摘要:

While diabetes mellitus is recognized clinically as a complication of alcohol dependence, in the last 15 years several large prospective studies have demonstrated a significant reduction in risk of incident type 2 diabetes in moderate drinkers. In this article, we review prospective studies on the association between alcohol consumption and incidence of diabetes.Few prospective studies have demonstrated an unequivocal positive association between alcohol use and incidence of diabetes. A number of large prospective studies have now demonstrated an inverse association: typically a 40% risk reduction after controlling for other major risk factors. Studies based on cohorts of health professionals have not demonstrated an increased risk of diabetes with heavier consumption, but these cohorts contain few heavy drinkers. Some cohorts drawn from the general population have shown a J- or U-shaped association between level of alcohol consumption and incidence of diabetes. Frequent moderate drinking has been reported to be associated with lower risk than infrequent drinking. There have been contradictory reports on the importance of the type of alcoholic beverage and whether the effect of alcohol differs according to the bodyweight of the drinker.We conclude that like many other chronic diseases, there is a delicate balance between the harmful and beneficial effects of alcohol on the incidence of diabetes. In moderate amounts, drinking is associated with a reduced risk of diabetes, whereas in higher amounts with an increased risk.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Ghrelin, a 28 amino acid-acylated peptide predominantly produced by the stomach, displays strong growth hormone (GH)-releasing activity. It is mediated by the hypothalamic-pituitary GH secretagogue (GHS) receptors, which are specific to a family of synthetic, orally active molecules known as GHSs.However, despite their potent and reproducible GH-releasing activity, the potential clinical use of GHSs as orally active growth-promoting agents or anabolic anti-aging drugs has not been confirmed. Ghrelin and GHSs also exert other actions mediated through central and peripheral receptors, including stimulation of adrenocorticotrophic hormone and prolactin secretion, influence on insulin secretion and glucose metabolism, orexigenic effects and modulatory activity on the neuroendocrine and metabolic response to starvation, influence on exocrine gastro-entero-pancreatic functions, cardiovascular effects and modulation of cell proliferation and apoptosis.The discovery of ghrelin and the characterization of these GH-independent biological activities has widened the knowledge of some critical aspects of neuroendocrinology and suggests possible roles for GHSs and ghrelin in the treatment of pathophysiological conditions, including those unrelated to disorders of GH secretion.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Patients with Noonan syndrome, which is thought to have an incidence of 1:1000 to 1:2500 live births, have variable hypogonadism together with features such as pulmonary valvular stenosis, dysmorphism, deafness, visual problems, cryptorchidism, clotting disorders, and short stature. Noonan syndrome is now known to be associated with mutations in the PTPN11 gene encoding the protein tyrosine phosphatase SHP-2 on chromosome 12 (12q24.1). This discovery will facilitate both knowledge of the true incidence and phenotypic diversity. There are poor genotype-phenotype correlations in Noonan syndrome, and the currently defined gene abnormalities only account for a minority of those identified on a clinical basis.Puberty in patients with Noonan syndrome generally occurs spontaneously but is typically delayed. Mean adult height is 162.5cm (men) and 153cm (women), although standards are based on relatively small samples of largely cross-sectional data and are subject to ascertainment bias. Available evidence suggests that there may be disturbance of the growth hormone/insulin-like growth factor axis in Noonan syndrome and that somatropin (growth hormone therapy) dose-dependently improves vertical growth in the short to medium term. Final height data from a number of European studies will be available later in 2003.Noonan syndrome patients with echocardiographic features of hypertrophic cardiomyopathy may be at particular risk from somatropin therapy because of its known effects on cardiac muscle mass; these patients have generally been excluded from trials of somatropin.Unbiased evidence for the efficacy and safety of somatropin therapy in Noonan syndrome will come from appropriately controlled studies of sufficiently large numbers of patients defined on such a basis and followed to final height. This is now possible but will require international cooperation. Nevertheless, the clinical relevance of somatropin therapy in Noonan syndrome and other short stature syndromes will be dependent on looking beyond improvement in final height (even if achievable) to psychological and quality of life outcomes.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Pancreatic islet cell transplantation as a treatment for diabetes has hitherto been confined to small patient cohorts with limited success. This article summarizes the results of islet cell transplantation before and after the advent of the new ‘Edmonton protocol’of immunosuppression and management of the donor pancreas. Adopting this regimen has achieved unprecedented success and renewed interest in this potential cure for diabetes. Central to recent improvements in the technique has been the transplantation of an adequate islet mass. Improved methods to procure, isolate, and purify islets for clinical use are now being adopted as a new ‘gold standard’. The use of new immunosuppressive drugs has further improved clinical results. Corticosteroid sparing-based regimens, and agents such as humanized monoclonal antibodies, are likely to form the mainstay of immunosuppressive protocols with the aim of achieving donor-specific tolerance. Alternative sources of islet cells are also required to expand the technique in an era of reduced numbers of donor pancreata. Manipulation of stem cells and xenotransplantation may yet yield sufficient islets to overcome the problem of donor shortage. Islet cell transplantation now forms the basis of a prospective multicenter trial under the aegis of the Immune Tolerance Network. The results of this are awaited, but it appears that islet cell transplantation may yet emerge as an effective treatment option for some members of the diabetic population.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Ethinylestradiol 20 µg/day plus norelgestromin 150 µg/day have been formulated into a transdermal patch for hormonal contraception. The predominant mechanism of action for transdermal ethinylestradiol/norelgestromin (Ortho Evra™, Evra™) is inhibition of ovulation by suppression of gonadotropins. It suppresses follicular development, induces changes to the endometrium that reduce the probability of implantation, and increases the viscosity of cervical mucus, which may prevent sperm penetration into the uterus.Two large randomized, nonblind efficacy studies demonstrated that transdermal ethinylestradiol/norelgestromin was as efficacious in preventing pregnancy as oral triphasic ethinylestradiol/levonorgestrel or oral ethinylestradiol/desogestrel. A large, noncomparative study also showed transdermal ethinylestradiol/norelgestromin to have good contraceptive efficacy. Moreover, in the two comparative trials, women using transdermal ethinylestradiol/norelgestromin had higher rates of perfect compliance than women using oral contraception. Age did not affect the rate of perfect compliance in women using the transdermal ethinylestradiol/norelgestromin patch, whereas the rate of compliance reduced with younger age in oral contraceptive users. Pooled results from three efficacy studies found that 1.8% of patches were replaced as a result of complete detachment and 2.9% because of partial detachment. Physical exercise, water immersion, and living in a humid climate did not affect patch adhesion.Transdermal ethinylestradiol/norelgestromin was generally well tolerated in clinical trials. The most common menstrual disturbances were breakthrough bleeding/spotting and dysmenorrhea. The incidence of discontinuation of treatment because of an adverse event was ≤3.2%, with the most common reason being application-site reactions.ConclusionsTransdermal ethinylestradiol/norelgestromin offers a well tolerated, effective, reversible, and easy-to-use method of hormonal contraception with an increased likelihood of compliance relative to oral contraceptives.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

New treatments and treatment protocols for endocrine disorders are evolving rapidly, and research and development activity in the endocrinology field is high. Optimal therapy remains contentious in some areas. To help you keep up-to-date with the latest advances worldwide on all aspects of drug therapy and management of endocrine disorders, this section of the journal brings you information selected from the rapid drug news alerting serviceInpharma Weekly1. Each issue contains easy-to-read summaries of the most important research and development news, clinical studies, treatment guidelines, pharmacoeconomic and adverse drug reaction news, and expert opinion pieces published in the world's top endocrinology journals.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS