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1.  Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes 
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.
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.
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.
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.
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.
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.
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.
Although the management status of obesity has improved during the recent years, more effective strategy to control obesity is needed.
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.
We investigated the prevalence, awareness, treatment, and control rate of hypertension in Korean adults with diabetes using nationally representative data.
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).
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).
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.
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.
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.
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).
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.
Although the management status of dyslipidemia has improved during recent years, effective strategy is required for achieving better prevention, treatment, and control of dyslipidemia.
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.
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.
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%.
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.
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.
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.
PMCID: PMC3283828  PMID: 22363916
Diabetes mellitus, type 2; Diabetic neuropathies; Diabetic peripheral neuropathy; Pain
7.  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.
PMCID: PMC4306371  PMID: 25649811
8.  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.
PMCID: PMC4192805  PMID: 25309799
Thyroid neoplasms; Papillary; Neoplasm metastasis; Sorafenib
9.  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.
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).
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.
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%.
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.
PMCID: PMC4083026  PMID: 25003073
Diabetes mellitus; Glycemic control; Korea; Korea National Health and Nutrition Examination Survey
10.  Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey 
Diabetes & Metabolism Journal  2014;38(2):109-119.
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.
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.
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.
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.
PMCID: PMC4021298  PMID: 24851205
Albuminuria; Chronic renal disease; Diabetes mellitus; Diabetic nephropathy; Korea
11.  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.
PMCID: PMC3950191  PMID: 24627824
Diabetes; Peripheral nervous system diseases; Prevalence; Quality of life
12.  Validity of the medical outcomes study sleep scale in patients with painful diabetic peripheral neuropathy in Korea 
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.
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).
The MOS Sleep Scale showed good reliability in the evaluation of PDN in Korean type 2 diabetic patients.
PMCID: PMC4020237  PMID: 24843687
Diabetic neuropathies; Pain; Sleep
13.  Natural Course of Cytologically Benign Thyroid Nodules: Observation of Ultrasonographic Changes 
Endocrinology and Metabolism  2013;28(2):110-118.
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.
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).
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.
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.
PMCID: PMC3811716  PMID: 24396664
Thyroid nodule; Neoplasms; Ultrasonography; Growth; Tumor burden
14.  Predictive Clinical Parameters and Glycemic Efficacy of Vildagliptin Treatment in Korean Subjects with Type 2 Diabetes 
Diabetes & Metabolism Journal  2013;37(1):72-80.
The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes.
In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics.
Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (ΔHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment.
Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.
PMCID: PMC3579155  PMID: 23439802
Diabetes mellitus; Dipeptidyl peptidase 4; Dipeptidyl peptidase 4 inhibitor; Vildagliptin
15.  Effects of a 6-Month Exenatide Therapy on HbA1c and Weight in Korean Patients with Type 2 Diabetes: A Retrospective Cohort Study 
Diabetes & Metabolism Journal  2012;36(5):364-370.
While many studies have shown the good efficacy and safety of exenatide in patients with diabetes, limited information is available about exenatide in clinical practice in Korean populations. Therefore, this retrospective cohort study was designed to analyze the effects of exenatide on blood glucose level and body weight in Korean patients with type 2 diabetes mellitus.
We reviewed the records of the patients with diabetes who visited Seoul St. Mary's Hospital and for whom exenatide was prescribed from June 2009 to October 2011. After excluding subjects based on their race/ethnicity, medical history, whether or not they changed more than 2 kinds of oral hypoglycemic agents with exenatide treatment, loss to follow-up, or whether they stopped exenatide therapy within 6 months, a total of 52 subjects were included in the final analysis.
The mean glycated hemoglobin (HbA1c) level and weight remarkably decreased from 8.5±1.7% to 6.7±1.0% (P<0.001) and from 82.3±15.8 kg to 78.6±16.3 kg (P<0.001), respectively. The multiple regression analysis indicated that the reduction in HbA1c level was significantly associated with a shorter duration of diabetes, a higher baseline HbA1c level, and greater weight reduction, whereas weight loss had no significant correlation with other factors. No severe adverse events were observed.
These results suggest that a 6-month exenatide injection therapy significantly improved patients' HbA1c levels and body weights without causing serious adverse effects in Korean patients with type 2 diabetes.
