The association of higher levels of within-normal-limits liver enzymes and the prevalence of the metabolic syndrome

Arie Steinvil1, Itzhak Shapira1, Orit Kliuk Ben-Bassat1, Michael Cohen1, Yaffa Vered2, Shlomo Berliner1, Ori Rogowski1
1Departments of Medicine "D" & "E", The Tel-Aviv Sourasky Medical Center, 6 Weizman St, Tel Aviv, 64239, Israel
2the Central Laboratory of the Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Tóm tắt

AbstractBackgroundMetabolic syndrome (MetS) is frequently characterized by elevated liver enzymes, including gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT). Our objective was to evaluate the range of prevalence of MetS in apparently healthy individuals whose liver enzyme concentrations were all within-normal-range.MethodsWe have performed a cross sectional analysis on participants of the Tel-Aviv medical center inflammation survey (TAMCIS) recruited between the years 2003-2009. Analyzed were a cohort of 6,561 men and 3,389 women.ResultsThe prevalence of MetS increased significantly from the first quintile to the fifth for both GGT and ALT, all the five quintiles being in the normal range. Logistic regression analysis for the presence of MetS showed crude odds ratios of 2.7 and 2.4 between the first and fourth quintiles and 3.6 and 3.2 for the fifth quintile in men and women respectively for ALT. For GGT the respective odds being 3.6 and 3.2 for the fourth quintile and 3.9 and 3.4 for the fifth quintile in men and women, respectively.ConclusionsA relatively high prevalence of MetS was noted in a cohort of apparently healthy individuals with liver enzyme concentrations within-normal-limits. Practical consequences include the need to follow up these enzyme concentrations as continuous variables and to take into consideration that even relatively small elevations within the normal range might reflect the presence of dysmetabolism.

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Dekker JM, Girman C, Rhodes T, Nijpels G, Stehouwer CD, Bouter LM, Heine RJ: Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn Study. Circulation. 2005, 112: 666-673. 10.1161/CIRCULATIONAHA.104.516948.

Jeppesen J, Hansen TW, Rasmussen S, Ibsen H, Torp-Pedersen C, Madsbad S: Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease: a population-based study. J Am Coll Cardiol. 2007, 49: 2112-2119. 10.1016/j.jacc.2007.01.088.

Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. Jama. 2002, 288: 2709-2716. 10.1001/jama.288.21.2709.

Malik S, Wong ND, Franklin SS, Kamath TV, L'Italien GJ, Pio JR, Williams GR: Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation. 2004, 110: 1245-1250. 10.1161/01.CIR.0000140677.20606.0E.

Devers MC, Campbell S, Shaw J, Zimmet P, Simmons D: Should liver function tests be included in definitions of metabolic syndrome? Evidence from the association between liver function tests, components of metabolic syndrome and prevalent cardiovascular disease. Diabet Med. 2008, 25: 523-529. 10.1111/j.1464-5491.2008.02408.x.

Andre P, Balkau B, Vol S, Charles MA, Eschwege E: Gamma-glutamyltransferase activity and development of the metabolic syndrome (International Diabetes Federation Definition) in middle-aged men and women: Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. Diabetes Care. 2007, 30: 2355-2361. 10.2337/dc07-0440.

Nannipieri M, Gonzales C, Baldi S, Posadas R, Williams K, Haffner SM, Stern MP, Ferrannini E: Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study. Diabetes Care. 2005, 28: 1757-1762. 10.2337/diacare.28.7.1757.

Hanley AJ, Williams K, Festa A, Wagenknecht LE, D'Agostino RB, Haffner SM: Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. Diabetes. 2005, 54: 3140-3147. 10.2337/diabetes.54.11.3140.

Liangpunsakul S, Chalasani N: Unexplained elevations in alanine aminotransferase in individuals with the metabolic syndrome: results from the third National Health and Nutrition Survey (NHANES III). Am J Med Sci. 2005, 329: 111-116. 10.1097/00000441-200503000-00001.

