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1.  Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes 
Aims/Introduction
Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients.
Materials and Methods
The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed.
Results
Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were ‘very satisfied’ or ‘satisfied’ with the combined basal insulin and acarbose therapy.
Conclusions
Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone.
doi:10.1111/jdi.12261
PMCID: PMC4364857  PMID: 25802730
Acarbose; Long-acting insulin; Type 2 diabetes
2.  Prevalence, Awareness, and Management of Obesity in Korea: Data from the Korea National Health and Nutrition Examination Survey (1998-2011) 
Diabetes & Metabolism Journal  2014;38(1):35-43.
Background
Obesity is a risk factor for diabetes and several cardiovascular diseases. This study was to investigate the trends in the prevalence, awareness, and management status of obesity among the Korean population for recent 13 years.
Methods
The prevalence, subjective awareness, and management of obesity were investigated in adults aged ≥19 years by using the data from the Korea National Health and Nutrition Examination Surveys (KNHANES) 1998 to 2011.
Results
The number of participants was 8,117, 5,826, 5,500, 3,025, 6,756, 7,506, 6,255, and 6,155 in the KNHANES in years 1998, 2001, 2005, 2007, 2008, 2009, 2010, and 2011, respectively. The prevalence of obesity was 26.9%, 29.2%, 32.9%, 32.5%, 32.0%, 32.6%, 32.0%, and 32.0% in 1998, 2001, 2005, 2007, 2008, 2009, 2010, and 2011, respectively, while the overall prevalence of obesity and abdominal obesity increased by 1.19-fold and 1.24-fold respectively in 2011 compared against 2001. In general, a gradual increase in the prevalence of severe obesity has been observed as years go by. Furthermore, trends of improvements in obesity awareness and management rates were visible over the period of surveys.
Conclusion
Although the management status of obesity has improved during the recent years, more effective strategy to control obesity is needed.
doi:10.4093/dmj.2014.38.1.35
PMCID: PMC3950193  PMID: 24627826
Diabetes mellitus; Korea; Obesity; Prevalence
3.  Higher Prevalence and Awareness, but Lower Control Rate of Hypertension in Patients with Diabetes than General Population: The Fifth Korean National Health and Nutrition Examination Survey in 2011 
Diabetes & Metabolism Journal  2014;38(1):51-57.
Background
We investigated the prevalence, awareness, treatment, and control rate of hypertension in Korean adults with diabetes using nationally representative data.
Methods
Using data of 5,105 adults from the fifth Korea National Health and Nutrition Examination Survey in 2011 (4,389 nondiabetes mellitus [non-DM]), 242 newly diagnosed with DM (new-DM), and 474 previously diagnosed with DM (known-DM), we analyzed the prevalence of hypertension (mean systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive medication) and control rate of hypertension (blood pressure [BP] <130/80 mm Hg).
Results
The prevalence of hypertension in diabetic adults was 54.6% (44.4% in new-DM and 62.6% in known-DM, P<0.0001 and P<0.0001, respectively) compared with non-DM adults (26.2%). Compared to non-DM, awareness (85.7%, P<0.001) and treatment (97.0%, P=0.020) rates were higher in known-DM, whereas no differences were found between new-DM and non-DM. Control rate among all hypertensive subjects was lower in new-DM (14.9%), compared to non-DM (35.1%, P<0.001) and known-DM (33.3%, P=0.004). Control rate among treated subjects was also lower in new-DM (25.2%), compared to non-DM (68.4%, P<0.0001) and known-DM (39.9%, P<0.0001).
Conclusion
Higher prevalence and low control rate of hypertension in adults with diabetes suggest that stringent efforts are needed to control BP in patients with diabetes, particularly in newly diagnosed diabetic patients.
doi:10.4093/dmj.2014.38.1.51
PMCID: PMC3950195  PMID: 24627828
Blood pressure; Diabetes mellitus; Hypertension; Korea National Health and Nutrition Examination Survey
4.  Prevalence and Management of Dyslipidemia in Korea: Korea National Health and Nutrition Examination Survey during 1998 to 2010 
Diabetes & Metabolism Journal  2013;37(6):433-449.
Background
Dyslipidemia is a major risk factor of cardiovascular disease. The aim of this study was to investigate the changing trends in the prevalence and management status of dyslipidemia among Korean adults.
Methods
The prevalence of dyslipidemia and the rates of awareness, treatment, and control of dyslipidemia were investigated in adults aged ≥20 years from the Korea National Health and Nutrition Surveys (KNHANES) 1998 to 2010. The updated National Cholesterol Education Program criteria was used, which define dyslipidemia as having one or more of the following lipid abnormalities: hypercholesterolemia (total cholesterol ≥240 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), hypertriglyceridemia (≥150 mg/dL), hyper-low density lipoprotein (LDL) cholesterolemia (≥160 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), and hypo-high density lipoprotein (HDL)-cholesterolemia (<40 mg/dL in men and <50 mg/dL in women).
