Association of adiposity, measures of metabolic dysregulation, and elevated alanine aminotransferase in subjects with normal body mass index

Open access


Background: Differences in body fat (BF) distribution in patients with normal body mass index (BMI) with elevated alanine aminotransferase (ALT) remains poorly described.

Objective: To determine the relationship between total BF, waist circumference (WC), insulin resistance (IR), and cardiometabolic risk profile in subjects with elevated ALT and normal BMI.

Methods: We analyzed cross-sectional data from 4,914 US participants in the third National Health and Nutrition Examination Survey database, who were ≥20 years of age, had normal BMI, and had body composition assessed by bioimpedance.

Results: Mean ± SD age was 41.4 ± 0.3 years, and 58% participants were women. BF was 20 ± 0.1% in men and 29.9 ± 0.1% in women. As total BF increased by tertiles, there was a tendency towards a higher prevalence of nonalcoholic fatty liver disease in men (6.1%, 6.5%, 9.5%, P = 0.13), but not in women (8.7%, 8.2%, 10.7%, P = 0.71). As WC increased by tertiles, there was a higher prevalence of elevated ALT in men (2.6%, 8.6%, 6.6%, P < 0.0001), but not in women. As ALT increased, men had significantly higher levels of nonhigh density lipoprotein cholesterol (HDL-C), increased apolipoprotein B, increased IR, and lower levels of C-reactive protein, whereas, women had higher levels of non-HDL-C and increased IR.

Conclusion: In subjects with normal BMI, increased WC is associated with a higher prevalence of elevated ALT in men, but not in women. Higher levels of ALT correlated with a poor cardiometabolic risk profile.

1. Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007; 45:846-54.

2. Church TS, Kuk JL, Ross R, Priest EL, Biltoft E, Blair SN. Association of cardiorespiratory fitness, body mass index, and waist circumference to nonalcoholic fatty liver disease. Gastroenterology. 2006; 130: 2023-30.

3. Park SH, Kim BI, Kim SH, Kim HJ, Park DI, Cho YK, et al. Body fat distribution and insulin resistance: beyond obesity in nonalcoholic fatty liver disease among overweight men. J Am Coll Nutr. 2007; 26:321-6.

4. Duvnjak M, Lerotic I, Barsic N, Tomasic V, Virovic Jukic L, Velagic V. Pathogenesis and management issues for non-alcoholic fatty liver disease. World J Gastroenterol. 2007; 13:4539-50.

5. Bouloumie A, Curat CA, Sengenes C, Lolmede K, Miranville A, Busse R. Role of macrophage tissue infiltration in metabolic diseases. Curr Opin Clin Nutr Metab Care. 2005; 8:347-54.

6. Wan YP, Xu RY, Fang H, Lu LP, Zhang XM, Cai W. [The prevalence of non-alcoholic fatty liver disease and its related risk factors in 1180 school children in Shanghai]. Zhonghua Gan Zang Bing Za Zhi. 2007; 15: 644-8.

7. Kim HJ, Kim HJ, Lee KE, Kim DJ, Kim SK, Ahn CW, et al. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med. 2004; 164:2169-75.

8. Hsieh SD, Yoshinaga H, Muto T. Waist-to-height ratio, a simple and practical index for assessing central fat distribution and metabolic risk in Japanese men and women. Int J Obes Relat Metab Disord. 2003; 27:610-6.

9. Chumlea WM, Guo SS. Assessment and prevalence of obesity: application of new methods to a major problem. Endocrine. 2000; 13:135-42.

10. Chumlea WC, Guo SS, Kuczmarski RJ, Flegal KM, Johnson CL, Heymsfield SB, et al. Body composition estimates from NHANES III bioelectrical impedance data. Int J Obes Relat Metab Disord. 2002; 26:159 6-609.

11. Plan and operation of the Third National Health and Nutrition Examination Survey, 1988-94. Series 1: programs and collection procedures. Vital Health Stat 1. 1994;32:1-407.

12. Chumlea WC, Guo SS, Zeller CM, Reo NV, Baumgartner RN, Garry PJ, et al. Total body water reference values and prediction equations for adults. Kidney Int. 2001; 59:2250-8.

13. Sun SS, Chumlea WC, Heymsfield SB, Lukaski HC, Schoeller D, Friedl K, et al. Development of bioelectrical impedance analysis prediction equations for body composition with the use of a multicomponent model for use in epidemiologic surveys. Am J Clin Nutr. 2003; 77:331-40.

14. Sui X, LaMonte MJ, Laditka JN, Hardin JW, Chase N, Hooker SP, et al. Cardiorespiratory fitness and adiposity as mortality predictors in older adults. JAMA. 2007; 298:2507-16.

15. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28:412-9.

16. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004; 27:1487-95.

17. Ruhl CE, Everhart JE. Leptin concentrations in the United States: relations with demographic and anthropometric measures. Am J Clin Nutr. 2001; 74: 295-301.

18. Muntner P, He J, Chen J, Fonseca V, Whelton PK. Prevalence of non-traditional cardiovascular disease risk factors among persons with impaired fasting glucose, impaired glucose tolerance, diabetes, and the metabolic syndrome: analysis of the Third National Health and Nutrition Examination Survey (NHANES III). Ann Epidemiol. 2004; 14:686-95.

19. Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002; 137:1-10.

20. Rohrmann S, Crespo CJ, Weber JR, Smit E, Giovannucci E, Platz EA. Association of cigarette smoking, alcohol consumption and physical activity with lower urinary tract symptoms in older American men: findings from the third National Health And Nutrition Examination Survey. BJU International. 2005; 96:77-82.

