BACKGROUND: The National Health Insurance Service (NHIS) recently signed an agreement to provide limited open access to the databases within the Korean Diabetes Association for the benefit of Korean subjects with diabetes. Here, we present the history, structure, contents, and way to use data procurement in the Korean National Health Insurance (NHI) system for the benefit of Korean researchers. METHODS: The NHIS in Korea is a single-payer program and is mandatory for all residents in Korea. The three main healthcare programs of the NHI, Medical Aid, and long-term care insurance (LTCI) provide 100% coverage for the Korean population. The NHIS in Korea has adopted a fee-for-service system to pay health providers. Researchers can obtain health information from the four databases of the insured that contain data on health insurance claims, health check-ups and LTCI. RESULTS: Metabolic disease as chronic disease is increasing with aging society. NHIS data is based on mandatory, serial population data, so, this might show the time course of disease and predict some disease progress, and also be used in primary and secondary prevention of disease after data mining. CONCLUSION: The NHIS database represents the entire Korean population and can be used as a population-based database. The integrated information technology of the NHIS database makes it a world-leading population-based epidemiology and disease research platform.
Aging ; Chronic Disease ; Data Mining ; Delivery of Health Care ; Epidemiology ; Insurance, Health ; Insurance, Long-Term Care ; Korea ; Metabolic Diseases ; National Health Programs* ; Secondary Prevention

BACKGROUND: We evaluated the disease profile and clinical management, including the status of both glycemic control and complications, in patients with diabetes who were transferred to referral hospitals in Korea. METHODS: Patients referred to 20 referral hospitals in Gyeongsangnam/Gyeongsangbuk-do and Jeollanam/Jeollabuk-do with at least a 1-year history of diabetes between January and June 2011 were retrospectively reviewed using medical records, laboratory tests, and questionnaires. RESULTS: A total of 654 patients were enrolled in the study. In total, 437 patients (67%) were transferred from clinics and 197 (30%) patients were transferred from hospitals. A total of 279 patients (43%) visited higher medical institutions without a written medical request. The main reason for the referral was glycemic control in 433 patients (66%). Seventy-three patients (11%) had received more than one session of diabetic education. Only 177 patients (27%) had been routinely self-monitoring blood glucose, and 146 patients (22%) were monitoring hemoglobin A1c. In addition, proper evaluations for diabetic complications were performed for 74 patients (11%). The most common complication was neuropathy (32%) followed by nephropathy (31%). In total, 538 patients (82%) had been taking oral hypoglycemic agents. A relatively large number of patients (44%) had been taking antihypertensive medications. CONCLUSION: We investigated the clinical characteristics of diabetic patients and identified specific problems in diabetic management prior to the transfer. We also found several problems in the medical system, which were divided into three medical institutions having different roles in Korea. Our findings suggested that the relationships among medical institutions have to be improved, particularly for diabetes.
Blood Glucose ; Diabetes Complications ; Diabetes Mellitus ; Education ; Humans ; Hypoglycemic Agents ; Korea ; Medical Records ; Referral and Consultation* ; Retrospective Studies ; Surveys and Questionnaires

BACKGROUND: Until recently, genome-wide association study (GWAS)-based findings have provided a substantial genetic contribution to type 2 diabetes mellitus (T2DM) or related glycemic traits. However, identification of allelic heterogeneity and population-specific genetic variants under consideration of potential confounding factors will be very valuable for clinical applicability. To identify novel susceptibility loci for T2DM and glycemic traits, we performed a two-stage genetic association study in a Korean population. METHODS: We performed a logistic analysis for T2DM, and the first discovery GWAS was analyzed for 1,042 cases and 2,943 controls recruited from a population-based cohort (KARE, n=8,842). The second stage, de novo replication analysis, was performed in 1,216 cases and 1,352 controls selected from an independent population-based cohort (Health 2, n=8,500). A multiple linear regression analysis for glycemic traits was further performed in a total of 14,232 nondiabetic individuals consisting of 7,696 GWAS and 6,536 replication study participants. A meta-analysis was performed on the combined results using effect size and standard errors estimated for stage 1 and 2, respectively. RESULTS: A combined meta-analysis for T2DM identified two new (rs11065756 and rs2074356) loci reaching genome-wide significance in CCDC63 and C12orf51 on the 12q24 region. In addition, these variants were significantly associated with fasting plasma glucose and homeostasis model assessment of beta-cell function. Interestingly, two independent single nucleotide polymorphisms were associated with sex-specific stratification in this study. CONCLUSION: Our study showed a strong association between T2DM and glycemic traits. We further observed that two novel loci with multiple diverse effects were highly specific to males. Taken together, these findings may provide additional insights into the clinical assessment or subclassification of disease risk in a Korean population.
Blood Glucose ; Cohort Studies ; Diabetes Mellitus, Type 2* ; Fasting ; Genetic Association Studies ; Genome-Wide Association Study* ; Homeostasis ; Humans ; Linear Models ; Male ; Polymorphism, Single Nucleotide ; Population Characteristics