Results
The number of participants was 6,921, 4,894, 5,312, 2,733, 6,295, 6,900, and 5,738 in KNHANES 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Age-standardized prevalence rates of dyslipidemia were 54.0%, 65.8%, 66.5%, 60.6%, 58.7%, 58.9%, and 59.0% in 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Hypertriglyceridemia and hypo-HDL-cholesterolemia were the two most frequent lipid abnormalities. The overall prevalence of hypercholesterolemia and hyper-LDL-cholesterolemia increased by 1.36- and 1.35-fold in 2010 compared with 2007, respectively. Awareness, treatment, and control rates of dyslipidemia improved over the period of surveys in both sexes. In 2010, about 30% of dyslipidemic patients who received lipid-lowering treatment reached target levels.
Conclusion
Although the management status of dyslipidemia has improved during recent years, effective strategy is required for achieving better prevention, treatment, and control of dyslipidemia.
doi:10.4093/dmj.2013.37.6.433
PMCID: PMC3881328  PMID: 24404515
Dyslipidemia, Korea; Prevalence
5.  Prevalence of Diabetes and Prediabetes according to Fasting Plasma Glucose and HbA1c 
Diabetes & Metabolism Journal  2013;37(5):349-357.
Background
Due to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c) has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG) level only or the combination of FPG and HbA1c tests.
Methods
Data from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time <8 hours, missing values from fasting glucose or HbA1c level, previous diagnosis of diabetes made by physicians, or current use of antidiabetic medications. Diabetes was defined as FPG ≥126 mg/dL, previous diagnosis of diabetes made by a medical doctor, current use of antidiabetic medications, and/or HbA1c ≥6.5%. Prediabetes was defined as FPG of 100 to 125 mg/dL and/or HbA1c of 5.7% to 6.4%.
Results
When we used FPG only, the prevalence of diabetes and prediabetes were 10.5% (men, 12.6%; women, 8.5%) and 19.3% (men, 23.8%; women, 14.9%), respectively. When HbA1c was included as a diagnostic test, the prevalence of diabetes and prediabetes increased to 12.4% (men, 14.5%; women, 10.4%) and 38.3% (men, 41%; women, 35.7%), respectively. Participants with HbA1c ≥6.5% and fasting glucose level <126 mg/dL were older and had lower estimated glomerular filtration rate.
Conclusion
We concluded that using fasting glucose level only may result in an underestimation of diabetes and prediabetes. HbA1c is an acceptable complementary diagnostic test for diabetes in Korean patients. However, national standardization is needed to order to use HbA1c as a diagnostic method of diabetes and prediabetes.
doi:10.4093/dmj.2013.37.5.349
PMCID: PMC3816136  PMID: 24199164
Diabetes mellitus; Hemoglobin A, glycosylated; Korea National Health and Nutrition Examination Survey; Prediabetic state; Prevalence
6.  Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus in Korea 
Diabetes & Metabolism Journal  2012;36(1):6-12.
Diabetic peripheral neuropathy (DPN), a common and troublesome complication in patients with type 2 diabetes mellitus (T2DM), contributes to a higher risk of diabetic foot ulcer and lower limb amputation. These situations can negatively impact the quality of life of affected individuals. Despite its high prevalence and clinical importance, most diabetes mellitus patients not only do not recognize the presence of diabetic neuropathy, but also do not report their symptoms to physicians or other health care providers. Therefore, DPN is usually under diagnosed and undertreated. For early detection and appropriate intervention for DPN, a careful history, physical with neurologic examination, and prompt treatment are needed in T2DM patients.
doi:10.4093/dmj.2012.36.1.6
PMCID: PMC3283828  PMID: 22363916
Diabetes mellitus, type 2; Diabetic neuropathies; Diabetic peripheral neuropathy; Pain
7.  Prevalence and Associated Factors of Diabetic Retinopathy in Rural Korea: The Chungju Metabolic Disease Cohort Study 
Journal of Korean Medical Science  2011;26(8):1068-1073.
