Previously, we have shown the long-term efficacy and biocompatibility of chitosan-coated alginate... more Previously, we have shown the long-term efficacy and biocompatibility of chitosan-coated alginate capsule in allogeneic islet transplantation with canine models of diabetes. In this study, we compared the efficacy and immune response of chitosan-coated alginate capsule in xenogeneic islet transplantation with non-human primates (NHPs). Porcine islets were encapsulated alginate crosslinked with BaCl2, followed by suspension in chitosan solution. Encapsulated porcine islets were transplanted intraperitoneally in NHPs with and without immunosuppressants. Anti-αGal IgM and IgG was measured from the day of transplantation. After transplantation of encapsulated porcine islets, hyperglycemia and exogenous insulin requirements were decreased in the NHP recipients. Porcine C-peptide was detected in plasma after transplantation, but decreased with time. Anti-αGal IgM and IgG began to increase a week after transplantation in NHP without immunosuppressants, while they showed little increase in ...
In general, obesity is a major contributor to metabolic syndrome (MetS) and is associated with in... more In general, obesity is a major contributor to metabolic syndrome (MetS) and is associated with insulin resistance (IR). Metabolically obese but normal weight (MONW) individuals present metabolic abnormalities and features of MetS despite having a normal range of body mass index (BMI). In recent years, different subtypes of obesity have been introduced, including metabolically healthy obese (MHO) and metabolically obese obese (MOO). Also, it has been reported that vitamin D and parathyroid hormone (PTH) are possibly linked with MetS. In this study, we aimed to evaluate the association between serum 25(OH)D, serum PTH, and the risk of metabolic obesity in four subtypes using nationally representative survey data for a Korean population conducted between 2008 and 2010. Of the 29,235 Korean participants, 18,997 subjects aged under 50 years were excluded. Participants with diabetes (n = 1,520), renal insufficiency (glomerular filtration rate [GFR] < 45 ml/min/1.73 m2, chronic kidney d...
Insulin resistance is one of the most important contributing factors to cardiovascular disease. T... more Insulin resistance is one of the most important contributing factors to cardiovascular disease. This study aimed to investigate the association between coronary artery stenosis (CAS) and triglyceride glucose index (TyG index), a simple insulin resistance marker, in asymptomatic subjects with type 2 diabetes. We recruited asymptomatic adults with type 2 diabetes but without previous history of coronary heart disease (n = 888). Significant CAS was defined as maximum intraluminal stenosis ≥70 % by coronary CT angiography. TyG index was calculated as log [fasting triglycerides (mg/dl) x fasting glucose (mg/dl)/2]. Mean age was 63.8 ± 9.5 and 58.9 % of the subjects were men. We analyzed the participants according to the tertile of TyG index. The TyG index was correlated with HOMA-IR (r = 0.397, P < 0.001), and subjects with higher tertile of TyG index were younger but showed worse clinical and metabolic parameters. The prevalence of CAS was higher in subjects with higher tertile of Ty...
International journal of clinical pharmacology and therapeutics, Jan 3, 2016
The American College of Cardiology/American Heart Association (ACC/AHA) guidelines are based on s... more The American College of Cardiology/American Heart Association (ACC/AHA) guidelines are based on studies with a limited number of Asian subjects; therefore, they are difficult to apply to Asian patients, including Korean patients. Data were extracted from the clinical data warehouse system of Seoul St. Mary's hospital (January 2010 - December 2012) to determine the percent change in low-density lipoprotein cholesterol (LDL-C) levels at an average 3 and 6 months from baseline. Statins with statistically similar lowering effects were placed in one group (group A, B, or C). The proportions of patients who achieved LDL-C < 100 mg/dL were compared between baseline LDL-C levels: low ( < 130 mg/dL), medium (130 - 160 mg/dL), and high (> 160 mg/dL). The majority of the 9 statins of various doses (2,349 patients) were effective at 3 months, with additional, smaller decreases at 6 months. The LDL-C lowering effect of group A (atorvastatin (20 mg), rosuvastatin (10 mg)) was ~ 45%; ...
