• Entsar A Saad Chemistry Department, Faculty of Science, Damietta University, Damietta, Egypt
  • Salem A. Habib Department of Biochemistry, Faculty of Science, University of Tabuk, Saudi Arabia
  • Wael A. Refai Internal Medicine Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
  • Amira A. Elfayoumy Chemistry Department, Faculty of Science, Damietta University, Damietta, Egypt


Objective: Great interest is directed to inflammation and oxidative stress involvement in type 2 diabetes pathogenesis. Many researchers suggest they play roles but exactly how is still not clear enough. This encouraged us to investigate relations and potential inter-relationships between them and insulin resistance in type 2 diabetes in its early stage. Whether metformin drug alone, as frequently prescribed, is enough for type 2 diabetes management in this early stage was an objective.Methods: Blood sugar indices, adiponectin (ADIPOQ), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), nitric oxide (NO), C-reactive protein (CRP), liver and kidney function tests and lipid profile were monitored in non-diabetic volunteers, pre-diabetic and newly diagnosed type 2 diabetic patients before and after metformin drug utilization for 5 mo.Results: MDA, inflammation markers and alanine aminotransferase (ALT) were elevated, and blood sugar indices and lipid profile showed pathological alterations in diabetics compared to non-diabetics; changes were worse in type 2 cases. They were improved to different degrees by metformin treatment except for pancreatic β-cells function and ADIPOQ level showed no significant improvements and it couldn’t normalize ALT.Conclusion: Results reflected significant relations and inter-relationships between oxidative stress and inflammation markers in type 2 diabetes in its early stage and indicated that metformin may need to be combined with another drug. 
Keywords: Free radicals, Lipid peroxidation, Oxidative stress, Inflammation, Pre-diabetes, Metformin


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1. Sreenivas RA, Meera S, William E, Kumar JS. Correlation between glycemic control and lipid profile in type 2 diabetic patients: HbA1c as an indicator of dyslipidemia. Asian J Pharm Clin Res 2014;7:153-5.
2. Dhaliwall C, Erinmacpherson, Richardson J. Effectiveness of telephone-delivered interventions for increasing physical activity levels in persons with type 2 diabetes or hypertension: a systematic review. J Crit Rev 2015;2:6-11.
3. Saad EA, Hassanien MH, El-Hagrasy MA, Radwan KH. Antidiabetic, hypolipidemic and antioxidant activities and protective effects of Punica granatum peels powder against pancreatic and hepatic tissues injuries in streptozotocin induced IDDM in rats. Int J Pharm Pharm Sci 2015;7:397-402.
4. Jain R, Jain P, Jain P. A review on treatment and prevention of diabetes mellitus. Int J Curr Pharm 2016;8:16-8.
5. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American diabetes association and the European association for the study of diabetes. Diabetes Care 2009;32:193-203.
6. Liberty IA, Kodim N. Assess prediabetes risk, as a golden period for prevention of diabetes. Asian J Pharm Clin Res 2017;10:349-53.
7. Melmed S. Type 2 diabetes mellitus. In: Williams Textbook of Endocrinology. 13th ed. Philadelphia, Pa.: Elsevier; 2016.
8. Rehman K, Akash MSH. Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? Rehman Akash J Biomed Sci 2016;23:87.
9. Sepehri Z, Kiani Z, Nasiri AA, Kohan F. Toll-like receptor 2 and type 2 diabetes. Cell Mol Biol Lett 2016;21:2.
10. Gustafson B. Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb 2010;17:332-41.
11. Al-Dahr MSH, Jiffri EH. Increased adipose tissue expression of tumor necrosis factor-alpha and insulin resistance in obese subjects with type II diabetes. World J Med Sci 2010;5:30-5.
12. Koch A, Sanson E, Voigt S, Helm A, Trautwein C, Tacke F. Serum adiponectin upon admission to the intensive care unit may predict mortality in critically ill patients. Crit Care 2011;26:166-74.
13. Coppola A, Marfella R, Coppola L, Tagliamonte E, Fontana D, Liguori E, et al. Effect of weight loss on coronary circulation and adiponectin levels in obese women. Int J Cardiol 2009;134:414–6.
14. Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor. Clin Chim Acta 2007;380:24-30.
15. Manisundar N, Julius A, Amudhan A, Hemalatha VT, Manigandan T. Nitric oxide as an inflammatory biomarker in oral and systemic diseases-a systematic review. Middle-East J Sci Res 2014;20:881-6.
16. Bhatia S, Shukla R, Madhu SV, Gambhir JK, Prabhu KM. Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy. Clin Biochem 2003;36:557–62.
17. Saad EA. Curative and protective effects of L-arginine on carbon tetrachloride induced hepatotoxicity in mice. Biochem Biophys Res Commun 2012;423:147-51.
