β-cell replication is the primary mechanism subserving the postnatal expansion of β-cell mass in humans

OBJECTIVE-Little is known about the capacity, mechanisms, or timing of growth in β-Cell mass in humans. We sought to establish if the predominant expansion of β-Cell mass in humans occurs in early childhood and if, as in rodents, this coincides with relatively abundant β-Cell replication. We also sought to establish if there is a secondary growth in β-Cell mass coincident with the accelerated somatic growth in adolescence. RESEARCH DESIGN AND METHODS-To address these questions, pancreas volume was determined from abdominal computer tomographies in 135 children aged 4 weeks to 20 years, and morphometric analyses were performed in human pancreatic tissue obtained at autopsy from 46 children aged 2 weeks to 21 years. RESULTS-We report that 1) β-Cell mass expands by several- fold from birth to adulthood, 2) islets grow in size rather than in number during this transition, 3) the relative rate of β-Cell growth is highest in infancy and gradually declines thereafter to adulthood with no secondary accelerated growth phase during adolescence, 4) β-Cell mass (and presumably growth) is highly variable between individuals, and 5) a high rate of β-Cell replication is coincident with the major postnatal expansion of β-Cell mass. CONCLUSIONS-These data imply that regulation of β-Cell replication during infancy plays a major role in β-Cell mass in adult humans.