RESUMO
AIMS: Recent epidemiological studies have suggested an association between sarcopenia and non-alcoholic fatty liver disease (NAFLD) in the general population, prompting our investigation into the gender-specific association between sarcopenia and NAFLD in patients with type 2 diabetes mellitus (T2DM). METHODS: In this cross-sectional study, 4210 patients with T2DM were recruited from the Seoul Metabolic Syndrome Cohort. Appendicular skeletal muscle mass (ASM) was estimated from bioimpedance analysis measurements, and the skeletal muscle mass index (SMI) was calculated by dividing the sum of ASM by body weight. Sarcopenia was defined as a gender-specific SMI value>2 standard deviations (SDs) below the mean for healthy young adults. NAFLD was defined as the presence of hepatic steatosis on ultrasonography with no other causes of chronic liver disease. RESULTS: Among the entire study population (mean age: 57.4±10.8 years), 1278 (30.4%) had NAFLD and 1240 (29.5%) had sarcopenia, and the prevalence of NAFLD was significantly higher in those with sarcopenia: 46.2% vs 25.1% (P<0.001) in men; 38.3% vs 25.4% (P<0.001) in women. Sarcopenia was significantly associated with higher risk of NAFLD in men (adjusted odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.15-2.17), whereas the association was attenuated in women after adjusting for clinical risk factors. CONCLUSION: Sarcopenia is independently associated with NAFLD in men with T2DM, which suggests that sarcopenia may be a risk factor for NAFLD in men with T2DM.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Sarcopenia/epidemiologia , Adulto , Idoso , Composição Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores SexuaisRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Antígenos HLA-DR/genética , Adolescente , Adulto , Idade de Início , Índice de Massa Corporal , Peptídeo C/sangue , Criança , Feminino , Genótipo , Antígenos HLA-DQ/genética , Humanos , Imunogenética/métodos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
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.
Assuntos
Doença da Artéria Coronariana/fisiopatologia , Resistência à Insulina , Composição Corporal , Doença da Artéria Coronariana/dietoterapia , Doença da Artéria Coronariana/patologia , Dieta , Feminino , Humanos , Coreia (Geográfico) , Lipídeos/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Extracellular Mg(2+) directly modulates voltage-dependent activation in ether-à-go-go (eag) potassium channels, slowing the kinetics of ionic and gating currents (Tang, C.-Y., F. Bezanilla, and D.M. Papazian. 2000. J. Gen. Physiol. 115:319-337). To exert its effect, Mg(2+) presumably binds to a site in or near the eag voltage sensor. We have tested the hypothesis that acidic residues unique to eag family members, located in transmembrane segments S2 and S3, contribute to the Mg(2+)-binding site. Two eag-specific acidic residues and three acidic residues found in the S2 and S3 segments of all voltage-dependent K(+) channels were individually mutated in Drosophila eag, mutant channels were expressed in Xenopus oocytes, and the effect of Mg(2+) on ionic current kinetics was measured using a two electrode voltage clamp. Neutralization of eag-specific residues D278 in S2 and D327 in S3 eliminated Mg(2+)-sensitivity and mimicked the slowing of activation kinetics caused by Mg(2+) binding to the wild-type channel. These results suggest that Mg(2+) modulates activation kinetics in wild-type eag by screening the negatively charged side chains of D278 and D327. Therefore, these residues are likely to coordinate the bound ion. In contrast, neutralization of the widely conserved residues D284 in S2 and D319 in S3 preserved the fast kinetics seen in wild-type eag in the absence of Mg(2+), indicating that D284 and D319 do not mediate the slowing of activation caused by Mg(2+) binding. Mutations at D284 affected the eag gating pathway, shifting the voltage dependence of Mg(2+)-sensitive, rate limiting transitions in the hyperpolarized direction. Another widely conserved residue, D274 in S2, is not required for Mg(2+) sensitivity but is in the vicinity of the binding site. We conclude that Mg(2+) binds in a water-filled pocket between S2 and S3 and thereby modulates voltage-dependent gating. The identification of this site constrains the packing of transmembrane segments in the voltage sensor of K(+) channels, and suggests a molecular mechanism by which extracellular cations modulate eag activation kinetics.
Assuntos
Magnésio/farmacologia , Canais de Potássio/fisiologia , Sequência de Aminoácidos , Animais , Sítios de Ligação/fisiologia , Drosophila/fisiologia , Cinética , Magnésio/química , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Técnicas de Patch-Clamp , Xenopus/fisiologiaRESUMO
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.
