[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.
[Show abstract][Hide abstract] ABSTRACT: It was previously reported in Korea that there were 1·4 case per million per year of acromegaly. This was low in comparison with the extrapolated values of Western European countries. We expected that the incidence of acromegaly would be much higher now because of recently improved medical facilities, diagnostic tools and coverage of medical insurance to all the population of South Korea.
The purpose of this nationwide survey was to examine the incidence and prevalence of patients with acromegaly, mode of treatment and outcome of surgical treatment of recent 5 years.
We requested and collected the medical records of all possible patients with acromegaly from 74 secondary or tertiary medical institutes in Korea from 2003 to 2007 retrospectively.
Date of diagnosis and treatment, tumour size, pre- and postoperative hormonal level, treatment modality and usage of medication were collected.
During 5 years, 1350 patients with acromegaly had been registered. The average annual incidence was 3·9 cases per million during this period, and prevalence had increased up to 27·9 cases per million in 2007. Male/female ratio was 1:1·2, and mean age at diagnosis was 44·1 years. Macroadenoma was dominant (82·9%). Transsphenoidal adenoidectomy was used the most as primary treatment (90·4%).
This Korean acromegaly survey offers a realistic overview of the predominant epidemiological characteristics of acromegaly in Korea. Annual incidence was at a similar level with western countries. Efforts to diagnose and control the disease earlier are recommended.
[Show abstract][Hide abstract] ABSTRACT: Research on the relationship between urinary albumin excretion and serum cystatin C in diabetes is restricted to cross-sectional studies. In this study, we investigated how well serial measurements of serum cystatin C level reflect changes in the urinary albumin excretion rate.
We enrolled and retrospectively collected data on 1,058 participants with type 2 diabetes who were older than 18 years and who had more than 3 years of follow-up with serial measurements of albuminuria and serum cystatin C at an outpatient clinic.
With the use of a linear mixed model, we found that the albuminuria level for each patient over time corresponded with the annual change in serum cystatin C-based estimated glomerular filtration rate (cysC-eGFR) but did not correspond with the creatinine-based eGFR calculated by the modification of diet in renal disease formula (MDRD-eGFR). The discrepancy in the direction of the trend was smaller with cysC-eGFR than with MDRD-eGFR.
Serum cystatin C level reflects the trend in albuminuria level more accurately than serum creatinine level in Korean type 2 diabetes mellitus patients.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the effect of common adiponectin gene polymorphisms on dietary intervention-mediated changes in adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) indexes.
A total of 363 subjects with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes followed a dietary intervention (replacement of cooked refined rice with whole grains and an increase in vegetable intake) and regular walking for 12 weeks without any medication. Adiponectin gene single nucleotide polymorphisms (SNPs) (45, 276, and -11377) were examined in these subjects.
After this dietary intervention, fasting glucose levels decreased in all three SNP 45T>G genotype groups. Subjects with the SNP 45TT genotype showed increased adiponectin levels and decreased HOMA-IR indexes. Haplotype analysis revealed that homozygous carriers of the TG haplotype (45TT and 276GG) and heterozygous carriers of the TG haplotype (TG/X) showed a reduction in the HOMA-IR index after adjustment for baseline levels. Significant differences were observed in changes in HOMA-IR indexes and adiponectin concentrations according to the 45-276 TG haplotype in overweight-obese, but not in normal-weight subjects: the greatest decrease in HOMA-IR indexes and the greatest increase in adiponectin levels were shown in overweight-obese subjects with the TG/TG haplotype.
ADIPOQ genetic variants can affect circulating adiponectin levels and insulin resistance indexes in subjects with IFG or newly diagnosed type 2 diabetes in response to dietary intervention.
Diabetes care 02/2009; 32(4):552-8. DOI:10.2337/dc08-1605 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased levels of inflammatory markers, such as interleukin-6 (IL-6), are associated with type 2 diabetes (T2DM). We investigated the association of IL-6 gene polymorphisms with T2DM and circulating levels of IL-6 in Koreans.
A total of 1477 subjects with normal glucose tolerance and 476 T2DM patients were included.
We examined IL-6 -174G-->C, -572C-->G, -597G-->A and -1363G-->T promoter region polymorphisms. The main outcome measures were the odds ratio (OR) on T2DM risk and serum concentrations of IL-6 and high-sensitivity C-reactive protein (hs-CRP).