Thyroid : official journal of the American Thyroid Association, 2012
Galectin-3 (G3) immunostaining of fine-needle aspiration (FNA) samples from thyroid nodules is ve... more Galectin-3 (G3) immunostaining of fine-needle aspiration (FNA) samples from thyroid nodules is very useful for the diagnosis of malignancy. The objective of the present study was to determine whether the absence of G3 immunostaining in preoperative FNA samples is associated with favorable clinicopathological parameters, including lymph node (LN) metastasis, in papillary thyroid carcinoma (PTC). The records of 868 patients with PTC who had prethyroidectomy ultrasonography-guided FNA with G3 immunostaining between January 2006 and December 2009 were retrospectively reviewed. G3 immunostaining was considered positive if the percentage of tumor cells showing definite cytoplasmic immunostaining exceeded 5%. Patients who had negative G3 immunostaining of FNA samples were assigned to the G3-negative (G3N) group; whereas those who had positive G3 immunostaining were assigned to the G3-positive (G3P) group. There were 92 patients who were assigned to the G3N group (10.6%) because of the nega...
Thyroid : official journal of the American Thyroid Association, 2012
Positron emission tomography/computed tomography (PET/CT) scan has a role in the surveillance of ... more Positron emission tomography/computed tomography (PET/CT) scan has a role in the surveillance of patients with a history of thyroid carcinoma. Its efficacy after remnant ablation as far as detecting persistent or recurrent thyroid carcinoma before other surveillance methods is not known, however. In intermediate-to-high risk thyroid carcinoma patients we studied whether PET/CT scan, performed 6-12 months after the first remnant ablation, could provide more information than ultrasonography (US) and thyrotropin-stimulated serum thyroglobulin (Tg) determination with diagnostic whole-body scan (DxWBS). We studied 71 subjects with differentiated thyroid cancer (DTC) who were intermediate-to-high risk for persistent/recurrent disease and who had received PET/CT scan, US, and DxWBS simultaneously with stimulated Tg levels 6-12 months after remnant ablation. To evaluate the diagnostic efficacy of PET/CT scan, the sensitivity, specificity, positive predictive value, negative predictive value...
OBJECTIVE—The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not... more OBJECTIVE—The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not been evaluated yet. The aim of this study was to determine whether Lp(a) is an independent risk factor for deteriorating renal function in type 2 diabetic patients with nephropathy. RESEARCH DESIGN AND METHODS—We conducted this prospective study in type 2 diabetic patients with overt proteinuria. Patients were divided into two groups according to their baseline serum Lp(a) level. Group 1 had Lp(a) levels ≤30 mg/dl (n = 40) and group 2 had Lp(a) levels >30 mg/dl (n = 41). Patients were followed for 2 years. Progression of diabetic nephropathy was defined as a greater than twofold increase of follow-up serum creatinine concentration from the baseline value. RESULTS—At baseline and during the follow-up, there was no difference in HbA1c and lipid profile between groups 1 and 2. However, serum creatinine was significantly higher in group 2 than in group 1 after 1 year (148.3 ± 78.0 vs. 10...
OBJECTIVE The aim of this study was to investigate the development of severe hypoglycemia (SH) in... more OBJECTIVE The aim of this study was to investigate the development of severe hypoglycemia (SH) in the presence of cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS From January 2001 to December 2002, a total of 894 patients with type 2 diabetes were enrolled. A cardiovascular autonomic function test (AFT) was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to Valsalva maneuver, and standing. From the results for each of the three tests (0 for normal, 1 for abnormal), a total AFT score of 1 was defined as early CAN, and an AFT score of ≥2 was defined as definite CAN. RESULTS The median follow-up time was 9.5 years. The mean age was 54.5 ± 10.1 years, and the mean duration of diabetes was 8.9 ± 6.3 years. One hundred ninety-six patients (31.4%) showed an abnormal cardiovascular AFT score at baseline. Sixty-two patients (9.9%) experienced 77 episodes of SH (1.33 per 100 pati...
Organ transplantation is now the treatment of choice for many patients with life-threatening chro... more Organ transplantation is now the treatment of choice for many patients with life-threatening chronic diseases. A new set of side effects unique to these groups of patients has become recognized, and bone disease is one of these complications. However, little is known about the effects of myeloablative treatment followed by bone marrow transplantation (BMT) on bone mineral metabolism. We have prospectively investigated 31 patients undergoing BMT for hematologic diseases. Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones, and the biochemical markers of bone turnover were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months, and 1 year after BMT. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry before BMT and 1 year after BMT. The serum carboxy-terminal cross-linked telopeptide of type I collagen increased progressively until 4 weeks after BMT. Thereafter, it began to decrease and reached basal values after 1 year. Serum osteocalcin decreased progressively until 3 weeks after BMT. After that, it increased and reached basal values after 3 months. No distinct differences were observed in the serum biochemical turnover markers between males and females, or between patients who received total body irradiation and those who did not. One year after BMT, lumbar spine BMD had decreased by 2.2%, and total proximal femoral BMD had decreased by 6.2%. Eighty-six percent of the women (12/14) went into a menopausal state immediately after BMT. This was caused by high gonadotropin levels and low estradiol levels. In contrast, gonadotropin levels and testosterone levels did not change significantly in the male patients after BMT. In conclusion, the rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in post-BMT bone loss.