Assuntos
RNA Mensageiro/metabolismo , Receptores de Estrogênio/metabolismo , Animais , Células da Medula Óssea/metabolismo , Osso e Ossos/metabolismo , Células Cultivadas , Primers do DNA/metabolismo , Receptor alfa de Estrogênio , Receptor beta de Estrogênio , Feminino , Especificidade de Órgãos , Ovariectomia , Ovário/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/metabolismoRESUMO
The molecular events leading to the development of GH-producing pituitary tumors remain largely unknown. We hypothesized that activating mutations of the GHRH receptor might occur in a subset of GH-producing pituitary tumors. Genomic DNA samples from 54 GH-producing pituitary tumor tissues were screened for mutations of the GHRH receptor. Eleven homozygous or heterozygous nucleotide substitutions [169G > A (A57T), 338C > T (P113L), 363G > T (E121D), 409C > T (H137Y), 547G > A (D183N), 673G > A (V225I), 749G > A (W250X), 760G > A (V254M), 785G > A (S262N), 880G > A (G294R), 1268G > A (C423Y)] were found in 12 patients (22.2%). The 169G > A substitution (A57T) appears to be a polymorphism (4 patients, 7.4%). E121D and V225I were each found in 2 patients. In 1 patient with the V225I sequence, the substitution was not found in genomic DNA from peripheral leukocytes, suggesting a somatic mutation. A patient with a heterozygous W250X mutation was homozygous for the C423Y substitution. These variant GHRH receptors were studied in transfected TSA-201 cells to evaluate the functional consequences of the amino acid changes. None of the GHRH receptor variants was associated with basal elevation of intracellular cAMP. GHRH induced variable cAMP responses. With the W250X and G294R variants, there was no cAMP stimulation by GHRH, indicating that the mutations are inactivating. Expression of the W250X GHRH receptor on the cell membrane was severely decreased and GHRH binding to the G294R GHRH receptor was impaired. Although GHRH receptor variants are common in GH- producing pituitary adenomas, constitutively activating mutations, as a mechanism for GH-producing pituitary tumors appear to be rare.
Assuntos
Hormônio do Crescimento Humano/metabolismo , Mutação , Neoplasias Hipofisárias/genética , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Membrana Celular/fisiologia , AMP Cíclico/metabolismo , Primers do DNA , Éxons , Variação Genética , Heterozigoto , Homozigoto , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Estrutura Secundária de Proteína , Receptores de Neuropeptídeos/química , Receptores de Neuropeptídeos/fisiologia , Receptores de Hormônios Reguladores de Hormônio Hipofisário/química , Receptores de Hormônios Reguladores de Hormônio Hipofisário/fisiologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
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.
Assuntos
Povo Asiático , Osteoporose/genética , Receptores de Calcitriol/genética , Adulto , Feminino , Genótipo , Humanos , Coreia (Geográfico)/etnologia , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose/sangue , Reação em Cadeia da Polimerase , Valores de ReferênciaRESUMO
We investigated the potential different effects of a chronic alcohol intake on glucose metabolism according to nutritional status in growing rats. Eighty weanling 4-week-old male Sprague Dawley rats were fed with low (5%, wt/wt) or control (22%) protein diet for 8 weeks. Each group was subdivided into alcohol (5 g/kg(-1) x day(-1)) or saline gavage rats during the last 4 weeks. At 12 weeks of age, we measured the weights of the body, pancreas, and epididymal fat; glycogen synthase activity of gastrocnemius muscle; and insulin content of the pancreas. We performed an ip glucose tolerance test and a euglycemic hyperinsulinemic clamp test. Weight gain was almost arrested in protein-deficient rats. The relative weight and insulin content of the pancreas and glycogen synthase activity were not different among the four groups, but the relative amount of epididymal fat decreased only in protein-deficient saline rats. Insulin response after glucose challenge and glucose disposal rate during the euglycemic clamp were both markedly decreased in protein-deficient saline rats, but not changed in protein-deficient alcohol rats. Protein-deficiency per se causes deterioration both in insulin secretory function and in sensitivity, but these defects are protected by a chronic alcohol intake. In a protein-sufficient state, alcohol intake gives no additional effects on glucose metabolism. Therefore, according to individual nutritional status, the metabolic effect of alcohol intake appears differently.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Glucose/metabolismo , Estado Nutricional/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Dieta , Epididimo/metabolismo , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Glicogênio Sintase/metabolismo , Insulina/metabolismo , Masculino , Músculo Esquelético/metabolismo , Tamanho do Órgão/fisiologia , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Deficiência de Proteína/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
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)
Assuntos
Ácidos Graxos não Esterificados/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/metabolismo , Hipolipemiantes/farmacologia , Obesidade/sangue , Pirazinas/farmacologia , Adulto , Estudos de Coortes , Sinergismo Farmacológico , Hormônio do Crescimento/sangue , Humanos , Cinética , Masculino , Obesidade/fisiopatologia , Valores de Referência , Fatores de TempoRESUMO
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.
