IGF-I and Free Fatty Acids Isn Glucose Metabolism in Acromegaly

The Role of Insulin-like Growth Factor-I (IGF-I) and Free Fatty Acids in Insulin Resistance, Insulin Secretion and Glucose Metabolism Abnormalities in Acromegaly

Background Glucose metabolism abnormalities are frequent in acromegaly. Insulin resistance (IR) correlates with the intensity of acromegaly and Insulin-like Growth factor-I (IGF-I) correlates better with IR than growth hormone (GH). Insulin secretion (IS) is significantly reduced in hyperglycemic acromegalics as compared with those with normal glucose levels. IS is independent of acromegaly intensity.

The aim of this study is to show that in active acromegaly: 1) IGF-I does not cause IR but is just a better marker of acromegaly intensity than GH; 2) high GH levels induce IR through free fatty acids (FFA); 3) hyperglycemia is caused by a defficient IS on a background of IR.

Methods Intensity of acromegaly will be assessed using serum levels of GH, IGF-I and IGF binding globulin-3. IR and IS will be assessd using an intravenous glucose tolerance test acording to Bergman model. FFA will be directly measured in plasma.

Inclusion Criteria:

• active acromegaly based on following criteria: minimum GH in oral glucose tolerance test (OGTT) over 1 ng/mL and serum IGF-I over upper limit of normal for age and sex
• age between 18 and 65 years old

Exclusion Criteria:

• more than one previous pituitary surgical intervention for acromegaly
• present medical treatment for acromegaly (somatostatin analogs, GH-receptor blockers, dopaminergic agonists)
• previous pituitary radiotherapy
• present medical treatment for hyperglycemia (oral antidiabetic drugs, insulin, etc)
• pituitary failure, treated or not
• medical or surgical conditions which, in the oppinion of the principal investigator, could impact on study results or patient's safety
• fasting blood glucose over 200 mg/dL or HbA1c over 8%.
• body mass index less than 20 or over 35 kg/mp