The diminished ability of cells to respond to the action of insulin in transporting glucose (sugar) from the bloodstream into muscle and other tissues. Insulin resistance typically develops with obesity and heralds the onset of type 2 diabetes. It is as if insulin is “knocking” on the door of muscle. The muscle hears the knock, opens up, and lets glucose in. But with insulin resistance, the muscle cannot hear the knocking of the insulin (the muscle is “resistant”). The pancreas makes more insulin, which increases insulin levels in the blood and causes a louder “knock.” Eventually, the pancreas produces far more insulin than normal and the muscles continue to be resistant to the knock. As long as one can produce enough insulin to overcome this resistance, blood glucose levels remain normal. Once the pancreas is no longer able to keep up, blood glucose starts to rise, initially after meals, eventually even in the fasting state. Type 2 diabetes is now overt.