Insulin Resistance as an Underlying Cause of Type 2 Diabetes in Adults Born with Low Birth Weight: A Narrative Review.

Abstract

Insulin, secreted by pancreatic β-cells, regulates blood glucose levels. Insulin resistance (IR), characterized by diminished cellular responsiveness, increases insulin demand, imposing stress on β-cells. This leads to β-cell decompensation, which contributes to the development of type 2 diabetes (T2D). A growing body of evidence connects early-life exposures, such as low birth weight (LBW), to a heightened risk of developing non-communicable diseases (NCD) such as T2D in adulthood. This comprehensive review synthesizes findings from 15 observational studies identified through a PubMed search to explore the specific biological mechanisms that link LBW to IR and T2D. The paper critically examines several prominent hypotheses, theories, and models that propose how endogenous responses to intrauterine conditions initiate a programming that can lead to lasting structural and functional changes in key metabolic organs. In individuals with fetal programming, the combination of impaired insulin sensitivity and compensatory insulin action is considered a precursor to impaired glucose tolerance and T2D, particularly in those who underwent rapid catch-up growth during childhood. Regular monitoring of LBW individuals can enable early intervention, such as lifestyle changes, to reduce the risk of IR and T2D. However, improving the early environment by providing care for women of reproductive age, especially during pregnancy, is a cost-effective strategy to address LBW and curb the NCD pandemic.