Homozygosity for the rare G allele IL-6 -572C-->G was associated with a higher risk of T2DM [OR 1.69 (95%CI 1.11-2.58), P = 0.015]. Serum IL-6 concentrations were associated with the IL-6 -572C-->G genotype in control subjects (G/G: 2.33 +/- 0.41: C/G: 1.53 +/- 0.09: C/C: 1.72 +/- 0.08 ng/l, P = 0.023). Also in the control group, subjects homozygous for the rare G allele showed significantly higher concentrations of hs-CRP than C/C and C/G carriers (G/G: 13.6 +/- 2.9: C/G: 9.2 +/- 0.6: C/C: 7.8 +/- 0.4 mg/l, P = 0.003). The C-allele at the IL-6 -174 SNP was very rare (< 0.01) and -597G-->A and -1363G-->T were monomorphic in this population.
Our data demonstrate that the IL-6 -572G/G genotype is associated with higher serum IL-6 and hs-CRP concentrations and with increased risk for T2DM.
[Show abstract][Hide abstract] ABSTRACT: We investigated the association between the Gly82Ser (G82S) polymorphism in the receptor for advanced glycation end products (RAGE) gene and circulating levels of soluble RAGE (sRAGE), advanced glycation end products (AGEs), and inflammatory markers in nondiabetic/nonobese Koreans. A total of 1096 men and 580 women aged 30 to 69 years and with body mass index of 18.5 to 29.9 kg/m(2) were recruited. Anthropometrics, lipid profiles, glucose, insulin, insulin resistance (IR), RAGE G82S polymorphism, sRAGE, AGEs, and inflammatory markers were measured. There was a significant association between G82S genotypes and plasma sRAGE concentrations (P < .001). sRAGE concentrations were significantly higher in subjects with the G/G genotype (1038 +/- 33 pg/mL) than in those with the G/S (809 +/- 19 pg/mL) or the S/S (428 +/- 43 pg/mL) genotype. Furthermore, the G82S genotypes in the RAGE gene were associated with serum AGE (P = .033), homeostasis model assessment for insulin resistance (HOMA-IR) (P < .001), plasma tumor necrosis factor alpha (TNF-alpha) (P = .033), serum C-reactive protein (CRP) (P= .002), and urinary excretion of 8-epi-prostaglandin F(2alpha) (P = .028) after adjusting for sex, age, body mass index, cigarette smoking, and alcohol drinking. Subjects with the S/S genotype showed higher levels of serum AGE, HOMA-IR, plasma TNF-alpha, serum CRP, and 8-epi-prostaglandin F(2alpha) than those with the G/G or G/S combination. The sRAGE levels showed a negative relation with high-sensitivity CRP (r = -0.250; P < .001). The AGE concentrations showed a positive relation with TNF-alpha levels (r = 0.398; P < .001). Subjects with homozygosity for the minor S allele (S/S) of the G82S polymorphism had higher risk factors for cardiovascular disease, such as low sRAGE levels, inflammation, oxidative stress, and IR, compared with those bearing at least one G allele.
[Show abstract][Hide abstract] ABSTRACT: A mutation in codon 631 of exon 11 of the RET proto-oncogene is extremely rare in the patients with multiple endocrine neoplasia type 2A (MEN 2A). We report here on a rare extracellular mutation of the RET gene that led to the substitution of a tyrosine for an aspartate in codon 631 (D631Y, GAC to TAC) in two Korean families with MEN 2A. Eleven individuals from two unrelated families were found to have the D631Y germline mutation. Among them, medullary thyroid carcinoma (MTC) was identified in five patients: four of them had MEN 2A and one had familial MTC. They had tumors 2 cm or less in the greatest dimension that were limited to the thyroid, and they had a relatively old age above 30 at the time of diagnosis. Pheochromocytoma was detected in six patients including the four patients who had MEN 2A. All had adrenal tumors greater than 3 cm in the greatest dimension, and four of them had bilateral tumors. Two of six patients suffering with pheochromocytoma had no clinical evidence of MTC at the time of diagnosis. None had any evidence of hyperparathyroidism. This genetic profile might be related to the less vigorous clinical disease behavior and the late onset of MTC. In addition, pheochromocytoma might be the first manifestation prior to the development of MTC in some patients with the D631Y mutation. This report is the first description of the clinical characteristics of the D631Y germline mutation in the families with MEN 2A.
