ESPE Yearbook of Paediatric Endocrinology

Eur J Endocrinol. 2021 May 24;185(1):77-85. doi: 10.1530/EJE-20-1332. PMID: 33914700.

Brief Summary: This case control study assessed beta-cell function and glucose metabolism in large for gestational age (LGA) infants in relation to their weight and growth parameters at 2 years of age. In LGA infants, changes in growth parameters were associated with changes in insulin resistance and beta-cell dysfunction.

It is known that high birth weight and LGA are associated with higher risk of developing type 2 diabetes in adulthood. Being born LGA is associated with insulin resistance at or shortly after birth and during childhood or adolescence, and also with lower beta-cell function at birth. However, it is unknown whether LGA is associated with insulin resistance and beta-cell dysfunction in infancy (0–2 years, a critical period of rapid postnatal growth and development). So, in this study the authors hypothesized that LGA may be associated with insulin resistance or lower beta-cell function in infancy, and infancy growth patterns (changes in length) may affect insulin resistance or beta-cell function.

This study showed that LGA was not associated with insulin resistance or beta-cell dysfunction in infancy but there were associations with infant growth parameters. Both accelerated and decelerated growth in length during infancy were associated with beta-cell dysfunction. Accelerated growth in length during mid-infancy was associated with higher HOMA-IR, whereas decelerated growth in length during late infancy was associated with lower HOMA-IR. Accelerated and decelerated changes in weight during infancy were not associated with any significant changes in insulin resistance as assessed by HOMA-IR.

So how does decelerated or accelerated growth in length during infancy affect beta-cell function? The answer is not completely clear but growth in length reflects bone growth and there may be a link between bone and pancreas. Bone marrow cells co-transplanted with islets improves islet vascularization and function in mice (1). Osteoprotegerin, a critical factor involved in bone metabolism, promotes islet cell proliferation in rats (2). Since nutrition is the main driver of decelerated or accelerated growth in infants, both insufficient and excessive nutrition during early and late infancy may be harmful for cell function. However, these observations require confirmation in larger cohort studies.

References: 1. Sakata N, Chan NK, Chrisler J, Obenaus A, Hathout E. Bone marrow cell co-transplantation with islets improves their vascularization and function. Transplantation 2010 89 686–693. 2. Tang S, Xin Y, Yang M, Zhang D, Xu C. Osteoprotegerin promotes islet β cell proliferation in intrauterine growth retardation rats through the PI3K/AKT/FoxO1 pathway. International Journal of Clinical and Experimental Pathology 2019 12 2324–2338.