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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increasing incidence of endometrial cancer caused by a higher life expectancy and a number of other facters (i.e. obesity, diabetes, hypertension, lower pregnancy rate) as well as the unfavorable location for early detection when compared with cervical cancer has initiated this review in order to single out women with increased risk. Clinical characteristics of patients with endometrial cancer represented by age, menstrual disorders, reduced fertility, obesity, diabetes, hypertension, hirsutism, hyperplasia of the ovarian stroma or hilus cells in connection with an increased oestrogen effect in the vaginal smear and proliferative changes of the endometrium can be explained by extraglandular respectively peripheral aromatization of androgens to oestrogens, particular by the conversion of androstenedione to oestrone. This is supported by an increased plasma oestrone/oestradiol-ratio and increased conversion rate with age and overweight. In vivo- and in vitro-investigations have demonstrated the participation of adipose tissue in peripheral oestrogene production. The compiled data point towards the importance of the extraglandular oestrone production for the etiology of endometrial cancer by effecting the endometrium over a long period of time. The counter action of the normally cyclic changes of oestradiol and progesterone is lacking. Therefore, a dysoestrogenic effect of oestrone upon the endometrium can be fully effective, depending on the hormone receptor content of the respective endometrium. Based upon these data including recent publications, pre- and postmenopausal oestrogen therapy has to be critically reevaluated.
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PMID:[Endometrial cancer and extraglandular oestrogen biosynthesis (author's transl)]. 32 98

We have carried out studies on cultured human fibroblasts in an attempt to trace the origins of age-dependent disorders to the cellular and molecular levels. Three interrelated areas are discussed. First, skin donors with diabetes mellitus (a disease complex that features inappropriate hyperglycemia) produce cultured fibroblasts with a moderate reduction in growth capacity, while two inherited disorders of inappropriate hyperglycemia and premature aging, progeria and Werner syndrome, yield fibroblast cultures with more severely impaired growth capacity. Second, there is a decreased response of progeria level and donor age; evidence is presented that this defective hormone responsiveness in aging cells may reside at the hormone receptor on the surface membrane, the cyclic AMP system, the intracellular enzymatic machinery, or all of these sites. Third, tissue factor, a procoagulant that activates the extrinsic clotting mechanism, is more abundant in cells from the premature aging syndromes of progeria and Werner syndrome. Fibroblast aging in vitro may help to explain various concomitants of normal aging and diabetes mellitus including cell dropout, impairment of hormone responsiveness, and increased atherothrombosis.
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PMID:In vitro studies of age-associated diseases. 42 66

The present paper presents studies of the sexual behavior characteristics and the associated changes of LH releasing factor and of sex hormone receptor concentrations in hypothalamic regions involved in the regulation of sexual behavior activity and hypophyseal gonadotropic function (the anterior preoptic and mediobasal regions) of rats with streptozotocin-induced diabetes. The activities of both motivational and copulative components of sex behavior of such rats were found reduced. These changes were parallelled by LH-RH reduction in the median eminence and in the synaptosomal fraction of the anterior preoptic and mediobasal regions. An increased concentration of estradiol nuclear receptors was found in the anterior preoptic region, that may be responsible for the male feminization in diabetes and for weaker male sexual activity parameters. Blood levels of LH and FSH in experimental rats were virtually the same as in the reference animals, whereas prolactin and testosterone levels were reduced in the presence of elevated estradiol content. The majority of the detected hormonal shifts and sexual behavior characteristics normalized after compensatory insulin therapy. The authors come to a conclusion on the neuroendocrine disorders at the level of the CNS in animals with experimental diabetes during the formation of the motivational and copulative components of sexual behavior.
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PMID:[Disorder of neuroendocrine regulation of sexual behavior of male rats with streptozotocin-induced diabetes]. 130 50

