Relation between weight gain and beta-cell secretory activity and non-esterified fatty acid production in 7-year-old African children: results from the Birth to Ten study

Aims/hypothesis. This study aimed to assess the effects of fetal and childhood growth on beta-cell activity and insulin sensitivity in 7-year-old children. Methods. Insulin, des-31,32 proinsulin, proinsulin, non-esterified fatty acids and glucose concentrations were measured in oral glucose tolerance tests in 152 South African children for whom longitudinal weight data was available. Results. Children with low weights at birth and 7 years (low-low) had relatively low beta-cell activity whereas children with low birth weight and high weight at 7 years (low-high) had relatively high beta-cell activity. The low-low group had higher 30-min glucose concentrations than children with high birth weights. When each insulin-related peptide was expressed as a percentage of all these peptides the low-low children had the highest percentage of insulin but the lowest of the prohormones. The low-high children had the lowest percentage of insulin but the highest of the prohormones. Non-esterified fatty acid concentrations were lowest and their suppression post-glucose load highest in the low-high group. Conculsion/interpretation. Poor fetal and neonatal growth give rise to low beta-cell numbers compensated for by increased efficiency of proinsulin processing to insulin, Poor fetal followed by higher postnatal growth results in low beta-cell numbers and reduced whole-body glucose uptake which leads to reduced efficiency in the processing of proinsulin. Growth in utero and postnatally therefore have profound effects on beta-cell activity and insulin sensitivity with poor fetal coupled with high postnatal growth being detrimental to these processes but not detrimental to the suppression of lipolysis.