kyoil Suh

OBJECTIVE To examine the contribution of obesity to insulin resistance and abnormalities of intracellular glucose and fat metabolism in NIDDM. RESEARCH DESIGN AND METHODS Glucose turnover measurements and indirect calorimetry were performed in 10 obese non-insulin-dependent diabetes mellitus (NIDDM) and 10 lean NIDDM subjects (body mass index 35.3 ± 1.0 vs. 24.1 ± 0.5 kg/m2 P < 0.001) in the basal state and during hyperinsuhnemic (720 pmol · m-2 · min-1) euglycemic (5.0-5.5 mmol/1) clamps. RESULTS Obese and lean NIDDM subjects demonstrated similar basal rates of glucose uptake (GU) (1.15 ± 0.08 vs. 1.26 ± 0.08 mmol/min, NS) as well as oxidative (0.49 ± 0.07 vs. 0.53 ± 0.05 mmol/min, NS) and nonoxidative (0.67 ± 0.10 vs. 0.73 ± 0.12 mmol/min, NS) glucose metabolism. During hyperinsuhnemic glucose clamp studies, rates of GU were lower in obese NIDDM subjects (34.1 ± 2.3 vs. 55.2 ± 3.8 μmol · kg fat-free mass [FFM]-1 · min-1, P ≥ 0.001) as were rates of oxidative (14.1 ± 1.3 vs. 22....

To determine whether improved metabolic control with long term glyburide treatment alters intracellular glucose metabolism independent of effects on glucose uptake (GU), we studied eight obese patients with noninsulin-dependent diabetes mellitus before and 7 months after glyburide therapy. Indirect calorimetry and skeletal muscle biopsies were performed in the basal state and during 300 pmol/m2.min insulin infusions, with glucose turnover rates determined by [3-3H]glucose turnover. During the glucose clamps, rates of GU were matched before and after treatment using equivalent hyperinsulinemia and variable levels of hyperglycemia. After glyburide treatment, rates of GU were decreased in the basal state [4.16 +/- 0.57 vs. 3.29 +/- 0.37 mg/kg fat free mass (FFM)/min; P < 0.05], but similar during glucose clamps (11.53 +/- 1.42 vs. 11.93 +/- 1.32 mg/kg FFM.min; P = NS) according to study design. In both the basal state and during glucose clamps after glyburide therapy, rates of glucose oxidative metabolism (Gox) increased by 68-78% [1.21 +/- 0.16 vs. 2.03 +/- 0.31 mg/kg FFM.min (P < 0.05) and 3.13 +/- 0.51 vs. 5.58 +/- 0.55 mg/kg FFM.min (P < 0.05), respectively], and rates of nonoxidative glucose metabolism decreased [2.96 +/- 0.68 vs. 1.25 +/- 0.21 mg/kg FFM.min (P < 0.05) and 8.40 +/- 1.50 to 6.30 +/- 1.40 mg/kg FFM.min (P < 0.01), respectively]. Circulating plasma FFA levels and rates of fat oxidation (Fox) remained unchanged in both the basal state and during clamp studies. Skeletal muscle glycogen synthase (GS) activity, expressed as fractional velocity, was unchanged by glyburide therapy (2.2 +/- 0.8 vs. 2.7 +/- 0.3% in the basal state and 7.3 +/- 1.8 vs. 6.1 +/- 0.9% during clamps; both P = NS). In summary, at both matched (during clamp studies) and unmatched (during basal studies) rates of GU, improved metabolic control with glyburide therapy resulted in marked improvement of Gox independent of the effects on GU. The improvement in Gox was not associated with changes in Fox, circulating FFA, or muscle GS activity. These data indicate that long term metabolic control achieved by glyburide therapy markedly improves Gox, but not skeletal muscle GS activity, in noninsulin-dependent diabetes mellitus independent of GU and Fox.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve the clinical outcomes remain elusive. We evaluated whether empagliflozin, an SGLT2 inhibitor, ameliorates mitochondrial dysfunction and inflammatory milieu of the kidneys in T2DM patients. We prospectively measured copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) and urinary interleukin-1β (IL-1β) in healthy volunteers (n = 22), in SGLT2 inhibitor-naïve T2DM patients (n = 21) at baseline, and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Both urinary mtDNA copy numbers and IL-1β levels were higher in the T2DM group than in healthy volunteers. Baseline copy numbers of serum mtCOX-3 in the T2DM group were lower than those in heal...

