Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter February 15, 2018

Higher D-lactate levels are associated with higher prevalence of small dense low-density lipoprotein in obese adolescents

  • Reyna Rodríguez-Mortera , Claudia Luevano-Contreras , Sergio Solorio-Meza , Russell Caccavello , Yasmin Bains , Ma Eugenia Garay-Sevilla and Alejandro Gugliucci EMAIL logo

Abstract

Background:

Childhood obesity is associated with insulin resistance (IR), increased levels of small dense low-density lipoprotein (sd-LDL) as well as with augmented hepatic de novo lipogenesis, which implies increased triose phosphate fluxes that may lead to increased methylglyoxal (MG) and its catabolic end product D-lactate. We hypothesized that obese adolescents have increased D-lactate serum levels associated with high incidence of sd-LDL.

Methods:

This is a cross-sectional study where the anthropometric characteristics, atherogenic dyslipidemia complex, sd-LDL (Lipoprint, Quantimetrix) and D-lactate (kinetic enzymatic analysis) were explored in 30 lean vs. 30 obese adolescents (16 females and 14 males per group) without metabolic syndrome (MetS). Endothelial function by flow-mediated dilation (FMD, by ultrasound) and arterial lesion by carotid intima media thickness (CIMT, by ultrasound) were also measured.

Results:

The mean age of participants was 16.8 ± 1.4 years. Obese adolescents had a body mass index of 32.7 ± 3.8 vs. 21.8 ± 2.1 in lean participants. The obesity group showed higher D-lactate levels: 6.2 ± 3.0 vs. 4.5 ± 2.5 μmol/L, higher levels of insulin: 15 (9.6–23.5) vs. 7.9 (6.5–10.5) μIU/mL; triglyceride (TG): 1.46 (1.1–1.8) vs. 0.84 (0.6–1.2) mmol/L; non-high-density lipoprotein-cholesterol (NON-HDL-C): 2.8 ± 0.9 vs. 2.3 ± 0.7 mmol/L; total cholesterol (TC)/HDL-C) index: 2.9 ± 0.7 vs. 2.4 ± 0.5; TG/HDL-C index: 2.2 (1.5–2.8) vs. 1.1 (0.8–1.8); %LDL-3: 4.2 ± 4.07 vs. 1.9 ± 2.7; smaller LDL size: 270.6 ± 3 vs. 272.2 ± 1.1 Å. D-lactate correlated positively with LDL-2: r = 0.44 and LDL-3 (sd-LDL): r = 0.49 and negatively with large LDL-1: r = −0.48 and LDL size: r = −0.46; (p<0.05, p<0.01, p<0.001 and p<0.0001, respectively). Obese adolescents showed higher CIMT: 0.51 ± 0.08 vs. 0.46 ± 0.08 mm and lower FMD: 20.3% ± 6.7% vs. 26.0% ± 9.3%.

Conclusions:

Obese adolescents display subclinical signs of IR and endothelial dysfunction. Higher serum sd-LDL levels correlated positively with D-lactate levels. These findings suggest an association between atherogenic dyslipoproteinemia and whole body MG fluxes already detectable in apparently healthy obese adolescents.


Corresponding author: Alejandro Gugliucci, MD, PhD, Professor and Associate Dean of Research, Touro University-California, 1310 Club Drive, 94592, Vallejo, CA, USA; and Glycation, Oxidation and Disease Laboratory, Department of Research, College of Osteopathic Medicine, Touro University, Vallejo, CA, USA, Phone: +1 707 638 5237, Fax: +1 707 638 5998

Acknowledgments

The authors would like to thank all the participants and parents/caregivers who volunteered for this study.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Grant DAIP University of Guanajuato (Project 011/2015) and Touro University-California (069).

