| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Program in Nutritional Metabolism, 2Pulmonary and Critical Care Medicine, 3Athinoula A. Martinos Center for Biomedical Imaging, 5Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; 4University of Puerto Rico School of Medicine, San Juan, Puerto Rico, and Department of Physical Medicine and Rehabilitation, Harvard Medical School and Spaulding Rehabilitation Hospital, Boston, Massachusetts; 6Department of Infectious Diseases, Skejby Hospital, Aarhus, Denmark; and 7Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Submitted 12 October 2006 ; accepted in final form 31 January 2007
Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30–40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (–0.8 ± 0.5 vs. +0.7 ± 0.3 mg·kg–1·min–1, P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/nuclear DNA (–52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9). 31P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures (r2 = 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity.
human immunodeficiency virus; insulin resistance; magnetic resonance spectroscopy
This article has been cited by other articles:
|
|
 |
|
  J. Fuller A 39-Year-Old Man With HIV-Associated Lipodystrophy JAMA, September 3, 2008; 300(9): 1056 - 1066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Grinspoon, C. Grunfeld, D. P. Kotler, J. S. Currier, J. D. Lundgren, M. P. Dube, S. E. Lipshultz, P. Y. Hsue, K. Squires, M. Schambelan, et al. State of the Science Conference: Initiative to Decrease Cardiovascular Risk and Increase Quality of Care for Patients Living With HIV/AIDS: Executive Summary Circulation, July 8, 2008; 118(2): 198 - 210. [Full Text] [PDF]
|
|
|
|
|
|
C. Grunfeld, D. P. Kotler, D. K. Arnett, J. M. Falutz, S. M. Haffner, P. Hruz, H. Masur, J. B. Meigs, K. Mulligan, P. Reiss, et al. Contribution of Metabolic and Anthropometric Abnormalities to Cardiovascular Disease Risk Factors Circulation, July 8, 2008; 118(2): e20 - e28. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dagogo-Jack HIV Therapy and Diabetes Risk Diabetes Care, June 1, 2008; 31(6): 1267 - 1268. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Gkrania-Klotsas and A.-E. Klotsas HIV and HIV treatment: effects on fats, glucose and lipids Br. Med. Bull., December 1, 2007; 84(1): 49 - 68. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