The aim of the present study was to evaluate the independent predictors of coronary artery stenos... more The aim of the present study was to evaluate the independent predictors of coronary artery stenosis in patients with type 2 diabetes mellitus (DM) and subclinical atherosclerosis. A total of 232 patients with type 2 DM and subclinical atherosclerosis underwent multislice computed tomography coronary angiography. Subclinical atherosclerosis was determined by the carotid intima-media thickness (IMT) or carotid plaque. Multislice computed tomography coronary angiography revealed significant coronary stenosis (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% in diameter) in 71 subjects (31%). The subjects who had significant coronary stenosis were much older and had had a longer duration of DM. In particular, the log-transformed albumin/creatinine ratio (ACR) was greater in the subjects with significant coronary stenosis compared to the subjects without significant coronary stenosis. The age- and gender-adjusted odds ratio for significant coronary stenosis increased in proportion to albuminuria with a given estimated glomerular filtration rate. The ACR as a continuous variable (odds ratio 4.167, 95% confidence interval 1.497 to 11.599) or categorical variable (ACR &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;30 μg/mg, odds ratio 4.619, 95% confidence interval 1.562 to 13.659) was associated with an increased risk of significant coronary stenosis, independent of conventional cardiovascular risk factors. In receiver operating characteristic analysis, the ACR had an additive effect with carotid IMT for predicting significant coronary stenosis (area under the curve 0.625 with carotid IMT; area under the curve 0.710 with carotid IMT plus ACR, p = 0.0144). In conclusion, the presence of albuminuria is an independent predictor for significant coronary stenosis in patients with type 2 DM and subclinical atherosclerosis.
Previously, we have shown the long-term efficacy and biocompatibility of chitosan-coated alginate... more Previously, we have shown the long-term efficacy and biocompatibility of chitosan-coated alginate capsule in allogeneic islet transplantation with canine models of diabetes. In this study, we compared the efficacy and immune response of chitosan-coated alginate capsule in xenogeneic islet transplantation with non-human primates (NHPs). Porcine islets were encapsulated alginate crosslinked with BaCl2, followed by suspension in chitosan solution. Encapsulated porcine islets were transplanted intraperitoneally in NHPs with and without immunosuppressants. Anti-αGal IgM and IgG was measured from the day of transplantation. After transplantation of encapsulated porcine islets, hyperglycemia and exogenous insulin requirements were decreased in the NHP recipients. Porcine C-peptide was detected in plasma after transplantation, but decreased with time. Anti-αGal IgM and IgG began to increase a week after transplantation in NHP without immunosuppressants, while they showed little increase in ...
In general, obesity is a major contributor to metabolic syndrome (MetS) and is associated with in... more In general, obesity is a major contributor to metabolic syndrome (MetS) and is associated with insulin resistance (IR). Metabolically obese but normal weight (MONW) individuals present metabolic abnormalities and features of MetS despite having a normal range of body mass index (BMI). In recent years, different subtypes of obesity have been introduced, including metabolically healthy obese (MHO) and metabolically obese obese (MOO). Also, it has been reported that vitamin D and parathyroid hormone (PTH) are possibly linked with MetS. In this study, we aimed to evaluate the association between serum 25(OH)D, serum PTH, and the risk of metabolic obesity in four subtypes using nationally representative survey data for a Korean population conducted between 2008 and 2010. Of the 29,235 Korean participants, 18,997 subjects aged under 50 years were excluded. Participants with diabetes (n = 1,520), renal insufficiency (glomerular filtration rate [GFR] < 45 ml/min/1.73 m2, chronic kidney d...