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Alawan A. Global status report on noncommunicable diseases. World Health Organization (WHO). Geneva Switzerland, 2011.Search in Google Scholar

2. Gutiérrez JP, Rivera-Dommarco J, Shamah-Levy T, Villalpando-Hernández S, Franco A, Cuevas-Nasu L, et al. Encuesta Nacional de Salud y Nutrición 2012. Resultados Nacionales. Cuernavaca, México: Instituto Nacional de Salud Pública (MX), 2012. https://ensanut.insp.mx/informes/ENSANUT2012ResultadosNacionales.pdf.Search in Google Scholar

3. Kohen-Avramoglu R, Theriault A, Adeli K. Emergence of the metabolic syndrome in childhood: an epidemiological overview and mechanistic link to dyslipidemia. Clin Biochem 2003;36:413–20.10.1016/S0009-9120(03)00038-9Search in Google Scholar

4. Jago R, Harrell JS, McMurray RG, Edelstein S, El Ghormli L, Bassin S. Prevalence of abnormal lipid and blood pressure values among an ethnically diverse population of eighth-grade adolescents and screening implications. Pediatrics 2006;117:2065–73.10.1542/peds.2005-1716Search in Google Scholar PubMed PubMed Central

5. Gidding SS. Cardiovascular risk factors in adolescents. Curr Treat Options Cardiovasc Med 2006;8:269–75.10.1007/s11936-006-0047-1Search in Google Scholar PubMed

6. Goran MI, Ball GD, Cruz ML. Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J Clin Endocrinol Metab 2003;88:1417–27.10.1210/jc.2002-021442Search in Google Scholar PubMed

7. Manco M, Bottazzo G, DeVito R, Marcellini M, Mingrone G, Nobili V. Nonalcoholic fatty liver disease in children. J Am Coll Nutr 2008;27:667–76.10.1080/07315724.2008.10719744Search in Google Scholar PubMed

8. Doyon A, Kracht D, Bayazit AK, Deveci M, Duzova A, Krmar RT, et al. Carotid artery intima-media thickness and distensibility in children and adolescents: reference values and role of body dimensions. Hypertension 2013;62:550–6.10.1161/HYPERTENSIONAHA.113.01297Search in Google Scholar PubMed

9. Urbina EM, Williams RV, Alpert BS, Collins RT, Daniels SR, Hayman L, et al. Noninvasive assessment of subclinical atherosclerosis in children and adolescents: recommendations for standard assessment for clinical research: a scientific statement from the American Heart Association. Hypertension 2009;54:919–50.10.1161/HYPERTENSIONAHA.109.192639Search in Google Scholar PubMed

10. Jourdan C, Wühl E, Litwin M, Fahr K, Trelewicz J, Jobs K, et al. Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens 2005;23:1707–15.10.1097/01.hjh.0000178834.26353.d5Search in Google Scholar PubMed

11. Madhu K, Manjunath C, Rawal J, Irani P. Atherogenic dyslipidemia. Indian J Endocrinol Metab 2013;17:969.10.4103/2230-8210.122600Search in Google Scholar PubMed PubMed Central

12. Armiliato GN. High-fructose intake in obesity-related nonalcoholic fatty liver disease. J Gastrointest Dig Syst 2015;5:281–7.10.4172/2161-069X.1000281Search in Google Scholar

13. Schwarz JM, Noworolski SM, Wen MJ, Dyachenko A, Prior JL, Weinberg ME, et al. Effect of a high-fructose weight-maintaining diet on lipogenesis and liver fat. J Clin Endocrinol Metab 2015;100:2434–42.10.1210/jc.2014-3678Search in Google Scholar PubMed PubMed Central

14. Thornalley PJ. Glyoxalase I – structure, function and a critical role in the enzymatic defense against glycation. Biochem Soc Trans 2003;31:1343–8.10.1042/bst0311343Search in Google Scholar PubMed

15. Masania J, Malczewska-Malec M, Razny U, Goralska J, Zdzienicka A, Kiec-Wilk B, et al. Dicarbonyl stress in clinical obesity. Glycoconj J 2016;33:581–9.10.1007/s10719-016-9692-0Search in Google Scholar PubMed PubMed Central

16. Charakida M, Masi S, Lüscher TF, Kastelein JJ, Deanfield JE. Assessment of atherosclerosis: the role of flow-mediated dilatation. Eur Heart J 2010;31:2854–61.10.1093/eurheartj/ehq340Search in Google Scholar PubMed

17. Głowińska-Olszewska B, Tołwińska J, Łuczyński W, Konstantynowicz J, Bossowski A. Cardiovascular risk in nonobese hypertensive adolescents: a study based on plasma biomarkers and ultrasonographic assessment of early atherosclerosis. J Hum Hypertens 2013;27:191–6.10.1038/jhh.2012.11Search in Google Scholar PubMed

