Navarrete-Tapia U, Narváez C, Izaguirre-Gutiérrez F, Domínguez-Borgua A, Gutiérrez-Salmeán G, Ceballos G, Meaney E

Language: English
References: 43
Page: 26-33
PDF size: 245.38 Kb.

ABSTRACT

Background: It is known that there are different metabolic phenotypes associated with obesity, each of them imposing distinct cardiovascular risk. Metformin is a drug with wide and diverse applications in cardiometabolic disorders. Aims: To determine the effect of metformin on lipid profile, glucose metabolism and anthropometric variables of different phenotypes of obesity. Material and methods: We conducted a «before and after» clinical trial in order to evaluate the response to metformin treatment (850 mg/day for 24 weeks). Variables like body weight, body mass index (BMI), waist-hip index (WHI), blood pressure, glycemia, total cholesterol (TC) and its fractions, HDL, LDL as well as triglycerides and TC/HDL-c and TG/HDL-c lipoprotein indexes were analyzed at baseline and at the end of the trial. Results: HDL-c and TC/HDL-c ratios showed a considerable improvement after treatment. A reduction in LDL fraction was observed. Triglyceride levels had no significant changes. An average weight reduction of 0.48 Kg was obtained alongside with an improvement of the BMI. Both systolic and diastolic blood pressures did not show meaningful changes. Conclusions: Sustained administration of metformin had a beneficial effect on lipid profile, weight reduction and cardiovascular risk predictors.

REFERENCES

1. Mendis S, Davis S, Norrving B. Organizational update: the world health organization global status report on noncommunicable diseases 2014; one more landmark step in the combat against stroke and vascular disease. Stroke. 2015; 46 (5): e121-e122.

2. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006; 444 (7121): 875-880.

3. Bays H. Central obesity as a clinical marker of adiposopathy; increased visceral adiposity as a surrogate marker for global fat dysfunction. Curr Opin Endocrinol Diabetes Obes. 2014; 21 (5): 345-351.

4. Hashimoto Y, Tanaka M, Okada H, Senmaru T, Hamaguchi M, Asano M et al. Metabolically healthy obesity and risk of incident CKD. Clin J Am Soc Nephrol. 2015; 10 (4): 578-583.

5. Ruderman NB, Schneider SH, Berchtold P. The “metabolically-obese”, normal-weight individual. Am J Clin Nutr. 1981; 34 (8): 1617-1621.

6. Samaropoulos XF, Hairston KG, Anderson A, Haffner SM, Lorenzo C, Montez M et al. A metabolically healthy obese phenotype in hispanic participants in the IRAS family study. Obesity (Silver Spring). 2013; 21 (11): 2303-2309.

7. Karelis AD, Faraj M, Bastard JP, St-Pierre DH, Brochu M, Prud’homme D et al. The metabolically healthy but obese individual presents a favorable inflammation profile. J Clin Endocrinol Metab. 2005; 90 (7): 4145-4150.

8. Manu P, Ionescu-Tirgoviste C, Tsang J, Napolitano BA, Lesser ML, Correll CU. Dysmetabolic Signals in “Metabolically Healthy”. Obes Res Clin Pract. 2012; 6 (1): e9-e20.

9. Cherqaoui R, Kassim TA, Kwagyan J, Freeman C, Nunlee-Bland G, Ketete M et al. The metabolically healthy but obese phenotype in African Americans. J Clin Hypertens (Greenwich). 2012; 14 (2): 92-96.

10. Denis GV, Obin MS. Metabolically healthy obesity’: origins and implications. Mol Aspects Med. 2013; 34 (1): 59-70.

11. Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999-2004). Arch Intern Med. 2008; 168 (15): 1617-1624.

12. Lee K. Metabolically obese but normal weight (MONW) and metabolically healthy but obese (MHO) phenotypes in Koreans: characteristics and health behaviors. Asia Pac J Clin Nutr. 2009; 18 (2): 280-284.

13. Gomez-Huelgas R, Narankiewicz D, Villalobos A, Warnberg J, Mancera-Romero J, Cuesta AL et al. Prevalence of metabolically discordant phenotypes in a mediterranean population-The IMAP study. Endocr Pract. 2013; 19 (5): 758-768.

14. Fanghanel-Salmon G, Gutierrez-Salmean G, Samaniego V, Meaney A, Sanchez-Reyes L, Navarrete U et al. Obesity phenotypes in urban middle-class cohorts; the prit-lindavista merging evidence in Mexico: the opus prime study. Nutr Hosp. 2015; 32 (01): 182-188.

15. American Diabetes A. Standards of medical care in diabetes-2015 abridged for primary care providers. Clin Diabetes. 2015; 33 (2): 97-111.

16. Rena G, Pearson ER, Sakamoto K. Molecular mechanism of action of metformin: old or new insights? Diabetologia. 2013; 56 (9): 1898-1906.

17. Kappe C, Patrone C, Holst JJ, Zhang Q, Sjoholm A. Metformin protects against lipoapoptosis and enhances GLP-1 secretion from GLP-1-producing cells. J Gastroenterol. 2013; 48 (3): 322-332.

18. Ikeda T, Iwata K, Murakami H. Inhibitory effect of metformin on intestinal glucose absorption in the perfused rat intestine. Biochem Pharmacol. 2000; 59 (7): 887-890.

