Introduction: As we know endothelial dysfunction is an initial stage of vascular complications in type 2 diabetes mellitus (DM). Hypoglycaemic drugs have shown a beneficial effect on endothelial function. Insulin is a regulator hormone for endothelial function in vessels. But, there was a controversial report on the effect of exogenous insulin on endothelial function in type 2 diabetes subjects.
Aim and objectives: The study has been designed to observe the effect of insulin therapy on endothelial dysfunction in type 2 diabetic subjects without any complications.
Materials and methods: This Study include 120 Subjects (60-Diabetics and 60-Healthy Controls). MDA was manually estimated by thiobarbituric acid reactive substances (TBARS) method and anti-oxidant capacity was estimated as FRAP.19 NO was measured by using kinetic cadmium reduction method.
Result: Significantly high level of body mass index (BMI) was identified in insulin-treated subjects than subjects with hypoglycemic drugs and healthy controls. Nitric oxide (NO) has shown significantly lower in insulin-treated subjects compared to subjects with hypoglycemic drugs and healthy controls. There was no sign in the levels of lipid profile and oxidative stress in between two treatment groups.
Conclusion: Significant effect of insulin therapy was observed on endothelial dysfunction in type 2 DM. Exogenous insulin itself may cause endothelial dysfunction by hyperinsulinemia because of a high-fat diet or high dosage of insulin.
Stefan RM, Nita C, Craciun A, Rusu A, Hancu N. Effect of the early intensive multifactorial therapy on the cardiovascular risk in patients with newly diagnosed type 2 diabetes: an observational, prospective study. Clujul Medical 2015;88(2):168.
Buchan DS, Thomas NE, and Baker JS. Novel risk factors of cardiovascular disease and their associations between obesity, physical activity and physical fitness. Journal of public health research 2012;1(1):59.
De Pablo P, Dietrich T, Karlson EW. Antioxidants and other novel cardiovascular risk factors in subjects with rheumatoid arthritis in a large population sample. Arthritis Care and Research 2007; 57(6): 953-962.
Atul A, Aggarwal S, Veneet D, Yadav NH. Diabetic Nephropathy: An Updated Review. International Journal of Chemical and Analytical Sciences 2010;1(3):50-57.
Thorand B, Baumert J, Chambless L, Meisinger C, Kolb H, Doring A, et al. Elevated markers of endothelial dysfunction predict type 2 diabetes mellitus in middle-aged men and women from the general population. Arteriosclerosis, thrombosis, and vascular biology. 2006 Feb 1;26(2):398-405.
Horstman LL, Jy W, Jimenez JJ, Ahn YS. Endothelial microparticles as markers of endothelial dysfunction. Front Biosci 2004;9(1):118-135.
Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation 2004;109(23 suppl 1):III-27.
Gkaliagkousi, E., Shah, A., and Ferro, A. Review: Pharmacological and non-pharmacological treatment of endothelial dysfunction: relevance to diabetes. The British Journal of Diabetes and Vascular Disease 2007;7(1):5-10.
Caballero AE, Saouaf R, Lim SC, Hamdy O, Abou-Elenin K, O'Connor C, et al. The effects of troglitazone, an insulinsensitizing agent, on the endothelial function in early and late type 2 diabetes: a placebo-controlled randomized clinical trial. Metabolism. 2003 Feb 1;52(2):173-180.
Arcaro G, Cretti A, Balzano S, Lechi A, Muggeo M, Bonora E, Bonadonna RC. Insulin causes endothelial dysfunction in humans sites and mechanisms. Circulation 2002;105(5):576-582.
Cardillo C, Nambi SS, Kilcoyne CM., Choucair WK, Katz A, Quon M J, Panza J. A. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation 1999;100(8):820-825.
Lott JA, Turner K. Evaluation of Trinder's glucose oxidase method for measuring glucose in serum and urine. Clinical chemistry 1975;21(12):1754-1760.
Engbaek F, Christensen SE, Jespersen B. Enzyme immunoassay of hemoglobin A1c: analytical characteristics and clinical performance for patients with diabetes mellitus, with and without uremia. Clinical chemistry 1989; 35(1): 93-97.
Allain CC, Poon LS, Chan CS, Richmond WFPC, Fu PC. Enzymatic determination of total serum cholesterol. Clinical chemistry 1974;20(4):470-475.
Jacobs NJ, and VanDemark PJ. Method of triglyceride estimation. Arch. Biochem. Biophys 1960;8:250-255.
Grove TH. Effect of reagent pH on determination of high-density lipoprotein cholesterol by precipitation with sodium phosphotungstate-magnesium. Clinical chemistry 1979;25(4):560-564.
Warnick GR, Knopp RH, Fitzpatrick V, Branson L. Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cut points. Clinical Chemistry 1990;36(1):15-19.
Lefevre G, Beljean-Leymarie M, Beyerle F, Bonnefont-Rousselot D, Cristol JP, Therond P, et al. Evaluation of lipid peroxidation by measuring thiobarbituric acid reactive substances. In Annales de biologie clinique 1997;5(3):305-319.
Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Analytical biochemistry 1996;239(1):70-76.
