Abstract:
:Troglitazone is a novel once-daily oral antidiabetic agent for the treatment of type 2 diabetes patients. Here, we report the overall dose response characteristics of troglitazone, with respect to effects on metabolic control, using a pharmacodynamic model. Data from week 12 from two previously reported double-blind, randomized, parallel-group, placebo-controlled, dose-ranging multicentre studies examining once-daily doses of 10, 30, 100, 200, 400, 600 and 800 mg of troglitazone were combined for the analyses. The pharmacodynamic relationships for relevant parameters of metabolic control were modelled using a nonlinear regression modelling programme. The troglitazone dose-concentration relationship was linear over 10-800 mg. Using an inhibitory sigmoid Emax model, ED50 values of approximately 100 mg and 200 mg were found for fasting serum glucose and triglycerides, respectively. The 200 mg dose for HbA1c showed an inconsistent reduction compared with placebo between the two studies; this illustrates the difficulties associated with comparing results from different assay techniques. Insulin and nonesterified fatty acid reductions compared with placebo were not consistent between studies, and no pharmacodynamic modelling was possible. No changes in body weight were observed at any dose. Troglitazone was as well tolerated as placebo across the dose range investigated. This pharmacodynamic analysis has established that 200-600 mg once daily can be considered the therapeutic dose range of troglitazone that significantly improves metabolic control in type 2 diabetes patients.
journal_name
Ann Medjournal_title
Annals of medicineauthors
Young MA,Eckland DJ,Eastmond R,Lettis Sdoi
10.3109/07853899808999405subject
Has Abstractpub_date
1998-04-01 00:00:00pages
206-12issue
2eissn
0785-3890issn
1365-2060journal_volume
30pub_type
临床试验,杂志文章,多中心研究,随机对照试验abstract::Insulin resistance in humans is not always accompanied by obesity, since severe insulin resistance also characterizes patients lacking subcutaneous fat such as those with HAART- (highly-active antiretroviral therapy)-associated lipodystrophy. Both obese and lipodystrophic patients, however, have an increase in the amo...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890510037383
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND AND AIMS:Prospective data on development of venous obstruction after electrode implantation are limited. We performed a prospective study on 150 patients undergoing first pacemaker implantation. METHODS:Venographies at base-line and 6 months postimplantation in all patients, 50 patients included into a long...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.1080/07853890802498961
更新日期:2009-01-01 00:00:00
abstract:AIM:To evaluate if pulse pressure (PP) is a risk predictor for atrial fibrillation (AF) in a longitudinal study of 60-year-old men and women from Stockholm (n = 4,232), free from AF at baseline, with primary end-point incident AF. METHODS:AF diagnoses were obtained from the national hospital discharge register. The es...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853890.2015.1100321
更新日期:2015-01-01 00:00:00
abstract::Among the approximately 7,000 cytogenetically abnormal childhood and adult B- and T-lineage acute lymphoblastic leukemias (ALL) published to date, numerous recurring chromosomal aberrations and abnormality patterns have been identified, and it has been clearly shown that the cytogenetic features often correlate closel...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890410018808
更新日期:2004-01-01 00:00:00
abstract::In three patients with attacks of acute intermittent porphyria we found markedly impaired functions of the left ventricle accompanied by ECG changes that returned to normal after administration of heme arginate or cytochrome C administration. In nine patients with other types of porphyria, and in one patient with acut...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853898909149205
更新日期:1989-08-01 00:00:00
abstract::The calcium-sensing receptor is a G protein-coupled receptor that has a key role in extracellular calcium homeostasis, regulating the secretion of parathyroid hormone and the reabsorption of urinary calcium appropriate to the prevailing calcaemic environment. Molecular abnormalities of the calcium-sensing receptor are...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:
更新日期:2002-01-01 00:00:00
abstract:AIMS:This investigation was designed to explore the role of IL-1RN genotype in unexplained infant deaths (including sudden infant death syndrome (SIDS)), non-infectious infant deaths, and infectious infant deaths, and to investigate whether IL-1RN genotype is related to the finding of organisms in normally sterile site...
