International Journal of Pediatrics Table 2: Univariate regression analysis between VO2max and metabolic risk factors. Age Tanner stage BMI z score Fat Free Mass kg Fat Free Mass % Fat Mass kg Fat Mass % Systolic BP Diastolic BP Fasting Glucose Fasting Insulin HOMA-IR Triglycerides HDL Cholesterol LDL Cholesterol AST ALT Sedimentation rate Fibrinogen 4. Discussion P .0062 .0018 <.0001 <.0001 .0002 <.0001 <.0001 <.0001 .124 .072 .220 <.0001 <.0001 .010 .019 .509 .770 .0007 .0002 .0005 F 7,64 10.043 83.809 48.949 14.576 43.856 92.285 56.838 14.26 8.012 T −2.976 −3.169 −9.55 −6.99 −3.818 6.622 −9.761 −7.539 −5.52 −4.98 −2.59 2.36 −3.421 −3.776 −2.831 CRF and adiposity are associated with metabolic risk factors and cardiac and vascular risks; it is known that these risks are already present in youth [2, 28]. The main roles are attributed either to ﬁtness or fatness [3, 8]. In fact an inﬂuence of both variables could be expected owing to the relationships between obesity and movement eﬃciency [29] which lately led to social exclusion, but diﬀerences in statistical analysis, ways of assessing metabolic risk, adiposity, and/or taking account of gender and sexual development could explain at least part of these discrepancies. The potential metabolic interdependence between these risks lead to the concept of metabolic syndrome. Currently this concept is debated [18, 19], and these risk factors could have only statistical relations. So studying the individual relationships between each of them and with ﬁtness or adiposity could be of interest to understand the mechanisms involved in the health risks of obesity; it could also give more speciﬁc aims to improve the eﬃciency of prevention campaigns [30]. The present study showed mainly a relation between CRF (VO2max) and insulin metabolism in girls; VO2max was signiﬁcantly related to diastolic BP in boys and to ALT in girls. Age was mainly involved in the relationships with insulin and lipids in boys and with inﬂammation in girls. Apart from the relationship between inﬂammation parameters in boys, the degree of adiposity did not appear to play a main inﬂuence on the early occurrence of risk factors. None of these relationships depended on pubertal development. 3 It seemed useful to address current adiposity and not only BMI which is the sum of fat free and fat mass [20]; a previous study shows that measured fat mass is a better variable to assess the metabolic risk of obesity, owing to the endocrine and inﬂammatory actions of adipose tissue [1, 21]; most of the studies use BMI as marker of adiposity [13]; their conclusions could be taken with caution since an increased BMI can be associated with an increased muscle mass, speciﬁcally in active boys. Subjects of the present study did not fulﬁl the criteria of metabolic syndrome, whatever the deﬁnition used; it is known that the risk of developing MS factors increases with the degree of overweight [1, 10, 18]. In some reports, the relationships between MS and CRF only occur at high degrees of adiposity [9]. Our regression analysis showed a direct eﬀect of age on inﬂammation and lipoproteins, from young age and from a moderate degree of excess adiposity; these observations, added to the early development of arterial dysfunction [28] and the relationship between child obesity and its complications in adult [31], support a precocious treatment of overweight in youth. When it is assessed, no eﬀect of pubertal status is observed [9]. Diﬀerences were found between boys and girls in the relationships between risk factors (lipid proﬁle, insulin resistance) and ﬁtness by some authors [7, 32, 33] and not by others [9]; such diﬀerences were expected, due to the diﬀerence in insulin sensitivity between both sexes [34]. They should not result from sex hormones, since no eﬀect of pubertal stage was found; more diﬀerences are found in lifestyle; boys are more active than girls, and physical activity aﬀects all cardiovascular risks [7, 17]. Imperatore ﬁnds a signiﬁcant association between insulin sensitivity and CRF only in boys [7]; however, since only BMI was measured, this association could have resulted from a higher muscle mass in boys rather than from an increased adiposity; the relationship between fasting glucose and CRF disappears when body fat is taken into account; in the same report, HOMA and fasting glucose are negatively associated with CRF only in the higher body fat tertile [9]; Gutin ﬁnds also a relationship between VO2max and the percentage of body fat mass [21, 32] while others ﬁnd no relationship between VO2max and insulin sensitivity [11]. CRF could interact with metabolic risk factors through insulin resistance. Insulin resistance is reported as the key mechanism in the development of metabolic complications of obesity [1], yet these models usually do not take physical activity or CRF into account. Physical training enhances insulin sensitivity in the exercised muscle and enhances muscle contraction-induced glucose uptake in the muscle; the mechanisms include postreceptor insulin signalling, increased glycogen synthesis, and enhanced muscle capillar- ization and blood ﬂow [35]. Obesity is a low-grade inﬂammation disease, positively associated with body fat and negatively with CRF [9]; this inﬂammation, yet not included in MS criteria, is a possible pathway in its pathogenesis: it induces insulin resistance and MS; insulin resistance promotes inﬂammation further through an increase in free fatty acids [17].