Increased glucose turnover and glucose cycling in acromegalic patients with normal glucose tolerance

Abstract

To characterize the diabetogenic effects of growth hormone, we simultaneously measured glucose turnover with 2-3H- and 6-3H-glucose in six acromegalic patients with normal fasting blood glucose and oral glucose tolerance tests. Eight healthy volunteers served as controls. All subjects were studied under both basal conditions and during glucose infusion (2 mg X kg-1 X min-1). We determined true glucose production and irreversible glucose uptake using 6-3H-glucose and glucose cycling (difference between 2-3H- and 6-3H-glucose). After an overnight fast, glucose production was higher than normal in the acromegalic patients (2.18 +/- 0.15 vs 1.85 +/- 0.03 mg X kg-1 X min-1, p less than 0.05) despite hyperinsulinaemia. The metabolic clearance rate was normal. During the glucose infusion, glucose production was not suppressed as effectively in the acromegalic patients as in controls nor was glucose uptake augmented, while metabolic clearance rate was decreased. In acromegaly, basal glucose cycling was increased (0.44 +/- 0.08 vs 0.25 +/- 0.07 mg X kg-1 X min-1, p less than 0.05). Furthermore cycling of endogenous glucose measured during glucose infusion was also augmented (0.41 +/- 0.05 vs 0.24 +/- 0.05 mg X kg-1 X min-1, p less than 0.05). Hence the increase of glucose cycling (70%) was much more pronounced than that of glucose production (17%). In conclusion, small defects in glucose metabolism in acromegaly can be detected with sensitive tracer methods. These derangements are confined to the liver under fasting conditions, but are of both hepatic and extrahepatic origin during glucose loading.