This study was aimed to investigate the prevalence of diabetic retinopathy and its associated factors in rural Korean patients with type 2 diabetes. A population-based, cross-sectional diabetic retinopathy survey was conducted from 2005 to 2006 in 1,298 eligible participants aged over 40 yr with type 2 diabetes identified in a rural area of Chungju, Korea. Diabetic retinopathy was diagnosed by a practicing ophthalmologist using funduscopy. The overall prevalence of diabetic retinopathy in the population was 18% and proliferative or severe non-proliferative form was found in 5.0% of the study subjects. The prevalence of retinopathy was 6.2% among those with newly diagnosed type 2 diabetes and 2.4% of them had a proliferative or severe non-proliferative diabetic retinopathy. The odds ratio of diabetic retinopathy increased with the duration of diabetes mellitus (5-10 yr: 5.2- fold; > 10 yr: 10-fold), postprandial glucose levels (> 180 mg/dL: 2.5-fold), and HbA1c levels (every 1% elevation: 1.34-fold). The overall prevalence of diabetic retinopathy in rural Korean patients was similar to or less than that of other Asian group studies. However, the number of patients with proliferative or severe non-proliferative diabetic retinopathy was still high and identified more frequently at the time of diagnosis. This emphasizes that regular screening for diabetic retinopathy and more aggressive management of glycemia can reduce the number of people who develop diabetic retinopathy.
doi:10.3346/jkms.2011.26.8.1068
PMCID: PMC3154343  PMID: 21860558
Diabetic Retinopathy; Prevalence; Risk Factors
8.  The Effect of Cilostazol on Glucose Tolerance and Insulin Resistance in a Rat Model of Non-insulin Dependent Diabetes Mellitus 
Background:
it has been reported that many peripheral vasodilating drugs might improve insulin resistance. Cilostazol, a antithrombotic agent, increases peripheral blood flow in non-insulin dependent diabetic patients. The effect of cilostazol treatment on insulin resistance in streptozotocin (STZ)-induced non-insulin dependent diabetic Wistar rats was examined.
Methods:
About a half of two-day old neonate siblings were injected intraperitoneally with STZ and maintained for six months, at which time they were compared with age-matched control rats for intraperitoneal glucose tolerance test (IPGTT) and for glucose infusion rate (GINF) in a euglycemic hyperinsulinemic glucose-clamp study. After that, these studies were also performed after feeding rat chow containing cilostazol (100 mg/kg/day) to rats with STZ-induced non-insulin dependent diabetes mellitus for four-weeks and compared with those of age-matched control rats.
Results:
In the intraperitoneal glucose tolerance test studies, plasma glucose levels of STZ-induced non-insulin dependent diabetic rats were significantly higher and plasma insulin levels significantly lower than those of age-matched control rats in the age of six months. Glucose infusion rate was lower in STZ-induced non-insulin dependent diabetic rats than those of age-matched control rats. However, after a four-week cilostazol treatment, glucose infusion rate of STZ-induced non-insulin dependent diabetic rats was not significantly different from that of control rats.
Conclusion:
These findings suggested that cilostazol may improve insulin resistance in STZ-induced non-insulin dependent diabetic rats.
doi:10.3904/kjim.2001.16.2.87
PMCID: PMC4531709  PMID: 11590907
Cilostazol; Insulin resistance; Streptozotocin-induced non-insulin dependent diabetic rat; Euglycemic hyperinsulinemic clamp technique; Glucose tolerance test
9.  Effects of Cyclosporin A on Insulin Binding and Action in Isolated Fat Cells of Rat 
To study the effect of cyclosporin A (CsA) on glucose metabolism in peripheral insulin target cells, we studied the intraperitoneal glucose tolerance test (i.p. GTT), insulin binding, glucose transport and lipogenesis in isolated adipocytes of CsA-treated male Wistar rats. The rats were treated for 7 days with an intramuscular injection of vehicle (control group), or 5 (group I) or 50 mg/kg body weight (group II) of CsA dissolved in ethanol. The results of i.p. GTT in group II showed markedly impaired glucose tolerance with significantly decreased basal and glucose-stimulated serum insulin levels. In isolated adipocytes of CsA-treated rats, the insulin bindings were decreased by 26% in group I and 32% in group II. The maximum insulin-stimulated glucose transports were decreased by 34% in group I and 41% in group II. The maximum insulin-stimulated lipogenesis was decreased by 33% in group I and 37% in group II. There was a right shift of the dose response curves for insulin of glucose transport and lipogenesis of both CsA-treated groups.
In conclusion, these results suggest that CsA produces significant functional changes of pancreatic B cells and also induces insulin resistance in adipocytes due to combined receptor and postreceptor defects in insulin action.
