Effect of Lifestyle Modification and Metformin on Fetuin-A in Metabolic Syndrome
Abstract
Objective. To evaluate the effects of lifestyle modification and metformin on fetuin-A in metabolic syndrome (MetS) as defined in 2006 by the International Diabetes Federation (IDF).
Methodology. Forty MetS subjects were randomly assigned to treatment with placebo (n=20) or metformin (n=20) in addition to lifestyle modification for 12 weeks.
Results. All 40 participants completed the study. After 12 weeks, both groups had significant reductions in weight (p<0.001), body mass index (BMI) (p<0.001), waist circumference (WC) (p<0.001), systolic blood pressure (SBP) (p<0.001), and diastolic blood pressure (DBP) (p<0.001). The placebo group also had significant improvement in fasting plasma glucose (FPG) (p<0.001) and C-reactive protein (CRP) (<0.05). Weight, BMI, WC, FPG, 2-hour postprandial glucose (2h-PPG), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fetuin-A in the metformin group decreased significantly compared to the placebo group. Reduction of plasma fetuin-A was significantly associated with TG in the metformin group.
Conclusion. Lifestyle modification and treatment with metformin for 12 weeks improved cardio-metabolic risk factors in MetS and reduced fetuin-A levels. Further investigations are required to confirm the effects of lifestyle modification and metformin after an extended follow-up period.
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References
Bruce KD, Byrne CD. The metabolic syndrome: Common origins of a multifactorial disorder. Postgrad Med J. 2009;85(1009):614-21.
Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-607.
Srinivas PR, Wagner AS, Reddy LV, et al. Serum alpha 2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level. Mol Endocrinol. 1993;7(11):1445-55.
Stefan N, Hennige AM, Staiger H, et al. Alpha 2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care. 2006;29(4):853-7.
Ix JH, Wassel CL, Chertow GM, et al. Fetuin-A and change in body composition in older persons. J Clin Endocrinol Metab. 2009;94(11):4492-8.
Mori K, Emoto M, Yokoyama H, et al. Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care. 2006;29(2):468.
Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365(9468):1415-28.
Miller WC, Koceja DM, Hamilton EJ. A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention. Int J Obes Relat Metab Disord. 1997;21(10):941-7.
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). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854-65.
Sharoff CG, Hagobian TA, Malin SK, et al. Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals. Am J Physiol Endocrinol Metab. 2010;298(4):E815-23.
Glueck CJ, Fontaine RN, Wang P, et al. Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism. 2001;50(7):856-61.
Wulffelé MG, Kooy A, de Zeeuw D, et al. The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: A systematic review. J Intern Med. 2004;256(1):1-14.
Pasquali R, Gambineri A, Biscotti D, et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab. 2000;85(8):2767-74.
Lin HZ, Yang SQ, Chuckaree C, et al. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med. 2000;6(9):998-1003.
WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157-63.
International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. Brussels: International Diabetes Federation, 2006. http://www.idf.org/webdata/docs/ IDF_Meta_def_final.pdf.
Misra A, Misra R, Wijesuriya M. The metabolic syndrome in South Asians. In: Mohan V, Rao Gundu HR, eds. Type 2 diabetes in South Asians. Epidemiology, risk factors and prevention. New Delhi: Jaypee Bros., 2007;76-96.
Perkeni. Konsensus Pengelolaan dan Pencegahan Diabetes Mellitus Tipe 2 Di Indonesia, 2011. Perkumpulan Endokrinologi Indonesia.
Grundy SM. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab. 2004;89(6):2595-600.
Reinehr T, Roth CL. Fetuin-A and its relation to metabolic syndrome and fatty liver disease in obese children before and after weight loss. J Clin Endocrinol Metab. 2008;93(11):4479-85.
Ohkawara K, Tanaka S, Miyachi M, et al. A dose-response relation between aerobic exercise and visceral fat reduction: Systematic review of clinical trials. Int J Obes. 2007;31(12):1786-97.
Wing RR, Hill JO. Successful weight loss maintenance. Ann Rev Nutr 2001;21:323-41.
