Journal of Thrombosis and Thrombolysis

, Volume 37, Issue 2, pp 165–170 | Cite as

Platelet activity in Chinese obese adolescents with and without insulin resistance

Article

Abstract

To investigate the platelet activity in Chinese obese adolescents with and without insulin resistance. A cross-sectional study was performed in 159 obese Chinese adolescents to investigate their platelet activity using anthropometrics and biochemical parameters, oral glucose tolerance test and platelet testing. An index of insulin sensitivity, homeostasis model assessment of insulin resistance (HOMA-IR), and plasma fibrinogen, prothrombin fragment 1.2 (PT 1.2), fibrinopeptide A (FPA) and the levels of aggregation to collagen 1 μg/ml, adenosine diphosphate (ADP) 10 μmol/L and arachidonic acid (AA) 0.5 mmol/L were measured. Obese adolescents with insulin resistance had significantly higher HOMA-IR, glucose response curve (AUC), insulin AUC, PT 1.2, FPA and fibrinogen and aggregation (to collagen 1 μg/ml, ADP 10 μmol/L and AA 0.5 mmol/L) comparison with obese adolescents without insulin resistance (P < 0.05). Moreover, a positive correlation was found between both aggregation (to collagen, ADP and AA) and HOMA-IR (ρ = 0.716; P < 0.01, ρ = 0.682; P < 0.01 and ρ = 0.699; P < 0.01, respectively), glucose AUC (ρ = 0.479; P < 0.01, ρ = 0.416; P < 0.01 and ρ = 0.458; P < 0.01, respectively) and insulin AUC (ρ = 0.585; P < 0.01, ρ = 0.511; P < 0.01 and ρ = 0.576; P < 0.01, respectively) in obese adolescents with insulin resistance. Insulin resistance is a major determinant of platelet activation in Chinese obese adolescents.

Keywords

Platelet activity Insulin resistance Obese adolescents 

Introduction

Obesity is one of the leading preventable causes of death worldwide which increasing prevalence trends are reported. Epidemiological studies recently documented a dramatic increment of childhood obesity in westernized societies [1]. The prevalence of adolescent obesity has increased in Brazil (from 4.2 to 14.3 % in 1975 and 1997), China (from 6.4 to 7.7 % in 1991 and 1997), and the United States (from 15.4 to 25.6 % in 1988–1994) [2]. This trend is of particular concern because obesity in childhood is associated with increased obesity-related morbidities and mortality in adulthood [3]. Childhood obesity, which can promote early vascular abnormalities, also represents a strong independent cardiovascular disease risk factor in adults who were overweight in childhood [4].

Obese subjects have shown a variety of platelet function abnormalities, including increased adhesiveness and activation in vitro/vivo and reduced sensitivity to physiological agonists. Platelet hyper-reactivity/activation is seen in patients with obesity and is believed to play a central role amongst different events which accelerates the risk of atherothrombosis as well as exaggerated thrombosis when an atherosclerotic plaque has ruptured [5]. Recent data suggest that human platelets have insulin receptors that modulate platelet function [6], thus causing the lack of the physiological action exerted by insulin on platelet function, such as reduction of the pro-aggregatory properties of agonists, including adenosine diphosphate (ADP), collagen, thrombin, epinephrine [7]; activation of endothelial NO synthase, with increased NO formation and intra-platelet concentrations of cyclic adenosine monophosphate (cAMP); sensitization of platelets to the inhibitory actions of prostacyclin (PGI2) and NO on aggregation [8]. Insulin resistant couples vascular and metabolic pathophysiology by triggering a series of mechanisms, including inflammation endothelial dysfunction and vasoconstriction, predisposing insulin resistant individuals to accelerated atherosclerosis and thrombosis [9]. In addition, insulin resistance has been linked with prothrombotic risk and suppressed fibrinolysis as a consequence of elevated levels of plasminogen activator inhibitor-1 [10].

