S K Lim

Kwandong University, Seoul, Seoul, South Korea

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Publications (75)213.68 Total impact

  • Article: Serotypes of salmonella isolated from faeces of patients with acute diarrhoea in gwangju area, Korea, during 2000-2009.
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    ABSTRACT: The purpose of this study was to determine the changing pattern of Salmonella serotypes causing acute diarrhoea in humans in Gwangju area, Korea, during 2000-2009. A total of 596 Salmonella isolated from culture of 29 896 faecal samples of patients with acute diarrhoea were included in this study. Faecal samples were collected from local hospitals and clinics in Gwangju area during January 2000-December 2009. The mean annual frequency of isolates for the 10 years was 2.0% (range, 0.9-6.0). The isolates were serologically classified into 43 different serotypes. The 10 most common serotypes were Salmonella Enteritidis (47.9%), S. Typhimurium (20.4%), S. Braenderup (3.2%), S. Montevideo (2.9%), S. Paratyphi B (2.9%), S. London (2.3%), S. Bardo (1.7%), S. Virchow (1.7%), S. Infantis (1.5%) and S. Typhi (1.5%), accounting for 86% of all the isolates. Temporal variations were observed in the distribution of different Salmonella serotypes over the years, and only S. Enteritidis and S. Typhimurium were persistent throughout the study period. Although age specificity varied with serotypes, Salmonella was isolated most frequently from children below 5 years of age (179/596, 30.0%). A seasonal trend was apparent, and the highest rates were found in the summer months. This is the first report of the annual frequency of isolation of Salmonella serotypes, and seasonal and age-specific patterns of salmonellosis in humans in Gwangju area, Korea, over a decade-long period.
    Zoonoses and Public Health 09/2012; 59(7):482-9. · 1.89 Impact Factor
  • Article: Prevalent vertebral fractures predict subsequent radiographic vertebral fractures in postmenopausal Korean women receiving antiresorptive agent.
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    ABSTRACT: The relationship between prevalent vertebral fractures and new vertebral fractures in Korean women has not been previously studied. We found that prevalent vertebral fracture is a strong risk factor for subsequent radiographic vertebral fracture, independent of age and spine bone mineral density (BMD) in postmenopausal Korean women receiving antiresorptive agents. The presence of prevalent vertebral fractures increases the risk of subsequent vertebral fractures. This observational study examined whether prevalent vertebral fractures influenced future incident vertebral fracture in postmenopausal women receiving antiresorptive treatment. Using the medical records, we retrospectively assessed 1,200 postmenopausal women who had visited the osteoporosis clinic. Among them, we selected patients whose BMD was measured at least once a year for 3 years. We excluded patients whose lateral spine X-ray film at baseline or follow-up period was missing, which is the key assessment. In the end, we analyzed 666 postmenopausal women. The mean duration of follow-up period was 3.2 years. The majority of patients (83%) received bisphosphonates or raloxifene during the mean duration of 3.2 years. Fifty-five of the 666 women had new incident radiographic vertebral fractures during the follow-up period. Prevalent vertebral fractures were associated with a five-fold increased risk (odd ratio 5.7, 95% CI 3.09-10.74) of incident vertebral fractures after adjusting for age. These associations remained significant after the adjustment for multiple confounding factors (odd ratio 4.4, 95% CI 1.97-9.75). The risk of incident vertebral fracture increased with the number of prevalent vertebral fractures at baseline: 3.4 (95% CI 1.54-7.70) for those with a single fracture and 7.4 (95% CI 3.10-17.54) for those with two or more after adjustment for age and spine BMD. We confirmed that prevalent vertebral fracture is a strong risk factor for new vertebral fractures, independent of age and spine BMD in postmenopausal Korean women receiving antiresorptive agents.
    Osteoporosis International 03/2011; 22(3):781-7. · 4.58 Impact Factor
  • Article: Differences in femoral neck geometry associated with age and ethnicity.