Insulin resistance is one of the most important contributing factors to cardiovascular disease. T... more Insulin resistance is one of the most important contributing factors to cardiovascular disease. This study aimed to investigate the association between coronary artery stenosis (CAS) and triglyceride glucose index (TyG index), a simple insulin resistance marker, in asymptomatic subjects with type 2 diabetes. We recruited asymptomatic adults with type 2 diabetes but without previous history of coronary heart disease (n = 888). Significant CAS was defined as maximum intraluminal stenosis ≥70 % by coronary CT angiography. TyG index was calculated as log [fasting triglycerides (mg/dl) x fasting glucose (mg/dl)/2]. Mean age was 63.8 ± 9.5 and 58.9 % of the subjects were men. We analyzed the participants according to the tertile of TyG index. The TyG index was correlated with HOMA-IR (r = 0.397, P < 0.001), and subjects with higher tertile of TyG index were younger but showed worse clinical and metabolic parameters. The prevalence of CAS was higher in subjects with higher tertile of Ty...
International journal of clinical pharmacology and therapeutics, Jan 3, 2016
The American College of Cardiology/American Heart Association (ACC/AHA) guidelines are based on s... more The American College of Cardiology/American Heart Association (ACC/AHA) guidelines are based on studies with a limited number of Asian subjects; therefore, they are difficult to apply to Asian patients, including Korean patients. Data were extracted from the clinical data warehouse system of Seoul St. Mary's hospital (January 2010 - December 2012) to determine the percent change in low-density lipoprotein cholesterol (LDL-C) levels at an average 3 and 6 months from baseline. Statins with statistically similar lowering effects were placed in one group (group A, B, or C). The proportions of patients who achieved LDL-C < 100 mg/dL were compared between baseline LDL-C levels: low ( < 130 mg/dL), medium (130 - 160 mg/dL), and high (> 160 mg/dL). The majority of the 9 statins of various doses (2,349 patients) were effective at 3 months, with additional, smaller decreases at 6 months. The LDL-C lowering effect of group A (atorvastatin (20 mg), rosuvastatin (10 mg)) was ~ 45%; ...
Thyroid : official journal of the American Thyroid Association, 2012
Galectin-3 (G3) immunostaining of fine-needle aspiration (FNA) samples from thyroid nodules is ve... more Galectin-3 (G3) immunostaining of fine-needle aspiration (FNA) samples from thyroid nodules is very useful for the diagnosis of malignancy. The objective of the present study was to determine whether the absence of G3 immunostaining in preoperative FNA samples is associated with favorable clinicopathological parameters, including lymph node (LN) metastasis, in papillary thyroid carcinoma (PTC). The records of 868 patients with PTC who had prethyroidectomy ultrasonography-guided FNA with G3 immunostaining between January 2006 and December 2009 were retrospectively reviewed. G3 immunostaining was considered positive if the percentage of tumor cells showing definite cytoplasmic immunostaining exceeded 5%. Patients who had negative G3 immunostaining of FNA samples were assigned to the G3-negative (G3N) group; whereas those who had positive G3 immunostaining were assigned to the G3-positive (G3P) group. There were 92 patients who were assigned to the G3N group (10.6%) because of the nega...
Thyroid : official journal of the American Thyroid Association, 2012
Positron emission tomography/computed tomography (PET/CT) scan has a role in the surveillance of ... more Positron emission tomography/computed tomography (PET/CT) scan has a role in the surveillance of patients with a history of thyroid carcinoma. Its efficacy after remnant ablation as far as detecting persistent or recurrent thyroid carcinoma before other surveillance methods is not known, however. In intermediate-to-high risk thyroid carcinoma patients we studied whether PET/CT scan, performed 6-12 months after the first remnant ablation, could provide more information than ultrasonography (US) and thyrotropin-stimulated serum thyroglobulin (Tg) determination with diagnostic whole-body scan (DxWBS). We studied 71 subjects with differentiated thyroid cancer (DTC) who were intermediate-to-high risk for persistent/recurrent disease and who had received PET/CT scan, US, and DxWBS simultaneously with stimulated Tg levels 6-12 months after remnant ablation. To evaluate the diagnostic efficacy of PET/CT scan, the sensitivity, specificity, positive predictive value, negative predictive value...
