Relationship between Glucose Intolerance and Insulin Resistance in Acromegaly

Abstract

To investigate the role and mechanisms of insulin resistance in glucose intolerance in acromegaly, we performed the 75 g oral glucose tolerance test (OGTT) and euglycemic clamp studies in four acromegalic patients before and after transsphenoidal adenomectomy.
The preoperative glucose curves of three patients obtained as a result of the 75 g OGTT, defined as borderline-type on the basis of JDS criteria in 1982, improved after surgery and their insulin levels, which were normal or hyperresponse type before surgery, were lower after surgery in keeping with the reduction in serum growth hormone levels. In the one patient with low preoperative insulin responses defined as the diabetic-type glucose curves and insulin responses failed to change after surgery in spite of a decrease in serum growth hormone levels.
In the euglycemic clamp study, the insulin dose-response curves of the glucose metabolic clearance rate (MCR) were shifted both downward and to the right in all cases before surgery, meaning decreased sensitivity and responsiveness to insulin. After surgery, insulin sensitivity or responsiveness to insulin improved in the borderline cases, but remained unchanged in the diabetic case.
In conclusion, insulin resistance (decreased sensitivity and responsiveness to insulin) plays an important role in glucose intolerance in acromegaly. Although the main cause of insulin resistance in borderline cases can be ascribed to increased serum GH levels, its cause in diabetic cases remains to be elucidated.