Endocrine Abstracts

Objective: There is a complex cross-talk between bone and glucose metabolism. The surrogate markers of bone metabolism are osteocalcin (for bone formation) and CTx (for bone resorption). The osteoblast-derived protein osteocalcin has recently been shown to affect glucose homeostasis.

Aim of the study: To investigate the relationship between markers of bone metabolism and parameters reflecting bone composition, glucose homeostasis and insulin resistance in patients with chronic GH and IGF1 excess.

Patients: Twenty-three patients with active acromegaly were studied (11 males, age: 50.6±3.4 years, BMI: 26.7±0.9 kg/m², duration of disease 5.3±0.6 years, IGF1 735±46 ng/ml, GH level 15±3 μg/l). Seven patients had microadenoma. Five patients were operated, one was treated with radiotherapy and none with somatostatin analogue. Eight patients had T2DM.

Methods: At baseline glucose, insulin, GH, IGF1, osteocalcin and CTx were measured. In nondiabetic patients an oral glucose tolerance test (OGTT) was performed. Peak and area under the curve (AUC) for glucose and insulin, indexes of basal insulin resistance (HOMA-IR) and basal insulin secretion (HOMA-%B) were analyzed. Body composition (body fat, lean body mass) was analyzed using dual-energy X-ray absorptiometry.

Results: In patients with active acromegaly both serum osteocalcin (49.9±7.1 ng/ml) and CTx (1072±139 pg/ml),as well as HOMA-IR (5.6±0.6) were significantly increased,irrespective they had or did not have T2DM. HOMA-%B was significantly lower in diabetic patients (56.7±30.6) compared with nondiabetic patients (137.4±25.9; P=0.05). Osteocalcin positively correlated with CTx (R=0.928, P=0.0001). Osteocalcin and CTx inversely correlated with BMI (P=0.01) and CTx inversely correlated with percentage of fat mass (R=−0.473, P=0.05). Both bone markers correlated positively with IGF1 (P=0.01). Osteocalcin positively correlated with peak insulin during OGTT (R=0.643, P=0.018) and with AUCOGTT insulin (R=0.522, P=0.05).Bone markers were not associated with HOMA-IR, HOMA-%B or lean mass.

Conclusion: Active acromegaly is associated with high bone turnover. Serum osteocalcin is positively associated with IGF1 and insulin during OGTT. It is tempting to speculate that insulin and IGF1 promote osteocalcin production which in turn may act to improve glucose metabolism by stimulating beta cell secretion.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.