[Show abstract][Hide abstract] ABSTRACT: Homeostasis model assessment of insulin resistance (HOMA-IR) is a less invasive, inexpensive, and less labor-intensive method to measure insulin resistance (IR) as compared with the glucose clamp test. The aim of this study was to evaluate the validity of HOMA-IR by comparing it with the euglycemic clamp test in determining IR. We assessed the validity of HOMA-IR by comparing it with the total glucose disposal rate measured by the 3-hour euglycemic-hyperinsulinemic clamp in subjects with type 2 diabetes (n = 47), impaired glucose tolerance (n = 21), and normal glucose tolerance (n = 22). There was a strong inverse correlation (r = -0.558; P < .001) between the log-transformed HOMA-IR and the total glucose disposal rate. There was moderate agreement between the 2 methods in the categorization according to the IR (weighted kappa = 0.294). The magnitude of the correlation coefficients was smaller in the subjects with a lower body mass index (BMI <25.0 kg/m2 , r = -0.441 vs BMI > or =25.0 kg/m2 , r = -0.615; P = .032), a lower HOMA-beta cell function (HOMA- beta <60.0, r = -0.527 vs HOMA- beta > or =60.0, r = -0.686; P = .016), and higher fasting glucose levels (fasting glucose < or =5.66 mmol/L, r = -0.556 vs fasting glucose >5.66 mmol/L, r = -0.520; P = .039). The limitation of the validity of the HOMA-IR should be carefully considered in subjects with a lower BMI, a lower beta cell function, and high fasting glucose levels such as lean type 2 diabetes mellitus with insulin secretory defects.
[Show abstract][Hide abstract] ABSTRACT: We often encounter diabetic patients with anemia in whom the causes of anemia were not clearly identified despite differential hematologic studies. We therefore studied the clinical and biochemical characteristics of diabetic patients with anemia of uncertain cause and measured erythropoietin (Epo) concentrations in 35 diabetic subjects without significant diabetic renal disease. Among 62 medical records of diabetic patients with anemia, showing no evidence of advanced diabetic nephropathy (creatinine clearance > or = 30 mg/kg/1.73 m2), the causes of the anemia were not able to be identified in 28 cases (45.2%). In addition, we enrolled 35 diabetic patients with uncertain causes of anemia in order to evaluate the serum Epo responsiveness to anemia, and compared levels to a group of non-diabetic subjects also with anemia. The serum Epo concentrations of diabetic patients (17.6 +/- 8.1 mIU/ml) were significantly lower than those of non-diabetic patients with similar degree of decrease in hemoglobin concentrations (144.9 +/- 108.0 mIU/ml, P<0.001). The hemoglobin concentrations of diabetic patients correlated with creatinine clearance (r = 0.34, P = 0.03), serum creatinine (r = -0.49, P = 0.003) and albumin excretion rate (r = -0.44, P = 0.009), but showed no relation to age, duration of diabetes, glycated hemoglobin, presence of retinopathy or neuropathy. We concluded that reduced Epo responsiveness to anemia could explain the anemia present in diabetic patient but without advanced diabetic nephropathy. This may reflect early renal interstitial damage.
Diabetes Research and Clinical Practice 12/1999; 46(3):223-9. DOI:10.1016/S0168-8227(99)00097-2 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Insulin deficiency and counterregulatory hormone excess are the basic process in the development of diabetic ketoacidosis (DKA). Somatostatin, which suppresses the secretion of glucagon and growth hormone, has been known to attenuate the rate of gluconeogesis and ketogenesis in insulin-dependent diabetes mellitus patients. However, the therapeutic efficacy of somatostatin has not been approved to be practical in the treatment of manifest DKA. To examine the additive effect of octreotide, the synthetic long-acting somatostatin analogue SMS 201-995, to conventional treatment of manifest DKA, we compared the correction time of acidosis, ketonuria, and hyperglycemia of patients treated with an intravenous infusion of low-dose insulin (4 units per hour) plus subcutaneous injection of octreotide (50 microg every 6 hours) by low-dose insulin alone. The correction time for hyperglycemia and acidosis did not show any difference between groups (p = 0.089, p = 0.82). However, the time for disappearance of ketonuria of the octreotide-treated group (38.0 +/- 32.0 h) was reduced significantly compared to other group (68.3 +/- 26.0 h) (p = 0.048). These results indicated that the addition of octreotide to conventional treatment of DKA might improve the correction of ketosis, but would not allow more rapid control of acidosis and hyperglycemia in manifest DKA.
