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Question #851

Please refer to the graph below and indicate the parameter that best describes Curve 3.



Answer: D. Insulin Resistance

Educational Critique:  Generally, type 2 diabetes is characterized by increasing insulin resistance at target tissues, although the underlying reasons for this increasing resistance are not yet well understood. Insulin-dependent process, such as glucose uptake by peripheral tissues, inhibition of hepatic gluconeogenesis and inhibition of lipolysis are all impaired, leading to elevated plasma glucose. Initially, the ?-cells are able to secrete enough insulin to compensate for this hyperglycemia and insulin levels at this time may appear normal to elevated (hyperinsulinemia). However, progressive ?-cell insulin secretory loss, the driving force in the progression from normal glucose tolerance to IGT to frank type 2 diabetes, eventually occurs leading to postprandial hyperglycemia and further loss of ?-cell functionality. The underlying cause of this loss is uncertain, but is most likely a combination of environmental/genetic factors and functional and anatomic defects, but interventions that improve glycemia can help offset the degree of ?-cell dysfunction. Hepatic glucose production also increases due to increased pancreatic ?-cell glucagon secretion. Eventually, the combination of increasing resistance, increasing hepatic glucose production and decreasing insulin secretion lead to fasting hyperglycemia as well as postprandial hyperglycemia.