In our study, SGA children, who had made a height catch-up growth accompanied by a BMI catch-up growth, had significantly higher values of insulin resistance index compared to AGA children. This finding showed that the development of insulin resistance was associated with height and BMI catch-up growth in SGA children, which increased with age. These data were not in complete accordance with several previous reports [9, 17, 18]. The majority of previous studies did not analyse the contribution of BMI catch-up growth to insulin resistance during postnatal catch-up growth, though the strong association between low birth weight and insulin resistance has been described [9, 17, 19]. In our study population, △BMI SDS values were higher in SGA children than in AGA children. Because the high degree of BMI usually reflects the excess accumulation of fat in the body, our data suggest that there was body fat accumulation in SGA children, especially with catch-up growth in height during childhood and that the excess fat contributes to the development of insulin resistance in SGA children. SGA children with higher current BMI were more insulin-resistant than AGA children, in spite of their similar weight and BMI. The data also suggested that insulin resistance may precede the development of obesity. Other studies have suggested that low birth weight is a risk factor for the later development of abdominal or truncal obesity, and SGA children with catch-up weight gain show a dramatic transition toward central adiposity, which enhances insulin resistance [20–23]. Accordingly, the measures used to control overweight when gaining linear catch-up growth in childhood seem to be important in the prevention of insulin resistance in SGA children. Our findings indicated that height catch-up growth was an important influential factor for insulin resistance in SGA children. Our work might contribute to understanding the involvement of catch-up growth in the pathogenesis of insulin resistance in SGA groups. The implications of our results in relation to catch-up in height might be of potential importance when considering GH treatment.
Decreased adiponectin and IGFBP-1 levels and increased triglyceride levels are considered to reflect impaired insulin sensitivity and predict insulin resistance. Data on adiponectin, IGFBP-1 and triglyceride levels in SGA children in the literature have varied [24–27]. Adiponectin is one of the adipokines produced exclusively by adipocytes. Adiponectin knockout mice develop glucose intolerance, insulin resistance, and hyperlipidemia, especially when fed high-fat diets . Decreased levels of plasma adiponectin have been found to be related to obesity, type 2 diabetes, and cardiovascular disease. Cianfarani et al. reported that the serum adiponectin levels were lower in SGA children (aged 8.6±3.5yr) than in short-normal children born AGA . These differences were not observed in the research of Lopez-Bermejo et al. whose extensive analysis revealed that the group of overweight SGA children had lower serum adiponectin concentrations than lean SGA children . Research on preterm infants had shown that the change in the serum adiponectin levels closely correlated to gains in body weight in AGA and SGA children . One important finding of the present study was that adiponectin was not only associated with BMI catch-up, but also with linear catch-up growth in pre-pubertal SGA children. Our study also showed that adiponectin was inversely associated with insulin resistance markers. The results highlight that BMI and linear catch-up might be two independent determinants of hypoadiponectinemia in SGA children. Previous studies have shown that low birth weight followed by catch-up in body fat, especially visceral fat during childhood, even within the normal weight range, was associated with a higher risk of developing insulin resistance [20, 22]. Our study also showed that the decreased adiponectin levels were associated with postnatal body fat accumulation in SGA children and added new information on this association because it showed the relevant role of fat and height catch-up. To the best of our knowledge, the relationship between linear catch-up and adiponectin are novel and may contribute to understanding the involvement of adiponectin in the pathogenesis of insulin resistance in SGA children.
IGFBP-1, produced in the liver, is suppressed by insulin through binding to insulin-response elements in the IGFBP-1 gene promoter, which forms a link between glucose metabolism and IGF axis . Insulin resistance and impaired glucose tolerance are observed in IGFBP-1 transgenic mice . Reduced serum IGFBP-1 levels are considered to reflect hyperinsulinemia and cardiovascular risk in adults and obese children [32, 34]. Kamoda T et al. reported that the levels of serum IGFBP-1 were similar in short children born SGA and AGA . Kistner A et al. investigated the serum markers of insulin resistance in adults born SGA and reported that lower IGFBP-1 and triglyceride levels were observed in the SGA group compared to the AGA group despite with normal BMI . In our study, there were no marked differences in IGFBP-1 and triglyceride levels between SGA children with height and BMI catch-up growth and their age-matched controls. In SGA children, especially non-catch-up growth subjects, the lower BMI may have influenced IGFBP-1and triglyceride levels, although we had adjusted for BMI. Further analysis showed that IGFBP-1 correlated significantly with the HOMA-IR. values. These differences and correlations were not observed with triglyceride levels. In this instance, our results were similar to the results published by Evagelidou EN et al., who reported that SGA children, although more insulin-resistant, had similar triglyceride levels to AGA children in pre-puberty . Our findings indicated that adiponectin might be a more effective marker than IGFBP-1 and triglyceride for monitoring insulin resistance in SGA children with catch-up growth. However, these three markers were not sensitive enough at this age stage in non-obese SGA children.
We need to be aware of the limitations in interpreting the results of this study. The major limitation of the present study is the relatively small sample size. Another limitation is that the study design was based on retrospective data collecting. The third limitation is that both body fat and insulin resistance were studied using surrogate variables. These limitations might suggest that the results are not easily applicable to the whole population of pre-pubertal SGA children. However, we have presented the presence of four different SGA populations compared to normal controls in the exploration of system-wide adiponectin, IGFBP-1, triglyceride levels and insulin resistance in SGA children, while considering height and fat catch-up growth.
In conclusion, our study showed that children born SGA with catch-up growth for height and BMI are more insulin-resistant than children born AGA. Our study indicated that interventions to control overweight development in childhood seem to be important for preventing insulin resistance. Furthermore, lower levels of adiponectin were closely correlated with height and BMI catch-up growth in SGA children. Adiponectin may be a more useful marker than IGFBP-1 and triglyceride for monitoring insulin resistance in SGA children with catch-up growth.