21. Chitturi S, Farrell GC, Hashimoto E, Saibara T, Lau GK, Sollano JD. Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines. J Gastroenterol Hepatol. 2007; 22:778-87.

22. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome-a new worldwide definition. Lancet. 2005; 366(9491):1059-62.

23. Romero-Corral A, Somers VK, Sierra-Johnson J, Thomas RJ, Collazo-Clavell ML, Korinek J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond). 2008; 32:959-66.

24. Demerath EW, Schubert CM, Maynard LM, Sun SS, Chumlea WC, Pickoff A, et al. Do changes in body mass index percentile reflect changes in body composition in children? Data from the Fels Longitudinal Study. Pediatrics. 2006; 117:e487-95.

25. Dervaux N, Wubuli M, Megnien JL, Chironi G, Simon A. Comparative associations of adiposity measures with cardiometabolic risk burden in asymptomatic subjects. Atherosclerosis. 2008; 201:413-7.

26. Han TS, Lean ME, Seidell JC. Waist circumference remains useful predictor of coronary heart disease. BMJ. 1996; 312:1227-8.

27. Kvist H, Sjostrom L, Tylen U. Adipose tissue volume determinations in women by computed tomography: technical considerations. Int J Obes. 1986; 10:53-67.

28. Smith SR, Lovejoy JC, Greenway F, Ryan D, deJonge L, de la Bretonne J, et al. Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism. 2001; 50:425-35.

29. Han TS, Carter R, Currall JE, Lean ME. The influence of fat free mass on prediction of densitometric body composition by bioelectrical impedance analysis and by anthropometry. Eur J Clin Nutr. 1996; 50:542-8.

30. Ryo M, Maeda K, Onda T, Katashima M, Okumiya A, Nishida M, et al. A new simple method for the measurement of visceral fat accumulation by bioelectrical impedance. Diabetes Care. 2005; 28: 451-3.

31. Nagai M, Komiya H, Mori Y, Ohta T, Kasahara Y, Ikeda Y. Development of a new method for estimating visceral fat area with multi-frequency bioelectrical impedance. Tohoku J Exp Med. 2008; 214:105-12.

32. Kim JA, Park HS. Association of abdominal fat distribution and cardiometabolic risk factors among obese Korean adolescents. Diabetes Metab. 2008; 34:126-30.

33. Rexrode KM, Carey VJ, Hennekens CH, Walters EE, Colditz GA, Stampfer MJ, et al. Abdominal adiposity and coronary heart disease in women. JAMA. 1998; 280:1843-8.

34. Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat is an independent predictor of all-cause mortality in men. Obesity (Silver Spring). 2006; 14:336-41.

35. Romero-Corral A, Lopez-Jimenez F, Sierra-Johnson J, Somers VK. Differentiating between body fat and lean mass-how should we measure obesity? Nat Clin Pract Endocrinol Metab. 2008; 4:322-3.

36. Romero-Corral A, Somers VK, Sierra-Johnson J, Korenfeld Y, Boarin S, Korinek J, et al. Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J. 2010; 31: 737-46.

37. Rosito GA, Massaro JM, Hoffmann U, Ruberg FL, Mahabadi AA, Vasan RS, et al. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation. 2008; 117:605-13.

38. Chaston TB, Dixon JB. Factors associated with percent change in visceral versus subcutaneous abdominal fat during weight loss: findings from a systematic review. Int J Obes (Lond). 2008; 32:619-28.

39. Ross R, Rissanen J, Hudson R. Sensitivity associated with the identification of visceral adipose tissue levels using waist circumference in men and women: effects of weight loss. Int J Obes Relat Metab Disord. 1996; 20:533-8.

40. Lovejoy JC, Smith SR, Rood JC. Comparison of regional fat distribution and health risk factors in middle-aged white and African American women: The Healthy Transitions Study. Obes Res. 2001; 9: 10-6.

41. Carroll JF, Chiapa AL, Rodriquez M, Phelps DR, Cardarelli KM, Vishwanatha JK, et al. Visceral fat, waist circumference, and BMI: impact of race/ethnicity. Obesity (Silver Spring). 2008; 16:600-7.

42. Yokoyama H. [Gamma glutamyl transpeptidase (gammaGTP) in the era of metabolic syndrome]. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2007; 42:110-24.

43. Lee MY, Koh SB, Koh JH, Nam SM, Shin JY, Shin YG, et al. Relationship between γ-glutamyltransferase and metabolic syndrome in a Korean population. Diabet Med. 2008; 25:469-75.

44. Monami M, Bardini G, Lamanna C, Pala L, Cresci B, Francesconi P, et al. Liver enzymes and risk of diabetes and cardiovascular disease: results of the Firenze Bagno a Ripoli (FIBAR) study. Metabolism. 2008; 57: 387-92.

45. Kim DJ, Noh JH, Cho NH, Lee BW, Choi YH, Jung JH, et al. Serum γ-glutamyltransferase within its normal concentration range is related to the presence of diabetes and cardiovascular risk factors. Diabet Med. 2005; 22:1134-40.

Journal Information

IMPACT FACTOR 2017: 0.209
5-year IMPACT FACTOR: 0.243

CiteScore 2018: 0.30

SCImago Journal Rank (SJR) 2018: 0.172
Source Normalized Impact per Paper (SNIP) 2018: 0.237


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 392 360 76
PDF Downloads 296 290 71