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    ABSTRACT: We studied femoral geometry in relation to age and ethnicity in a cross-sectional study. Age-associated cortical thinning showed the most pronounced effect, and Koreans studied here had thicker cortices and lower buckling ratios than those reported for other races. Cortical thickness may thus be a major determinant of hip fracture risk. The rate of hip fracture varies by age and ethnicity. The geometric properties of the femur influence femoral strength and fragility, but differences in femoral geometry according to age and ethnicity are poorly understood. To explain the high prevalence of hip fractures in the elderly and the relatively low hip fracture rate in Asian populations, we studied age-related changes and ethnic differences in femoral geometry. We recruited 214 peri- or postmenopausal women aged 46 to 85 years (mean age, 60.6 years). Their proximal femoral bone mineral densities (BMD) were measured by quantitative computed tomography and further analyzed geometric properties. We observed large declines in trabecular volumetric bone mineral density associated with aging (33.03% less than the reference value in the oldest group, respectively). Cortical thickness decreased remarkably with age as well, and only 53.94% of the baseline value remained in the oldest group. As a result, the cortical buckling ratio increased geometrically and reached 239.14% of the reference value in the oldest group. In comparisons with other ethnic groups, Korean subjects had thicker cortices than their American, European, and African counterparts. In this cross-sectional study, cortical thickness showed a pronounced age-associated decrease, and the cortical buckling ratio showed a strong age-associated increase. This may in part explain the higher rates of hip fractures in the elderly. When compared with other races, Asians had thicker cortical bone and lower buckling ratios, which may partially explain the lower prevalence of hip fractures in Asians.
    Osteoporosis International 10/2010; 22(7):2165-74. · 4.58 Impact Factor
  • Article: The effect of mosapride (5HT-4 receptor agonist) on insulin sensitivity and GLUT4 translocation.
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    ABSTRACT: We investigated the effect of mosapride, 5HT-4 (5-hydroxytryptamine) agonist, on blood glucose level and insulin sensitivity in subjects with impaired glucose tolerance (IGT) and conducted an in vitro study to evaluate the action mechanism. Thirty IGT patients were randomly assigned to receive either mosapride or placebo for 2 weeks. Biochemical profiles and insulin sensitivity index from euglycemic hyperinsulinemic clamp test were assessed before and after treatment. In cultured myotubes from human skeletal muscle cells, insulin- and mosapride-induced GLUT4 translocation and tyrosine phosphorylation of IRS-1 were determined. After 2 weeks of treatment with mosapride, glucose disposal rates were significantly increased up to those of control (mosapride 5.47+/-1.72 vs 7.06+/-2.13, P=0.004, placebo 5.42+/-1.85 vs 5.23+/-1.53mgkg(-1)min(-1)). Fasting plasma glucose (FPG) and insulin levels were decreased. Mosapride increased the contents of GLUT4 in plasma membrane representing the increased recruitment of glucose transporters from intracellular pool. While insulin treatment on human skeletal muscle cell resulted in an increased tyrosine phosphorylation of IRS-1, mosapride did not have any effect. Mosapride is effective in decreasing FPG without stimulating insulin secretion in IGT subjects, possibly by inducing GLUT4 translocation in skeletal muscles.
    Diabetes research and clinical practice 03/2010; 87(3):329-34. · 2.16 Impact Factor
  • Article: The effect of rosiglitazone on insulin sensitivity and mid-thigh low-density muscle in patients with Type 2 diabetes.
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    ABSTRACT: We examined the effect of rosiglitazone on insulin sensitivity, abdominal fat and mid-thigh intramuscular fat distribution, and plasma concentrations of adipocytokines in patients with Type 2 diabetes. Rosiglitazone was administered at a daily dose of 4 mg to 42 Type 2 diabetes patients [age 32-70 years, body mass index (BMI) 17.5-32.6 kg/m(2), 15 women, 27 men] for 12 weeks. Various anthropometric and metabolic profiles, plasma adiponectin, leptin, and resistin levels were measured, and insulin resistance was calculated from the short insulin tolerance test. Body fat composition was assessed by computed tomography. Twelve weeks' rosiglitazone treatment resulted in improved insulin resistance despite increases in body weight and BMI. There was a significant decrease in abdominal visceral adipose tissue area (145 +/- 65.6 vs. 129 +/- 73.1 cm(2), P = 0.049). Mid-thigh low-density muscle area (TLDMA) increased from 23 +/- 9.6 to 26 +/- 8.2 cm(2) (P = 0.009). There were significant changes in plasma adipocytokines, but they were not significantly correlated with changes in insulin resistance. Rosiglitazone treatment resulted in an improvement of insulin responsiveness in Type 2 diabetic subjects, which was associated with the redistribution of visceral and subcutaneous adipose tissue, an increase in TLDMA, and changes in serum adipocytokine levels. Further studies are needed to elucidate the insulin sensitizing mechanism of rosiglitazone on peripheral skeletal muscles.