journal_title:Annals of medicine
pub_type: 杂志文章
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更新日期:2010-01-01 00:00:00
abstract::The aetiology of insulin-dependent diabetes (IDDM) involves genetic predisposition, a major component of which has been mapped in the HLA complex, near to or identical with genes encoding class II molecules. In Caucasian populations IDDM is strongly associated with the serologically defined HLA-DR3 and DR4 antigens, w...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899109148086
更新日期:1991-10-01 00:00:00
abstract::On theoretical grounds, an apo E receptor defect should be manifested by the accumulation of lipoprotein remnants that are normally cleared by this receptor and cannot be processed by the normal apo B, E receptor (LDL-receptor). Furthermore, the defect should not be selective for a specific apo E phenotype since none ...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853899109148042
更新日期:1991-04-01 00:00:00
abstract::A number of biochemical markers in maternal serum have been proposed for first trimester screening for Down's syndrome. The most promising four are pregnancy associated plasma protein A (PAPP-A), the free beta sub-unit of human chorionic gonadotrophin (hCG) (free beta glycoprotein sub-unit), unconjugated oestriol (uE3...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853899409147323
更新日期:1994-02-01 00:00:00
abstract:INTRODUCTION:Aiming at identifying biomarkers for hypertrophic cardiomyopathy (HCM), the serum proteome was explored through a two-dimensional gel-based proteomic approach (2D-DIGE) coupled with mass spectrometry and database interrogation. METHODS:Serum samples from 20 male HCM patients and their sex- and age-matched...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853890.2013.792555
更新日期:2013-06-01 00:00:00
abstract:INTRODUCTION:As individuals age, the prevalence of neurocognitive and mental health disorders increases. Current biomedical treatments do not completely address the management of these conditions. Despite new pharmacological therapy the challenges of managing these diseases remain.There is increasing evidence that the ...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.1080/07853890.2020.1808239
更新日期:2020-12-01 00:00:00
abstract::Leukocyte adhesion to endothelium is essential for the development of an appropriate immune-inflammatory response. The vital importance of leukocyte-endothelial adhesive interactions in host defense and homeostasis is illustrated by the clinical manifestations of patients with congenital defects of leukocyte adhesion ...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899909115974
更新日期:1999-06-01 00:00:00
abstract:INTRODUCTION:Inflammation is an important contributor to the development of chronic diseases. We examined whether a healthy Nordic diet, also called the Baltic Sea diet, associates with lower concentrations of inflammatory markers. METHODS:We used two independent cross-sectional studies: the DILGOM study including Fin...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853890.2013.870020
更新日期:2014-03-01 00:00:00
abstract::Epidemiological and experimental studies indicate an inverse relationship between the risk of colon cancer development and intake of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). All NSAIDs are known inhibitors of cyclo-oxygenase, the enzyme responsible for converting arachidonic acid to prostagland...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899708999342
更新日期:1997-06-01 00:00:00
abstract::In the aetiological diagnosis of pulmonary infections in patients affected by haematological malignancies we evaluated the utility of bronchoalveolar lavage (BAL). One hundred and twenty-seven BAL were performed in 119 patients. In our series, we identified the agent of pneumonia in 53.5% of episodes with the best res...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853899709007478
更新日期:1997-12-01 00:00:00
abstract::The question why low-density lipoprotein (LDL) stranded in the subendothelium of arteries should acquire the proinflammatory properties that initiate and sustain atherogenesis has puzzled researchers for decades. The most popular concept contends that oxidative processes are crucial because oxidized LDL (ox-LDL) produ...