Assuntos
Doenças Ósseas Metabólicas/metabolismo , Estrogênios/metabolismo , Pós-Menopausa , Idoso , Estatura , Índice de Massa Corporal , Peso Corporal , Densidade Óssea , Doenças Ósseas Metabólicas/patologia , Doenças Ósseas Metabólicas/urina , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hidroxiestronas/urina , Hidroxilação , Pessoa de Meia-Idade , Esteroide 16-alfa-HidroxilaseRESUMO
Islets were isolated from the pancreata of Sprague-Dawley rats and transplanted into streptozotocin-induced diabetic outbred Wistar rats. The effect of transplantation of islets into the cisterna magna on the diabetic state of the recipients was compared with that of the conventional transplantation of islets into liver via the portal vein. After successful intraportal (IP) transplantation, rejection took place between days 7 and 15 in all diabetic recipients. All of the eleven rats surviving after stereotaxic implantation of islets into the cisterna magna returned to normoglycemia within 7 days after transplantation. Nine of the recipients with intra-cisterna magna (IM) islet allografts were still normoglycemic at 210 days after transplantation. The glucose disappearance rate of the IM transplant rats was slower than that of the IP transplant rats, and blood glucose returned to the normal basal level within 5 hr following glucose administration. Although the insulin levels were almost undetectable in cerebrospinal fluid before IM transplantation, the insulin levels were markedly increased after IM transplantation and twice as great in CSF than blood. Thus, these findings indicate that the cisterna magna can serve as an immunologically privileged site for implantation of allogeneic pancreatic islets, and islets in CSF can regulate and maintain normal glucose homeostasis via secretion of insulin across the blood-brain barrier.
Assuntos
Diabetes Mellitus Experimental/cirurgia , Transplante das Ilhotas Pancreáticas , Transplante Heterotópico , Animais , Glicemia/análise , Cisterna Magna , Feminino , Rejeição de Enxerto , Transplante das Ilhotas Pancreáticas/imunologia , Ratos , Ratos EndogâmicosRESUMO
BACKGROUND: Our study was undertaken to investigate the pathogenesis and possible risk factors for postrenal transplantation diabetes mellitus (PTDM). METHODS: We recruited 114 patients with normal glucose tolerance (NGT) and performed both 75-g oral glucose tolerance tests (OGTT) and short insulin tolerance tests 1 week before and 9-12 months after transplantation. RESULTS: The subjects were classified into three groups by World Health Organization criteria on the basis of OGTT after transplantation: (a) 36 (31.6%) subjects with normal glucose tolerance; (b) 51 (45.7%) subjects with impaired glucose tolerance (IGT); and (c) 27 (23.7%) subjects with postrenal transplantation diabetes mellitus. Dosages of steroid and cyclosporine were equivalent among the three groups. Before transplantation, the fasting and 2-hr plasma glucose and proinsulin/insulin (PI/I) ratios were significantly higher in the IGT and PTDM groups than in the NGT group, but the insulin sensitivity index (ISI) was not significantly different among the three groups. In addition, the area under the curve-insulin on OGTT was significantly lower in the PTDM group than in the NGT group. After transplantation, however, the ISI was increased in all groups. Furthermore, the ISI and PI/I ratios revealed significantly higher values in the PTDM group than in the NGT group after transplantation. CONCLUSIONS: These results revealed that fasting and 2-hr plasma glucose levels, as well as the proinsulin/insulin ratio before transplantation, are both possible indicators of beta-cell dysfunction and may be predictors for the development of PTDM. Furthermore, beta-cell dysfunction, rather than insulin resistance, was proven to be the main factor for the pathogenesis of PTDM.
Assuntos
Diabetes Mellitus/etiologia , Resistência à Insulina , Ilhotas Pancreáticas/fisiopatologia , Transplante de Rim/efeitos adversos , Adulto , Glicemia/análise , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Proinsulina/sangueRESUMO
We present a 55-year-old female with a thyrotropin (TSH)-secreting pituitary adenoma who had been treated with somatostatin analog octreotide acetate (SMS 201-995) for 4 months. Subcutaneous injection of 100 micrograms octreotide acetate twice daily resulted in significant reduction of the TSH, thyroid hormone, and tumor size. During the treatment, there was no evidence of any side effects. We may conclude that octreotide acetate administration is an effective treatment in patients with TSH-secreting pituitary adenoma for suppressing TSH hypersecretion and reducing the size of the tumor.
Assuntos
Adenoma/tratamento farmacológico , Octreotida/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Tireotropina/metabolismo , Adenoma/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Adeno-Hipófise , Neoplasias Hipofisárias/metabolismoRESUMO
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.
Assuntos
Proteínas de Transporte/metabolismo , Intolerância à Glucose/etiologia , Obesidade/complicações , Obesidade/metabolismo , Tecido Adiposo/patologia , Adulto , Antropometria , Peso Corporal/fisiologia , Hormônio do Crescimento Humano/fisiologia , Humanos , Insulina/metabolismo , Secreção de Insulina , Fator de Crescimento Insulin-Like I/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade/patologiaRESUMO
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.