OBJECTIVE The association between thyroid autoimmunity and nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we aimed to investigate the relationship between thyroid autoimmunity and NAFLD in a large cohort of euthyroid subjects. METHODS We analyzed clinical and biochemical data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 1,589 middle-aged participants aged 45-65 years, with normal thyroid function, were included in this study. NAFLD was defined as a hepatic steatosis index of >36. We estimated the odds ratios (ORs) for NAFLD according to anti-thyroid peroxidase antibody (TPOAb) positivity by using logistic regression models, and adjusted for potential confounders. RESULTS Overall, 24% (n=378) of the subjects had NAFLD. Subjects with NAFLD showed a higher positivity for TPOAb (11% vs. 7%, p=0.014) compared to those without NAFLD. TPOAb positivity was a significant risk factor for NAFLD [OR 1.668, 95% confidence interval (CI) 1.019-2.730, p=0.042] even after adjusting for confounding variables, including age, sex, household income, education, smoking, alcohol consumption, walking activity, abdominal obesity, elevated blood pressure, dyslipidemia and hyperglycemia. In addition, TPOAb positivity predicted the risk of advanced liver fibrosis (OR 3.112, 95% CI 1.256-7.713, p=0.014) in subjects with NAFLD, independent of the confounding variables. CONCLUSION In euthyroid subjects, thyroid autoimmunity is associated with NAFLD and advanced liver fibrosis, independent of known metabolic risk factors. Large longitudinal studies in the future will help clarify the causality.

Background The association between thyroid hormone levels and pulmonary function in euthyroid population is still unclear. We aimed to examine the relationship between thyroid function and lung function in a large cohort study of euthyroid subjects. Methods We analyzed biochemical and spirometry data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 1,261 middle-aged participants aged 45–65 years with spirometry tests and normal thyroid function were included in this study. The subjects were grouped according to free thyroxine (fT4) (ng/dL) quartiles (Q1, 0.89–1.09; Q2, 1.10–1.19; Q3, 1.20–1.30; Q4, 1.31–1.76). Obstructive lung pattern was defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.7. The probability of obstructive lung patterns according to fT4 quartiles was assessed using logistic regression models, adjusted for potential confounders. Results Overall, 10.9% of the subjects had an obstructive lung pa...

Hyperthyroidism may be associated or present with a variety of neuromuscular disorders, including thyrotoxic myopathy, exophthalmic ophthalmoplegia, periodic paralysis and myasthenia gravis. In contrast to muscle, peripheral nerve involvement in hyperthyroidism is exceedingly rare, and has received little attention. Paraplegia-like weakness during severe hyperthyroidism was first described by Charcot in 1889, and called Basedow's paraplegia' by Joffory in 1894. However, there has been no reported case in Korea. A 38-year-old woman was admitted for evaluation of progressive weakness and a gait disturbance. Her endocrinological results were compatible with hyperthyroidism. The polyneuropathy was also confirmed with sequential electrophysiological studies of the nerves and muscles. Drug therapy for hyperthyroidism resulted in resolution of the clinical neurological symptoms and progressive improvement of elcctrophysiological findings. Hyperthyroidisms are common medical disorde...

Adrenal myelolipomas are rare benign tumors, composed of a variable mixture of mature adipose tissue and hematopoietic tissue. These tumors are frequently detected incidentally and are usually asymptomatic, and hormonally inactive. During a routine health checkup, a 52-year-old man was found to have a tumor on the bilateral adrenal glands. Abdominal computed tomography revealed a well-defined, heterogeneously enhanced bilateral adrenal mass, suggesting a myelolipoma. The hormonal evaluation revealed adrenocorticotropic hormone (ACTH) dependent Cushing syndrome. The patient underwent left adrenalectomy, and transsphenoidal resection of a pituitary mass. The final diagnosis was adrenal myelolipoma associated with Cushing disease. Growth of right adrenal myelolipoma was detected during the 7-year follow-up. There were enhancing pituitary lesions in repeat magnetic resonance imaging of the sellar region, which implies persistent or recurrent pituitary adenoma. This case reinforces relat...

Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort. A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders. Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting...

