Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The introduction of novel antipsychotics for the treatment of patients with serious psychiatric illness has alleviated the burden of managing some of the side effects of conventional agents. However, the novel agents may also cause adverse events. The long-term adverse events of concern include weight gain, diabetes, tardive dyskinesia (TD), and those associated with hyperprolactinemia. Recent studies with the novel agents have prompted clinicians to revisit antipsychotic-induced weight gain. Clinically significant weight gain puts patients at risk for coronary heart disease, hypertension, type II diabetes, dyslipidemia, and some types of cancer. More recently, case reports of glucose abnormalities and diabetes have emerged, indicating that some novel antipsychotics may be associated with altered glucose metabolism or insulin sensitivity. The novel antipsychotics may also have a lower propensity for causing TD than the conventional antipsychotics. Side effects associated with hyperprolactinemia include galactorrhea, gynecomastia, and menstrual and sexual dysfunction. All of these adverse events can cause patients to become non-compliant and may thus predispose them to relapse. In this review, the authors summarize the literature on the long-term side effects of the novel antipsychotics and examine the severity of the problem, with recommendations for management. When selecting treatments, clinicians should consider the side-effect profiles of the various antipsychotic agents.
 ...
PMID:Long-term adverse effects of novel antipsychotics. 1599 Apr 91

Antipsychotics are associated with a wide range of adverse effects, several of which may represent a serious health risk to patients. There is an increased concern about metabolic disturbances associated with antipsychotics, including weight gain, dyslipidemia, hyperglycemia, and type 2 diabetes. However, little is known about the mechanisms underlying antipsychotic-induced metabolic disturbances and, in particular, those related to the induction of abnormal glucose metabolism and diabetes. The present article aimed to identify those receptor(s) that are most likely to be involved with or mediate antipsychotics-induced diabetes. Two independent measures taken from literature to indicate the risk of type 2 diabetes associated with 25 typical and atypical antipsychotic drugs were considered, along with their binding affinities to 21 specific receptors (obtained from the resources of Prous Science Integrity). A range of both exploratory and predictive statistical analyses were applied, including principal component factorial analysis, multivariable linear regression analysis, and discriminant analysis. Binding affinities (pKi) to human neurotransmitter receptors and monoaminergic transporters were used as independent variables (predictors). Measures to determine the risk to induce new-onset type 2 diabetes associated with each antipsychotic, logistic regression odds-ratio (dOR) and a discrete scale-based risk (three levels: 'low,' 'moderate,' 'high'), were used as the dependent variables (criteria). Similarly, parallel analyses were also conducted for other measures (average effective therapeutic dose) or adverse effects (weight gain, extrapyramidal side effects, hyperprolactinemia, anticholinergic, hypotension, and sedation) associated with antipsychotics, where underlying mechanisms have been previously established and, therefore, serve as positive-control references. Affinity for the cholinergic muscarinic M3 receptor subtype was presented as the best predictor for the propensity of antipsychotics to induce type 2 diabetes. This was independently revealed by means of multiple linear regression analysis, using the dOR as criterion (R=0.90, p<0.0001), and discriminant analysis, using the scale-based risk of type 2 diabetes (3 levels) as criterion (Wilks' lambda=0.33, chi2=14.11, p<0.001). To our knowledge, this study provides the first direct evidence to indicate that antipsychotic agents with high binding affinity to the muscarinic M3 receptor are associated with an elevated risk for type 2 diabetes. Rationale of the M3 receptor involvement in this adverse effect is discussed further in relation to M3 receptor mediation of glucose-dependent parasympathetic acetylcholine regulation of insulin secretion by pancreatic beta-cells. This study is the first in a series of investigations that aim to further our understanding of mechanisms underlying adverse drug effects.
 ...
PMID:Research on adverse drug events. I. Muscarinic M3 receptor binding affinity could predict the risk of antipsychotics to induce type 2 diabetes. 1608 16

In transsexual people, cross-sex hormone therapy is an important component of medical treatment. In male-to-female transsexuals, feminizing effects should be achieved before irreversible sex reassignment surgery (SRS) is considered. The most common treatment regimen in male-to-female transsexuals is a combination of ethinyl oestradiol and cyproterone acetate, with the exception of transdermal oestradiol-17beta in individuals over the age of 40. The mortality and morbidity rates with this treatment regimen have been reported in more than 800 patients. Typical side effects include venous thrombosis, elevated liver enzymes, symptomatic gallstones, hyperprolactinaemia and depression. Sixty male-to-female transsexuals were treated with monthly injections of gonadotropin-releasing hormone agonist (GnRHa) and oral oestradiol-17beta valerate for 2 years to achieve feminisation until SRS. There was a significant decline in gonadotropins, total testosterone and calculated free testosterone. In general, the treatment regimen was well accepted. An equal increase in breast size was achieved compared to common hormone therapy. Two side effects were documented. One, venous thrombosis, occurred in a patient with a homozygous MTHFR mutation. One patient was found to be suffering from symptomatic preexisting gallstones. No other complications were documented. Liver enzymes, lipids, and prolactin levels were unchanged. Significantly increased oestradiol and SHBG serum levels were detectable. In addition, an increase in bone mass density, in the femoral neck and lumbar spine, was recorded. We conclude that cross-sex hormone treatment of male-to-female transsexuals using GnRHa and oestradiol-17beta valerate is effective, and side effects and complication rates can be reduced using the treatment regimen presented here.
Exp Clin Endocrinol Diabetes 2005 Dec
PMID:Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist. 1632 Jan 57

