RESUMO
Postmenopausal osteoporosis (PMO) is the most common type of primary osteoporosis (OP), a systemic skeletal disease. Although many factors have been revealed to contribute to the occurrence of PMO, specific biomarkers for the early diagnosis and therapy of PMO are not available. In the present study, a weighted gene coexpression network analysis (WGCNA) was performed to screen gene modules associated with menopausal status. The turquoise module was verified as the clinically significant module, and 12 genes (NUP133, PSMD12, PPWD1, RBM8A, CRNKL1, PPP2R5C, RBM22, PIK3CB, SKIV2L2, PAPOLA, SRSF1 and COPS2) were identified as 'real' hub genes in both the proteinprotein interaction (PPI) network and coexpression network. Furthermore, gene expression analysis by microarray in blood monocytes from pre and postmenopausal women revealed an increase in the expression of these hub genes in postmenopausal women. However, only the expression of peptidylprolyl isomerase domain and WD repeat containing 1 (PPWD1) was correlated with bone mineral density (BMD) in postmenopausal women. In the validation set, a similar expression pattern of PPWD1 was revealed. Functional enrichment analysis revealed that the fatty acid metabolism pathway was significantly abundant in the samples that exhibited a higher expression of PPWD1. Collectively, PPWD1 is indicated as a potential diagnostic biomarker for the occurrence of PMO.
Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Monócitos/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Osteoporose Pós-Menopausa/metabolismo , Feminino , Humanos , Monócitos/patologia , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/patologiaRESUMO
BACKGROUND: Hyperandrogenemia is more common in puberty and reproductive age, but relatively rare in postmenopausal women. Postmenopausal virilization may result from androgen-producing tumors. Androgen-secreting adrenal tumors are rare in clinical practice and are diagnosed as adrenocortical carcinoma, most of which can co-secrete androgen and cortisol. Highly elevated serum testosterone level with normal adrenal androgens such as dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and androstenedione is usually regarded as ovary origin. Here we describe an unusual case of a postmenopausal woman with markedly elevated serum testosterone level, while DHEAS, androstenedione, 17-hydroxyprogesterone and cortisol were within the normal range. CASE PRESENTATION: A 67-year-old postmenopausal woman with hirsutism in the upper lip and armpit, accompanied by clitoromegaly for 5 months. Hormonal evaluation showed markedly elevated serum testosterone level (714.8 ng/ml), whereas DHEAS, androstenedione, 17-hydroxyprogesterone, and cortisol were within the normal range. Imaging examination showed a mass of 1.5 cm in diameter in the left adrenal gland and normal appearance of both ovaries. PET-CT indicated that it was a case of benign adrenal adenoma and excluded ovarian abnormalities and other ectopic tumors. Thus, a pure testosterone-secreting adrenal tumor was suspected and then adrenalectomy was performed. Histology and immunohistochemistry furtherly confirmed the benign adrenocortical adenoma with immunohistochemistry positive for inhibin α, melan A, ß-captenin, SYN (focal), Ki-67(< 3%), and negative for chromogranin (CgA), cytokeratin (CK), S-100, P53. After surgery, the level of testosterone returned to normal range and the clinical symptoms also subsided. CONCLUSIONS: Pure testosterone-secreting adrenal adenomas are extremely rare, but it can induce severe hyperandrogenism and virilization. The source identification of hyperandrogenemia only based on the levels of testosterone, DHEAS and androstenedione is limited. It is important to evaluate not only ovaries but also adrenals in all women with virilization particularly during menopause, even their androstenedione, DHEA and DHEAS level are normal.
Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Adenoma Adrenocortical/sangue , Biomarcadores/sangue , Testosterona/sangue , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Adenoma Adrenocortical/patologia , Adenoma Adrenocortical/cirurgia , Idoso , Feminino , Humanos , Pós-Menopausa , PrognósticoRESUMO
Papillary thyroid carcinoma (PTC) is a common thyroid malignancy. Elderly patients have more severe disease and more complications following postoperative endocrine therapy to control thyroid-stimulating hormone (TSH) levels. We aimed to identify optimal postoperative serum TSH levels in elderly patients to prevent recurrence and metastasis and minimize complications. This retrospective cohort study collected data of 87 consecutive elderly patients (age >75) who underwent surgery for PTC with postoperative levothyroxine therapy (50-150 µg/d) between January 2006 and June 2008 and were followed until 2013. After 24 patients with TSH fluctuations and incomplete data were excluded, 73 patients were grouped based on postoperative TSH levels: Group A, 0.3-0.5 mIU/mL; Group B, 0.1-0.3 mIU/mL; and Group C <0.1 mIU/mL (n = 24, 25, 24, respectively). Subjects' baseline, preoperative data, postoperative complications and 1-, 3- and 5-year follow-up data were compared between groups. No significant differences in gender, age (median age of 80 years old), surgery type or clinical characteristics were found between groups (all p value >0.05). Postoperatively, all subjects had normal ECG and neck ultrasound, no osteoporosis, and no differences in survival rate or metastasis. Five-year follow-up revealed significant differences in development of arrhythmias, osteoporosis, insomnia and anxiety between Groups B (0.1-0.3 mIU/mL) and C (<0.1 mIU/mL) compared to Group A (0.3-0.5 mIU/mL). Postoperative incidence of PTC recurrence and metastasis remained stable in elderly patients undergoing thyroid surgery and endocrine therapy but complications increased significantly with increasing TSH levels. Controlling TSH to lower limits of normal may help prevent PTC recurrence and metastasis and reduce complications in this high-risk population.
Assuntos
Carcinoma/cirurgia , Hipotireoidismo , Recidiva Local de Neoplasia , Complicações Pós-Operatórias , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Tireotropina/sangue , Tiroxina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Carcinoma Papilar , China , Feminino , Terapia de Reposição Hormonal/métodos , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/etiologia , Masculino , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodosRESUMO
Congenital X-linked adrenal hypoplasia (AHC) is a rare disease characterized by primary adrenal insufficiency before adolescence and by hypogonadotropic hypogonadism (HHG) during adolescence. In this paper, we present a Chinese family with AHC. Two brothers, misdiagnosed with adrenal insufficiency of unknown etiology at the age of 9, were correctly diagnosed with AHC when delayed puberty, HHG, and testicular defects were observed. We investigated the clinical features and identified the dosage-sensitive sex reversal AHC critical region of the X chromosome gene 1 (DAX-1) mutation in this kindred. Direct sequencing of the DAX-1 gene revealed that the two siblings have a novel mutation (1268delA) of which their mother is a heterozygous carrier. This mutation causes a frameshift and a premature stop codon at position 436, encoding a truncated protein. It is important to increase knowledge of the mutational spectrum in genes related to this disease, linking phenotype to genotype.
Assuntos
Insuficiência Adrenal/genética , Receptor Nuclear Órfão DAX-1/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação , Adulto , Humanos , Hipoadrenocorticismo Familiar , MasculinoRESUMO
BACKGROUND: At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone. METHODS: This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment. RESULTS: At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 µU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 µU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups. CONCLUSIONS: Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated. REGISTRATION NUMBER: ChiCTR-TRC-13003776.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Metformina/efeitos adversos , Metformina/uso terapêutico , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico , Adulto , Glicemia/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/sangue , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Tiazóis/administração & dosagemRESUMO
Objectives KLF8 is a member of KLF transcription factors which play an important tolr in oncogenesis. It is barely expressed in normal human epithelial cells but highly overexpressed in several types of human cancer cell lines. In the present study, we investigate the role of KLF8 in oral cancer and the effects of KLF8 knockdown via lentivirus mediated siRNA infection in human adenosquamos carcinoma CAL 27 cells. Study Design We developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral cancer cells. Downregulation of KLF8 was confirmed by evaluating GFP expressions, RT-PCR and western blot analysis. Finally, the effects of KLF8 downregulation were analyzed by MTT assay and colony formation assays. Results The expression levels of KLF8 mRNA and proteins are reduced in CAL 27 cells that transfected with 21-nt siRNA against KLF8. Lentivirus-mediated silencing of KLF8 reduces cell proliferation and colonies number, thereby indicating the role of KLF8 in cell proliferation and tumorigenesis. Conclusions These results strongly suggest that KLF8 is essential for growth of CAL 27 cancer cells. A better understanding of KLF8 function and processing may provide novel insights into the clinical therapy of oral cancer (AU)
Assuntos
Humanos , Fatores de Transcrição Kruppel-Like/análise , Neoplasias Bucais/patologia , Lentivirus/patogenicidade , Proliferação de Células , Receptor Xedar/análiseRESUMO
OBJECTIVES: KLF8 is a member of KLF transcription factors which play an important tolr in oncogenesis. It is barely expressed in normal human epithelial cells but highly overexpressed in several types of human cancer cell lines. In the present study, we investigate the role of KLF8 in oral cancer and the effects of KLF8 knockdown via lentivirus mediated siRNA infection in human adenosquamos carcinoma CAL 27 cells. STUDY DESIGN: We developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral cancer cells. Downregulation of KLF8 was confirmed by evaluating GFP expressions, RT-PCR and western blot analysis. Finally, the effects of KLF8 downregulation were analyzed by MTT assay and colony formation assays. RESULTS: The expression levels of KLF8 mRNA and proteins are reduced in CAL 27 cells that transfected with 21-nt siRNA against KLF8. Lentivirus-mediated silencing of KLF8 reduces cell proliferation and colonies number, thereby indicating the role of KLF8 in cell proliferation and tumorigenesis. CONCLUSIONS: These results strongly suggest that KLF8 is essential for growth of CAL 27 cancer cells. A better understanding of KLF8 function and processing may provide novel insights into the clinical therapy of oral cancer.