Assuntos
Ácidos Graxos não Esterificados/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/sangue , Hipolipemiantes/farmacologia , Obesidade/sangue , Pirazinas/farmacologia , Adulto , Humanos , Hipolipemiantes/administração & dosagem , Masculino , Pirazinas/administração & dosagemRESUMO
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)
Assuntos
Ácidos Graxos não Esterificados/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/sangue , Hipertireoidismo/sangue , Hipolipemiantes/farmacologia , Pirazinas/farmacologia , Administração Oral , Adulto , Hormônio do Crescimento/fisiologia , Humanos , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/metabolismo , Hipolipemiantes/administração & dosagem , Hipolipemiantes/uso terapêutico , Masculino , Pirazinas/administração & dosagem , Pirazinas/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the GH secretion and clarify the factors influencing the GH secretion in women with polycystic ovarian syndrome (PCOS). DESIGN: Comparison of the GH response to L-dopa with or without pyridostigmine (inhibitor of acetylcholinesterase) pretreatment and insulin response to oral glucose tolerance test in patients with PCOS and matched controls. SETTING: Outpatients and healthy volunteers studied at a clinical research unit of a university hospital. PATIENTS, PARTICIPANTS: Ten women with PCOS and 9 controls with regular cycles were recruited. INTERVENTIONS: After an overnight fast, each subject underwent a GH stimulation test with L-dopa with or without pyridostigmine pretreatment. Plasma insulin and glucose levels were measured after a 75-g glucose load. MAIN OUTCOME MEASURES: Plasma GH, insulin-like growth factor I (IGF-I), insulin, and nonesterified fatty acids. RESULTS: Growth hormone responses and GH area under the response curve (AUC) to L-dopa were significantly lower in PCOS than those in controls. Pyridostigmine enhanced the GH response to L-dopa significantly in PCOS. Insulin responses and insulin AUC to oral glucose load were significantly higher in PCOS than those in controls. Plasma IGF-I levels of PCOS were significantly higher than controls. Insulin AUC had a positive correlation with plasma IGF-I levels but an inverse correlation with GH AUC in PCOS and controls. CONCLUSION: Our result indicated that decreased GH secretion of PCOS may be associated with a high somatostatin activity and a high plasma IGF-I level.
Assuntos
Hormônio do Crescimento/metabolismo , Insulina/sangue , Levodopa/farmacologia , Síndrome do Ovário Policístico/metabolismo , Brometo de Piridostigmina/farmacologia , Adolescente , Adulto , Feminino , Teste de Tolerância a Glucose , Hormônio do Crescimento/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Síndrome do Ovário Policístico/sangue , Pré-MedicaçãoRESUMO
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.
Assuntos
Tecido Adiposo/anatomia & histologia , Depressores do Apetite/uso terapêutico , Ciclobutanos/uso terapêutico , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Obesidade/tratamento farmacológico , Adiponectina , Tecido Adiposo/efeitos dos fármacos , Adulto , Índice de Massa Corporal , Humanos , Coreia (Geográfico) , Obesidade/fisiopatologia , Pré-MenopausaRESUMO
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.
Assuntos
Metabolismo Basal , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Hipertrigliceridemia/epidemiologia , Albuminúria , Índice de Massa Corporal , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/urina , Progressão da Doença , Feminino , Humanos , Hipertrigliceridemia/complicações , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologia , Valores de ReferênciaRESUMO
The euglobulin fibrinolytic activity was measured in 56 non-insulin-dependent diabetics and 118 age-matched healthy controls before and after venous occlusion for 5 min at 100 mmHg of the left antecubital vein. In the basal state, fibrinolytic activity was impaired in diabetics compared with controls (93.1 +/- 6.7 vs 101.6 +/- 0.9 BAU) (P less than 0.05) and plasma fibrinogen level was increased but this did not reach statistical significance (467.3 +/- 264.1 vs 359.2 +/- 200.2 mg/dl). In diabetics, stimulated fibrinolysis following venous occlusion was depressed compared with controls (110.6 +/- 3.9 vs 121.6 +/- 1.9 BAU) (P less than 0.05). No relation of fibrinolytic activity to age, duration of diabetes, obesity, serum triglyceride, HbA1c, or 24 h proteinuria was demonstrated. In the diabetic retinopathy group, the fibrinolytic activity was lower than in the non-retinopathy group. Diabetics with long-standing diabetes (10 years or more) who remained free from retinopathy had significantly increased fibrinolytic activity than the diabetics with short-standing diabetes (less than 10 years) who have developed retinopathy (P less than 0.05). These findings imply a poor fibrinolytic activity, not in all diabetics, but only in those with retinopathy, and this may play a role in the development of diabetic retinopathy.