Sun J, Zhang X, Broderick M, Fein H. Measurement of nitric oxide production in biological systems by using Griess reaction assay. Sensors 2003;3(8):276-284.
Sukumar P, Viswambharan H, Imrie H, Cubbon RM, Yuldasheva N, Gage M, Galloway S, Skromna A, Kandavelu P, Santos CX, Gatenby VK. Nox2 NADPH oxidase has a critical role in insulin resistance–related endothelial cell dysfunction. Diabetes. 2013 Jun 1;62(6):2130-2134.
Ceriello A, Assaloni, R, Da Ros R, Maier A, Piconi L, Quagliaro L, Giugliano D. Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation 2005;111(19):2518-2524.
Edwin Ho, Galougahi KK, Liu CC, Bhindi R, Figtree GA. Biological markers of oxidative stress: applications to cardiovascular research and practice. Redox biology 2013;1(1):483-491.
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). The Lancet 1998;352(9131):854-865.
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Matthews DR. Management of hyperglycemia in type 2 diabetes: a patient-centred approach position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care 2012;35(6):1364-1379.
Hollander P. Anti-diabetes and anti-obesity medications: effects on weight in people with diabetes. Diabetes Spectrum 2007;20(3):159.
Khan R. Weight gain and insulin therapy. The British Journal of Diabetes and Vascular Disease 2004;4(4):264-267.
Mazzola N. Review of current and emerging therapies in type 2 diabetes mellitus. The American journal of managed care 2012;18(1 Suppl):S17-S26.
Yki-Järvinen H, Kauppinen-Mäkelin R, Tiikkainen M, Vähätalo M, Virtamo H, Nikkilä K, et al. Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. Diabetologia 2006;49(3):442-451.
Solano MP, Goldberg RB. Lipid management in type 2 diabetes. Clinical Diabetes 2006;24(1):27.
Hisalkar PJ, Patne AB, Fawade MM. Assessment of plasma antioxidant levels in type 2 diabetes patients. Int J Biol Med Res 2012;3(2):1796-1800.
Alam R, Khan S, Salman KA. MDA and antioxidants status in type 2 diabetes mellitus. National Journal of Integrated research in Medicine 2013;4(6):75-78.
Valabhji J, Elkeles RS. Dyslipidaemia in type 2 diabetes: epidemiology and biochemistry. The British Journal of Diabetes and Vascular Disease 2003;3(3):184-189.
Kassem SA, Raz I. Is there evidence that oral hypoglycemic agents reduce cardiovascular morbidity or mortality? No. Diabetes care 2009;32(suppl 2):S337-S341.
Toledo, FG, Sniderman AD, Kelley DE. Influence of hepatic steatosis (fatty liver) on severity and composition of dyslipidemia in type 2 diabetes. Diabetes care 2006;29(8):1845- 1850.
Ajjan RA, Grant PJ. Cardiovascular disease prevention in patients with type 2 diabetes: the role of oral anti-diabetic agents. Diabetes and Vascular Disease Research 2006;3(3):147-158.
Song F, Jia W, Yao Y, Hu Y, Lei L, Lin J, et al. and Liu, L. Oxidative stress, antioxidant status and DNA damage in patients with impaired glucose regulation and newly diagnosed Type 2 diabetes. Clinical Science 2007;112(12):599-606.
Wolff SP, Dean RT. Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation'in diabetes. Biochemical Journal 1987;245(1):243-250.
Jain SK, Lim G. Pyridoxine and pyridoxamine inhibits superoxide radicals and prevents lipid peroxidation, protein glycosylation, and (Na++ K+)-ATPase activity reduction in high glucose-treated human erythrocytes. Free Radical Biology and Medicine 2001;30(3):232-237.
Tiwari BK, Pandey KB, Abidi AB, Rizvi SI. Markers of oxidative stress during diabetes mellitus. Journal of biomarkers 2013;2013:1-8.
Davis BJ, Xie Z, Viollet B, Zou MH. Activation of the AMPactivated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes 2006;55(2):496-505.
Triggle CR, Ding H. Cardiovascular impact of drugs used in the treatment of diabetes. Therapeutic advances in chronic disease 2014;5(6):245-268.
Tousoulis D, Kampoli AM, Stefanadis C. Diabetes mellitus and vascular endothelial dysfunction: current perspectives. Current vascular pharmacology 2012;10(1):19-32.
Hamilton, S. J., Chew, G. T., and Watts, G. F. Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus. Diabetes and Vascular Disease Research 2007;4(2):89-102.
De Vriese AS, Verbeuren TJ, Van de Voorde J, Lameire NH, and Vanhoutte, P. M. Endothelial dysfunction in diabetes. British journal of pharmacology 2000;130(5):963-974.
Shanik MH, Xu Y, Skrha J, Dankner R, Zick Y, Roth J. Insulin resistance and hyperinsulinemia: Is hyperinsulinemia the cart of the horse?. Diabetes care 2008;31:S262-S268.
Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006; 2006;444(7121):840-846.
Cao W, Yu LH, Tao H, Zhenqi L. Excess exposure of insulin may be the primary cause of insulin resistance. Am J Physiol Endocrinol Metab 2010;298:E372.