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Published online January 17, 2008
Diabetes Care 31:802-804, 2008
DOI: 10.2337/dc07-1655
© 2008 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Original Research

Alternative Methods of Insulin Sensitivity Assessment in Obese Children and Adolescents

Sophia M. Rössner, MD1, Martin Neovius, PHD2, Scott M. Montgomery, PHD3,4,5, Claude Marcus, MD, PHD6 and Svante Norgren, MD, PHD1

1 Division of Pediatrics, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden
2 Department of Medicine, Karolinska Institute, Stockholm, Sweden
3 Clinical Epidemiology Unit, Karolinska Institute, Stockholm, Sweden
4 Clinical Research Centre, Örebro University Hospital, Örebro, Sweden
5 Department of Primary Care and Social Medicine, Charing Cross Hospital, Imperial College, London, U.K.
6 National Childhood Obesity Centre, Department for Clinical Science, Intervention and Technology, Division of Pediatrics, Karolinska Institute, Stockholm, Sweden

Address correspondence and reprint requests to Dr. Sophia Rössner, B57, Karolinska Universitetssjukhuset Huddinge, SE-141 86 Stockholm, Sweden. E-mail: sophia.rossner{at}karolinska.se


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
OBJECTIVE—To validate fasting indexes against minimal model analysis (MMOD) of the frequently sampled intravenous glucose tolerance test (FSIVGTT) in an obese pediatric population.

RESEARCH DESIGN AND METHODS—FSIVGTT-MMOD results were compared with homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin with the sample stratified by sex, puberty, and sensitivity index (Si) median in 191 children (82 males and 109 females, 13.9 ± 2.9 years of age, BMI 36.9 ± 6.2 kg/m2, BMI SD score 6.1 ± 1.6).

RESULTS—Across pubertal groups, correlation coefficients between Si and HOMA-IR ranged from –0.43 to –0.78 in males and from –0.53 to –0.57 in females (age and BMI adjusted, P < 0.05 in all instances). Similar results were seen for fasting insulin. In females, the relationship was significantly weaker in more-insulin-resistant subjects.

CONCLUSIONS—The validity of fasting indexes in explaining Si was sex dependent, varied with pubertal stage, and in females was influenced by degree of insulin sensitivity. In obese pediatric populations, we generally discourage the use of fasting indexes, although the validity varies within subgroups.

Abbreviations: DEXA, dual-energy X-ray absorptiometry • FSIVGTT, frequently sampled intravenous glucose tolerance test • HOMA-IR, homeostasis model assessment of insulin resistance • MMOD, minimal model analysis • QUICKI, quantitative insulin-sensitivity check index


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
Obesity in children and adolescents (1–6) with the complication of insulin resistance requires accurate methods for insulin sensitivity assessment. Minimal model analysis (MMOD) of the frequently sampled intravenous glucose tolerance test (FSIVGTT) (7) is a well-validated method. However, alternative methods for routine clinical use have been developed using fasting plasma glucose and insulin concentrations, such as homeostasis model assessment of insulin resistance (HOMA-IR) (8) and quantitative insulin-sensitivity check index (QUICKI) (9).

In obese children and adolescents, the use of fasting indexes has been promoted (10,11) as well as discouraged (12). We performed FSIVGTT-MMOD among obese participants ranging from children to young adults and compared results with fasting indexes, aiming to evaluate these as surrogate measures of insulin sensitivity in an obese pediatric population.


   RESEARCH DESIGN AND METHODS—
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
RESULTS--
 CONCLUSIONS--
 References
 
The study included 191 overweight or obese Swedish participants, ranging from children to young adults. Patients with mental, endocrine, or metabolic disorders (except mild dyslipidemia) were excluded. Anthropometric and pubertal assessments were performed (13,14), BMI SD score calculated (15), and dual-energy X-ray absorptiometry (DEXA) scan performed (16). The study protocol was approved by the local ethics committee, and written informed consent was obtained.

FSIVGTT was performed according to standard protocol (7,16,17) with sensitivity index (Si) calculated by computer program MINMOD version 3.0 (by R. Bergman 1994). Fasting insulin and glucose were analyzed using standard laboratory techniques, and HOMA-IR and QUICKI were calculated as previously described (8,9).

Results are reported as the mean ± SD. Fasting indexes and Si were transformed logarithmically. Analyses were sex stratified and the sample divided into groups of prepubertal (Tanner stage I), pubertal (Tanner stages II and III), and postpubertal (Tanner stages IV and V) (13,14). Partial correlation coefficients were calculated with adjustment for BMI and age. To explore the effect of insulin resistance on the relationship between Si and fasting indexes, a variable denoting high/low Si was tested in regression models (determined as above/below median). An interaction term between indexes and the high/low variable was included to investigate potential effect modification. When testing for interaction, adjustment was made for main effects. P values <0.05 were considered statistically significant. Because QUICKI and HOMA-IR showed consistently highly similar results, only HOMA-IR results are reported.