doi:10.3904/kjim.1989.4.2.142
PMCID: PMC4534984  PMID: 2486843
Cyclosporin A; Insulin resistance; Insulin binding; Glucose transport; Lipogenesis
10.  Morphological Change in Pancreatic Islets, Insulin Binding and Intracellular Glucose Metabolism in Adipocytes of Streptozotocin-induced Diabetic Rats* 
To examine the diabetogenic mechanism of streptozotocin, a histological study was performed on the pancreatic islets of male Wistar rats 7 days after an intravenous injection of streptozotocin (75 mg/kg). Furthermore, for the investigation into mechanism of insulin resistance in the insulin-dependent diabetic rats, insulin binding, glucose transport, and lipogenesis were studied in the isolated adipocytes of streptozotocin-induced diabetic rats. 1) The rate of weight gain in the control rats and the diabetic rats were 2.2 ± 1.8 g/day and −2.4 ± 2.1 g/day, respectively (p<0.05). The serum insulin levels in the control rats and the diabetic rats were 23.1 ± 10.8 μU/ml and 16.9 ± 10.6 μU/ml respectively (p<0.05). The plasma glucagon levels in the control rats and the diabetic rats were 165.7 ± 124.9 pg/ml. and 151.2 ± 78.2 pg/ml, respectively (p>0.1).2) Microscopic examination of the pancreatic islets of the diabetic rats revealed a severe degranulation and disintegration of B cells. Electron microscopic examination showed a disruption of the intracytoplasmic organelles of B cells with complete degranulation. But the morphology of A cells was normal.3) Maximal specific insulin binding to receptors in the adipocytes of the diabetic rats (2.10 ± 0.30%) showed an increase compared with that of the control rats (1.12 ± 0.21 %) (p<0.05).4) Insulin receptor concentration in the adipocytes of the diabetic rats (2.33 ± 0.43 ng/0.5 × 105 cells) also showed an increase compared with that of control rats (1.03 ± 0.15 ng/0.5 × 105 cells) (p<0.05).5) The average affinities in the adipocytes of the diabetic rats slightly decreased in the low receptor occupancy state compared with that of the control rats.6) Basal and insulin-stimulated glucose transports in adipocytes of the diabetic rats decreased compared with that of the control rats. The maximal glucose transport in the adipocytes of the diabetic rats was 31.7% of the control value (p<0.005).7) Basal and insulin-stimulated lipogenesis in adipocytes of the diabetic rats decreased compared with that of the control rats. The maximal lipogenesis in the adipocytes of the diabetic rats was 38.4% of the control value (p<0.005).
It can be concluded that streptozotocin produces a diabetogenic mechanism in Wistar rats by directly injuring the pancreatic B cells and inducing hypoinsulinemia. The insulin resistance in the streptozotocin-induced diabetic rats results from the defects in the intracellular glucose metabolism such as glucose transport and lipogenesis.
doi:10.3904/kjim.1987.2.1.8
PMCID: PMC4534923  PMID: 3154820
Streptozotocin; Streptozotocin-induced diabetic rats; Insulin resistance
11.  Triglyceride glucose index, a marker of insulin resistance, is associated with coronary artery stenosis in asymptomatic subjects with type 2 diabetes 
Background
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.
Methods
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].
Results
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 TyG compared with those with lower tertile of TyG (14 % vs. 7.8 %, P = 0.022). On multiple regression analysis, the highest tertile of TyG index was an independent risk factor for CAS after adjustment for other confounders (odds ratio, 3.19 [95 % CI, 1.371–7.424]). Subgroup analysis showed that TyG index showed more significant association with CAS in patients with risk factors such as old age, longer duration of diabetes, poor glycemic control, no statin use, and male gender.
Conclusion
Higher TyG index is associated with increased risk of CAS in asymptomatic subjects with type 2 diabetes, particularly when they have risk factors for cardiovascular disease.
Trial registration
This study was retrospectively registered in ClinicalTrials. gov with the registration number of NCT02070926 in Feb 23, 2014.
doi:10.1186/s12944-016-0324-2
PMCID: PMC5024477  PMID: 27633375
Atherosclerosis; Coronary; TyG index; Type 2 diabetes
12.  Obesity, metabolic health, and mortality in adults: a nationwide population-based study in Korea 
Scientific Reports  2016;6:30329.
BMI, metabolic health status, and their interactions should be considered for estimating mortality risk; however, the data are controversial and unknown in Asians. We aimed to investigate this issue in Korean population. Total 323175 adults were followed-up for 96 (60–120) (median [5–95%]) months in a nationwide population-based cohort study. Participants were classified as “obese” (O) or “non-obese” (NO) using a BMI cut-off of 25 kg/m2. People who developed ≥1 metabolic disease component (hypertension, diabetes, dyslipidaemia) in the index year were considered “metabolically unhealthy” (MU), while those with none were considered “metabolically healthy” (MH). The MUNO group had a significantly higher risk of all-cause (hazard ratio, 1.28 [95% CI, 1.21–1.35]) and cardiovascular (1.88 [1.63–2.16]) mortality, whereas the MHO group had a lower mortality risk (all-cause: 0.81 [0.74–0.88]), cardiovascular: 0.73 [0.57–0.95]), compared to the MHNO group. A similar pattern was noted for cancer and other-cause mortality. Metabolically unhealthy status was associated with higher risk of all-cause and cardiovascular mortality regardless of BMI levels, and there was a dose-response relationship between the number of incident metabolic diseases and mortality risk. In conclusion, poor metabolic health status contributed more to mortality than high BMI did, in Korean adults.
doi:10.1038/srep30329
PMCID: PMC4957204  PMID: 27445194
13.  Association of serum calcium concentrations with fibrinogen and homocysteine in nondiabetic Korean subjects 
Medicine  2016;95(24):e3899.
