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Insulin resistance is associated with at least threefold increased risk for prothrombotic state in severely obese youngsters

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Abstract

Obesity in childhood increases the risk for early adult cardiovascular disease. However, the underlying mechanism is not fully known. The aims of this study were to measure levels of prothrombotic factors and examine their possible association with obesity and insulin resistance in obese children and adolescents. A total of 313 obese children and adolescents were recruited. In a cross-sectional design, we measured anthropometric parameters, plasminogen activator inhibitor-1-antigen (PAI-1-Ag), von Willebrand factor-antigen (vWF-Ag), fibrinogen (FB), lipids, fasting glucose, and insulin (FI) levels. Insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA-IR) index. Boys presented significantly higher PAI-1-Ag levels than girls (82.6 vs. 71.3 ng/ml, p = 0.01). Higher levels of PAI-1-Ag (96.8 vs. 69 ng/ml, p < 0.001), vWF-Ag (123.5 vs. 107.6%, p = 0.004) but not FB (353.1 vs. 337.6 mg/dl, p = 0.137) were found in insulin-resistant (IR) participants after adjusted for age, gender, and pubertal stage. IR patients were at 2.98 (CI: 1.084–8.193) and 4.86 (CI: 1.119–15.606) times greater risk for high PAI-1-Ag and vWF-Ag levels, respectively. All three prothrombotic factors were positively correlated with body mass index (BMI) and FI levels (p < 0.05), but only PAI-1-Ag and vWF-Ag were significantly correlated with HOMA-IR index (p ≤ 0.001). After adjustment for confounding factors, both BMI and HOMA-IR indices remained significantly associated with PAI-1-Ag (r 2 = 0.225, p < 0.001) and vWF-Ag levels (r 2 = 0.077, p = 0.003). Conclusion: This study shows that obesity in youngsters, when accompanied with insulin resistance, is associated with at least threefold increased risk for elevated levels of prothrombotic factors, contributing to the early development of atherothrombosis. This impaired prothrombotic state may partially explain the increased risk for developing cardiovascular disease later in adulthood.

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Abbreviations

BMI:

Body mass index

CI:

Confidence interval

FG:

Fasting glucose

FI:

Fasting insulin

FB:

Fibrinogen

HDL-c:

High-density lipoprotein cholesterol

HOMA-IR:

Homeostasis model assessment for insulin resistance

IGT:

Impaired glucose tolerance

IR:

Insulin-resistant

LDL-c:

Low-density lipoprotein cholesterol

MS:

Metabolic syndrome

NIR:

Non insulin-resistant

OR:

Odds ratio

PAI-1-Ag:

Plasminogen activator inhibitor-1-antigen

SD:

Standard deviation

TC:

Total cholesterol

TG:

Triglycerides

vWF-Ag:

von Willebrand factor-antigen

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The authors did not have any financial support during the research and have no conflicts of interest to disclose.

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Authors and Affiliations

  1. 4th Department of Pediatrics, Medical School, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Ring Road Nea Efkarpia, 564 03, Thessaloniki, Greece

    Assimina Galli-Tsinopoulou, Ioannis Kyrgios, Ioanna Maggana, Eleni Z. Giannopoulou, Eleni P. Kotanidou, Charilaos Stylianou & George Varlamis

  2. Haemostasis Unit, Department of Haematology, Papageorgiou General Hospital, Thessaloniki, Greece

    Emmanouil Papadakis & Ioannis Korantzis

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  1. Assimina Galli-Tsinopoulou
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  2. Ioannis Kyrgios
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  4. Eleni Z. Giannopoulou
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Correspondence to Assimina Galli-Tsinopoulou.

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Galli-Tsinopoulou, A., Kyrgios, I., Maggana, I. et al. Insulin resistance is associated with at least threefold increased risk for prothrombotic state in severely obese youngsters. Eur J Pediatr 170, 879–886 (2011). https://doi.org/10.1007/s00431-010-1370-9

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