Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and safety of intracavernosal alprostadil was evaluated for the treatment of erectile dysfunction in men with type I or type II diabetes mellitus. This was an open-label, flexible dose-escalating study involving 336 men (77% of whom were Asian/Oriental) enrolled by 15 centres in Australia, Canada and seven countries in Asia. The effective alprostadil dose, ie the dose producing penile rigidity adequate for intercourse and lasting up to 60 min, was established by titration at the clinic prior to entry into the 6 month self-treatment home phase. All men were fully trained in the self-injection technique before entry into the home phase. Efficacy and safety were assessed using patient and partner diaries and by interview at clinic visits during the titration phase and after 1, 3 and 6 months of treatment. An effective home dose was established by titration for 94% of the 336 men (median dose 20 microg, range 2.5-60 microg). Of 278 (83%) men who entered the home phase, 277 men (247 with type II diabetes and 30 with type I diabetes) had evaluable data for alprostadil dosage and clinical response. During the home phase, a satisfactory erectile response was achieved after 99% of injections, and the median alprostadil dose remained unchanged. The initial home dose and clinical response were similar in type I and type II diabetic men. Treatment was generally well tolerated with a low incidence of penile pain (24%) In conclusion, intracavernosal alprostadil was effective and well tolerated in type I and type II diabetic men with erectile dysfunction of mixed aetiology.
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PMID:Intracavernosal alprostadil is effective for the treatment of erectile dysfunction in diabetic men. 1191 46

Hypertension is poorly controlled in most patients. The control rate, defined as a systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg, is 27% in the USA, despite data documenting the reduction of cardiovascular events by treating diastolic hypertension and isolated systolic hypertension. Control rate is even lower for patients with renal insufficiency and type 2 diabetes mellitus. Thus, monotherapy is unlikely to achieve blood pressure control. Supported by the 6th Joint National Committee Report (JNC VI), interest has been sparked in the use of fixed low-dose combination drugs as first-line treatment of hypertension. The rationale is to enhance hypertension control by using drugs that are additive while avoiding complex regimens that result in non-compliance. When low doses of two drugs are used, adverse drug reactions are fewer compared with the maximal dose of each drug tested separately. Multifactorial trials document the efficacy of hydrochlorothiazide (HCTZ) 6.25 mg in combination with bisoprolol 2.5-10 mg once daily. DBP control rates have been 64-77% and equal to or superior to HCTZ 25 mg once daily, amlodipine 2.5-10 mg once daily, enalapril 5-40 mg once daily or losartan 50-100 mg and losartan 50 mg with 12.5 mg HCTZ once daily. This low-dose combination has a side-effect profile similar to placebo. Erectile dysfunction and hypokalaemia are uncommon. Fixed-dose combination antihypertensive drugs simplify dosing regimens, improve compliance, improve hypertension control, decrease dose-dependent side-effects, and reduce cost as the first-line treatment of hypertension.
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PMID:Fixed low-dose combination in first-line treatment of hypertension. 1199 95

Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of DAN has not been fully appreciated. The reported prevalence of DAN varies widely depending on the cohort studied and the methods of assessment. In randomly selected cohorts of asymptomatic individuals with diabetes, approximately 20% had abnormal cardiovascular autonomic function. DAN frequently coexists with other peripheral neuropathies and other diabetic complications, but DAN may be isolated, frequently preceding the detection of other complications. Major clinical manifestations of DAN include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, "brittle diabetes," and hypoglycemic autonomic failure. DAN may affect many organ systems throughout the body (e.g., gastrointestinal [GI], genitourinary, and cardiovascular). GI disturbances (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, and fecal incontinence) are common, and any section of the GI tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control. Upper-GI symptoms should lead to consideration of all possible causes, including autonomic dysfunction. Whereas a radiographic gastric emptying study can definitively establish the diagnosis of gastroparesis, a reasonable approach is to exclude autonomic dysfunction and other known causes of these upper-GI symptoms. Constipation is the most common lower-GI symptom but can alternate with episodes of diarrhea. Diagnostic approaches should rule out autonomic dysfunction and the well-known causes such as neoplasia. Occasionally, anorectal manometry and other specialized tests typically performed by the gastroenterologist may be helpful. DAN is also associated with genitourinary tract disturbances including bladder and/or sexual dysfunction. Evaluation of bladder dysfunction should be performed for individuals with diabetes who have recurrent urinary tract infections, pyelonephritis, incontinence, or a palpable bladder. Specialized assessment of bladder dysfunction will typically be performed by a urologist. In men, DAN may cause loss of penile erection and/or retrograde ejaculation. A complete workup for erectile dysfunction in men should include history (medical and sexual); psychological evaluation; hormone levels; measurement of nocturnal penile tumescence; tests to assess penile, pelvic, and spinal nerve function; cardiovascular autonomic function tests; and measurement of penile and brachial blood pressure. Neurovascular dysfunction resulting from DAN contributes to a wide spectrum of clinical disorders including erectile dysfunction, loss of skin integrity, and abnormal vascular reflexes. Disruption of microvascular skin blood flow and sudomotor function may be among the earliest manifestations of DAN and lead to dry skin, loss of sweating, and the development of fissures and cracks that allow microorganisms to enter. These changes ultimately contribute to the development of ulcers, gangrene, and limb loss. Various aspects of neurovascular function can be evaluated with specialized tests, but generally these have not been well standardized and have limited clinical utility. Cardiovascular autonomic neuropathy (CAN) is the most studied and clinically important form of DAN. Meta-analyses of published data demonstrate that reduced cardiovascular autonomic function as measured by heart rate variability (HRV) is strongly (i.e., relative risk is doubled) associated with an increased risk of silent myocardial ischemia and mortality. The determination of the presence of CAN is usually based on a battery of autonomic function tests rather than just on one test. Proceedings from a consensus conference in 1992 recommended that three tests (R-R variation, Valsalva maneuver, and postural blood pressure testing)or longitudinal testing of the cardiovascular autonomic system. Other forms of autonomic neuropathy can be evaluated with specialized tests, but these are less standardized and less available than commonly used tests of cardiovascular autonomic function, which quantify loss of HRV. Interpretability of serial HRV testing requires accurate, precise, and reproducible procedures that use established physiological maneuvers. The battery of three recommended tests for assessing CAN is readily performed in the average clinic, hospital, or diagnostic center with the use of available technology. Measurement of HRV at the time of diagnosis of type 2 diabetes and within 5 years after diagnosis of type 1 diabetes (unless an individual has symptoms suggestive of autonomic dysfunction earlier) serves to establish a baseline, with which 1-year interval tests can be compared. Regular HRV testing provides early detection and thereby promotes timely diagnostic and therapeutic interventions. HRV testing may also facilitate differential diagnosis and the attribution of symptoms (e.g., erectile dysfunction, dyspepsia, and dizziness) to autonomic dysfunction. Finally, knowledge of early autonomic dysfunction can encourage patient and physician to improve metabolic control and to use therapies such as ACE inhibitors and beta-blockers, proven to be effective for patients with CAN.
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PMID:Diabetic autonomic neuropathy. 1271 21