Abstract
Considerable evidence shows that increased serum calcium levels are associated with metabolic disorders, cardiovascular disease, and increased mortality. This study investigated whether serum calcium, within a normal range, is significantly associated with serum fibrinogen and homocysteine, markers of increased cardiovascular disease risk in nondiabetic Korean subjects.
A cross-sectional analysis was performed on 1096 subjects (mean age, 55.1 ± 11.1 years; 36.1% women) undergoing a general health checkup. Serum biochemistry was analyzed including serum albumin-corrected calcium (Cac), insulin resistance (IR, using homeostasis model assessment [HOMA]), fibrinogen, and homocysteine.
Compared with patients within the lowest Cac quartile, those with higher Cac levels had increased fibrinogen and homocysteine levels as well as an increased proportion of smoking, dyslipidemia, and HOMA-IR. Correlation analyses revealed linear relationships for Cac with fibrinogen and homocysteine in both genders. After adjustment for confounding factors, serum Cac was significantly associated with high fibrinogen (odds ratio [OR] for the highest vs the lowest quartile = 1.76, 95% confidence interval [CI] = 1.09–2.83, P = 0.02) and homocysteine (OR = 1.83, 95% CI = 1.07–3.11, P = 0.027). Multivariate regression models showed that Cac was linearly associated with fibrinogen (standardized β = 0.14, P < 0.001) and homocysteine (standardized β = 0.07, P = 0.009).
High normal calcium concentrations were independently associated with increased levels of fibrinogen and homocysteine. Further investigation is needed to validate whether slightly increased calcium levels within the normal range indicate a higher risk of cardiovascular disease.
doi:10.1097/MD.0000000000003899
PMCID: PMC4998474  PMID: 27310988
atherosclerosis; calcium; fibrinogen; homocysteine
14.  High glucose and palmitate increases bone morphogenic protein 4 expression in human endothelial cells 
Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) aff ect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of infl ammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.
doi:10.4196/kjpp.2016.20.2.169
PMCID: PMC4770107  PMID: 26937213
Bone morphogenic protein 4; Diabetes mellitus; Free fatty acid; High glucose
15.  Relationship between metabolic syndrome and thyroid nodules in healthy Koreans 
Background/Aims:
This study evaluated the relationship between thyroid nodules and metabolic syndrome (MS) and its components in apparently healthy Koreans.
Methods:
We reviewed the records of 3,298 subjects with no noticeable symptoms who underwent thyroid ultrasound imaging as part of a routine check-up between July 2009 and June 2010; of these, 1,308 were excluded based upon predefined criteria. Among the remaining 1,990 patients, we examined the association between MS and its components and the incidence of thyroid nodules.
Results:
Of the 1,990 subjects included in this study, 38.4% (n = 764) had thyroid nodules and 12.7% (n = 253) had MS. Female sex, older age, higher body mass index, larger waist circumference, higher glycated hemoglobin level, lower thyroid stimulating hormone level, and presence of MS were all closely related with the presence of thyroid nodules (all p < 0.05). Furthermore, the relevant number of MS components showed a positive linear correlation with the occurrence of thyroid nodules (p < 0.001). Evidence of MS alone was not independently associated with thyroid nodules after adjusting for sex and age in a multivariate binary logistic regression analysis; however, glycated hemoglobin for females and waist circumference for males, as well as both age and thyroid stimulating hormone for all patients, were identified as independent predictors for the existence of thyroid nodules (all p < 0.05).
Conclusions:
This study suggests a positive relationship between the components of MS and thyroid nodules in an ostensibly healthy Korean population. Our data support the idea that the recent increase in thyroid nodules is partly due to increases in both MS and obesity.
doi:10.3904/kjim.2016.31.1.98
PMCID: PMC4712440  PMID: 26767863
Thyroid nodule; Metabolic syndrome; Obesity
16.  Refractory Graves' Disease Successfully Cured by Adjunctive Cholestyramine and Subsequent Total Thyroidectomy 
Endocrinology and Metabolism  2015;30(4):620-625.
The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with thionamides or inorganic iodine. But several cases of refractory Graves' disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves' disease who complained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves' disease. One kind of thionamides and β-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including β-blockers, inorganic iodine, and two thionamides. She experienced hepatotoxicity from the thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunctive agent for preoperative preparation in patients with severe hyperthyroid Graves's disease that is resistant to conventional therapies.
doi:10.3803/EnM.2015.30.4.620
PMCID: PMC4722420  PMID: 26394731
Graves disease; Drug resistance; Cholestyramine resin
17.  Ambient Temperature and Prevalence of Obesity: A Nationwide Population-Based Study in Korea 
PLoS ONE  2015;10(11):e0141724.
