ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 OC3.4 | DOI: 10.1530/endoabs.63.OC3.4

Restoration of basal glucose turnover after disease control in acromegaly depends on treatment modality: a prospective, investigator-initiated trial

Mai C Arlien-Søborg1, Jakob Dal2, Michael Madsen1, Morten Høgild1, Astrid Hjelholt1, Niels Jessen1, Niels Møller1 & Jens Otto Lunde Jørgensen1

1Aarhus University Hospital, Aarhus, Denmark; 2Aalborg University Hospital, Aalborg, Denmark.

Background: Growth Hormone (GH) reversibly suppresses insulin-stimulated glucose uptake in skeletal muscle, but less is known about GH effects on glucose metabolism in the basal state. Somatostatin suppresses GH as well as insulin, and may also exert direct effects in skeletal muscle. This may have therapeutic implications in the treatment of acromegalic patients with a somatostatin analogue (SA).

Aim: To study basal and insulin-stimulated glucose metabolism in patients with acromegaly before and after disease control by either surgery-alone (surgery) or SA treatment.

Patients and methods: 21 patients (10 surgery and 11 SA) were studied before and after treatment during a 3 h basal period followed by a 3 h hyperinsulinemic, euglycemic glucose clamp (HEC) combined with glucose tracer infusion, indirect calorimetry, muscle biopsies, and MR spectroscopy to quantify ectopic lipid in liver (IHL) and muscle (IMCL).

Results: IGF-I levels (μg/l) normalised after treatment [696±57 vs. 211±21] with no treatment-specific difference (P=0.72). GH-dependent gene expression in muscle (IGF-I and SOCS2) also declined after treatment (P< 0.05). The glucose infusion rate (GIR) during the HEC (mg/kg/min) increased after treatment (P=0.001) regardless of modality (P=0.51) [GIR: 3.3±0.4 (before) vs. 4.7±0.5 (after)]. Basal glucose levels declined after surgery but not after SA, whereas SA significantly suppressed insulin levels compared to surgery (P<0.000). Treatment decreased the basal state endogenous glucose production (EGP) [1.96±0.1 vs. 1.47±0.1 (P=0.007)], but less so after SA (P=0.02). By contrast, basal state glucose disposal (Rd) was lower after SA compared to surgery (P<0.000). Moreover, Rd after SA was dominated by non-oxidative glucose disposal, whereas the opposite was true after surgery (P < 0.01). Ectopic fat did not predict insulin sensitivity in either group.

Conclusions: 1) Stimulated insulin sensitivity (HEC) improves after disease control in acromegaly independent of treatment modality, 2) Basal glucose metabolism also restores after disease control but less so, after SA, 3) The absence of association between insulin sensitivity and body composition including ectopic fat is unique for acromegaly.