18. Bruno RM, Bianchini E, Faita F, Taddei S, Ghiadoni L. Intima media thickness, pulse wave velocity, and flow mediated dilation. Cardiovasc Ultrasound 2014;12:34.10.1186/1476-7120-12-34Search in Google Scholar PubMed PubMed Central

19. Litwin M, Niemirska A. Intima-media thickness measurements in children with cardiovascular risk factors. Pediatr Nephrol 2009;24:707–19.10.1007/s00467-008-0962-3Search in Google Scholar PubMed

20. CDC. National Health and Nutrition. Examination survey. Antrophometry procedures manual. Available from: http://www.cdc.gov/nchs/data/nhanes/nhanes_07_08/manual_an.pdf.Search in Google Scholar

21. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. National high blood pressure education program working group on high blood pressure in children and adolescents. Pediatrics 2004;114(2 Suppl 4th):555–76.10.1542/peds.114.S2.555Search in Google Scholar

22. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. Br Med J 2000;320:1240–3.10.1136/bmj.320.7244.1240Search in Google Scholar PubMed PubMed Central

23. Amato MC, Giordano C, Galia M, Criscimanna A, Vitabile S, Midiri M, et al. Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care 2010;33:920–2.10.2337/dc09-1825Search in Google Scholar PubMed PubMed Central

24. Arrebola-Moreno AL, Laclaustra M, Kaski JC. Noninvasive assessment of endothelial function in clinical practice. Rev Esp Cardiol 2012;65:80–90.10.1016/j.rec.2011.10.004Search in Google Scholar

25. Montalcini T, Romeo S, Fava A, Pujia A. Carotid intima-media thickness: a target or a marker? Am J Ther 2014;21:535–9.10.1097/MJT.0b013e318255bc26Search in Google Scholar

26. Hoefner DM, Hodel SD, O’Brien JF, Branum EL, Sun D, Meissner I, et al. Development of a rapid, quantitative method for LDL subfractionation with use of the quantimetrix lipoprint LDL system. Clin Chem 2001;47:266–74.10.1093/clinchem/47.2.266Search in Google Scholar

27. Gugliucci A, Lustig RH, Caccavello R, Erkin-Cakmak A, Noworolski SM, Tai VW, et al. Short-term isocaloric fructose restriction lowers apoC-III levels and yields less atherogenic lipoprotein profiles in children with obesity and metabolic syndrome. Atherosclerosis 2016;253:171–7.10.1016/j.atherosclerosis.2016.06.048Search in Google Scholar

28. McLellan AC, Phillips SA, Thornalley PJ. Fluorimetric assay of d-lactate. Anal Biochem 1992;206:12–6.10.1016/S0003-2697(05)80004-1Search in Google Scholar

29. Simşek E, Balta H, Balta ZD. Childhood obesity-related cardiovascular risk factors and carotid intima-media thickness. Turk J Pediatr 2010;52:601–11.Search in Google Scholar

30. Mittelman SD, Gilsanz P, Mo AO, Wood J, Dorey F, Gilsanz V. Adiposity predicts carotid intima-media thickness in healthy children and adolescents. J Pediatr 2010;156:592–7.10.1016/j.jpeds.2009.10.014Search in Google Scholar PubMed

31. Amato MC, Giordano C. Visceral adiposity index: an indicator of adipose tissue dysfunction. Int J Endocrinol 2014;2014:1–7.10.1155/2014/730827Search in Google Scholar PubMed PubMed Central

32. Rodríguez-Morán M, Guerrero-Romero F, Aradillas-García C, Bermudez-Peña C, Simental-Mendia LE, Vargas Morales JM, et al. Atherogenic indices and prehypertension in obese and non-obese children. Diabetes Vasc Dis Res 2013;10:17–24.10.1177/1479164112440713Search in Google Scholar PubMed

33. Mansour M, Nassef YE, Shady MA, Aziz AA, Malt HA. Metabolic syndrome and cardiovascular risk factors in obese adolescent. Open access Maced J Med Sci 2016;4:118–21.10.3889/oamjms.2016.037Search in Google Scholar PubMed PubMed Central

34. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J 2013;12:1–8.10.1186/1475-2891-12-7Search in Google Scholar PubMed PubMed Central