PMCID: PMC3486983  PMID: 23130321
Diabetes mellitus, type 2; Exenatide; Glucagon-like peptide 1; Treatment outcome
16.  Diabetic Peripheral Neuropathy Is Associated With Increased Arterial Stiffness Without Changes in Carotid Intima–Media Thickness in Type 2 Diabetes 
Diabetes Care  2011;34(6):1403-1405.
This study was conducted to investigate the association of diabetic peripheral neuropathy (DPN) with both arterial stiffness and intima–media thickness (IMT).
We conducted a cross-sectional analysis of 731 subjects with type 2 diabetes. DPN was diagnosed on the basis of neuropathic symptoms, insensitivity to a 10-g monofilament, abnormal pin-prick sensation, and abnormal current perception threshold. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI), and IMT was assessed by B-mode ultrasonography.
Patients with DPN had higher CAVI than those without DPN in multivariate-adjusted models, whereas no differences in IMT were observed between patients with and without DPN after adjustment for age and sex. In the multivariate analysis, CAVI was a significant determinant of DPN (odds ratio 1.36 [95% CI 1.13–1.65], P = 0.001).
DPN is significantly associated with arterial stiffness without carotid intimal changes in patients with type 2 diabetes.
PMCID: PMC3114324  PMID: 21515840
17.  Relationship between Vitamin D, Parathyroid Hormone, and Bone Mineral Density in Elderly Koreans 
Journal of Korean Medical Science  2012;27(6):636-643.
There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.
PMCID: PMC3369450  PMID: 22690095
Vitamin D; Intact Parathyroid Hormone; Bone Density; Age; Sex
18.  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.
PMCID: PMC3154343  PMID: 21860558
Diabetic Retinopathy; Prevalence; Risk Factors
19.  Exercise Treadmill Test in Detecting Asymptomatic Coronary Artery Disease in Type 2 Diabetes Mellitus 
Diabetes & Metabolism Journal  2011;35(1):34-40.
The present study was designed to develop criteria for screening patients with type 2 diabetes mellitus (T2DM) for asymptomatic coronary artery disease (CAD).
A total of 213 patients with T2DM without typical angina or chest pain were studied between 2002 and 2007. We also evaluated 53 patients with T2DM who had reported chest discomfort using an exercise treadmill test (ETT).
Thirty-one of the 213 asymptomatic patients had positive ETT results. We performed coronary angiography on 23 of the 31 patients with a positive ETT and found that 11 of them had significant coronary stenosis. The main differences between the patients with significant stenosis and those with a negative ETT were age (63.1±9.4 vs. 53.7±10.1 years, P=0.008) and duration of diabetes (16.0±7.5 vs. 5.5±5.7 years, P<0.001). The positive predictive value (PPV) of the ETT was calculated to be 47.8%. The PPV of the ETT increased to 87.5% in elderly patients (≥60 years) with a long duration of diabetes (≥10 years). The latter value is similar to that of patients with T2DM who presented with chest discomfort or exertional dyspnea. The PPV of the ETT in symptomatic patients was 76.9%.
In the interest of cost-effectiveness, screening for asymptomatic CAD could be limited to elderly patients with a duration of diabetes ≥10 years.
PMCID: PMC3080575  PMID: 21537411
Diabetes mellitus; Duration of diabetes; Exercise treadmill test; Silent myocardial ischemia
20.  Clinical Significance of Observation without Repeated Radioiodine Therapy in Differentiated Thyroid Carcinoma Patients with Positive Surveillance Whole-Body Scans and Negative Thyroglobulin 
Currently, there is no consensus on the necessity of repeated radioiodine therapy (RAI) in patients who show iodine uptake in the thyroid bed on a diagnostic whole-body scan (DxWBS) despite undetectable thyroglobulin (Tg) levels after remnant ablation. The present study investigated the clinical outcomes of scan-positive, Tg-negative patients (WBS+Tg-) who did or did not receive additional RAI.
We retrospectively reviewed 389 differentiated thyroid carcinoma patients who underwent a total thyroidectomy and received high-dose RAI from January 2003 through December 2005. The patients were classified according to surveillance DxWBS findings and TSH-stimulated Tg levels 6 to 12 months after the initial RAI.
