PEDIATRICS Vol. 120 No. 6 December 2007, pp. e1426-e1433 (doi:10.1542/10.1542/peds.2007-0189)
ARTICLE |
Fasting Nonesterified Fatty Acid Profiles in Childhood and Their Relationship With Adiposity, Insulin Sensitivity, and Lipid Levels
a Clinical Sciences South Bristol, University of Bristol and Bristol Royal Hospital for Children, Bristol, United Kingdom
b Biochemical Genetics Metabolic Laboratory, Southmead Hospital, Bristol, United Kingdom
c School of Applied Sciences, University of Glamorgan, Glamorgan, Wales, United Kingdom
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ABSTRACT |
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OBJECTIVE. The objective of this study was to examine the major constituent of nonesterified fatty acids in children with respect to auxologic parameters, insulin sensitivity, and lipid levels, because nonesterified fatty acid levels are elevated in obesity and are important in the development of comorbidities.
METHODS. Fasting blood samples were obtained from 73 children (43 girls; 49 obese; median [range] age: 11.4 [0.9–17.6] years). Concentrations of the major circulating nonesterified fatty acids (myristate, palmitate, oleate, stearate, and arachidate) were determined by gas chromatography mass spectrometry, alongside measurement of insulin, adiponectin, and lipid profiles.
RESULTS. The sum of all nonesterified fatty acids was significantly higher in obese versus normal-weight children, although gender (but not age or puberty) was an important determinant, with the difference remaining significant only in boys. Overall, obese children had higher concentrations of myristate, palmitate, and oleate but not stearate or arachidate. Age was an important determinant of myristate and arachidate, whereas gender proved more important for palmitate and stearate. Fasting insulin concentrations were not associated with either total nonesterified fatty acid concentrations or any of the individual nonesterified fatty acids, although a positive correlation was found between adiponectin and total nonesterified fatty acid concentrations that was independent of obesity status and that seemed mediated by changes in palmitate and stearate. Serum total cholesterol and low-density lipoprotein (but not high-density lipoprotein) levels seemed to correlate positively with circulating concentrations of palmitate, oleate, and stearate, whereas serum triacylglycerols correlated with myristate, palmitate, and oleate concentrations.
CONCLUSIONS. Nonesterified fatty acid concentrations are elevated in obese children, primarily as a result of increases in myristate, palmitate, and oleate. Independent effects of nonesterified fatty acids on circulating adiponectin levels and lipid parameters were observed, although we found no relationship between nonesterified fatty acid concentrations and the insulin resistance identified with obesity.
Key Words: fatty acid • obesity • adiponectin • children • puberty • insulin • lipids
Abbreviations: NEFA—nonesterified fatty acid • SDS—SD score • SCD-1—stearoyl CoA desaturase 1 • ELISA—enzyme-linked immunosorbent assay • CV—coefficient of variation • HDL—high-density lipoprotein • LDL—low-density lipoprotein
The number of obese children throughout the world continues to increase,1 which is concerning given the associated comorbidities such as impaired glucose tolerance,2 type 2 diabetes,3 nonalcoholic fatty liver disease,4 and the metabolic syndrome.5 Circulating concentrations of nonesterified fatty acids (NEFAs) are elevated in obese adults and are implicated in reductions in insulin sensitivity and endothelial function.6,7 Prepubertal children, however, differ in their response to an intravenous fat emulsion challenge compared with pubertal children and adults,8 and their exposure to sex steroids (which are known to influence triacylglycerol synthesis9,10) is minimal; therefore, for a more full understanding the role of NEFAs in childhood obesity and the consequent development of associated comorbidities, it is important that we investigate these processes in obese and normal-weight children across the age and pubertal spectrum. A recent study from Germany11 that examined the concentrations of circulating fatty acids in 57 obese and 10 normal-weight children found significantly elevated concentrations in the obese children (median [interquartile range] 440 µmol/L [340–610] vs 290 µmol/L [110–470]; P = .023). Furthermore, in this study, reductions in BMI SD scores (SDSs) >0.5 during 1 year led to a significant reduction in NEFA concentrations (550 µmol/L [640–770] changing to 510 µmol/L [370–540]; P = .044), an effect not seen in less successful children. This mirrored the results from a much earlier trial12 in 1978 that also showed improvements in NEFA concentrations in obese children who were able to lose weight and indicate that changes in total circulating concentrations of NEFAs are related to adiposity in childhood.