    Diabetic Medicine 01/2010; 27(1):30-6. · 2.90 Impact Factor
  • Article: Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia.
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    ABSTRACT: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of bisphosphonate therapy. The incidence of BRONJ is known to be low among patients treated with oral bisphosphonates. We investigated the prevalence, demographics, clinical manifestations, and treatment outcome of 24 patients with oral BRONJ in Asian populations. The long-term safety of oral bisphosphonates is clinically important considering the rare but potentially serious complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ) versus the effect of reducing and preventing osteoporotic fracture. The incidence of BRONJ is known to be low among patients treated with oral bisphosphonates around the world. However, the prevalence in those taking oral bisphosphonates for osteoporosis in Asian populations is unknown. Moreover, a recent article, showing that the majority of reported patients who received alendronate were Asian American, raised concern about the prevalence of oral BRONJ in Asian populations. The objective of this study was to investigate the estimated prevalence, clinical characteristics, and treatment outcome of oral BRONJ in Asian populations. From October 2005 to December 2008, a retrospective review of medical charts identified 24 patients receiving oral bisphosphonates diagnosed as BRONJ at the Department of Oral and Maxillofacial Surgery, Yonsei University Dental Hospital, Seoul, South Korea. The estimated prevalence of oral BRONJ was 0.05-0.07%. The average oral bisphosphonate treatment duration was 43.1 months (range, 5-120 months). Treatment with oral antibiotics and/or surgery including sequestrectomy or alveolectomy showed relatively favorable results. The prevalence of oral BRONJ in Korea is similar to that reported previously in Western populations. We suggest that recognition of BRONJ and appropriate management pre- and post-dental surgery might reduce the frequency of BRONJ among patients receiving oral bisphosphonates.
    Osteoporosis International 08/2009; 21(5):847-53. · 4.58 Impact Factor
  • Article: Serum parathyroid hormone is associated with carotid intima-media thickness in postmenopausal women.
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    ABSTRACT: To test whether parathyroid hormone (PTH) might be related to the development of atherosclerosis in postmenopausal women, we measured serum levels of PTH, the carotid intima-media thickness (IMT), and other clinical and biochemical parameters. One hundred and seven postmenopausal women were recruited for this study. The serum level of PTH was measured by immunoradiometric assay, and carotid IMT was measured with high resolution B-mode ultrasonography. On the basis of bivariate correlation analyses or unpaired t-tests, the body mass index (BMI), waist circumference, estimated glomerular filtration rate, and 25-hydroxyvitamin D were not associated with carotid IMT. In contrast, age (r = 0.414, p < 0.001), serum level of PTH (r = 0.304, p = 0.001), hypertension (p < 0.001), and hypercholesterolaemia (p = 0.004) were related to carotid IMT. On the basis of multiple regression analysis, the serum level of PTH (beta = 0.198, p = 0.029), as well as age (beta = 0.309, p = 0.001) and hypertension (beta = 0.262, p = 0.006), were independent predictors of carotid IMT. Our results have demonstrated that serum PTH is an independent determinant of carotid IMT in postmenopausal women. This result suggests that serum PTH, even in the reference range, might be associated with the development of atherosclerosis or cardiovascular diseases in postmenopausal women. Further study is necessary in males and premenopausal women to fully elucidate the clinical significance of this finding.
    International Journal of Clinical Practice 09/2008; 62(9):1352-7. · 2.41 Impact Factor
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    Article: Vitamin D inadequacy in postmenopausal women in Eastern Asia.
