it has been reported that insulin sensitivity is decreased during puberty , and that this is associated with a compensatory increase of insulin secretion(1,2,3,4,5,6 ) . however , most of these previously reported studies were conducted in white and black children , and there is a lack of corresponding data in japanese adolescents . on the other hand , peripheral fat accumulation has been reported to increase insulin resistance through secretion of adipocytokines from fat cells(7 , 8) . some japanese studies have demonstrated insulin resistance associated with a compensatory increase of insulin secretion in obese children(9 , 10 ) . to examine the effect of puberty on the insulin sensitivity without the influence of obesity , we examined the parameters reflecting insulin resistance in non - obese prepubertal and pubertal japanese children . the study subjects were 201 japanese school students , consisting 95 males and 106 females , aged 11.5  2.6 ( 616 ) yr . there was no significant difference in mean age between genders ( 11.3  2.8 vs. 11.7  2.3 , p=0.3932 ) . the mean height and body weight were 144.0  7.0  cm and 39.0  8.9  kg in males and 147.5  6.7  cm and 40.8  8.5  kg in females , respectively . the mean height and weight in prepubertal students were 131.4  6.0  cm and 29.8  6.9  kg in males ( mean age : 9.1  2.8 yr ) and 126.5  5.7  cm and 26.8  5.5  kg in females ( mean age : 8.4  2.3 yr ) , respectively . that in pubertal students were 159.0  7.1  cm and 50.4  10.5  kg in males ( mean age : 13.4  2.6 yr ) and 155.3  5.5  cm and 48.8  8.4  kg in females ( mean age : 13.7  2.5 yr ) , respectively . none of the subjects were obese , with the mean percent of overweight being 0.7  10.5% ( 19.219.8 ) at the time of the study . there was no statistical difference in percent of overweight between the genders ( males vs. females : 0.9  10.5 vs. 0.5  10.7 , p=0.8450 ) . the students participated in a urine glucose screening program at schools in the tokyo metropolitan area(11 ) and exhibited no glucose intolerance . overnight fasting plasma values of insulin ( firi ) and homa - r were measured , with concomitant measurement of the plasma glucose ( fpg ) levels in the subjects at the time of the screening program . we examined the relation between insulin resistance assessed by firi levels and homeostasis model assessment insulin resistance ( homa - r ) and the parameters reflecting insulin resistance including sex , age and pubertal development among the subjects . prepubertal children were in tanner stage i , and pubertal children were beyond tanner stage ii . according to the tanner stage , 142 children were in prepubertal and 59 were in pubertal . sex- , age- and height - matched ideal weight ) / sex- , age- and height - matched ideal weight  100 ( % ) . homa - r was an acceptable alternative for estimating insulin resistance and was calculated by fpg ( mg / dl )  iri ( u / ml ) / 405 . pg was measured by a glucose oxidase method , and iri was measured using a radioimmunoassay . the mann - whitney u test was used to detect differences between the two groups . the mean values of fpg , firi and homa - r among the subjects were 89.6  7.3 ( 70109 )  mg / dl , 9.0  3.6 ( 1.724.4 ) u / ml and 2.0  0.9 ( 0.35.2 ) , respectively . figure 1fig . 1 distribution of fbg , iri and homa - r among the subjects . shows the distribution of these values . figure 2fig . 2 comparison of iri and homa - r between sex . shows a comparison of firi and homa - r between genders . the mean value of firi was significantly higher in females than in males ( 8.3  3.4 vs. 9.6  3.7 u / ml , p=0.0060 ) . there was no statistical deference in homa - r between genders ( 2.1  0.9 vs. 1.9  0.9 , p=0.0547 ) . figure 3fig . 3 comparison of iri and homa - r between pubertal ( p ) and prepubertal ( pp ) subjects . shows a comparison of firi and homa - r between prepubertal and pubertal students . there was no significant difference in percent of overweight between prepubertal and pubertal students ( prepubertal , 0.9  9.4 ; pubertal , 1.4  11.0 ; p=0.1638 ) . pubertal students showed significantly higher values of firi and homa - r as compared with prepubertal students ( firi and homa - r : 10.0  3.4 vs. 6.5  2.8 u / ml , and 2.3  0.8 vs. 1.4  0.7 , p<0.0001 , respectively ) . a similar relationship was also seen for males ( firi and homa - r : 9.5  3.1 vs. 6.3  2.8 u / ml and 2.2  0.8 vs. 1.4  0.7 , p<0.0001 , respectively ) and females ( firi and homa - r : 10.3  3.5 vs. 6.9  2.8 u / ml and 2.3  0.8 vs. 1.5  0.6 , p<0.0001 , respectively ) . comparison of iri and homa - r between pubertal ( p ) and prepubertal ( pp ) subjects . 