Abstract
This review examines the impact of early life exposures on glucose metabolism in the offspring and explores potential metabolic mechanisms leading to type 2 diabetes in childhood. One in five adolescents is diagnosed with prediabetes. Recent studies have elucidated the impact of early exposures such as maternal diabetes, but also hyperglycemia below the threshold of gestational diabetes, obesity, hyperlipidemia, and paternal obesity on the future metabolic health of the offspring. Mechanisms affecting the developmental programing of offspring toward type 2 diabetes include epigenetic modifications, alterations in stem cell differentiation, metabolome and microbiome variation, immune dysregulation, and neonatal nutrition. The risk of type 2 diabetes in offspring is increased not only by diabetes exposure in utero but also by exposure to a heterogeneous milieu of factors that accompany maternal obesity that provoke a vicious cycle of metabolic disease. The key period for intervention to prevent type 2 diabetes is within the first 1000days of life.
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