Skip to main content
SpringerLink
Log in

Lipoprotein-associated phospholipase A2 activity in obese adolescents with and without type 2 diabetes

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) was identified as a strong predictor for cardiovascular events. Furthermore, it is highly associated with obesity. The role of Lp-PLA2 in diabetes mellitus is controversial and analyses, especially in adolescents with type 2 diabetes (T2D), are missing. Therefore, we compared Lp-PLA2 activity between two obese age-, sex-, and BMI-matched cohorts of adolescents with and without T2D. Relationships between Lp-PLA2 activity and age, BMI, hemoglobin A1c, lipids, and adipokines were evaluated. Lp-PLA2 activity was analyzed in serum of 72 obese adolescents without T2D (mean age 15.2 ± 1.6 years) and in 65 obese adolescents with T2D (mean age 15.5 ± 1.8 years). Clinical data were obtained from the Diabetes-Patienten-Verlaufsdokumentation (DPV) registry. Surprisingly, obese adolescents with T2D had lower levels of Lp-PLA2 activity than obese children without T2D (160.2 ± 45.0 versus 180.9 ± 35.6 nmol/min/ml, p = 0.003), but this decrease could only be detected in male (158.8 ± 45.3 versus 190.8 ± 31.3 nmol/min/ml, p < 0.001) and not in female adolescents (162.1 ± 45.5 versus 167.7 ± 37.1 nmol/min/ml, p = 0.60). In multiple linear regression analysis, differences in Lp-PLA2 activity between cohorts remained large and significant (ß-coefficient: −31.60, 95% confidence interval [−49.27;−13.93], p < 0.001). Furthermore, Lp-PLA2 activity was positively associated with BMI (ß-coefficient: 2.04 [0.68;3.40], p = 0.004) and negatively associated with the adipokines leptin (ß-coefficient: −0.53 [−0.89;−0.17], p = 0.004) and adiponectin (ß-coefficient: −3.06, [−5.63;−0.48], p = 0.02). Elevated mean glucose concentrations in adolescents with T2D were not associated with an increase but with a decrease of Lp-PLA2 activity. Hence, in young patients with T2D the Lp-PLA2 activity as a risk predictor for cardiovascular events needs further investigation.

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

  • American Diabetes Association (2016) Standards of medical care in diabetes-2016: summary of revisions. Diabetes care 39(Suppl 1):S4–5

  • Awa WL, Boehm BO, Rosinger S et al (2013) HLA-typing, clinical, and immunological characterization of youth with type 2 diabetes mellitus phenotype from the German/Austrian DPV database. Pediatr Diabetes 14(8):562–574

    Article  CAS  PubMed  Google Scholar 

  • Burchardt P, Zawada A, Kaczmarek J et al (2016) Association between adjunctive metformin therapy in young type 1 diabetes patients with excess body fat and reduction of carotid intima-media thickness. Pol Arch Med Wewn 126(7–8):514–520

    PubMed  Google Scholar 

  • Charniot JC, Khani-Bittar R, Albertini JP et al (2013) Interpretation of lipoprotein-associated phospholipase A2 levels is influenced by cardiac disease, comorbidities, extension of atherosclerosis and treatments. Int J Cardiol 168(1):132–138

    Article  CAS  PubMed  Google Scholar 

  • Cheraghi A, Mahmoudi M, Jafarian K et al (2015) Comparison of serum LP-PLA2 level and some nutritional factors between well-controlled and poorly-controlled diabetic patients. Acta Med Iran 53(11):690–696

    PubMed  Google Scholar 

  • Cole TJ (1990) The LMS method for constructing normalized growth standards. Eur J Clin Nutr 44(1):45–60

    CAS  PubMed  Google Scholar 

  • Constantinides A, van Pelt LJ, van Leeuwen JJ et al (2011) Carotid intima media thickness is associated with plasma lipoprotein-associated phospholipase A2 mass in nondiabetic subjects but not in patients with type 2 diabetes. Eur J Clin Investig 41(8):820–827

    Article  CAS  Google Scholar 

  • da Silva IT, Timm AD, Damasceno NRT (2013) Influence of obesity and cardiometabolic makers on lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity in adolescents: the healthy young cross-sectional study. Lipids Health Dis 12:19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fortunato J, Blaha V, Bis J et al (2014) Lipoprotein-associated phospholipase A(2) mass level is increased in elderly subjects with type 2 diabetes mellitus. J Diabetes Res 2014:278063

