Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
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Erectile dysfunction (E. D.) affects millions of men in the whole world. The prevalence of erectile dysfunction in the best conducted study, the Massachusetts Male Aging Study (MMAS), was 52% of male subjects aged 40 to 70 years. ED is strongly associated with age. Multiple risk factors, such as chronic illness, hypertension, diabetes, medication, operation in the pelvis, smoking and alcohol consumption, have a negative influence on erectile function.
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PMID:[Epidemiology and age-related risk factors of erectile dysfunction]. 1074 86

Erectile disfunction (E. D.) is more common in older men but may affect younger men too. Diabetes mellitus, coronary heart disease and hypertension are often associated with E. D. The majority of the patients are treated medically for erectile dysfunction and, recently, oral therapy has become most important since Viagra has been approved. New phosphodiesterase blockers are in preclinical evaluation since then. Phentolamine and apomorphine will become available soon for the treatment of E. D. It is important to know about the etiology of E. D. as well as the mechanisms by which drugs may improve erection in order to decide which drug is appropriate for a particular patient.
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PMID:[Oral therapy of erectile dysfunction]. 1074 89

To determine whether a difference in HbA(1c) could be safely sustained between a standard therapy (STD) arm and an intensive therapy (INT) arm, while maintaining HbA(1c) levels in both arms within a range acceptable in community practice. The effects of intensive treatment on various parameters were studied in this feasibility trial. We report here the results of 24 months of INT on peripheral and autonomic neuropathy.A prospective trial was conducted in five medical centers in 153 men of 60 +/- 6 years of age who had a known diagnosis of diabetes for 7.8 +/- 4 years. They were randomly assigned to a standard insulin treatment group (one morning injection per day) or to an intensive therapy group designed to attain near-normal glycemia and a clinically significant separation of glycohemoglobin from the standard arm. A four-step plan was used in the intensive therapy group along with daily self-monitoring of glucose: (1) an evening insulin injection, (2) the same injection adding daytime glipizide, (3) two injections of insulin alone, and (4) multiple daily injections. Peripheral neuropathy was diagnosed clinically by a history and physical examination, and by abnormal autonomic neuropathy Valsalva ratio (VR < 1.2) and RR variation (RRV < 10). An average HbA(1c) separation of 2.07% was achieved with INT, having HbA(1c) at or below 7.3% (p = 0. 001 versus STD). Baseline prevalence of peripheral neuropathy was 53% in STD, and 48% in INT. By 24 months, the prevalence increased to 69% in STD (p = 0.005 versus baseline), and to 64% in INT (p = 0. 008 versus baseline, but no different than STD). Though INT did not reverse all elements of peripheral neuropathy, there was a decreased prevalence of cranial neuropathy (p = 0.053 versus STD) and more frequent preservation of touch sensation in the upper extremities (p = 0.03 versus STD) in INT. At baseline, an abnormal Valsalva ratio and/or RR variation was seen in 38% of STD and 31% of INT. By 24 months in STD, the prevalence rose to 55% (p = 0.0067 versus baseline), and in INT, to 48% (p = 0.012 versus baseline and no different from STD). The prevalence of erectile dysfunction increased from 53% at baseline to 73% at 2 years, p = 0.002 in STD, and from 51% to 73% at 2 years (p = 0.003 versus baseline) and no different from STD. There was no change in the frequency of abnormal gastrointestinal or sweating symptoms. Our conclusion was that 2 years of meticulous glycemic control did not decrease overall prevalence of peripheral or autonomic neuropathy. In fact, the prevalence rose equivalently and significantly in both treatment arms. There was some benefit, however, in decreased frequency of cranial neuropathy and better preservation of touch sensation in INT.
J Diabetes Complications
PMID:The effects of intensive glycemic control on neuropathy in the VA cooperative study on type II diabetes mellitus (VA CSDM). 1076 7

