Although insulin resistance is characteristic in people with type 2 diabetes and those at risk of it, evidence also exists for beta-cell dysfunction and impaired insulin secretion that progresses over time, including Impaired first-phase insulin secretion A loss of normally pulsatile insulin secretion An increase in proinsulin secretion signaling, indicating impaired insulin processing An accumulation of islet amyloid polypeptide (a protein normally secreted with insulin) Hyperglycemia itself may impair insulin secretion, because high glucose levels desensitize beta cells, cause beta-cell dysfunction (glucose toxicity), or both.