sildenafil-citrate and Prediabetic-State

Sildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance.. The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function.. This was a randomized, double-blind, placebo-controlled study.. This trial was conducted at Vanderbilt Clinical Research Center.. Participants included overweight individuals with prediabetes.. Subjects were randomized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months. Subjects underwent a hyperglycemic clamp prior to and at the end of treatment.. The primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion.. Twenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per μU/mL*100 (95% confidence interval, 0.01 to 3.67 mg/kg/min per μU/mL*100; P = .049), after adjusting for baseline insulin sensitivity index and body mass index. In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion (P > .30). Sildenafil decreased plasminogen activator inhibitor-1 (P = .01), without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 μg/mg Cr. This effect persisted 3 months after sildenafil discontinuation.. Three-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function.

Topics: Adult; Albuminuria; Double-Blind Method; Endothelium, Vascular; Female; Fibrinolysis; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Hemodynamics; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Overweight; Phosphodiesterase 5 Inhibitors; Plasminogen Activator Inhibitor 1; Prediabetic State; Sildenafil Citrate

To evaluate the results of using Sildenafil in the form of an oral spray (Gent) for the treatment of erectile dysfunction (ED) in men with type 2 diabetes mellitus (DM) and prediabetes.. A total of 60 patients were divided into two groups of 30 people. The group 1 included patients with prediabetes, while group 2 consisted of patients with type 2 DM. All men had proven ED. The severity of ED was assessed using the International Index of Erectile Function (IIEF-5). To assess the state of penile blood flow, all patients underwent Doppler ultrasound before and after treatment. Patients with prediabetes used Sildenafil in the form of oral spray (Gent) 25 mg (2 doses) 1 time per day for 1 month, patients with type 2 diabetes received 50 mg (4 injections) every other day for 1 month. In addition, most of the subjects took metformin and followed diet therapy.. In patients of both groups, the administration of Sildenafil oral spray led to a decrease in body weight, waist circumference, a decrease in insulin and Hemoglobin A1C level without changing of hypoglycemic therapy in those with type 2 DM. In men with prediabetes, a decrease in fasting insulin levels was found. During treatment, half of the persons with impaired glucose metabolism had an increase in the testosterone level. According to IIEF-5, a decrease in the severity of ED in both groups of patients was seen. In men with prediabetes, the average IIEF-5 score increased from 15.98 to 21.57 points (p<0.05), while in patients with type 2 DM it improved from 12.18 to 18.44 points (p<0.05). Doppler ultrasound indicated a significant increase in the maximum systolic blood flow velocity and arterial resistivity index after treatment with Sildenafil oral spray in patients with both prediabetes and type 2 diabetes.. Sildenafil oral spray can be effectively used for the treatment of ED in men with type 2 DM and prediabetes.

Topics: Diabetes Mellitus, Type 2; Erectile Dysfunction; Humans; Insulins; Male; Oral Sprays; Piperazines; Prediabetic State; Purines; Sildenafil Citrate; Treatment Outcome

Erectile dysfunction frequently coexists with coronary artery disease and has been proposed as a potential marker for silent coronary artery disease in type 2 diabetes. In the present study, we comparatively assessed the structural and functional changes of both penile arteries (PAs) and coronary arteries (CAs) from a prediabetic animal model. PAs and CAs from 17- to 18-wk-old obese Zucker rats (OZRs) and from their control counterparts [lean Zucker rats (LZRs)] were mounted in microvascular myographs to evaluate vascular function, and stained arteries were subjected to morphometric analysis. Endothelial nitric oxide (NO) synthase (eNOS) protein expression was also assessed. The internal diameter was reduced and the wall-to-lumen ratio was increased in PAs from OZRs, but structure was preserved in CAs. ACh-elicited relaxations were severely impaired in PAs but not in CAs from OZRs, although eNOS expression was unaltered. Contractions to norepinephrine and 5-HT were significantly enhanced in both PAs and CAs, respectively, from OZRs. Blockade of NOS abolished endothelium-dependent relaxations in PAs and CAs and potentiated norepinephrine and 5-HT contractions in arteries from LZRs but not from OZRs. The vasodilator response to the phosphodiesterase 5 inhibitor sildenafil was reduced in both PAs and CAs from OZRs. Pretreatment with SOD reduced the enhanced vasoconstriction in both PAs and CAs from OZRs but did not restore ACh-induced relaxations in PAs. In conclusion, the present results demonstrate vascular inward remodeling in PAs and a differential impairment of endothelial relaxant responses in PAs and CAs from insulin-resistant OZRs. Enhanced superoxide production and reduced basal NO activity seem to underlie the augmented vasoconstriction in both PAs and CAs. The severity of the structural and functional abnormalities in PAs might anticipate the vascular dysfunction of the more preserved coronary vascular bed.

Topics: Acetylcholine; Animals; Arteries; Cholesterol; Coronary Vessels; Endothelium, Vascular; Enzyme Inhibitors; Erectile Dysfunction; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Nitroarginine; Obesity; Penis; Piperazines; Prediabetic State; Purines; Rats; Rats, Zucker; Sildenafil Citrate; Sulfones; Superoxides; Triglycerides; Vasoconstriction; Vasodilation; Vasodilator Agents