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    ABSTRACT: To review data on the prevalence of vitamin D inadequacy and its causes in postmenopausal women in Eastern Asia. Research design and method: Data were obtained from the published biomedical literature as well as abstracts and posters presented at scientific meetings. Using MEDLINE, EMBASE and BIOSIS databases (to July 2007), epidemiological studies were identified using the search terms: 'human', 'vitamin D', 'vitamin D deficiency', 'vitamin D inadequacy', 'vitamin D insufficiency' and 'hypovitaminosis D', 'osteomalacia' and 'osteoporosis'. Additional references were also identified from the bibliographies of published articles. The prevalence of vitamin D inadequacy in studies of postmenopausal women (ambulatory or with osteoporosis or related musculoskeletal disorders) in Eastern Asia ranged from 0 to 92%, depending on the cut-off level of serum 25-hydroxycholecalciferol [25(OH)D] that was applied (range < or =6-35 ng/mL [< or = 15-87 nmol/L]). One large international study found that 71% of postmenopausal women with osteoporosis in Eastern Asia had vitamin D inadequacy, defined as serum levels of 25(OH)D < 30 ng/mL (75 nmol/L). Prevalence rates using this cut-off level were 47% in Thailand, 49% in Malaysia, 90% in Japan and 92% in South Korea. High prevalences of vitamin D inadequacy were evident in two studies using a lower 25(OH)D level cut-off value of < 12 ng/mL (30 nmol/L) - 21% in China and 57% in South Korea. Dietary deficiency and inadequate exposure or reactivity to sunlight (due to lifestyle choices, cultural customs and/or aging) were identified as important risk factors for vitamin D inadequacy. Non-uniform, epidemiological studies indicate a high prevalence of vitamin D inadequacy in postmenopausal women in Eastern Asia. Recommended remedial approaches are education campaigns and broad-based provision of vitamin D supplementation.
    Current Medical Research and Opinion 01/2008; 24(1):99-106. · 2.38 Impact Factor
  • Article: The clinical and immunogenetic characteristics of adult-onset type 1 diabetes mellitus in Korea.
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    ABSTRACT: Although the HLA class II alleles and immunological abnormalities are associated with type 1 diabetes mellitus (T1DM) in all racial groups, there are considerable variations in the genotypes and the prevalence of autoantibodies. In order to investigate the characteristics of the immunogenetic patterns and to use these as an early diagnostic tool and guideline for a therapeutic plan, we examined the clinical characteristics and the patterns of anti-GAD antibody (GADA), IA-2 antibody (IA-2A), HLA-DR and HLA-DQ in Korean adult-onset T1DM patients. Adult-onset patients had higher serum C-peptide levels than child-onset patients. In adult-onset patients, the prevalence of GADA and IA-2A were 59.5% and 15.3% respectively, and increased frequencies of HLADR4 and-DR9 were found. The frequencies of HLADQA1,-DQB1 and-DQ heterodimers were similar to those of the control, but child-onset patients had high frequencies of the HLA-DR3,-DR4,-DR9, DQA1*0301, DQA1*0501 and DQB1*0201 genotypes. In conclusion, Korean adult-onset T1DM patients had a lower prevalence of GADA, which was comparable to that found in Caucasian patients. The detection of GADA might help to predict the insulin dependency of adult-onset diabetes. Difference in the frequencies of diabetes associated with HLA type suggests that there might be a heterogeneity in the pathogenesis of diabetes according to the age of onset.
    Acta Diabetologica 07/2007; 44(2):45-54. · 2.78 Impact Factor
  • Article: Analysis of adrenal masses by 18F-FDG positron emission tomography scanning.
