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Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion.

Gareth HawkesRobin N BeaumontJessica TyrrellGrace M PowerAndrew WoodMarkku LaaksoLilian Fernandes SilvaMichael BoehnkeXianyong YinTom G RichardsonGeorge Davey SmithTimothy M Frayling
Published in: medRxiv : the preprint server for health sciences (2023)
High BMI in adulthood is associated with higher risk of type two diabetes, coupled with lower insulin sensitivity and secretion.Richardson et al [2020] used genetics to show that high BMI in childhood does not appear to increase the risk of type diabetes independently from its effect on adult BMI.We asked: does high childhood BMI affect insulin related traits such as fasting glucose and insulin sensitivity, independently of adulthood BMI?We used genetics to show that high childhood BMI has a protective effect on seven insulin sensitivity and secretion traits, including fasting glucose and measures of insulin sensitivity and secretion, independently of adulthood BMI.Our work has the potential to turn conventional understanding on its head - high BMI in childhood improves insulin sensitivity (when adjusting for knock on effects to high adult BMI) and opens up important questions about plasticity in childhood and compensatory mechanisms.
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