass index. Lean, but centrally obese, T2D patients in late diabetes experience more tubular damage, regardless of the presence of albuminuria.

Published
2018

47. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Author

Adrian F Hernandez, Jennifer B Green, Salim Janmohamed, Ralph B D'Agostino, Christopher B Granger, Nigel P Jones, Lawrence A Leiter, Anne E Rosenberg, Kristina N Sigmon, Matthew C Somerville, Karl M Thorpe, John J V McMurray, Stefano Del Prato, John J.V. McMurray, Ralph B. D'Agostino, Christopher B. Granger, Adrian F. Hernandez, Lawrence A. Leiter, Robert M Califf, Rury Holman, David DeMets, Matthew Riddle, Shaun Goodman, Darren McGuire, Karen Alexander, Adam Devore, Chiara Melloni, Chetan Patel, David Kong, Gerald Bloomfield, Matthew Roe, Pierluigi Tricoci, Rob Harrison, Renato Lopes, Robin Mathews, Rajendra Mehta, William Schuyler Jones, Sreekanth Vemulapalli, Thomas Povsic, Zubin Eapen, Keith Dombrowski, Brad Kolls, Dedrick Jordan, Andrew Ambrosy, Stephen Greene, Aditya Mandawat, Jay Shavadia, Lauren Cooper, Abhinav Sharma, Patricia Guimaraes, Daniel Friedman, Matt Wilson, Patricia Endsley, Tracy Gentry, Jeannie Collier, Kathleen Perez, Kourtnei James, Jennifer Roush, Connie Pope, Christina Howell, Megan Johnson, Matt Bailey, Joanna Cole, Teresa Akers, Beth Vandyne, Betsy Thomas, Jenny Rich, Susan Bartone, Gail Beaulieu, Kim Brown, Tuan Chau, Tamra Christian, Rebecca Coker, Deb Greene, Trevorlyn Haddock, Wendy Jenkins, Ghazala Haque, Marsha Marquess, Jean Pesarchick, Renee Rethaford, Allegra Stone, Firas Al Kawas, Michelle Anderson, Robert Enns, Isaac Sinay, Chantal Mathieu, Victor Yordanov, Irene Hramiak, Martin Haluzik, Søren Galatius, Bruno Guerci, Michael Nauck, Ilias Migdalis, Choon Beng Kathryn Tan, Gyozo Kocsis, Andrea Giaccari, Moon Kyu Lee, Ernesto German Cardona Muñoz, Jan Cornel, Kare Birkeland, Miguel Pinto, Louie Tirador, Martyna Olesinska-Mader, Marina Shestakova, Larry Distiller, Jose Lopez-Sendon, Bjorn Eliasson, Chern-En Chiang, Suphot Srimahachota, Boris Mankovsky, M Angelyn Bethel, Kathleen Dungan, Mikhail Kosiborod, Andres Alvarisqueta, Jorge Baldovino, Diego Besada, Pedro Calella, Maria Cecilia Cantero, Patricia Castaño, Alejandro Chertkoff, Jesus Cuadrado, Luis De Loredo, Andrea Dominguez, Maria Vanesa Español, Hernan Finkelstein, Gustavo Frechtel, Jose Fretes, Natalia Garrido Santos, Joaquin Gonzalez, Marcos Litvak, Juan Loureyro, Laura Maffei, Natacha Maldonado, Diego Mohr Gasparini, Silvia Orio, Federico Perez Manghi, Nelson Rodriguez Papini, Jorgelina Sala, Pablo Schygiel, Georgina Sposetti, Maria Ulla, Fernando Verra, Silvina Zabalua, Cesar Zaidman, Laurent Crenier, Corinne Debroye, Francis Duyck, André Scheen, Luc Van Gaal, Chris Vercammen, Velichka Damyanova, Stefan Dimitrov, Snezhina Kovacheva, Lachezar Lozanov, Viktor Margaritov, Rositsa Mihaylova-Shumkova, Antoaneta Nikolaeva, Zhasmina Stoyanova, Ronald Akhras, Yves Beaudry, Jacques Bedard, Joseph Berlingieri, Raja Chehayeb, Stephen Cheung, James Conway, Jean Cusson, Anthony Della Siega, Richard Dumas, Peter Dzongowski, Murdo Ferguson, Daniel Gaudet, Francois Grondin, Anil Gupta, Milan Gupta, Frank Halperin, Pierre-Alain Houle, Michael Jones, Simon Kouz, Christopher Kovacs, Daniel Landry, Eva Lonn, William O'Mahony, Sean Peterson, Dennis Reich, Alan Rosenbloom, Francois St-Maurice, Barna Tugwell, Saul Vizel, Vincent Woo, Tomas Brychta, Vladimir Cech, Eva Dvorakova, Tomas Edelsberger, Katarina Halciakova, Jarmila Krizova, Jiri Lastuvka, Martin Piperek, Vera Prymkova, Lea Raclavska, Elena Silhova, Robin Urbanek, Jan Vrkoc, Ulla Andersen, Jens Brønnum-Schou, Jens Hove, Jan Skov Jensen, Lars Kober, Ole Peter Kristiansen, Per Lund, Thomas Melchior, Ole Nyvad, Morten Schou, Alain Boye, Didier Cadinot, Didier Gouet, Patrick Henry, Laurence Kessler, Jean-Daniel Lalau, Catherine Petit, Jean-Francois Thuan, Christel Voinot, Julien Vouillarmet, Christoph Axthelm, Dirk Berger, Tasso Bieler, Andreas Birkenfeld, Jochen Bott, Klaus Busch, Karel Caca, Julia Chevts, Torsten Donaubauer, Rudolf Erlinger, Klaus Funke, Josef Grosskopf, Andreas Hagenow, Monika Hamann, Manfred Hartard, Peter Heymer, Wolfgang Huppertz, Gabriele Illies, Stephan Jacob, Thomas Jung, Gerd Kahrmann, Petra Kast, Monika Kellerer, Hans-Peter Kempe, Andrei Khariouzov, Gerhard Klausmann, Christiane Klein, Uwe Kleinecke-Pohl, Klaus Kleinertz, Thorsten Koch, Christine Kosch, Babette Lorra, Joerg Luedemann, Matthias Luttermann, Stephan Maxeiner, Karsten Milek, Andrea Moelle, Gerhard Neumann, Ruth Nischik, Edith Oehrig-Pohl, Georg Plassmann, Lars Pohlmeier, Felix Proepper, Stefan Regner, Werner Rieker, Ludger Rose, Holger Samer, Joachim Sauter, Frank Schaper, Clemens Schiffer, Juergen Schmidt, Bernd-M. Scholz, Joerg Schulze, Alexander Segner, Jochen Seufert, Helena Sigal, Joerg Steindorf, Juergen Stockhausen, Petra Stuebler, Heidrun Taeschner, Dietrich Tews, Diethelm Tschoepe, Karl Wilhelm, Helga Zeller-Stefan, Iakovos Avramidis, Stavros Bousboulas, Magdalini Bristianou, Georgios Dimitriadis, Moses Elisaf, Kalliopi Kotsa, Andreas Melidonis, Asimina Mitrakou, Emmanouil