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    ABSTRACT: This study aimed to analyse the characteristics of adrenal masses visible in the computerised tomography (CT) scans which have been also evaluated by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET), and to characterise the features of 18F-FDG PET scans associated with various adrenal endocrine tumours, especially benign functional tumours. 18F-FDG PET scans of 105 patients with adrenal masses on the CT scan were analysed. Positive uptakes in the 18F-FDG PET scans were seen in 60 malignant tumours (54 metastasic lesions, six primary adrenal cancers) and seven benign tumours. The positive predictive value of 18F-FDG PET imaging to characterise an adrenal mass as a malignant tumour was 90%; the corresponding negative predictive value to rule out malignancy was also 90%. Benign adrenal tumours were smaller than that of malignant lesions (p<0.05). The mean standardised uptake value max (SUVmax) of the metastatic lesions [8.4+/-6.5 (microCi/g)/microCi/kg] was significantly higher than that of the benign adrenal tumours [2.4+/-1.2 (microCi/g)/microCi/kg, p<0.001]. Examination of only the primary adrenal lesions revealed that all adrenocortical carcinomas, two of three cases of pheochromocytomas, three of five neuroblastomas and two of four cases of primary aldosteronism showed positive 18F-FDG uptake. In conclusion, for patients presenting adrenal masses with a high probability of malignancy, 18F-FDG PET can be used to differentiate malignant from benign adrenal lesions. However, the 18F-FDG PET uptake did not show an always consistent pattern for endocrine tumours, which was probably due to the variability inherent in 18F-FDG uptake. This study suggests that 18F-FDG PET scanning can offer supporting data to localise and characterise adrenal tumours.
    International Journal of Clinical Practice 05/2007; 61(5):802-9. · 2.41 Impact Factor
  • Article: Ectopic Cushing's syndrome due to concurrent corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) secreted by malignant gastrinoma.
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    ABSTRACT: Ectopic Cushing's syndrome due to various malignancies is not uncommon. However, a few cases of ectopic Cushing's syndrome caused by corticotropin-releasing hormone (CRH), or CRH with adrenocorticotropic hormone (ACTH) have been reported. A 28-year-old woman presented with acute upper gastrointestinal bleeding caused by an active ulcer, located atypically in the 2nd portion of duodenum. Further work-up revealed high gastrin levels and abdominal computed tomography (CT) scans showed a large pancreatic head mass with multiple liver metastases. The serum cortisol and ACTH levels were checked due to hypokalemia with metabolic alkalosis and recent amenorrhea. Cortisol and ACTH were both highly elevated with pituitary hyperplasia and elevated CRH. The existence of ectopic ACTH and CRH in the liver biopsy was also demonstrated immunohistochemically. Since an operation was not feasible, chemotherapy was conducted using paclitaxel and etoposide. These two drugs were chosen according to the IN VITRO chemotherapy response assay to maximize the treatment. This report demonstrates concurrent ACTH- and CRH-related ectopic Cushing's syndrome caused by malignant gastrinoma with multiple liver metastases that was treated with marginal success using a multidisciplinary medical approach.
    Experimental and Clinical Endocrinology &amp Diabetes 02/2007; 115(1):13-6. · 1.69 Impact Factor
  • Article: Effects of a combined alendronate and calcitriol agent (Maxmarvil) on bone metabolism in Korean postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study.
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    ABSTRACT: A randomized, double-blind, prospective, 24-week clinical trial was performed to evaluate the effects of a combinative agent, Maxmarvil, of calcitriol (0.5 mug) and alendronate (5 mg) on bone metabolism in postmenopausal women. A total of 217 postmenopausal women with osteoporosis were enrolled; 199 patients were randomly assigned to one of two treatment groups (Maxmarvil group or alfacalcidol group). None of the patients were vitamin-D-deficient, as assessed by serum 25-hydroxyvitamin D (25(OH)D), nor had they received any drugs affecting bone metabolism before enrollment. Bone mineral densities (BMD) of L1-L4 and the femur were measured by dual-energy X-ray absorptiometry (DXA) at the initial assessment and after 6 months of treatment. Serum biochemical assays, including serum calcium, 24-h urinary calcium excretion, and bone turnover markers (both bone-specific alkaline phosphatase [bsALP] and urine N-telopeptide [NTx]), were performed at the baseline and after 3 and 6 months of treatment. In the Maxmarvil group, the BMD of the lumbar spine increased up to 2.42+/-0.5% from the baseline after 6 months (p<0.05). On the other hand, the change in BMD in the alfacalcidol group was 0.28+/-0.5% after 6 months. There was no significant difference in femoral BMD between the two groups. The levels of bsALP and NTx were significantly lower in the Maxmarvil group than in the alfacalcidol group (-22.04+/-3.9% vs. -11.42+/-2.8% [p<0.05] and -25.46+/-5.2% vs. 1.24+/-6.2% [p<0.001], respectively). Interestingly, there was a significantly smaller amount of 24-h urinary calcium in the Maxmarvil group (p<0.05). Our study demonstrates that a combination of calcitriol and alendronate is quite effective in preventing bone loss, with the advantage of lesser hypercalciuric effect of calcitriol in the postmenopausal osteoporotic women.
