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Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in the patients with diabetes mellitus. Oxidative stress has been postulated to be a major contributor to the pathogenesis of these events. There is considerable evidence that many biochemical pathways that are adversely affected by hyperglycemia are associated with the generation of reactive oxygen species, and this ultimately leads to increased oxidative stress in a variety of tissues. In the absence of appropriate compensation by the endogenous antioxidant defense network, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause cellular damage and contribute to the late complications of diabetes. Hyperglycemia increases oxidant production by multiple pathways rather than by a single dominant pathway. Glucose can undergo nonenzymatic reactions to form gluco-oxidants and glycated products, which can be oxidants. Metabolism of excessive intracellular glucose can occur by several processes such as aldose reductase, mitochondrial oxidative phosphorylation, activation of NAD(P)H oxidases, and the alteration of the NADPH/NADP ratios. Reactive oxygen species participate in vascular smooth muscle cell growth and migration, modulation of endothelial function, including abnormal endothelium-dependent relaxation and the expression of a proinflammatory phenotype, and modification of the extracellular matrix. All of these events contribute to the development of diabetic microvascular and macrovascular complications, suggesting that the sources of reactive oxygen species and the signaling pathways that they modify may represent important therapeutic targets.
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BACKGROUND Idiopathic central diabetes insipidus (CDI) can be diagnosed when it occurs in the absence of a genetic or secondary cause known to be responsible for diabetes insipidus (DI). Some studies have reported that idiopathic CDI in adults shows a more benign clinical course than in children and young patients. However, the clinical characteristics and progress of this disorder have not been fully described. Therefore, we investigated the clinical courses of adult patients over the age of sixteen years with idiopathic central DI. METHODS: We reviewed the medical records of all patients who had documented cases of idiopathic CDI from 1989 to 2005, and studied clinical features, hormone data, and imaging studies at diagnosis and during at least 1-year of follow-up. RESULTS: There were 9 male (30.0%) and 21 female (70.0%) patients with a mean age of 39.3 years at diagnosis and a mean follow-up duration of 6.9 years. At diagnosis, deficits in anterior pituitary hormones were documented in 6 patients (20%), hyperprolactinemia in 4, and hypogonadism in 2. Two patients had an anterior pituitary hormone deficiency that was newly detected at a mean 3.4 years after the onset of DI. On initial MRI, the posterior pituitary was not hyperintense in 7 of the 30 patients (23.3%), but pituitary stalk thickening was observed in 15 (50.0%). After a mean follow-up of 6.9 years (range: 1 to 18), follow-up pituitary MRI showed improvement or no changes in patients with initial MRI findings of a pituitary abnormality, and no development of new lesions in 7 patients with a normal pituitary finding on initial MRI. CONCLUSION: Two of the 30 patients with idiopathic CDI developed an anterior pituitary hormone deficiency during follow-up, but no subject showed any aggravation on follow-up MRI. No patient showed a newly developed pituitary abnormality on follow-up MRI after a negative finding on the initial MRI.
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Kyung Sun Park, Jung Im Rue, Soo Kyung Kim, In Jae Kim, Sang Wook Lim, Seok Won Park, Yu Lee Kim, Dong Hoon Cha, Yong Wook Cho, Young Kil Choi, Sang Jong Lee
J Korean Endocr Soc. 2006;21(6):490-496. Published online December 1, 2006
BACKGROUND Common carotid artery intima-media thickness (IMT), which is increased in patients with overt hypothyroidism, is an independent risk factor of the atherosclerosis-related disease. This study was performed to compare serum lipid level and common carotid artery IMT among patients with overt hypothyroidism, subclinical hypothyroidism and euthyroidism. METHODS: Patients with newly-diagnosed subclinical (n=32) and overt (n=32) hypothyroidism were selected for this study. All of the patients and an age- and sex-matched euthyroidism cohort were checked for clinical characteristics and serum lipid levels. Common carotid artery IMT was also measured using high resolution B-mode ultrasonography. RESULTS: Statistically significant differences were observed between the total cholesterol levels of patients with subclinical hypothyroidism and those with euthyroidism. When common carotid artery IMT measured by ultrasonography, subclinical (0.67 +/- 0.11 mm) and overt (0.71 +/- 0.12 mm)) hypothyroidism showed significantly increased mean IMT compared to that of euthyroidism (0.58 +/- 0.07 mm, P < 0.05, respectively), but no differences were found between subclinical and overt hypothyroidism. CONCLUSION: We concluded that subclinical hypothyroidism is related to increased common carotid artery IMT as well as dyslipidemia. Therefore, we recommend that treatment principle of subclinical hypothyroidism be established through large-scale, prospective studies performed to determine the effect of thyroid hormone replacement on the reduction of common carotid artery IMT.
