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Peripheral insulin resistance and resulting hyperlipidemia and hyperglycemia can overwhelm the capacity of the β-cell, leading to lipotoxicity and glucotoxicity. Lipotoxicity and glucotoxicity can trigger oxidative stress, generation of reactive oxygen species (ROS) and lead to endoplasmic reticulum (ER) stress and apoptosis; these detrimental pathways impair β-cell adaptation in pregnancy and can lead to gestational diabetes mellitus (GDM).
