BACKGROUND: The aim of this study was to investigate the association between regional body fat distribution, especially leg fat mass, and the prevalence of diabetes mellitus (DM) in adult populations. METHODS: A total of 3,181 men and 3,827 postmenopausal women aged 50 years or older were analyzed based on Korea National Health and Nutrition Examination Surveys (2008 to 2010). Body compositions including muscle mass and regional fat mass were measured using dual-energy X-ray absorptiometry. RESULTS: The odds ratios (ORs) for DM was higher with increasing truncal fat mass and arm fat mass, while it was lower with increasing leg fat mass. In a partial correlation analysis adjusted for age, leg fat mass was negatively associated with glycosylated hemoglobin in both sexes and fasting glucose in women. Leg fat mass was positively correlated with appendicular skeletal muscle mass and homeostasis model assessment of β cell. In addition, after adjusting for confounding factors, the OR for DM decreased gradually with increasing leg fat mass quartiles in both genders. When we subdivided the participants into four groups based on the median values of leg fat mass and leg muscle mass, higher leg fat mass significantly lowered the risk of DM even though they have smaller leg muscle mass in both genders (P<0.001). CONCLUSION: The relationship between fat mass and the prevalence of DM is different according to regional body fat distribution. Higher leg fat mass was associated with a lower risk of DM in Korean populations. Maintaining leg fat mass may be important in preventing impaired glucose tolerance.
Absorptiometry, Photon ; Adipose Tissue* ; Adult ; Arm ; Body Composition ; Body Fat Distribution* ; Diabetes Mellitus* ; Fasting ; Female ; Glucose ; Hemoglobin A, Glycosylated ; Homeostasis ; Humans ; Korea ; Leg ; Male ; Muscle, Skeletal ; Odds Ratio ; Prevalence

BACKGROUND/AIMS: Serum fibroblast growth factor-21 (FGF-21) levels are elevated in obesity, metabolic syndrome, and type 2 diabetes. Clinical studies have demonstrated an association between FGF-21 and nonalcoholic fatty liver (NAFL) in the general population. This study investigated the association between FGF-21 and NAFL in Korean men with type 2 diabetes. METHODS: Clinical and biochemical metabolic parameters were measured in 135 Korean men with type 2 diabetes (mean age: 56.2 +/- 9.2 years; HbA1C: 7.6 +/- 1.5%). Serum FGF-21 was determined by enzyme-linked immunosorbent assay. NAFL severity was assessed by ultrasound of the liver. High-grade (hg) NAFL was defined as moderate or severe fatty liver. RESULTS: The patients were divided into three subgroups according to NAFL severity: normal (17.0%), low-grade (50.4%), and high-grade (32.6%). Patients with hgNAFL had a larger waist circumference and higher body mass index (BMI), homeostatic model assessment-estimated insulin resistance (HOMA-IR) score, and triglyceride (TG), liver enzyme, and FGF-21 levels than those with a normal liver. FGF-21 correlated positively with BMI, serum creatinine (Cr), TG, liver enzymes, and high-sensitivity C-reactive protein, but negatively with high density lipoprotein (HDL). In multivariate regression analysis, Cr and TG were independently associated with FGF-21. BMI, TG, HDL, HOMA-IR, and FGF-21 correlated strongly with hgNAFL. The odds ratio (OR) of a 1-standard-deviation increase in FGF-21 predicting hgNAFL was 2.39 (95% confidence interval, 1.55-3.68). The OR remained significant after adjustment for Cr, TG, BMI, and HOMA-IR. CONCLUSIONS: Our findings suggest an independent association of serum FGF-21 with NAFL in Korean men with type 2 diabetes.
Body Mass Index ; C-Reactive Protein ; Creatinine ; Enzyme-Linked Immunosorbent Assay ; Fatty Liver* ; Fibroblasts* ; Humans ; Insulin Resistance ; Lipoproteins ; Liver ; Male ; Obesity ; Odds Ratio ; Triglycerides ; Ultrasonography ; Waist Circumference

Agranulocytosis is a rare but the most serious life-threatening complication of antithyroid drug therapy. Most cases of agranulocytosis occur within the first 3 months of antithyroid drug therapy, but some cases happen several years after starting treatment. However, there is a paucity of data on the delayed onset of agranulocytosis. We report a case of methimazole-induced agranulocytosis with suppurative pharyngotonsillitis occurring during the long-term treatment. A 48-year-old woman with Graves' disease visited our hospital with sore throat and high fever (39.2degrees C). She had continuously been treated with methimazole for the preceding 7 years-15 to 40 mg daily from Jul 2007 until Apr 2014 and 50 mg daily from May 2014 until September 2014. A month ago, the dose of methimazole had been reduced to 10 mg daily due to transient neutropenia. Her initial blood tests showed an absolute neutrophil count of 40/microL. Moreover, physical examination showed right neck enlargement. We stopped methimazole, and she was empirically treated with broad-spectrum antibiotics and granulocyte colony stimulating factor. Neck CT scan detected enlarged right tonsils and lymph node. Cervical lymph node biopsy only showed acute and chronic inflammation. About 3 weeks after she recovered, 10 mCi of radioiodine ablation therapy was performed. This case suggests that the sign of agranulocytosis should be carefully monitored in patients with Graves' disease, throughout the course of treatment with methimazole, even under the long-term therapy.
Agranulocytosis* ; Anti-Bacterial Agents ; Biopsy ; Colony-Stimulating Factors ; Drug Therapy ; Female ; Fever ; Granulocytes ; Graves Disease* ; Hematologic Tests ; Humans ; Inflammation ; Lymph Nodes ; Methimazole ; Middle Aged ; Neck ; Neutropenia ; Neutrophils ; Palatine Tonsil ; Pharyngitis ; Physical Examination ; Tomography, X-Ray Computed