The World Health Organization defines sexual health as "a state of physical, emotional, mental and sexual well-being related to sexuality." This broad definition goes beyond simply inquiring about sexual dysfunction and ideally fits the model of patient-centered primary care. As we observe that sexual health and physical health are often closely related, discussions about sexual activity can be very revealing. Sexual intimacy appears positively related to loving relationship satisfaction and stability. Sexual problems have a clear negative impact on both the quality of life and emotional state regardless of age. Learning about specific sexual dysfunctions among men can reveal a variety of as-yet-undiagnosed comorbid pathologic conditions such as: (i) depression and other emotional illnesses; (ii) psychosocial stress; (iii) actual cardiovascular disease as well as related risk factors such as hypertension, diabetes, and/or hyperlipidemia; (iv) hyperprolactinemia; and (v) low serum testosterone. Specific sexual dysfunctions among women can reveal pathologic conditions such as: (i) depression and other adverse imitational and psychosocial conditions; (ii) low serum estrogen or testosterone; and/or (iii) vaginal or pelvic disorders. A discussion about sexual health can be accomplished efficiently in a primary care office with the inquiring clinician having the option to deal with any sexual problems and dysfunctions directly, or to refer the patient to an appropriate specialized care source.
 ...
PMID:Sexual health inquiry and support is a primary care priority. 1640 13

Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. Although the great majority of pregnant women have no pre-existing endocrine abnormalities, a small number of women can have certain endocrine alterations that could potentially lead to recurrent pregnancy losses. It is estimated that approximately 8 to 12% of all pregnancy losses are the result of endocrine factors. During the preimplantation period, the uterus undergoes important developmental changes stimulated by estrogen, and more importantly, progesterone. Progesterone is essential for the successful implantation and maintenance of pregnancy. Therefore, disorders related to inadequate progesterone secretion by the corpus luteum are likely to affect the outcome of the pregnancy. Luteal phase deficiency, hyperprolactinemia, and polycystic ovarian syndrome are some examples. Several other endocrinological abnormalities such as thyroid disease, hypoparathyroidism, uncontrolled diabetes, and decreased ovarian reserve have been implicated as etiologic factors for recurrent pregnancy loss.
 ...
PMID:Endocrinology of recurrent pregnancy loss. 1641 76

The aim of the study is to investigate whether platelet activity is increased by hyperprolactinemia during pregnancy as reflected by beta-thromboglobulin level. Forty-eight healthy, pregnant, and 30 healthy, non-pregnant women were investigated with respect to platelet count, collagen/ADP and collagen/epinephrine closure times, beta-thromboglobulin and prolactin levels. The comparison of the variables between the two groups was made by Mann-Whitney U test. The correlation analyses were performed by Spearman's rank correlation test. Our results revealed that platelet counts, collagen/ADP and collagen/epinephrine closure times and beta-thromboglobulin showed no statistically significant differences between pregnant and non-pregnant women. We found no significant correlation between prolactin and collagen/ADP closure time (r = 0.175), between prolactin and collagen/epinephrine closure time (r = -0.112) and between prolactin and beta-thromboglobulin (r = 0.220) in pregnant women. Our findings suggest that platelet activity is comparable during pregnant and non-pregnant states and there is no significant effect of prolactin on platelet function in vivo as reflected by beta-thromboglobulin level.
Exp Clin Endocrinol Diabetes 2006 Apr
PMID:Hyperprolactinemia of pregnancy is not associated with increased in vivo platelet activity and shortened in vitro bleeding times. 1670 51