BACKGROUND: The effect of livingstone potato (Plectranthus esculenthus N.E.Br) on diabetes and its complications in Streptozotocin induced diabetic rats was investigated. The duration of the experiment was 4 weeks. METHODS: The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The liver and kidney function parameters in the serum of the rats were determined using Biosystem Kits. RESULTS: The diabetic rats given livingstonepotato incorporated feeds, had 129.7% decrease in their hyperglycemia with corresponding amelioration of their elevated urinary protein, sugars, specific gravity, renal growth, liver growth as well as 15.64% decrease in body weights compared with the nondiabetic rats that had 5.54% decrease in blood glucose and 20.39% increase in body weight unlike the diabetic control rats that had 18.34% decrease in blood glucose and 52.68% decrease in body weight. There were significant differences (P<0.05) in the relative liver, pancreas, and kidney weights of the diabetic rats given livingstone potato feeds compared with the diabetic control while there were no significant differences (P>0.05) in the relative heart weights of all the rats in the three different groups. In terms of liver and kidney function parameters, values obtained for the diabetic rats given livingstone potato incorporated feeds were not significantly different from that of the nondiabetic rats except for total bilurubin, aspartate transaminase, and creatinine (P>0.05) while they were significantly different from the values obtained for the diabetic control rats (P<0.05). In addition, the serum amylase of the diabetic control rats were significantly higher (P<0.05) than that of the nondiabetic and diabetic rats treated with livingstone potato incorporated feeds. CONCLUSION: Results show the antidiabetic actions of livingstone potato and its ability to ameliorate glomerular complication and liver hypertrophy in diabetics.
Amylases ; Animals ; Aspartate Aminotransferases ; Blood Glucose ; Body Weight ; Carbohydrates ; Creatinine ; Diabetes Complications ; Glucose ; Heart ; Hyperglycemia ; Hypertrophy ; Kidney ; Liver ; Pancreas ; Rats* ; Solanum tuberosum* ; Specific Gravity ; Streptozocin* ; Weights and Measures

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist has a wide-ranging influence on multiple components of metabolic syndrome. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a useful animal model of metabolic syndrome. To determine genes related to metabolic syndrome, we examined overlapping genes that are simultaneously decreased by PPAR-gamma agonists and increased in OLETF rats using microarrays in two different models. METHODS: In the first microarray analysis, PPAR-gamma agonist-treated db/db mice were compared to standard diet-fed db/db mice. In the second microarray analysis, OLETF rats were compared to Long-Evans Tokushima Otsuka (LETO) rats (control of OLETF rats). RESULTS: Among the overlapping genes, in the present study, we validated that lipocalin-2 expression was significantly decreased in the visceral adipose tissue of PPAR-gamma agonist-treated db/db mice compared to standard diet-fed db/db mice and increased in OLETF rats compared to LETO rats using real time reverse transcription polymerase chain reaction. Furthermore, we showed for the first time that lipocalin-2 expression was significantly increased in the visceral adipose tissues of obese humans compared with nonobese humans. In addition, the expression level of lipocalin-2 in human visceral adipose tissue had a significant positive correlation with body mass index, serum interleukin-6, adipocyte fatty acid binding protein levels, and white blood cell count. CONCLUSION: Lipocalin-2 was confirmed to be a significant adipokine affected by PPAR-gamma agonist and obesity in the present study. Also, for the first time in human visceral adipose tissue, it was determined that the expression of lipocalin-2 from obese humans was significantly increased and correlated with circulating inflammatory markers.
Adipocytes ; Adipokines ; Animals ; Body Mass Index ; Carrier Proteins ; Genes, Overlapping ; Humans ; Interleukin-6 ; Intra-Abdominal Fat ; Leukocyte Count ; Mice ; Microarray Analysis ; Models, Animal ; Obesity ; Peroxisomes ; Polymerase Chain Reaction ; PPAR gamma ; Rats ; Rats, Inbred OLETF ; Reverse Transcription ; Transcriptome*