   RESULTS—
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
CONCLUSIONS--
 References
 
The study included 191 overweight or obese participants (82 males and 109 females, aged 13.9 ± 2.9 years [median 14.0 years, range 5.5–22.8], BMI 36.9 ± 6.2 kg/m2 [35.8 kg/m2, 24.2–60.3], BMI SD score 6.1 ± 1.6 [6.0, 2.7–14.0], DEXA 45.7 ± 5.2% [45.6%, 27.2–58.8]). Tanner stage (I/II/III/IV/V) for males was 37.8/14.6/12.2/14.6/20.7% and for females was 8.3/9.2/2.8/16.5/46.8%, respectively. Males were heavier (3.1 kg, P = 0.001), were taller (2.9 cm, P < 0.001), had higher fasting glucose (0.1 mmol/l, P = 0.022), and were less adipose (2.6%, P = 0.001). Statistically significant differences in Tanner stage were found (P < 0.001). DEXA results showed that 99% were above the 98th percentile in body fat percentage (age and sex adjusted) (18).

The relationships between HOMA-IR, fasting insulin, and Si are presented in Table 1, stratified by sex and pubertal status. The female prepubertal group was too small to provide any reliable results (n = 6). In both sexes, the pubertal group had the highest correlation coefficients. When including the high/low Si variable in regression analysis, in females the relationship appeared to vary with degree of insulin sensitivity, while variations in HOMA-IR explained 33.7% of the variation in Si for subjects with high Si (P < 0.001); the corresponding number for subjects with low Si was only 3.2% (P = 0.197). Fasting insulin explained 14.1% of the variation in Si in female subjects with high Si (P < 0.004), with a corresponding number for subjects with low Si of 0.3% (P = 0.715). In males, no such interactions were detected either graphically (parallel lines) or in regression analysis. The Pearson correlation coefficient of HOMA-IR to fasting insulin was 0.81 (males 0.87, females 0.78, P < 0.001 in all instances).


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  		Table 1— Partial correlation coefficients of ln Si to ln HOMA-IR and ln fasting insulin adjusted for age and BMI

 

   CONCLUSIONS—
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
References
 
We found sex-dependent differences in the explanatory power of fasting indexes, with consistently better ability to explain the variation in Si among males. In both sexes the explanatory power varied with pubertal status, surprisingly showing highest correlations in the pubertal groups, where insulin sensitivity is known to be low (19). When stratifying for high/low Si, the relationship was significantly weaker in the more-insulin-resistant females, in which fasting indexes exhibited virtually no explanatory value at all. HOMA-IR yielded little additional explanatory value compared with fasting insulin alone.

The validity of fasting indexes in children and adolescents has been investigated with correlations of HOMA-IR and clamp or FSIVGTT ranging from 0.4 to 0.9 (10,20–23). Conwell et al. (10) found fasting indexes to correlate strongly with Si of the FSIVGTT-MMOD, concluding that these are valid tools in obese children and adolescents. The high correlation seen in the Conwell study of 18 individuals in three repeated tests (r = –0.9 for HOMA-IR and Si, P < 0.001) is not found in our larger study, although the correlation in pubertal males is reasonably high. The results in most of our subgroups are in better agreement with the study by Cutfield et al. (24), in which fasting indexes exhibited only weak correlation with the Si of the FSIGVTT-MMOD (r = –0.4, P < 0.001 for HOMA-IR and Si). Brandou et al. (12), who examined fasting indexes in obese and lean children at varying stages of puberty, found no correlation between HOMA-IR or QUICKI and Si. Also, in the present study, for each given value of the fasting indexes there was a wide spread in Si, which warrants careful interpretation.

In summary, we have shown the validity of HOMA-IR and fasting insulin in explaining Si as determined by the FSIVGTT in obese children and adolescents to be sex dependent as well as influenced by pubertal stage and in females by level of insulin sensitivity. In pubertal males, HOMA-IR and fasting insulin correlated reasonably well with FSIVGTT-MMOD, whereas in pre- and postpubertal subgroups the correlation was low. In females, the strength of the association was generally weaker, especially among the most insulin-resistant participants. Thus, in obese pediatric populations, especially those at risk of altered glucose homeostasis, we discourage the use of these measures.


   Acknowledgments
 
This work was supported by grants from Stiftelsen Samariten, the Frimurare Barnhuset Foundation, the Stockholm City Council, and the Swedish Medical Research Council (9941).


   Footnotes
 
Published ahead of print at http://care.diabetesjournals.org on 17 January 2008. DOI: 10.2337/dc07-1655.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received for publication August 22, 2007. Accepted for publication January 4, 2008.


   References
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 

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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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