Glucose storage deficiency as a cause of insulin resistance in obese-hyperinsulinaemic diabetes.

Continuous indirect calorimetry has been used to measure the amount of glucose both stored and oxidized during the three hours following a 100 g oral glucose load in groups of normal and diabetic subjects. In normal subjects, a much greater amount of glucose was stored (62 g) than oxidized (19 g) above basal oxidation, emphasizing the greater importance of glucose storage in glucose disposal. Impairment of glucose oxidation alone, as shown in experimental conditions of increased plasma FFA levels was shown to affect glucose tolerance to a limited extent only whereas marked glucose intolerance always accompanied decreased glucose storage. Impairment of glucose storage was observed not only in patients with decreased insulin secretion, but also in hyperinsulinaemic-obese diabetics. In these last case, the presence of a normal rate of glucose oxidation demonstrates that their apparent insulin resistance was not resulting from deficiency of peripheral glucose oxidation, but from a major alteration in glucose storage. This alteration was reversed in great part through a 3-d fast. Whatever the nature of the underlying biochemical mechanisms, this study shows that insulin resistance can occur not only from lack of peripheral glucose oxidation, but also from impairment of the capacity of the storing tissues to store glucose in the first hours following immediately oral glucose intake.