Glucose intolerance in adults born with intrauterine growth retardation (IUGR) may involve peripheral insulin resistance and/or abnormal endocrine pancreas development during fetal life. We quantified insulin-containing cells in deceased human fetuses with IUGR (<10th percentile, n = 21) or normal growth (control fetuses, n = 15). Paraffin-embedded pancreatic tissues from fetuses older than 32 weeks were obtained from two fetopathology departments. Mean gestational age was 36 weeks in both groups. Tissues with lysis and those fetuses with defects, aneuploidy, or genetic abnormalities were excluded. For each subject, six pancreatic sections spaced evenly throughout the organ were immunostained with anti-insulin antibody. Total tissue and insulin-positive areas were measured by computer-assisted quantitative morphometry. Results were expressed in percentages. To evaluate islet morphogenesis, the percentages of β-cells inside and outside islets were determined. Islet density was similar in the two groups (P = 0.86). The percentage of pancreatic area occupied by β-cells (β-cell fraction) was not correlated with gestational age (r = 0.06 and P = 0.97 in IUGR fetuses; r = 0.12 and P = 0.67 in control fetuses) or body weight (r = 0.16 and P = 0.47 in IUGR fetuses; r = 0.24 and P = 0.39 in control fetuses). Mean β-cell fraction was 2.53% in the IUGR fetuses and 2.86% in the control fetuses (P = 0.47). The percentage of β-cells located within islets was identical in the two groups (mean 35%). Our data militate against a primary developmental pancreatic abnormality in human IUGR, leaving peripheral insulin resistance as the most likely mechanism of glucose intolerance in adults born with IUGR.
F.B. is currently affiliated with the Neonatology Department, Centre Hospitalo-Universitaire, Angers, France.
Address correspondence and reprint requests to Michel Polak, Pediatric Endocrinology and Diabetes Unit, INSERM U457, Hôpital Robert Debré, 48, Boulevard Sérurier, 75019 Paris, France. E-mail:.
Received for publication 29 June and accepted in revised form 7 November 2001.
IUGR, intrauterine growth retardation.