The relationship between iodine intake and development of thyroid diseases shows a U-shaped curve with an increase of risk in both deficient and excessive iodine intakes. Our aim was to investigate the relationship between iodine intake and thyroid cancer in patients with thyroid nodules in an iodine-replete area. Retrospective analysis of 1170 patients with thyroid nodules was performed. Urinary iodine concentration (UIC) was measured by inductively-coupled plasma mass spectrometry. Predictive factors for thyroid cancer were evaluated using multivariate logistic regression models. The median UIC in all patients with thyroid nodules was 360 μg/L (range from 4 to 9631 μg/L). More than half of the patients (650/1170, 56 %) belonged to the category of excessive iodine intake (UIC ≥ 300 μg/L) according to WHO iodine recommendations. Patients with thyroid cancer were more likely to be distributed in UIC < 300 μg/L and in UIC ≥ 2500 μg/L than those with benign thyroid nodules. Male gen...

The purpose of this study was to determine the clinicopathologic characteristics of patients with papillary thyroid carcinoma (PTC) by the number of tumor foci. A retrospective analysis of 2095 patients with PTC was performed. The study population was divided into 4 groups based on the number of tumor foci: N1 (1 tumor focus), N2 (2 foci), N3 (3 foci), and N4 (4 or more foci). An increasing number of tumor foci was significantly associated with older age at diagnosis (p = .006), cervical lymph node metastasis (p < .001), and advanced TNM stage of disease (p = .001) at initial surgery. The multivariate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the N2, N3, and N4 groups compared to the N1 group for lateral lymph node metastasis were OR 1.53 (95% CI, 1.05-2.22), OR 2.57 (95% CI, 1.50-4.42), and OR 2.88 (95% CI, 1.42-5.84), respectively. An increase in the number of tumor foci was strongly associated with older age at diagnosis, cervical lymph node metastasis, and advanced TNM stage of PTC. The number of tumor foci independently predicted lateral lymph node metastasis. © 2014 Wiley Periodicals, Inc. Head Neck, 2014.

Background: Hydatidiform mole (H-mole) is characterized by the neoplastic proliferation of trophoblasts. Only 1-10% of patients with partial H-mole will develop a trophoblastic tumor, but 18-29% of those with complete H-mole will develop a persistent trophoblastic tumor. Therefore, the early diagnosis and monitoring after operation of an H-mole disease are very important. Recently, the pregnancy associated plasma protein-A (PAPP-A) was proved to have a similar role as that of IGF binding protein-4 (IGFBP-4) protease, which has shown an increasing function in fetal growth and development by degradation of IGFBP-4 and an increase in IGF in the serum during pregnancy. Our hypothesis is 'the H-mole, which shows placental hyperplasia will also have an IGFBP-4 protease activity, which may be used as in the early diagnosis and monitoring of H-mole disease'. Methods: Serum samples from 6 non-pregnant, 18 pregnant (5 in the 1st trimester, 10 in the 2nd, and 3 in the 3rd), 12 postpart...

Background Fine-needle aspiration is the gold standard, but malignancy rate of the indeterminate cytology is reported as 20-50 %. We aimed to evaluate the efficacy of shear wave elastography (SWE) added to ultrasonogram in the differential diagnosis of thyroid nodules. Methods We retrospectively reviewed the medical records of 258 consecutive patients. Thyroid nodules were divided in to 4 categoies according to maximum elasticity (EMax) and nodule depth/width (D/W) ratio; Category 1 (EMax ≥42.6 kPa & D/W<0.9), Category 2 (EMax <42.6 kPa & D/W<0.9 ), Category 3 (EMax ≥42.6 kPa & D/W≥ 0.9) and Category 4 (EMax<46.2 kPa & D/W≥ 0.9 ). The cutoff value of EMax was set using ROC curve analysis to predict nodular hyperplasia (NH) from follicular neoplasm (FN). Cutoff value ​​for nodule D/W ratio was set using ROC curve analysis for malignancy. Results NH was the most prevalent pathology group in category 1, FN in category 2 and PTC in category 3. The category 3 demonstrated the...