Obesity is associated with impaired insulin signaling, and intra-abdominal fat deposition is highly related to insulin resistance [11]. In this regard, it worth mentioning that obese children were more likely to exhibit insulin resistantance in comparison with nonobese children. Insulin resistance represent a major cardiovascular disease risk factor which can accelerate atherosclerosis and thrombosis and is also linked to proatherogenic inflammation [12]. Conditions linked to insulin resistance and obesity are generally associated with platelet activation that, in turn, accelerated atherosclerosis and thrombosis. However, the association of obesity and insulin resistance is not necessarily present in all obese subjects [11]. To date, platelet activity in obese adolescents with and without insulin resistance has not been investigated in detail. The purpose of this study is to investigate the platelet activity in Chinese obese adolescents with and without insulin resistance.

Subjects and methods

Study population

The study population consisted of 159 obese Chinese adolescents (Sex: 76 males and 83 females; mean age: 16.3 + 2.5 years) who were referred to our outpatient unit at the Department of Endocrinology of West China Hospital of Sichuan University. Obese adolescents were consecutively selected among those who were referred to the outpatient unit for obesity between 2010 and 2012 according to the following exclusion criteria: presence of concomitant diseases, i.e. renal, liver, and/or cardiovascular diseases; hypertension; bleeding disorders; hemorrhagic events; autoimmune diseases; or serious gastrointestinal disorders. In addition, individuals were also ineligible if they were taking anticoagulants, antiplatelet agents, or nonsteroidal anti-inflammatory drugs in the past 1 year. Informed consent was obtained from both the parents and the patient.

Anthropometrics and biochemical parameters

Patients’ height was measured using a stadiometer, and weight was measured using a clinical balance scale with the participants wearing light indoor clothing. Waist circumference was measured midway between the lower rib margin and the iliac crest, and hip circumference was measured at the widest point over the great trochanters. Both circumferences were measured in the standing position and at the end of a gentle expiration. The waist-to-hip ratio (WHR) was calculated to assess body fat distribution. Body mass index (BMI) was calculated for each subject using the formula weight (kilograms)/height (meters2). After an overnight fast, blood samples were taken in obese children subjects to measure total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, blood glucose and insulin concentrations and HbA1c levels.

Oral glucose tolerance test

A 75 g oral glucose tolerance test was performed after an overnight fast. Venous blood samples were obtained in the fasted state and 30, 60, 90, and 120 min after glucose ingestion for the measurement of plasma glucose and insulin concentrations. The area under the curve for glucose and insulin were calculated using the trapezoid method. The insulin sensitivity index (ISI) was calculated from the oral glucose tolerance test using the method of Matsuda [13]. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as (fasting glucose (mg/dl) × fasting insulin (μU/ml)/22.5.

Platelet testing

Peripheral venous blood was immediately mixed with ethylenediaminetetraacetic acid (for complete blood cell counts) or 3.2 % sodium citrate (for platelet function testing and fibrinogen levels). Platelet counts were determined by automated cell counter (ACT-Diff; Beckman- Coulter, Miami, FL). Whole blood impedance aggregometry was measured in a Chrono-Log dualchannel lumi-aggregometer (Havertown, PA) after samples were stimulated with collagen (1 μg/ml), ADP (10 μmol/L), or arachidonic acid (AA) (0.5 mmol/L). Peak platelet responses within 5 min of agonist stimulation were automatically recorded for aggregation (inohms). Plasma fibrinogen was measured using an automated optical clot detection device (Behring Coagulation System; Dade-Behring, Newark, DE). The same technician processed all samples on the same equipment to minimize measurement variation. The platelet technicians were blinded to the sex, race, and medical history of participants.

Statistical analysis

Statistical analysis was performed using SPSS15.0. Results are expressed as mean ± standard deviation. The glucose response curve (AUC) and insulin AUC were determined using the trapezoidal rule. The Kolmogorov–Smirnov test was used to determine whether the data were random samples from a normal distribution. Categoric variables were examined using contingency table arrays and the χ2 statistic. Obese Adolescents without and with insulin resistance were compared with a t test for independent samples for variables that were normally distributed. When necessary, a nonparametric test (Mann–Whitney U test) was used. The correlation studies were performed by linear regression analysis, using Pearson’s correlation coefficient ρ; P < 0.05 was considered significant.

