Insulin has been available for the treatment of diabetes mellitus for more than fifty years, yet many puzzling clinical phenomena remain unexplained. Examination of plasma insulin concentration by radioimmunoassay has repeatedly demonstrated a divergence between the absolute concentration of plasma insulin and the simultaneous concentration of glucose. This apparent discrepancy is well documented in patients with “prediabetes” and is commonly recognized in emergent diabetic ketoacidosis. In these situations, plasma insulin levels may actually be elevated but are seemingly ineffective in reducing blood glucose concentration. The concept of “resistance” to the action of insulin has been aptly applied to such clinical situations, but the pathophysiology of the phenomenon remains obscure.

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