Pagkalos, Nikolaos Papanas, Angelos Pappas, Christos Sampanis, Nikolaos Tentolouris, Apostolos Tsapas, Glykeria Tzatzagou, Risa Ozaki, Csaba Hajdú, Eleonóra Harcsa, Laszlo Konyves, János Mucsi, Zsolt Pauker, Gizella Petró, Zsolt Plés, Katalin Revesz, Vangel Sándor, Viktor Vass, Angelo Avogaro, Massimo Boemi, Riccardo Bonadonna, Agostino Consoli, Salvatore De Cosmo, Paolo Di Bartolo, Francesco Dotta, Simona Frontoni, Marianna Galetta, Alessandra Gambineri, Carmine Gazzaruso, Francesco Giorgino, Davide Lauro, Emanuela Orsi, Giuseppe Paolisso, Gabriele Perriello, Piermarco Piatti, Antonio Pontiroli, Paola Ponzani, Angela Albarosa Rivellese, Giorgio Sesti, Giancarlo Tonolo, Roberto Trevisan, Chul Woo Ahn, Sei-Hyun Baik, Bong-Soo Cha, Choon-Hee Chung, Hak Chul Jang, Chong-Jin Kim, Hye Soon Kim, In Joo Kim, Eun Young Lee, Hyoung Woo Lee, Kwan-Woo Lee, Keon-Woong Moon, June Namgung, Kyong Soo Park, Soon Jib Yoo, Jaemyung Yu, Edmundo-Alfredo Bayram Llamas, Jose-Luis Cervantes-Escárcega, Luis Fernando Flota-Cervera, José Gerardo González-González, Sara Pascoe-Gonzalez, Emilia Susana Pelayo-Orozco, Santiago-Paulino Ramirez-Diaz, Arturo Saldana-Mendoza, Carlos Sánchez Jerjes-Díaz, Jose Juan Torres-Colores, Maricela Vidrio-Velázquez, Juan Villagordoa-Mesa, Hugo Peter Beijerbacht, Reginald G.E.J. Groutars, Boudewijn A Hoek, Pieter A.M. Hoogslag, Adriaan Kooy, Johannes A. Kragten, Aloysius G. Lieverse, Hendrik P. Swart, Eric P. Viergever, Jørn Ahlqvist, John Cooper, Hanne Gulseth, Gaute Guttormsen, Cecilie Wium, Hugo Arbañil, Jorge Calderon, Luis Camacho, Augusto Dextre Espinoza, Elizabeth Garrido, Alejandro Luna, Helard Manrique, Frederick Massucco Revoredo, Rolando Vargas Gonzales, Luis Zapata Rincon, Carlos Zubiate, Geraldine Ebo, Ellen Morales-Palomares, Malgorzata Arciszewska, Marek Banach, Renata Bijata-Bronisz, Tadeusz Derezinski, Waldemar Gadzinski, Jacek Gajek, Katarzyna Klodawska, Ewa Krzyzagorska, Andrzej Madej, Pawel Miekus, Jaroslaw Opiela, Piotr Romanczuk, Anna Siegel, Ewa Skokowska, Andrzej Stankiewicz, Teresa Stasinska, Iwona Trznadel-Morawska, Robert Witek, Sergey Aksentyev, Irina Bondar, Irina Demidova, Alexander Dreval, Olga Ershova, Gagik Galstyan, Alla Garganeeva, Nadezhda Izmozherova, Victoria Karetnikova, Marina Kharakhulakh, Aleksandr Khokhlov, Zhanna Kobalava, Olga Koshelskaya, Elena Kosmacheva, Vladimir Kostin, Natalia Koziolova, Anatoly Kuzin, Victor Lesnov, Tatyana Lysenko, Valentin Markov, Alexander Mayorov, Sergey Moiseev, Svetlana Myasoedova, Nina Petunina, Andrey Rebrov, Ludmila Ruyatkina, Julia Samoylova, Olga Sazonova, Natalia Shilkina, Nadezhda Sokolova, Olga Vasilevskaya, Nelli Verbovaya, Elena Vishneva, Sergey Vorobyev, Natalya Vorokhobina, Olga Zanozina, Elena Zhdanova, Tatyana Zykova, Lesley Burgess, Kathleen Coetzee, Saleem Dawood, Landman Lombard, Ellen Makotoko, Rajendran Moodley, Wessels Oosthuysen, Mohamed Sarvan, Carlos Calvo Gómez, Isidoro Cano Rodríguez, Almudena Castro Conde, Angel Cequier Fillat, Guillem Cuatrecasas Cambra, Fernando de Álvaro Moreno, Luis De Teresa Parreño, Javier Delgado Lista, José Ramón Domínguez Escribano, Santiago Durán García, Javier Elvira González, José María Fernández Rodríguez, Alberto Goday Arno, Ricardo Gomez Huelgas, José Ramón González Juanatey, Antonio Hernandez Mijares, Víctor Alfonso Jiménez Díaz, Esteban Jodar Gimeno, Tomás Lucas Morante, Monica Marazuela, Nieves Martell Claros, Didac Mauricio Puente, Elena Mena Ribas, Juan Francisco Merino Torres, Pedro Mezquita Raya, Andreu Nubiola Calonge, Xavier Ordoñez Sánchez, Jose Maria Pascual Izuel, Verónica Perea Castilla, Antonio Pérez Pérez, Isabel Perez Soto, Miguel Quesada Charneco, Angustias Quesada Simón, Josep Redón Mas, Antonia Rego Iraeta, Maria Rodriguez Alvarez, Irene Rodríguez Rodríguez, José Sabán Ruiz, Alfonso Soto González, Francisco Tinahones Madueno, Carlos Trescoli Serrano, Angels Ulied Armiñana, Erasmus Bachus, Katarina Berndtsson Blom, Ken Eliasson, Pekka Koskinen, Hans Larnefeldt, Cornelia Lif-Tiberg, Carina Linderfalk, Gustav Lund, Pia Lundman, Linda Moris, Åke Olsson, Staffan Salmonsson, Johan Sanmartin Berglund, Folke Sjöberg, Stefan Söderberg, Ingemar Torstensson, Jung-Fu Chen, Kai Jen Tien, Shih-Ting Tseng, Shih-Te Tu, Chih-Yuan Wang, Ji-Hung Wang, Arintaya Phrommintikul, Sukit Yamwong, Woravut Jintapakorn, Pisit Hutayanon, Nakarin Sansanayudh, Larysa Bazhan, Ivan Fushtey, Mariya Grachova, Vitaliy Katerenchuk, Vadym Korpachev, Nonna Kravchun, Oleksandr Larin, Galyna Mykhalchyshyn, Halyna Myshanych, Olga Oleksyk, Valeriia Orlenko, Nataliia Pashkovska, Nataliia Pertseva, Olena Petrosyan, Ivan Smirnov, Maryna Vlasenko, Tetiana Zlova, Myint Aye, Arun Baksi, Mathangi Balasubramani, Ronnie Beboso, Mark Blagden, Charles Bundy, Tobias Cookson, Allan Copland, Alistair Emslie-Smith, Fiona Green, Anthony Gunstone, Basil Issa, Ewart Jackson-Voyzey, Andrew Johnson, Malcolm Maclean, John McKnight, Solomon Muzulu, Ian O'Connell, Babatunde Oyesile, Catherine Patterson, Ewan Pearson, Sam Philip, Paul Smith, Usha Sukumaran, Jalal Abbas, Gaurav Aggarwala, Faiq Akhter, James Andersen, Moise Anglade, Georges