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Query: UMLS:C0011854 (type 1 diabetes)
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To improve diabetes care according to the St. Vincent Declaration an interdisciplinary working group on erectile dysfunction in patients with diabetes was installed in the Departments of Internal Medicine, Urology and Psychiatry at the University of Graz. The screening and basic diagnostic procedures are performed in the diabetes clinic in the Department for Internal Medicine. To inform the patients about the options of treatment of diabetic erectile dysfunction and to determine prevalence data an anonymous questionnaire with a pre-stamped envelope was sent to 133 male patients with diabetes mellitus type I (IDDM). 59 (44%) of the questionnaires were returned and could be analyzed. Mean age and diabetes duration were representative for the male diabetes population. The prevalence of erectile dysfunction in this group was 49%. 7% of the patients were completely impotent. None of the patients reported the use of erection aids as a vacuum device or intracavernosal injection of smooth muscle-relaxant drugs. The prevalence of erectile dysfunction is high among patients with diabetes mellitus type I. Modern management offers satisfactory success in most cases, therefore screening for erectile dysfunction and adequate therapy should be offered to all patients.
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PMID:[Erectile dysfunction in patients with type I diabetes mellitus]. 856 Sep 2

We determined arterial venous and sinusoidal factors in 20 patients with insulin dependent diabetes mellitus and erectile dysfunction by performing dynamic infusion cavernosometry (DIC), colour flow Doppler ultrasonography, penile biothesiometry and corpus cavernosum electromyography (CCE). DIC, colour flow Doppler ultrasonography and penile biothesiometry were done in standard fashion except for CCE. Paradoxical increase in the electrical activity of corpus cavernosum after intracavernous (IC) papaverine was called a discoordination that was due to cavernous smooth muscle contraction instead of relaxation. Arterial and accompanying pathologies were found in 10 (50%) patients. In 3 (15%) of them pure arterial pathology, in 6 (30%) patients arterial and veno-occlusive dysfunction (VOD) and in one patient arterial pathology with abnormal biothesiometry were found. VOD and accompanying pathologies were found in 12 (60%) patients. In 6 (30%) of them VOD and arterial, in 4 (20%) patients VOD and discoordination and in 2 (10%) patients VOD and abnormal biothesiometric values were present. A higher frequency and coexistence of VOD and discoordination pattern were observed. In conclusion, patients with diabetic impotence show a wide range pathophysiology of erection and the evaluation of these patients must include multistep techniques.
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PMID:Multifactorial evaluation of diabetic erectile dysfunction. 906 35

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

The occurrence of both autoimmune endocrinopathies and endocrinopathies caused by other reasons is called polyglandular autoimmune syndrome (PAS-syndrome). In a 34 years old man with weakness, weight loss and erectile dysfunction we found low cortisol caused by an autoimmune adrenalitis and low testosterone caused by a hypophysitis with impaired gonadotropin secretion. Thyroid autoantibodies and islet cell autoantibodies without any hormone deficiencies were further signs of a broad endocrine autoimmune syndrome. In the following 11 years the patient developed three autoimmune disorders: paradrenal glandular insufficiency, hypogonadism caused by hypophysitis, Diabetes mellitus type 1. In the same time several non endocrine autoimmune diseases became manifest: alopecia totalis, vitiligo, retrobulbar neuritis and keratoconjunctivitis.
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PMID:[Alopecia totalis, hypotension and erectile dysfunction in a 34 year old patient. Difficult clarification of a common cause]. 1580 Jul 77

Impaired endothelial nitric oxide synthase (eNOS) function is associated with erectile dysfunction in diabetes mellitus, but the exact molecular basis for the eNOS defect in the diabetic penis remains unclear. We investigated whether hyperglycemia increases O-GlcNAc modification of eNOS in the penis, preventing phosphorylation at the primary positive regulatory site on the enzyme and hampering mechanisms of the erectile response. Type I diabetes mellitus was induced in male rats by alloxan (140 mg/kg, i.p.). After 5 wk, the diabetic rat penis exhibited increased O-GlcNAc modification of eNOS and decreased eNOS phosphorylation at Ser-1177 at baseline compared with the control rat penis; eNOS phosphorylation at Thr-495, Ser-615, and Ser-633 was not affected. In addition, eNOS phosphorylation at Ser-1177 was impaired in the diabetic rat penis in response to penile blood flow (shear stress) elicited by electrical stimulation of the cavernous nerve (ES) and to recombinant human VEGF165. Phosphorylation of Akt, a mediator of shear stress-induced eNOS phosphorylation at Ser-1177, was decreased in the diabetic penis at baseline, but it was restored by ES. Erectile response to shear stress elicited by ES and to VEGF was decreased in diabetic compared with control rats. This work demonstrates that eNOS inactivation occurs in the diabetic penis by a glycosylation mechanism specifically at Ser-1177, by which the enzyme is rendered incapable of activation by fluid shear stress stimuli and VEGF signaling. In vivo penile erection paradigm supports the physiologic relevance of O-GlcNAc modification in vascular disorders associated with diabetes.
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PMID:Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction. 1608 13