Diabetes is the most common cause of erectile dysfunction (ED). Oxidative stress has been suggested to be a contributory factor in vascular complications of diabetes in various organs. In the present study, we investigated whether oxidative stress is associated with erectile function in non-insulin dependent diabetes mellitus (NIDDM) rats. Fifty-four Sprague-Dawley rats were the subjects of this study. In each rat, NIDDM was induced by an intraperitoneal injection of 90 mg/Kg of streptozotocin on the second day after birth. Based on the diabetic period, they were classified into either short-term or long-term diabetics (avg. 22 weeks, n=18 and avg. 38 weeks, n=20), respectively, and their age-matched controls (n=16). To evaluate the erectile function in each rat, the intracavernous pressure, and latency to maximal pressure, following cavernous nerve stimulation (frequency: 1 Hz, intensity: 3 - 6 V, pulse width: 1 msec, pulse duration: 1 min.) was analyzed. To evaluate both oxidative stress from reactive oxygen species, and antioxidant function as a defense against them, total malondialdehyde and glutathione levels were measured in the corpus cavernosum of the penis, using a spectrophotometric assay. The intracavernous pressure following cavernous nerve stimulation was significantly lower in the long-term (49.8 +/- 9.4 cmH2O) than the short-term diabetics (75.9 +/- 14.8 cm H2O), and markedly decreased in the diabetic rats, compared with their age-matched controls (long-term controls; 60.7 +/- 17.2 cmH2O, short-term controls; 95.2 +/- 20.4 cmH2O). The malondialdehyde content in the corpus cavernosum was markedly increased in the diabetics (2.13 +/- 0.27 nM/mg protein) compared to the controls (1.48 +/- 0.22 nM/mg protein). Furthermore, the glutathione level was significantly decreased in the diabetics, compared to age-matched controls (short-term control; 218.3 +/- 25.6 microM/mg protein, long-term control; 150.2 +/- 9.8 microM/mg protein). In the diabetic groups, it was more significantly decreased in the long-term diabetics (134.8 +/- 11.3 microM/mg protein) than in short-term diabetics (182.1 +/- 18.8 microM/mg protein). NIDDM causes erectile dysfunction, which slowly progresses. Oxidative stress to cavernous tissue may be a contributory factor in erectile dysfunction in diabetics.
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PMID:The role of free radical in the pathogenesis of impotence in streptozotocin-induced diabetic rats. 1272 63

The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis, obesity and sexual function in middle-aged men with type 2 diabetes and mild androgen deficiency. Forty-eight middle-aged men, with type 2 diabetes, (visceral) obesity and symptoms of androgen deficiency, were included in this open-label study. Twenty-four subjects received testosterone undecanoate (TU; 120 mg daily, for 3 months); 24 subjects received no treatment. Body composition was analyzed by bio-impedance. Parameters of metabolic control were determined. Symptoms of androgen deficiency and erectile dysfunction were scored by self-administered questionnaires. TU had a positive effect on (visceral) obesity: statistically significant reduction in body weight (2.66%), waist-hip ratio (-3.96%) and body fat (-5.65%); negligible changes were found in the control group. TU significantly improved metabolic control: decrease in blood glucose values and mean glycated hemoglobin (HbA1c) (from 10.4 to 8.6%). TU treatment significantly improved symptoms of androgen deficiency (including erectile dysfunction), with virtually no change in the control group. There were no adverse effects on blood pressure or hematological, biochemical and lipid parameters, and no adverse events. Oral TU treatment of type 2 diabetic men with androgen deficiency improves glucose homeostasis and body composition (decrease in visceral obesity), and improves symptoms of androgen deficiency (including erectile dysfunction). In these men, the benefit of testosterone supplementation therapy exceeds the correction of symptoms of androgen deficiency and also includes glucose homeostasis and metabolic control.
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PMID:Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. 1280 74

The aims of this study were to determine the incidence rates of genital calcification in male hemodialysis patients based on ultrasonography findings and to identify risk factors for this condition. Twenty-three male end-stage renal disease (ESRD) patients (mean age, 51.4 +/- 12.1 years) who were on maintenance hemodialysis underwent penile and scrotal ultrasonography. For each case, we recorded the underlying renal disease and measured serum levels of phosphorus, intact parathormone, and calcium x phosphorus product. Patients were also questioned about erectile dysfunction. The control group consisted of 22 consecutive patients (mean age, 51 years) with type 2 diabetes mellitus with normal renal function who underwent penile and scrotal ultrasonography for various reasons. In the ESRD group, ultrasound revealed calcification of the tunica albuginea of the corpora cavernosa in 15 patients (65%) and calcification of the epididymis in 16 patients (70%; 14 bilateral and 2 unilateral cases). Twenty patients (87%) showed calcification of the epididymis and/or the tunica, and 10 (43%) showed calcification of both these tissues. The rates of epididymal and penile calcification in the ESRD patients and the controls were significantly different (P <.001 for both). There were no significant differences between patients with and without penile and epididymal calcification with respect to age, hemodialysis duration, frequencies of elevated serum phosphorus, elevated serum intact parathormone, elevated calcium x phosphorus product, and frequency of erectile dysfunction (ED) (P >.05 for all). Ultrasonography revealed high rates of penile (tunica albuginea of the corpora cavernosa) and epididymal calcification (65% and 70%, respectively) in the ESRD patients studied, but no association was found between risk factors such as age, underlying renal disease, hemodialysis duration, frequencies of elevated serum phosphorus, elevated serum intact parathormone, and elevated calcium x phosphorus product.
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PMID:Calcification of the epididymis and the tunica albuginea of the corpora cavernosa in patients on maintenance hemodialysis. 1529 6