Ross R, Janssen I, Dawson J, et al. Exercise-induced reduction in obesity and insulin resistance in women: a randomized controlled trial. Obes Res. 2004;12(5):789-98.
Stone NJ, Bilek S, Rosenbaum S. Recent National Cholesterol Education Program Adult Treatment Panel III update: adjustments and options. Am J Cardiol. 2005;96(4A):53E-9E.
Kelley GA, Kelley KS. Effects of aerobic exercise on lipids and lipoproteins in adults with type 2 diabetes: A meta-analysis of randomized-controlled trials. Public Health. 2007;121(9):643-55.
Kodama S, Tanaka S, Saito K, et al. Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: A meta-analysis. Arch Intern Med. 2007;167(10): 999-1008.
Stefanick ML, Mackey S, Sheehan M, et al. Effects of diet and exercise in men and postmenopausal women with low levels of HDL-C cholesterol and high levels of LDL-C cholesterol. N Engl J Med. 1998;339(1):12-20.
Whelton SP, Chin A, Xin X, et al. Effect of aerobic exercise on blood pressure: A meta-analysis of randomized, controlled trials. Ann Intern Med. 2002;136(7):493-503.
Bacon SL, Sherwood A, Hinderliter A, et al. Effects of exercise, diet and weight loss on high blood pressure. Sports Med. 2004;34(5):307-16.
Cornier MA, Dabelea D, Hernandez TL et al. The metabolic syndrome. Endocrine Rev. 2008;29(7):777-822.
Hennige AM, Staiger H, Wicke C, et al. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One. 2008;3(3):e1765.
Ridker PM. High-sensitivity C-reactive protein: Potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation. 2001;103(13):1813-8.
Ridker PM, Buring JE, Cook NR, et al. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14719 initially healthy American women. Circulation. 2003;107(3):391-7.
González AS, Guerrero DB, Soto MB, et al. Metabolic syndrome, insulin resistance and the inflammation markers C-reactive protein and ferritin. Eur J Clin Nutr. 2006;60(6):802-9.
Deepa R, Velmurugan K, Arvind Ket, al. Serum levels of interleukin 6, C-reactive protein, vascular cell adhesion molecule 1, and monocyte chemotactic protein 1 in relation to insulin resistance and glucose intolerance—The Chennai Urban Rural Epidemiology Study (CURES). Metabolism. 2006;55(9):1232-8.
Guldiken S, Demir M, Arikan E, et al. The levels of circulating markers of atherosclerosis and inflammation in subjects with different degrees of body mass index: Soluble CD40 ligand and high-sensitivity C-reactive protein. Thromb Res. 2007;119(1):79-84.
Bahia L, Aguiar LG, Villela N, et al. Relationship between adipokines, inflammation, and vascular reactivity in lean controls and obese subjects with metabolic syndrome. Clinics (Sao Paulo). 2006;61(5):433-40.
González AS, Guerrero DB, Soto MB, et al. Metabolic syndrome, insulin resistance and the inflammation markers C-reactive protein and ferritin. Eur J Clin Nutr. 2006;60(6):802-9.
Clearfield MB. C-reactive protein: A new risk assessment tool for cardiovascular disease. J Am Osteopath Assoc. 2005;105(9):409-16.
van Dielen FM, Buurman WA, Hadfoune M, et al. Macrophage inhibitory factor, plasminogen activator inhibitor-1, other acute phase proteins, and inflammatory mediators normalize as a result of weight loss in morbidly obese subjects treated with gastric restrictive surgery. J Clin Endocrinol Metab. 2004;89:4062-8.
Devaraj S, Rogers J, Jialal I. Statins and biomarkers of inflammation. Curr Atheroscler Rep. 2007;9(1):33-41.
Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.
Orchard TJ, Temprosa M, Goldberg R, et al. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: The Diabetes Prevention Program randomized trial. Ann Intern Med. 2005;142(8):611-9.
Ratner R, Goldberg R, Haffner S, et al. Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Diabetes Care. 2005;28(4):888-94.
Mazza A, Fruci B, Garinis GA, et al. The role of metformin in the management of NAFLD. Exp Diabetes Res. 2012;2012:716404.
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