Results

Study population characteristics

The physical characteristics and the main laboratory variables for both obese adolescents with and without insulin resistance are shown in Table 1. The average age and BMI of obese adolescents was 14.1 ± 3.2 years and 36.6 ± 6.1 kg/m2, respectively. According to the adopted inclusion criteria, compared with obese adolescents without insulin resistance, Obese adolescents with insulin resistance had similar systolic and diastolic blood pressure levels, weight, BMI, waist circumference, WHR, serum lipid profile, HbA1c, and glucose concentrations. In contrast, fasting insulin concentrations were higher in obese adolescents with insulin resistance than in those without insulin resistance. Concordant to this, significantly higher degrees of insulin resistance was present in obese adolescents with insulin resistance who manifested with higher HOMA-IR (5.7 ± 2.0 vs. 2.5 ± 0.6, P = 0.012), glucose AUC (18.3 ± 1.2 vs. 13.8 ± 0.6 103 mg min/dl, P = 0.0061) and insulin AUC (13.9 ± 2.4 vs. 6.7 ± 1.8 103 μU·min/ml, P = 0.0098) when compared with obese adolescents without insulin resistance. There were no statistical differences with regards to all measures of adherence between obese participants without and with insulin resistance.
Table 1

General characteristics of the study population

 

Obese adolescents without insulin resistance

Obese adolescents with insulin resistance

P value

N

81

78

 

Female (%)

34 (41.97 %)

42 (53.84 %)

NS

Age (year)

13.4 ± 3.7

14.8 ± 2.8

NS

Systolic blood pressure (mmHg)

110.8 ± 13.1

118.0 ± 10.9

NS

Diastolic blood pressure (mmHg)

69.4 ± 6.2

65.5 ± 7.3

NS

Weight (Kg)

77.3 ± 10.9

80.5 ± 13.1

NS

BMI (Kg/m2)

33.6 ± 2.8

32.8 ± 3.1

NS

Waist circumference (cm)

87.5 ± 7.2

90.8 ± 6.7

NS

WHR

0.97 ± 0.17

0.98 ± 0.20

NS

Total cholesterol (mg/dl)

179 ± 21

188 ± 27

NS

HDL cholesterol (mg/dl)

41 ± 9

45 ± 6

NS

LDL cholesterol (mg/dl)

99 ± 10

105 ± 13

NS

Triglycerides (mg/dl)

185 ± 18

199 ± 21

NS

HbA1c (%)

4.1 ± 0.9

4.6 ± 1.2

NS

Glucose (mg/dl)

92.3 ± 9.6

89.6 ± 12.6

NS

Insulin (μU/ml)

67.4 ± 5.3

86.4 ± 6.4

<0.05

HOMA-IR

2.5 ± 0.6

5.7 ± 2.0

<0.05

Glucose AUC(× 103 mg·min/dl)

13.8 ± 0.6

18.3 ± 1.2

<0.05

Insulin AUC(× 103 μU·min/ml)

6.7 ± 1.8

13.9 ± 2.4

<0.05

Data are presented as mean ± SD

NS not significant

Platelet function among obese adolescents

To determine whether insulin resistance was responsible for increased platelet activity in obese participants, platelet activation amongst obese adolescents with and without insulin resistance were further compared (Table 2). All platelet function tests were performed adopting the same protocols. Obese adolescents with insulin resistance showed higher levels of prothrombin fragment 1.2 (PT 1.2) (0.75 ± 0.06 vs. 0.76 ± 0.04 mmol/L; P < 0.05), fibrinopeptide A (FPA) (7.78 ± 1.54 vs.7.56 ± 1.23 ng/ml; P < 0.05) and fibrinogen (403 ± 32 vs.388 ± 24 ng/ml; P < 0.05) when compared with obese subjects without insulin resistance. Similarly, significantly higher platelet activation was present in obese adolescents with insulin resistance, as indicated by their higher levels of aggregation to collagen 1 μg/ml (26.6 ± 3.6 vs.24.3 ± 2.7 ohms; P < 0.05), aggregation to ADP 10 μmol/L (14.7 ± 3.4 vs.8.7 ± 2.7 ohms; P < 0.01) and aggregation to AA 0.5 mmol/L (17.2 ± 3.0 vs.11.8 ± 2.1 ohms; P < 0.01) in comparison with obese subjects without insulin resistance.
Table 2