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The Effect of Brief Thyroid Functional Changes on Arterial Stiffness in Patients Who Preparing Radioactive Iodine Administration Ho-Su Kim, Jae-Hoon Jung, Jung Hwa Jung, Soo Kyoung Kim, Sungsu Kim, Jeong Rang Park, Rock Bum Kim, Jong Ryeal Hahm International Journal of Thyroidology.2015; 8(2): 161. CrossRef
Changes of Body Composition, Blood Concentrations of Lipid Profiles and Thyroid Hormone After Exercise Training in Hypothyroid-induced Rat Kijin Kim The Korean Journal of Obesity.2012; 21(1): 65. CrossRef
BACKGROUND Recent studies suggest a possible pathogenic linkage between the osteoporosis and atherosclerosis. We investigated the relationship between cardiovascular risk factors, including high sensitivity C-reactive protein (hs-CRP), insulin resistance, lipid profiles and bone metabolism in Korean females. METHODS: Anthropometric measurements were performed on 437 women (mean age 52 yrs), and cardiovascular risk factors, including fasting blood glucose, fasting blood insulin, lipid profiles and hs-CRP, measured. An atherogenic index was calculated using the serum total cholesterol level divided by the high-density lipoprotein cholesterol (HDL-C) level. The lumbar spine bone mineral density (BMD) was measured using dual X-ray absorptiometry. RESULTS: From bivariate analyses, the lumbar spine BMD showed negative correlations with age, systolic and diastolic blood pressures, serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride levels and atherogenic index, and a positive correlation with the HDL-C level. After adjustment for age and BMI, the atherogenic index and HDL-C showed consistent correlation with the lumbar spine BMD. The log-transformed hs-CRP showed no correlation with the lumbar spine BMD. In premenopausal women, age, BMI and atherogenic index showed significant associations with the lumbar spine BMD and the atherogenic index showed consistently significant correlation, even after adjustment for age and BMI. In postmenopausal women, only age and BMI showed significant correlations with the lumbar spine BMD. From multiple linear regression analyses of all the study subjects, age, BMI, atherogenic index and the presence of menopause were found to be determinants of the lumbar spine BMD (R2 = 0.422, p < 0.05), which was consistently significant in analysis performed on premenopausal women (R2 = 0.157, P < 0.05). In postmenopausal women, age and BMI were found to be the determinants of the lumbar spine BMD (R2 = 0.257, P < 0.05). CONCLUSIONS: The lumbar spine BMD was negatively correlated with the atherogenic index in all and in premenopausal women. The menopause seems to play an important role in the relationship of cardiovascular risk factors with BMD in Korean females.
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Comparison of Relationship between Biochemical Indices and Bone Mineral Densityof Pre- and Post- Menopausal Women in Gyeongnam Area Mi-Young Park, Sung-Hee Kim Journal of the East Asian Society of Dietary Life.2017; 27(4): 408. CrossRef
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BACKGROUND Endothelial dysfunction, a pathological feature of obesity, can predict the occurrence of cardiovascular disease. The endothelial function was compared in obese, non-obese, and type 2 diabetic women, and the effect of weight loss on endothelial function in obese premenopausal women was also investigated. METHODS: Twenty type 2 diabetes patients, 35 obese and 20 non-obese non-diabetic subjects were recruited. Both the endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIV) were measured. The body composition, serum lipid, serum adiponectin and resistin were also measured. Weight loss in obese women was obtained by 6 months of calorific restriction, aerobic exercise and medication (sibutramine or orlistat). RESULTS: EDV was significantly impaired in the type 2 diabetes and obese groups compared to the control group (6.0 +/- 1.3% in diabetes group, 6.7 +/- 3.9% in obese group, 12.4 +/- 4.1% in control group, P < 0.01, respectively). The mean weight loss after 6 months was 8.5 +/- 3.2 kg (P < 0.001) in the obese group. There was a significant increase in EDV after weight loss (from 5.8 +/- 3.5% to 12.3 +/- 3.9%, P < 0.05). There was no change in EIV after weight loss. In addition, weight loss was associated with significant reductions in the levels of high-sensitivity C-reactive protein (hs-CRP) and serum triglyceride (P < 0.05, respectively). However, there were no significant changes in the serum adiponectin and resistin levels after weight loss. CONCLUSIONS: Our data demonstrated that weight loss was associated with improved endothelial function in obese premenopausal women, as assessed by brachial artery EDV and reduced hs-CRP.
