Skip to main content
SpringerLink
Log in

Insulin resistance and exercise capacity in male children and adolescents with non-alcholic fatty liver disease

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Insulin resistance (IR) and obesity may be associated with impaired response to physical exercise. We aimed at assessing physical capacity in obese children with biopsy proven non-alcoholic fatty liver disease (NAFLD) as compared to normal weight and obese children without fatty liver disease. All male subjects, 20 NAFLD and 31 control individuals (20 obese, without NAFLD and 11 normal weight children) took part in the study. We evaluated changes in cardiovascular parameters during a bicycle–ergometer exercise test (James’ test). Duration, power of exercise, heart rate (HR), blood pressure (BP), pulse pressure, cardiac output (ICO) and total peripheral vascular resistance indexed for height (ITPVR) were recorded at rest (r) and peak (p) exercise. The homeostatic model assessment was used to determine insulin resistance (HOMA-IR) and beta-cell action (HOMA-beta cell). In NAFLD and obese subjects, fasting leptin, insulin secretion, insulinogenic index (IGI), muscle insulin sensitivity (MISI) and hepatic insulin resistance index (HIRI) were assayed. Children with NAFLD were the most insulin-resistant (P = 0.001), and showed higher HIRI than obese controls (P = 0.05). At rest, they had the lowest values of SBPr (P = 0.001 vs. controls and P ≤ 0.05 vs. obese controls); during the test, the highest values of ICOp (P = 0.005), ΔICO (P = 0.003) and ΔTRVPp (P ≤ 0.0001). NAFLD and obese controls both had impaired ΔHRp (P ≤ 0.0001). However, obese controls were not able to reduce peripheral resistance during the test. HOMA-IR explained 28% of variance in ΔICO of the whole sample, (P ≤ 0.0001). In obese children with or without NAFLD, increased IR and body weight may induce cardiovascular compensatory changes in response to physical exercise with fairly different pathogenetic mechanisms, which are likely to be dependent on the different degree of IR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Targher G, Arcaro G (2007) Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 191:235–240

    Article  PubMed  CAS  Google Scholar 

  2. Kopp W (2005) Pathogenesis and aetiology of essential hypertension: role of dietary carbohydrate. Med Hypotheses 64:782–787

    Article  PubMed  CAS  Google Scholar 

  3. Manco M, Marcellini M, Devito R, Comparcola D, Sartorelli MR, Nobili V (2008) Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes 32:381–387

    Article  CAS  Google Scholar 

  4. National High Blood Pressure Education Program Working Group on Hypertension Control in Children, Adolescents (1996) Update on the 1987 task force report on high blood pressure in children and adolescents. Pediatrics 98:649–658

    Google Scholar 

  5. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Diabetes Care 26:S5–S20

  6. Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S et al (2007) The metabolic syndrome in children and adolescents—an IDF consensus report. Pediatr Diabetes 8:299–306

    Article  PubMed  Google Scholar 

  7. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320:1–6

    Article  Google Scholar 

  8. Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height–weight formula validated in infants, children, and adults. J Pediatr 9:62–66

    Google Scholar 

  9. Tanner JM (1981) Growth and maturation during adolescence. Nutr Rev 39:43–55

    Article  PubMed  CAS  Google Scholar 

  10. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  PubMed  CAS  Google Scholar 

  11. Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C (2005) Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115:e500–e503

    Article  PubMed  Google Scholar 

  12. Sluiter WJ, Erkelens DW, Reitsma WD, Doorenbos H (1976) Glucose tolerance and insulin release, a mathematical approach I. Assay of the beta-cell response after oral glucose loading. Diabetes 25:241–244

    Article  PubMed  CAS  Google Scholar 

  13. Phillips DI, Clark PM, Hales CN, Osmond C (1994) Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med 11:286–292

    Article  PubMed  CAS  Google Scholar 

  14. Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470

    Article  PubMed  CAS  Google Scholar 

  15. Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA (2007) Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care 30:89–94

    Article  PubMed  CAS  Google Scholar 

  16. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ (2005) Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for non alcoholic fatty liver disease. Hepatology 41:1313–1321

    Article  PubMed  Google Scholar 

  17. James FW, Kaplan S, Glueck CJ, Tsay JY, Knight MJ, Sarwar CJ (1980) Responses of normal children and young adults to controlled bicycle exercise. Circulation 61:902–912

    PubMed  CAS  Google Scholar 

  18. De Simone G, Devereux RB, Daniels SR, Mureddu GF, Roman MJ, Kimball TR, Greco R, Witt S, Contaldo F (1997) Stroke volume and cardiac output in normotensive children and adults. Assessment of relations with body size and impact of overweight. Circulation 95:1837–1843

    PubMed  Google Scholar 

  19. Giordano U, Ciampalini P, Turchetta A, Santilli A, Calzolari F, Crinò A, Alpert BS, Calzolari A (2003) Cardiovascular hemodynamics: Relationship with insulin resistance in obese children. Pediatr Cardiol 24:548–552

    Article  PubMed  CAS  Google Scholar 

  20. Rabbia F, Silke B, Conterno A, Grosso T, De Vito B, Rabbone I, Chiandussi L, Veglio F (2003) Assessment of cardiac autonomic modulation during adolescent obesity. Obes Res 11:541–548