Although CHD is the leading cause of death in women, little is known about their response to and recovery from an acute MI. The medical and nursing care offered to women following an MI is based primarily on research studies of men. Few studies have included only women, and those that have compared women and men are limited by sample sizes that are too small for meaningful comparisons and study variables that reflect men's concerns (e.g., specific risk factors or return to work issues). Women's cardiovascular anatomy and physiology differ somewhat from men's. Women average smaller chests, hearts, and coronary artery vessel diameters and different body fat distributions. Their cardiovascular systems are designed to adapt to the extraordinary demands of pregnancy and childbirth and do so by modifying diastolic, rather than systolic, function. Similar physiologic changes are often seen in response to exercise. Women's higher levels of estrogen and progesterone influence lipid metabolism and hormone receptor activity. Thus, diagnostic tests that are based on research with men (e.g., ECGs and exercise stress tests), show more false-positive and false-negative results in women. Additionally, therapeutic interventions (e.g., PTCA and CABG) that were developed for men have been less effective for women. CHD is apparently expressed differently in women. Diabetes mellitus is a strong, independent risk factor for CHD in women and results in a risk similar to that of nondiabetic men. More women present with angina as an initial manifestation of CHD than with MI and rarely have sudden cardiac death. Women experience more complications than men and a higher mortality following acute MI. They derive less benefit from medical or surgical therapy and experience more side effects. Many aspects of women's response to acute MI reflect gender rather than biologic differences. Women's worlds, the sociocultural contexts within which they live, and their activities are qualitatively different from men's. The nursing care offered to women should be based on sound scientific rationale that responds to these unique experiences and concerns.
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PMID:Acute myocardial infarction in women. 159 51

BB/E rats spontaneously develop a form of autoimmune diabetes resembling insulin-dependent diabetes mellitus (IDDM) in humans. IDDM results from central destruction of the insulin-producing beta-cells of the pancreatic islets. Herein, we report that the outbreak of IDDM in BB/E rats is preceded by the spontaneous development of an anti-idiotypic antibody to a particular antibody to insulin made by the rats. This anti-idiotype, designated anti-DM-id, behaves as an antibody to the insulin-hormone receptor. Thus, a spontaneous anti-idiotypic antibody network whose products can affect the peripheral utilization of insulin seems to accompany the central destruction of beta-cells in developing IDDM.
Diabetes 1990 Dec
PMID:Insulin-mimicking anti-idiotypic antibodies in development of spontaneous autoimmune diabetes in BB/E rats. 224 74

Congenital hyperthyroidism is a very rare disease. But, for each affected child it has to be considered as a serious condition because of the negative impact of hyperthyroidism on fetal and postnatal development. If the manifestation occurs during fetal life tachycardia, cardiac arrhythmia, growth retardation and, most significant, prematurity are the consequences. Postnatal signs of hyperthyroidism are irritability, tachycardia, hypertension, poor weight gain and thyroid enlargement. Even cardiac failure may occur if hyperthyroidism is severe and treatment not adequate which explains the high early mortality rate of 16%. The main complication of persistent hyperthyroidism in the neonatal period and during infancy is craniosynostosis. Severe developmental delay or even mental retardation can be the consequence of inadequate high T4-levels during fetal and neonatal life. Congenital hyperthyroidism was first recognized in infants born to mothers with Graves' disease. The description of transplacental passage of the maternal thyroid stimulating antibodies elucidated the molecular mechanism in this major group of patients with "autoimmune congenital hyperthyroidism". In contrast to this transient, self-limited character of "autoimmune congenital hyperthyroidism", due to the clearance of maternal antibodies from the infant's circulation, some cases of persistent congenital hyperthyroidism without signs of thyroid autoimmunity have been recognized. Activating mutations in the thyroid-stimulating hormone receptor were described recently as the underlying molecular pathogenesis in this group of "non-immune congenital hyperthyroidism". Therefore the possibility of a molecular differential diagnosis of both groups of congenital hyperthyroidism now exists and opens the opportunity of optimal treatment for each patient.
Exp Clin Endocrinol Diabetes 1997
PMID:Congenital hyperthyroidism. 943 7