journal_title:Annals of medicine
pub_type: 社论
doi:10.3109/07853899809002596
更新日期:1998-12-01 00:00:00
abstract::Alcoholism is a complex disorder involving both genetic and environmental factors and interactions between them. Localizing and characterizing the genetic influences on susceptibility to alcohol dependence may provide new insights into pathology and new avenues for treatment and prevention. However, because of the com...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890310004903
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND AIMS:A mild increase in liver enzyme levels is sometimes observed in patients with diabetic ketosis or ketoacidosis. The aim of the present study was to assess the cause and prevalence of the elevation of liver transaminase levels in fulminant and acute-onset type 1 diabetic patients experiencing diabetic ke...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.1080/07853890802032711
更新日期:2008-01-01 00:00:00
abstract::Research in developing countries is essential for the evaluation of the safety, efficacy and acceptability of both new and already available contraceptives. Research conducted by scientists in developing countries has also played an essential role in the development of new contraceptives. The continuous delivery of pr...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853899309147858
更新日期:1993-02-01 00:00:00
abstract::Steroids diffuse through polysiloxone at a constant rate, and steroids placed in the vagina rapidly pass through the vaginal epithelium into the circulation. Combining these principles led to the development of contraceptive vaginal rings (CVR) consisting of various progestins, with and without oestrogen, placed in fl...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899309164167
更新日期:1993-04-01 00:00:00
abstract::Thymoma is an unusual tumour, but it is the most common malignancy in the anterior mediastinum. This tumour is unique in its frequent association with paraneoplastic syndrome and its potential for indolent growth. The distinction between thymomas and other tumours which arise in the anterior or superior mediastinum is...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::The majority of patients with low back pain offer no objective clinical findings on which to make a diagnosis on the basis of physical examination. Therefore a diagnostic categorization of complaint based on duration and location is proposed. The justification for this organization is the assumption that the majority ...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853898909149215
更新日期:1989-10-01 00:00:00
abstract::Hypertension is a major cardiovascular risk factor with a multifactorial pathogenesis, including genetic and environmental factors. In addition to hypothesis-driven strategies, unbiased approaches such as genomics, proteomics, and metabolomics are useful tools to help unravel the pathophysiology of hypertension and as...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853890.2012.660494
更新日期:2012-06-01 00:00:00
abstract::Sleep and wakefulness are complex behaviors that are influenced by many genetic and environmental factors, which are beginning to be discovered. The contribution of genetic components to sleep disorders is also increasingly recognized as important. Point mutations in the prion protein, period 2, and the prepro-hypocre...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890500372047
更新日期:2005-01-01 00:00:00
abstract::The risk of cardiovascular disease is markedly increased in patients with type 2 diabetes with a prevalence twice as high compared to the background population. With the recognition of multiple concomitant risk factors for both microvascular as well as cardiovascular disease in type 2 diabetic patients, treatment stra...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890410033612
更新日期:2004-01-01 00:00:00
abstract::Atherosclerosis is an inflammatory disease of the vessel wall, characterized by the accumulation of leukocytes, especially macrophages and T-cells. Chemokines are small heparin-binding polypeptides, whose main function is to attract cells to the areas of developing inflammation. They function by ligating G-protein cou...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890310019961
更新日期:2004-01-01 00:00:00
abstract::Aim: We investigated the outcomes of transcatheter (TAVR) and surgical aortic valve replacement (SAVR) in Finland during the last decade. Methods: The nationwide FinnValve registry included data from 6463 patients who underwent TAVR or SAVR with a bioprosthesis for aortic stenosis from 2008 to 2017. Results: The annua...
journal_title:Annals of medicine
pub_type: 临床试验,杂志文章
doi:10.1080/07853890.2019.1614657
更新日期:2019-01-01 00:00:00
abstract::Dietary salt intake is the most important factor contributing to hypertension, but the salt susceptibility of blood pressure (BP) is different in individual subjects. Although the pathogenesis of salt-sensitive hypertension is heterogeneous, it is mainly attributable to an impaired renal capacity to excrete sodium (Na...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853890.2012.671538
更新日期:2012-06-01 00:00:00
abstract:INTRODUCTION:Maternal obesity has long-term consequences for the offspring's later health, including an increased risk of type 2 diabetes and cardiovascular disease. The underlying mechanisms explaining these associations are, however, not fully understood. METHODS:A total of 2003 individuals from the Helsinki Birth C...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853890.2015.1004360
更新日期:2015-03-01 00:00:00