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Biomedical subjects

K B Huh

Publications and source records attributed to K B Huh.

At least 37 records · Page 2Linked to original sources
PubMed1999

Reduced erythropoietin responsiveness to anemia in diabetic patients before advanced diabetic nephropathy.

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.

Aged↗
PubMed1999

Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults.

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 < 0.05). In the placebo group, there was a loss in lean body mass (-2.62 +/- 1.51 kg) and a negative nitrogen balance (-4.52 +/- 3.51 g/day). By contrast, the GH group increased in lean body mass (1.13 +/- 1.04 kg) and had a positive nitrogen balance (1.81 +/- 2.06 g/day). GH injections caused a 1.6-fold increase in IGF-I, despite caloric restriction. GH response to 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.

Adipose Tissue↗
PubMed1999

A PCR analysis of ERalpha and ERbeta mRNA abundance in rats and the effect of ovariectomy.

To study the relative abundance and the changes of both estrogen receptor alpha (ERalpha) and ERbeta mRNA before and after ovariectomy in major organs important to the regulation of calcium homeostasis, we compared the degree of mRNA expression of ERalpha to that of ERbeta in rat tissues by performing competitive reverse transcription polymerase chain reaction (RT-PCR) with internal standards. Both ERalpha and ERbeta were highly expressed in the ovary {ERalpha[(2.2 +/- 0.33) x 10(7) copies/microg of total RNA] > ERbeta[(1.2 +/- 0.33) x 10(5) copies/microg of total RNA]} as we expected. The bone marrow and renal cortex were very important target organs of estrogen because ERalpha was highly expressed approximately 2 x 10(5) copies/microg of total RNA, but marrow cells revealed only a very weak expression of ERbeta [(0.7 +/- 0.21) x 10(2) copies/microg of total RNA]. Both ERalpha and ERbeta were expressed in the trabecular bone [(3.2 +/- 0.56) x 10(3) copy/microg of RNA] and [(2.8 +/- 0.21) x 102 copy/microg of RNA], respectively. However, they were not detected in the cortical bone. In the jejunum, the expression of ERalpha was not detectable, while ERbeta was expressed very weakly [(1.1 +/- 0.24) x 10(2) copies/microg of total RNA]. The thyroid gland expressed low copy numbers of ERbeta [(6.0 +/- 0.23) x 10(2) copies/microg of total RNA], but the parathyroid gland was negative for both ERalpha and ERbeta mRNA. In cultured stromal cells, ERalpha and ERbeta mRNAs were not detected after a 24-h culture; however, the rates of mRNA expression of ERalpha and ERbeta reached approximately 105 copies/microg of total RNA and approximately 10(2) copies/microg of total RNA, respectively, after 9-, 11-, and 13-day cultures. After ovariectomy, the expression of ERalpha mRNA decreased abruptly in the bone marrow and renal cortex, and both ERalpha and ERbeta were barely detected in the trabecular bone. In conclusion, ERalpha might be the main ER in organs important for calcium homeostasis, except in the jejunum. The mRNA expression of ERalpha in the bone marrow and renal cortex decreased abruptly after ovariectomy, which may partially explain why the effect of estrogen deficiency can be amplified and why trabecular bone loss is more predominant than cortical bone loss shortly after surgical or natural menopause.

Animals↗
PubMed1999

GH-binding protein in obese men with varying glucose tolerance: relationship to body fat distribution, insulin secretion and the GH-IGF-I axis.

Bioelectrical impedance for measurement of total body fat and computed tomography for visceral and subcutaneous fat at umbilicus levels were performed in 34 obese and 10 lean men. Insulin secretion in response to an oral glucose tolerance test (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP) and IGF-I were measured. Obese subjects were divided into three groups according to the OGTT. The obese type II diabetes mellitus group had the highest GHBP levels and the most visceral fat. GHBP levels were most strongly correlated with the ratio of visceral fat area to body weight (VWR) above any other parameters (r = 0.725, P<0.001). The insulin and free fatty acid (FFA) areas under curves (AUC) during the OGTT, and the IGF-I level, were also positively correlated with GHBP levels (r = 0.474, P<0.005; r = 0.572, P<0.005; r = 0.453. P<0.005). GH-AUC to the L-dopa stimulation test was negatively correlated with GHBP levels (r = -0.432. P<0.005). Stepwise multiple linear regression analysis showed that VWR, FFA-AUC and insulin-AUC significantly contributed to the variability of GHBP (r2 = 0.58). In conclusion, we demonstrated that: (i) visceral fat amount mainly determined GHBP levels in obese men with varying glucose tolerance: (ii) hyperglycemia per se did not influence the GHBP level, whereas insulin and FFA could play a role in regulation of GHBP: and (iii) although GH was not the main regulator of GHBP, the unchanged IGF-I level despite GH hyposecretion suggests that increased GHBP levels reflect GH hypersensitivity in order to compensate for decreased GH secretion in obesity.