Forty-four of the 389 patients (11.3%) showed thyroid bed uptake on a DxWBS despite negative Tg levels (WBS+Tg-). There was no difference in clinical and pathological parameters between WBS+Tg- and WBS-Tg- patients, except for an increased frequency of thyroiditis in the WBS+Tg- group. Among the 44 WBS+Tg- patients, 27 subjects were treated with additional RAI; 25 subjects showed no uptake in subsequent DxWBS. Two patients were evaluated only by ultrasonography (US) and displayed no persistent/recurrent disease. The other 17 patients received no further RAI; Eight patients and two patients showed no uptake and persistent uptake, respectively, on subsequent DxWBS. Six patients presented negative subsequent US findings, and one was lost to follow-up. Over the course of 53.2 ± 10.1 months, recurrence/persistence was suspicious in two patients in the treatment group.
There were no remarkable differences in clinical outcomes between observation and treatment groups of WBS+Tg- patients. Observation without repeated RAI may be an alternative management option for WBS+Tg- patients.
PMCID: PMC2997970  PMID: 21179279
Iodine radioisotopes; Thyroglobulin; Thyroid neoplasms; Whole body scan
21.  Analysis of a novel AVPR2 mutation in a family with nephrogenic diabetes insipidus 
Congenital nephrogenic diabetes insipidus (NDI) is a rare X-linked recessive disorder associated with germ-line mutations of the arginine vasopressin (AVP) receptor type 2 (AVPR2) gene. Recent molecular studies have demonstrated that insensitivity of renal tubule cells to AVP is associated with AVPR2 mutations. We identified a novel deletion mutation at nucleotide position 302 (302delC), in a Korean NDI family, that results in a frameshift and a truncated receptor protein. To identify the mutant AVPR2 protein we developed an expression vector for the AVPR2 mutation by a PCR-based restriction fragment replacement strategy. COS-7 cells were transiently transfected with expression vectors for the wild-type and mutant genes, and we analyzed AVP-induced cyclic adenosine monophos-phate (cAMP) responses, and assessed the localization of AVPR2 receptors, in the transfected COS-7 cells. In the cells expressing the mutant gene, the maximum AVP-induced cAMP response was reduced and the truncated receptor proteins were retained within the cytoplasmic compartment. These results suggest that the novel frameshift AVPR2 (302delC) mutation is responsible for the AVP resistance in the family with congenital NDI.
PMCID: PMC3048978  PMID: 21394280
Nephrogenic diabetes insipidus; vasopression; AVPR2; frameshift mutation
22.  Progression of Cardiovascular Autonomic Dysfunction in Patients With Type 2 Diabetes 
Diabetes Care  2008;31(9):1832-1836.
OBJECTIVE—We investigated whether cardiovascular autonomic dysfunction was associated with glycemic control status over time in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—From 1999 to 2000, cardiovascular autonomic nerve function testing (AFT) was performed on patients with type 2 diabetes (n = 1,021) and was followed-up in 2006 and February 2008. Tests for cardiovascular autonomic functions measured heart rate variability parameters (expiration-to-inspiration [E/I] ratio, responses to the Valsalva maneuver, and standing). AFT scores were determined from the results of the each test as follows: 0 for normal and 1 for abnormal. We began with those who had a score of 0 and assessed the changes in total score along with biannual A1C levels.
RESULTS—At follow-up, the development of cardiovascular autonomic dysfunction was 34.5% (E/I ratio 21.9%, Valsalva maneuver 77.8%, and posture 58.9%; n = 783). The development of cardiovascular autonomic dysfunction was higher in older patients (P < 0.001); in those with longer duration of diabetes (P < 0.001); of hypertension (P = 0.005), and of diabetic retinopathy (P < 0.001); and in those who had higher levels of microalbuminuria (P = 0.002). Logistic regression analysis revealed that the development of cardiovascular autonomic dysfunction was strongly associated with the mean A1C level during the follow-up period (mean A1C >9.0% vs. ≤7.0%, odds ratio 2.984, 95% CI 1.177–7.561; P = 0.021).
CONCLUSIONS—The development of cardiovascular autonomic dysfunction was independently associated with microvascular complications and glycemic control status during this 7.5-year follow-up in patients with type 2 diabetes.
PMCID: PMC2518354  PMID: 18509202
23.  Complication Reducing Effect of the Information Technology-Based Diabetes Management System on Subjects with Type 2 Diabetes 
We introduced a new information technology-based diabetes management system, called the Internet-based glucose monitoring system (IBGMS), and demonstrated its short-term and long-term favorable effects. However, there has been no report on clinical effects of such a new diabetes management system on the development of diabetic complications so far. This study was used to simulate the complication reducing effect of the IBGMS, given in addition to existing treatments in patients with type 2 diabetes.
