Background: A cardinal feature of acromegaly is insulin resistance. Patients with acromegaly are therefore predisposed to developing impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). It is therefore imperative to develop better biomarkers predicting the onset of IGT and T2DM in treated acromegalic patients. There is controversy whether GH or insulin-like growth factor 1 (IGF1) better predict the onset of IGT or T2DM in treated acromegalic patients. However the associations of overall GH and IGF1 exposure in patients with treated acromegaly have not been investigated previously.
Aim: To compare overall GH and IGF1 exposure in treated acromegalic patients classified according to the presence or absence of IGT and T2DM.
Methods: Records of 116 patients with treated acromegaly attending a single endocrine centre were examined retrospectively. T2DM and IGF were diagnosed using a 75g oral glucose tolerance test. GH and IGF1 burdens were calculated by multiplying the overall mean basal GH and mean IGF1 index during patient follow-up, by the number of years since diagnosis of acromegaly. IGF1 index was defined as serum IGF1 divided by the upper limit of reference range. GH and IGF1 burdens were compared between euglycaemic patients, and patients with IGT or T2DM.
Results: IGT and T2DM were present in 28 and 27% of treated acromegalic patients, respectively. The mean GH burden was significantly lower in euglycaemic patients when compared with patients with IGT or T2DM (mean GH burden in mcg/L: 46.1±5.2, euglycaemic; 80.7±20.1, IGT, P<0.01 versus euglycaemic; 65.0±13.0, T2DM, P<0.05 versus euglycaemic). Mean IGF1 burdens were not significantly different between patient groups.
Conclusion: These results suggest a strong association between overall GH exposure and abnormal glucose tolerance in patients with treated acromegaly. GH burden may therefore provide a useful prognostic marker in predicting the onset of IGT or T2DM in treated acromegalic patients.