35. Miyashita M, Okada T, Kuromori Y, Harada K. LDL particle size, fat distribution and insulin resistance in obese children. Eur J Clin Nutr 2006;60:416–20.10.1038/sj.ejcn.1602333Search in Google Scholar PubMed

36. Bekhet OH, Zeljkovic A, Vekic J, Paripovic D, Janac J, Joksic J, et al. Hypertension, lipoprotein subclasses and lipid transfer proteins in obese children and adolescents. Scand J Clin Lab Invest 2016;5513(July):1–7.10.1080/00365513.2016.1201849Search in Google Scholar PubMed

37. Stan S, Levy E, Delvin EE, Hanley JA, Lamarche B, O’Loughlin J, et al. Distribution of LDL particle size in a population-based sample of children and adolescents and relationship with other cardiovascular risk factors. Clin Chem 2005;51:1192–200.10.1373/clinchem.2004.046771Search in Google Scholar PubMed

38. Taşcılar ME, Özgen T, Cihan M, Abacı A, Yeşilkaya E, Eker I, et al. The effect of insulin resistance and obesity on low-density lipoprotein particle size in children. J Clin Res Pediatr Endocrinol 2010;2:63–6. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3005671&tool=pmcentrez&rendertype=abstract.10.4274/jcrpe.v2i2.63Search in Google Scholar PubMed PubMed Central

39. Muniyappa R, Srinivas PR. Dicarbonyl stress and atherosclerosis: is it all RAGE? Diabetes 2014;63:3587–9.10.2337/db14-0953Search in Google Scholar PubMed PubMed Central

40. Kimber L. Stanhope J-M, Havel PJ. Adverse metabolic effects of dietary fructose: results from recent epidemiological, clinical, and mechanistic studies. Nano 2008;6:2166–71.Search in Google Scholar

41. Lustig RH, Mulligan K, Noworolski SM, Tai VW, Wen MJ, Ayca EC, et al. Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome. Obesity (Silver Spring, Md) 2016;24:453–60.10.1002/oby.21371Search in Google Scholar PubMed PubMed Central

42. Lim JS, Mietus-Snyder M, Valente A, Schwarz J-M, Lustig RH. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol 2010;7:251–64.10.1038/nrgastro.2010.41Search in Google Scholar PubMed

43. Głowińska-Olszewska B, Tołwińska J, Urban M. Relationship between endothelial dysfunction, carotid artery intima media thickness and circulating markers of vascular inflammation in obese hypertensive children and adolescents. J Pediatr Endocrinol Metab 2007;20:1125–36.10.1515/JPEM.2007.20.10.1125Search in Google Scholar

44. Giannini C, de Giorgis T, Scarinci A, Cataldo I, Marcovecchio ML, Chiarelli F, et al. Increased carotid intima-media thickness in pre-pubertal children with constitutional leanness and severe obesity: the speculative role of insulin sensitivity, oxidant status, and chronic inflammation. Eur J Endocrinol 2009;161:73–80.10.1530/EJE-09-0042Search in Google Scholar PubMed

45. Cote AT, Harris KC, Panagiotopoulos C, Sandor GG, Devlin AM. Childhood obesity and cardiovascular dysfunction. J Am Coll Cardiol 2013;62:1309–19.10.1016/j.jacc.2013.07.042Search in Google Scholar PubMed

46. Koopman LP, McCrindle BW, Slorach C, Chahal N, Hui W, Sarkola T, et al. Interaction between myocardial and vascular changes in obese children: a pilot study. J Am Soc Echocardiogr [Internet] 2012;25:401–10.e1. Available from: http://dx.doi.org/10.1016/j.echo.2011.12.018.10.1016/j.echo.2011.12.018Search in Google Scholar PubMed

47. Tryggestad JB, Thompson DM, Copeland KC, Short KR. Obese children have higher arterial elasticity without a difference in endothelial function: the role of body composition. Obesity (Silver Spring) 2012;20:165–71.10.1038/oby.2011.309Search in Google Scholar PubMed PubMed Central

Received: 2017-8-17
Accepted: 2018-1-10
Published Online: 2018-2-15
Published in Print: 2018-6-27

©2018 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 25.4.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2017-0733/html
Scroll to top button