Insulin Sensitivity in Men With the Metabolic Syndrome

Summary

The metabolic syndrome is a medical condition defined by high levels of cholesterol in the blood, high blood pressure, central obesity (gain in fat around the region of the stomach), and insulin resistance (body responds less well to insulin). This state of impaired insulin resistance can lead to type 2 diabetes mellitus, which is one of the most common metabolic disorders in the U.S. Numerous studies have shown an inverse relationship between insulin resistance and testosterone levels in men, however, causality has not been established. This protocol investigates the role of testosterone in modulating insulin sensitivity in insulin resistant states such as the metabolic syndrome. The hypothesis is that testosterone administration will improve insulin sensitivity.

Conditions

• Metabolic Syndrome

Interventions

PROCEDURE

intravenous glucose tolerance test

The IVGTT (70) is a 4 hour study with baseline sampling for insulin and glucose, followed by the administration of 0.3 mg/kg infusion of glucose, and subsequent frequent samples through 180 minutes. At 20 minutes, subjects will receive a 0.03 U/kg infusion of regular human insulin over 45 seconds to enhance the insulin level to better help us assess the impact of insulin on glucose uptake and to facilitate minimal model analysis. The IVGTT will be administered at baseline and after 3 months.

DRUG

testosterone

transdermal 7.5 g/per day for 3 months

DRUG

anastrozole

tablet (per oral) 10.0 mg/ daily 3 months

DRUG

goserelin acetate implant

single depot injection 10.8 mg 3 months

PROCEDURE

aerobic capacity (VO2 Max)

This test is employed to assess VO2max in all subjects. O2 and CO2 will be collected and measured from the expired air during the exercise stress test and used to calculate VO2max. This test will be administered at baseline and after 3 months.

PROCEDURE

MRI

1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.

PROCEDURE

muscle biopsy

Biopsies (20-50mg) will be obtained from the vastus lateralis muscle under local anesthesia (1% lidocaine) using a 5 mm Bergström needle (65) with suction applied. The muscle biopsy will be performed at baseline and after 3 months.

PROCEDURE

measurement of resting metabolic rate (energy expenditure)

Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.

PROCEDURE

Dual energy x-ray absorptiometry

Total and regional percent body fat, fat mass, lean tissue mass and bone mineral content will be determined by DEXA (Lunar Prodigy version 8.50). DEXA provides an in vivo assessment of body composition with minimal requirements for subject cooperation and will be employed at baseline and after 3 months.

PROCEDURE

Fasting oral glucose tolerance test

To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.

Sponsors & Collaborators

• American Diabetes Association

  collaborator OTHER

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  lead NIH

Principal Investigators

• Frances J Hayes, MD · Massachusetts General Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

50 Years

Max Age

75 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-05-31

Primary Completion

2011-02-28

Completion

2011-03-31

Countries

• United States

Study Locations