OBJECTIVE—The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not... more OBJECTIVE—The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not been evaluated yet. The aim of this study was to determine whether Lp(a) is an independent risk factor for deteriorating renal function in type 2 diabetic patients with nephropathy. RESEARCH DESIGN AND METHODS—We conducted this prospective study in type 2 diabetic patients with overt proteinuria. Patients were divided into two groups according to their baseline serum Lp(a) level. Group 1 had Lp(a) levels ≤30 mg/dl (n = 40) and group 2 had Lp(a) levels >30 mg/dl (n = 41). Patients were followed for 2 years. Progression of diabetic nephropathy was defined as a greater than twofold increase of follow-up serum creatinine concentration from the baseline value. RESULTS—At baseline and during the follow-up, there was no difference in HbA1c and lipid profile between groups 1 and 2. However, serum creatinine was significantly higher in group 2 than in group 1 after 1 year (148.3 ± 78.0 vs. 10...
OBJECTIVE The aim of this study was to investigate the development of severe hypoglycemia (SH) in... more OBJECTIVE The aim of this study was to investigate the development of severe hypoglycemia (SH) in the presence of cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS From January 2001 to December 2002, a total of 894 patients with type 2 diabetes were enrolled. A cardiovascular autonomic function test (AFT) was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to Valsalva maneuver, and standing. From the results for each of the three tests (0 for normal, 1 for abnormal), a total AFT score of 1 was defined as early CAN, and an AFT score of ≥2 was defined as definite CAN. RESULTS The median follow-up time was 9.5 years. The mean age was 54.5 ± 10.1 years, and the mean duration of diabetes was 8.9 ± 6.3 years. One hundred ninety-six patients (31.4%) showed an abnormal cardiovascular AFT score at baseline. Sixty-two patients (9.9%) experienced 77 episodes of SH (1.33 per 100 pati...
Organ transplantation is now the treatment of choice for many patients with life-threatening chro... more Organ transplantation is now the treatment of choice for many patients with life-threatening chronic diseases. A new set of side effects unique to these groups of patients has become recognized, and bone disease is one of these complications. However, little is known about the effects of myeloablative treatment followed by bone marrow transplantation (BMT) on bone mineral metabolism. We have prospectively investigated 31 patients undergoing BMT for hematologic diseases. Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones, and the biochemical markers of bone turnover were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months, and 1 year after BMT. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry before BMT and 1 year after BMT. The serum carboxy-terminal cross-linked telopeptide of type I collagen increased progressively until 4 weeks after BMT. Thereafter, it began to decrease and reached basal values after 1 year. Serum osteocalcin decreased progressively until 3 weeks after BMT. After that, it increased and reached basal values after 3 months. No distinct differences were observed in the serum biochemical turnover markers between males and females, or between patients who received total body irradiation and those who did not. One year after BMT, lumbar spine BMD had decreased by 2.2%, and total proximal femoral BMD had decreased by 6.2%. Eighty-six percent of the women (12/14) went into a menopausal state immediately after BMT. This was caused by high gonadotropin levels and low estradiol levels. In contrast, gonadotropin levels and testosterone levels did not change significantly in the male patients after BMT. In conclusion, the rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in post-BMT bone loss.
The aim of the present study was to evaluate the independent predictors of coronary artery stenos... more The aim of the present study was to evaluate the independent predictors of coronary artery stenosis in patients with type 2 diabetes mellitus (DM) and subclinical atherosclerosis. A total of 232 patients with type 2 DM and subclinical atherosclerosis underwent multislice computed tomography coronary angiography. Subclinical atherosclerosis was determined by the carotid intima-media thickness (IMT) or carotid plaque. Multislice computed tomography coronary angiography revealed significant coronary stenosis (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% in diameter) in 71 subjects (31%). The subjects who had significant coronary stenosis were much older and had had a longer duration of DM. In particular, the log-transformed albumin/creatinine ratio (ACR) was greater in the subjects with significant coronary stenosis compared to the subjects without significant coronary stenosis. The age- and gender-adjusted odds ratio for significant coronary stenosis increased in proportion to albuminuria with a given estimated glomerular filtration rate. The ACR as a continuous variable (odds ratio 4.167, 95% confidence interval 1.497 to 11.599) or categorical variable (ACR &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;30 μg/mg, odds ratio 4.619, 95% confidence interval 1.562 to 13.659) was associated with an increased risk of significant coronary stenosis, independent of conventional cardiovascular risk factors. In receiver operating characteristic analysis, the ACR had an additive effect with carotid IMT for predicting significant coronary stenosis (area under the curve 0.625 with carotid IMT; area under the curve 0.710 with carotid IMT plus ACR, p = 0.0144). In conclusion, the presence of albuminuria is an independent predictor for significant coronary stenosis in patients with type 2 DM and subclinical atherosclerosis.
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Papers by Bong-yun Cha