Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly

Overview

To investigate the 60 month impact of surgery and somatostatin analogues (SSA) on glucose metabolism in acromegaly we will analyzed data from 100 patients with acromegaly according with different treatments (group A=with SSA only; group B= SSA followed by surgery; group C= surgery only; group D= surgery followed by SSA). At diagnosis and after 6-12 and 60 months were analyzed as primary outcome measure changes in fasting glucose and as secondary outcome measures changes of glycated hemoglobin (HbA1c) and insulin levels, HOMA-R and HOMA-β, representing insulin resistance and β-cell function, respectively. We will enrol 100 patients and expect half of them to have IGT or diabetes mellitus. We do not expect changes according with different treatment after 60 months while SSA-treated patients might experience deterioration of glucose tolerance after 6-12 months. We intend to look for predictors of deterioration of glucose tolerance.

Impaired glucose tolerance (IGT) and overt diabetes mellitus are frequently associated with acromegaly. Patients with acromegaly are insulin resistant both in the liver and in the periphery, displaying hyperinsulinemia and increased glucose turn-over in the basal post-absorptive states. The prevalence of diabetes mellitus and that of IGT in acromegaly is unknown but is reported to range 19-56% and 16-46% in different series. The increased cardiovascular morbidity and mortality associated with acromegaly may party be a consequence of the increased insulin resistance that frequently accompanies GH excess. Glucose tolerance may worsen in patients treated with somatostatin analogues (SSA), because insulin secretion, i.e. β-cell function, is also suppressed. SSA induce control of GH and IGF-I excess in approximately 60% of patients after 12 months of treatment with no significant difference as applied after unsuccessful surgery or as first-line in newly diagnosed patients and control of GH and IGF-I levels occur with an even higher prevalence after a longer period of treatment. The inhibitory effect of SSA on pancreatic insulin secretion might, however, complicate the overall effect of this treatment on glucose tolerance. We recently demonstrated that 12 months after first-line treatment with SSA or surgery produced a similar improvement in LV hypertrophy and diastolic filling while systolic function increased more evidently in SSA-treated patients, total/HDL-cholesterol ratio significantly reduced only in SSA-treated patients while fasting glucose levels significantly reduced only in surgery-treated patients. A normal pituitary function was found in 46.4% of SSA-treated and in 36.4% of surgery-treated patients, resulting unchanged in the former and slightly reduced in the latter. Both a direct effect of SSA and a more preserved pituitary function might explain these results. Longitudinal data of glucose tolerance in patients with acromegaly and with or without diabetes treated long-term with SSA or surgery or both are still very limited. In order to investigate whether SSA negatively impact glucose tolerance in acromegaly, we will analyze data collected prospectively during a 10 year period. We will compare the results of glucose tolerance at diagnosis after 6-12 months and after 60 months of treatment with SSA or surgery. Patients will be grouped according with their treatment (SSA only, surgery only, SSA followed by surgery and SSA followed by surgery and SSA) in order to establish the effects on glucose tolerance mediated by disease control and type of treatment.