18. Saad EA, Habib SA. Effect of crude extracts of some medicinal plants on the osmotic stability of human erythrocytes in vitro. J Free Radicals Antioxidants 2013;139:265-72.
19. Kalavacherla US, Ishaq M, Rao UR, Sachindranath A, Hepsiba T. Malondialdehyde as a sensitive marker of inflammation in patients with rheumatoid arthritis. J Assoc Physicians India 1994;42:775-6.
20. Saad EA. Non-invasive assessment of liver fibrosis using serum markers. J Pharm Chem Biol Sci 2014;2:59-76.
21. Saad EA, Toson EA, Ahmed GM. Clove or green tea administration antagonizes khat hepatotoxicity in rats. Int J Pharm Pharm Sci 2015;7:72-6.
22. Saad EA. Kidney response to L-arginine treatment of carbon tetrachloride induced hepatic injury in mice. Nat Sci 2013;5:1-6.
23. Habib S, Saad EA, Elsharkawy AA, Attia ZR. Pro-inflammatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with obesity in Egyptian non-diabetic obese children and adolescents. Adv Med Sci 2015;60:981-71.
24. Saad EA, Hassanien MM, Elneely EA. Iron(III) diacetylmonoxime-2-hydrazinopyridine complex: a new prospective antitumor drug. Appl Organometal Chem 2016;31:e3684. Doi:10.1002/aoc.3684.
25. Saad EA, Hassanien MM, El-Lban FW. Nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex can inhibit Ehrlich solid tumor growth in mice: a potential new antitumor drug. Biochem Biophys Res Commun 2017;484:579-85.
26. Saad EA, Hassanien MM, El-Mezayen H, ELmenawy NM. Regression of murine ehrlich ascites carcinoma using synthesized cobalt complex. Med Chem Commun 2017;8:1103-11.
27. Noberasco G, Odetti P, Boeri D, Maiello M, Adezati L. Malondialdehyde (MDA) level in diabetic subjects. Relationship with blood glucose and glycosylated hemoglobin. Bionred Pharmucother 1991;45:193-6.
28. David F, Farley J, Huang H, Lavoie JP, Laverty S, Farley, et al. Cytokine and chemokine gene expression of IL-1beta stimulated equine articular chondrocytes. Vet Surg 2007;36:221–7.
29. Chokkalingam V, Tel J, Wimmers F, Liu X, Semenov S, Thiele J, et al. Probing cellular heterogeneity in cytokine-secreting immune cells using droplet-based microfluidics. Lab Chip 2013;13:4740–4.
30. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001;286:327-34.
31. Swaroop JJ, Rajarajeswari D, Naidu JN. Association of TNF-α with insulin resistance in type 2 diabetes mellitus. Indian J Med Res 2012;135:127–30.
32. Aguirre V, Uchida T, Yenush L, Davis R, White MF. The c-Jun NH 2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phsosphorylation of Ser . J Biol Chem 2000;275:9047-54.
33. Zou C, Shao J. Role of adipocytokines in obesity-associated insulin resistance. J Nutr Biochem 2008;19:277-86.
34. Bluher M, Kratzsch J, Paschke R. Plasma levels of tumor necrosis factor-alpha, angiotensin II, growth harmone, and IGF-1 are not elevated in insulin-resistant obese individuals with impaired glucose tolerance. Diabetes Care 2001;24:328-34.
35. Toson ESA, Habib SA, Saad EA, Harraz NH. Toxic and anti-fertility effects of Alocasia macrorrhiza and Calotropis procera ethanolic extracts on male mice. Int J Biochem Photon 2014;195:328-38.
36. Gopal MN, Sridhar C. A validated stability indicating a ultra-performance liquid chromatographic method for simultaneous determination of metformin hydrochloride and empagliflozin in bulk drug and tablet dosage form. Int J Appl Pharm 2017;9:45-50.
37. Rojas LBA, Gomes MB. Metformin: an old but still the best treatment for type 2 diabetes. Diabetol Metab Syndr 2013;5:6.
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How to Cite
Saad, E. A., S. A. Habib, W. A. Refai, and A. A. Elfayoumy. “MALONDIALDEHYDE, ADIPONECTIN, NITRIC OXIDE, C-REACTIVE PROTEIN, TUMOR NECROSIS FACTOR-ALPHA AND INSULIN RESISTANCE RELATIONSHIPS AND INTER-RELATIONSHIPS IN TYPE 2 DIABETES EARLY STAGE IS METFORMIN ALONE ADEQUATE IN THIS STAGE”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 9, no. 10, Oct. 2017, pp. 176-81, doi:10.22159/ijpps.2017v9i10.21149.
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