Assuntos
Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/patologia , Regulação para Baixo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , RNA Interferente Pequeno/fisiologia , Proteínas Repressoras/biossíntese , Carcinoma Adenoescamoso/virologia , Proliferação de Células , Humanos , Fatores de Transcrição Kruppel-Like , Infecções por Lentivirus , Neoplasias Bucais/virologia , Células Tumorais CultivadasRESUMO
BACKGROUND: Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH (1-34) in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. METHODS: A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded. RESULTS: rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment (4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P < 0.01). There was only a small but significant increase of femoral neck BMD after 18 months (2.6%, P < 0.01) in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH (1-34) group than those in the elcatonin group after 6, 12, and 18 months (serum bone-specific alkaline phosphatase (BSAP) 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P < 0.01; urinary C-telopeptide/creatinine (CTX/Cr) 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P < 0.01). rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% (6/112) in elcatonin group and 3.2% (11/341) in rhPTH (1-34) group (P = 0.303). Both treatments were well tolerated. Hypercaluria (9.4%) and hypercalcemia (7.0%) in rhPTH (1-34) group were transient and caused no clinical symptoms. Pruritus (8.2% vs. 2.7%, P = 0.044) and redness of injection site (4.4% vs. 0, P = 0.024) were more frequent in rhPTH (1-34). Nausea/vomiting (16.1% vs. 6.2%, P = 0.001) and hot flushes (7.1% vs. 0.6%, P < 0.001) were more common in elcatonin group. CONCLUSIONS: rhPTH (1-34) was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment. rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH (1-34) is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis.
Assuntos
Calcitonina/análogos & derivados , Osteoporose Pós-Menopausa/tratamento farmacológico , Hormônio Paratireóideo/uso terapêutico , Idoso , Densidade Óssea/efeitos dos fármacos , Calcitonina/uso terapêutico , China , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the design and the Mainland China subgroup baseline characteristics of the study to evaluate the efficacy and safety of alogliptin versus placebo in subjects with type 2 diabetes (T2DM) as monotherapy, add-on to metformin or add-on to pioglitazone. METHODS: This was a multi-center, randomized, double-blind, placebo-controlled, 16-week study comparing alogliptin (ALO, 25 mg, 1/d) versus placebo (PLA) as monotherapy (A), add-on to metformin (B) or add-on to pioglitazone ± metformin (C). The T2DM subjects with glycosylated hemoglobin A1c(HbA1c) between 7% and 10% and aged between 18 years and 75 years were enrolled and randomized to the alogliptin group and the placebo group in 1: 1 ratio with 16 weeks treatment. All patients were followed up every 4 weeks. The safety endpoints consisted of the incidence of hypoglycemia and other adverse events. RESULTS: A total of 491 patients were enrolled in the Mainland China subgroup of the study (181 in group A, 186 in group B and 124 in group C). In each treatment group, the baseline characteristics including age, gender, body mass index, diabetes duration, HbA1c, fasting plasma glucose, body weight, daily dosage of metformin and daily dosage of pioglitazone were all well balanced. CONCLUSION: The demographic data, medical history, glycemic profile and treatment regimen at baseline in Mainland China subgroup are well balanced. The result of this study will provide the clinical evidence for the use of alogliptin in Chinese T2DM patients.