Although hypopituitarism is a known complication of traumatic head injury, it may be under-recognized due to its subtle clinical manifestations. To address this issue, we determine the prevalence of neuroendocrine abnormalities in patients rehabilitating from severe traumatic brain injury (Glasgow Coma Scale < or = 8). 76 patients (mean age 39 +/- 14 yr; range 18-65; 53 males and 23 females; BMI 25.8 +/- 4.2 kg/m2; mean +/- SD) with a severe traumatic brain injury, an average of 22 +/- 10 months before this study (median, 20 months), underwent a series of standard endocrine tests, including TSH, free T4, T4, T3, prolactin, testosterone (males), estradiol (females), cortisol, ACTH, GH, and IGF-I. All subjects also underwent GH response to GHRH + arginine. Growth hormone deficiency (GHD) was defined as a GH response < 9 microg/L to GHRH + arginine and was confirmed by ITT (< 3 microg/L). Pituitary deficiency was shown in 24% of the patients (18/76). 8% (n = 6) had GHD (GH-peak range [GHRH + arginine]: 2.8-6.3 microg/L; GH-peak range [ITT]: 1.5-2.2 microg/L; IGF-I range: 62-174 microg/L). 17% (n = 13) had hypogonadism (total testosterone < 9.5 nmol/L and low gonadotropins in 12 males; low estradiol, and low gonadotropins in 1 female). Total testosterone levels did not correlate with BMI or age. 2 males with hypogonadism also showed a mild hyperprolactinemia (33 and 41 ng/ml). 3% (n = 2) patients had partial ACTH-deficiency (cortisol-peak [ITT] 392 and 417 nmol/L) and 3% (n = 2) had TSH-deficiency. In summary, we have found hypopituitarism in one-fourth of patients with predominantly secondary hypogonadism and GHD. These findings strongly suggest that patients who suffer head trauma must routinely include neuroendocrine evaluations.
Exp Clin Endocrinol Diabetes 2006 Jun
PMID:Hypopituitarism following severe traumatic brain injury. 1686 91

Endocrine disease frequently interrupts sexual function, and sexual dysfunction may signal serious endocrine disease. Diabetic autonomic neuropathy and endothelial dysfunction impair erectile function, and phosphodiesterase inhibition produces only moderate benefit. The effect of diabetes on women's sexual function is complex: the most consistent finding is a correlation between sexual dysfunction and depression. Reductions in testosterone level in men are associated with low sexual desire and reduced nocturnal erections and ejaculate volume, all of which improve with testosterone supplementation. The age-dependent decline in testosterone production in men is not associated with precise sexual symptoms, and supplementation has not been shown to produce sexual benefit. In women, sexual dysfunction has not been associated with serum testosterone, but this may be confounded by limitations of assays at low concentrations and by the greater importance of intracellular production of testosterone in women than in men. Testosterone supplementation after menopause does improve some aspects of sexual function in women, but long-term outcome data are needed. More research on the sexual effects of abnormal adrenal and thyroid function, hyperprolactinaemia, and metabolic syndrome should also be prioritised. We have good data on local management of the genital consequences of oestrogen lack, but need to better understand the potential role of systemic oestrogen supplementation from menopause onwards in sexually symptomatic women.
 ...
PMID:Sexual dysfunction in men and women with endocrine disorders. 1744 19

The safety of the atypical antipsychotic quetiapine as used in general practice in England was examined by prescription-event monitoring (PEM). Patients were identified from dispensed National Health Service (NHS) prescriptions issued by general practitioners (GPs) for quetiapine between October 1997 and July 1999. The outcome data were event reports obtained by sending questionnaires ('green forms') to the prescribing doctor at Least 6 months after the first prescription for an individual patient. Green forms with clinically useful information on 1728 patients (median age 39 years (IQR 30-56); 53% female) were received. The most frequently reported event during the first month of treatment was 'drowsiness/sedation' (47; 3% cohort). This was also the most frequently reported specified adverse drug reaction (ADR) to quetiapine (7; 11% of 65 reported ADRs) and the highest reported clinical reason for stopping quetiapine (51; 6% of the 734 reported reasons for stopping). There was a low incidence of extrapyramidal disease (21 during treatment, 1% of cohort) and hyperprolactinaemia (three during treatment, 0.2%) in this study. Three cases of diabetes mellitus in this cohort were reported to be a new diagnosis. Six pregnancies were reported during treatment with quetiapine, five of which were exposed during the first trimester only. There were four Live births with no reported congenital abnormaLities. Fifty-six deaths were reported during this study (3% cohort). The most frequently reported causes of death reLated to the cardiovascular (18) and respiratory (15) systems. The results of this post-marketing surveillance study demonstrated that quetiapine is generally well-tolerated when used in general practice.
 ...
PMID:The safety of quetiapine: results of a post-marketing surveillance study on 1728 patients in England. 1765 26

While there are many effective antipsychotics available to clinicians for treating schizophrenia or bipolar mania, the onset of antipsychotic-associated prolactin-related and metabolic adverse effects can diminish the effectiveness of treatment. Increased levels of prolactin (hyperprolactinemia) associated with some antipsychotics raises the risk of sexual side effects. The increased appetite and/or sedation (reduced activity levels) induced by other antipsychotics can lead to weight gain, dyslipidemia, and high blood pressure and, if unchecked, ultimately to cardiovascular disease, diabetes, and metabolic syndrome. Clinicians should take steps to help their patients avoid unnecessary risks associated with antipsychotic use. These steps include monitoring risk factors for developing these illnesses by taking careful patient histories and baseline measurements of patients' weight and blood chemistry. Patients should be made aware of potential metabolic and prolactin-related side effects, and periodic checks should also be made to watch for changes in weight, body mass index, waist size, blood pressure, fasting glucose, or lipid levels that could be harmful and may increase risk for cardiovascular disease.
 ...
PMID:Prolactin-related and metabolic adverse effects of atypical antipsychotic agents. 1848 6


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>