Argoud, Mehrdad Ariani, Reswan Ashdji, Ladan Bakhtari, Subhash Banerjee, Andrew Bartlett, Howard Baum, Harold Bays, Richard Beasley, Renata Belfort de Aguiar, Sabrina Benjamin, Ravi Bhagwat, Anuj Bhargava, Bruce Bode, Christina Bratcher, Toby Briskin, Andrew Brockmyre, Raymond Broughton, Judith Brown, Madhusudan Budhraja, Kevin Cannon, Jewell Carr, Harold Cathcart, Arvind Cavale, Louis Chaykin, Deanna Cheung, Richard Childress, Allan Cohen, Jonathan Condit, Erin Cooksey, George Mitchell Cornett, Ira Dauber, William Davila, Luis De Armas, Julius Dean, Robert Detweiler, Ernesto Diaz, Michael Di Giovanna, Isaac Dor, Waymon Drummond, Donald Eagerton, John Earl, Charles Eaton, Howard Ellison, Neil Farris, Thomas Fiel, Anthony Firek, Brian First, Les Forgosh, William French, Winston Gandy, Ronald Garcia, Santosh Gill, Murray Gordon, Michael Guice, Siva Gummadi, Jonathan Hackenyos, Kristen Hairston, Lenita Hanson, Lindsay Harrison, Israel Hartman, John Heitner, Srini Hejeebu, Paul Hermany, Carlos Hernandez-Cassis, Horacio Hidalgo, Alexander Higgins, Hassan Ibrahim, Shahram Jacobs, David Johnson, Parag Joshi, Steven Kaster, Daniel Kellum, Christopher Kim, Ellen Kim, William Kirby, Albert Knouse, Steven Kulback, Mariananda Kumar, Tulsidas Kuruvanka, Ajay Labroo, William Lasswell, John Lentz, Thomas Lenzmeier, David Lewis, Zhaoping Li, Michael Lillestol, Raymond Little, Richard Lorraine, Cecilia McKeown-Biagas, Robert McNeill, Anand Mehta, Alan Miller, Joseph Moran, Emily Morawski, Venkatesh Nadar, Thomas O'Connor, Alberto Odio, Reginald Parker, Rajesh Patel, Lawrence Phillips, George Raad, Aref Rahman, Marina Raikhel, Ajit Raisinghani, Raj Rajan, Neda Rasouli, Frank Rauzi, Kathryn Rohr, Hal Roseman, Sergio Rovner, Fadi Saba, Richard Sachson, Alex Schabauer, Ricky Schneider, Timothy Schuchard, John Sensenbrenner, Yshay Shlesinger, Narendra Singh, Kanagaratnam Sivalingam, Larry Stonesifer, Daniel Storey, David Suh, Mohammed Tahir, Anjanette Tan, Marilyn Tan, Alain Taylon, Maitreya Thakkar, Devjit Tripathy, Gabriel Uwaifo, Amarnath Vedere, Chandra Venugopal, Anthony Vo, Michelle Welch, James Welker, Alexander White, John Willis, Alan Wynne, Shahram Yazdani, Anne Rosenberg, Lauren Price, Kristina Sigmon, Yuliya Lokhngina, Weibing Xing, Robert Overton, Murray Stewart, Janet Stead, Alistair Lindsay, Vickas Patel, Jorge Ross, Joseph Soffer, Shruti Daga, Margaret Sowell, Prashant Patel, Louisa Garvey, Jessica Ackert, Sybil Abraham, Mary Beth Sabol, Desma Altobelli, JuYoung Ha, Mangesh Kulkarni, Matthew Somerville, Drusilla Noronha, Ed Casson, Eddie Zang, Chamandeep Sandhu, Rakesh Kumar, David Chen, Lin Taft, Rajivkumar Patel, June Ye, Jennifer Shannon, Tim Wilson, Charleen Babi, Diane Miller, Karl Thorpe, Rachael Russell, Georgina Bull, Belinda Hereghty, Eva Fernandez-Salazar, Troy Longley, Jill Donaldson, Marie Jarosz, Karen Murphy, Patricia Adams, Peter Smith, Rachel James, Jackie Richards, Sangeeta Sedani, Denise Althouse, David Watson, Jamie Lorimer, Steven Lauder, Ron Schultheis, Terese Womer, Ella Wraight, Wenyan Li, Emma Price-Olsen, Anthony Watson, Aoife Kelly, Patricia McLaughlin, John Fleming, Jessica Schubert, Debra Schleiden, Tara Harris, Rahul Prakash, Jody Breneman, Sameer Deshpande, Aarti Saswadkar, Aditi Kumari, Aditi Shitut, Amruta Raorane, Anisha Karmalkar, Ankita Mhambrey, Archana Bhosale, Ashok Vaphare, Ashwini P Patil, Chaitali Khandelwal, Fayaz Shaik, Madhumitha Nadar, Mounika Karka, Neha Kadgaonkar, Nikita Gupta, Nutan Aher, Omkar Potnis, Pallavi Naicker, Rakesh Shinde, Richa Sharma, Rupali Godse, Sheetal Solanki, Shruti Sahu, Snehal Dumbre, Somesh Kumar, Suradnya Patil, Trisha Mandal, Hernandez, Adrian F, Green, Jennifer B, Janmohamed, Salim, D'Agostino, Ralph B, Granger, Christopher B, Jones, Nigel P, Leiter, Lawrence A, Rosenberg, Anne E, Sigmon, Kristina N, Somerville, Matthew C, Thorpe, Karl M, Mcmurray, John J V, Del Prato, Stefano, Mcmurray, John J. V., D'Agostino, Ralph B., Granger, Christopher B., Hernandez, Adrian F., Leiter, Lawrence A., Califf, Robert M, Holman, Rury, Demets, David, Riddle, Matthew, Goodman, Shaun, Mcguire, Darren, Alexander, Karen, Devore, Adam, Melloni, Chiara, Patel, Chetan, Kong, David, Bloomfield, Gerald, Roe, Matthew, Tricoci, Pierluigi, Harrison, Rob, Lopes, Renato, Mathews, Robin, Mehta, Rajendra, Schuyler Jones, William, Vemulapalli, Sreekanth, Povsic, Thoma, Eapen, Zubin, Dombrowski, Keith, Kolls, Brad, Jordan, Dedrick, Ambrosy, Andrew, Greene, Stephen, Mandawat, Aditya, Shavadia, Jay, Cooper, Lauren, Sharma, Abhinav, Guimaraes, Patricia, Friedman, Daniel, Wilson, Matt, Endsley, Patricia, Gentry, Tracy, Collier, Jeannie, Perez, Kathleen, James, Kourtnei, Roush, Jennifer, Pope, Connie, Howell, Christina, Johnson, Megan, Bailey, Matt, Cole, Joanna, Akers, Teresa, Vandyne, Beth, Thomas, Betsy, Rich, Jenny, Bartone, Susan, Beaulieu, Gail, Brown, Kim, Chau, Tuan, Christian, Tamra, Coker, Rebecca, Greene, Deb, Haddock, Trevorlyn, Jenkins, Wendy, Haque, Ghazala, Marquess, Marsha, Pesarchick, Jean, Rethaford, Renee, Stone, Allegra, Al