Research Design and Methods
The CORE Diabetes Model, a peer-reviewed, published, validated computer simulation model, was used to project long-term clinical outcomes in type 2 diabetes patients receiving the IBGMS in addition to their existing treatment. The model combined standard Markov submodels to simulate the incidence and progression of diabetes-related complications.
The addition of IBGMS was associated with improvements in reducing diabetic complications, mainly microangiopathic complications, including diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and diabetic foot ulcer. The IBGMS also delayed the development of all diabetic complications for more than 1 year.
This study demonstrated that the simulated IBGMS, compared to existing treatment, was associated with a reduction of diabetic complications. As a result, it provides valuable evidence for practical application to the public in the world.
PMCID: PMC2769703  PMID: 19885180
diabetic complications; health economics; Internet; simulation
24.  Prevalence and Clinical Characteristics of the Metabolic Syndrome in Middle-Aged Korean Adults 
The aim of this study was to analyze the prevalence and clinical characteristic of the metabolic syndrome of adults, over 40 years old, living in Korea.
This study was carried out for 2 years, 2003-2004, on total 5,330 individuals (2,197 men and 3,133 women) selected by the stratified random cluster sampling among adults over 40 years old. Metabolic syndrome was defined based on both the NCEP-ATP III criteria and Modified ATP III criteria applying the WHO-APR (Asian Pacific Region)'s abdominal obesity criteria (waist circumference > 90 cm in men, 80 cm in women) instead of NCEP-ATP III criteria.
Using NCEP-ATP III criteria, the age-adjusted overall prevalence of metabolic syndrome was 24.8% (17.6% in men, 30.0% in women). Age-adjusted overall prevalence of metabolic syndrome as defined by modified-ATP III criteria was 34.3% (26.3% in men, 40.1% in women). The prevalence of metabolic syndrome for each age group (40-49, 50-59, 60-69, ≥ 70) in men was as follows: 18.8%, 17.4%, 18.3%, 14.5%. In women: 22.3%, 32.7%, 39.9%, 39.3%. The prevalence of hypertriglyceridemia (triglycerides ≥ 1.7 mmol/l) was well correlated with the changing pattern of the prevalence of metabolic syndrome both in men and women.
The peak age of metabolic syndrome in men was age 40 through 49, and the prevalence decreased with aging. Therefore, early intervention for risk factors of metabolic syndrome might be required in men. On the other hand, prevention for cardiovascular disease will be needed for perimenopausal women due to considerably increased prevalence in the age 50 through 59.
PMCID: PMC3891077  PMID: 16491829
Prevalence; Metabolic syndrome
25.  The Effect of Simvastatin on the Proliferation and Differentiation of Human Bone Marrow Stromal Cells 
Journal of Korean Medical Science  2005;20(3):438-444.
Statins have been postulated to affect the bone metabolism. Recent experimental and epidemiologic studies have suggested that statins may also have bone protective effects. This study assessed the effects of simvastatin on the proliferation and differentiation of human bone marrow stromal cells (BMSCs) in an ex vivo culture. The bone marrow was obtained from healthy donors. Mononuclear cells were isolated and cultured to osteoblastic lineage. In the primary culture, 10-6 M simvastatin diminished the mean size of the colony forming units-fibroblastic (CFU-Fs) and enhanced matrix calcification. At near confluence, the cells were sub-cultured. Thereafter, the alkaline phosphatase (ALP) activities of each group were measured by the time course of the secondary culture. Simvastatin increased the ALP activity in a dose dependent manner, and this stimulatory effect was more evident during the early period of culture. A 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was performed during the secondary culture in order to estimate the effect of simvastatin on the proliferation of human BMSCs. When compared to the control group, simvastatin significantly decreased the proliferation of cells of each culture well. 10-6 M of simvastatin also significantly enhanced the osteocalcin mRNA expression level. This study shows that simvastatin has a stimulatory effect on bone formation through osteoblastic differentiation, and has an inhibitory effect on the proliferative potential of human BMSCs
PMCID: PMC2782200  PMID: 15953866
Simvastatin; Osteoblasts; Cell Proliferation; Cell Differentiation; Bone Marrow Cells; Stromal Cells

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