Erectile dysfunction (ED) has been defined by the National Institutes of Health Consensus Conference in 1993 as the inability to achieve and/or maintain an erection adequate for penetration and completion of satisfactory intercourse.1 Erectile dysfunction, the preferred term, is more accurate and less pejorative than impotence.An estimated 20-30 million American men are affected with ED of varying degrees of severity. The Massachusetts Male Aging Study published in 1994 reviewed 1,211 men between the ages of 40 and 70; 52% reported ED with 9.6% having mild, 22.2% moderate, and 17.2% complete or severe ED.2 The National Health and Social Life Survey, authored by Laumann et al.,3 reviewed a population of men and women between the ages of 18 and 59. Of note, female sexual dysfunction exceeded male sexual dysfunction, with 43% of women complaining of sexual function problems. Interestingly, except for lubrication, this seemed to decrease with age in women. On the other hand, 31% of the men complained of sexual problems that increased with age.Erectile dysfunction is an age-dependent problem. Approximately 2% of men are affected at 40 years of age and about 25% or more at 65 years of age.4 However, ED is not an inevitable result of aging. Rather, as a man matures it is most likely that he will experience more of the neurovascular insults resulting in ED.The development of an erection and satisfactory sexual function is a complex process. As suggested by Melman et al.,5 "Erection is truly at least a sensory-motor-neuro-hormonal-vascular-psycho-social-cultural-interpersonal event." There are two main classifications of ED, psychogenic and organic. Current thinking suggests that up to 80% of ED is primarily of organic etiology. Yet, there is always a psychogenic factor.6 Erectile dysfunction may signal serious underlying and potential life-threatening diseases, such as diabetes, hypertension, cardiovascular disease, peripheral vascular disease, and other neurologic and endocrine disorders. Therefore, questions regarding sexual function should be part of routine medical evaluation.
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PMID:Erectile dysfunction: a review of a common problem in rapid evolution. 1084 Feb 16

Vasculogenic erectile dysfunction (ED) is associated with collagen replacement of the cavernosal smooth muscle, mediated by an increase in transforming growth factor (TGF)-production secondary to hypoxemia. We tested the hypothesis that human ED is the result of an increase in apoptosis of the cavernosal smooth muscle cells with replacement by collagen, mediated by the TGFbeta upregulation. We also examined the tissue for proteins associated with apoptosis. Human cavernosal tissue was procured from impotent men at the time of prosthesis insertion. Normal corpous cavernosum served as a control. The TUNEL assay was used to assess apoptosis. Immunohistochemistry staining was used to detect TGFbeta and Bcl-2 expression, while Western blot analysis was used to detect expression of Bcl-2, p53, and hypoxia-inducible factor (HIF)-1a. Immunohistochemistry showed downregulation of TGFbeta protein expression in the corpus cavernosum of men with ED. Apoptotic nuclei were noted in cavernosal smooth muscle from a potent man but were not found in cavernosal tissue from men with ED. To gain insight into the possible mechanism of apoptosis in men with ED, the proto-oncogene Bcl-2, a potential inhibitor of apoptosis, was examined. Both immunohistochemistry and Western analysis revealed the presence of Bcl-2 in the cavernosal nerve of a potent man but its absence in cavernosal tissue from men with ED. Thus, loss of Bcl-2 expression correlated with the loss of apoptosis. In contrast, Western blotting demonstrated upregulation of p53 and HIF-1a expression in the cavernosal tissues from the men with ED and diabetes. Male ED follows an active process characterized by a loss of TGFb expression, apoptosis, and Bcl-2 expression. However, there is upregulation of p53 and HIF-1a in men with diabetes. These data support the possibility of hypoxia-mediated ED in diabetes via upregulation of p53 and HIF-1a but does not substantiate a role for TGFbeta in ED.
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PMID:Loss of TGFbeta, Apoptosis, and Bcl-2 in Erectile Dysfunction and Upregulation of p53 and HIF-1alpha in Diabetes-Associated Erectile Dysfunction. 1085 11

Several pharmacological treatments for erectile dysfunction (ED) have recently been introduced. This study performed during 1999 shows that in Sweden mostly men in their 60's, often with circulatory disease and/or diabetes, where the ones who were treated for ED. The most frequently used drug (80%) is sildenafil (Viagra). The mean consumption is 4.8 tablets per month, the same consumption as for intracavernous prostaglandin injections. The pattern of prescription doesn't differ between general practitioners and urological surgeons. No evidence for "overconsumption" became evident in the study. Presently, the majority of men who seek help for ED are middle-aged, have circulatory disease and are prescribed sildenafil (Viagra).
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PMID:[Viagra is first choice preparation in the treatment of erectile dysfunction. Access to a variety of methods makes individual treatment possible]. 1088 22