Adipose Tissue↗
PubMed1999

The validity of random urine specimen albumin measurement as a screening test for diabetic nephropathy.

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.

Adult↗
PubMed1999

Intermittent parathyroid hormone treatment can promote linear growth in the ovariectomized growing rat.

To compare the effect of intermittent parathyroid hormone (PTH) treatment with that of estrogen treatment on epiphyseal growth in ovariectomized rats, 46 Sprague-Dawley female rats aged 9-10 weeks (about 200-220 g) were either ovariectomized or sham operated. From 6 weeks after ovariectomy (ovx), rats were daily injected with subcutaneous human recombinant PTH (1-84)-dosed 30 micrograms/kg (the low dose PTH-treated group) or 300 micrograms/kg (the high dose PTH-treated group), 17 beta-estradiol (the 17 beta-estradiol-treated group, 30 micrograms/kg) or vehicle (the ovx-alone group), 5 times a week for 4 weeks. The decalcified sections of the distal femoral epiphyseal plate were analyzed on light microscopy after H&E stain, and the lengths of the zones of proliferation, maturing and hypertrophic chondrocytes were measured. The length of the growth plate, the zone of proliferation and the zone of hypertrophic chondrocyte in the ovx-alone group were significantly shorter than those of the sham-operated group. The treatment of 17 beta-estradiol speeded up the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes even though the length of the growth plate was comparable to that of the sham-operated group. Both low and high dose PTH treatments increased the length of the growth plate, and those lengths were comparable to that of the sham-operated group. The fractions of proliferating, maturing and hypertrophic zone in the low dose PTH-treated group were also comparable to those of the sham-operated group. However, high dose PTH treatment slowed down the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes to a greater extent, and therefore the fraction of proliferating chondrocytes of the high dose PTH-treated group was larger than that of the low dose PTH-treated group (73.8 +/- 1.8 Vs 63.3 +/- 1.3%, p < 0.005). From these results, we showed that intermittent PTH treatment could promote linear growth in the ovariectomized growing rat. We propose that PTH may be an alternative drug candidate for promoting linear growth of long bones without the risk for early closure of the growth plate.

Animals↗
PubMed1997

Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone.

OBJECTIVES: We investigated the effect of obesity on the serum levels of total and free IGF-1 and their relationship to the circulating levels of insulin and IGF binding proteins (IGFBPs) in age and sex-matched groups. SUBJECTS: The study included 43 obese subjects (ideal body weight; IBW > 120%) and 45 controls (IBW < 100%). All of the subjects were male. MEASUREMENT: Total IGF-1, free IGF-1, IGFBP-1, IGFBP-2, IGFBP-3, and insulin were measured in obese subjects and normal control subjects. RESULTS: No significant differences in the circulating levels of total and IGFBP-3 were observed between the obese and control groups. In contrast to total IGF-1, free IGF-1 in obese subjects was significantly increased compared to normal controls (P < 0.05). Serum total and free IGF-1 were inversely correlated with age (r = -0.42, P = 0.001, and -0.44, P = 0.001). Fasting serum insulin concentrations were elevated in all the obese subjects (P < 0.05) and positively correlated with IBW (r = 0.57, P = 0.001). The levels of serum GH and IGFBP-1 were suppressed in all the obese subjects (P < 0.05). IGFBP-1 was inversely correlated with IBW (r = -0.51, P = 0.001) and serum insulin concentrations (r = -0.48, P = 0.001). The IGFBP-2 concentrations were also suppressed in obese subjects and inversely related to free IGF-1 (r = -0.48, P = 0.001). Using multiple linear regression analysis, total IGF-1 and insulin concentrations were positively correlated (r = 0.58, P = 0.001) and free IGF-1 and IGFBP-1 concentrations were negatively correlated (r = -0.57, P = 0.001). CONCLUSION: We confirmed that total IGF-1 and IGFBP-3 concentrations were not significantly different between the obese and control groups, despite GH hyposecretion in obesity. We also found that free IGF-1 concentrations were higher in obese subjects than in normal controls. It seems likely that overnutrition and chronic hyperinsulinaemia in obesity may alter this regulated growth response by insulin stimulation of IGF-1 production and suppression of hepatic IGFBP-1 and IGFBP-2 production, which may inhibit IGF-1 bioactivity.