Kawas, Fira, Anderson, Michelle, Enns, Robert, Sinay, Isaac, Mathieu, Chantal, Yordanov, Victor, Hramiak, Irene, Haluzik, Martin, Galatius, Søren, Guerci, Bruno, Nauck, Michael, Migdalis, Ilia, Tan, Choon Beng Kathryn, Kocsis, Gyozo, Giaccari, Andrea, Lee, Moon Kyu, Muñoz, Ernesto German Cardona, Cornel, Jan, Birkeland, Kare, Pinto, Miguel, Tirador, Louie, Olesinska-Mader, Martyna, Shestakova, Marina, Distiller, Larry, Lopez-Sendon, Jose, Eliasson, Bjorn, Chiang, Chern-En, Srimahachota, Suphot, Mankovsky, Bori, Bethel, M Angelyn, Dungan, Kathleen, Kosiborod, Mikhail, Alvarisqueta, Andre, Baldovino, Jorge, Besada, Diego, Calella, Pedro, Cantero, Maria Cecilia, Castaño, Patricia, Chertkoff, Alejandro, Cuadrado, Jesu, De Loredo, Lui, Dominguez, Andrea, Español, Maria Vanesa, Finkelstein, Hernan, Frechtel, Gustavo, Fretes, Jose, Garrido Santos, Natalia, Gonzalez, Joaquin, Litvak, Marco, Loureyro, Juan, Maffei, Laura, Maldonado, Natacha, Mohr Gasparini, Diego, Orio, Silvia, Perez Manghi, Federico, Rodriguez Papini, Nelson, Sala, Jorgelina, Schygiel, Pablo, Sposetti, Georgina, Ulla, Maria, Verra, Fernando, Zabalua, Silvina, Zaidman, Cesar, Crenier, Laurent, Debroye, Corinne, Duyck, Franci, Scheen, André, Van Gaal, Luc, Vercammen, Chri, Damyanova, Velichka, Dimitrov, Stefan, Kovacheva, Snezhina, Lozanov, Lachezar, Margaritov, Viktor, Mihaylova-Shumkova, Rositsa, Nikolaeva, Antoaneta, Stoyanova, Zhasmina, Akhras, Ronald, Beaudry, Yve, Bedard, Jacque, Berlingieri, Joseph, Chehayeb, Raja, Cheung, Stephen, Conway, Jame, Cusson, Jean, Della Siega, Anthony, Dumas, Richard, Dzongowski, Peter, Ferguson, Murdo, Gaudet, Daniel, Grondin, Francoi, Gupta, Anil, Gupta, Milan, Halperin, Frank, Houle, Pierre-Alain, Jones, Michael, Kouz, Simon, Kovacs, Christopher, Landry, Daniel, Lonn, Eva, O'Mahony, William, Peterson, Sean, Reich, Denni, Rosenbloom, Alan, St-Maurice, Francoi, Tugwell, Barna, Vizel, Saul, Woo, Vincent, Brychta, Toma, Cech, Vladimir, Dvorakova, Eva, Edelsberger, Toma, Halciakova, Katarina, Krizova, Jarmila, Lastuvka, Jiri, Piperek, Martin, Prymkova, Vera, Raclavska, Lea, Silhova, Elena, Urbanek, Robin, Vrkoc, Jan, Andersen, Ulla, Brønnum-Schou, Jen, Hove, Jen, Jensen, Jan Skov, Kober, Lar, Kristiansen, Ole Peter, Lund, Per, Melchior, Thoma, Nyvad, Ole, Schou, Morten, Boye, Alain, Cadinot, Didier, Gouet, Didier, Henry, Patrick, Kessler, Laurence, Lalau, Jean-Daniel, Petit, Catherine, Thuan, Jean-Francoi, Voinot, Christel, Vouillarmet, Julien, Axthelm, Christoph, Berger, Dirk, Bieler, Tasso, Birkenfeld, Andrea, Bott, Jochen, Busch, Klau, Caca, Karel, Chevts, Julia, Donaubauer, Torsten, Erlinger, Rudolf, Funke, Klau, Grosskopf, Josef, Hagenow, Andrea, Hamann, Monika, Hartard, Manfred, Heymer, Peter, Huppertz, Wolfgang, Illies, Gabriele, Jacob, Stephan, Jung, Thoma, Kahrmann, Gerd, Kast, Petra, Kellerer, Monika, Kempe, Hans-Peter, Khariouzov, Andrei, Klausmann, Gerhard, Klein, Christiane, Kleinecke-Pohl, Uwe, Kleinertz, Klau, Koch, Thorsten, Kosch, Christine, Lorra, Babette, Luedemann, Joerg, Luttermann, Matthia, Maxeiner, Stephan, Milek, Karsten, Moelle, Andrea, Neumann, Gerhard, Nischik, Ruth, Oehrig-Pohl, Edith, Plassmann, Georg, Pohlmeier, Lar, Proepper, Felix, Regner, Stefan, Rieker, Werner, Rose, Ludger, Samer, Holger, Sauter, Joachim, Schaper, Frank, Schiffer, Clemen, Schmidt, Juergen, Scholz, Bernd-M., Schulze, Joerg, Segner, Alexander, Seufert, Jochen, Sigal, Helena, Steindorf, Joerg, Stockhausen, Juergen, Stuebler, Petra, Taeschner, Heidrun, Tews, Dietrich, Tschoepe, Diethelm, Wilhelm, Karl, Zeller-Stefan, Helga, Avramidis, Iakovo, Bousboulas, Stavro, Bristianou, Magdalini, Dimitriadis, Georgio, Elisaf, Mose, Kotsa, Kalliopi, Melidonis, Andrea, Mitrakou, Asimina, Pagkalos, Emmanouil, Papanas, Nikolao, Pappas, Angelo, Sampanis, Christo, Tentolouris, Nikolao, Tsapas, Apostolo, Tzatzagou, Glykeria, Ozaki, Risa, Hajdú, Csaba, Harcsa, Eleonóra, Konyves, Laszlo, Mucsi, Jáno, Pauker, Zsolt, Petró, Gizella, Plés, Zsolt, Revesz, Katalin, Sándor, Vangel, Vass, Viktor, Avogaro, Angelo, Boemi, Massimo, Bonadonna, Riccardo, Consoli, Agostino, De Cosmo, Salvatore, Di Bartolo, Paolo, Dotta, Francesco, Frontoni, Simona, Galetta, Marianna, Gambineri, Alessandra, Gazzaruso, Carmine, Giorgino, Francesco, Lauro, Davide, Orsi, Emanuela, Paolisso, Giuseppe, Perriello, Gabriele, Piatti, Piermarco, Pontiroli, Antonio, Ponzani, Paola, Rivellese, Angela Albarosa, Sesti, Giorgio, Tonolo, Giancarlo, Trevisan, Roberto, Ahn, Chul Woo, Baik, Sei-Hyun, Cha, Bong-Soo, Chung, Choon-Hee, Jang, Hak Chul, Kim, Chong-Jin, Kim, Hye Soon, Kim, In Joo, Lee, Eun Young, Lee, Hyoung Woo, Lee, Kwan-Woo, Moon, Keon-Woong, Namgung, June, Park, Kyong Soo, Yoo, Soon Jib, Yu, Jaemyung, Llamas, Edmundo-Alfredo Bayram, Cervantes-Escárcega, Jose-Lui, Flota-Cervera, Luis Fernando, González-González, José Gerardo, Pascoe-Gonzalez, Sara, Pelayo-Orozco, Emilia Susana, Ramirez-Diaz, Santiago-Paulino, Saldana-Mendoza, Arturo, Jerjes-Díaz, Carlos Sánchez, Torres-Colores, Jose Juan, Vidrio-Velázquez, Maricela, Villagordoa-Mesa, Juan, Beijerbacht, Hugo Peter, Groutars, Reginald G. E. J., Hoek, Boudewijn A, Hoogslag, Pieter A. M., Kooy, Adriaan, Kragten, Johannes A., Lieverse, Aloysius G., Swart, Hendrik P., Viergever, Eric P., Ahlqvist, Jørn, Cooper, John, Gulseth, Hanne, Guttormsen, Gaute, Wium, Cecilie, Arbañil, Hugo, Calderon, Jorge, Camacho, Lui, Espinoza, Augusto Dextre, Garrido, Elizabeth, Luna, Alejandro, Manrique, Helard, Revoredo, Frederick Massucco, Gonzales, Rolando Varga, Rincon, Luis Zapata, Zubiate, Carlo, Ebo, Geraldine, Morales-Palomares, Ellen, Arciszewska, Malgorzata, Banach, Marek, Bijata-Bronisz, Renata, Derezinski, Tadeusz, Gadzinski, Waldemar, Gajek, Jacek, Klodawska, Katarzyna, Krzyzagorska, Ewa, Madej, Andrzej, Miekus, Pawel, Opiela, Jaroslaw, Romanczuk, Piotr, Siegel, Anna, Skokowska, Ewa, Stankiewicz, Andrzej, Stasinska, Teresa, Trznadel-Morawska, Iwona, Witek, Robert, Aksentyev, Sergey, Bondar, Irina, Demidova, Irina, Dreval, Alexander, Ershova, Olga, Galstyan, Gagik, Garganeeva, Alla, Izmozherova, Nadezhda, Karetnikova, Victoria, Kharakhulakh, Marina, Khokhlov, Aleksandr, Kobalava, Zhanna, Koshelskaya, Olga, Kosmacheva, Elena, Kostin, Vladimir, Koziolova, Natalia, Kuzin, Anatoly, Lesnov, Victor, Lysenko, Tatyana, Markov, Valentin, Mayorov, Alexander, Moiseev, Sergey, Myasoedova, Svetlana, Petunina, Nina, Rebrov, Andrey, Ruyatkina, Ludmila, Samoylova, Julia, Sazonova, Olga, Shilkina, Natalia, Sokolova, Nadezhda, Vasilevskaya, Olga, Verbovaya, Nelli, Vishneva, Elena, Vorobyev, Sergey, Vorokhobina, Natalya, Zanozina, Olga, Zhdanova, Elena, Zykova, Tatyana, Burgess, Lesley, Coetzee, Kathleen, Dawood, Saleem, Lombard, Landman, Makotoko, Ellen, Moodley, Rajendran, Oosthuysen, Wessel, Sarvan, Mohamed, Calvo Gómez, Carlo, Cano Rodríguez, Isidoro, Castro Conde, Almudena, Cequier Fillat, Angel, Cuatrecasas Cambra, Guillem, de Álvaro Moreno, Fernando, De Teresa Parreño, Lui, Delgado Lista, Javier, Domínguez Escribano, José Ramón, Durán García, Santiago, Elvira González, Javier, Fernández Rodríguez, José María, Goday Arno, Alberto, Gomez Huelgas, Ricardo, González Juanatey, José Ramón, Hernandez Mijares, Antonio, Jiménez Díaz, Víctor Alfonso, Jodar Gimeno, Esteban, Lucas Morante, Tomá, Marazuela, Monica, Martell Claros, Nieve, Mauricio Puente, Didac, Mena Ribas, Elena, Merino Torres, Juan Francisco, Mezquita Raya, Pedro, Nubiola Calonge, Andreu, Ordoñez Sánchez, Xavier, Pascual Izuel, Jose Maria, Perea Castilla, Verónica, Pérez Pérez, Antonio, Perez Soto, Isabel, Quesada Charneco, Miguel, Quesada Simón, Angustia, Redón Mas, Josep, Rego Iraeta, Antonia, Rodriguez Alvarez, Maria, Rodríguez Rodríguez, Irene, Sabán Ruiz, José, Soto González, Alfonso, Tinahones Madueno, Francisco, Trescoli Serrano, Carlo, Ulied Armiñana, Angel, Bachus, Erasmu, Berndtsson Blom, Katarina, Eliasson, Ken, Koskinen, Pekka, Larnefeldt, Han, Lif-Tiberg, Cornelia, Linderfalk, Carina, Lund, Gustav, Lundman, Pia, Moris, Linda, Olsson, Åke, Salmonsson, Staffan, Sanmartin Berglund, Johan, Sjöberg, Folke, Söderberg, Stefan, Torstensson, Ingemar, Chen, Jung-Fu, Tien, Kai Jen, Tseng, Shih-Ting, Tu, Shih-Te, Wang, Chih-Yuan, Wang, Ji-Hung, Phrommintikul, Arintaya, Yamwong, Sukit, Jintapakorn, Woravut, Hutayanon, Pisit, Sansanayudh, Nakarin, Bazhan, Larysa, Fushtey, Ivan, Grachova, Mariya, Katerenchuk, Vitaliy, Korpachev, Vadym, Kravchun, Nonna, Larin, Oleksandr, Mykhalchyshyn, Galyna, Myshanych, Halyna, Oleksyk, Olga, Orlenko, Valeriia, Pashkovska, Nataliia, Pertseva, Nataliia, Petrosyan, Olena, Smirnov, Ivan, Vlasenko, Maryna, Zlova, Tetiana, Aye, Myint, Baksi, Arun, Balasubramani, Mathangi, Beboso, Ronnie, Blagden, Mark, Bundy, Charle, Cookson, Tobia, Copland, Allan, Emslie-Smith, Alistair, Green, Fiona, Gunstone, Anthony, Issa, Basil, Jackson-Voyzey, Ewart, Johnson, Andrew, Maclean, Malcolm, Mcknight, John, Muzulu, Solomon, O'Connell, Ian, Oyesile, Babatunde, Patterson, Catherine, Pearson, Ewan, Philip, Sam, Smith, Paul, Sukumaran, Usha, Abbas, Jalal, Aggarwala, Gaurav, Akhter, Faiq, Andersen, Jame, Anglade, Moise, Argoud, George, Ariani, Mehrdad, Ashdji, Reswan, Bakhtari, Ladan, Banerjee, Subhash, Bartlett, Andrew, Baum, Howard, Bays, Harold, Beasley, Richard, Belfort de Aguiar, Renata, Benjamin, Sabrina, Bhagwat, Ravi, Bhargava, Anuj, Bode, Bruce, Bratcher, Christina, Briskin, Toby, Brockmyre, Andrew, Broughton, Raymond, Brown, Judith, Budhraja, Madhusudan, Cannon, Kevin, Carr, Jewell, Cathcart, Harold, Cavale, Arvind, Chaykin, Loui, Cheung, Deanna, Childress, Richard, Cohen, Allan, Condit, Jonathan, Cooksey, Erin, Cornett, George Mitchell, Dauber, Ira, Davila, William, De Armas, Lui, Dean, Juliu, Detweiler, Robert, Diaz, Ernesto, Di