    Article  PubMed  Google Scholar 

  21. Krasnoff JB, Painter PL, Wallace JP, Nathan MB, Meriman RB (2008) Health-related fitness and physical activity in patients with non alcoholic fatty liver disease. Hepatology 47:1158–1165

    Article  PubMed  CAS  Google Scholar 

  22. Manco M, Nobili V (2008) Reduced cardio-respiratory fitness in obesity with and without nonalcoholic fatty liver disease. Hepatology 48:690

    Article  PubMed  Google Scholar 

  23. Hirsch JR, Leibel L, Mackintosh R, Augirre A (1991) Heart rate variability as a measure of autonomic function during weight change in humans. Am J Physiol 261:R1418–R1423

    PubMed  CAS  Google Scholar 

  24. Peterson HR, Rothschild M, Weinberg CR, Fell RD, McLeish KR, Pfeifer MA (1988) Body fat and the activity of the autonomic nervous system. N Engl J Med 318:1077–1083

    PubMed  CAS  Google Scholar 

  25. Rossi M, Marti G, Ricordi L, Fornasari G, Finardi G, Fratino P, Bernardi L (1989) Cardiac autonomic dysfunction in obese subjects. Clin Sci 76:567–572

    PubMed  CAS  Google Scholar 

  26. Valensi P, Phan Thi BN, Lormeau B, Pariès J, Attali JR (1995) Cardiac autonomic function in obese patients. Int J Obes Relat Metab Disord 19:113–118

    PubMed  CAS  Google Scholar 

  27. Valensi P (2003) Cardiovascular Vagosympathetic Activity in Rats with Ventromedial. Hypothal Obes Res 11:54–64

    Article  Google Scholar 

  28. Brands MW, Hildebrandt DA, Mizelle HL, Hall JE (1991) Sustained hyperinsulinemia increases arterial pressure in conscious rats. Am J Physiol 260:R764–R768

    PubMed  CAS  Google Scholar 

  29. Edwards JG, Tipton CM (1989) Influences of exogenous insulin on arterial pressure measurements of the rat. J Appl Physiol 67:2335–2342

    PubMed  CAS  Google Scholar 

  30. Reaven GM, Lithell H, Landsberg L (1996) Hypertension and associated metabolic abnormalities. The role of insulin resistance and the sympathoadrenal system. N Engl J Med 334:374–381

    Article  PubMed  CAS  Google Scholar 

  31. Brands MW, Mizelle HL, Gaillard CA, Hildebrandt DA, Hall JE (1991) The hemodynamic response to chronic hyperinsulinemia in conscious dogs. Am J Hypertens 4:164–168

    PubMed  CAS  Google Scholar 

  32. Landsberg L (1986) Diet, obesity and hypertension: a hypothesis involving insulin, the sympathetic nervous system and adaptive thermogenesis. QJM 236:1081–1090

    Google Scholar 

  33. Ruggeri P, Brunori A, Cogo CE, Storace D, Di Nardo F, Burattini R (2006) Enhanced sympathetic reactivity associated with insulin resistance in the young Zucker rat. Am J Physiol Regul Integr Comp Physiol 291:R376–R382

    PubMed  CAS  Google Scholar 

  34. Buñag RD, Krizsan D, Itoh H (1991) Sympathetic activation by chronic insulin treatment in conscious rats. J Pharmacol Exp Ther 259:131–138

    PubMed  Google Scholar 

  35. Reaven GM (1991) Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in the aetiology and clinical course of hypertension. Am J Med 90:7S–12S

    Article  PubMed  CAS  Google Scholar 

  36. Huang W, Hsieh P, Jin J (2004) Attenuation of insulin-mediated pressor effect and nitric oxide release rats with fructose-induced insulin resistance. Am J Hypertens 17:707–711

    Article  Google Scholar 

  37. Okitolonda W, Brichard SM, Henquin JC (1987) Repercussions of chronic protein-calorie malnutrition on glucose homeostasis in the rat. Diabetologia 30:946–951

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Scientific Directorate, “Bambino Gesù” Children’s Hospital and Research Institute, S. Onofrio 4 square, 00165, Rome, Italy

    Melania Manco

  2. Cardiorespiratory and Sport Medicine Unit, “Bambino Gesù” Children’s Hospital and Research Institute, 00165, Rome, Italy

    Ugo Giordano & Attilio Turchetta

  3. Department of Radiology, “Bambino Gesù” Children’s Hospital and Research Institute, 00165, Rome, Italy

    Rodolfo Fruhwirth

  4. Dietology Service, “Bambino Gesù” Children’s Hospital and Research Institute, 00165, Rome, Italy

    Monica Ancinelli

  5. Liver Unit, “Bambino Gesù” Children’s Hospital and Research Institute, 00165, Rome, Italy

    Matilde Marcellini & Valerio Nobili

Authors
  1. Melania Manco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ugo Giordano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Attilio Turchetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rodolfo Fruhwirth
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Monica Ancinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matilde Marcellini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Valerio Nobili
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Melania Manco.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manco, M., Giordano, U., Turchetta, A. et al. Insulin resistance and exercise capacity in male children and adolescents with non-alcholic fatty liver disease. Acta Diabetol 46, 97–104 (2009). https://doi.org/10.1007/s00592-008-0063-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-008-0063-6

Keywords

Search

Navigation