Platelet Function among obese adolescents without and with insulin resistance

 

Obese adolescents without insulin resistance

Obese adolescents with insulin resistance

P value

PT 1.2 (mmol/L)

0.62 ± 0.04

0.75 ± 0.06

0.039

FPA (ng/ml)

6.06 ± 0.43

7.78 ± 0.54

0.022

Fibrinogen (ng/ml)

358 ± 24

403 ± 32

0.010

Aggregation to collagen 1 μg/ml, ohms

21.3 ± 1.7

26.6 ± 2.6

0.004

Aggregation to ADP 10 μmol/L, ohms

8.7 ± 2.7

14.7 ± 3.4

<0.001

Aggregation to arachidonic acid 0.5 mmol/L, ohms

11.8 ± 2.1

17.2 ± 2.0

<0.001

Data are presented as mean ± SD

Correlation studies

To test the hypothesis that platelet function and activity may be affected by insulin resistance in obese adolescents, the above parameters were tested for possible correlations with HOMA-IR, glucose AUC and insulin AUC (Table 3). No correlations were found between platelet function, platelet activity, HOMA-IR, glucose AUC and insulin AUC levels in obese adolescents without insulin resistance. On the contrary, positive correlation was found both between the platelets changes and insulin resistance in obese adolescents with insulin resistance, while no significant correlations were found between both glucose AUC and PT 1.2, FPA and fibrinogen (ρ = 0.325, ρ = 0.302 and ρ = 0.358, respectively). PT 1.2 was positively related with HOMA-IR and insulin AUC in obese adolescents with insulin resistance (ρ = 0.483; P < 0.05 and ρ = 0.421; P < 0.05, respectively) and FPA was positively related with HOMA-IR and insulin AUC (ρ = 0.460; P < 0.05 and ρ = 0.414; P < 0.05, respectively). No correlations were found between fibrinogen, HOMA-IR and insulin AUC (ρ = 0.478; P < 0.05 and ρ = 0.427; P < 0.05, respectively). Moreover, positive correlations were also found between aggregation (to collagen, ADP and AA) and HOMA-IR (ρ = 0.716; P < 0.01, ρ = 0.682; P < 0.01 and ρ = 0.699; P < 0.01, respectively), glucose AUC (ρ = 0.479; P < 0.01, ρ = 0.416; P < 0.01 and ρ = 0.458; P < 0.01, respectively), and insulin AUC (ρ = 0.585; P < 0.01, ρ = 0.511; P < 0.01 and ρ = 0.576; P < 0.01, respectively) in insulin resistance subjects.
Table 3

Correlation coefficients (ρ) between both insulin resistance and the level of platelets function and activity in obese adolescents without and with insulin resistance

 

Obese adolescents without insulin resistance

Obese adolescents with insulin resistance

HOMA-IR

Glucose AUC(×103 mg·min/dl)

Insulin AUC(×103 μU·min/ml)

HOMA-IR

Glucose AUC(×103 mg·min/dl)

Insulin AUC(×103 μU·min/ml)

ρ

P

ρ

P

ρ

P

ρ

P

ρ

P

ρ

P

PT 1.2 (mmol/l)

0.202

NS

0.145

NS

0.173

NS

0.483

0.02

0.325

NS

0.421

0.04

FPA (ng/ml)

0.147

NS

0.071

NS

0.119

NS

0.460

0.01

0.302

NS

0.414

0.02

Fibrinogen (ng/ml)

