Type 2 diabetes and impaired glucose tolerance are associated with increased overall GH exposure in treated acromegalic patients
H Clarke, CN Jayasena, A Comninos, M Donaldson, K Meeran, WS Dhillo
Imperial Centre for Endocrinology
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 (IGF-1) better predict the onset of IGT or T2DM in treated acromegalic patients. However the associations of overall GH and IGF-1 exposure in patients with treated acromegaly have not been investigated previously.
AIM: To compare overall GH and IGF-1 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 IGF-1 burdens were calculated by multiplying the overall mean basal GH and mean IGF-1 index during patient follow-up, by the number of years since diagnosis of acromegaly. IGF-1 index was defined as serum IGF-1 divided by the upper limit of reference range. GH and IGF-1 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 vs. euglycaemic; 65.0±13.0, T2DM, p<0.05 vs. euglycaemic). Mean IGF-1 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.