Gastric cancer is one of the most common cancers in the world. The aims of this study were to evaluate the association between polymorphisms in TFF gene family, TFF1, TFF2, and TFF3 and the risk of gastric cancer (GC) and GC subgroups in a Korean population via a case-control study. The eight polymorphisms in TFF gene family were identified by sequencing and genotyped with 377 GC patients and 396 controls by using TaqMan genotyping assay. The rs184432 TT genotype of TFF1 was significantly associated with a reduced risk of GC (odds ratio, [OR) = 0.45; 95% confidence interval, [CI] = 0.25-0.82; P = 0.009), more protective against diffuse-type GC (OR = 0.20; 95% CI = 0.05-0.89; P = 0.035) than GC (OR = 0.34; 95% CI = 0.14-0.82; P = 0.017) in subjects aged < 60 yr, and correlated with lymph node metastasis negative GC and diffuse-type GC (OR = 0.44; 95% CI = 0.23-0.86; P = 0.016 and OR = 0.20; 95% CI = 0.05-0.87; P = 0.031, respectively). In addition, a decreased risk of lymph node metastasis negative GC and diffuse-type GC was observed for rs225359 TT genotype of TFF1 (OR = 0.46, 95% CI = 0.24-0.88; P = 0.020 and OR = 0.21, 95% CI = 0.05-0.88; P = 0.033, respectively). These findings suggest that the rs184432 and rs225359 polymorphisms in TFF1 have protective effects for GC and contribute to the development of GC in Korean individuals.
Adult ; Aged ; Biomarkers, Tumor/*genetics ; Female ; Genetic Markers/genetics ; Genetic Predisposition to Disease/epidemiology/genetics ; Humans ; Incidence ; Male ; Middle Aged ; Peptides/*genetics ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/genetics ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Assessment/methods ; Sensitivity and Specificity ; Stomach Neoplasms/*epidemiology/*genetics ; Tumor Suppressor Proteins/*genetics

PURPOSE: Current management for patients with differentiated thyroid cancer includes near total thyroidectomy and radioactive iodine therapy followed by administration of supraphysiological doses of levothyroxine (L-T4). Although hyperthyroidism is a well known risk factor for osteoporosis, the effects of L-T4 treatment on bone mineral density (BMD) in patients with thyroid cancer do not appear to be as significant as with endogenous hyperthyroidism. In this study, we evaluated the impact of long-term suppressive therapy with L-T4 on BMD and bone turn over markers in Korean female patients receiving L-T4 suppressive therapy. METHODS: We enrolled 94 female subjects (mean age, 50.84 +/- 11.43 years) receiving L-T4 after total or near total thyroidectomy and radioactive iodine therapy for thyroid cancer (mean follow-up period, 12.17 +/- 4.27 years). The subjects were divided into three groups by thyroid stimulating hormone (TSH) level (group 1 with TSH level < or =0.001 microIU/mL, group 2 with TSH level between 0.001 and 0.17 microIU/mL, group 3 with TSH level >0.17 microIU/mL) and four groups by quartile of free T4 level. L-T4 dosage, BMD (examined by dual-energy x-ray absorptiometry), and bone turnover markers were evaluated according to TSH and free T4 levels. RESULTS: No significant decrease was detected in BMD or bone turnover markers according to TSH level or free T4 level. Also, the prevalence of osteoporosis and osteopenia was not different among groups. CONCLUSION: Long-term L-T4 suppressive therapy after thyroid cancer management did not affect bone density or increase the prevalence of osteoporosis even though TSH levels were supraphysiologically suppressed.
Bone Density* ; Bone Diseases, Metabolic ; Female ; Follow-Up Studies ; Humans ; Hyperthyroidism ; Iodine ; Osteoporosis ; Prevalence ; Risk Factors ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Thyrotropin ; Thyroxine*