0.129

NS

0.063

NS

0.082

NS

0.478

0.01

0.358

NS

0.427

0.02

Aggregation to collagen 1 μg/ml, ohms

0.255

NS

0.217

NS

0.213

NS

0.716

<0.01

0.479

<0.01

0.585

<0.01

Aggregation to ADP 10 μmol/L, ohms

0.272

NS

0.209

NS

0.200

NS

0.682

<0.01

0.416

<0.01

0.511

<0.01

Aggregation to arachidonic acid 0.5 mmol/L, ohms

0.299

NS

0.221

NS

0.228

NS

0.699

<0.01

0.458

<0.01

0.576

<0.01

NS not significant

Discussion

In this study, insulin sensitivity as well as platelet function in 159 Chinese obese adolescents with and without insulin resistance were assessed. Fasting insulin concentrations, HOMA-IR, glucose AUC, insulin AUC, PT 1.2, FPA, aggregation to collagen 1 lg/ml, ADP 1 μmol/L, and arachidonic acid 0.5 mmol/L were higher in obese adolescents with insulin resistance in comparison with obese subjects without insulin resistance. Greater insulin resistance was found to be associated with progressively greater platelet reactivity when platelet activation was assessed by collagen 1 μg/ml, ADP 10 μmol/L and AA 0.5 mmol/L in obese adolescents with insulin resistance. On the contrary, correlations were not found between the platelet function, platelet activity, HOMA-IR, Glucose AUC and Insulin AUC levels in obese adolescents without insulin resistance. Thus, our results suggested that insulin resistance increases platelet activity in obese adolescents.

Increased platelet reactivity has been associated with a greater risk of subsequent cardiac events in apparently healthy subjects [14], in patients with previous myocardial infarction [15], and in patients undergoing percutaneous coronary interventions [16]. The constellation of cardiovascular risk factors that is frequently associated with obesity in adults has been demonstrated to affect obese children as well [17]. The recent epidemic of childhood obesity has become a leading public health issue in Western countries because of the possible later clinical consequences, such as cardiovascular disease [18]. Moreover, recent data suggest that obesity at adolescence is a strong predictor of coronary heart disease during adulthood [19], which is independent of the persistence of obesity [15]. Therefore, obesity in childhood may represent the trigger for the development of permanent platelet function abnormalities that, in turn, increases the risk of cardiovascular disease in adulthood.

Previous studies have demonstrated increased activation of platelets in obese subjects and Basili et al. [20] showed that platelet activation were increased in obese subjects compared with lean women by testing the thromboxane metabolite in urine and the CD40 ligand in blood. A study consisted of 40 obese Caucasian school children showed obese children have higher levels of markers of platelet activation (soluble P-selectin and CD40 ligand) than healthy weight children [21]. In addition, another team lead by Schneider reported that greater BMI was associated with higher platelet reactivity in response to 1 μm ADP as assessed by surface expression of P-selectin (r = 0.29, P < 0.0001) in patients with type 2 diabetes [22]. Consistent with previous results, our studies have showed a significant positive correlation both aggregation (to collagen, ADP and AA) and HOMA-IR (ρ = 0.716, ρ = 0.682; and ρ = 0.699, respectively), glucose AUC (ρ = 0.479, ρ = 0.416 and ρ = 0.458, respectively) and insulin AUC (ρ = 0.585, ρ = 0.511 and ρ = 0.576, respectively) in obese adolescents with insulin resistance.

