Effects of sildenafil on lipid profile and glycemic control in patients with type 2 diabetes mellitus and metabolic syndrome
Keywords:Sildenafil, Obesity, Type 2 diabetes mellitus, Metabolic syndrome
Background: Insulin resistance impairs nitric oxide (NO) bioavailability; obesity promotes a state of metabolic syndrome and damages the vascular endothelium by altering lipid profile. Phosphodiesterase-5 (PDE-5) inhibitors restore NO signaling may improve metabolic parameters through a number of mechanisms. We hypothesized that daily administration of the PDE-5 inhibitor; sildenafil will improve fasting plasma glucose (FPG), triglyceride (TG) levels and body weight, in obese diabetic patients.
Methods: Totally, 25 obese diabetic male patients with metabolic syndrome treated with sildenafil 25 mg daily for 3 months. Body weight, FPG levels, and lipid profile were determined monthly.
Results: Treatment with sildenafil caused a reduction in fasting glucose levels, fasting TGs, cholesterol, low-density lipoprotein (LDL), very-LDL and increased high-density lipoprotein; body weight was significantly reduced.
Conclusion: We have provided the first evidence that sildenafil therapy improve glycemic control, lipid profile and body mass index in diabetic patients with metabolic syndrome.
Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome: definitions and controversies. BMC Med. 2011;9:48.
Matsuzawa Y, Funahashi T, Nakamura T. The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism. J Atheroscler Thromb. 2011;18(8):629-39.
Lugnier C. PDE inhibitors: a new approach to treat metabolic syndrome? Curr Opin Pharmacol. 2011;11(6):698-706.
Karelis AD, Pasternyk SM, Messier L, St-Pierre DH, Lavoie JM, Garrel D, et al. Relationship between insulin sensitivity and the triglyceride-HDL-C ratio in overweight and obese postmenopausal women: a MONET study. Appl Physiol Nutr Metab. 2007;32(6):1089-96.
Ho JE, Arora P, Walford GA, Ghorbani A, Guanaga DP, Dhakal BP, et al. Effect of phosphodiesterase inhibition on insulin resistance in obese individuals. J Am Heart Assoc. 2014;3(5):e001001.
Onesi SO, Ignatius UE. Metabolic syndrome: performance of five different diagnostic criterias. Indian J Endocrinol Metab. 2014;18(4):496-501.
Ayala JE, Bracy DP, Julien BM, Rottman JN, Fueger PT, Wasserman DH. Chronic treatment with sildenafil improves energy balance and insulin action in high fat-fed conscious mice. Diabetes. 2007;56(4):1025-33.
Tooke J. The association between insulin resistance and endotheliopathy. Diabetes Obes Metab. 1999;1 Suppl 1:
Polte T, Schröder H. Cyclic AMP mediates endothelial protection by nitric oxide. Biochem Biophys Res Commun. 1998;251(2):460-5.
Aboryag NB, Mahmoud AM, Ramadan SA. Sildenafil alleviate insulin sensitivity via attenuating oxidative stress and proinflammatory cytokine production in diabetic rats. Int J Pharm Bio Sci. 2013;4(4):B427-36.
Handa P, Tateya S, Rizzo NO, Cheng AM, Morgan-Stevenson V, Han CY, et al. Reduced vascular nitric oxide-cGMP signaling contributes to adipose tissue inflammation during high-fat feeding. Arterioscler Thromb Vasc Biol. 2011;31(12):2827-35.
Tateya S, Rizzo NO, Handa P, Cheng AM, Morgan-Stevenson V, Daum G, et al. Endothelial NO/cGMP/VASP signaling attenuates Kupffer cell activation and hepatic insulin resistance induced by high-fat feeding. Diabetes. 2011;60(11):2792-801.
Lasar D, Julius A, Fromme T, Klingenspor M. Browning attenuates murine white adipose tissue expansion during postnatal development. Biochim Biophys Acta. 2013;1831(5):960-8.
Mitschke MM, Hoffmann LS, Gnad T, Scholz D, Kruithoff K, Mayer P, et al. Increased cGMP promotes healthy expansion and browning of white adipose tissue. FASEB J. 2013;27(4):1621-30.