Insulin Resistance and Body Composition in Preterm Born Children During Prepubertal Ages

Feyza Darendeliler; Firdevs Bas; Ruveyde Bundak; Asuman Coban; Ozlem Sancakli; Sema Kabatas Eryilmaz; Banu Kucukemre; Rian Disci; Gulbin Gokcay; Semih Aki; Zeynep Ince; Nurten Eskiyurt


Clin Endocrinol. 2008;68(5):773-779. 

In This Article

Subjects and Methods

A total of 93 (41 females, 52 males) premature born children with a gestational age of ≤ 37 completed weeks (37 weeks and 6 days) who were followed in the Neonatology Unit for their growth were included in the study. As the control group, 86 (44 females, 37 males) children born at term (> 37 completed gestational weeks) were studied. Both the preterm and the term children were divided into two groups with respect to their birth weight and/or length for their gestational age. Those with a birth weight and/or length < 10th percentile[18,19] were accepted as SGA and those with a birth weight and/or length 10th percentile as AGA. Thus, we had preterm SGA group (n = 30; 16 females, 14 males), preterm AGA group (n = 63; 25 females, 38 males), term SGA group (n = 42; 25 females, 17 males) and term AGA group (n = 44; 19 females, 25 males). All children were prepubertal (testicular volume < 4 ml in boys, breast stage1 in girls and no pubic hair in both sexes),[20] and at least 2 years of age at investigation to allow them to have completed their CUG. Mean chronological age (range) was 4·6 years (3·2-6·9) in the preterm SGA group; 4·7 years (2·9-7·1) in the preterm AGA group; 4·5 (2·9-7·7) in the term SGA group and 3·8 (2·8-6·7) in the term AGA group. Term children were recruited from the control group of an ongoing parallel study. The reason why 10th percentile was chosen as the cutoff for definition of SGA is that nearly all metabolic studies done in preterm infants have used this cutoff in their studies.[15,16] Birth data and anthropometric parameters of the groups at investigation are seen in Table 1 .

The preterm group included 11 pairs of twins and one triplet. None of the children had neurological impairment, severe systemic diseases or malformations.

Medical history regarding gestational age, weight and length at birth and details of postnatal history of the children were taken from the hospital files and of infancy from the parents. Gestational age was determined by the mother's last menstrual period and/or antenatal fetal ultrasound examination and if not conclusive by the Ballard assessment.[21]

Following physical examination, anthropometric measurements, including height and weight, were taken by standard methods,[22] using Harpenden equipment for height/length. Parental heights were also measured. BMI of the children was calculated as weight (kg)/height (m)2. Target height was calculated as mother's height + father's height/2 −6·5 for girls and +6·5 for boys. Values of height, weight, target height[23] and BMI,[24] and also birth data[25] were expressed as standard deviation score (SDS). Corrected height for target height (target height SDS minus recent height SDS) was denoted as height SDScorrected.

The difference (Δ) between birth length SDS and current height SDS was denoted as Δ height SDS and the difference (Δ) between birth weight and current weight SDS as Δ weight SDS.

Education level of the parents were evaluated at three levels: elementary school level (total 8 years of education) = 1, high school level = 2 and university level = 3.

After an overnight fast, serum samples were drawn for glucose, insulin, IGF-I, IGFBP-3, IGFBP-1, free T4 (fT4), thyrotropin (TSH), leptin and lipid levels, including cholesterol, triglyceride, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions.

Sera were stored at -70 °C until hormonal assays were done. The samples were run in the same assays using same kits. Biochemical analyses were done immediately.

Insulin resistance was evaluated by basal insulin level, which has been shown to be reliable in nondiabetic children[26] and also as homeostasis model assessment for insulin resistance (HOMA-IR), calculated as insulin (µU/ml) × glucose (mmol/l)/22·5.[27] HOMA-IR values showed high correlation with fasting insulin levels (P < 0·0001). Due to inadequate sample size, insulin measurement was not available in two (out of 30) patients in preterm SGA and six (out of 63) patients in preterm AGA group.

Body composition was evaluated by dual-energy X-ray absorptiometry (DEXA) (GE-LUNAR DPX-NT, General Electric Comp Medical Systems, Lunar, Madison, WI). Absolute (kg) whole body fat and lean body mass (LBM) were assessed as well as fat content in the truncal region according to the manufacturer's set point, which was defined as the area bordered by a horizontal line below the chin, vertical borders lateral to the ribs and oblique lines passing through the femoral necks.[28] Coefficients of variation for scanning precision are 2·0% and 1·1% for fat and LBM, respectively.[29] Fat mass, lean mass and abdominal fat were assessed; body composition data were corrected for differences in height, as recommended by Wells et al.,[30] which is calculated as LBM/height2 and fat mass/height2 and expressed as kg/m2.

This study was approved by the ethical committee. Written consent was obtained from the families and children.

Biochemical and Hormonal Assays. Biochemical investigations including serum glucose were done by standard equipment and methods (Roche Diagnostics, using Cobas Integra kits, Basel, Switzerland) by hexokinase enzymatic method. Leptin (ng/ml) was measured by immunoradiometric assay (IRMA) by Diagnostic systems Laboratory (DSL)-23100i kit (Webster, TX). The limit of sensitivity was 0·10 µg/l. IGF-I (nmol/l) was measured by IRMA method using DSL-5600 kit (Webster, TX). The limit of sensitivity was 0·10 nmol/l. IGFBP-3 (nmol/l), also measured by IRMA method (DSL-6600, Webster, TX), has a limit of sensitivity of 0·01 nmol/l. IGFBP-1 (µg/l), measured by IRMA (DSL-7800, Webster, TX), has a limit of sensitivity of 0·33 µg/l. Insulin (pmol/l) was measured by RIA method (DSL-1600, Webster, TX), and the lowest limit of detection at the 95% confidence level was 9·3 pmol/l. Because there were quite number a of children with insulin values below this cutoff level, standards were diluted to be able to measure values between 0·7 and 9·3 pmol/l. fT4 (pmol/l) was measured by [125I] RIA KIT, by Institute of Isotopes Ltd, Budapest, Hungary, TSH (mU/l) was measured by IRMA using DSL-5300 kit, Webster, TX.

An SPSS-12 program was used for statistical analyses. Comparison between the means was done by parametric tests. Skewed data of IGF-I, IGFBP-3, IGFBP-1, leptin, insulin and HOMA-IR were normalized by log transformation to use parametric tests. These values are expressed as geometric mean ± SEM. All other parameters were expressed as arithmetic mean ± SEM. Simple regression analyses were used to determine univariate relationships. Two-way ANOVA was done to investigate the effect of gestational age and birth weight on insulin levels. Significance was granted for P ≤ 0·05.


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