    Osteoporosis International 12/2006; 17(12):1801-7. · 4.58 Impact Factor
  • Article: A case of primary antiphospholipid syndrome and Type 2 diabetes mellitus with large artery thromboses successfully treated by abdominal stent implantation.
    Diabetic Medicine 12/2004; 21(11):1258-9. · 2.90 Impact Factor
  • Article: Sibutramine improves fat distribution and insulin resistance, and increases serum adiponectin levels in Korean obese nondiabetic premenopausal women.
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    ABSTRACT: The aim of this study was to evaluate the effects of sibutramine on body composition and fat distribution, insulin resistance, and serum adiponectin levels in obese women. A total of 28 obese, premenopausal women (mean age, 34.5 +/- 13.7 years; BMI, 31.00 +/- 4.10 kg/m2) was studied before and after 12-week-course of sibutramine (10mg/day). Sibutramine treatment reduced body mass index (P < 0.05) and total body fat (P < 0.05). Abdominal subcutaneous and visceral fat areas (ASFA and AVFA) and mid-thigh low density muscle areas (LDMA) measured by computed-tomography decreased significantly (all, P < 0.05). Insulin resistance (IR) calculated from the homeostasis model assessment (HOMA) method decreased (P < 0.05) and serum adiponectin levels increased significantly (P < 0.05). In our sequential data, the changes of fasting serum insulin levels and the HOMA-IR scores, serum free fatty acids and triglyceride levels, serum adiponectin levels and the mid-thigh LDMA preceded significant changes of body weight, total body fat, and abdominal fat distribution, suggesting sibutramine might improve insulin sensitivity directly by alterations of fatty acid metabolism or secondarily by increasing serum adiponectin levels. Conclusively, sibutramine improved fat distribution and insulin resistance, and increased serum adiponectin levels in Korean obese nondiabetic premenopausal women.
    Diabetes Research and Clinical Practice 12/2004; 66 Suppl 1:S139-44. · 2.75 Impact Factor
  • Article: An implication of hypertriglyceridemia in the progression of diabetic nephropathy in metabolically obese, normal weight patients with type 2 diabetes mellitus in Korea.
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    ABSTRACT: This study was undertaken to investigate diverse risk factors affecting the progression of diabetic nephropathy (DN) by observing the changes of 24 h urinary albumin excretion (24 h UAE) in 90 abdominally obese, normal weight, type 2 diabetic patients with normo- or micro-albuminuria. Patients were divided into three groups according to the 24h UAE; normo-, micro-, and macro-albuminuria group. After 4 years of follow-up, patients were divided into either progression or non-progression group according to the changes of 24 h UAE. About 37% of the normo-albuminuria group and 18% of the micro-albumiuria group were classified into the progression group. The initial serum creatinine levels and the initial and follow-up post-prandial plasma glucose levels were significantly higher in the progression group than in the non-progression group. Most remarkably, the initial and follow-up serum triglyceride (TG) levels (190 +/- 132 versus 132 +/- 49 mg/dl and 191 +/- 124 versus 133 +/- 41 mg/dl, P < 0.01 in both) were significantly higher in the progression group than in the non-progression group, suggesting hypertriglyceridemia might be included in the progression factors of DN. The increases in 24-hour UAE were positively associated with the initial and follow-up post-prandial plasma glucose levels (P < 0.05 in both), the initial and follow-up serum creatinine levels (P < 0.05 in both), and the initial serum TG levels (P < 0.05). Whereas, insulin users or patients with retinopathy at follow-up (P < 0.05 in both) showed more rapid progression of albuminuria, ACE inhibitors or acarbose (P < 0.05 in both) use turned out to protect against it.