Background
Recent studies have suggested a possible association between outdoor or indoor temperature and obesity. We aimed to examine whether ambient temperature is associated with the prevalence of obesity or abdominal obesity in the Korean population.
Methods
Data on anthropometric, socio-demographic, laboratory and lifestyle factors were retrieved from National Health Insurance System data obtained in 2009–2010. Thirty years (1981 to 2010) of meteorological parameters for 71 observation areas were acquired from the Korea Meteorological Administration. Included in this analysis were 124,354 individuals. A body mass index (BMI) ≥ 25 kg/m2 and a waist circumference (WC) ≥ 90 cm (men) or 85 cm (women) were considered to represent obesity and abdominal obesity, respectively.
Results
The mean annual temperature (MAT) ranged from 6.6°C to 16.6°C, and BMI was positively correlated with MAT (r = 0.0078, P = 0.0065). WC was positively correlated with MAT (r = 0.0165, P < 0.0001) and negatively correlated with the number of days with mean temperature < 0°C (DMT0; r = –0.0129, P = 0.0002). After adjusting for age, sex, smoking status, alcohol consumption, exercise, income, residential area and altitude, the odds ratios (95% CI) for obesity and abdominal obesity in the highest quintile MAT group were 1.045 (1.010, 1.081) and 1.082 (1.042, 1.124), respectively, compared with the lower four quintiles of the MAT group. Similarly, subjects in the area of the lowest quintile of DMT0 had significantly higher odds of abdominal obesity compared with the higher four quintile groups of DMT0.
Conclusion
This study finds an association between ambient temperature and prevalence of obesity in the Korean population when controlling for several confounding factors. Adaptive thermogenesis might be a possible explanation for this phenomenon.
doi:10.1371/journal.pone.0141724
PMCID: PMC4629885  PMID: 26524686
18.  Effects of 6-Month Sitagliptin Treatment on Insulin and Glucagon Responses in Korean Patients with Type 2 Diabetes Mellitus 
Diabetes & Metabolism Journal  2015;39(4):335-341.
Background
This study aimed to evaluate the effect of sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, on insulin secretion and glucagon suppression in Korean subjects with type 2 diabetes mellitus.
Methods
Twenty-four subjects underwent a 75-g oral glucose tolerance test (OGTT) before and after 6 months of sitagliptin treatment. Sitagliptin, insulin, and sulfonylurea were withdrawn for 3 days before OGTT to eliminate any acute effects on β-cell insulin or α-cell glucagon secretion. Venous samples were drawn five times during each OGTT to measure plasma glucose, insulin, and glucagon. Indices on insulin secretion and resistance were calculated.
Results
Early phase insulin secretion, measured by the insulinogenic index significantly increased after 6 months of sitagliptin treatment, especially in the higher baseline body mass index group and higher baseline glycosylated hemoglobin (HbA1c) group. There were no significant differences in the insulin resistance indices before and after sitagliptin treatment. Although no significant differences were observed in the absolute levels of glucagon and the glucagon-to-insulin ratio, there was a significant reduction in the percentile change of glucagon-to-insulin ratio at 30- and 120-minute during the OGTT.
Conclusion
Although the HbA1c level did not decrease significantly after 6 months of sitagliptin treatment, an increase in insulin secretion and reduction in early phase postprandial plasma glucagon-to-insulin ratio excursion was confirmed in Korean subjects with type 2 diabetes.
doi:10.4093/dmj.2015.39.4.335
PMCID: PMC4543198  PMID: 26301196
Dipeptidyl-peptidase 4 inhibitors; Glucagon; Glucose tolerance test; Insulin; Korea
19.  Identification of Intermediate- to High-Risk Papillary Thyroid Carcinoma Patients Who May Be Safely Managed without the Performance of Delayed Stimulated Thyroglobulin Measurements following Total Thyroidectomy and Radioactive Iodine Therapy 
Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients. Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis. Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%. Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures.
doi:10.1155/2015/318916
PMCID: PMC4306371  PMID: 25649811
20.  Accelerated Disease Progression after Discontinuation of Sorafenib in a Patient with Metastatic Papillary Thyroid Cancer 
Endocrinology and Metabolism  2014;29(3):388-393.