  • Gregson J, Stirnadel-Farrant HA, Doobaree IU, Koro C (2012) Variation of lipoprotein associated phospholipase A2 across demographic characteristics and cardiovascular risk factors: a systematic review of the literature. Atherosclerosis 225(1):11–21

    Article  CAS  PubMed  Google Scholar 

  • Hatoum IJ, Hu FB, Nelson JJ, Rimm EB (2010) Lipoprotein-associated phospholipase A2 activity and incident coronary heart disease among men and women with type 2 diabetes. Diabetes 59(5):1239–1243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwashima Y, Katsuya T, Ishikawa K et al (2004) Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 43(6):1318–1323

    Article  CAS  PubMed  Google Scholar 

  • Krebs A, Doerfer J, Krause A et al (2016) Lipoprotein-associated phospholipase A2 activity and low-density lipoprotein subfractions after a 2-year treatment with atorvastatin in adolescents with type 1 diabetes. J Pediatr Endocrinol Metab 29(10):1181–1186

    Article  CAS  PubMed  Google Scholar 

  • Lin XH, Xu MT, Tang JY et al (2016) Effect of intensive insulin treatment on plasma levels of lipoprotein-associated phospholipase A2 and secretory phospholipase A2 in patients with newly diagnosed type 2 diabetes. Lipids Health Dis 15(1):203

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lp PLASC, Thompson A, Gao P et al (2010) Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet 375(9725):1536–1544

    Article  CAS  Google Scholar 

  • Macphee CH (2001) Lipoprotein-associated phospholipase A2: a potential new risk factor for coronary artery disease and a therapeutic target. Curr Opin Pharmacol 1(2):121–125

    Article  CAS  PubMed  Google Scholar 

  • Mayer O Jr, Seidlerova J, Filipovsky J et al (2014) Unexpected inverse relationship between impaired glucose metabolism and lipoprotein-associated phospholipase A2 activity in patients with stable vascular disease. Eur J Intern Med 25(6):556–560

    Article  CAS  PubMed  Google Scholar 

  • Nagel G, Rapp K, Wabitsch M et al (2008) Prevalence and cluster of cardiometabolic biomarkers in overweight and obese schoolchildren: results from a large survey in southwest Germany. Clin Chem 54(2):317–325

    Article  CAS  PubMed  Google Scholar 

  • Nelson TL, Biggs ML, Kizer JR et al (2012) Lipoprotein-associated phospholipase A2 (Lp-PLA2) and future risk of type 2 diabetes: results from the Cardiovascular Health Study. J Clin Endocrinol Metab 97(5):1695–1701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson TL, Kamineni A, Psaty B et al (2011) Lipoprotein-associated phospholipase A(2) and future risk of subclinical disease and cardiovascular events in individuals with type 2 diabetes: the Cardiovascular Health Study. Diabetologia 54(2):329–333

    Article  CAS  PubMed  Google Scholar 

  • Oei HH, van der Meer IM, Hofman A et al (2005) Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study. Circulation 111(5):570–575

    Article  CAS  PubMed  Google Scholar 

  • Onat A, Hergenc G, Can G, Ugur M, Nartop F (2011) Dual activity of serum lipoprotein-associated phospholipase A(2) yielding positive and inverse associations with cardiometabolic risk. Clin Chem Lab Med 49(8):1349–1357

    Article  CAS  PubMed  Google Scholar 

  • Prince RL, Kuk JL, Ambler KA, Dhaliwal J, Ball GD (2014) Predictors of metabolically healthy obesity in children. Diabetes Care 37(5):1462–1468

    Article  CAS  PubMed  Google Scholar 

  • Reinehr T, Hinney A, de Sousa G, Austrup F, Hebebrand J, Andler W (2007) Definable somatic disorders in overweight children and adolescents. J Pediatr 150(6):618–622

    Article  PubMed  Google Scholar 

  • Reinehr T, Karges B, Meissner T et al (2015) Fibroblast growth factor 21 and fetuin-A in obese adolescents with and without type 2 diabetes. J Clin Endocrinol Metab 100(8):3004–3010

    Article  CAS  PubMed  Google Scholar 

  • Reinehr T, Widhalm K, l’Allemand D et al (2009) Two-year follow-up in 21,784 overweight children and adolescents with lifestyle intervention. Obesity 17(6):1196–1199

    PubMed  Google Scholar 

  • Reinehr T, Woelfle J, Wiegand S et al (2016) Leptin but not adiponectin is related to type 2 diabetes mellitus in obese adolescents. Pediatr Diabetes 17(4):281–288

    Article  CAS  PubMed  Google Scholar 

  • Sakka S, Siahanidou T, Voyatzis C et al (2015) Elevated circulating levels of lipoprotein-associated phospholipase A2 in obese children. Clin Chem Lab Med 53(7):1119–1125

