Relationship between Regional Body Fat Distribution and Diabetes Mellitus: 2008 to 2010 Korean National Health and Nutrition Examination Surveys

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.

Association between Serum Fibroblast Growth Factor-21 Levels and Nonalcoholic Fatty Liver in Korean Men with Type 2 Diabetes / 대한내과학회지

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.

A Case of Methimazole-induced Agranulocytosis Accompanied by Suppurative Pharyngotonsillitis in a Patient with Graves' disease under Long-term Treatment / 계명의대학술지

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.

Bone mineral density and bone turnover markers in patients on long-term suppressive levothyroxine therapy for differentiated thyroid cancer

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 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.

Factors Influencing Glycemic Control Response of Sitagliptin / 임상당뇨병

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.

Peroxisome proliferator-activated receptor delta agonist attenuates hepatic steatosis by anti-inflammatory mechanism

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.

Role of HbA1c in the Screening of Diabetes Mellitus in a Korean Rural Community

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%.

A Case of Trophoblastic Tumor Associated with Papillary Thyroid Cancer / 대한내과학회지

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.

Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model

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.

Optimal Waist Circumference Cutoff Values for Metabolic Syndrome Diagnostic Criteria in a Korean Rural Population

The Korean Society for the Study of Obesity (KSSO) has defined the waist circumference cutoff value of central obesity as 90 cm for men and 85 cm for women. The purpose of this investigation was to determine the corresponding waist circumference values. A total of 3,508 persons in the Korean Rural Genomic Cohort Study were enrolled in this survey. Receiver operating characteristic (ROC) curve analysis was used to find appropriate waist circumference cutoff values in relation to insulin resistance determined by homeostasis model assessment for insulin resistance (HOMA-IR), body mass index (BMI), and components of metabolic syndrome. The optimal waist circumference cutoff values were 87 cm for men and 83 cm for women by ROC analysis to HOMA-IR and 86 cm for men and 83 cm for women by ROC analysis to value with more than two components of metaobolic syndrome. By using a BMI > or =25 kg/m2, 86 cm for men and 82 cm for women were optimal waist circumference cutoff values. In this study, we suggest that the most reasonable waist circumference cutoff values are 86-87 cm for men and 82-83 cm for women.

A case of dyke-davidoff-masson syndrome associated with hypopituitarism and diabetes mellitus / 대한내과학회지

Dyke-Davidoff-Masson syndrome (DDMS) is a rare condition characterized by asymmetric cerebral hemispheric growth with unilateral atrophy, ipsilateral compensatory osseous hypertrophy, hyperpneumatization of the paranasal sinuses and mastoid cells, and contralateral paresis. Varying degrees of hemiparesis, hemiplegia, seizures, mental retardation, and facial asymmetry can be associated with DDMS. We report the case of a 26-year-old man with DDMS associated with hypopituitarism who complained of polydipsia and polyuria. After an oral glucose tolerance test, he was diagnosed with type 2 diabetes. There is no report of DDMS associated with other pituitary dysfunction or hyperglycemia. Clinicians should consider the possibility of coexisting pituitary dysfunction or type 2 diabetes in patients with DDMS, as it is obviously important for the patient's outcome.

A case of acromegaly with empty sella syndrome associated with colonic neoplasm / 대한내과학회지

Acromegaly is a disorder caused by hypersecretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). The most common cause of acromegaly is a pituitary GH-producing adenoma. Complete or partial disappearance of the adenoma, probably as a result of hemorrhage or infarction, may lead to empty sella. A case of acromegaly with empty sella syndrome has rarely been reported in Korea. It has been suggested that acromegaly might be associated with the incidence of colon neoplasm. Here, we describe a case of acromegaly with empty sella syndrome in a patient who was diagnosed with colon cancer.