    Diabetes Research and Clinical Practice 12/2004; 66 Suppl 1:S169-72. · 2.75 Impact Factor
  • Article: The 10th and 11th residues of short length N-terminal PTH(1-12) analogue are important for its optimum potency.
    S-K Lim, E J Lee, H-Y Kim, W Lee
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    ABSTRACT: The 10th and 11th residues of parathyroid hormone PTH(1-12) analogues were substituted to study the structure and function of PTH analogues. The substitution of Ala(10) of [Ala(3,10,12)(Leu(7)/Phe(7))Arg(11)]rPTH(1-12)NH(2) with Glu(10) and/or the Arg(11) with Ile(11) markedly decreased cAMP generating activity. Data from circular dichroism (CD) and the nuclear magnetic resonance (NMR) structural analysis of [Ala(3,10,12)(Leu(7)/Phe(7))Arg(11)]rPTH(1-12)NH(2) revealed tight alpha-helical structures, while the Glu(10) and/or Ile(11) substituted analogues showed unstable alpha-helical structures. We conclude that 10th and 11th residues are important for stabilizing its helical conformation and that destabilization of the alpha-helical structure, induced by substituting the above residues, remarkably affect its biological potency.
    European Journal of Allergy and Clinical Immunology 08/2004; 64(1):25-32. · 1.30 Impact Factor
  • Article: Insulin sensitivity in physically fit and unfit children of parents with Type 2 diabetes.
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    ABSTRACT: First-degree relatives of patients with Type 2 diabetes mellitus (T2DM) are often reported to be insulin resistant. We wanted to identify early metabolic abnormalities in this condition, and determine whether they are altered by regular physical training. We measured insulin sensitivity using the euglycaemic glucose clamp technique and insulin response to oral glucose in 10 unfit (did not participate in routine physical exercise) offspring of T2DM parents and 10 unfit control subjects, and compared them with six fit (routinely swam for 3 h/day 5 days/week) offspring of T2DM parents and six fit controls with no family history of T2DM. Unfit offspring had a higher plasma glucose response than the other three groups. The mean area under the glucose curve was also significantly higher in unfit offspring than in the other three groups (12.6 +/- 0.6 vs. 10.4 +/- 0.4, 9.6 +/- 0.5, and 9.5 +/- 0.7 mmol/l per hour for the unfit controls, fit offspring and fit controls, respectively; P < 0.05). The corresponding insulin response of unfit offspring was significantly higher at 60 min in the oral glucose tolerance test (OGTT) that that of fit offspring or fit controls. In addition, the mean area under the insulin curve was significantly greater in unfit offspring than in either fit offspring or fit controls (868 +/- 172 vs. 294 +/- 71, 287 +/- 43 mmol/l per hour, respectively; P < 0.05). Moreover, the glucose disposal rate (GDR), measured using a euglycaemic clamp, was significantly lower in unfit and fit offspring than in unfit and fit controls (5.6 +/- 0.3 vs. 8.6 +/- 0.3 mg/kg per minute; P < 0.01 and 9.3 +/- 0.9 vs. 12.1 +/- 0.8 mg/kg per minute, respectively; P < 0.015), whereas the GDR was similar in unfit controls and fit offspring (8.6 +/- 0.4 vs. 9.3 +/- 0.9 mg/kg per minute; P > 0.05). These results support the concept that early metabolic abnormalities, as reflected by a decreased GDR (insulin sensitivity) in the offspring of T2DM patients, may be improved by increased physical fitness.
    Diabetic Medicine 02/2004; 21(1):59-63. · 2.90 Impact Factor
  • Article: Therapeutic effect of recombinant human erythropoietin on anaemia with erythropoietin deficiency in diabetic patients.