Objective Recent studies have reported that thyroid hormone levels are associated with metabolic syndrome (MetS) even in euthyroid subjects. However, the association between thyroid autoimmunity and MetS is uncertain. We aimed to investigate the relationship between thyroid autoimmunity and MetS in a large cohort study of euthyroid subjects. Methods A total of 4,775 participants aged ≥19 years from the Korea National Health and Nutrition Examination Survey VI (2013-2015) with anti-thyroid peroxidase antibody (TPOAb) results and normal thyroid functions were included in this study. Subjects were grouped according to thyroid autoimmunity (positivity of TPOAb). We estimated the odds ratios (ORs) for MetS according to TPOAb positivity using logistic regression models, adjusted for potential confounders. Results Among the study subjects, 25% (n=1,206) were diagnosed with MetS. Subjects with MetS showed higher median TPOAb levels (6.3 vs 6.8 IU/mL, p<0.001) and higher positivity of TPO...

IntroductionRecent studies have suggested that extracellular circulating and urinary mitochondrial DNA (mtDNA) are associated with mitochondrial dysfunction in obesity and type 2 diabetes mellitus (T2DM). However, the changes to cell-free serum and urinary mtDNA after bariatric surgery in patients with obesity with T2DM have not been investigated to date.Research design and methodsWe prospectively recruited patients with obesity (n=18), and with obesity and T2DM (n=14) who underwent bariatric surgery, along with healthy volunteers (HV) as a control group (n=22). Serum and urinary mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) copy numbers were measured using quantitative PCR (qPCR). The mtDNA copy numbers of patients with obesity (with and without T2DM) were followed up 6 months after surgery.ResultsThe copy numbers of urinary mtND-1 and mtCOX-3 in patients with obesity, with or without T2DM, were higher than tho...

Background and Aims Recent evidences has shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes of type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve clinical outcomes are unclear. Mitochondrial dysfunction plays a principal role in the pathophysiology of T2DM and its complications. We hypothesized empagliflozin, an SGLT2 inhibitor improves mitochondrial dysfunction in T2DM patients. Method We prospectively recruited healthy volunteers (n = 22) and SGLT2 naïve T2DM patients (n = 21). Copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) were measured using quantitative polymerase chain reaction in healthy volunteers and T2DM patients at baseline and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Results Patients with T2DM were ol...

Background Although shear wave elastography (SWE) is reported to be useful in detecting malignant thyroid nodules, it shows a wide range of cut-off values of elasticity index (EI) in detecting malignant nodules. The cause of discrepancy remains unclear. Fibrosis of the tumors is known to increase the EI in SWE, and matching of SWE and surgical histopathology has not been fully illustrated in thyroid cancer. We aimed to evaluate the reproducibility of the new total nodular region of interest (ROI) method excluding the subjective features of focal circular ROI placement and to determine the lesion that causes the elevation of EI on SWE and on histopathology. Methods A total of 29 thyroid cancers from 28 patients were included. We evaluated the reproducibility of EI in the new total nodular ROI using Q-Box Trace program and compared the EI in focal nodular ROI using a 3-mm circular area. We analyzed the correlation between fibrosis and EI. Result The coefficient of variation (CV) of th...

Aims. To evaluate shear-wave elastography (SWE) as a tool to detect postoperative cervical lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC). Methods. Forty-three LNs of 43 patients with PTC undergoing ultrasound (US) and SWE before ultrasound-guided fine-needle aspiration (FNA) for the evaluation of postoperative cervical LN recurrences were analyzed. The mean (EMean), minimum (EMin), maximum (EMax), and standard deviation (ESD) of SWE elasticity indices were measured. Results. Among 43 indeterminate or suspicious LNs, 12 were malignant and 31 were benign. The EMean, EMin, EMax, and ESD values were significantly higher in malignant LNs than in benign LNs (EMean: 37.1 kPa in malignant versus 11.8 kPa in benign LNs, P<0.001; EMin: 11.3 kPa versus 5.1 kPa, P=0.046; EMax: 50.5 kPa versus 23.7 kPa, P<0.001; and ESD: 7.8 kPa versus 4.1 kPa, P=0.006). EMax had the highest accuracy (93.0%) when applied with a cut-off value of 37.5 kPa. It had a positive li...