Distant metastases from papillary thyroid carcinoma (PTC) are rare and are associated with a poor prognosis. Here, we describe a patient with metastatic PTC who was treated with a tyrosine kinase inhibitor (TKI, sorafenib) for several months that was acutely exacerbated by discontinuation. A 43-year-old male was diagnosed with PTC in February 2004 and underwent total thyroidectomy followed by two courses of high-dose radioactive iodine (RAI) therapy. Despite two additional courses of high-dose RAI therapy, lung and muscle metastases were developed. Treatment with sorafenib was begun in September 2010. After 11 months treatment of sorafenib, newly developed metastatic lesions were found in mediastinal lymph nodes, liver, and bones. Considered as treatment failure, the administration of sorafenib was discontinued. Two weeks after sorafenib treatment was stopped, the disease progressed abruptly and caused death of the patient by respiratory failure. In our patient, PTC progressed rapidly after the cessation of sorafenib treatment. Patients with several other types of cancer have also experienced such rapid disease progression, termed "flare-ups." Physicians should be aware that flare-ups may occur in advanced PTC patients following the cessation of TKI therapy.
doi:10.3803/EnM.2014.29.3.388
PMCID: PMC4192805  PMID: 25309799
Thyroid neoplasms; Papillary; Neoplasm metastasis; Sorafenib
21.  Current Status of Glycemic Control of Patients with Diabetes in Korea: The Fifth Korea National Health and Nutrition Examination Survey 
Diabetes & Metabolism Journal  2014;38(3):197-203.
Background
The Korea National Health and Nutrition Examination Survey (KNHANES) III (2005) reported that 22.9% of individuals with diabetes have a glycated hemoglobin (HbA1c) <6.5% and that 43.5% have an HbA1c <7%. We investigated the levels of glycemic control and the factors associated with glycemic control using data from the KNHANES V (2010 to 2012).
Methods
Subjects with diabetes diagnosed by a physician or those taking antidiabetic medications were classified as individuals with known diabetes. Of 1,498 subjects aged ≥30 years with diabetes, we excluded 157 individuals who were missing HbA1c data. A total of 1,341 subjects were included in the final analysis.
Results
The prevalence of known diabetes was 7.7% (n=1,498, estimated to be 2.32 million people). The proportions of well-controlled diabetes meeting a HbA1c goal of <6.5% and <7% were 27% and 45.6%, respectively. HbA1c increased as the duration of diabetes increased. HbA1c in subjects with a duration of diabetes ≤5 years was lower than in subjects with a duration >5 years. HbA1c in the group taking only oral hypoglycemic agents (OHAs) was significantly lower than that in the group administered only insulin or OHA and insulin in combination. In logistic regression analysis, a longer duration of diabetes, insulin use and the absence of chronic renal failure were associated with HbA1c levels >6.5%.
Conclusion
The level of adequate glycemic control was similar to but slightly improved compared with previous levels. The glycemic control of long-standing diabetes patients is more difficult even though they receive insulin treatment.
doi:10.4093/dmj.2014.38.3.197
PMCID: PMC4083026  PMID: 25003073
Diabetes mellitus; Glycemic control; Korea; Korea National Health and Nutrition Examination Survey
22.  Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey 
Diabetes & Metabolism Journal  2014;38(2):109-119.
Background
Diabetic nephropathy is a leading cause of end stage renal disease and is associated with an increased risk of cardiovascular mortality. It manifests as albuminuria or impaired glomerular filtration rate (GFR), and the prevalence of diabetic nephropathy varies with ethnicity. The prevalence of diabetic nephropathy and its determinants in Korean adults have not previously been studied at the national level. This cross-sectional study was undertaken to ascertain the prevalence and determinants of albuminuria and chronic kidney disease (CKD) in Korean patients with diabetes.
Methods
The Korea National Health and Nutrition Examination Survey (KNHANES) V, conducted in 2011, was used to define albuminuria (n=4,652), and the dataset of KNHANES IV-V (2008-2011) was used to define CKD (n=21,521). Selected samples were weighted to represent the entire civilian population in Korea. Albuminuria was defined as a spot urine albumin/creatinine ratio >30 mg/g. CKD was defined as a GFR <60 mL/min/1.73 m2.
Results
Among subjects with diabetes, 26.7% had albuminuria, and 8.6% had CKD. Diabetes was associated with an approximate 2.5-fold increased risk of albuminuria, with virtually no difference between new-onset and previously diagnosed diabetes. Only systolic blood pressure was significantly associated with albuminuria, and old age, high serum triglyceride levels, and previous cardiovascular disease (CVD) were related with CKD in subjects with diabetes.
Conclusion
Korean subjects with diabetes had a higher prevalence of albuminuria and CKD than those without diabetes. Blood pressure was associated with albuminuria, and age, triglyceride level, and previous CVD were independent determinants of CKD in subjects with diabetes.
doi:10.4093/dmj.2014.38.2.109
PMCID: PMC4021298  PMID: 24851205
Albuminuria; Chronic renal disease; Diabetes mellitus; Diabetic nephropathy; Korea
23.  Current Status of Diabetic Peripheral Neuropathy in Korea: Report of a Hospital-Based Study of Type 2 Diabetic Patients in Korea by the Diabetic Neuropathy Study Group of the Korean Diabetes Association 
Diabetes & Metabolism Journal  2014;38(1):25-31.