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    ABSTRACT: The aim of this study was to investigate the therapeutic effect of recombinant human erythropoietin (rHuEpo) on anaemia with erythropoietin deficiency in diabetic patients. Twenty diabetic patients with anaemia and Epo deficiency were enrolled. All patients were treated with rHuEpo (Epokine; 4000 U/day s.c., three times a week) for 8 weeks. The responder group (n = 14) had significant increments in haemoglobin compared with the non-responder group (n = 6) (P < 0.05). No significant differences were found between the responder and non-responder groups in terms of duration of diabetes mellitus, serum creatinine level, 24-h urine albumin excretion rates, frequency of diabetic microangiopathy, or HbA1c. There was no difference between the two groups in terms of serum iron and total iron-binding capacity (TIBC). Serum ferritin level was significantly higher in the responder group than in the non-responder group (240.3 +/- 108.4, 25.8 +/- 3.0 micro g/l, P < 0.05), as was transferrin saturation (32.7 +/- 7.9%, 21.2 +/- 5.3%, P < 0.05). rHuEpo could be useful in the treatment of anaemia with erythropoietin deficiency in diabetic patients, and the degree of iron storage and functional iron deficiency might be the main cause of hyporesponsiveness to rHuEpo.
    Diabetic Medicine 08/2003; 20(8):661-4. · 2.90 Impact Factor
  • Article: NMR structure of a minimum activity domain of human parathyroid peptide hormone: structural origin of receptor activation.
    J Jung, S-K Lim, Y Kim, W Lee
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    ABSTRACT: Parathyroid hormone (PTH) which increases osteoblast numbers and bone formation by activating bone-lining cells to osteoblasts plays an important role in calcium and phosphate homeostasis and bone remodeling by activating PTH receptors. To determine the structural origin of a minimum activity domain of hPTH, we initiated a detailed structural determination of the hPTH(H14) in aqueous solution using NMR spectroscopy. Circular dichroism and NMR data demonstrated that hPTH(H14) maintains a typical helical conformation in both membrane-mimicking environments and 30% TFE solution. The solution structure clearly showed that the residues from Ser(3) to Leu(11) of hPTH(H14) formed a stable helical structure, especially having charged side-chains oriented in opposite directions relative to one another for optimum interaction with the receptor molecule.
    European Journal of Allergy and Clinical Immunology 12/2002; 60(5):239-46. · 1.30 Impact Factor
  • Article: The effects of recombinant human parathyroid hormone, rhPTH(1-84), on bone mass in undernourished rats.
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    ABSTRACT: Energy intake restriction reduces bone formation both in protein-energy malnourished children and in undernourished rats, and such conditions might cause partial or irreversible bone loss. Because the use of anti-resorptive agents in this situation is seemingly limited, we examined the effect of the anabolic agent, recombinant human parathyroid hormone (rhPTH(1-84)), on bones in undernourished conditions. First, the osteopenic changes of rat bones with 40% restricted diet for 4 weeks were confirmed. Subsequently, another set of the rats were randomized into four groups and studied for 8 weeks: the freely fed group (control group); the restricted diet, then freely fed group (restriction-ad libitum group); the restricted diet-vehicle-treated group (restriction-vehicle group); and the restricted diet-PTH-treated group (restriction-PTH group). In the restriction-vehicle group, total femoral bone mineral density (BMD) was lower and femoral length was shorter than the control group by 15.4% and 8.1% respectively (P<0.05). In the restriction-ad libitum group, these parameters recovered fully to those of the control group. In the case of intermittent PTH treatment in the persistent undernourished state, the BMD of total femur caught up with those of the control or the restriction-ad libitum group. However, the femoral length remained shorter than those of the other groups. Serum osteocalcin was significantly reduced in continuously undernourished rats, whereas it was elevated in the restriction-PTH group. In conclusion, BMD of total femur was low in undernourished rats. However, it increased after re-feeding ad libitum or intermittent PTH treatment. We suggest that rhPTH(1-84) may be a possible therapeutic agent for ongoing bone loss, especially in patients in a chronically undernourished condition.
    Journal of Endocrinology 10/2002; 174(3):419-25. · 3.55 Impact Factor