19. Lupi R, Del Guerra S, Fierabracci V, Marselli L, Novelli M, Patane G et al. Lipotoxicity in human pancreatic islets and the protective effect of metformin. Diabetes. 2002; 51 (Suppl 1): S134-S137.

20. Cicero AF, Tartagni E, Ertek S. Metformin and its clinical use: new insights for an old drug in clinical practice. Arch Med Sci. 2012; 8 (5): 907-917.

21. Yanovski JA, Krakoff J, Salaita CG, McDuffie JR, Kozlosky M, Sebring NG et al. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes. 2011; 60 (2): 477-485.

22. Diehl LA, Fabris BA, Barbosa DS, De Faria EC, Wiechmann SL, Carrilho AJ. Metformin increases HDL3-cholesterol and decreases subcutaneous truncal fat in nondiabetic patients with HIV-associated lipodystrophy. AIDS Patient Care STDS. 2008; 22 (10): 779-786.

23. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009; 120 (16): 1640-1645.

24. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation. 2005; 111 (5): 697-716.

25. Meaney E, Vela A, Samaniego V, Meaney A, Asbun J, Zempoalteca JC et al. Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study. Clin Exp Pharmacol Physiol. 2008; 35 (8): 895-903.

26. Zhang Y, Hu C, Hong J, Zeng J, Lai S, Lv A, et al. Lipid profiling reveals different therapeutic effects of metformin and glipizide in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2014; 37 (10): 2804-2812.

27. Hollenbeck CB, Johnston P, Varasteh BB, Chen YD, Reaven GM. Effects of metformin on glucose, insulin and lipid metabolism in patients with mild hypertriglyceridaemia and non-insulin dependent diabetes by glucose tolerance test criteria. Diabetes Metab. 1991; 17 (5): 483-489.

28. Rodriguez Y, Giri M, Feyen E, Christophe AB. Effect of metformin vs. placebo treatment on serum fatty acids in non-diabetic obese insulin resistant individuals. Prostaglandins Leukot Essent Fatty Acids. 2004; 71 (6): 391-397.

29. Fendri S, Debussche X, Puy H, Vincent O, Marcelli JM, Dubreuil A et al. Metformin effects on peripheral sensitivity to insulin in non diabetic obese subjects. Diabetes Metab. 1993; 19 (2): 245-249.

30. Pedroza-Tobias A, Trejo-Valdivia B, Sanchez-Romero LM, Barquera S. Classification of metabolic syndrome according to lipid alterations: analysis from the Mexican National Health and Nutrition Survey 2006. BMC Public Health. 2014; 14: 1056.

31. Aguilar-Salinas CA, Olaiz G, Valles V, Torres JM, Gomez PFJ, Rull JA et al. High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey. J Lipid Res. 2001; 42 (8): 1298-1307.

32. Quintero-Castillo D, Luz-Araujo H, Guerra-Velazquez M, Reyna-Villasmil E, Santos Bolivar J, Torres-Cepeda D et al. Lipid profile in obese and non-obese women with polycystic ovary syndrome treated with metformin. Endocrinol Nutr. 2010; 57 (6): 262-267.

33. Giugliano D, De Rosa N, Di Maro G, Marfella R, Acampora R, Buoninconti R et al. Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women. Diabetes Care. 1993; 16 (10): 1387-1390.

34. Aghahosseini M, Aleyaseen A, Safdarian L, Moddaress-Hashemi S, Mofid B, Kashani L. Metformin 2,500 mg/day in the treatment of obese women with polycystic ovary syndrome and its effect on weight, hormones, and lipid profile. Arch Gynecol Obstet. 2010; 282 (6): 691-694.

35. O’Donnell CJ, Elosua R. Cardiovascular risk factors. Insights from Framingham Heart Study. Rev Esp Cardiol. 2008; 61 (3): 299-310.

36. Pereira MA, Weggemans RM, Jacobs DR, Jr., Hannan PJ, Zock PL, Ordovas JM et al. Within-person variation in serum lipids: implications for clinical trials. Int J Epidemiol. 2004; 33 (3): 534-541.

37. Marcovina SM, Gaur VP, Albers JJ. Biological variability of cholesterol, triglyceride, low- and high-density lipoprotein cholesterol, lipoprotein(a), and apolipoproteins A-I and B. Clin Chem. 1994; 40 (4): 574-578.

38. Millan J, Pinto X, Munoz A, Zuniga M, Rubies-Prat J, Pallardo LF et al. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manag. 2009; 5: 757-765.

39. Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, Buring JE. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation. 1997; 96 (8): 2520-2525.

40. Stampfer MJ, Sacks FM, Salvini S, Willett WC, Hennekens CH. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction. N Engl J Med. 1991; 325 (6): 373-381.

41. Quispe R, Manalac RJ, Faridi KF, Blaha MJ, Toth PP, Kulkarni KR et al. Relationship of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to the remainder of the lipid profile: The very large database of lipids-4 (VLDL-4) study. Atherosclerosis. 2015; 242 (1): 243-250.

42. Weiler MCS, Wollinger LM, Marin D, Genro JP, Contini V, Morelo Dal Bosco S. Waist-to-height ratio (WHtR) and triglyceride to HDL-C ratio (TG/HDL-c) as predictors of cardiometabolic risk. Nutr Hosp. 2015; 31 (5): 2115-2121.

43. Maturu A, DeWitt P, Kern PA, Rasouli N. The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of beta-cell function in African American women. Metabolism. 2015; 64 (5): 561-565.