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Quesada JL, Vinagre I, de Juan-Franco E et al (2012) Effect of improving glycemic control in patients with type 2 diabetes mellitus on low-density lipoprotein size, electronegative low-density lipoprotein and lipoprotein-associated phospholipase A2 distribution. Am J Cardiol 110(1):67–71

    Article  CAS  PubMed  Google Scholar 

  • Tellis CC, Tselepis AD (2009) The role of lipoprotein-associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma. Biochim Biophys Acta 1791(5):327–338

    Article  CAS  PubMed  Google Scholar 

  • Turer AT, Scherer PE (2012) Adiponectin: mechanistic insights and clinical implications. Diabetologia 55(9):2319–2326

    Article  CAS  PubMed  Google Scholar 

  • Tzotzas T, Filippatos TD, Triantos A, Bruckert E, Tselepis AD, Kiortsis DN (2008) Effects of a low-calorie diet associated with weight loss on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in healthy obese women. Nutr, Metab Cardiovasc Dis : NMCD 18(7):477–482

    Article  CAS  PubMed  Google Scholar 

  • Weyer C, Funahashi T, Tanaka S et al (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86(5):1930–1935

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Joan C. Han, MD, (Division of Pediatric Endocrinology, Department of Pediatrics, University of Tennessee Health Science Center) for critical revision of the manuscript.

Funding

This study was supported in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the DZD (Pediatric diabetes biomaterial bank pedBMB, grant numbers 01GI1109B, 82DZD01801 and 82DZD01802). T.R. received grant support from the BMBF Obesity Network (grant numbers 01GI1120A and 01GI1120B). Additional funding was provided by the European Foundation for the Study of Diabetes (EFSD), the German Diabetes Association (DDG) and the German Competence Net Obesity (grant number 01GI1130). The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

Author information

Authors and Affiliations

  1. Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children’s Hospital, Medical Faculty, 40225, Düsseldorf, Germany

    Julia Seyfarth, Christina Reinauer, Ertan Mayatepek & Thomas Meissner

  2. German Center for Diabetes Research (DZD), 85674, München-Neuherberg, Germany

    Julia Seyfarth, Annika Hoyer, Christina Bächle, Michael Roden, Joachim Rosenbauer, Reinhard W. Holl & Thomas Meissner

  3. Department of Pediatric Endocrinology, Diabetes and Nutrition Medicine, Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, 45711, Datteln, Germany

    Thomas Reinehr

  4. Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center at Heinrich-Heine University Düsseldorf, 40225, Düsseldorf, Germany

    Annika Hoyer, Christina Bächle & Joachim Rosenbauer

  5. Division of Endocrinology and Diabetes, German Center for Diabetes Research (DZD), RWTH Aachen University, 52074, Aachen, Germany

    Beate Karges

  6. Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

    Michael Roden

  7. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center at Heinrich-Heine University Düsseldorf, 40225, Düsseldorf, Germany

    Michael Roden

  8. Department of Pediatrics, Medical University Innsbruck, Innsbruck, Austria

    Sabine E. Hofer

  9. Department of Pediatric Endocrinology and Diabetes, Charité Children’s Hospital, 13353, Berlin, Germany

    Susanna Wiegand

  10. Pediatric Endocrinology Division, Children’s Hospital, University of Bonn, 53113, Bonn, Germany

    Joachim Woelfle

  11. Hospital for Children and Adolescents, University of Leipzig, 04103, Leipzig, Germany

    Wieland Kiess

  12. Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, 89081, Ulm, Germany

    Reinhard W. Holl

Authors
  1. Julia Seyfarth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Reinehr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annika Hoyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christina Reinauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christina Bächle
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Beate Karges
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ertan Mayatepek
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael Roden
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sabine E. Hofer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Susanna Wiegand
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Joachim Woelfle
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Wieland Kiess
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Joachim Rosenbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Reinhard W. Holl
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Thomas Meissner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julia Seyfarth.

Ethics declarations

Conflicts of interest

None.

Additional information

Communicated by: Verena Peters

Electronic supplementary material

ESM 1

(PPTX 90.1 kb)

ESM 2

(PPTX 50.2 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Seyfarth, J., Reinehr, T., Hoyer, A. et al. Lipoprotein-associated phospholipase A2 activity in obese adolescents with and without type 2 diabetes. J Inherit Metab Dis 41, 73–79 (2018). https://doi.org/10.1007/s10545-017-0100-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-017-0100-0

Search

Navigation