BACKGROUND: The Survey of Autonomic Symptom (SAS) scale was reported as an easy instrument to assess the autonomic symptoms in patients with early diabetic neuropathy. In this study, we investigated the relationship between the SAS scale and the parameters of cardiac autonomic neuropathy (CAN) in Korean patients with diabetic peripheral neuropathy (DPN). METHODS: The SAS scale was tested in 30 healthy controls and 73 patients with DPN at Chonbuk National University Hospital, in Korea. The SAS score was compared to the parameters of the CAN test and the total symptom score (TSS) for DPN in patients with DPN. RESULTS: The SAS symptom score and total impact score were increased in patients with DPN compared to the control group (P=0.01), particularly in sudomotor dysfunction (P=0.01), and vasomotor dysfunction (P=0.01). The SAS score was increased in patients with CAN compared to patients without CAN (P<0.05). Among the diverse CAN parameters, the valsalva ratio and postural hypotension were associated with the SAS score (P<0.05). However, there was no association between the SAS scale and TSS for DPN, and TSS for DPN did not differ between patients with and without CAN. CONCLUSION: SAS is a simple instrument that can be used to assess autonomic symptoms in patients with diabetes and can be used as a screening tool for autonomic neuropathy, particularly for CAN.
Diabetic Neuropathies ; Humans ; Hypotension, Orthostatic ; Jeollabuk-do ; Korea ; Mass Screening ; Peripheral Nervous System Diseases*

BACKGROUND: Metabolic syndrome (MetS) is constellation of cardiovascular risk factors. There are three typically used definitions of MetS proposed by WHO, IDF and NCEP-ATP III. We conducted this study to compare the associations of MetS by WHO, IDF and NCEP-ATP III definition to various metabolic markers of coronary heart diseases in Korean type 2 diabetes patients. METHODS: We enrolled 151 Korean type 2 diabetes patients in one hospital. Anthropometric and biochemical parameters, including high-sensitivity C-reactive protein (hsCRP), homocysteine, uric acid were measured. And then, we divided MetS group from non-MetS group according to three other definitions. RESULTS: Serum hsCRP level was higher in those with MetS group than non-MetS group by WHO definition (0.33 +/- 0.36 mg/dL vs 0.18 +/- 0.26 mg/dL, P < 0.001). But, there are no difference in MetS group and non-MetS group by IDF and NCEP-ATPIII definition. (By IDF, 0.28 +/- 0.31 mg/dL vs 0.25 +/- 0.34 mg/dL, P = 0.64; By NCEP-ATP III, 0.28 +/- 0.33 mg/dL vs 0.22 +/- 0.32 mg/dL, P = 0.41). Uric acid and homocysteine levels were higher in those with MetS by WHO definition (P < 0.05). Similarly, analyses according to IDF and NCEP ATP III definition showed no significant difference. CONCLUSION: In conclusion, WHO definition of MetS has a stronger relationship with the biochemical markers of coronary heart disease in Korean type 2 diabetes patients.
Adenosine Triphosphate ; Biomarkers ; C-Reactive Protein ; Cardiovascular Diseases ; Coronary Disease ; Diabetes Mellitus ; Homocysteine ; Humans ; Risk Factors ; Uric Acid

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome including insulin resistance, hypertension, dyslipidemia, central obesity, type 2 diabetes, and cardiovascular disease. In NAFLD, insulin resistance plays an important role in the progression of liver damage. In this study, we evaluated insulin resistance, plasma adiponectin, hepatic steatosis, and their association in adults with normal liver transaminase concentrations. METHODS: We analyzed 111 subjects, aged over 20 years old, who visited the Health Management Center at Chung-Ang University Hospital between May 2006 and August 2006. They had neither history nor clinical evidence of diabetes, cardiovascular or liver disease. They were divided into three groups by the degree of hepatic steatosis based on ultrasound findings. Anthropometric parameters were measured and blood samples were drawn after eight hours of fasting. RESULTS: Hepatic steatosis had a positive correlation with body mass index, waist circumference, blood pressure, triglycerides, HOMA-IR, and QUICKI. Moreover, it had a negative correlation with high-density lipoprotein cholesterol and adiponectin. Triglycerides, Adiponectin, and QUICKI were independent variables in predicting the degree of hepatic steatosis. CONCLUSION: This finding suggests that triglycerides and plasma adiponectin are independent predictors of hepatic steatosis in adults with normal liver transaminase concentrations.
Adiponectin ; Adult ; Aged ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Dyslipidemias ; Fatty Liver ; Humans ; Hypertension ; Insulin Resistance ; Lipoproteins ; Liver ; Liver Diseases ; Obesity, Abdominal ; Plasma ; Triglycerides ; Waist Circumference