Goessling W, Massaro JM, Vasan RS, D'Agostino RB, Ellison RC, Fox CS: Aminotransferase Levels and 20-Year Risk of Metabolic Syndrome, Diabetes, and Cardiovascular Disease. Gastroenterology. 2008, 135 (6): 1935-44. 10.1053/j.gastro.2008.09.018. 1944.e

Emdin M, Passino C, Michelassi C, Titta F, L'Abbate A, Donato L, Pompella A, Paolicchi A: Prognostic value of serum gamma-glutamyl transferase activity after myocardial infarction. Eur Heart J. 2001, 22: 1802-1807. 10.1053/euhj.2001.2807.

Jousilahti P, Rastenyte D, Tuomilehto J: Serum gamma-glutamyl transferase, self-reported alcohol drinking, and the risk of stroke. Stroke. 2000, 31: 1851-1855.

Lee DH, Silventoinen K, Hu G, Jacobs DR, Jousilahti P, Sundvall J, Tuomilehto J: Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women. Eur Heart J. 2006, 27: 2170-2176. 10.1093/eurheartj/ehl086.

Lee DS, Evans JC, Robins SJ, Wilson PW, Albano I, Fox CS, Wang TJ, Benjamin EJ, D'Agostino RB, Vasan RS: Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study. Arterioscler Thromb Vasc Biol. 2007, 27: 127-133. 10.1161/01.ATV.0000251993.20372.40.

Meisinger C, Doring A, Schneider A, Lowel H: Serum gamma-glutamyltransferase is a predictor of incident coronary events in apparently healthy men from the general population. Atherosclerosis. 2006, 189: 297-302. 10.1016/j.atherosclerosis.2006.01.010.

Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H: Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults. Circulation. 2005, 112: 2130-2137. 10.1161/CIRCULATIONAHA.105.552547.

Wannamethee G, Ebrahim S, Shaper AG: Gamma-glutamyltransferase: determinants and association with mortality from ischemic heart disease and all causes. Am J Epidemiol. 1995, 142: 699-708.

Turgut O, Yilmaz A, Yalta K, Karadas F, Birhan Yilmaz M: gamma-Glutamyltransferase is a promising biomarker for cardiovascular risk. Medical hypotheses. 2006, 67: 1060-1064. 10.1016/j.mehy.2006.04.010.

Fraser A, Harris R, Sattar N, Ebrahim S, Davey Smith G, Lawlor DA: Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women's Heart and Health Study and meta-analysis. Diabetes Care. 2009, 32: 741-750. 10.2337/dc08-1870.

Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S: Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006, 44: 865-873. 10.1002/hep.21327.

Kain K, Carter AM, Grant PJ, Scott EM: Alanine aminotransferase is associated with atherothrombotic risk factors in a British South Asian population. J Thromb Haemost. 2008, 6: 737-741. 10.1111/j.1538-7836.2008.02935.x.

Sattar N, Scherbakova O, Ford I, O'Reilly DS, Stanley A, Forrest E, Macfarlane PW, Packard CJ, Cobbe SM, Shepherd J: Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study. Diabetes. 2004, 53: 2855-2860. 10.2337/diabetes.53.11.2855.

Steinvil A, Berliner S, Bromberg M, Cohen M, Shalev V, Shapira I, Rogowski O: Micro-inflammatory changes in asymptomatic healthy adults during bouts of respiratory tract infections in the community: potential triggers for atherothrombotic events. Atherosclerosis. 2009, 206: 270-275. 10.1016/j.atherosclerosis.2009.01.045.

Rogowski O, Steinvil A, Berliner S, Cohen M, Saar N, Ben-Bassat OK, Shapira I: Elevated resting heart rate is associated with the metabolic syndrome. Cardiovasc Diabetol. 2009, 8: 55-10.1186/1475-2840-8-55.