Most studies that examine NEFAs in children and that demonstrate elevated concentrations in obese individuals use an enzymatic, colorimetric method (Wako Chemicals USA, Inc/Randox Laboratories, Richmond, VA) to determine total circulating NEFA concentrations.13 Although these types of assays provide important data pertaining to the total concentrations of NEFAs, they give no information on the relative amounts of saturated and unsaturated fatty acids. This might be crucial for a number of reasons. First, diet may directly affect circulating concentrations of saturated and unsaturated fats either through variations in fat intake14 or through the generation of palmitate from dietary glucose and its subsequent conversion to monounsaturated NEFAs by the action of stearoyl CoA desaturase 1 (SCD-1; converts palmitate to palmitoleic acid and stearate to oleate).15 Furthermore, it seems that variations in the type of dietary fat may substantially affect the deposition and modeling of triacylglycerols in adipose tissue during childhood growth, and this may be an important factor in determining a child's susceptibility to the development of later obesity.16 Second, the majority of circulating NEFAs arise from lipolysis from adipose sites, and because the fatty acid composition of adipose tissue seems to be depot-specific,17 variations in the type of saturated and unsaturated NEFAs released during pulsatile lipolysis may have important effects on metabolism.18 Finally, saturated and unsaturated NEFAs seem to have specific, differential effects on muscle insulin signaling in vitro,19,20 evident even in biopsies derived from children21; therefore, differences in circulating concentrations may have an impact on the development of insulin resistance in susceptible individuals. We therefore sought to investigate whether circulating concentrations of the major NEFAs (myristate [14:0], palmitate [16:0], stearate [18:0], oleate [18:1(n-9)], and arachidate [20:0]) are influenced by obesity, as well as explore whether there are associations between circulating concentrations and either general lipid parameters, such as cholesterol and triacylglycerols, or markers of whole-body insulin sensitivity (fasting insulin and adiponectin). Our primary hypothesis was that obesity may alter the relative contributions of the predominant saturated and unsaturated NEFAs, which would prove important in the development of insulin resistance.
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METHODS |
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Patients
After an overnight fast, blood samples were obtained from children who attended our obesity clinic22 (n = 49) as part of routine analysis of lipid parameters and insulin sensitivity, as well as a group of normal-weight school children (n = 24). Pubertal assessment was performed by clinical examination in obese patients and by self-reporting in healthy children,23 for whom a formal examination was not deemed appropriate. The clinical onset of puberty was defined by a testicular volume of at least 4 mL for at least 1 testicle for boys and a stable Tanner breast stage of at least B2 for girls, whereas self-reporting children were deemed to be pubertal when they had any genital (G2 or higher) or breast (B2 or higher) development, respectively. Height was measured to the nearest 0.1 cm by using a Holtain stadiometer (Harpenden, Crosswell, United Kingdom), and weight was measured on SECA (Birmingham, United Kingdom) scales to the nearest 0.1 kg. BMI was calculated as weight (kg)/height (m2), and BMI SDS (representing increases or decreases at approximately the 50th centile for age) was calculated by using the British 1990 growth reference data supplied by the Child Growth Foundation. Obesity was defined as being present when the BMI SDS was greater than +2.37 in boys and +2.25 in girls, United Kingdom figures that have been derived by extrapolating the adult cutoff of 30 kg/m2 back into childhood.24 Clinical details are shown in Table 1. One child was younger than 3 years, but because this result did not seem different from the rest, data from this child were not excluded from analysis. Blood samples were immediately separated and stored at –80°C. Specific ethical approval for sampling healthy school children was obtained from the School of Applied Sciences Ethics Committee at the University of Glamorgan (Glamorgan, Wales, United Kingdom), and metabolic analysis in the obese children was undertaken as part of their routine clinical evaluation.
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Materials
All of the major circulating NEFAs (myristate [tetradecanoic acid], palmitate [hexadecanoic acid], oleic acid [octadecanoic acid], stearate [octadecanoic acid], and arachidate [eicosanoic acid]) were purchased from Sigma (Dorset, United Kingdom). The internal standards, tetradecanoic-6-6-d2 acid, hexadecanoic-3,3-d2 acid, octadecanoic-2,2-d2 acid, octadecanoic-2,2-d2 acid, and eicosanoic,20,20,20-d3 acid were purchased from CDN Isotopes (Pointe-Claire, Quebec, Canada). Ethyl acetate, chloroform, and acetonitrile were analytical grade and purchased from VWR (Leicestershire, United Kingdom). The derivatization reagent N-methyl-N-(tert-butyldimethylsilyl) trifluoroacetamide was purchased from Pierce Biotechnology (Rockford, IL). Adiponectin enzyme-linked immunosorbent assay (ELISA) assay kits were donated for this study by Metachem Diagnostics (Northampton, United Kingdom).