4 correlation between age and iri and homa - r in the subjects . shows the correlation between age at the time of study and firi and homa - r . both the firi levels and homa - r were positively correlated with age ( r=0.280 for firi , r=0.300 for homa - r , p<0.0001 , respectively ) . the present study demonstrated significantly higher firi and homa - r values in pubertal subjects than prepubertal subjects among non - obese japanese children without diabetes . thus , a decrease in insulin sensitivity during puberty , generally associated with a compensatory increase in insulin secretion , is seen not only in caucasians and blacks , but also in the japanese . bloch et al.(2 ) demonstrated that the insulin resistance level in pubertal children was approximately 30% higher than that in prepubertal children , as assessed by the euglycemic - hyperinsulinemic clamp technique . however , the mechanisms underlying insulin resistance during puberty have not yet been clearly elucidated . a selective effect of sex hormones appears to be unlikely because the concentrations of sex hormones would be even higher in adults , who show a higher sensitivity to insulin than adolescents . furthermore , yki - jrvinen(15 ) showed that insulin - mediated glucose metabolism in normal women was not affected during the menstrual cycle , despite the different levels of sex hormones during this period . on the other hand , the insulin resistance during puberty is most likely explained by the increased secretion of growth hormone ( gh ) during puberty . several studies have shown that hypersecretion of gh deteriorates insulin sensitivity in normal adolescents(1 , 2 , 5 , 16 , 17 ) . amiel et al.(1 ) demonstrated an inverse correlation between the mean 24-h levels of gh and insulin - stimulated glucose metabolism , and bloch et al.(2 ) showed a negative correlation between insulin sensitivity and igf-1 levels in white children . the present study also demonstrated that females exhibited higher levels of insulin resistance than males during puberty , despite the absence of any significant difference in percent of overweight between the genders . this difference is likely to be due to the difference in body composition , that is , the percent body fat , between male and female adolescents . females , especially during adolescence , show a higher body fat mass than males(18 , 19 ) . nakanishi et al.(19 ) reported that the increased body fat mass and enhanced insulin resistance in pubertal females were associated with higher leptin levels in these subjects . in recent years , the prevalence of obese children in japan has been increasing , and childhood type 2 diabetes is detected at a relatively high frequency by a urine glucose screening programs at schools(11 ) . obesity is known to be one of the major factors predisposing to the development of type 2 diabetes . puberty is also considered to be a risk factor because of increased insulin resistance , as demonstrated in the present study . the international society for pediatric and adolescent diabetes ( ispad ) has proposed that obese adolescents in high - risk ethnic groups with a family history of type 2 diabetes should be screened for glucose intolerance(20 ) . it is very important to screen children with risk factors for type 2 diabetes to prevent the onset and progression of the disease . we demonstrated a significant increase of the insulin resistance during puberty in japanese children without diabetes , which is consistent with the results of previous studies in white and black children . the decreased insulin sensitivity observed during puberty in normal adolescents is compensated for by an increase of the insulin secretion . further studies using special techniques , such as the insulin clamp technique(2 , 21 ) , may be necessary to endorse the findings of the present study .
we examined whether non - obese japanese children without diabetes exhibited insulin resistance during puberty . 
 the study subjects were 201 japanese school students , consisting 95 males and 106 females , aged 11.5  2.6 yr . 
 none of the subjects were obese , with the mean percent of overweight being 0.7  10.5% , or had diabetes at the time of the study . 
 overnight fasting plasma values of insulin ( firi ) and homa - r were measured , with concomitant measurement of the plasma glucose ( fpg ) levels . 
 the mean fpg , firi and homa - r values were 89.6  7.3 ( 70109 )  mg / dl , 9.0  3.6 ( 1.724.4 ) u / ml and 2.0  0.9 ( 0.35.2 ) , respectively . 
 the mean firi value was significantly higher in females than in males ( 8.3  3.4 vs. 9.6  3.7 u / ml , p=0.0060 ) . 
 the firi and homa - r values of the pubertal students were significantly higher compared with those of the prepubertal students ( firi , 10.0  3.4 vs. 6.5  2.8 u / ml ; homa - r , 2.3  0.8 vs. 1.4  0.7 ; p<0.0001 for both ) . 
 similar trends were observed between the two genders . the mean firi levels and homa - r values 
 were positively correlated with age ( firi , r=0.280 , p<0.0001 ; homa - r , r=0.300 , p<0.0001 ) . in conclusion , we demonstrated that the firi and homa - r values were significantly associated with pubertal development in non - obese japanese children without diabetes , consistent with the results of studies in white and black children .