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to reduce blood glucose in type 2 diabetes by prolonging the activity of circulating incretins. However, the factors that affect the efficacy of sitagliptin have not yet been demonstrated. Therefore, we studied them in a Korean population. METHODS: We performed a retrospective analysis in patients taking sitagliptin in Wonju Christian Hospital. One hundred-fifty patients whose serum HbA1c ranged from 6.5% to 11% participated in this study. These patients were divided into two groups: responder and non-responder. The responder group consisted of subjects with glucose lowering greater than 5% of baseline HbA1c. The others were in non-responder group. We analyzed anthropometric data and biochemical markers in all groups, then compared responder group and non-responder group by logistic regression. RESULTS: The change in HbA1c level across all groups was 8.25 +/- 0.82% to 7.64 +/- 1.03% (P value = 0.000). There were 93 and 57 patients in responder and non-responder group, respectively. The responder group had lower BMI, body fat (kg), body fat (%) than the non-responder group (P value = 0.024, P value = 0.029, P value = 0.025), and the HbA1c lowering effect of sitagliptin was greater in male than female (P value = 0.000). CONCLUSION: In this study, HbA1c was effectively lowered in 62% of the patients. The factors that affect the efficacy of sitagliptin were BMI, body fat (kg) body fat (%), and sex. Based on these results, we conclude that sitagliptin lowers glucose more effectively in non-obese male patients.
Adipose Tissue ; Biomarkers ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Dipeptidyl Peptidase 4 ; Dipeptidyl-Peptidase IV Inhibitors ; Female ; Glucose ; Humans ; Incretins ; Kangwon-do ; Logistic Models ; Male ; Retrospective Studies ; Sitagliptin Phosphate

BACKGROUND: Recently, the measurement of glycated hemoglobin (HbA1c) was recommended as an alternative to fasting plasma glucose or oral glucose tolerance tests for diagnosing diabetes mellitus (DM). In this study, we analyzed HbA1c levels for diabetes mellitus screening in a Korean rural population. METHODS: We analyzed data from 10,111 subjects from a Korean Rural Genomic Cohort study and generated a receiver operating characteristic curve to determine an appropriate HbA1c cutoff value for diabetes. RESULTS: The mean age of the subjects was 56.3+/-8.1 years. Fasting plasma glucose and 2-hour plasma glucose after 75 g oral glucose tolerance tests were 97.5+/-25.6 and 138.3+/-67.1 mg/dL, respectively. The mean HbA1c level of the subjects was 5.7+/-0.9%. There were 8,809 non-DM patients (87.1%) and 1,302 DM patients (12.9%). A positive relationship between HbA1c and plasma glucose levels and between HbA1c and 2-hour plasma glucose levels after oral glucose tolerance tests was found in a scatter plot of the data. Using Youden's index, the proper cutoff level of HbA1c for diabetes mellitus screening was 5.95% (sensitivity, 77%; specificity, 89.4%). CONCLUSION: Our results suggest that the optimal HbA1c level for DM screening is 5.95%.
Cohort Studies ; Diabetes Mellitus ; Fasting ; Glucose ; Glucose Tolerance Test ; Hemoglobin A, Glycosylated ; Hemoglobins ; Humans ; Mass Screening ; Plasma ; ROC Curve ; Rural Population ; Sensitivity and Specificity

Although peroxisome proliferator receptor (PPAR)-alpha and PPAR-gamma agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-delta has not been fully investigated. In this study, we examined the effects of the PPAR-delta agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-delta agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-gamma coactivator (PGC)-1alpha gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-alpha and MCP-1 was also examined in supernatant of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-alpha, MCP-1, and PGC-1alpha were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-delta agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1alpha gene expression, and improvement of insulin signaling.
Animals ; Anti-Inflammatory Agents/*pharmacology/therapeutic use ; Blood Glucose ; Cytokines/genetics/metabolism ; Diabetes Mellitus/blood/immunology/metabolism ; Fatty Liver/blood/*drug therapy/immunology ; Glucose Tolerance Test ; Hep G2 Cells ; Humans ; Insulin Resistance ; Liver/metabolism ; Male ; PPAR delta/*agonists/metabolism ; Rats ; Rats, Long-Evans ; Thiazoles/*pharmacology/therapeutic use ; Triglycerides/metabolism

BACKGROUND: While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model. METHODS: Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9). RESULTS: At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-beta, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups. CONCLUSION: These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-beta and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.
Albuminuria ; Animals ; Chemokine CCL2 ; Collagen Type IV ; Diabetic Nephropathies ; Losartan ; Malondialdehyde ; Oxidative Stress ; Proteinuria ; Rats ; RNA, Messenger ; Spironolactone ; Transforming Growth Factor beta ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A

Thyroid cancer is one of the most common endocrine malignancies. It is known that thyroid cancer can develop during reproductive periods, possibly due to the effects of sex hormones and growth factors such human chorionic gonadotrophin (HCG). Some data suggest that elevated HCG levels during pregnancy or gestational trophoblastic disease can stimulate thyroid cellular proliferation and promote cancer formation; however, a case of papillary thyroid cancer accompanied by a gestational trophoblastic tumor has not been reported. Here, we report the case of a 44-year-old woman with papillary thyroid cancer during treatment for a gestational trophoblastic tumor.
Adult ; Cell Proliferation ; Chorion ; Female ; Gestational Trophoblastic Disease ; Gonadal Steroid Hormones ; Humans ; Intercellular Signaling Peptides and Proteins ; Pregnancy ; Reproduction ; Thyroid Gland ; Thyroid Neoplasms ; Trophoblastic Neoplasms ; Trophoblasts