Hyun Won Shin, In Kyung Jeong, Goo Yeong Cho, Cheul Young Choi, Jong Yeop Kim, Yeong Je Chae, Min Ho Cho, Byung Wan Lee, Seong Jin Lee, Chul Young Park, Eun Gyoung Hong, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yu, Sung Hee Ihm, Moon Ki Choi, Hyung Joon Yoo, Sung Woo Park
J Korean Endocr Soc. 2006;21(6):515-525. Published online December 1, 2006
BACKGROUND It is known that patients with hypopituitarism have a high mortality rate due to the presence of atherosclerosis, cardiovascular diseases and stroke. The aim of this study was the effect of growth hormone (GH) on the atherosclerotic markers and the adipocytokine levels. METHOD: The study was conducted on 13 adult patients with hypopituitarism and growth hormone deficiency (GHD), and they had been stabilized after receiving hormone replacement therapy for other insufficient pituitary hormones, other than GH, for more than one year. Before treatment with GH, we compared the lipid metabolism, glucose metabolism, cardiovascular risk factors and adipocytokine levels, including adiponectin, leptin, TNF-alpha and IL-6, between the GHD patients and 13 healthy adults who were of a similar age and gender distribution. Patients with GHD were treated with 1 U/day of GH for 6 months. We measured insulin-like growth factor-I (IGF-I), blood pressure, body composition, lipid metabolism, glucose metabolism and hs-CRP, cardiac function, adiponectin, leptin, TNF-alpha and IL-6 levels, flow mediated vasodilation (FMD) and nitroglycerin mediated vasodilation (NMD) before and after GH treatment. RESULTS: The patients with hypopituitarism and GHD showed significantly higher levels of total cholesterol (P = 0.002), low-density lipoprotein cholesterol (LDL-C) (P = 0.036), hs-CRP (P = 0.0087) and leptin (P < 0.001) than did the normal healthy adults. However, there was no difference between the normal adults and the patients with GHD for the systolic and diastolic BP, the levels of apoA, apoB, fasting blood glucose(FBG) and HOMA-IR. In the subjects with GHD after treatment with GH, the level of fat mass (P = 0.0017), total cholesterol (P = 0.004), LDL-C (P = 0.001), leptin (P = 0.013), TNF-alpha (P < 0.001) and hs-CRP (P = 0.0001) were significantly reduced, while lean body mass (P = 0.0161), FFA (P = 0.049) and FMD (P = 0.0051) showed a significant increase. However, there was no significant difference in the level of the systolic and diastolic BP, LDL-C, apoA, apoB, LP (a), HOMA-IR, ejection fraction, left ventricular posterior wall, E/A ratio, intraventricular septum, NMD, intima-media thickness, adiponectin, IL-6, FBG and fasting insulin before and after GH treatment. CONCLUSION: The subjects with GHD were vulnerable to cardiovascular disease. GH therapy for 6 months had a positive effect on their various cardiovascular risk factors.
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Molecular Biology of Atherosclerosis In-Kyung Jeong Endocrinology and Metabolism.2010; 25(3): 166. CrossRef
BACKGROUND To develop somatic gene therapy model for diabetes mellitus, it is the most important to control it by glucose concentration. In order to develop the myoblasts that produce insulin by glucose concentration, the transfection of genes of human insulin, rat glucokinase and rat GLUT2 was conducted using C2C12, the murine myoblast cell line. METHODS: pMLC-hINSmut plasmid vector to which human insulin cDNA was inserted in C2C12 cell line, pCB7/GLUT2 and pCB7/GK to which GLUT2 and glucokinase were inserted. Based on the inserted gene, C2C12/INS-GLUT2, C2C12/INS-GK and C2C12/INS-GK-GLUT2 were prepared. In each cell line, its mRNA and protein expression were measured. Also, the capability of producing insulin in low glucose (2.7 mM) and high glucose (25 mM) were compared. RESULTS: 1. It was observed that C2C12/INS-GLUT2, C2C12/INS-GK, C2C12/INS-GK-GLUT2 cell line expressed mRNA and protein of transfected genes, respectively. 2. As for the insulin production depending on the glucose concentration in C2C12/INS, it slightly increased from 0.049 +/- 0.003 micro U/10(6) cells/hr to 0.197 +/- 0.022 micro U/10(6) cells/hr. However, in C2C12/GK-GLUT2-INS, it showed the most evident increase: from 0.251 +/- 0.074 micro U/10(6) cells/hr to 1.325 +/- 0.221 micro U/10(6) cells/hr. 3. The expression of insulin gene decreased in proportion to the insulin production capability, reaching the minimum point at the 8th week. CONCLUSION: Genetically engineered murine myoblast secreted insulin depending on the glucose concentration in vitro and was able to cause its decrement when transplanted. However, it should be continued to study the method to maintain the consistent genetic expression in somatic cell therapy.
