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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-0476
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 8 3051-3057
Copyright © 2008 by The Endocrine Society

Assessment of Adiponectin and Leptin as Biomarkers of Positive Metabolic Outcomes after Lifestyle Intervention in Overweight and Obese Children

Valentina M. Cambuli, M. Cristina Musiu, Michela Incani, Monica Paderi, Roberto Serpe, Valeria Marras, Efisio Cossu, M. Gisella Cavallo, Stefano Mariotti, Sandro Loche and Marco G. Baroni

Endocrinology and Metabolism (V.M.C., M.I., M.P., E.C., S.M., M.G.B.), Division of Oncology (R.S.), Department of Medical Sciences, University of Cagliari, 09042 Cagliari, Italy; Pediatric Endocrine Unit (M.C.M., V.M., S.L.), Regional Hospital for Microcitaemia, 09124 Cagliari, Italy; and Departments of Clinical and Medical Therapy (M.G.C.) and Clinical Sciences (V.M.C.), University "La Sapienza" of Rome, 00161 Rome Italy

Address all correspondence and requests for reprints to: M. G. Baroni, M.D. Ph.D., Department of Medical Sciences, Endocrinology and Metabolism, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, Polo di Monserrato, 09042 Monserrato (CA), Italy. E-mail: marcobaroni{at}pacs.unica.it.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Background: A number of metabolic changes are caused by childhood obesity, including insulin resistance, diabetes, and dyslipidemia. To counteract them, lifestyle modification with changes in dietary habits and physical activity is the primary intervention. Anthropometric parameters may not identify all positive changes associated with lifestyle modifications, whereas circulating adipokines may represent an alternative as biomarkers. The aim of this study was to evaluate adiponectin and leptin levels as markers of positive metabolic outcomes in childhood obesity.

Methods: Changes in clinical, anthropometric, and metabolic parameters, including adiponectin and leptin, were assessed in 104 overweight and obese children before and after 1 yr of lifestyle intervention. Obesity and overweight were defined according to the Italian body mass index reference tables for age and sex. Fifty-four normal-weight children were evaluated as controls. Forty-eight of the children (47.5%) returned for follow-up at 1 yr.

Results: Compared with normal-weight children, overweight and obese subjects differed significantly at baseline for glycemia, insulinemia, homeostasis model assessment for insulin resistance, adiponectinemia (5.8 vs. 18.2 µg/ml in controls), low-density lipoprotein-cholesterol, and triglycerides. These parameters were all higher in the overweight/obese children. At follow-up, most parameters improved in overweight/obese children. The most significant changes were observed in adiponectin concentration, which increased by 245% (P < 0.0001), reaching the levels observed in normal-weight children. Leptin levels showed changes unrelated to positive metabolic outcomes, remaining high at 1 yr of follow-up in overweight/obese children. Regardless of changes in weight status, children with lifestyle intervention reported changes in homeostasis model assessment for insulin resistance and in adiponectin that were associated with loss of fat mass.

Conclusions: After lifestyle intervention, adiponectin increased regardless of changes in weight, whereas no consistent changes was observed in serum leptin. Therefore, circulating adiponectin may represent a good biomarker to evaluate the efficacy of lifestyle intervention in overweight/obese children.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
The prevalence of childhood obesity is increasing worldwide (1, 2, 3). Analysis in Italian children shows a similar phenomenon, with a prevalence of excess body weight of 26.9% in males and 21.2% in females (4, 5). Childhood obesity is directly linked to abnormalities in blood pressure, lipids, and insulin action in later life as well as to the risk of diabetes mellitus and coronary artery disease (6, 7). Moreover, diseases of typical onset in adult age such as type 2 diabetes and dyslipidemia are being more frequently observed in obese children and adolescents (8, 9, 10).

With increasing body weight, in particular fat mass, insulin resistance develops, and this is believed to play a major role in the determination of impaired metabolisms at this early age (11).