The most common physical risk factors for erectile dysfunction (ED) are atherosclerosis, heart disease, hypertension and diabetes. Since accessibility to easy and efficacy drug for ED therapy, GPs are increasingly at the front line in the management of ED and are often best-placed to discuss this problem with cardiovascular male patients. This consensus aims to provide practical advice on the management of ED in patients with diagnosed cardiovascular disease and also addresses the assessment of the cardiovascular risk in restoring sexual activity in these patients. A risk assessment algorithm has been drawn up to aid clinicians in deciding the level of cardiovascular risk that would be associated with a return of sexual activity as well as criteria for referral to specialists for further cardiac evaluation. Treatment options are briefly reviewed and follow-up process identified.
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PMID:[Consensus on the clinical approach to erectile dysfunction in patients with cardiovascular disease]. 1094 13

Despite the well-documented relationship of socioeconomic factors (SEF) to various health problems, the relationship of SEF to erectile dysfunction (ED) is not well understood. As such, the goals of this paper are: (1) to determine whether incident ED is more likely to occur among men with low SEF; and (2) to determine whether incident ED varies by SEF after taking into consideration other well-established ED risk factors that are also associated with SEF such as smoking, diabetes, and high blood pressure. We used data from 797 participants in the longitudinal population-based Massachusetts Male Aging Study (baseline 1987-1989, follow-up 1995-1997) who were free of ED at baseline and had complete data on ED and all risk factors. ED was determined by a self-administered questionnaire and its relationship to SEF was assessed using logistic regression. We first analyzed the age-adjusted relationship of education, income, and occupation to incidence of ED. The results show that men with low education (O.R. = 1.46, 95% C.I. = 1.02-2.08) or men in blue-collar occupations (O.R. = 1.68, 95% C.I. = 1.16-2.43) are significantly more likely to develop ED. For the multivariate model, due to multicollinearity among education, income, and occupation, we ran three separate models. After taking into consideration all the other risk factors--age, lifestyle and medical conditions--the effect of occupation remained significant. Men who worked in blue-collar occupations were one and a half times more likely to develop ED compared to men in white-collar occupations (O.R. = 1.55, 95% C.I. = 1.06-2.28).
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PMID:Socioeconomic factors and incidence of erectile dysfunction: findings of the longitudinal Massachussetts Male Aging Study. 1097 36

Erectile dysfunction (ED) is a common problem in general medical practice affecting especially the elderly and those with cardiovascular disease and diabetes mellitus. A study was undertaken by questionnaire distributed to consecutive adult male attendees at 62 general medical practices. 1240 completed questionnaires were available for analysis. The mean age of participants was 56.4y (range 18-91 y). 488 men (39.4%) reported ED: 119 (9.6%) 'occasionally', 110 (8.9%) 'often', and 231 (18.6%) 'all the time' (complete ED). Among 707 men aged 40-69y 240 (33.9%) reported ED and 84 (11.9%) had complete ED. The prevalence of complete ED increased with age, rising from 2.0% in the 40-49 y age group to 44.9% in the 70-79 y age group. Only 11.6% of men with ED had received treatment. Hypertension, ischaemic heart disease, peripheral vascular disease and diabetes mellitus were frequently associated with ED. 40% of diabetic men aged 60 y or older had ED all the time.
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PMID:Erectile dysfunction in general medicine practice: prevalence and clinical correlates. 1098 11

Apomorphine SL (TAP Holdings, Deerfield, IL) is a centrally acting treatment for erectile dysfunction (ED) that has been undergoing phase III trials. Over 3000 men have received apomorphine SL and over 75,000 doses have been taken. In the first three phase III parallel arm cross-over double-blind studies 854 patients were given a total of 8263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 y old and outcome measures included per attempt rates of intercourse and erections firm enough for intercourse as well as psychometric instruments and partner responses. The majority (74.1%) had moderate and severe grades of ED on admission to the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia and 16% had diabetes. Erections occurred rapidly (10-25 min) and in 54.4% of attempts at 4 mg (vs 33.8% placebo). A majority of the attempts at intercourse (50.6%) were successful at 4 mg in patients when recorded on a per-attempt basis. The most common but infrequent and mild side effect of nausea decreases with use. The phase III trials of apomorphine SL show that there is a clinically important restoration of erectile function from this new formulation of apomorphine. It has a rapid and safe effect through action in the central nervous system. Apomorphine SL brings a new choice to the management of ED that will further benefit the millions of couples affected. International Journal of Impotence Research (2000) 12, Suppl 4, S67-S73.
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PMID:Apomorphine: an update of clinical trial results. 1103 90


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