Fasting hypoglycemia results from several mechanisms. Autoimmune hypoglycemia is one of the rare causes of hypoglycemia, and characterized by hyperinsulinemia, fasting hypoglycemia and the presence of autoantibodies to insulin or insulin receptor. We report here on a 64-year-old male patient with autoimmune hypoglycemia with end stage renal disease. He had no history of diabetes or insulin use. He had experienced several severe hypoglycemic events. The serum C-peptide level was 7.48 ng/mL and the insulin concentration was 115.4 micro U/mL when the fasting plasma glucose level was 88 mg/dL. The insulin to glucose ratio was 5.42, which suggested the presence of insulinoma. Yet the radiologic studies, including magnetic resonance cholangiopancreatography, endoscopic ultrasonography and selective calcium stimulated venous sampling revealed no evidence of insulinoma. The insulin autoantibody level was 62 micro U/mL. Therefore, we could diagnosis the autoimmune hypoglycemia. The hypoglycemia was treated with prednisolone and the patient recovered from this. His insulin level decreased to 21.11 micro U/mL and the insulin autoantibody level decreased to 34 micro U/mL. Hypoglycemia in the hemodialysis patients is not uncommon. One should bear in mind autoimmune hypoglycemia as one of the causes of hypoglycemia in patients with no history of diabetes.
Adult onset type II citrullinemia is an autosomal recessive disorder of the amino acid metabolism caused by a deficiency of liver specific argininosuccinate synthetase activity. This disease can occur at any age in life with recurrent episodes of neurological signs and symptoms such as disorientation, abnormal behaviors (aggression, irritability and hyperactivity), seizures, coma and potential death from brain edema, which are resulted from hyperammonemia. We should consider this rare metabolic disease for the adult patient who exhibits mental change and hyperammonemia without liver or brain disease. Recently. SLC25A13 gene, encoding the mitochondrial aspartate glutamate carrier protein named citrin, is demonstrated to be responsible for adult onset type II citrullinemia. We experienced a 39-year-old female who suffered from generalized weakness, dizziness and lethargy, and diagnosed as adult onset type II citrullinemia by highly elevated plasma citrulline and ammonia and the SLC25A13 gene mutation. We report here on this unusual case of adult onset type II citrullulinemia with a brief review of the related literature.
Methimazole has remained the cornerstone for the treatment of hyperthyroidism since 1940's and it is a well-tolerated antithyroid drug. Pancytopenia is one of the major side effects of methimazole, but its occurrence is very rare. There have been some case reports about methimazole-induced pancytopenia that was treated with recombinant human granulocyte colony-stimulating factor (G-CSF), but its usefulness is still controversial. We present here a case of a 50-year-old female who had been treated with methimazole for hyperthyroidism and she subsequently presented pancytopenia. G-CSF was given for 10 days and she successfully recovered from the pancytopenia.
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Cystic islet cell neoplasms are among the rarest entities in the differential diagnosis of cystic tumor of the pancreas, and this malady raises difficult clinical problems. The diagnosis of insulinoma could be difficult if the functional activity is incomplete, which possibly leads to blunted symptoms of hypoglycemia and failure in the laboratory to provide evidence of hyperinsulinemia. Furthermore, if the imaging shows a smaller tumor than usual or an unusual morphology like cyctic tumor, then physicians can become somewhat confused. We report here on a clinical case of cystic insulinoma with the typical neuroglycopenic symptoms and laboratory-confirmed hyperinsulinemia. At resection, a 2-cm cavitary mass without central necrosis was excised and this was confirmed histologically as a purely cystic insulioma. This is the first report of a functional cystic insulinoma of the pancreas in Korea. We suggest that the differential diagnosis of endocrine tumor must be considered for any pancreatic cyst, and especially when it is discovered in a patient who is clinically suggestive of having the associated syndrome.
Herein is reported the case of a 43-year-old woman, who experienced an acute aortic dissection associated with underlying Cushing's syndrome. The patient had central obesity and a moon face of ten years duration, but had never sought medical consultation. On the day of her presentation, she experienced a severe chest pain radiating to her back. Computed tomography revealed a Stanford type B acute aortic dissection and a left adrenal mass. From her hormonal study results, clinical symptoms and signs, she was diagnosed with Cushing's syndrome, which was due to a left adrenal adenoma. After medical treatment to stabilize the aortic dissection, she underwent left adrenalectomy. The aortic lesion of the present patient suggests that hypercortisolemia arising from Cushing's syndrome might be related to the development of acute aortic dissection.