Determination of NEFA Profiles
Plasma free fatty acids were extracted, separated, and quantified by adaptation of a previously published method.25 A total of 100 µL of plasma was extracted twice with ethyl acetate in glass tubes that contained a known quantity of deuterated internal standard for each fatty acid. The solvent layer was dried under nitrogen and derivatized by using N-methyl-N-(tert-butyldimethylsilyl) trifluoroacetamide. Gas chromatography mass spectrometry analysis was conducted on an Agilent (Santa Clara, CA) 6890N gas chromatograph interfaced to an Agilent 5973 mass selective detector with which NEFAs were detected by selective ion monitoring of the fragment ions at a mass/charge ratio of (M-57)+. Six-point calibration curves were drawn by using known quantities of each fatty acid.
Precision was established by analysis of both within- and between-batch variation of a patient pool of EDTA plasma held in the Clinical Chemistry department at Southmead Hospital (Bristol, United Kingdom; n = 27). The overall precision reflected previously published levels,25 and the coefficients of variation (CVs) were as follows: myristate, 6.6%; palmitate, 10.4%; oleate, 6.3%; stearate, 13.8%; and arachidate, 20.2%. Quality control was performed by using concentrations of NEFA solution (in chloroform) and concentrations of plasma-based commercial materials (seronorm lipid; BioStat Diagnostic Systems, Stockport, United Kingdom), which were run with each batch.
Determination of Adiponectin, Insulin, and Glucose Concentrations and Lipid Profiles
Fasting blood samples were also analyzed for total adiponectin concentrations by ELISA (Metachem Diagnostics; intra-assay CV: 4.3%; interassay CV: 5.3%); insulin, by ELISA (Dako Cytomation, Glostrup, Denmark; code no. K6219; intra-assay CV: 2.0%; interassay CV: 3.9%; minimum detectable limit: 1 mIU/L); and lipid profile (cholesterol, high-density lipoproteins [HDLs] and low-density lipoproteins [LDLs], and triacylglycerol concentrations), using an assay from the Olympus Diagnostics System Group (Center Valley, PA).
Statistical Analyses
Standard statistical tests were used throughout, with 2-sample Student's t tests used to compare the means of 2 groups and Pearson's correlation coefficients used to study the correlation between pairs of continuous variables. A series of multiple linear regression analyses were used to study the effects of gender, pubertal status and obesity (as binary variables), and age (as a continuous variable) on the total NEFA concentration and the component moieties. Interactions between the predictor variables were studied first in the presence of main effects. Nonsignificant variables were deleted in a backward manner. Similar approaches were used to look at determinants of the ratio of circulating unsaturated to saturated NEFAs. This ratio, together with insulin and triacylglycerol values, was logarithmically transformed before statistical analysis to remove skewness, and geometric means and ranges were used for their data summary. Stata 8.0 (Stata Corp, College Station, Texas) statistical software was used for the analysis. A 5% level of significance was adopted throughout.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Auxology, circulating NEFA profiles, and adiponectin concentrations were determined for all children in the study. Insulin and lipid profiles were available only for 63 children (48 obese/15 normal-weight) because 1 obese child had not had these tests requested and samples from normal-weight children were insufficient for the determination of insulin and lipids. Overall, these 63 children were representative of the group as a whole, although in the normal-weight group, there were more older (and pubertal) children who had bloods analyzed for insulin and lipids. Analysis of total and individual NEFA concentrations with respect to auxologic parameters was therefore possible in all 73 children, whereas assessment of their variation in relation to insulin and lipids was possible only in the subset of 63 children.
Total NEFA Concentrations
Mean total NEFA concentrations were significantly higher in obese compared with normal-weight children (Table 2). Additional regression analyses, however, showed a significant interaction between effects of gender and obesity on the total NEFA (P = .044) but no significant effect of age or pubertal status. The mean total NEFA concentration was significantly higher in obese boys than in normal-weight boys (463 µmol/L [SD: 137] vs 295 µmol/L [SD: 114]; P = .002), although the corresponding difference was not significant for girls (403 µmol/L [SD: 148] vs 384 µmol/L [SD: 157]; P = .714).
