Why does chronic hyperglycemia in type 2 diabetes reduce the effectiveness of insulin therapy over time, despite initially adequate doses?

💡 Explanation

Hyperglycemia causes prolonged insulin release, downregulating GLUT4 transporters in pancreatic beta cells, reducing their sensitivity to glucose and insulin. Because of this downregulation, insulin therapy becomes less effective over time, therefore requiring increased doses to maintain glycemic control, rather than improved glucose metabolism in other tissues.

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