The fat gene in mice represents a recessive mutation at the carboxypeptidase E (Cpe) locus. The mutant allele (Cpe(fat)) encodes a highly unstable enzyme and produces an obesity phenotype characterized by attenuated processing of prohormones such as proinsulin that require this exopeptidase for full maturation. This article presents a preliminary physiologic and endocrinologic characterization of the stock of C57BLKS/LtJ-Cpe(fat)/Cpe(fat) mice at the backcross generation (N10) currently distributed by The Jackson Laboratory. Although previously reported not to be diabetogenic at N5, an additional five backcrosses to the C57BLKS/J background resulted in a male-biased development of both obesity and diabetes. Major differences distinguishing this mutant stock from the phenotypes produced by either the diabetes (Lepr(db)) or obese (Lep(ob)) mutations on the same inbred strain background are lack of hyperphagia and hypercorticism, sensitivity of diabetic males to exogenous insulin, and a milder and male-biased diabetes syndrome that is not associated with widespread beta-cell necrosis and islet atrophy, and that often remits with age.
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PMID:Physiologic and endocrinologic characterization of male sex-biased diabetes in C57BLKS/J mice congenic for the fat mutation at the carboxypeptidease E locus. 1040 72

Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first quarter of 2003. In August 2001, Lehman Brothers predicted that launch would take place in the first half of 2002 and that the product would make sales of $475 million in 2003, rising to $875 million in 2004. In the same month, Deutsche Bank predicted that there would be worldwide sales of $50 million in 2003, rising to $400 million in 2005. At this time, analysts at Credit Suisse predicted a launch of the product in 2003, with sales of $70 million in that year, rising to $550 million in 2005. By October 2001, Deutsche Bank predicted sales of $50 million in 2004 and $250 million in 2005. In September 2001, Morgan Stanley predicted sales of $500 million in 2002, rising to $1250 million in 2006.
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PMID:Exubera. Inhale therapeutic systems. 1209 May 49

Insulin resistance is a fundamental feature of type 2 diabetes and is also associated with increased cardiovascular risk. The thiazolidinediones are insulin sensitizing agents which improve insulin resistance by combining with an intranuclear hormone receptor. They have been shown in human studies to both reduce insulin resistance and improve pancreatic beta-cell function. They are effective both as monotherapy and in combination with sulphonylureas or metformin in improving glycaemia, with evidence of improvement in other features of metabolic syndrome. They are generally well tolerated, do not cause hypoglycaemia and have the potential to provide sustained diabetic control and reduce cardiovascular risk. They appear to be an important advance in diabetes management but further work is still required to determine their true potential.
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PMID:Insulin-sensitizing agents--thiazolidinediones (glitazones). 1236 17

The discoveries that activated macrophages produce 1alpha25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), and that immune system cells express the vitamin D receptor (VDR), suggested that the vitamin D endocrine system influences immune system function. In this review, we compare and contrast how 1alpha,25-(OH)2D3 synthesis and degradation is regulated in kidney cells and activated macrophages, summarize data on hormone receptor function and expression in lymphocytes and myeloid lineage cells, and discuss how locally-produced 1alpha,25-(OH)2D3 may activate a negative feed-back loop at sites of inflammation. Studies of immunity in humans and animals lacking VDR function, or lacking vitamin D, are viewed to gain insight into the immunological functions of the vitamin D endocrine system. The strong associations between poor vitamin D nutrition, particular VDR alleles, and susceptibility to chronic mycobacterial infections, together with evidence that 1alpha,25-(OH)2D3 served as a vaccine adjuvant enhancing antibody-mediated immunity, suggest a model wherein high levels of 1alpha,25-(OH)2D3-liganded VDR transcriptional activity may promote the CD4+ T helper 2 (Th2) cell-mediated and mucosal antibody responses to cutaneous antigens in vivo. We also review a diverse and rapidly growing body of epidemiological, climatological, genetic, nutritional and biological evidence indicating that the vitamin D endocrine system functions in the establishment and/or maintenance of immunological self tolerance. Studies done in animal models of multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), inflammatory bowel disease (IBD), and transplantation support a model wherein the 1alpha,25-(OH)2D3 may augment the function of suppressor T cells that maintain self tolerance to organ-specific self antigens. The recent progress in infectious disease, autoimmunity and transplantation has stimulated a gratifying renaissance of interest in the vitamin D endocrine system and its role in immunological health.
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PMID:The immunological functions of the vitamin D endocrine system. 1288 8


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