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Individual NEFAs
Within the whole group, obese children had significantly higher mean concentrations of myristate, palmitate, and oleate but not stearate or arachidate (Table 2). In the subsequent regression modeling, none of the individual NEFAs was significantly related to puberty. The myristate concentrations showed a significant relationship with age (P = .001), although even after adjustment for age, the obese children exhibited myristate levels that were on average 3.81 µmol/L (95% confidence interval: 1.32–6.30) higher than those in normal-weight controls (Fig 1).
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Age was not significantly related to either palmitate or stearate concentrations, although for each of these 2 variables, there was a significant interaction between the effects of obesity status and gender (P = .038 and P = .008, respectively). The mean concentration of palmitate was significantly greater in obese versus normal-weight boys (186 µmol/L [SD: 56] vs 117 µmol/L [SD: 44]; P = .001), whereas the difference was not significant for girls (156 µmol/L [SD: 59] vs 147 µmol/L [SD: 55]; P = .641). Likewise, the mean concentration of stearate was significantly elevated in obese versus normal-weight boys (58 µmol/L [SD: 14] vs 43 µmol/L [SD: 11]; P = .020), whereas the difference was nonsignificant for girls (47 µmol/L [SD: 19] vs 56 µmol/L [SD: 21]; P = .146), accounting for stearate levels' not being significantly elevated in the obese group as a whole. The only significant determinant of circulating oleate concentrations was obesity, as shown in Table 2.
Age was the only significant determinant of arachidate (P = .038), although the relationship seemed to be strongly influenced by a few outlying observations (data not shown). The weak negative correlation, however, was confirmed by using nonparametric analysis (Kendall's 
= –0.190; P = .017).
To identify factors that were important in determining the relative concentrations of saturated and unsaturated NEFAs, we also determined the effects of age, gender, puberty, and obesity status on the total unsaturated/saturated ratio (determined as oleate/[myristate + palmitate + stearate + arachidate])). There was an overall group difference (shown in Table 2), and in subsequent regression modeling, the ratio of unsaturated/saturated NEFAs was found to be related to both age (P = .022) and obesity (P = .003). Figure 2 illustrates the fitted regression model.
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Relationship Between NEFAs and Insulin Sensitivity
As expected, the obese children had significantly higher fasting insulin concentrations than the nonobese group (geometric mean [range]: 13.3 mIU/L [2–53] vs 8.0 mIU/ l [1–23]; P = .017). Also, from a multiple regression model of the (logged) values, we found no gender difference (P = .796) but significantly higher fasting insulin results in pubertal children (P = .016), reflecting the decreased insulin sensitivity that is normally found in puberty. Effects as a result of obesity remained significant in this model (P = .007).
In separate analyses, no significant correlations were found, in the whole group or in either the obese or nonobese children, between fasting insulin concentrations and either the total NEFA concentrations or any of the component parts of the NEFA profile, or the ratio of unsaturated/saturated NEFAs. Finally, the NEFA variables were added individually to the regression model of insulin on puberty and obesity, and these confirmed no significant, independent effects of the NEFAs on insulin, either as main effects or as effect modifiers.
Also as predicted, obese children had significantly lower concentrations of adiponectin compared with their normal-weight peers (mean [SD]: 8.5 µg/mL [4.1] vs 12.2 µg/mL [6.1]; P = .003). A relationship with age was previously reported,26 and regression modeling here showed significant independent effects of both age and obesity on adiponectin (P = .017 and P = .001, respectively; Fig 3), with values for obese children being on average 3.9 µg/mL (95% confidence interval: 1.6–6.2) lower than for normal-weight control subjects. In contrast to previous studies,27 however, no differences were seen between the mean adiponectin levels of boys and girls or between prepubertal and pubertal children.
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Across all children, adiponectin was positively correlated with stearate (r = 0.323, P = .005) and arachidate (r = 0.260, P = .027) and negatively correlated with the unsaturated/saturated ratio (r = –0.238, P = .043). There were weak, nonsignificant correlations with total NEFA and palmitate, associations that were stronger among the obese children (r = 0.315, P = .027; and r = 0.346, P = .015, respectively). For examination of whether the relationship between adiponectin and NEFA concentrations was independent of the effects of age and obesity, the total and individual NEFA components were added individually to a regression model with these 2 predictors. These confirmed positive correlations between adiponectin and total NEFAs, palmitate, and stearate (Table 3).