Giovanna, Michael, Dor, Isaac, Drummond, Waymon, Eagerton, Donald, Earl, John, Eaton, Charle, Ellison, Howard, Farris, Neil, Fiel, Thoma, Firek, Anthony, First, Brian, Forgosh, Le, French, William, Gandy, Winston, Garcia, Ronald, Gill, Santosh, Gordon, Murray, Guice, Michael, Gummadi, Siva, Hackenyos, Jonathan, Hairston, Kristen, Hanson, Lenita, Harrison, Lindsay, Hartman, Israel, Heitner, John, Hejeebu, Srini, Hermany, Paul, Hernandez-Cassis, Carlo, Hidalgo, Horacio, Higgins, Alexander, Ibrahim, Hassan, Jacobs, Shahram, Johnson, David, Joshi, Parag, Kaster, Steven, Kellum, Daniel, Kim, Christopher, Kim, Ellen, Kirby, William, Knouse, Albert, Kulback, Steven, Kumar, Mariananda, Kuruvanka, Tulsida, Labroo, Ajay, Lasswell, William, Lentz, John, Lenzmeier, Thoma, Lewis, David, Li, Zhaoping, Lillestol, Michael, Little, Raymond, Lorraine, Richard, McKeown-Biagas, Cecilia, Mcneill, Robert, Mehta, Anand, Miller, Alan, Moran, Joseph, Morawski, Emily, Nadar, Venkatesh, O'Connor, Thoma, Odio, Alberto, Parker, Reginald, Patel, Rajesh, Phillips, Lawrence, Raad, George, Rahman, Aref, Raikhel, Marina, Raisinghani, Ajit, Rajan, Raj, Rasouli, Neda, Rauzi, Frank, Rohr, Kathryn, Roseman, Hal, Rovner, Sergio, Saba, Fadi, Sachson, Richard, Schabauer, Alex, Schneider, Ricky, Schuchard, Timothy, Sensenbrenner, John, Shlesinger, Yshay, Singh, Narendra, Sivalingam, Kanagaratnam, Stonesifer, Larry, Storey, Daniel, Suh, David, Tahir, Mohammed, Tan, Anjanette, Tan, Marilyn, Taylon, Alain, Thakkar, Maitreya, Tripathy, Devjit, Uwaifo, Gabriel, Vedere, Amarnath, Venugopal, Chandra, Vo, Anthony, Welch, Michelle, Welker, Jame, White, Alexander, Willis, John, Wynne, Alan, Yazdani, Shahram, Rosenberg, Anne, Price, Lauren, Sigmon, Kristina, Lokhngina, Yuliya, Xing, Weibing, Overton, Robert, Stewart, Murray, Stead, Janet, Lindsay, Alistair, Patel, Vicka, Ross, Jorge, Soffer, Joseph, Daga, Shruti, Sowell, Margaret, Patel, Prashant, Garvey, Louisa, Ackert, Jessica, Abraham, Sybil, Sabol, Mary Beth, Altobelli, Desma, Ha, Juyoung, Kulkarni, Mangesh, Somerville, Matthew, Noronha, Drusilla, Casson, Ed, Zang, Eddie, Sandhu, Chamandeep, Kumar, Rakesh, Chen, David, Taft, Lin, Patel, Rajivkumar, Ye, June, Shannon, Jennifer, Wilson, Tim, Babi, Charleen, Miller, Diane, Thorpe, Karl, Russell, Rachael, Bull, Georgina, Hereghty, Belinda, Fernandez-Salazar, Eva, Longley, Troy, Donaldson, Jill, Jarosz, Marie, Murphy, Karen, Adams, Patricia, Smith, Peter, James, Rachel, Richards, Jackie, Sedani, Sangeeta, Althouse, Denise, Watson, David, Lorimer, Jamie, Lauder, Steven, Schultheis, Ron, Womer, Terese, Wraight, Ella, Li, Wenyan, Price-Olsen, Emma, Watson, Anthony, Kelly, Aoife, Mclaughlin, Patricia, Fleming, John, Schubert, Jessica, Schleiden, Debra, Harris, Tara, Prakash, Rahul, Breneman, Jody, Deshpande, Sameer, Saswadkar, Aarti, Kumari, Aditi, Shitut, Aditi, Raorane, Amruta, Karmalkar, Anisha, Mhambrey, Ankita, Bhosale, Archana, Vaphare, Ashok, Patil, Ashwini P, Khandelwal, Chaitali, Shaik, Fayaz, Nadar, Madhumitha, Karka, Mounika, Kadgaonkar, Neha, Gupta, Nikita, Aher, Nutan, Potnis, Omkar, Naicker, Pallavi, Shinde, Rakesh, Sharma, Richa, Godse, Rupali, Solanki, Sheetal, Sahu, Shruti, Dumbre, Snehal, Kumar, Somesh, Patil, Suradnya, Mandal, Trisha, McMurray, John J V, McMurray, John J.V., DeMets, David, McGuire, Darren, Groutars, Reginald G.E.J., Hoogslag, Pieter A.M., McKnight, John, McNeill, Robert, Ha, JuYoung, McLaughlin, Patricia, Hernandez, A. F., Green, J. B., Janmohamed, S., D'Agostino, R. B., Granger, C. B., Jones, N. P., Leiter, L. A., Rosenberg, A. E., Sigmon, K. N., Somerville, M. C., Thorpe, K. M., Mcmurray, J. J. V., Del Prato, S., Califf, R. M., Holman, R., Demets, D., Riddle, M., Goodman, S., Mcguire, D., Alexander, K., Devore, A., Melloni, C., Patel, C., Kong, D., Bloomfield, G., Roe, M., Tricoci, P., Harrison, R., Lopes, R., Mathews, R., Mehta, R., Schuyler Jones, W., Vemulapalli, S., Povsic, T., Eapen, Z., Dombrowski, K., Kolls, B., Jordan, D., Ambrosy, A., Greene, S., Mandawat, A., Shavadia, J., Cooper, L., Sharma, A., Guimaraes, P., Friedman, D., Wilson, M., Endsley, P., Gentry, T., Collier, J., Perez, K., James, K., Roush, J., Pope, C., Howell, C., Johnson, M., Bailey, M., Cole, J., Akers, T., Vandyne, B., Thomas, B., Rich, J., Bartone, S., Beaulieu, G., Brown, K., Chau, T., Christian, T., Coker, R., Greene, D., Haddock, T., Jenkins, W., Haque, G., Marquess, M., Pesarchick, J., Rethaford, R., Stone, A., Al Kawas, F., Anderson, M., Enns, R., Sinay, I., Mathieu, C., Yordanov, V., Hramiak, I., Haluzik, M., Galatius, S., Guerci, B., Nauck, M., Migdalis, I., Tan, C. B. K., Kocsis, G., Giaccari, A., Lee, M. K., Munoz, E. 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Z., Zubiate, C., Ebo, G., Morales-Palomares, E., Arciszewska, M., Banach, M., Bijata-Bronisz, R., Derezinski, T., Gadzinski, W., Gajek, J., Klodawska, K., Krzyzagorska, E., Madej, A., Miekus, P., Opiela, J., Romanczuk, P., Siegel, A., Skokowska, E., Stankiewicz, A., Stasinska, T., Trznadel-Morawska, I., Witek, R., Aksentyev, S., Bondar, I., Demidova, I., Dreval, A., Ershova, O., Galstyan, G., Garganeeva, A., Izmozherova, N., Karetnikova, V., Kharakhulakh, M., Khokhlov, A., Kobalava, Z., Koshelskaya, O., Kosmacheva, E., Kostin, V., Koziolova, N., Kuzin, A., Lesnov, V., Lysenko, T., Markov, V., Mayorov, A., Moiseev, S., Myasoedova, S., Petunina, N., Rebrov, A., Ruyatkina, L., Samoylova, J., Sazonova, O., Shilkina, N., Sokolova, N., Vasilevskaya, O., Verbovaya, N., Vishneva, E., Vorobyev, S., Vorokhobina, N., Zanozina, O., Zhdanova, E., Zykova, T., Burgess, L., Coetzee, K., Dawood, S., Lombard, L., Makotoko, E., Moodley, R., Oosthuysen, W., Sarvan, M., Calvo Gomez, C., Cano Rodriguez, I., Castro Conde, A., Cequier Fillat, A., Cuatrecasas Cambra, G., de Alvaro Moreno, F., De Teresa Parreno, L., Delgado Lista, J., Dominguez Escribano, J. R., Duran Garcia, S., Elvira Gonzalez, J., Fernandez Rodriguez, J. M., Goday Arno, A., Gomez Huelgas, R., Gonzalez Juanatey, J. R., Hernandez Mijares, A., Jimenez Diaz, V. A., Jodar Gimeno, E., Lucas Morante, T., Marazuela, M., Martell Claros, N., Mauricio Puente, D., Mena Ribas, E., Merino Torres, J. F., Mezquita Raya, P., Nubiola Calonge, A., Ordonez Sanchez, X., Pascual Izuel, J. M., Perea Castilla, V., Perez Perez, A., Perez Soto, I., Quesada Charneco, M., Quesada Simon, A., Redon Mas, J., Rego Iraeta, A., Rodriguez Alvarez, M., Rodriguez Rodriguez, I., Saban Ruiz, J., Soto Gonzalez, A., Tinahones Madueno, F., Trescoli Serrano, C., Ulied Arminana, A., Bachus, E., Berndtsson Blom, K., Eliasson, K., Koskinen, P., Larnefeldt, H., Lif-Tiberg, C., Linderfalk, C., Lund, G., Lundman, P., Moris, L., Olsson, A., Salmonsson, S., Sanmartin Berglund, J., Sjoberg, F., Soderberg, S., Torstensson, I., Chen, J. -F., Tien, K. J., Tseng, S. -T., Tu, S. -T., Wang, C. -Y., Wang, J. -H., Phrommintikul, A., Yamwong, S., Jintapakorn, W., Hutayanon, P., Sansanayudh, N., Bazhan, L., Fushtey, I., Grachova, M., Katerenchuk, V., Korpachev, V., Kravchun, N., Larin, O., Mykhalchyshyn, G., Myshanych, H., Oleksyk, O., Orlenko, V., Pashkovska, N., Pertseva, N., Petrosyan, O., Smirnov, I., Vlasenko, M., Zlova, T., Aye, M., Baksi, A., Balasubramani, M., Beboso, R., Blagden, M., Bundy, C., Cookson, T., Copland, A., Emslie-Smith, A., Green, F., Gunstone, A., Issa, B., Jackson-Voyzey, E., Johnson, A., Maclean, M., Mcknight, J., Muzulu, S., O'Connell, I., Oyesile, B., Patterson, C., Pearson, E., Philip, S., Smith, P., Sukumaran, U., Abbas, J., Aggarwala, G., Akhter, F., Andersen, J., Anglade, M., Argoud, G., Ariani, M., Ashdji, R., Bakhtari, L., Banerjee, S., Bartlett, A., Baum, H., Bays, H., Beasley, R., Belfort de Aguiar, R., Benjamin, S., Bhagwat, R., Bhargava, A., Bode, B., Bratcher, C., Briskin, T., Brockmyre, A., Broughton, R., Brown, J., Budhraja, M., Cannon, K., Carr, J., Cathcart, H., Cavale, A., Chaykin, L., Cheung, D., Childress, R., Cohen, A., Condit, J., Cooksey, E., Cornett, G. M., Dauber, I., Davila, W., De Armas, L., Dean, J., Detweiler, R., Diaz, E., Di Giovanna, M., Dor, I., Drummond, W., Eagerton, D., Earl, J., Eaton, C., Ellison, H., Farris, N., Fiel, T., Firek, A., First, B., Forgosh, L., French, W., Gandy, W., Garcia, R., Gill, S., Gordon, M., Guice, M., Gummadi, S., Hackenyos, J., Hairston, K., Hanson, L., Harrison, L., Hartman, I., Heitner, J., Hejeebu, S., Hermany, P., Hernandez-Cassis, C., Hidalgo, H., Higgins, A., Ibrahim, H., Jacobs, S., Johnson, D., Joshi, P., Kaster, S., Kellum, D., Kim, C., Kim, E., Kirby, W., Knouse, A., Kulback, S., Kumar, M., Kuruvanka, T., Labroo, A., Lasswell, W., Lentz, J., Lenzmeier, T., Lewis, D., Li, Z., Lillestol, M., Little, R., Lorraine, R., McKeown-Biagas, C., Mcneill, R., Mehta, A., Miller, A., Moran, J., Morawski, E., Nadar, V., O'Connor, T., Odio, A., Parker, R., Patel, R., Phillips, L., Raad, G., Rahman, A., Raikhel, M., Raisinghani, A., Rajan, R., Rasouli, N., Rauzi, F., Rohr, K., Roseman, H., Rovner, S., Saba, F., Sachson, R., Schabauer, A., Schneider, R., Schuchard, T., Sensenbrenner, J., Shlesinger, Y., Singh, N., Sivalingam, K., Stonesifer, L., Storey, D., Suh, D., Tahir, M., Tan, A., Tan, M., Taylon, A., Thakkar, M., Tripathy, D., Uwaifo, G., Vedere, A., Venugopal, C., Vo, A., Welch, M., Welker, J., White, A., Willis, J., Wynne, A., Yazdani, S., Price, L., Lokhngina, Y., Xing, W., Overton, R., Stewart, M., Stead, J., Lindsay, A., Patel, V., Ross, J., Soffer, J., Daga, S., Sowell, M., Patel, P., Garvey, L., Ackert, J., Abraham, S., Sabol, M. B., Altobelli, D., Ha, J., Kulkarni, M., Noronha, D., Casson, E., Zang, E., Sandhu, C., Kumar, R., Chen, D., Taft, L., Ye, J., Shannon, J., Wilson, T., Babi, C., Miller, D., Russell, R., Bull, G., Hereghty, B., Fernandez-Salazar, E., Longley, T., Donaldson, J., Jarosz, M., Murphy, K., Adams, P., James, R., Richards, J., Sedani, S., Althouse, D., Watson, D., Lorimer, J., Lauder, S., Schultheis, R., Womer, T., Wraight, E., Li, W., Price-Olsen, E., Watson, A., Kelly, A., Mclaughlin, P., Fleming, J., Schubert, J., Schleiden, D., Harris, T., Prakash, R., Breneman, J., Deshpande, S., Saswadkar, A., Kumari, A., Shitut, A., Raorane, A., Karmalkar, A., Mhambrey, A., Bhosale, A., Vaphare, A., Patil, A. P., Khandelwal, C., Shaik, F., Nadar, M., Karka, M., Kadgaonkar, N., Gupta, N., Aher, N., Potnis, O., Naicker, P., Shinde, R., Sharma, R., Godse, R., Solanki, S., Sahu, S., Dumbre, S., Kumar, S., Patil, S., Mandal, T., Skin function and permeability, Dermatology, Hernandez, A, Green, J, Janmohamed, S, D'Agostino, R, Granger, C, Jones, N, Leiter, L, Rosenberg, A, Sigmon, K, Somerville, M, Thorpe, K, Mcmurray, J, Del Prato, S, Califf, R, Holman, R, Demets, D, Riddle, M, Goodman, S, Mcguire, D, Alexander, K, Devore, A, Melloni, C, Patel, C, Kong, D, Bloomfield, G, Roe, M, Tricoci, P, Harrison, R, Lopes, R, Mathews, R, Mehta, R, Schuyler