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Uracila/análogos & derivados , Adulto , China , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Projetos de Pesquisa , Resultado do Tratamento , Uracila/efeitos adversos , Uracila/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the effect and safety of HbA1c and glycemic control of acarbose chewable tablets in patients with type 2 diabetic. METHOD: A multicentre, randomized, double-blinded, double-dummy, positive controlled clinical trial was conducted. Two hundred thirty-four Chinese patients with type 2 diabetic were enrolled in eight clinical centres, who were divided randomly into the acarbose chewable tablet group (experimental group, n = 116) and the acarbose treatment group (control group, n = 118). RESULTS: Two hundred seven patients (88.5%) took part in the 12-week trial. At the beginning and end of the clinical trial, HbA1c and blood glucose as well as safety indexes were measured. After the treatment, the level of finger two-hour postprandial blood glucose (PPBG) was decreased 4.15 mmol/L (26.82%) and 3.54 mmol/L (22.77%), respectively, in the experiment group and the control group. The levels of venous two-hour PPBG in the experiment group and the control group were decreased 4.04 mmol/L (25.38%) and 2.75 mmol/L (17.26%), respectively, with the means of HbA1c lowering 11.67% and 12.44%, respectively. Fasting blood glucose (FBG) also was reduced significantly in both groups. Patients in both groups showed obvious weight reduction (P < 0.0001). There were no significant differences in the incidence of adverse events between the two groups. CONCLUSION: In summary, acarbose chewable tablets have a definite curative effect in treating type 2 diabetic patients as HbA1c and blood glucose levels decreased significantly after the 12-week treatment.
Assuntos
Acarbose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Acarbose/efeitos adversos , Glicemia/análise , Método Duplo-Cego , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversosRESUMO
BACKGROUND: Sulfonylurea receptor 1 (SUR1) and multidrug resistance protein 1 (MRP1) are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS: Fasting glucose, insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients. Insulin content, SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS: Insulinoma patients presented the typical demonstrations of Whipple's triad. Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L, and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose. Immunohistochemistry and immunofluorescence staining showed that SUR1 increased, but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS: The hypersecretion of insulin in insulinomas might be, at least partially, due to the enrichment of SUR1. In contrast, MRP1, which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Insulina/metabolismo , Insulinoma/metabolismo , Neoplasias Pancreáticas/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Receptores de Droga/metabolismo , Adulto , Glicemia/metabolismo , Peptídeo C/metabolismo , Feminino , Imunofluorescência , Teste de Tolerância a Glucose , Humanos , Imuno-Histoquímica , Secreção de Insulina , Insulinoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Receptores de SulfonilureiasRESUMO
Fulminant type 1 diabetes is a recently discovered subtype of idiopathic type 1 diabetes, defined as diabetes with an extremely rapid process of ß-cell destruction and progression to hyperglycemia and ketoacidosis. In this report, we present a case of fulminant type 1 diabetes in a 45-year-old Chinese woman, along with a review of the literature. The patient presented with sudden onset of polydipsia and polyuria after flu-like symptoms. Findings on admission included a high blood glucose level and ketoacidosis, but normal HbA1c level. The C-peptide stimulation test showed severe impairment of insulin secretion. Autoantibodies to glutamic acid decarboxylase (GAD) were negative. These results are compatible with the diagnosis of fulminant type 1 diabetes. Human leukocyte antigen-DR7 (HLA-DR7) was available in this case. It is concluded that this rapidly progressing type of diabetes exists, and we propose that HLA-DR7 might be predisposed to fulminant type 1 diabetes in Chinese patients.