Relationship between Menopausal Status and Metabolic Syndrome Components in Korean Women / 당뇨병

BACKGROUND: Postmenopausal status is associated with a 60% increased risk for metabolic syndrome. It is thought to be associated with decreased estrogens and increased abdominal obesity in postmenopausal women with metabolic syndrome. The purpose of this study was to investigate the association between metabolic syndrome components and menopausal status. METHODS: A total of 1,926 women were studied and divided into three groups according to their menstrual stage (premenopausal, perimenopausal or postmenopausal). The presence of metabolic syndrome was assessed using the National Cholesterol Education Program's (NCEP) Adult Treatment Panel III criteria. RESULTS: The prevalence of metabolic syndrome was 7.1% in premenopause, 9.8% in perimenopause, and 24.2% in postmenopause. The strong correlation was noted between the metabolic syndrome score and waist circumference in postmenopause (r = 0.56, P < 0.01) and perimenopause (r = 0.60, P < 0.01). Along the menopausal transition, the risk of metabolic syndrome increased with high triglyceride after the age-adjusted (odds ratio (OR) 1.517 [95% confidence interval (CI) 1.014~2.269] in perimenopausal women and OR 1.573 [95% CI 1.025~2.414] in postmenopausal women). In addition, the prevalence of metabolic syndromeincreased in accordance with elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels. CONCLUSION: Triglyceride and waist circumference were important metabolic syndrome components, though ALT and GGT may also be related for predicting metabolic syndrome during the transition to menopause.

Short Insulin Tolerance Test Can Determine the Effects of Thiazolidinediones Treatment in Type 2 Diabetes

PURPOSE: The short insulin tolerance test is a simple and reliable method of estimating insulin sensitivity. This study was designed to compare the insulin sensitizing effects of thiazolidinediones (TZDs) on the degree of insulin resistance, determined by a short insulin tolerance test (Kitt) in type 2 diabetic patients. PATIENTS AND METHODS: Eighty-three subjects (mean age = 57.87 +/- 10.78) with type 2 diabetes mellitus were enrolled and received daily one dose of rosiglitazone (4mg) or pioglitazone (15mg). The mean follow-up duration was 25.39 +/- 9.66 months. We assessed insulin sensitivity using HOMA-IR and the short insulin tolerance test before and after TZDs treatment. RESULTS: When we compared patients' characteristics before and after TZDs treatment, the mean fasting glucose level was significantly decreased (183.27 +/- 55.04 to 137.35 +/- 36.42mg/dL, p or = 2.5%/min; 3.50 +/- 0.75%/min to 2.75 +/- 1.12%/min, p = 0.002). CONCLUSION: The glucose lowering effects of TZDs by improving insulin resistance could be determined by using Kitt. However, Kitt may be a beneficial tool to determine TZDs' effects only when patients' Kitt values are less than 2.5%/min.

Beneficial Effects of Thiazolidinediones on Diabetic Nephropathy in OLETF Rats

PURPOSE: Diabetic nephropathy is the most serious of complications in diabetes mellitus. Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy; however, the mechanism underlying this effect has not been elucidated. We hypothesized that the vascular endothelial growth factor (VEGF) participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy because of the effect it has on VEGF. MATERIALS AND METHODS: 23 Otsuka- Long-Evans-Tokushima-Fatty (OLETF) rats and eight control Long-Evans-Tokushima-Otsuka (LETO) rats were divided into the following four groups: LETO group, control OLETF group, pioglitazone treated group (10mg/kg/day), and rosiglitazone treated group (3mg/kg/day). RESULTS: A progressive increase in urinary protein excretion was observed in the diabetic rats. Glomerular VEGF expression in the control OLETF rats was significantly higher than in the control LETO rats. However, there was a significant reduction in both the glomerular VEGF expression and the VEGF mRNA levels after treatment with pioglitazone and rosiglitazone. The twenty-four hour urine protein levels were significantly decreased in both groups of the treated OLETF rats. CONCLUSION: These results suggest that TZD may have beneficial effects on diabetic nephropathy by reducing the VEGF expression.

Relationship between clinical course and measures of atherosclerosis in diabetic foot / 대한내과학회지

No abstract available.

