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Rong Huang, Yu Dong, Anne Monique Nuyt, Emile Levy, Shu-Qin Wei, Pierre Julien, William D Fraser, and Zhong-Cheng Luo

Objective: Large birth size programs an elevated risk of type 2 diabetes in adulthood, but data are absent concerning glucose metabolic health impact in infancy. We sought to determine whether large birth size is associated with insulin resistance and β-cell function in infancy, and evaluate the determinants.

Design and Participants: In the Canadian 3D birth cohort, we conducted a nested matched (1:2) study of 70 large-for-gestational-age (LGA, birth weight >90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) control infants. The primary outcomes were homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) at age 2-years.

Results: HOMA-IR and HOMA-β were similar in LGA and OGA infants. Adjusting for maternal and infant characteristics, decelerated growth in length during early infancy (0-3 months) was associated a 25.8% decrease (95% confidence intervals 6.7-41.0%) in HOMA-β. During mid-infancy (3-12 months), accelerated growth in weight was associated with a 25.5% (0.35-56.9%) increase in HOMA-IR, in length with a 69.3% increase (31.4-118.0%) in HOMA-IR and a 24.5% (0.52-54.3%) increase in HOMA-β. Decelerated growth in length during late infancy (1-2 years) was associated with a 28.4% (9.5-43.4%) decrease in HOMA-IR and a 21.2% (3.9-35.4%) decrease in HOMA-β. Female sex was associated with higher HOMA-β, Caucasian ethnicity with lower HOMA-IR, and maternal smoking with lower HOMA-β.

Conclusions: The study is the first to demonstrate that large birth size is not associated with insulin resistance and β-cell function in infancy, but infancy growth pattern matters. Decelerated infancy growth may be detrimental to beta-cell function.