Insulin resistance is generally associated with platelet activation. In vitro and in vivo studies have showed that insulin inhibits platelet aggregation in healthy nonobese subjects, an effect that is blunted in obese individuals [23]. Thromboxane-dependent platelet activation in obesity is related to insulin resistance, per se, independently of vascular inflammation or adypocyte-derived adipokines associated with insulin resistance [12]. In the present study, the hypothesis that the platelet function and activity may be affected by insulin resistance in obese adolescents was investigated. Similar to previous studies, our results were also showed that significant platelet activation was present in obese adolescents with insulin resistance as indicated by their higher levels of aggregation to collagen 1 μg/ml (26.6 ± 3.6 vs. 24.3 ± 2.7 ohms; P < 0.05), aggregation to ADP 10 μmol/L (14.7 ± 3.4 vs. 8.7 ± 2.7 ohms; P < 0.01) and aggregation to AA 0.5 mmol/L (17.2 ± 3.0 vs.11.8 ± 2.1 ohms; P < 0.01) in comparison with obese subjects without insulin resistance. Moreover, no correlations was observed between platelet activity, HOMA-IR, glucose AUC and insulin AUC levels in obese adolescents without insulin resistance. On the contrary, platelet function and activity had shown a positive correlation with insulin resistance in obese adolescents. Insulin resistance and obesity are generally associated with platelet activation that, in turn, accelerated atherosclerosis and thrombosis. However, the association of obesity and insulin resistance is not necessarily present in all obese subjects [12].

In conclusion, our study provides clear evidence that Chinese obese adolescents with insulin resistance is associated with increased platelet activation. The amount of people gets this disease in adolescents becomes increasing and this disease tends to easily separate among the elders [24]. However several limitations of the studies should be emphasized. These include lack of randomization to obese adolescents, lack of generalizability of the findings to gynoid obese adolescents, and a small sample size. Despite these limitations, these preliminary findings may implicate that caloric restriction, exercise and insulin-sensitizing agents may modulate thromboxane-dependent platelet activation in obesity.

Notes

Financial disclosure

The present study was funded by the Natural Science Foundation of China (Grant number: 81272820).

