Whole-body insulin resistance is the earliest predictor of type 2 diabetes onset, and this mainly reflects muscle insulin resistance (26). However, careful separation of the contributions of muscle and liver have shown that early improvement in control of fasting plasma glucose level is associated only with improvement in liver insulin sensitivity (20,21). It is clear that the resumption of normal or near-normal diurnal blood glucose control does not require improvement in muscle insulin sensitivity. Although this finding may at first appear surprising, it is supported by a wide range of earlier observations. Mice totally lacking in skeletal muscle insulin receptors do not develop diabetes (27). Humans who have the PPP1R3A genetic variant of muscle glycogen synthase cannot store glycogen in muscle after meals but are not necessarily hyperglycemic (28). Many normoglycemic individuals maintain normal blood glucose levels with a degree of muscle insulin resistance identical to those with type 2 diabetes (29).

Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas. Insulin lowers the blood glucose level. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas. This release of insulin promotes the uptake of glucose into body cells. In patients with diabetes, the absence of insufficient production of or lack of response to insulin causes hyperglycemia. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a lifetime.