Diabetic peripheral neuropathy (DPN) is the most common complication associated with diabetes. DPN can present as a loss of sensation, may lead to neuropathic ulcers, and is a leading cause of amputation. Reported estimates of the prevalence of DPN vary due to differences in study populations and diagnostic criteria. Furthermore, the epidemiology and clinical characteristics of DPN in Korean patients with type 2 diabetes mellitus (T2DM) are not as well understood as those of other complications of diabetes such as retinal and renal disease. Recently, the Diabetic Neuropathy Study Group of the Korean Diabetes Association (KDA) conducted a study investigating the impact of DPN on disease burden and quality of life in patients with T2DM and has published some data that are representative of the nation. This review investigated the prevalence and associated clinical implications of DPN in Korean patients with diabetes based on the KDA study.
doi:10.4093/dmj.2014.38.1.25
PMCID: PMC3950191  PMID: 24627824
Diabetes; Peripheral nervous system diseases; Prevalence; Quality of life
24.  Validity of the medical outcomes study sleep scale in patients with painful diabetic peripheral neuropathy in Korea 
Abstract
Aims/Introduction
Sleep disturbances caused by painful diabetic neuropathy (PDN) might have substantial impacts on the multifaceted aspects of PDN, including quality of life. There are no convincing data on the validation or reliability of sleep problem measurements in patients with PDN in Korea. This large population‐based cross‐sectional study examined psychometric properties of the Medical Outcomes Study (MOS) Sleep Scale in patients with PDN in Korea.
Materials and Methods
Measurements of patient‐reported outcomes (Brief Pain Inventory‐short form, MOS Sleep Scale and EuroQoL Health [EQ‐5D]) were documented. PDN was diagnosed if the average daily pain intensity was ≥4 based on the visual analog scale or if patients were taking medication for their current pain.
Results
There were 577 patients with PDN (41.6% with diabetic peripheral neuropathy). The internal consistency of reliability for the MOS Sleep Scale was 0.80 as measured by Cronbach's alpha. The extent to which multiple items in a dimension were intercorrelated and formed a dimension measuring the same underlying concept (Pearson's correlation coefficient) ranged from 0.24 to 0.71 (all P < 0.001). Each item of the MOS Sleep Scale was significantly correlated with the average pain score and the pain interference score (Pearson's correlation coefficients ranged from 0.20 to 0.28 and from 0.29 to 0.40, respectively; all P < 0.001). The correlations between the EQ‐5D index and the MOS Sleep Scale ranged from −0.27 to −0.31 (all P < 0.001).
Conclusions
The MOS Sleep Scale showed good reliability in the evaluation of PDN in Korean type 2 diabetic patients.
doi:10.1111/jdi.12066
PMCID: PMC4020237  PMID: 24843687
Diabetic neuropathies; Pain; Sleep
25.  Natural Course of Cytologically Benign Thyroid Nodules: Observation of Ultrasonographic Changes 
Endocrinology and Metabolism  2013;28(2):110-118.
Background
The natural course of cytologically benign thyroid nodules remains unclear. The aim of this study was to evaluate whether ultrasonographic (US) changes are associated with changes in nodule volume during follow-up.
Methods
We retrospectively reviewed over 4 years of clinical records of patients with benign thyroid nodules as confirmed by fine needle aspiration (FNA). In total, 186 patients with 202 benign thyroid nodules were included for study. We assessed for changes in nodule volume and examined the cystic portion of the nodule as well as four US features (echogenicity, margin, calcification pattern, and shape).
Results
During follow-up (mean, 21.7±10.7 months) and using 50% as a cutoff value, nodule volumes increased in 11.8%, exhibited no change in 79.9%, and decreased in 8.3% of patients. Proportion of nodules demonstrating at least one US change was 20.8% (42/202). The most common US changes (in descending order of frequency) were cystic change, margin change, and calcification pattern change. Nodule shape and echogenicity rarely changed. Increased nodule volume was not significantly associated with any US features or with the number of FNAs but was associated with younger age at time of diagnosis.
Conclusion
Although a portion of thyroid nodules confirmed as benign showed US changes or volume changes during the follow-up period, these findings may only represent the natural course of benign nodules. Frequent follow-up with US might be needed for only a small number of cases with suspicious US findings.
doi:10.3803/EnM.2013.28.2.110
PMCID: PMC3811716  PMID: 24396664
Thyroid nodule; Neoplasms; Ultrasonography; Growth; Tumor burden

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