Erection is a neurovascular event that involves spinal and supra spinal pathways. The final common pathway involves the release of nitric oxide (NO) from both endothelial cells and neurons, which acts as a vasodilator causing penile engorgement and erection. NO is degraded by the enzyme phosphodiesterase (PDE) type 5 in the penis. Erectile dysfunction (ED), defined as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual performance, results when the neurovascular pathway is interrupted by medical conditions or drugs. A 15-item self-administered questionnaire, the International Index of Erectile Function (IIEF), is one of the most useful tools to evaluate erectile function (EF) in clinical trials, although of much less use in routine clinical practice. The MMAS (Massachusetts Male Aging Study) was the first major epidemiological investigation to study the prevalence of ED. The study found that ED was three times more common in patients with diabetes mellitus. The aetiopathogenesis of ED in diabetes is multifactorial, with vascular and neural factors being equally implicated. Hyperglycaemia is believed to give rise to biochemical perturbations that lead to these microvascular changes. In the MMAS, ED in diabetes was strongly correlated with glycaemic control, duration of disease and diabetic complications. The incidence increased with increasing age, duration of diabetes and deteriorating metabolic control, and was higher in individuals with type 2 diabetes than those with type 1.ED in men with diabetes often affects their quality of life and, as patients are often reluctant to come forward with their symptoms, a carefully taken history is one of the most useful approaches in identifying affected individuals. The PDE inhibitors have revolutionised the management of ED and oral drug therapy is currently first-line therapy for the condition. These agents act by potentiating the action of intracavernosal NO, thereby leading to a more sustained erection. Sildenafil was the first PDE5 inhibitor to undergo evaluation and has been studied extensively. More recently two other agents, vardenafil and tadalafil, have been introduced. All the drugs have been shown to be effective across a wide range of aetiologies of ED, including diabetes. The drugs have been shown to improve EF domain scores, penetration and maintenance of erection, resulting in more successful intercourse. Their effects are greater at higher doses. Sildenafil and vardenafil are shorter-acting agents, while tadalafil has a longer half-life allowing the user more flexibility in sexual activity. Common adverse effects include headache, nasal congestion and dyspepsia, all actions related to inhibition of PDE5. The drugs are generally well tolerated and withdrawal from the clinical studies as a result of drug-related adverse effects were rare. The use of PDE5 inhibitors in the presence of oral nitrates is absolutely contraindicated. The clinical studies to date have not evaluated the use of one drug in the case of treatment failure with another agent. Sublingual apomorphine, which stimulates central neurogenic pathways, is a new agent and may be a suitable alternative in those patients in whom PDE5 inhibitors are ineffective or contraindicated. In clinical trials, all IIEF domains except sexual desire were found to have improved after apomorphine. The median times to erection in these studies were 18.9 and 18.8 minutes for the 2 and 3mg doses, respectively. Intraurethral and intracavernosal alprostadil may be a useful alternative when oral drug therapy is ineffective or contraindicated. The management of ED in the diabetic patient may often involve a multidisciplinary approach where psychosexual counselling and specialist urologist advice is required in addition to the skills and expertise of the diabetologist. Finally, the introduction of the new oral agents have completely revolutionised the management of ED and allowed more individuals to come forward for treatment.
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PMID:New treatment options for erectile dysfunction in patients with diabetes mellitus. 1553 69