Adult↗
PubMed1997

Altered hydroxylation of estrogen in patients with postmenopausal osteopenia.

To study the possible contributions of the differences in estrogen metabolism to bone mass in postmenopausal osteopenia, spinal and femoral bone mineral densities (BMD) were measured, and 18 urinary metabolites of estrogen were analyzed by a gas chromatography-mass spectrometry assay system in 59 postmenopausal women (5-10 yr after menopause). The BMD of the spine and femoral neck showed positive correlations with body weight, height, and body mass index as we expected. Compared to nonosteopenic subjects, there were no significant differences in serum estrone (E1) and estradiol (E2) levels in patients with osteopenia. However, the urinary 16 alpha-hydroxyestrone [16 alpha-(OH)E1] level was significantly lower in patients with spinal osteopenia (P < 0.001). Among the 18 urinary metabolites of estrogen, the 16 alpha-(OH)E1 and 16 alpha-(OH)E1/2-hydroxyestrone [2-(OH)E1) ratio showed positive correlations with spinal BMD (P < 0.05), whereas 2-(OH)E2 showed a negative correlation with femoral neck BMD (P < 0.05). The urinary 16 alpha-(OH)E1 level also revealed a positive correlation with the age-matched z score of BMD in the spine (P < 0.05). In multiple stepwise regression analysis, weight, 16 alpha-(OH)E1, interaction between 16 alpha-(OH)E1 and 2-(OH)E2, 2-(OH)E2, and years after menopause were statistically significant for spinal BMD (r2 = 0.4968). For femoral neck BMD and weight, 16 alpha-(OH)E1 and 2-(OH)E2 were the independent determinants (r2 = 0.3369). In conclusion, the activity of estrogen 16 alpha-hydroxylase was decreased and/or the activity of estrogen 2-hydroxylase was enhanced in post-menopausal osteopenia. We speculated that these derangements may serve as contributing factors for the acceleration of bone loss in post-menopausal osteoporosis.

Aged↗
PubMed1996

Role of HLA class II alleles in Korean patients with IDDM.

MHC associations with IDDM in the Korean population were studied to investigate genetic susceptibility to this disorder. The frequencies of HLA-DR3, -DR4 and -DR9 were significantly higher in diabetic patients. However, the frequency of DR2 was significantly decreased in diabetic patients. DQA1*0301 and DQA1*0501 were positively and DQA1*0102 and DQA1*0201 negatively associated with IDDM. DQB1*0301 and DQB1*0601 were negatively associated with IDDM. Heterodimers DQA1*0301-DQB1*0201, DQA1*0501-DQB1*0201 and DQA1*0501-DQB1*0302 were positively associated with DQA1*0102-DQB1*0601 negatively associated with IDDM. The frequencies of DR3-DQA1*0301-DQB1*0201 and -DQA1*0501-DQB1*0201 were significantly higher in diabetic patients. The frequencies of DR4-DQA1*0301-DQB1*0201 and DR9-DQA1*0301-DQB1*0303 were significantly higher in diabetic patients. The presence of non-aspartic acid at position 57 of the DQ beta-chain was not associated with susceptibility to IDDM. However, the frequency of Arg 52 homozygotes was significantly higher in diabetic patients. These results suggest a role of the MHC molecule and also suggest racial differences in susceptibility to IDDM even within the Asian populations.

Adult↗
PubMed1996

Long-term administration of acipimox potentiates growth hormone response to growth hormone-releasing hormone by decreasing serum free fatty acid in obesity.