Jones, W, Vemulapalli, S, Povsic, T, Eapen, Z, Dombrowski, K, Kolls, B, Jordan, D, Ambrosy, A, Greene, S, Mandawat, A, Shavadia, J, Cooper, L, Sharma, A, Guimaraes, P, Friedman, D, Wilson, M, Endsley, P, Gentry, T, Collier, J, Perez, K, James, K, Roush, J, Pope, C, Howell, C, Johnson, M, Bailey, M, Cole, J, Akers, T, Vandyne, B, Thomas, B, Rich, J, 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Escribano, J, Duran Garcia, S, Elvira Gonzalez, J, Fernandez Rodriguez, J, Goday Arno, A, Gomez Huelgas, R, Gonzalez Juanatey, J, Hernandez Mijares, A, Jimenez Diaz, V, Jodar Gimeno, E, Lucas Morante, T, Marazuela, M, Martell Claros, N, Mauricio Puente, D, Mena Ribas, E, Merino Torres, J, Mezquita Raya, P, Nubiola Calonge, A, Ordonez Sanchez, X, Pascual Izuel, J, Perea Castilla, V, Perez Perez, A, Perez Soto, I, Quesada Charneco, M, Quesada Simon, A, Redon Mas, J, Rego Iraeta, A, Rodriguez Alvarez, M, Rodriguez Rodriguez, I, Saban Ruiz, J, Soto Gonzalez, A, Tinahones Madueno, F, Trescoli Serrano, C, Ulied Arminana, A, Bachus, E, Berndtsson Blom, K, Eliasson, K, Koskinen, P, Larnefeldt, H, Lif-Tiberg, C, Linderfalk, C, Lund, G, Lundman, P, Moris, L, Olsson, A, Salmonsson, S, Sanmartin Berglund, J, Sjoberg, F, Soderberg, S, Torstensson, I, Chen, J, Tien, K, Tseng, S, Tu, S, Wang, C, Wang, J, Phrommintikul, A, Yamwong, S, Jintapakorn, W, Hutayanon, P, Sansanayudh, N, Bazhan, L, Fushtey, 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Shaik, F, Nadar, M, Karka, M, Kadgaonkar, N, Gupta, N, Aher, N, Potnis, O, Naicker, P, Shinde, R, Sharma, R, Godse, R, Solanki, S, Sahu, S, Dumbre, S, Kumar, S, Patil, S, and Mandal, T

Subjects
Male, Placebo-controlled study, Myocardial Infarction, alanine aminotransferase, albiglutide, bilirubin, placebo, antidiabetic agent, glucagon like peptide 1, rGLP-1 protein, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Glucagon-Like Peptide 1, Cardiovascular Disease, Medicine(all), education.field_of_study, Subcutaneous, Medicine (all), albigutide, Hazard ratio, General Medicine, Middle Aged, Albiglutide, Stroke, Treatment Outcome, Tolerability, Cardiovascular Diseases, Female, type 2 diabetes, Type 2, Human, Adult, medicine.medical_specialty, Injections, Subcutaneous, Population, 030209 endocrinology & metabolism, Placebo, Injections, Subcutaneou, Drug Administration Schedule, Injections, 03 medical and health sciences, Double-Blind Method, Internal medicine, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, education, Aged, Diabetes Mellitus, Type 2, Hypoglycemic Agent, business.industry, Semaglutide, Settore MED/13 - ENDOCRINOLOGIA, Harmony, business
Abstract

Background: \ud Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.\ud \ud Methods: \ud We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.\ud \ud Findings: \ud Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p

Published
2018

49. Association of Thigh Muscle Mass with Insulin Resistance and Incident Type 2 Diabetes Mellitus in Japanese Americans

Author

Nan Hee Cho and Hye Soon Kim

Subjects
medicine.medical_specialty, Letter, endocrine system diseases, business.industry, Epidemiology, Endocrinology, Diabetes and Metabolism, Muscle, skeletal, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, Insulin resistance, medicine.disease, Diabetes mellitus, THIGH MUSCLE MASS, Thigh, Internal medicine, medicine, Original Article, Japanese americans, business, Body mass index
Abstract

Background Skeletal muscle plays a major role in glucose metabolism. We investigated the association between thigh muscle mass, insulin resistance, and incident type 2 diabetes mellitus (T2DM) risk. In addition, we examined the role of body mass index (BMI) as a potential effect modifier in this association. Methods This prospective study included 399 Japanese Americans without diabetes (mean age 51.6 years) who at baseline had an estimation of thigh muscle mass by computed tomography and at baseline and after 10 years of follow-up a 75-g oral glucose tolerance test and determination of homeostasis model assessment of insulin resistance (HOMA-IR). We fit regression models to examine the association between thigh muscle area and incidence of T2DM and change in HOMA-IR, both measured over 10 years. Results Thigh muscle area was inversely associated with future HOMA-IR after adjustment for age, sex, BMI, HOMA-IR, fasting plasma glucose, total abdominal fat area, and thigh subcutaneous fat area at baseline (P=0.033). The 10-year cumulative incidence of T2DM was 22.1%. A statistically significant interaction between thigh muscle area and BMI was observed, i.e., greater thigh muscle area was associated with lower risk of incident T2DM for subjects at lower levels of BMI, but this association diminished at higher BMI levels. Conclusion Thigh muscle mass area was inversely associated with future insulin resistance. Greater thigh muscle area predicts a lower risk of incident T2DM for leaner Japanese Americans.

Published
2019

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