BACKGROUND: Insulin resistance is very common in patients with nonalcoholic fatty liver disease (NAFLD). Glitazones improve insulin sensitivity by acting as a selective agonist of the peroxisome proliferators -activated receptor gamma (PPAR gamma), and were shown to activate AMP-activated protein kinase (AMPK) in skeletal muscle and the liver. Glitazones were also shown to reduce hepatic lipogenesis. The aim of this study was to investigate whether the protective mechanism of rosiglitazone on NAFLD is associated with AMPK activation. METHODS: Twelve OLETF rats were divided into 2 groups (control, treatment, n = 6 each). LETO rats served as controls. At 35 weeks of age, treatment group received rosiglitazone 4 mg/kg daily for 3 days. Fasting plasma glucose, insulin, free fatty acid, lactate and triglycerides were measured. Liver tissues from each group were processed for histological and hepatic triglyceride content analysis and western blotting. RESULTS: Fasting plasma glucose, insulin and triglycerides levels were significantly lower in treatment group than in control group. Histologic examination disclosed decreased hepatic steatosis in treatment group. Hepatic triglyceride content was also decreased in treatment group. Sterol regulatory binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) expression were increased and AMPK phosphorylation was reduced in OLETF rats compared with LETO rats, and these changes were reversed by rosiglitazone treatment. CONCLUSION: Rosiglitazone reduced hepatic steatosis in OLETF rats, and activated AMPK in the liver. These results suggest the role of AMPK activation in the protective action of rosiglitazone on NAFLD.
AMP-Activated Protein Kinases ; Animals ; Fasting ; Fatty Acid Synthetase Complex ; Fatty Liver ; Glucose ; Humans ; Insulin ; Insulin Resistance ; Lactic Acid ; Lipogenesis ; Liver ; Muscle, Skeletal ; Peroxisome Proliferators ; Phosphorylation ; Plasma ; Rats ; Rats, Inbred OLETF ; Thiazolidinediones ; Triglycerides

BACKGROUND: Epidermal Growth Factor (EGF) is one of the important growth factors involved in the epithelialization during cutaneous wound healing. Peptide EGF has been used for the treatment of diabetic foot ulcer. But the inferiority of cost-effectiveness and the inconvenience of daily application might have restricted its wide clinical usage. EGF gene therapy could dramatically improve the efficacy and inconvenience through long-term expression and bypassing the EGF degradation by hostile non-specific proteinases expressed in the wound bed. METHODS: EGF DNAs were amplified via PCR. For the more effective secretion from the transfected cell, we inserted furin cleavage site into EGF plasmids. The efficacy of novel plasmid pbeta-EGF was verified by transfection into the various animal cell lines, and the biologic potency of expressed EGF was confirmed via phosphorylation of PI3K and GSK3beta by Western blotting. RESULTS: We tested various kinds of human EGFs. One of the human EGF isoforms, EGF(828) including a membrane-anchoring domain was successfully released as the mature EGF protein in the cell culture media. Also EGF plasmid including furin cleavage site showed more than 2-fold increased EGF expression compared with the sequence without furin cleavage site. CONCLUSION: In conclusion, these findings suggest that mature EGF could be released easily out of cells by modifying EGF DNA sequence. Our novel EGF plasmid DNA could markedly increase the efficiency of non-viral gene therapy for diabetic foot ulcer.
Animals ; Base Sequence ; Cell Culture Techniques ; Cell Line ; Clone Cells ; Cloning, Organism ; Diabetes Mellitus ; Diabetic Foot ; DNA ; Epidermal Growth Factor ; Furin ; Genetic Therapy ; Glycogen Synthase Kinase 3 ; Humans ; Intercellular Signaling Peptides and Proteins ; Peptide Hydrolases ; Phosphorylation ; Plasmids ; Polymerase Chain Reaction ; Protein Isoforms ; Transfection ; Ulcer ; Wound Healing