Journal of Diabetes and its Complications 09/1999; 13(5-6):288-92. DOI:10.1016/S1056-8727(99)00059-8 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Growth hormone (GH) can induce an accelerated lipolysis. Impaired secretion of GH in obesity results in the consequent loss of the lipolytic effect of GH. Dietary restriction as a basic treatment for obesity is complicated by poor compliance, protein catabolism, and slow rates or weight loss. GH has an anabolic effect by increasing insulin-like growth factor (IGF)-I. We investigated the effects of GH treatment and dietary restriction on lipolytic and anabolic actions, as well as the consequent changes in insulin and GH secretion in obesity. 24 obese subjects (22 women and 2 men; 22–46 years old) were fed a diet of 25 kcal/kg ideal body weight (IBW) with 1.2 g protein/kg IBW daily and were treated with recombinant human GH (n = 12, 0.18 U/kg IBW/week) or placebo (n = 12, vehicle injection) in a 12-week randomized, double-blind and placebo-controlled trial. GH treatment caused a 1.6-fold increase in the fraction of body weight lost as fat and a greater loss of visceral fat area than placebo treatment (35.3 vs. 28.5%, p L-dopa stimulation was blunted in all subjects and it was increased after treatment in both groups. GH treatment did not induce a further increase in insulin levels during an oral glucose tolerance test (OGTT) but significantly decreased free fatty acid (FFA) levels during OGTT. The decrease in FFA area under the curve during OGTT was positively correlated with visceral fat loss. This study demonstrates that in obese subjects given a hypocaloric diet, GH accelerates body fat loss, exerts anabolic effects and improves GH secretion. These findings suggest a possible therapeutic role of low-dose GH with caloric restriction for obesity.
Hormone Research 02/1999; 51(2):78-84. DOI:10.1159/000023319 · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the validity of urine albumin concentration (UAC) and the urine albumin:creatine ratio (UACR) in a random urine specimen (RUS) for screening diabetic nephropathy in Korea, a total of 105 ambulatory diabetes mellitus patients (male:female, 52:53), ages 40-75 years (median 59 years) collected 105 RUSs after completing a timed 24 hour urine collection. Albumin was measured by immunonephelometry. According to the timed urinary albumin excretion rate (UAER) measured in the 24 hour collection (criterion standard), samples were classified normoalbuminuric (UAER < 20 micrograms/min; n = 50), microalbuminuric (UAER 20-200 micrograms/min; n = 30), and macroalbuminuric (UAER > 200 micrograms/min; n = 25). The receiver operating characteristics (ROC) curve of UAC and UACR in a RUS for screening of microalbuminuria (normo- and microalbuminuric samples; n = 80) and macroalbuminuria (micro- and macroalbuminuric samples; n = 55) were plotted. Pearson's coefficients of correlation of 24 hour UAER vs. UAC and UACR were 0.81 and 0.75, respectively (P < 0.001). The point of intersection with a 100%-to-100% diagonal for microalbuminuria were as follows: 31.0 mg/l for UAC and 32.5 mg/g for UACR; for macroalbuminuria 181 mg/l for UAC and 287.3 mg/g for UACR. The sensitivity and specificity of the cut-off points for microalbuminuria were 77% and 82% for UAC and 77% and 92% for UACR. The sensitivity and specificity of the cut-off points for macroalbuminuria were 84% and 90% for UAC and 88% and 90% for UACR. In present study, no difference was observed when comparing the performance of UAC and UACR based on a statistical comparison by McNemar test. The repeated measurements of UAC and UACR in the same individual were statistically similar and were correlated with each other. Based on these results, albumin measurements (UAC and UACR) in a RUS were considered as a valid test for screening diabetic nephropathy.
Yonsei Medical Journal 02/1999; 40(1):40-5. DOI:10.3349/ymj.1918.104.22.168 · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Unlike most secretory cells, high extra cellular calcium inhibits rather than stimulates hormonal secretion in several cells such as parathyroid cells, Juxtaglomerular cells and osteoclast. To gain further insight into the common but unique stimulus-secretion coupling mechanism in these cells, bovine parathyroid slices were incubated in various conditions of Krebs-Ringer (KR) solution containing essential amino acids. Parathyroid cells showed the inverse dependency of secretion on extra cellular calcium concentration as we expected. Ammonium acetate overcame the inhibitory effect of 2.5 mM of calcium and the maximum effect was as much as the five times of the basal value, while there was a little additive effect under 0 mM CaCl2. PTH secretion was biphasic according to the change of extra cellular osmolarity and the lowest response was observed at 300 mOsm/l. In Na-rich KR solution, high concentration of nigericin (> 10(-4)M) completely overcame the inhibitory effect of 2.5 mM CaCl2 and the maximum stimulatory effect was 8 times greater whereas it was only 2 times greater without CaCl2. In K-rich KR solution that abolished the K-gradient between the extra cellular solution and the cytoplasm, the rate of PTH secretion increased, and furthermore the addition of nigericin increased the rate of secretion significantly. The results above suggested that the osmotic swelling of the secretory vesicle in parathyroid cells might promote exocytosis as in Juxtaglomerular cells. We propose that the swelling of the vesicle is also prerequisite for secretion in several cells inhibited paradoxically by Ca++, whatever the signal transduction pathway for swelling of the secretory granules induced by the lowering of Ca++ in cytoplasm are.