Simultaneous pancreas-kidney transplantation (SPK) is the treatment of choice for patients with type 1 diabetes mellitus and end-stage renal disease (ESRD) because it improves survival, is cost-effective, and can mitigate secondary complications of diabetes. Patient-reported outcomes such as quality of life (QoL) have recently received increased attention among transplant recipients. However, the impact of erectile dysfunction on patient QoL has not been investigated in this high-risk group with a history of diabetes and uremia. We applied the International Index of Erectile Function (IIEF) to describe the prevalence and severity of self-reported changes in erectile function after transplantation, comparing the quality of well-being (QWB) index of subgroups of 101 consecutive male SPK recipients with varying degrees of erectile function. Only 21% of patients did not suffer from erectile dysfunction; 18% were classified as mild erectile dysfunction, 31% as mild to moderate, 21% as moderate, and 9% as severe according to the IIEF scores. Forty-one percent of patients reported subjective overall improvement in erectile dysfunction compared with their pretransplant status; 7% considered their sexual function to be worse than before, and 51% did not note any change. The QWB index was highest among the group of patients without erectile dysfunction, decreasing gradually but significantly with increasing severity. A direct impact of erectile dysfunction on QoL, as well as a confounding effect of underlying vascular comorbidities, could explain this finding.
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PMID:Sexual dysfunction after simultaneous pancreas-kidney transplantation. 1855 81

It has recently been demonstrated that > or = one-third of men with type 2 diabetes mellitus have low testosterone concentrations associated with inappropriately low luteinizing hormone and follicle-stimulating hormone concentrations. Hypogonadotropic hypogonadism in men with type 2 diabetes is associated with obesity but not duration of diabetes, elevated glycosylated hemoglobin, or the presence of microvascular complications of diabetes. Recent data show that hypogonadotropic hypogonadism is also observed frequently in nondiabetics with the metabolic syndrome or obesity, but it is not associated with type 1 diabetes. Low testosterone concentrations in men with type 2 diabetes have also been related to a higher C-reactive protein concentrations, lower hematocrit, increased total and regional adiposity, lower bone mineral density, and erectile dysfunction. This article discusses the pathophysiology of hypogonadotropic hypogonadism in men with type 2 diabetes and its signs and symptoms. Clinical trials are required to determine whether testosterone replacement therapy alleviates insulin resistance, inflammation, and symptoms related to sexual dysfunction care.
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PMID:Hypogonadotropic hypogonadism in men with type 2 diabetes. 1949 39

We performed a pilot study of PDE-5 inhibitors efficacy in the treatment of diabetic genital neuropathy. A total of 16 diabetic males (type 1 diabetes mellitus) having erectile dysfunction with symptoms of genital neuropathy entered the trial. These patients received tadalafil for 3 months. The results were assessed with sexological questionnaires and dynamics of genital neuropathy symptoms. Tadalafil treatment was found effective.
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PMID:[Treatment of erectile dysfunction of neurogenic genesis with inhibitors of phosphodiesterase of type 5 in patients with diabetes mellitus]. 2020 71

The metabolic syndrome (MetS) is an insulin-resistant state characterized by a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, elevated blood pressure and combined dyslipidemia. In this review, we discuss the potential of farnesoid X receptor (FXR) agonists in the treatment of erectile dysfunction (ED), a multifactorial disorder often comorbid with MetS. FXR not only regulates lipid and glucose homeostasis but also influences endothelial function and atherosclerosis, suggesting a regulatory role for this hormone nuclear receptor in the cardiovascular complications associated with the MetS, including ED. MetS induces ED via several mechanisms, and in particular through endothelial dysfunction in penile vessels. In a high-fat diet rabbit model of MetS, a 3-month treatment with the potent and selective FXR agonist INT-747 restores endothelium-dependent relaxation in isolated cavernous tissue, normalizing responsiveness to acetylcholine and to electrical field stimulation. Accordingly, eNOS expression in the penis is greatly up-regulated by INT-747 treatment. Experiments in a rat model of chemically-induced type 1 diabetes further demonstrate that INT-747 treatment preserves erectile function induced by electrical stimulation of the cavernous nerve. These results add a new facet to the pleiotropic activities mediated by FXR, and reveal novel beneficial effects of FXR activation with potential clinical relevance. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.
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PMID:Farnesoid X receptor activation improves erectile dysfunction in models of metabolic syndrome and diabetes. 2105 55

This study was designed to investigate the effect of vascular endothelial growth factor 164 adenovirus (Ad-VEGF(164))-transfected mesenchymal stem cells (MSC) on improving erectile function in diabetic rats. Forty-five male Sprague-Dawley rats were injected with streptozotocin to develop type 1 diabetes, whereas 10 served as normal controls. Diabetic rats were randomly divided into 3 groups: rats that underwent intracavernous injection with phosphate-buffered saline (DM+PBS), unmodified MSCs (DM+MSC), and Ad-VEGF(164)-transfected MSCs (DM+VMSC). Normal controls received intracavernous injection of PBS. Four weeks after injection, erectile function was measured by cavernous nerve electrostimulation. Penile tissue was harvested for histology and enzyme-linked immunoassay. Prior to injection, high expression of VEGF was confirmed in Ad-VEGF(164)-transfected MSCs by enzyme-linked immunoassay. Four weeks after injection, the erectile function, as well as the content of smooth muscle and endothelium in corpus cavernosum increased significantly in the MSC-injected groups compared with the DM+PBS group. There was a significant improvement of erectile function, the content of smooth muscle and endothelium, and the VEGF concentration in the corpus cavernosum in the DM+VMSC group compared with the DM+MSC group. Our study validates the effect of intracavernous injection of MSCs for diabetes-associated erectile dysfunction in an animal model. The combined strategy of MSC injection with VEGF gene therapy-enhanced therapy of MSCs for the treatment of diabetes-associated erectile dysfunction.
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PMID:Combined strategy of mesenchymal stem cell injection with vascular endothelial growth factor gene therapy for the treatment of diabetes-associated erectile dysfunction. 2131 Oct 50


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