Study of effects of metformin on C-reactive protein level in Type-2 diabetes mellitus

Niteshkumar C. Gamit, Naresh D. Kantharia, Khushbu B. Vaghasiya, Ankit J. Vataliya, Aashal B. Shah


Background: Diabetes mellitus (DM) is extremely common; represent a significant global health problem. Type-2 DM is considered to be associated with a low grade inflammation, which may play a significant role in development of cardiovascular complications evidenced by C-reactive protein (CRP) is a an extremely sensitive marker of systemic inflammation. The study was undertaken to check the effect of metformin on CRP level in Type-2 DM.

Methods: The study was prospective and non-randomized. Thirty newly diagnosed Type-2 DM selected for metformin therapy by medicine personnel were enrolled in the study based on inclusion and exclusion criteria. Patients were divided into pre-treatment (before starting metformin therapy) and post-treatment group. Fasting blood sugar (FBS), postprandial blood sugar (PP2BS), CRP level were measured at the time of enrolment and 3 months after starting metformin monotherapy.

Results: Results were analyzed using pair t-test. Metformin therapy was found to decrease CRP level significantly along with FBS, PP2BS level. p<0.05 value considered as statistically significant. Value was expressed as mean ± standard deviation.

Conclusions: Treatment with 3 months metformin monotherapy for newly diagnosed Type-2 DM has shown a significant decrease in high-sensitivity-CRP level in Type 2 diabetes. This positive effect may be because of the decreased in the expression of proinflammatory cytokines and other mediators, including adhesion molecules, suggests that these processes may contribute to atherogenesis because atherosclerosis is also an inflammatory condition. However, this effect is probably dependent on improving glycemic control.


C-reactive protein level, Type-2 Diabetes mellitus, Inflammatory marker, Atherosclerosis

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Badawi A, Klip A, Haddad P, Cole DE, Bailo BG, El-Sohemy A, et al. Type 2 diabetes mellitus and inflammation: prospects for biomarkers of risk and nutritional intervention. Diabetes Metab Syndr Obes. 2010;3:173-86.

Dandona P. Effects of antidiabetic and antihyperlipidemic agents on C-reactive protein. Mayo Clin Proc. 2008;83(3):333-42.

Xanthis A, Hatzitolios A, Koliakos G, Tatola V. Advanced glycosylation end products and nutrition – a possible relation with diabetic atherosclerosis and how to prevent it. J Food Sci. 2007;72(8):R125-9.

Garcia C, Feve B, Ferré P, Halimi S, Baizri H, Bordier L, et al. Diabetes and inflammation: fundamental aspects and clinical implications. Diabetes Metab. 2010;36(5):327-38.

Unwin N, Gan D, Whiting D. The IDF Diabetes Atlas: providing evidence, raising awareness and promoting action. Diabetes Res Clin Pract. 2010;87(1):2-3.

Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res. 2007;125(3):217-30.

Sir Michael Hurst. President 2013-15, International Diabetes Federation. Annual Report 2013 update. IDF Diabetes Atlas. 6th Edition; 2013: 1-40.

Abrahamian H, Endler G, Exner M, Mauler H, Raith M, Endler L, et al. Association of low-grade inflammation with nephropathy in type 2 diabetic patients: Role of elevated CRP-levels and 2 different gene-polymorphisms of proinflammatory cytokines. Exp Clin Endocrinol Diabetes. 2007;115(1):38-41.

Festa A, D’Agostino R, Howard G, Mykkänen L, Tracy RP, Haffner SM. Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: the insulin resistance atherosclerosis study. Kidney Int. 2000;58(4):1703-10.

Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047-53.

Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, et al. Epidemic obesity and type 2 diabetes in Asia. Lancet. 2006;368(9548):1681-8.

Fronczyk A, Molęda P, Safranow K, Piechota W, Majkowska L. Increased concentration of C-reactive protein in obese patients with type 2 diabetes is associated with obesity and presence of diabetes but not with macrovascular and microvascular complications or glycemic control. Inflammation. 2014;37(2):349-57.

Bray GA, Clearfield MB, Fintel DJ, Nelinson DS. Overweight and obesity: the pathogenesis of cardiometabolic risk. Clin Cornerstone. 2009;9(4):30-40.

Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest 2003;111(12):1805-12.

Navarro JF, Mora C, Maca M, Garca J. Inflammatory parameters are independently associated with urinary albumin in type 2 diabetes mellitus. Am J Kidney Dis. 2003;42(1):53-61.

Del Cañizo Gómez FJ, Fernández Pérez C, Moreno Ruiz I, de Gorospe Pérez-Jáuregui C, Silveira Rodríguez B, González Losada T, et al. Microvascular complications and risk factors in patients with type 2 diabetes. Endocrinol Nutr. 2011;58:163-8.

Nowak M, Wielkoszyński T, Marek B, Kos-Kudła B, Swietochowska E, Siemińska L, et al. Antioxidant potential, paraoxonase 1, ceruloplasmin activity and C-reactive protein concentration in diabetic retinopathy. Clin Exp Med. 2010;10(3):185-92.

Sindhu S, Singh HK, Salman MT, Fatima J, Verma VK. Effects of atorvastatin and rosuvastatin on high-sensitivity C-reactive protein and lipid profile in obese type 2 diabetes mellitus patients. J Pharmacol Pharmacother. 2011;2(4):261-5.

Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347(20):1557-65.

Uwaifo GI, Ratner RE. Differential effects of oral hypoglycaemic agents on glucose control and cardiovascular risk. Am J Cardiol. 2007;99 Suppl:51B-67.

Ajjan RA, Grant PJ. Cardiovascular disease prevention in patients with type 2 diabetes: the role of oral anti-diabetic agents. Diab Vasc Dis Res. 2006;3(3):147-58.

Kassem SA, Raz I. Is there evidence that oral hypoglycemic agents reduce cardiovascular morbidity or mortality? No. Diabetes Care. 2009;32 Suppl 2:S337-41.

Abdulkadir AA, Thanoon IA. Comparative effects of glibenclamide and metformin on C-reactive protein and oxidant/antioxidant status in patients with type II diabetes mellitus. Sultan Qaboos Univ Med J. 2012;12(1):55-61.

Pfützner A, Schöndorf T, Hanefeld M, Forst T. High-sensitivity C-reactive protein predicts cardiovascular risk in diabetic and nondiabetic patients: effects of insulin-sensitizing treatment with pioglitazone. J Diabetes Sci Technol. 2010;4(3):706-16.

Tsoyi K, Jang HJ, Nizamutdinova IT, Kim YM, Lee YS, Kim HJ, et al. Metformin inhibits HMGB1 release in LPS-treated RAW 264.7 cells and increases survival rate of endotoxaemic mice. Br J Pharmacol. 2011;162(7):1498-508.