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Relationship Between NEFAs and Components of a Standard Lipid Profile
As expected, the obese children (compared with normal-weight children) had significantly lower mean HDL values (normal-weight: 1.5 mmol/L [SD: 0.3]; obese children: 1.1 mmol/L [SD: 0.2]; P < .001), higher total cholesterol/HDL ratios (geometric mean [range]: 2.9 [1.9–3.9] vs 3.6 [2.3–5.8]; P < .001), and higher triacylglycerol values (geometric mean [range]: 0.6 mmol/L [0.3–1.1] vs 1.0 mmol/L [0.5–2.7]; P < .001). There were, however, no significant differences in either the total cholesterol or LDL values. Multiple regression analyses did not reveal any additional significant relationships between the lipid variables and gender, pubertal statu, and age, although triacylglycerols showed a slight but nonsignificant increase with age (P = .052).
Overall, the lipid parameters (except HDL) significantly correlated with total NEFAs, palmitate, oleate, and stearate but not arachidate (apart from stearate versus triacylglycerol, where the correlation did not reach significance). Myristate concentrations only seemed to correlate with triacylglycerol and total/HDL ratio. Scatter diagrams (data not shown) showed that there were similar relationships within both groups, and the correlation coefficients for the combined cohort are shown in Table 4. No significant correlations were seen between the unsaturated to saturated NEFA ratio and any part of the lipid profile.
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Given the group differences observed with respect to mean levels of HDL, ratios of total to HDL cholesterol, and triacylglycerol, multiple regression analyses were used to adjust for group difference. The correlations with the NEFAs were largely unchanged by these adjustments (Table 4). The group differences remained significant in all of these analyses, indicating that differences in HDL, ratios of total/HDL cholesterol, and triacylglycerol could not be explained by differences in the total NEFA or any of the NEFA components.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The prevalence of childhood obesity continues to increase and is associated with the development of insulin resistance and type 2 diabetes, as well as risk factors for future cardiovascular and liver disease.28 The presence of obesity-related complications in childhood, however, does not seem to depend solely on the actual level of obesity22 but is likely to depend on numerous other factors, including inherited susceptibility and environmental cues.29 Elevated circulating NEFA concentrations are seen in obesity and are thought to play a critical role in the development of obesity-related insulin resistance in susceptible individuals30; however, because the metabolic response to increased lipid exposure seems different in prepubertal children compared with adults,8 any relationship among NEFAs, adiposity, and insulin resistance might also prove different.
In this study, we aimed to examine the effects of obesity (using recognized BMI SDS cutoffs24) on circulating fasting NEFA concentrations in a group of 73 children. We were also interested in assessing whether fasting circulating NEFA concentrations correlated with measures of peripheral insulin sensitivity or components of a general lipid profile, established markers for future diabetes and heart disease, respectively.
Consistent with previous reports,11 we found that obese children displayed significantly elevated fasting circulating concentrations of NEFAs, compared with normal-weight individuals, although this significant increase was seen only in boys and not girls. The reasons for this are unclear but may be related to gender-specific differences in fat accumulation during childhood and adolescence.31 Another important finding was that the majority of the increase in NEFA concentrations seems to depend on significant increases in palmitate, oleate, and myristate, rather than stearate or arachidate. Okada et al32 also described significant elevations in myristate, palmitate, palmitoleic acid, and oleate but not stearate in obese children compared with normal-weight peers; however, in a multiple regression analysis, percentage of body fat, waist-to-height ratio, and waist-to-hip ratio were found to be significant determinants only of the concentration of circulating palmitoleic acid, a somewhat unexpected finding given that most of the other NEFAs were also raised in their obese children and that palmitoleic acid is a minor contributor to total circulating NEFA concentrations.33 Taken together, our data in accordance with those of Okada et al suggest that palmitate, oleate, and myristate are increased in children with higher BMI. Furthermore, we found that the ratio of unsaturated/saturated NEFAs seems significantly affected by age and obesity.
It is interesting that Okada et al32 also found that obese children had significantly higher palmitoleic acid/palmitate ratios (palmitoleic acid being the monounsaturated NEFA derived from saturated palmitate by SCD-1), suggesting increased SCD-1 activity in obese children.15 Our data also support this hypothesis.
