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.

Study Overview

• Status: Completed
• Conditions: Acromegaly

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• Romania
  • Bucharest, Romania, 011863
    • "C. I. Parhon" Institute of Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study will prospectively include patients with active acromegaly assessed in a tertiary center. All patients who meet inclusion and exclusion criteria will be invited consecutively to participate in the study until the proposed number of patients is reached.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The correlation coefficient between IGFBP-3 and insulin resistance assessed using Bergman model is non-inferior to the correlation coefficient between IGF-I and insulin resistance	2 years
Free fatty acids correlates significantly with insulin resistance assessed using Bergman model	2 years
Disposition index calculated using Bergman model is significantly reduced in subjects with glucose intolerance than in subjects with normal glucose tolerance	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
GH, IGF-I and IGFBP-3 significantly correlates with insulin resistance calculated using Bergman model	2 years
GH, IGF-I and IGFBP-3 significantly correlates with free fatty acids	2 years
GH, IGF-I and IGFBP-3 does not correlate with insulin sensitivity calculated using Bergman model	2 years
GH, IGF-I and IGFBP-3 does not correlate with disposition index	2 years
Disposition index after reduction of acromegaly activity by various treatments	3 months after surgery or start of medical treatment

Collaborators and Investigators

• Sponsor: Carol Davila University of Medicine and Pharmacy

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: March 7, 2014
• First Submitted That Met QC Criteria: March 7, 2014
• First Posted (Estimate): March 11, 2014

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: August 20, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Acromegaly
• Other Study ID Numbers: 28332