Recent studies have correlated serum cystatin C (CysC) with vascular complications, but few studies have investigated this correlation in diabetes patients without nephropathy. This study aimed to evaluate if higher serum CysC levels increase the risk for vascular complications in type 2 diabetes mellitus patients with normal renal function or mild renal impairment. A total of 806 consecutive patients with type 2 diabetes mellitus who were admitted to the diabetes center of Soonchunhyang University Hospital for blood glucose control were retrospectively reviewed. Patients with nephropathy were excluded. Subjects were categorized into quartiles of serum CysC levels (Q1, ≤0.65 mg/L; Q2, 0.66 to 0.79 mg/L; Q3, 0.80 to 0.94 mg/L; and Q4, ≥0.95 mg/L). The proportion of patients with diabetic retinopathy (DR) ( for trend <0.001), coronary heart disease (CHD) ( for trend <0.001), and stroke ( for trend <0.001) increased across the serum CysC quartiles. After adjustment for confoun...

Both deficient and excessive iodine intake leads to thyroid disease, which shows U-shaped curves. Our previous study showed that a relatively low [urinary iodine concentration (UIC) <300 μg/L] and extremely excessive (UIC ≥ 2500 μg/L) iodine intake were associated with thyroid cancer in Korea, an iodine-replete area. Papillary thyroid cancer (PTC) accounts for more than 97 % of thyroid cancer and 80% or more PTC cases harbor the BRAF mutation in Korea. We aimed to investigate the relationship between iodine intake and the prevalence of the BRAF mutation in PTC in Korea. UIC was measured by inductively coupled plasma mass spectrometry. The BRAF mutation was detected using both allele-specific polymerase chain reaction and mutant enrichment with 3'-modified oligonucleotide sequencing. Risk factors for the occurrence of BRAF mutations in PTC were evaluated using multivariate logistic regression models. The median UIC in all patients with PTC was 287 μg/L (range from 7 to 7, 426 ...

Several cross-sectional studies have reported that thyroid hormone levels are associated with cardiovascular risk markers and metabolic syndrome (MetS) even in euthyroid subjects. However, the prognostic role of serum thyroid hormone levels in the risk of incident MetS has not been elucidated. We aimed to investigate the associations of baseline serum thyroid hormone levels with the development of MetS in healthy subjects. This 6-year, cross-sectional, longitudinal and follow-up study was conducted in 12 037 euthyroid middle-aged subjects without MetS subjected to comprehensive health examinations. Subjects were grouped according to total triiodothyronine (T3) quartiles. The hazard ratio (HR) for the development of MetS according to T3 quartiles was estimated using Cox proportional hazards model. During the 6-year period, 3544 incident cases of MetS (29%) were identified. The proportion of subjects with incident MetS increased across the T3 quartiles (P for trend <0.001). The HR ...

Fine-needle aspiration biopsy (FNAB) cannot distinguish a follicular thyroid carcinoma (FTC) from a follicular adenoma in follicular lesions. We designed this study to determine whether the preoperative thyroglobulin (Tg) and change in serum Tg during thyroid-stimulating hormone (TSH) suppression can predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion. Among 854 patients who underwent thyroid surgery, the 198 patients who presented with thyroid nodules with a cytological diagnosis of follicular lesion were analyzed. Predictive factors for malignancy were evaluated using multivariate logistic regression models. Subgroup analyses of patients with TSH suppression therapy by levothyroxine were also conducted. Thirty-two patients (16%) had FTC, and 166 patients had confirmed benign nodules. The median preoperative serum Tg levels were significantly higher in patients with FTC compared to those with benign pathology (449 vs. 34 ng/mL, p < 0.001). The serum ...

To examine effects of free fatty acids (FFA) on insulin-stimulated glucose fluxes, euglycemic hyperinsulinemic (86 pmol . kg-1 . min-1) clamps were performed for 5 h in conscious rats with (n = 8) or without (n = 8) lipid-heparin infusion. Glucose infusion rate required to maintain euglycemia was not different between the two groups during the first 2 h of clamps but became significantly lower with lipid-heparin infusion in the 3rd h and thereafter. To investigate changes in intracellular glucose metabolism during lipid-heparin infusion, additional clamps (n = 8 each) were performed for 1, 2, 3, or 5 h with an infusion of [3-3H]glucose. Insulin-stimulated whole body glucose utilization (Rd), glycolysis, and glycogen synthesis were estimated on the basis of tracer concentrations in plasma during the final 40 min of each clamp. Similar to changes in glucose infusion rate, Rd was not different between the two groups in the 1st and 2nd h but was significantly lower with lipid-heparin in...