The Effect of Hormone Replacement Therapy on Carotid Intima-Media Thickness in Healthy Postmenopausal Women / 대한내분비학회지

BACKGROUND: Cardiovascular disease is the leading cause of death in postmenopausal women. The use of hormone replacement therapy (HRT) preventing for cardiovascular disease in postmenopausal women remains controversial. We investigated the effect of HRT on carotid intima-media thickness (IMT) according to the HRT duration in healthy postmenopausal women. METHODS: One hundred and twenty postmenopausal women (mean age: 55.4 +/- 3.3 years) were classified into never users, short-term, and long-term users according to the HRT duration. Carotid IMT was measured, and the clinical and biochemical cardiovascular risk factors were examined. RESULTS: The mean IMT was significantly thinner in the long-term users than that in the never users (0.62 +/- 0.11 vs. 0.71 +/- 0.14 mm, P < 0.01). Also, the maximal IMT was significantly thinner in the short-term and the long-term users. However, there is no significant difference in the mean and maximal IMTs between the estrogen alone and estrogen plus progestins used group. The period exposed to menopause was significantly shorter in the long-term users than that in the never users (1.8 +/- 2.3 vs. 4.3 +/- 3.3 years, P < 0.001). CONCLUSION: Our findings suggest that if HRT is initiated during early postmenopausal period before the onset of atherosclerosis, HRT may have a beneficial effect on the prevention of carotid atherosclerosis.

A Case of Adrenocortical Adenoma Causing Subclinical Cushing's Syndrome Mistaken for Liddle's Syndrome / 대한내분비학회지

Subclinical Cushing's syndrome is defined as an autonomous cortisol hyperproduction without specific clinical signs of cortisol excess, but detectable biochemically as derangements of the hypothalamic-pituitary-adrenal axis function. We report a case of a 33-year-old woman with subclinical Cushing's syndrome caused by left adrenocortical adenoma, mistaken for Liddle's syndrome. The patient complained of fatigue. Laboratory findings showed metabolic alkalosis, hypokalemia, high TTKG (transtubular K concentration gradient), low plasma renin activity, and low serum aldosterone level, that findings implied as Liddle's syndrome. So we performed further study. Hormonal and radiologic studies revealed subclinical Cushing's syndrome with a left adrenal mass. The adrenal mass was resected and pathologically diagnosed as adrenocortical adenoma. After the resection of the left adrenal mass, patient's hormonal levels showed normal range.

Acquired C1 inhibitor deficiency associated with SLE / 대한내과학회지

Acquired C1 inhibitor deficiency is a rare syndrome which usually presents with episodes of angioedema. The association of lupus erythematosus and angioneurotic edema has been previously reported but is usually related to hereditary C1 inhibitor deficiency. Currently the relationship between acquired C1 inhibior deficiency and lupus erythematosus is being discussed. So we report the case of a previously healthy 28-year-old woman, who developed simultaneously and acquired angioneurotic edema and systemic lupus erythematosus.

An analysis on the treatment outcome of acute asthma attack / 천식및알레르기

BACKGROUND AND OBJECTIVE: There has been little clinical data on the treatment outcome of patients with acute asthma attack in Korea. We designed a management protocol of acute asthma, and analyzed clinical p arameters obtained from this protocol. METHOD: A total of 32 cases with acute asthma were treated with oxygen, beta2 agonist, and methylprednisolone. Ipratropium was added in cases of severe attack. After 90 minutes, intravenous aminophylline was given to the patients with poor response. RESULT: Beta2 agonist and methylprednisolone were sufficient for symptom control in 17 cases. Ipratropium and aminophylline were added in 6 and 9 cases, respectively. There was no difference in improvement of PEF, heart rate, respiratory rate, PaO2, PaCO2, and SaO2 at 90 minutes and 8 hours between beta2 agonist inhalation and subcutaneous group. Serum potassium concentration levels significantly decreased in patients treated with ipratropium of aminophylline(n=15, 4.17+/-0.45 vs. 3.99+/-0.35mM/L, p0.05). CONCLUSION: Subcutaneous beta2 agonist may be an alternative to inhalant beta2 agonist for the emergency treatment of acute asthma, and we think a consensus regarding use of aminophylline in the emergency room should be made.