Hyperproinsulinaemia in acromegaly: evidence for abnormal pancreatic beta-cell function?

We investigated whether pancreatic beta-cell dysfunction has a role in the pathogenesis of glucose intolerance in acromegaly by comparing plasma intact proinsulin, immunoreactive insulin, C-peptide and glucose concentrations during a 75 g oral glucose load in six patients with active acromegaly and eight healthy volunteers. Only acromegalic patients with normal glucose tolerance were studied. Glucose concentrations were similar in acromegalic patients and controls. Acromegalic patients had higher fasting insulin (P < 0.005) and fasting C-peptide (P < 0.005) concentrations than controls. Although fasting proinsulin levels were higher in acromegalic patients than controls, this did not achieve statistical significance. Integrated insulin (P < 0.05), C-peptide (P < 0.05) and proinsulin (P < 0.005) concentrations were greater in acromegalic patients than control subjects. Integrated (P < 0.05) proinsulin:insulin molar ratios were higher in acromegalic patients than controls. Fasting and integrated insulin:C-peptide molar ratios were similar in acromegalic patients and controls. These results indicate that hyperproinsulinaemia contributes to the hyperinsulinaemia which characterizes active acromegaly. The disproportionate hyperproinsulinaemia in acromegaly suggests that prolonged and excessive growth hormone secretion may result in pancreatic beta-cell dysfunction which may predispose acromegalic subjects to glucose intolerance.