Rogowski O, Shapira I, Steinvil A, Berliner S: Low-grade inflammation in individuals with the hypertriglyceridemic waist phenotype: another feature of the atherogenic dysmetabolism. Metabolism. 2009, 58: 661-667. 10.1016/j.metabol.2009.01.005.

Rogowski O, Shapira I, Peretz H, Berliner S: Glycohaemoglobin as a determinant of increased fibrinogen concentrations and low-grade inflammation in apparently healthy nondiabetic individuals. Clin Endocrinol (Oxf). 2008, 68: 182-189.

Rogowski O, Shapira I, Shirom A, Melamed S, Toker S, Berliner S: Heart rate and microinflammation in men: a relevant atherothrombotic link. Heart. 2007, 93: 940-944. 10.1136/hrt.2006.101949.

Rogowski O, Toker S, Shapira I, Melamed S, Shirom A, Zeltser D, Berliner S: Values of high-sensitivity C-reactive protein in each month of the year in apparently healthy individuals. Am J Cardiol. 2005, 95: 152-155. 10.1016/j.amjcard.2004.08.086.

Steinvil A, Shirom A, Melamed S, Toker S, Justo D, Saar N, Shapira I, Berliner S, Rogowski O: Relation of educational level to inflammation-sensitive biomarker level. Am J Cardiol. 2008, 102: 1034-1039. 10.1016/j.amjcard.2008.05.055.

Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). Jama. 2001, 285: 2486-2497. 10.1001/jama.285.19.2486.

Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC: 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: 1640-1645. 10.1161/CIRCULATIONAHA.109.192644.

Barham D, Trinder P: An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst. 1972, 97: 142-145. 10.1039/an9729700142.

Fossati P, Prencipe L: Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem. 1982, 28: 2077-2080.

Izawa S, Okada M, Matsui H, Hotta Y, Hama H: A new direct method for measuring HDL-cholesterol which does not produce any biased values. Jpn J Med Pharm Sci. 1997, 37: 1385-1388.

Szasz G: Reaction-rate method for gamma-glutamyltransferase activity in serum. Clin Chem. 1976, 22: 2051-2055.

Bergmeyer HU, Horder M: International federation of clinical chemistry. Scientific committee. Expert panel on enzymes. IFCC document stage 2, draft 1; 1979-11-19 with a view to an IFCC recommendation. IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC method for alanine aminotransferase. J Clin Chem Clin Biochem. 1980, 18: 521-534.

Kotronen A, Westerbacka J, Bergholm R, Pietilainen KH, Yki-Jarvinen H: Liver fat in the metabolic syndrome. J Clin Endocrinol Metab. 2007, 92: 3490-3497. 10.1210/jc.2007-0482.

Paolicchi A, Emdin M, Passino C, Lorenzini E, Titta F, Marchi S, Malvaldi G, Pompella A: Beta-lipoprotein- and LDL-associated serum gamma-glutamyltransferase in patients with coronary atherosclerosis. Atherosclerosis. 2006, 186: 80-85. 10.1016/j.atherosclerosis.2005.07.012.

Anderson ME, Allison RD, Meister A: Interconversion of leukotrienes catalyzed by purified gamma-glutamyl transpeptidase: concomitant formation of leukotriene D4 and gamma-glutamyl amino acids. Proc Natl Acad Sci USA. 1982, 79: 1088-1091. 10.1073/pnas.79.4.1088.

Despres JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodes-Cabau J, Bertrand OF, Poirier P: Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008, 28: 1039-1049. 10.1161/ATVBAHA.107.159228.

Tenenbaum A, Fisman EZ, Motro M: Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). Cardiovascular diabetology. 2003, 2: 4-10.1186/1475-2840-2-4.

Patel DA, Srinivasan SR, Xu JH, Chen W, Berenson GS: Persistent elevation of liver function enzymes within the reference range is associated with increased cardiovascular risk in young adults: the Bogalusa Heart Study. Metabolism. 2007, 56: 792-798. 10.1016/j.metabol.2007.01.010.