Obesity is associated with an impairment of normal growth hormone (GH) secretion and blunted responses to all stimuli. A high plasma free fatty acid (FFA) level is frequently observed in obesity. FFA participates in the regulation of pituitary GH secretion. To determine whether the derangement of GH secretion in obesity is associated with high plasma FFA levels, tests with GH-releasing hormone (GHRH) and acipimox (ACX), an antilipolytic agent able to decrease FFA, were undertaken in six obese subjects and seven normal control subjects. In addition, the effect of prolonged suppression of FFA level on GH response to GHRH after administration of ACX for 1 month was also examined in each of the obese subjects. The GH response in obese subjects (median, 9.1 microg/L) to GHRH (1-29) (1 microg/kg intravenously [IV]) was significantly blunted as compared with normal control subjects (23.5 microg / L, P < .05). Basal FFA levels were higher in obese subjects (855.2 microEq / L than in normal control subjects (514.6 microEq / L, P < .05). One-dose ACX (500 mg) decreased FFA levels in both obese and normal subjects: the lowest FFA levels in obese subjects (158.3 microEq/L 2 to 2.5 hours after ACX were similar to those of normal control subjects (108.7 microEq/L). One-dose ACX potentiated GHRH-stimulated GH response in both obese and normal subjects. GH responses potentiated by ACX in obese subjects (27.1 microg/L) were similar to GH responses to GHRH in normal control subjects, but lower than in normal subjects treated with ACX plus GHRH (58.5 microg / L, P < .05). Thereafter, all of the obese subjects were treated with ACX for 1 month, after which the ACX plus GHRH tests were repeated. After 1 month of acipimox administration in the obese subjects, GH responses (38.8 microg/L) were significantly higher than those of obese subjects treated with GHRH and one-dose ACX plus GHRH (P < .05). They were similar to GH responses of normal control subjects receiving the one-dose ACX plus GHRH test. In conclusion, in obesity the prolonged suppression of FFA levels induced by long-term administration of ACX potentiated somatotrope responsiveness, likely acting at the pituitary level, suggesting that the duration of FFA suppression had an important relation to the magnitude of GH response.

Adult↗
PubMed1996

The role of insulin resistance in Korean patients with coronary atherosclerosis.

To determine whether dietary modification improves insulin resistance and coronary atherosclerosis, we randomly assigned 14 Korean patients to an experimental group (low-fat, low-cholesterol diet, high polyunsaturated/saturated fatty acid ratio, and calorie restriction) or to a control group (no dietary change). Coronary artery lesions were analyzed by quantitative coronary angiography, and postglucose insulin responses were measured. At baseline, there were no significant differences in body weight, BMI, waist-to-hip ratio (WHR), and plasma lipid and insulin levels between the two groups. After completion of the 1-year diet program, the experimental group showed significant reductions in body weight (66.0 +/- 3.2 to 61.6 +/- 3.8 kg [means +/- SE], P < 0.01) and WHR (O.96 +/- 0.01 to 0.93 +/- 0.01, P < 0.05). Total cholesterol (5.45 +/- 0.45 to 4.50 +/- 0.44 mmol/l, P < 0.05), LDL cholesterol (3.71 +/- 0.36 to 2.98 +/- 0.37 mmol/l, P < 0.05), and triglyceride (1.91 +/- 0.28 to 1.29 +/- 0.17 mmol/l, P < 0.05) were also significantly reduced in the experimental group. The mean insulin response during an oral glucose tolerance test was also significantly decreased (258.6 +/- 26.4 to 181.8 +/- 6.6 pmol/l, P < 0.05). In contrast, there were no significant changes in these parameters in the control group. When only coronary artery lesions > 50% stenosed were analyzed, the average percentage diameter stenosis regressed from 63.2 to 56.8% in the experimental group. However, there were no significant changes in the control group. Our trial suggests that decreases in body weight and WHR and an improvement in insulin resistance with a low-fat, low cholesterol diet and caloric restriction may reduce risk factors and reverse coronary atherosclerotic lesions in 1 year.

Body Composition↗
PubMed1996

Swelling of the vesicle is prerequisite for PTH secretion.

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.

Acetates↗
PubMed1995

Acipimox potentiates growth hormone response to growth hormone-releasing hormone by decreasing serum free fatty acid levels in hyperthyroidism.

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)

Administration, Oral↗
PubMed1995

Lack of association between vitamin D receptor genotypes and osteoporosis in Koreans.