Yonsei Medical Journal 02/1996; 37(1):59-67. DOI:10.3349/ymj.1922.214.171.124 · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hyperthyroidism is associated with an impairment of growth hormone (GH) responses to secretagogues. The aim of this study was to evaluate the effect of acipimox, an antilipolytic agent able to decrease free fatty acids (FFA), on GH response to GH-releasing hormone (GHRH) in hyperthyroid and normal control subjects. We studied six men with hyperthyroidism; seven normal men served as control subjects. Each subject underwent treatment with (1) 2 tablets of placebo orally or (2) 500 mg acipimox orally, 120 minutes before intravenous (IV) injection of 1 microgram/kg GHRH-(1-29)NH2. GH response to GHRH in hyperthyroid patients was markedly reduced; the mean peak GH response (9.6 +/- 1.0 microgram/L) and the area under the GH response curve (12.9 +/- 1.3 micrograms/L x 2 h) were lower than those of control subjects (25.7 +/- 1.8 micrograms/L, P < .05; 28.7 +/- 2.1 micrograms/L x 2 h, P < .05). Hyperthyroid patients had higher baseline levels of plasma FFA than control subjects (998.0 +/- 38.9 v 498.0 +/- 36.0 muEq/L, P < .01). Acipimox decreased FFA levels in both hyperthyroid and control subjects; the lowest FFA levels of hyperthyroid subjects induced by acipimox were similar to those of control subjects. After acipimox pretreatment, GH responses to GHRH increased significantly (P < .05); the mean peak plasma GH level (25.9 +/- 4.6 micrograms/L) was similar to the peak GH levels of control subjects during the GHRH test, and the area under the GH response curve (41.1 +/- 6.7 micrograms/L x 2 h) was even higher than that of control subjects with the GHRH test.(ABSTRACT TRUNCATED AT 250 WORDS)
[Show abstract][Hide abstract] ABSTRACT: Among autoantibodies detected in patients with insulin-dependent diabetes mellitus (IDDM), antibodies to 64,000(Mr) islet protein(64k), now recognized as glutamic acid decarboxylase(GAD), appear to be an even more predictive marker of IDDM than islet cytoplasmic antibody (ICA) or insulin autoantibody (IAA). We examined the relationships among 64k autoantibodies, pancreatic beta-cell function, HLA-DR antigens and HLA-DQ genes in patients with IDDM in Korea.
To identify the 64k autoantibody, the immunoprecipitation method was performed for 35 patients with IDDM and 10 normal controls. In patients with IDDM, serum C-peptide levels were measured and HLA-DR typings and HLA-DQA1 and DQB1 gene typings were performed.
12 of 35 (34%) patients with IDDM were positive for 64k autoantibody in contrast to none of 10(0%) normal controls. There were no differences in residual pancreatic beta-cell function between 64k autoantibody positive and negative groups. 64k autoantibody was detected more frequently in patients with recent (duration < 6 months, 10/25[40%]) and young -aged(aged < 15 years, 7/18[39%]) onset of IDDM. All of 3(100%) patients with HLA-DR3/DR4 heterotypes were positive in 64k autoantibody, in contrast to 1 of 7(14%) patients without HLA-DR3 nor DR4. The frequencies of HLA-DQA1*0301, HLA-DQB1*0201, DQB1* 0302 and DQB1*0303 gene types were higher in patients with 64k autoantibody (12/12 [100%]) vs. without 64k autoantibody 18/22[81%], 5/11[45%] vs. without 64k autoantibody 5/22[23%], 5/11[45%] vs. without 64k autoantibody 8/22[36%] and 6/11 [55%] vs. without 64k autoantibody 9/22[41%].
There results suggest that 64k autoantibodies have some relationship with HLA-DR, DQA1 and DQB1 genes, but not with residual pancreatic beta-cell function in Korean patients with IDDM.
The Korean Journal of Internal Medicine 02/1995; 10(1):1-9. DOI:10.3904/kjim.19126.96.36.199 · 1.43 Impact Factor