Oral Glucosamine for 6 Weeks at Standard Doses Does Not Cause or Worsen Insulin Resistance or Endothelial Dysfunction in Lean or Obese Subjects

• Published in: Diabetes (New York, N.Y.) Vol. 55; no. 11; pp. 3142 - 3150
• Main Authors: MUNIYAPPA, Ranganath, KARNE, Rajaram J, HALL, Gail, CRANDON, Sonja K, BRONSTEIN, Joel A, VER, Maria R, HORTIN, Glen L, QUON, Michael J
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.11.2006
• Subjects: Administration, Oral; Adult; Arthritis; Ascorbic Acid - therapeutic use; Biological and medical sciences; Blood circulation disorders; Blood Pressure - drug effects; Cardiovascular disease; Chromatography; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Dosage and administration; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucosamine; Glucosamine - administration & dosage; Glucosamine - pharmacology; Glucosamine - therapeutic use; Glucose; Health aspects; Heart Rate - drug effects; Humans; Insulin resistance; Insulin Resistance - physiology; Medical sciences; Metabolic diseases; Metabolism; Musculoskeletal system; Obesity; Obesity - physiopathology; Oral administration; Osteoarthritis; Overweight persons; Pharmacokinetics; Plasma; Reference Values; Thinness - physiopathology; Ultrasonic imaging; Vascular diseases; Veins & arteries; Endocrinopathy; Human; Obesity; Glucosamine; Diabetes mellitus; Nutrition disorder; Endothelial dysfunction; Insulin resistance; Nutritional status
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db06-0714

Oral Glucosamine for 6 Weeks at Standard Doses Does Not Cause or Worsen Insulin Resistance or Endothelial Dysfunction in Lean or Obese Subjects Ranganath Muniyappa 1 , Rajaram J. Karne 1 , Gail Hall 1 , Sonja K. Crandon 1 , Joel A. Bronstein 1 , Maria R. Ver 1 , Glen L. Hortin 2 and Michael J. Quon 1 1 Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland 2 Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland Address correspondence and reprint requests to Michael J. Quon, MD, PhD, Chief, Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, 10 Center Dr., Bldg. 10, Rm. 6C-205, Bethesda, MD 20892. E-mail: quonm{at}nih.gov Abstract Glucosamine is a popular nutritional supplement used to treat osteoarthritis. Intravenous administration of glucosamine causes insulin resistance and endothelial dysfunction. However, rigorous clinical studies evaluating the safety of oral glucosamine with respect to metabolic and cardiovascular pathophysiology are lacking. Therefore, we conducted a randomized, placebo-controlled, double-blind, crossover trial of oral glucosamine at standard doses (500 mg p.o. t.i.d.) in lean ( n = 20) and obese ( n = 20) subjects. Glucosamine or placebo treatment for 6 weeks was followed by a 1-week washout and crossover to the other arm. At baseline, and after each treatment period, insulin sensitivity was assessed by hyperinsulinemic-isoglycemic glucose clamp (SI Clamp ) and endothelial function evaluated by brachial artery blood flow (BAF; Doppler ultrasound) and forearm skeletal muscle microvascular recruitment (ultrasound with microbubble contrast) before and during steady-state hyperinsulinemia. Plasma glucosamine pharmacokinetics after oral dosing were determined in each subject using a high-performance liquid chromatography method. As expected, at baseline, obese subjects had insulin resistance and endothelial dysfunction when compared with lean subjects (SI Clamp [median {25th–75th percentile}] = 4.3 [2.9–5.3] vs. 7.3 [5.7–11.3], P < 0.0001; insulin-stimulated changes in BAF [% over basal] = 12 [−6 to 84] vs. 39 [2–108], P < 0.04). When compared with placebo, glucosamine did not cause insulin resistance or endothelial dysfunction in lean subjects or significantly worsen these findings in obese subjects. The half-life of plasma glucosamine after oral dosing was ∼150 min, with no significant changes in steady-state glucosamine levels detectable after 6 weeks of therapy. We conclude that oral glucosamine at standard doses for 6 weeks does not cause or significantly worsen insulin resistance or endothelial dysfunction in lean or obese subjects. AUC, area under the curve BAF, brachial artery blood flow HBP, hexosamine biosynthetic pathway HPLC, high-performance liquid chromatography MVI, microvascular imaging QUICKI, quantitative insulin sensitivity check index ROI, region of interest Footnotes R.M., R.J.K., and G.H. contributed equally to this work. DOI: 10.2337/db06-0714. Clinical trial reg. no. NCT00065377, clinicaltrials.gov. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted August 3, 2006. Received May 24, 2006. DIABETES