References

  1. 1.
    Slyper AH (2004) The pediatric obesity epidemic: causes and controversies. J Clin Endocrinol Metab 89(6):2540–2547PubMedCrossRefGoogle Scholar
  2. 2.
    Wang Y, Monteiro C, Popkin BM (2002) Trends of overweight and underweight in children and adolescents in the United States, Brazil, China, and Russia. Am J Clin Nutr 75(6):971–977PubMedGoogle Scholar
  3. 3.
    Maffeis C, Tatò L (2001) Long-term effect of childhood obesity on morbidity and mortality. Horm Res 55(Suppl 1):42–45PubMedCrossRefGoogle Scholar
  4. 4.
    Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH (1992) Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med 327(19):1350–1355PubMedCrossRefGoogle Scholar
  5. 5.
    Santilli F, Vazzana N, Liani R, Guagnano MT, Davì G (2012) Platelet activation in obesity and metabolic syndrome. Obes Rev 13(1):27–42PubMedCrossRefGoogle Scholar
  6. 6.
    Falcon C, Pfliegler G, Deckmyn H, Vermylen J (1988) The platelet insulin receptor: detection, partial characterization, and search for a function. Biochem Biophys Res Commun 157(3):1190–1196PubMedCrossRefGoogle Scholar
  7. 7.
    Trovati M, Anfossi G, Cavalot F, Massucco P, Mularoni E, Emanuelli G (1988) Insulin directly reduces platelet sensitivity to aggregating agents. Studies in vitro and in vivo. Diabetes 37(6):780–786PubMedCrossRefGoogle Scholar
  8. 8.
    Trovati M, Anfossi G, Massucco P, Mattiello L, Costamagna C, Piretto V, Mularoni E, Cavalot F, Bosia A, Ghigo D (1997) Insulin stimulates nitric oxide synthesis in human platelets and, through nitric oxide, increases platelet concentrations of both guanosine-3′, 5′-cyclic monophosphate and adenosine-3′, 5′-cyclic monophosphate. Diabetes 46(5):742–749PubMedCrossRefGoogle Scholar
  9. 9.
    Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116(7):1793–1801PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Grant PJ (2007) Diabetes mellitus as a prothrombotic condition. J Intern Med 262(2):157–172PubMedCrossRefGoogle Scholar
  11. 11.
    Kahn BB, Flier JS (2000) Flier obesity and insulinresistance. J Clin Invest 106(4):473–481PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Mather KJ, Kwan F, Corenblum B (2000) Hyperinsulinemia in polycystic ovary syndrome correlates with increased cardiovascular risk independent of obesity. Fertil Steril 73(1):150–156PubMedCrossRefGoogle Scholar
  13. 13.
    Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22(9):1462–1470PubMedCrossRefGoogle Scholar
  14. 14.
    Thaulow E, Erikssen J, Sandvik L, Stormorken H, Cohn PF (1991) Blood platelet counts and function are related to total and cardiovascular death in apparently healthy men. Circulation 84(2):613–617PubMedCrossRefGoogle Scholar
  15. 15.
    Trip MD, Cats VM, van Capelle FJ, Vreeken J (1990) Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 322(22):1549–1554PubMedCrossRefGoogle Scholar
  16. 16.
    Kabbani SS, Watkins MW, Ashikaga T, Terrien EF, Holoch PA, Sobel BE, Schneider DJ (2001) Platelet reactivity characterized prospectively: a determinant of outcome 90 days after percutaneous coronary intervention. Circulation 104(2):181–186PubMedCrossRefGoogle Scholar
  17. 17.
    Barlow SE, Dietz WH (1998) Obesity evaluation and treatment: expert committee recommendations. The maternal and child health bureau, health resources and services administration and the department of health and human services. Pediatrics 102(3):E29PubMedCrossRefGoogle Scholar
  18. 18.
    Srinivasan SR, Bao W, Wattigney WA, Berenson GS (1996) Adolescent overweight is associated with adult overweight and related multiple cardiovascular risk factors: the bogalusa heart study. Metabolism 45(2):235–240PubMedCrossRefGoogle Scholar
  19. 19.
    Gunnell DJ, Frankel SJ, Nanchahal K, Peters TJ, Davey Smith G (1998) Childhood obesity and adult cardiovascular mortality: a 57-year follow-up study based on Boyd Orr cohort. Am J Clin Nutr 67(6):1111–1118PubMedGoogle Scholar
  20. 20.
    Basili S, Pacini G, Guagnano MT, Manigrasso MR, Santilli F, Pettinella C, Ciabattoni G, Patrono C, Davì G (2006) Insulin resistance as a determinant of platelet activation in obese women. J Am Coll Cardiol 48(12):2531–2538PubMedCrossRefGoogle Scholar
  21. 21.
    Desideri G, De Simone M, Iughetti L, Rosato T, Iezzi ML, Marinucci MC, Cofini V, Croce G, Passacquale G, Necozione S, Ferri C (2005) Early activation of vascular endothelial cells and platelets in obese children. J Clin Endocrinol Metab 90(6):3145–3152PubMedCrossRefGoogle Scholar
  22. 22.
    Schneider DJ, Hardison RM, Lopes N, Sobel BE, Brooks MM (2009) Pro-thrombosis ancillary study group. Association between increased platelet p-selectin expression and obesity in patients with type 2 diabetes. Diabetes Care 32(5):944–949PubMedCrossRefGoogle Scholar
  23. 23.
    Trovati M, Mularoni EM, Burzacca S, Ponziani MC, Massucco P, Mattiello L, Piretto V, Cavalot F, Anfossi G (1995) Impaired insulin-induced platelet antiaggregating effect in obesity and in obese NIDDM patients. Diabetes 44(11):1318–1322PubMedCrossRefGoogle Scholar
  24. 24.
    Steinberger J, Daniels SR (2003) Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the atherosclerosis, hypertension, and obesity in the young committee (Council on Cardiovascular Disease in the Young) and the diabetes committee (Council on Nutrition, Physical Activity, and Metabolism)[J]. Circulation 107(10):1448–1453PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Huimin Lu
    • 4
  • Shundong Lei
    • 1
  • Jiuming Zhao
    • 2
  • Ni Chen
    • 3
  1. 1.Business School of Sichuan University/West China Second University Hospital, Sichuan UniversityChengduChina
  2. 2.Regenerative Medicine Research Center, West China HospitalSichaun UniversityChengduChina
  3. 3.Department of Pathology, West China HospitalSichuan UniversityChengduChina
  4. 4.Department of Hepatobiliopancreatic SurgeryWest China Hospital, Sichuan UniversityChengduChina

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