Assuntos
Diabetes Mellitus Tipo 1/classificação , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To compare the clinical efficacy and safety between recombinant human parathyroid hormone (rhPTH) (1-34) and elcatonin in the treatment of postmenopausal women with osteoporosis in China. METHODS: This 6 month, multicenter, randomized and controlled study enrolled 205 postmenopausal women with osteoporosis. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily or elcatonin 20 U weekly. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD) and biochemical markers of bone turnover were measured. In the meantime adverse events were recorded. RESULTS: The results showed that both rhPTH (1-34) and elcatonin increased L1-4 BMD significantly at the endpoint of the study, but femoral neck BMD did not change significantly. From baseline to endpoint, BMD of L1-4 and femoral neck in the rhPTH (1-34) group increased by 5.51% (P<0.01) and 0.65% (P>0.05), but BMD of L1-4 and femoral neck in elcatonin group increased by 1.55% (P<0.05) and 0.11% (P>0.05). Moreover, the rhPTH (1-34) group had better improvement in L1-4 BMD than the elcatonin group at 3, 6 months, but there was no difference of BMD in these two groups with regard to femoral neck. There were greater mean increases of the bone markers in the rhPTH (1-34) group than those in the elcatonin group at 3, 6 months [serum bone-specific alkaline phosphatase (BSAP) 36.79% vs 0.31%; 92.42% vs -0.17%; the ratio of urine N-telopeptide of type I collagen and creatinine (NTX/Cr) 48.91% vs -5.32%; 68.82% vs -10.86%]. Both kinds of treatment were well tolerated and there were no differences between the two groups in the rates of adverse events and serious adverse events. CONCLUSION: It is concluded that rhPTH (1-34) has more positive effects on bone formation than elcatonin as shown by the greater increments of L1-4 BMD and bone formation markers and the less occurrence of adverse events as well as no significant change in hepatic, renal or hemopoietic function.
Assuntos
Calcitonina/análogos & derivados , Osteoporose Pós-Menopausa/tratamento farmacológico , Hormônio Paratireóideo/uso terapêutico , Idoso , Calcitonina/uso terapêutico , China , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: Glycemic control prevents onset and progression of diabetes-related long-term complications. The objective of this study was to demonstrate that twice daily insulin lispro low mix 25 is noninferior to twice daily human insulin mix 30/70 in achieving glycemic control as measured by hemoglobin A1c (HbA1c), from baseline to endpoint, in patients with type 1 or 2 diabetes. METHODS: In this phase IV, crossover, open-label, multicenter study, 117 Chinese patients with diabetes were randomly assigned to one of two treatment sequence groups. One group received 12-week treatment with twice daily human insulin mix 30/70 followed by 12-week treatment with twice daily insulin lispro low mix 25, while the other group received the reverse treatment sequence. HbA1c, baseline-to-endpoint change in HbA1c, proportion of patients achieving target HbA1c
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina/análogos & derivados , Adolescente , Adulto , Idoso , Povo Asiático , Esquema de Medicação , Feminino , Humanos , Insulina/administração & dosagem , Insulina Lispro , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To investigate insulin secretion function and insulin resistance in Chinese newly diagnosed type 2 diabetes (obese and non-obese patients) in order to provide evidence for clinical treatment. METHODS: 408 newly diagnosed type 2 diabetes and 40 normal controls were recruited. Height, weight were measured, insulin and glucose of 0 min, 30 min, 60 min, 120 min during oral glucose tolerance test were examined. The patients with fasting glucose level greater than 8.3mmol/L were treatment with Gliclazide for 1 - 3 months. After normalization of the plasma glucose levels for more than 2 weeks, and withdraw this medication for 48 hours, then OGTT were repeated to assess IR and IS. RESULTS: The patients were divided into four groups based on fasting plasma glucose (DM1: FPG < 6.9mmol/L; DM2: 6.9 mmol/L < or = FPG < 8.3 mmol/L; DM3: 8.3 mmol/L < or = FPG < 9.7 mmol/L; DM4: FPG > or = 9.7 mmol/L). Every groups were further stratified to subgroups by cut point of BMI = 24 kg/m(2). Their insulin sensitivity and insulin secretion function compared between subgroups. (1) True insulin level in BMI > or = 24 (FPG < 6.9 mmol/L) subgroups were higher than control's (3.5 +/- 0.5 vs 3.2 +/- 0.6 natural logarithm) (P < 0.05). (2) In BMI > or = 24 subgroups, their insulin sensitivity were even worse than BMI < 24 groups', but their insulin secretion function were better at the same FPG level. (3) After intervention, the change of insulin sensitivity in BMI < 24 group was better than BMI > or = 24 group's (-4.7 +/- 0.9 vs -5.5 +/- 1.4 natural logarithm) (P < 0.05); but the change of insulin secretion function in BMI < 24 group was worse. CONCLUSION: (1) In newly diagnostic type 2 diabetes, insulin sensitivity and insulin secretion function were decreased with the increase of FPG, but they were different between obese and non-obese group. (2) Insulin secretion function was recovered better in obese group when eliminated glucose toxicity.
Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2/diagnóstico , Resistência à Insulina , Insulina/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Teste de Tolerância a Glucose , Humanos , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To compare the clinical efficacy and safety of domestic orlistat and imported orlistat in Chinese overweight and obese patients. METHODS: In a randomized, double-blinded and positive-controlled study, 228 adults (BMI 24- < 40 kg/m(2)) evaluated at seven research centers were randomized to receive domestic orlistat or imported orlistat 120 mg 3 times a day with an energy-controlled diet for 24 weeks. RESULTS: After 24 weeks, domestic orlistat treated patients got significant weight-loss (5.0 +/- 3.7) kg, which was comparable with that of imported orlistat treated patients (4.5 +/- 3.5) kg (P = 0.3922). Compared with the findings before treatment, there was significant decrease of systolic blood pressure (4.4 +/- 11.5) mm Hg (1 mm Hg = 0.133 kPa) and serum levels of TC (0.54 +/- 0.79) mmol/L and LDL-C (0.32 +/- 0.64) mmol/L in the domestic orlistat treated group (compared with levels of baseline, P < 0.0001). There was no significant difference between the two groups in the changes of blood pressure and lipid levels. Both groups had similar adverse event profiles, most of which were mild and transient gastrointestinal events. There were no serious adverse events in both groups. CONCLUSIONS: Domestic orlistat combined with a light low-energy diet promoted significant weight loss, which was comparable with that of imported orlistat after 24 weeks of treatment. There was also improvement in blood pressure and serum levels of TC and LDL-C. Domestic orlistat was as effective and safe as imported orlistat in the treatment of obesity.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Lactonas/uso terapêutico , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Adolescente , Adulto , Idoso , Fármacos Antiobesidade/administração & dosagem , Povo Asiático , Método Duplo-Cego , Feminino , Humanos , Lactonas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Orlistate , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) given by injection is a new seventh class drug of biological products, which is prepared by adopting gene recombination technique. rhPTH (1-34) is mainly used to treat osteoporosis, especially for postmenopausal women. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. METHODS: Two hundred and five women with osteoporosis were enrolled in a 6-month, multicenter, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 microg (200 U) daily or elcatonin 20 U weekly. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), as well as biochemical markers of bone turnover were measured. Adverse events were recorded. RESULTS: rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin at 3 months and 6 months (2.38% vs 0.59%, P < 0.05; 5.51% vs 1.55%, P < 0.01), but there were no significant increases of BMD in these two groups at femoral neck. There were larger mean increases in bone markers in the rhPTH (1-34) group than in the elcatonin group at 3 months and 6 months (serum bone-specific alkaline phosphatase (BSAP) 36.79% vs 0.31%; 92.42% vs -0.17%; urinary N-telopeptide/creatinine (NTX/Cr) 48.91% vs -5.32%; 68.82% vs -10.86%). Both treatments were well tolerated and there were no significant differences detected between the two groups in the proportion of any adverse events and any serious adverse events (67.0% vs 59.0%; 0 vs 0). CONCLUSIONS: rhPTH (1-34) has more positive effects on bone formation, as shown by the larger increments of lumbar BMD and bone formation markers, than elcatonin, with only mild adverse events and no significant change in the liver, kidney or hematological indices.
Assuntos
Calcitonina/análogos & derivados , Osteoporose Pós-Menopausa/tratamento farmacológico , Hormônio Paratireóideo/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Idoso , Calcitonina/farmacologia , Calcitonina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Osteogênese/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Proteínas Recombinantes/farmacologiaRESUMO
OBJECTIVE: To study the possible association between C-reactive (CRP) and insulin resistance (IR) as well as the pathogenesis of type 2 diabetes macrovascular complication. METHODS: Serum CRP was measured by ultrasensitive immuoturbidimetric, which was determined on type 2 diabetes (T2DM) with or without macrovascular complication (70 and 60 cases respectively) and on normal controls (90 cases). IR was estimated by homeostasis model assessment (HOMA-IR). RESULTS: Results showed that the concentration of CRP was higher in T2DM with or without macrovascular complications than that in the healthy subjects (P < 0.01), while it was higher in diabetic patients with macrovascular complications than that in diabetic patients without macrovascular complications (P < 0.01). In diabetic patients with macrovascular complications, person correlation analysis indicated that there existed positive correlations between CRP and FINS, HOMA-IR, triglyceride (TG) while stepwise linear regression showed that usCRP and HOMA-IR, TG having linear correlation. CONCLUSION: CRP seemed to play a role in the initiation and progression of atherosclerosis in type 2 diabetes, possibly was by the way of IR.