In terms of the relationship between circulating NEFA concentrations and insulin sensitivity, we were unable to demonstrate any significant association (using fasting insulin as a valid surrogate marker34), suggesting that circulating NEFA concentrations per se do not have a direct impact on peripheral insulin sensitivity in children. In this respect, it may be that local tissue NEFA concentrations are more important or that other factors play a more important role in the determination of whole-body peripheral insulin sensitivity. We did, however, unexpectedly find a positive correlation between circulating adiponectin concentrations and total NEFA levels, an effect that seemed mainly mediated through changes in palmitate and stearate. A previous report35 showed that increases in circulating adiponectin levels after weight loss correlate with improvements in serum lipid parameters and that this effect seems independent of both body composition and insulin sensitivity. In fact, postprandial increases in free fatty acid levels after the ingestion of an oral fat load in adults have been shown to be associated with significant increases in adiponectin levels.36 Our data, along with these findings, suggest a relationship between NEFA and adiponectin concentrations that is independent of body composition or insulin sensitivity. Furthermore, although changes seen in palmitate, oleate, and stearate in children with obesity mirror changes in total cholesterol, LDL, and triacylglycerol levels, our data show that elevated NEFAs are not causative for this dyslipidemia.
Unfortunately, we were unable to evaluate dietary intake during this study. Given our findings and that intake is a major determinant of NEFA concentrations, it would be interesting now to investigate further how variation in the fat component of each child's diet relates to individual variation in circulating NEFA profiles.
One specific limitation of our study design should be highlighted. Although it is important in these types of studies to identify pubertal stage as accurately as possible (because it is an important confounding variable), it was believed inappropriate to expose the normal-weight children to a clinical examination for determination of pubertal stage, meaning that we had to rely on self-reporting questionnaires. It is therefore possible that the pubertal stage may not have been correctly identified in these individuals, especially in those with a degree of adrenarche. This is important because adrenarche is known to be related to both body composition and insulin resistance. Furthermore, the numbers of children in the different pubertal groups was relatively small; taken together, we therefore believe that definite conclusions regarding pubertal effects on NEFAs cannot be made from this study. In addition, a large number of statistical comparisons were made in this study, and it is possible that some that were deemed "statistically significant" occurred by chance. Additional studies may now be warranted to investigate these associations in larger cohorts of normal-weight and obese children.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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We have described the effects of obesity on NEFA profiles during childhood and adolescence and demonstrated that obese children exhibit elevated concentrations of fasting circulating NEFAs compared with their normal-weight peers. The majority of this increase seems to be the result of elevations in palmitate, oleate, and myristate. We have also shown that increases in NEFA concentrations in children are associated with higher circulating levels of adiponectin (independent of adiposity) and that increases in NEFAs are associated with but not causative of increases in other lipid parameters. Furthermore, our data, in accordance with those of Okada et al,32 support the idea that SCD-1 activity may be elevated in obese children. Taken together, these data further improve our understanding of the relationship between circulating NEFA concentrations and insulin resistance in childhood obesity. The lack of association between circulating NEFA concentrations and fasting measures of total-body insulin sensitivity was a surprising finding, given the wealth of published data showing that NEFAs play an important role in the development of insulin resistance. A potential explanation is that childhood obesity is associated with derangements in tissue-specific concentrations of certain NEFAs that may then directly influence the development of insulin resistance in particular individuals. Additional investigation in this area may allow the identification of obese children who are most at risk for developing obesity-related disease.
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ACKNOWLEDGMENTS |
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Dr Sabin is a Diabetes UK Clinical Training Fellow (BDA:RD 03/0002642).
We thank Dr Janet Stone in the Clinical Chemistry Department (Bristol Royal Infirmary) for assistance with the study. We are also grateful for the help provided by Metachem Diagnostics, Inc, which kindly donated adiponectin ELISA kits for this study.
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FOOTNOTES |
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Accepted May 9, 2007.
Address correspondence to Julian P.H. Shield, MD, Royal Hospital for Children, Institute of Child Health, Department of Paediatric Endocrinology and Metabolism, Upper Maudlin Street, Bristol BS2 8AE, United Kingdom. E-mail: j.p.h.shield{at}bris.ac.uk
The authors have indicated they have no financial relationships relevant to this article to disclose.
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