Although the increase of adipose tissue, particularly visceral, per se is a risk factor of insulin resistance, its secretory products (adipokines) are acquiring a recognized role as determinants of insulin resistance (12). A number of adipokines, including TNF-{alpha}, IL-6, leptin, and adiponectin have been shown to affect insulin sensitivity through the modulation of insulin signaling (13). Adiponectin, in particular, mediates insulin action improving peripheral insulin sensitivity and is inversely related to insulin resistance, showing lower levels in obesity, type 2 diabetes, and metabolic syndrome (14). Adiponectin levels are negatively correlated to body fat and insulin sensitivity (15, 16, 17, 18) and predict type 2 diabetes (19) in obese children also.

Serum leptin is also believed to play a role in obesity (20). Several studies have shown a relationship between leptin levels and energy balance in obese children; however, the results are inconclusive, with leptin levels that either decrease (21, 22) or remain unchanged (23) after exercise or dietary intervention. Leptin resistance has been called on to explain these discrepancies, but it is also possible that central regulation of energy expenditure is influenced by numerous other pathways, making it difficult to identify a unique role for leptin.

It is widely recognized that lifestyle intervention with modification of dietary habits and physical activity is the most important measure to modify weight excess (24, 25, 26) in childhood and adolescence. Simple anthropometric parameters, such as weight or body mass index (BMI), may not identify all the positive changes that are associated with lifestyle modifications. Recently Bell et al. (27) demonstrated that in obese children an exercise training program reduces insulin resistance, measured by euglycemic-hyperinsulinemic clamp, independently of changes in body weight or composition. If circulating adipokine levels are related to the changes in insulin sensitivity of a subject, then they may also represent a simpler and alternative biomarker of positive outcomes.

Based on these observations, the aims of this study were to: 1) investigate changes in clinical, anthropometric, and metabolic [glycemia, insulinemia, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol, triglycerides] parameters in overweight and obese children after 1 yr of lifestyle intervention (educational intervention on diet and physical exercise), 2) evaluate whether the observed changes in overweight and obese children after intervention are comparable with baseline characteristics of a group of normal weight children, and 3) investigate adiponectin and leptin levels in overweight and obese children before and after lifestyle intervention and to assess whether adiponectin or leptin could be useful as biomarkers of improved insulin sensitivity.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

One hundred four overweight or obese children (51 male and 53 female), attending the Obesity Clinic of the Pediatric Endocrine Unit of the Regional Hospital for Microcitaemia, Cagliari, were consecutively recruited for this study. Fifty-four normal weight children, without any endocrine, cardiovascular, gastrointestinal, or renal disorders, were also enrolled in the study as controls. The study was approved by the local ethical committee, and informed consent was obtained from the children or their legal guardians.

Overweight and obesity were defined according to the recently published Italian growth charts for height, weight, and BMI in people aged 2–20 yr (28). Pubertal developmental stages were determined according to Tanner (29), and the children were divided into two groups: prepubertal (Tanner’s stage I), and pubertal (Tanner’s stages II-V), as previously described (23). None of the subjects were taking any form of medication. Exclusion criteria were the presence of endocrine disorders or genetic syndromes, including syndromic obesity.

Of the initial 104 children, 48 returned after 1 yr of lifestyle intervention. In these children the same parameters evaluated at baseline were recorded, together with all changes in anthropometric variables.

Lifestyle intervention consisted in an educational program that involved dietary and physical activity modifications. To the child and his/her parents, dietary guidelines, considering also the dietary habits and age of children, were proposed, recommending the adoption of a normocaloric Mediterranean diet based on a balanced distribution of carbohydrates (55%), proteins (15%), and lipids (30% total, with less than 10% saturated fat). Modifications in physical activity consisted in the recommendation to perform aerobic exercise three to five times per week for at least 45–60 min. Finally, children were advised to reduce sedentary behavior (particularly television and video games) to less than 2 h a day. All children, with their parents, were evaluated after 6 months and after 1 yr from the beginning of the program. At the 6-month evaluation, children were assessed for changes in weight and height and reviewed for compliance to the lifestyle recommendations.

Clinical and metabolic parameters

Fasting glycemia, insulin, total cholesterol, LDL- and HDL-cholesterol, triglycerides, adiponectin, and leptin were measured in all overweight and obese children. The same parameters were tested in the group of overweight and obese children who returned after 1 yr of lifestyle intervention. In normal-weight children, all the above parameters were measured at baseline.

Weight loss was classified as substantial if children weight status changed from obesity to overweight or to normal weight and from overweight to normal weight. These changes were defined according to the reference percentiles of BMI in Italian growth charts (28).

All the overweight and obese subjects underwent bioelectric impedance for the determination of fat-free mass, fat mass, and percent total body water. Resistance and reactance were measured with the subject supine in the morning between 0800 and 0900 h after fasting overnight, with an impedance analyzer with four body surface electrodes and a conduction current of less than 0.8 µA and 50 kHz (model BIA 101; Akern Srl, Florence, Italy). Total fat mass was determined by subtracting fat-free mass from total body weight.

Adiponectin was assayed by RIA (human adiponectin specific RIA kit; Linco Research, Inc., St. Charles, MO). The lower detection limit of this method is 1 ng/ml. Intra- and interassay coefficients of variation are 2.0 and 2.6%, respectively. Leptin was measured by ELISA (human leptin ELISA; IVD Biovendor, Modrice, Czech Republic). Intra- and interassay coefficients of variation were between 1.6 and 6.8% and between 7.9 and 14.6%, respectively.

To estimate insulin resistance in our population, the homeostasis model assessment for insulin resistance (HOMA-IR) (30) was used.

Statistical analysis

Categorical variables were compared by {chi}2 or Fisher’s exact test. Differences between continuous variables were evaluated by two-tailed Student’s t test for unpaired or paired data where applicable and by ANOVA. Adiponectin was correlated to HOMA-IR using linear correlation. Multiple linear regression analysis was performed to estimate the association with changes in parameters known to influence adiponectin levels. In this model, the relationship between adiponectin and the changes in percent fat mass, Tanner stage, weight, and HOMA-IR from baseline were analyzed. P < 0.05 were taken as statistically significant. All statistical analyses were performed using the 15.0 version of SPSS/WIN package (SPSS, Chicago, IL).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Clinical characteristics of overweight/obese children

At baseline 104 overweight/obese children (35 overweight and 69 obese) were studied (clinical characteristics in Table 1Go). When divided by sex, significantly higher HOMA-IR (4.7 ± 2.6 vs. 3.7 ± 1.9; P < 0.038) and leptin (23.5 ± 15 vs. 15.9 ± 12.2; P < 0.009) were observed in females. No other differences were found according to gender.


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  		TABLE 1. Comparison of clinical and biochemical characteristics at baseline in overweight/obese children (group A), compared with normal-weight controls (group B), and comparison at baseline (group C) and after 1 yr of intervention (group D) in the 48 overweight/obese children who returned at follow-up

 
When we compared children by pubertal stage, pubertal children showed higher HOMA-IR (5 ± 2.8 vs. 3.7 ± 1.7; P < 0.004) and insulinemia (23.6 ± 11.4 vs. 16.8 ± 6.8; P < 0.001). In prepubertal children adiponectin levels were higher (6.3 ± 3.8 vs. 4.9 ± 3.2; P < 0.049), whereas serum leptin was significantly lower (15.8 ± 11.5 vs. 26 ± 15.7; P < 0.001) than pubertal children. Finally, when obese children were compared with overweight subjects, both insulinemia (21.2 ± 10.6 vs. 15.9 ± 5.2; P < 0.008) and HOMA-IR (3.4 ± 1.2 vs. 4.6 ± 2.6; P < 0.022) resulted significantly higher, regardless of their pubertal stage.

Clinical differences of overweight/obese children, compared with normal-weight controls at baseline

At baseline, together with the 104 overweight and obese children, 54 normal-weight controls were also studied. The clinical and biochemical characteristics of these two groups are shown in Table 1Go. The two groups did not differ in gender distribution, age, and pubertal stage.

The two groups showed highly significant differences in glycemia (P < 0.009), insulinemia, LDL- and HDL-cholesterol, and triglycerides (all P < 0.0001), already configuring a metabolic phenotype in the overweight and obese children at this early age. HOMA-IR was almost twice in children with excess body weight compared to the controls.

Adiponectin levels resulted significantly different in overweight and obese children, compared with normal-weight subjects, in which adiponectin levels were 3 times higher (18.2 ± 8 vs. 5.7 ± 3.7; P < 0.0001) than their obese counterparts. Leptin levels were significantly higher (P < 0.0001) in the overweight and obese group. When analyzed in the whole population, adiponectin serum levels were negatively correlated to insulin resistance index HOMA-IR (r2 = 0.078; P < 0.001), whereas leptin levels were positively related (r2 = 0.17; P < 0.0001).

Characteristics of overweight/obese children after 1 yr of lifestyle intervention

After 1 yr of lifestyle intervention (diet and physical exercise), 48 children returned for the follow-up evaluation. Of these, according to the definition of weight loss in Subjects and Methods, 16 children substantially reduced their weight, 31 showed no change in weight status and only one child increased his weight. Nine of the 28 prepubertal children at baseline (32.14%) were in a pubertal stage at follow-up.

At follow-up, regardless of the outcome on body weight, mean fasting plasma glucose (P < 0.024), insulinemia (P < 0.018), HOMA-IR (P < 0.013), and fat mass (P < 0.0001) were significantly reduced, compared with baseline values (Table 1Go). No significant change was observed in lipid parameters.

Adiponectin levels showed a marked increase over baseline, from 5.9 ± 4 to 14.7 ± 9.2 (P < 0.0001). Moreover, the increased adiponectin levels correlated significantly with the decrement in percent fat mass (r2 = 0.18; P < 0.013) observed at the end of follow-up. To further demonstrate the independent association between changes in percent fat mass and changes in adiponectin levels, multiple linear regression analysis was used to examine this association in the presence of other factors known to possibly influence adiponectin levels, including changes in Tanner stage, weight, and HOMA-IR. The multivariate analysis confirmed that the changes in percent fat mass were the only significant and independent determinant of adiponectin changes (F = 7.2, P < 0.02; data not shown).

At variance with what was expected, leptin levels increased after 1 yr of intervention, going from 18.4 ± 14.3 to 23.4 ± 14.7 (P < 0.025) (Table 1Go), and no correlation was seen between leptin levels and percent fat mass.

When the differences from baseline in metabolic parameters between the children who lost weight and those without changes in weight status were analyzed, we observed significant decrements in glycemia (P < 0.031), total- and LDL-cholesterol (P < 0.04), and leptin (P < 0.031) in children with weight loss, whereas no significant difference from baseline was observed in the reduction in insulin and HOMA-IR (Table 2Go). Moreover, both children with and without changes in weight status had the same percent fat mass loss, suggesting in the latter subjects a qualitative, more than a quantitative, difference in body weight at follow-up. Finally, at 1 yr no differences in the changes in adiponectin levels were seen between the two groups of children (Table 2Go). Thus, regardless of significant weight changes, insulin, HOMA-IR, adiponectin, and percent fat mass were all improved in all children, indicating that the lifestyle intervention may have determined an improvement of the metabolic status in our population.


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  		TABLE 2. Analysis of the differences at 1 yr (from baseline) in metabolic parameters between the children who lost weight and those without changes in weight status

 
To further confirm these observations, the children who returned at 1 yr follow-up were then compared with the normal-weight children, regardless of the positive outcome in weight status (Table 1Go). The obese children at follow-up showed adiponectin levels similar to those of the normal weight subjects (14.7 ± 9.2 vs. 18.2 ± 8; P = NS); mean glycemia, total and LDL-cholesterol, and triglycerides values were also similar to those observed in normal-weight subjects (all P = NS). However, significant differences in insulin levels, HOMA-IR, and leptin (P < 0.0001 for all comparisons) were observed (Table 1Go).

When we compared only the obese/overweight children who lost weight with the normal-weight children, no differences were observed for most of the parameters, including insulin, HOMA-IR, and adiponectin levels, further indicating the positive effects of lifestyle changes on these factors (Table 3Go). Leptin levels, however, were still higher in obese/overweight children with weight loss, compared with the normal-weight children, suggesting that, despite "normalization" of the metabolic status, leptin did not follow these positive changes.


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  		TABLE 3. Comparison between children with weight loss at 1-yr of follow-up and normal-weight controls

 
Adiponectin, but not leptin, as biomarker of positive outcomes

From the above observations, it emerges that leptin levels showed changes in disagreement with the positive outcomes after intervention (Fig. 1AGo). Leptin was higher in overweight and obese children, compared with normal-weight children at baseline (P < 0.0001). Leptin remained high at 1 yr of follow-up in all overweight and obese children, even in those who lost weight (Fig. 1AGo). Thus, leptin levels remained constantly above the levels observed in normal-weight children.


Figure 1
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  		FIG. 1. Changes in leptin (A) and adiponectin (B) levels in overweight /obese children at baseline and after 1 yr of intervention. Overweight and obese children are divided in two subgroups, showing results in children with weight loss and in children without. *, P < 0.001, comparing normal-weight (nw) with overweight and obese children (ow/ob) at baseline and in the two subgroups after 1 yr of lifestyle intervention (A). §, P < 0.0001 in the comparison between overweight and obese children at baseline and normal-weight children and between overweight and obese at baseline and after 1 yr follow-up (B). Data are expressed as means and SD.

 
Adiponectin levels at baseline were markedly different (P < 0.0001) between overweight and obese children and controls (Fig. 1BGo). After 1 yr of lifestyle intervention, a highly significant rise (P < 0.0001) in adiponectin serum levels, reaching levels similar to those found in normal weight children was observed, regardless of substantial changes in body weight.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
This study shows that lifestyle modification in overweight/obese children, even without detectable weight loss, determines positive changes in clinical and metabolic parameters. All the children who followed the dietary and physical activity recommendations improved their metabolic status. In particular, we observed that adiponectin levels almost trebled in overweight/obese children after 1 yr follow-up, together with the improvement in parameters related to insulin resistance, including insulin and HOMA-IR index.

Childhood obesity is a recognized risk factor of dyslipidemia, hypertension, metabolic syndrome, and diabetes mellitus in later life. Twenty-five-year projections suggest that obesity in adolescence will determine a significant increase in rates of coronary artery disease among future young adults (6, 7). In obese children, the process of atherosclerosis has been shown to start at an early age (31). A very recent report by Beauloye et al. (32) demonstrates that carotid intima-media thickness is increased in obese children, representing a very early sign of atherosclerosis. In these subjects, low adiponectin was the only independent determinant of early intima-media thickness after correction for classical risk factors. The use of adiponectin as a potential screening tool for insulin resistance and atherosclerosis in children has been suggested by a number of studies (17, 18, 32, 33); however, its role as an indicator of metabolic change after intervention has not been thoroughly investigated.

In our study, adiponectin levels in overweight and obese children were significantly lower at baseline, compared with normal-weight children, confirming previous observations (16, 34). After lifestyle intervention, adiponectin levels, together with several other metabolic parameters, were significantly improved, potentially resulting from weight loss, improvement of metabolic status, or both.

The novelty of our study is that, even without changes in body weight, children who followed dietary and physical activity recommendations obtained a positive result at the end of the study. This result contrasts with a previous study (35) in which no metabolic changes were observed in children who did not lose weight, but it is in agreement with a very recent report that shows that insulin sensitivity, measured by the gold-standard method euglycemic-hyperinsulinemic clamp, increases in obese children after 2 months of structured exercise (27). The result of this study was observed without significant changes in body weight or body composition. Furthermore, our data are partially in line with the results of a study by Balagopal et al. (36). In this 3-month study, adiponectin levels increased in eight obese children after a structured lifestyle intervention, and this increase was correlated to a decrease in fat mass, regardless of changes in body weight. At variance with our results, the seven children undergoing a nonstructured overweight intervention did not show changes in these parameters. It could be hypothesized that the short intervention time may have been insufficient to detect greater changes.

Among the positive changes measured in our children, the increase of adiponectin appears as an early biomarker of improved insulin sensitivity. Within the whole group of overweight and obese children, several metabolic parameters involved in insulin sensitivity (glycemia, insulin HOMA-IR, adiponectin, percent fat mass) were significantly improved, confirming the positive impact of lifestyle intervention. When we looked at which of these parameters related to insulin action had reached levels similar to the values observed in normal weight children, only glycemia and adiponectin were normalized. Adiponectin in particular increased by 245% from baseline (from 5.9 to 14.7 µg/ml) at the end of the study. It is important to point out that the changes in adiponectin were significantly and independently associated with changes in percent fat mass. It has to be highlighted that even those children who did not lose weight obtained a significant reduction in percent fat mass. The role of adiponectin as marker of positive metabolic changes is further confirmed by the observation that the increasing adiponectin levels corresponded to the improvement of all the other metabolic parameters (see Tables 1Go and 3Go).

The present study also shows that leptin, at variance with adiponectin, cannot be used as a reliable biomarker of positive metabolic outcomes of lifestyle intervention in overweight and obese children. Indeed, leptin has also been proposed as a marker of metabolic variations in obesity and insulin resistance (reviewed in Ref. 20). However, several observations point toward a role of leptin in states of energy deficiency rather than being a predictor of the metabolic syndrome (37). In our study, leptin levels showed changes in disagreement with the positive outcomes after intervention. Contrary to what was expected, leptin remained higher at 1 yr of follow-up in overweight and obese children. Leptin increased significantly in those children without weight loss (from 18.6 ± 14.4 to 26.8 ± 14.6; P < 0.005) but also in those children who did lose weight no significant changes from their baseline (from 17.1 ± 12.8 to 16.4 ± 12.7; P = NS) were observed, suggesting that leptin does not follow directly the changes in body weight. This is in agreement with the data reported by Reinehr et al. (23), which showed that leptin levels did not significantly change in obese children who lost weight and increased in those who did not change their weight status. Thus, within the major adipokines, leptin does not appear to be the best tool to measure insulin sensitivity or metabolic changes.

One possible limitation of our study is that a number of children were lost at follow-up. Although some of them may have moved away, the most plausible reason is that they did not adhere to lifestyle recommendations. Despite the fact that we had a reduction in the number of study subjects, our sample size is similar to, and in some cases larger than, reference studies on this issue (22, 23, 34, 35). Another possible confounding factor may be the number of children who changed pubertal status during the follow-up. Nine (seven males and two female) of the prepubertal children were in puberty at the end of the study. It is recognized that adiponectin levels progressively decline with physical and pubertal development, especially in boys (38). However, in this subgroup of children, we found a relevant increment in adiponectin mean levels (from 5.6 to 15.2 µg/ml; P < 0.0009) together with a nonsignificant decrement in insulinemia and HOMA-IR, suggesting that, in children with excess body weight, lifestyle intervention counteracted the expected physiological decline of adiponectinemia and insulin sensitivity. Leptin, as shown previously (23, 35), increased in pubertal children at follow-up (P < 0.05 data not shown). This increment is expected in puberty, and it is not modified by lifestyle intervention, similarly to prepubertal children.

Other parameters, together with adiponectin, changed when compared with baseline. However, these changes, although significant, are comprised within a small range of values. For example, fasting glycemia decreases significantly from 90.7 mg/dl at baseline to 88.5 mg/dl at the end of the study. This change is clearly of little use in clinical practice. Similarly, insulin levels show the same small variation, always within the normal range. Adiponectin levels, on the other hand, underwent a significant increment (+245%) in our children, suggesting that this marker could be useful to define the metabolic status of a subject in the clinical routine. Longitudinal studies are necessary to confirm these observations and define the predictive value of adiponectin on metabolic and clinical outcomes.

In conclusion, our study confirms the positive effects of simple dietary and physical activity recommendations on metabolic and clinical parameters in overweight/obese children. When simple markers to detect and monitor metabolic alterations were investigated, adiponectin provided the best measure for this objective. Further studies are needed to confirm the efficacy of periodical circulating adiponectin measurements in the management of overweigh/obese children.


   Acknowledgments
 
We thank all the children and adolescents who participated in the study. We also thank Professor Minerba for suggestions and Mark Wheaton for linguistic assistance.


   Footnotes
 
This work was supported by research grants from the University of Cagliari (ex-60% 2006–07) and the Sardinian Regional Government awarded to Marco G. Baroni. Valentina M. Cambuli was awarded the 2007 "Alberto Malliani" prize for her research project on obesity and diabetes in childhood by the Italian Society of Internal Medicine.

Disclosure Statement: The authors have nothing to disclose.

First Published Online May 20, 2008

Abbreviations: BMI, Body mass index; HDL, high-density lipoprotein; HOMA-IR, homeostasis model assessment for insulin resistance; LDL, low-density lipoprotein.

Received February 29, 2008.

Accepted May 7, 2008.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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