The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essential cofactor for nitric oxide (NO) synthase that synthesizes NO from l-arginine. Reduced levels of GSH, due both to a hyperglycaemia-induced increase of free radical production and to a decrease of NADPH levels [like in diabetes mellitus (DM)], can hamper the endothelial cell functions. This condition may play an important role in the aetiology of some clinical signs, like erectile dysfunction (ED). The aim of this study was to test the hypothesis that GSH concentration is reduced in patients with ED and type 2 diabetes mellitus. We studied 111 male patients with ED: 64 with diabetes (ED/DM) and 47 without diabetes (ED/wDM); 20 patients with diabetes but without ED (DM) and 26 male normal subjects as a control group (C). The GSH red blood cell concentration was significantly lower in ED than in C (X +/- SD; 1782.12 +/- 518.02 vs. 2269.20 +/- 231.56 mumol/L, p < 0.001). In particular, GSH was significantly reduced in ED/DM vs. ED/wDM (1670.74 +/- 437.68 vs. 1930.63 +/- 581.01 micromol/L, p < 0.01). In DM, GSH was significantly lower than in C and significantly higher than in ED/DM (2084.20 +/- 118.14 vs. 2269.20 +/- 231.56 and vs. 1670.74 +/- 437.68 micromol/L, p < 0.002 and p < 0.001 respectively). GSH showed a negative correlation with fasting glucose concentrations (r = -0.34, p < 0.01) and with the duration of DM (r = -0.25, p < 0.05). A GSH depletion can lead to a reduction of NO synthesis, thus impairing vasodilation in the corpora cavernosa.
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PMID:Glutathione levels in patients with erectile dysfunction, with or without diabetes mellitus. 1591 May 41

The cyclic nucleotide signalling pathway mediates the smooth-muscle relaxing effects of nitric oxide necessary for normal erectile function. Down-regulation of this pathway is central to the pathophysiology of many forms of erectile dysfunction (ED), which is often associated with other chronic diseases (e.g. hypertension, type 2 diabetes mellitus) and treatments (e.g. certain drugs, radical prostatectomy). Conversely, selective inhibition of the enzyme that catalyses the degradation of cGMP (phosphodiesterase type 5, PDE-5) promotes erectile responses to sexual stimulation. The successful launch and commercialization of the selective PDE5 inhibitor (PDE5I) sildenafil transformed the treatment of ED, not only by providing an effective, well tolerated oral ED therapy, but also by fostering greater candour about the problem among men. Sildenafil is highly effective in promoting erectile responses across a wide spectrum of severity and causes of ED, including patients with ED that is often refractory to treatment. The recent advent of vardenafil, which has the highest in vitro potency of all available PDE5Is, and tadalafil, which has a prolonged half-life that may enable couples to have sexual activity with less planning, represent further advances. Other PDE5Is offering further potential improvements are under active investigation.
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PMID:Phosphodiesterase type 5 inhibitors for erectile dysfunction. 1604 13

Diagnosis of erectile dysfunction (ED) requires anamnestic investigation, being rarely spontaneously declared by patients. ED occurs frequently in diabetes mellitus, and anecdotal evidence suggests that ED occurs in obesity and in hypothyroidism. The aim of this study was to evaluate the prevalence of ED in patients affected by thyroid disorders (hypothyroidism and hyperthyroidism), in comparison with control subjects and with patients at risk for ED, such as patients with obesity and with type II diabetes mellitus, and the role of age. Spontaneous deposition and International Index of Erectile Dysfunction (IIEF)-5 questionnaire were considered for control subjects and for all patients. Spontaneous deposition of ED occurred for three diabetic patients, never for obese patients, thyroid patients and controls, confirming the value of IIEF-5 in detecting ED. ED was more frequent in obese subjects (42%), and in patients affected by thyroid diseases (59%), than in controls (30%), although less frequent than in type II diabetes mellitus (81%). Both below and above the age of 50 years, ED score was worse in thyroid patients than in control subjects, while ED was more frequent in obese patients than in control subjects only below the age of 50 years.
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PMID:Prevalence of erectile dysfunction in thyroid disorders: comparison with control subjects and with obese and diabetic patients. 1607 3


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