To evaluate whether common allelic variants in the gene encoding the vitamin D receptor (VDR) were useful in predicting differences in bone mineral density (BMD) and bone turnover rate in Koreans, we analyzed the restriction pattern of the polymerase chain reaction product of the VDR gene with the Bsm1 enzyme and serum osteocalcin in patients with osteoporosis. The prevalence of the BB genotype in the controls was extremely low when compared with that in other reports: the BB, Bb, and bb genotypes accounted for 1.4%, 12.9%, and 85.7%, respectively. Only 2.8% of those patients with osteoporosis had the BB genotype. In contrast, 12.5% had the Bb genotype, and 84.7% had the bb genotype. The prevalence of the BB genotype in patients with severe osteoporosis was also extremely low: the BB, Bb, and bb genotypes accounted for 0%, 12.4%, and 87.6%, respectively. Compared with the mean serum osteocalcin level of the pre- and post-menopausal controls, the level in patients with severe osteoporosis was higher, and this was statistically significant. As expected, a negative correlation was observed between the serum osteocalcin levels and the age-matched Z scores for spinal BMD. However, no correlation was found in the femoral neck BMD. These results suggest that restriction fragment length polymorphism analysis of the VDR gene with a Bsm1 restriction enzyme in Koreans is not helpful for early detection of patients at risk of developing osteoporosis. This is true even in patients with a high rate of bone turnover. Our data suggest extreme ethnic differences in the pattern of prevalence of the VDR allele.

Adult↗
PubMed1995

Acipimox potentiates growth hormone (GH) response to GH-releasing hormone with or without pyridostigmine by lowering serum free fatty acid in normal and obese subjects.

Obesity is associated with an impairment of normal GH secretion and blunted responses to all stimuli. Recent reports suggest that increased somatostatinergic activity is the basis for the GH derangement of obesity. However, the basic mechanism of this alteration is still being debated. The high plasma free fatty acid (FFA) is frequently observed in obesity. FFA participates in the regulation of pituitary GH secretion. To determine whether the derangement of GH secretion in obesity is associated with high plasma FFA levels, several tests with GHRH with or without pyridostigmine (PYR) and acipimox (ACX), antilipolytic agents able to decrease FFA, were undertaken in six obese and seven normal control subjects. In obese subjects, the GH response (mean peak +/- SEM: 8.9 +/- 1.1 ug/L) to GHRH-(1-29) (1 ug/kg, i.v.) was significantly blunted when compared with the response in normal control subjects (25.7 +/- 1.8 ug/L; P < 0.05). After PYR (120 mg), the response to GHRH was enhanced in the obese subjects (21.4 +/- 4.9 ug/L; P < 0.05) and was similar to that of the controls with GHRH only, but remained significantly reduced compared with controls treated with PYR plus GHRH (43.2 +/- 6.0 ug/L; P < 0.05). Basal FFA levels were higher than those of normal controls (P < 0.05). ACX (500 mg) decreased FFA levels in both obese and normal subjects; the lowest FFA levels of obese subjects at 15 min were similar to those of normal controls. ACX also potentiated GHRH-stimulated GH response in both obese and normal subjects. The GH responses potentiated by ACX in obesity (22.7 +/- 5.5 ug/L) were similar to those of PYR plus GHRH in obese subjects and GHRH in normal controls, but they were lower than those of control treated with ACX plus GHRH (50.8 +/- 6.7 ug/L; P < 0.05). After the combined pretreatment with ACX and PYR, GH responses in obesity (44.1 +/- 6.0 ug/L) were significantly higher than those in GHRH test, PYR plus GHRH, and ACX plus GHRH in obese subjects (P < 0.05), and they were similar to PYR plus GHRH or ACX plus GHRH in normal controls. However their enhanced GH responses were reduced compared with the control with ACX plus PYR plus GHRH (64.9 +/- 4.5 ug/L; P < 0.05). Our results are in agreement with the hypothalamic hypothesis: an increase in somatostatinergic tone is responsible for the blunted GH response to GHRH in obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Relationships among 64k autoantibodies, pancreatic beta-cell function, HLA-DR antigens and HLA-DQ genes in patients with insulin-dependent diabetes mellitus in Korea.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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%]. CONCLUSIONS: 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.

Adolescent↗
PubMed1994

IGF-I of serum and vitreous fluid in patients with diabetic proliferative retinopathy.

Vitreous fluid and serum were obtained at the time of vitrectomy from 15 subjects with diabetic proliferative retinopathy and 6 control subjects. The mean serum IGF-I (IGF-I level: 1 nM/l = 7.7 ng/ml) concentrations were 15.40 +/- 4.97 nM/l in controls and 16.24 +/- 4.32 nM/l in diabetic patients. The mean vitreous IGF-I concentration was 1.05 +/- 0.30 nM/l in controls and 0.91 +/- 0.50 nM/l in diabetic patients. There were no significant differences between the two groups, and serum IGF-I concentrations were not correlated with vitreous IGF-I concentrations in the patients with diabetic proliferative retinopathy. These data suggest that IGF-I may not be a risk factor for the development of proliferative diabetic retinpathy.

Adult↗