Effects of Oral Glucosamine on Insulin and Blood Vessel Activity in Normal and Obese People

Overview

This study will examine whether glucosamine affects the way the body responds to insulin. Insulin is a hormone that causes the body to use glucose (sugar). Insulin does not work as well in overweight people, causing a condition called insulin resistance. Insulin also increases the flow of blood into muscle by opening inactive blood vessels. This study will test whether glucosamine, a nutritional supplement that many people take to treat arthritis, can cause or worsen insulin resistance or change how blood vessels react to insulin in normal weight and overweight people. Healthy normal weight and overweight volunteers between 21 and 65 years of age may be eligible for this study. Candidates will be screened with a brief physical examination, medical history, and blood and urine tests. After screening, participants will have three additional outpatient clinic visits for the following procedures: Visit 1 * Glucose clamp test to measure the body's response to insulin: For this procedure, a needle is placed in a vein of each arm, one for drawing blood samples, and one for infusing glucose and a potassium solution. The glucose is infused continuously during this 4-hour test and blood is drawn frequently to monitor glucose and insulin levels. After the test, blood glucose levels are monitored for another 2 hours to make sure they remain at an adequate level to prevent hypoglycemia (low blood sugar). * Blood flow measurement: Blood flow in the brachial artery of the arm is measured to assess how many capillaries (very small blood vessels) are being used to supply nutrients and oxygen to the muscle in the forearm. This test is done at the same time as the glucose clamp test. Blood flow is measured using a technique called contrast ultrasound. A small amount of contrast agent consisting of gas-filled bubbles the size of red blood cells is infused over 10 minutes through one of the catheters placed in the vein for the glucose clamp test. The contrast agent is infused twice, once at the beginning of the glucose clamp test and once at the end of the test. The contrast material creates a signal in response to ultrasound that provides information about the distribution of capillaries in the forearm. * Assignment to medication group: Participants are randomly assigned to take either glucosamine or placebo three times a day by mouth for 6 weeks. At the end of the 6 weeks, no study drug is taken for 1 week, and then participants "cross-over" medications, those who took glucosamine for the first 6 weeks take placebo for the next 6 weeks and vice versa. Visits 2 and 3 For these visits, the glucose clamp test and blood flow measurements are repeated. Visit 2 is scheduled at the end of the first 6-week treatment period, and Visit 3 is scheduled at the end of the second 6-week treatment period.

Glucosamine is a popular over-the-counter nutritional supplement that many people use for the treatment of osteoarthritis. Intravenous administration of glucosamine to animals or humans causes significant metabolic insulin resistance and vascular endothelial dysfunction. Moreover, experiments with various cell lines have implicated elevated glucosamine levels in the development of insulin resistance. However, there are no published studies examining the potential effects of oral glucosamine administration to modulate insulin sensitivity or capillary recruitment in humans. This is a significant concern because insulin resistance and vascular dysfunction contribute importantly to major public health problems including diabetes, obesity, hypertension, and cardiovascular diseases. Normal healthy volunteers and obese insulin resistant subjects will be enrolled in a randomized double-blind, placebo-controlled, crossover study to evaluate the effects of oral glucosamine to modulate insulin sensitivity and insulin-stimulated capillary recruitment. The reference standard hyperinsulinemic isoglycemic glucose clamp technique will be used to assess insulin sensitivity before treatment, after placebo or oral glucosamine (500 mg p.o. TID for 6 weeks), and after completion of the crossover. In addition, insulin-stimulated capillary recruitment will be measured at the same time as the glucose clamp studies by using the ultrasound microbubble contrast technique to assess blood flow in the brachial artery and capillary recruitment in forearm skeletal muscle in response to hyperinsulinemia. Finally, plasma glucosamine levels will be measured just prior to each glucose clamp study using an HPLC method. The results of this study will determine if oral glucosamine administration causes significant insulin resistance and impairment in insulin-stimulated capillary recruitment in healthy volunteers or worsens insulin resistance and capillary recruitment in obese subjects. In addition, our study will provide important information about how plasma glucosamine levels change with commonly used oral doses of glucosamine.